Inhibition of endocytic uptake of severe acute respiratory syndrome coronavirus 2 and endo-lysosomal acidification by diphenoxylate.

Cell culture-based screening of a chemical library identified diphenoxylate as an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The observed 50% effective concentrations ranged between 1.4 and 4.9 µM against the original wild-type strain and its variants. Time-of-addition experiments indicated that diphenoxylate is an entry blocker targeting a host factor involved in viral infection. Fluorescence microscopic analysis visualized that diphenoxylate prevented SARS-CoV-2 particles from penetrating the cell membrane and also impaired endo-lysosomal acidification. Diphenoxylate exhibited a synergistic inhibitory effect on SARS-CoV-2 infection in human lung epithelial Calu-3 cells when combined with a transmembrane serine protease 2 (TMPRSS2) inhibitor, nafamostat. This synergy suggested that efficient antiviral activity is achieved by blocking both TMPRSS2-mediated early and endosome-mediated late SARS-CoV-2 entry pathways. The antiviral efficacy of diphenoxylate against SARS-CoV-2 was reproducible in a human tonsil organoids system. In a transgenic mouse model expressing the obligate SARS-CoV-2 receptor, human angiotensin-converting enzyme 2, intranasal administration of diphenoxylate (10 mg/kg/day) significantly reduced the viral RNA copy number in the lungs by 70% on day 3. This study underscores that diphenoxylate represents a promising core scaffold, warranting further exploration for chemical modifications aimed at developing a new class of clinically effective antiviral drugs against SARS-CoV-2.

Correction: Quantitative assessment of cardiomyocyte mechanobiology through high-throughput cantilever-based functional well plate systems.

Correction for 'Quantitative assessment of cardiomyocyte mechanobiology through high-throughput cantilever-based functional well plate systems' by Jongyun Kim et al., Analyst, 2023, 148, 5133-5143, https://doi.org/10.1039/D3AN01286G.

Quantitative assessment of cardiomyocyte mechanobiology through high-throughput cantilever-based functional well plate systems.

Proper regulation of the in vitro cell culture environment is essential for disease modelling and drug toxicity screening. The main limitation of well plates used for cell culture is that they cannot accurately maintain energy sources and compounds needed during cell growth. Herein, to understand the importance of perfusion in cardiomyocyte culture, changes in contractile force and heart rate during cardiomyocyte growth are systematically investigated, and the results are compared with those of a perfusion-free system. The proposed perfusion system consists of a Peltier refrigerator, a peristaltic pump, and a functional well plate. A functional well plate with 12 wells is made through injection moulding, with two tubes integrated in the cover for each well to continuously circulate the culture medium. The contractile force of cardiomyocytes growing on the cantilever surface is analysed through changes in cantilever displacement. The maturation of cardiomyocytes is evaluated through fluorescence staining and western blot; cardiomyocytes cultured in the perfusion system show greater maturity than those cultured in a manually replaced culture medium. The pH of the culture medium manually replaced at intervals of 3 days decreases to 6.8, resulting in an abnormal heartbeat, while cardiomyocytes cultured in the perfusion system maintained at pH 7.4 show improved contractility and a uniform heart rate. Two well-known ion channel blockers, verapamil and quinidine, are used to measure changes in the contractile force of cardiomyocytes from the two systems. Cardiomyocytes in the perfusion system show greater stability during drug toxicity screening, proving that the perfusion system provides a better environment for cell growth.

Carboxylate-functionalized dragon fruit peel powder as an effective adsorbent for the removal of Rhodamine B (cationic dye) from aqueous solution: adsorption behavior and mechanism.

In this study, we used a simple and low-toxicity chemical treatment to make a carboxylate-functionalized dragon fruit peel powder (CF-DFPP) from dragon fruit peel to improve its capacity for adsorbing Rhodamine B (RhB) from an aqueous medium. Field Emission-Scanning Electron Microscopy/Energy-Dispersive X-ray (FE-SEM/EDX), point of zero charges (pHPZC), Brunauer-Emmett-Teller (BET), and Fourier Transform Infrared (FT-IR) analyses were performed to characterize the adsorbent materials. The adsorption performance and mechanism for the removal of RhB were examined. The kinetic, isotherm and thermodynamic parameters were employed to evaluate the adsorption mechanism. Compared to other models, the Langmuir isotherm and PSO kinetic models better defined the experimental data. CF-DFPP adsorbent exhibited a maximum adsorption efficiency of 228.7 mg/g at 298 K for RhB adsorption. Thermodynamic analysis revealed that the adsorption of RhB by CF-DFPP was spontaneous (ΔGo < 0) and exothermic (ΔHo < 0) nature of the process. Different eluting agents were used in desorption tests, and NaOH was revealed to have greater desorption efficiency (96.8%). Furthermore, regeneration examinations revealed that the biosorbent could effectively retain RhB, even after six adsorption/desorption cycles. These findings demonstrated that the CF-DFPP might be a novel material for removing RhB from an aqueous medium.

Stress induced self-rollable smart-stent-based U-health platform for in-stent restenosis monitoring.

To date, several smart stents have been proposed to continuously detect biological cues, which is essential for tracking patients' critical vital signs and therapy. However, the proposed smart stent fabrication techniques rely on conventional laser micro-cutting or 3D printing technologies. The sensors are then integrated into the stent structure using an adhesive, conductive epoxy, or laser micro-welding process. The sensor packaging method using additional fabrication processes can cause electrical noise, and there is a possibility of sensor detachment from the sent structure after implantation, which may pose a significant risk to patients. Herein, we are demonstrating for the first time a single-step fabrication method to develop a smart stent with an integrated sensor for detecting in-stent restenosis and assessing the functional dynamics of the heart. The smart stent is fabricated using a microelectromechanical system (MEMS)-based micromachining technology. The proposed smart stent can detect biological cues without additional power and wirelessly transmit the signal to the network analyzer. The cytocompatibility of the smart stent is confirmed through a cytotoxicity test by monitoring the cell growth, proliferation, and viability of the cultured cardiomyocytes. The capacitance of the smart stent exhibits an excellent linear relationship with the applied pressure. The exceptional sensitivity of the pressure sensor enabled the proposed smart stent to detect biological cues during in vivo analysis. The preliminary findings confirmed the proposed smart stent's higher level of structural integrity, durability and repeatability. Finally, the practical feasibility of the smart stent is demonstrated by monitoring diastole and systole at various beat rates using a phantom. The results of the phantom study showed a similar pattern to the human model, indicating the potential use of the proposed multifunctional smart stent for real-time applications.

Multi-layered polymer cantilever integrated with full-bridge strain sensor to enhance force sensitivity in cardiac contractility measurement.

In this study, we developed a multi-layered functional cantilever for real-time force measurement of cardiomyocytes in cell culture media. The functional cantilever with a full-bridge circuit configuration was composed of one polydimethylsiloxane (PDMS) and two polyimide (PI) layers, forming two resistive sensors on each upper side of the two PI layers. The PI layers were chemically bonded using an oxygen plasma treatment, with a thin composite layer consisting of Cr/SiO2/PDMS. These greatly improved the force sensitivity and the long-term reliability of the integrated strain sensor operating in liquids. The nanogrooved PDMS top layer bonded on the upper PI layer was employed to further improve the growth of cardiomyocytes on the functional cantilever. The difference in resistance changes and response characteristics was confirmed by evaluating the characteristics of the multi-layered polymer cantilevers with half-bridge and full-bridge circuit configurations. We also employed the cantilever devices to measure the contraction force of cardiomyocytes for 16 days and side effects in real time in human-induced pluripotent stem cells treated with the cardiovascular drug verapamil. The sensor-integrated cantilever devices are expected to be utilized as a novel biomedical sensor for evaluating the mechanobiology of cardiomyocytes, as well as in drug screening tests.

Antioxidative and anti-inflammatory activity of psiguadial B and its halogenated analogues as potential neuroprotective agents.

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: ß-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased H2O2-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl2 in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.

Metal-Organic Cooperative Catalysis in C-H and C-C Bond Activation.

Transition-metal-catalyzed activation of C-H and C-C bonds is a challenging area in synthetic organic chemistry. Among various methods to accomplish these processes, the approach using metal-organic cooperative catalytic systems is one of the most promising. In this protocol, organic molecules as well as transition metals act as catalysts to bring about reactions, which proceed with high efficiencies and selectivities. Various metal-organic cooperative catalytic systems developed for C-H and C-C bond activation reactions are discussed in this review. Also discussed are how each metal-organic cooperative catalyst affects the reaction mechanism and what kinds of substrates can be applied in each of the catalytic processes.

Hydroxamic acid mediated heterogeneous Fenton-like catalysts for the efficient removal of Acid Red 88, textile wastewater and their phytotoxicity studies.

Heterogeneous Fenton-like catalyst and its industrial application are increasingly given importance for its non-selective mineralization of organic pollutants in broad pH range. Current study, utilized an aromatic hydroxamic acid derivative 2-hydroxypyridine-N-oxide (HpO), for the construction of iron-Hpo ligand catalyst supported on granular activated carbon (GAC). 8-Hydroxyquinoline and citric acid as non-hydroxamic aromatic and aliphatic Fenton-like catalysts were used for comparative evaluation of the efficiency with targeted catalyst (iron-HpO-GAC). This novel catalyst iron-HpO-GAC exhibits excellent efficiency in Acid Red 88 dye removal in the presence of hydrogen peroxide as oxidant at acidic, basic as well as at neutral conditions. Operational conditions for the catalytic oxidation including temperature, dye concentration, pH and catalyst dosage were systematically investigated and analyzed through kinetic studies. Thermodynamic analysis of the catalytic dye removal revealed that the system could oxidize pollutants faster with less activation energy requirement. Higher level of recyclability and stability of the catalyst with less iron leaching was achieved. Finally, the real time application of the catalyst was investigated through successful repeated treatment for actual industrial wastewater. The phytotoxicity assay (with respect to plant Phaseolus mungo) revealed that the degradation of Acid Red 88 and dye wastewater produced nontoxic metabolites which increases its potential application. This study emphasizes the viability of hydroxamate mediated efficient Fenton-like oxidation as a novel approach in designing economically viable pollutant removal technology.

Synthesis and evaluation of an orally available "Y"-shaped biaryl peroxisome proliferator-activated receptor δ agonist.

In this study, we designed and synthesized several novel "Y"-shaped biaryl PPARδ agonists. Structure-activity relationship (SAR) studies demonstrated that compound 3a was the most active agonist with an EC50 of 2.6 nM. We also synthesized and evaluated enantiospecific R and S isomers of compound 3a to confirm that R isomer (EC50 = 0.7 nM) shows much more potent activity than S isomer (EC50 = 6.1 nM). Molecular docking studies between the PPAR ligand binding domain and enantiospecific R and S isomers of compound 3a were performed. In vitro absorption, distribution, metabolism, excretion, and toxicity (ADMET) and in vivo PK profiles show that compound 3a possesses superior drug-like properties including good bioavailability. Our overall results clearly demonstrate that this orally administrable PPARδ agonist 3a is a viable drug candidate for the treatment of various PPARδ-related disorders.

Removal of anionic dyes (Reactive Black 5 and Congo Red) from aqueous solutions using Banana Peel Powder as an adsorbent.

The adsorption characteristics of Reactive Black 5 (RB5) and Cong Red (CR) onto Banana Peel Powder (BPP) from aqueous solution were investigated as a function of pH, contact time, initial dye concentration and temperature. The BPP was characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) analysis. FTIR results revealed that hydroxyl (-OH), amine (-NH) and carboxyl (-CË­O) functional groups present on the surface of BPP. The SEM results show that BPP has an irregular and porous surface morphology which is adequate for dye adsorption. The equilibrium data were analyzed using Langmuir and Freundlich isotherm models. Experimental results were best represented by the Langmuir isotherm model. The adjustments of models were confirmed by the Chi-square (χ2) test and the correlation coefficients (R2). The maximum monolayer adsorption capacities of RB5 and CR on BPP calculated from Langmuir isotherm model were 49.2 and 164.6mg/g at pH 3.0 and 298K. Experimental data were also tested in terms of adsorption kinetics using pseudo-first-order and pseudo-second-order kinetic models. The results showed that the adsorption processes of both RB5 and CR followed well pseudo-second-order kinetic models. The calculated thermodynamic parameters ΔG°, ΔH° and ΔS° showed that the adsorption of RB5 and CR onto BPP was feasible, spontaneous and endothermic in the temperature range 298-318K. The RB5 and CR were desorbed from BPP using 0.1M NaOH. The recovery for both anionic dyes was found to be higher than 90%. Based on these it can be concluded that BPP can be used as an effective, low cost, and eco-friendly adsorbent for CR removal than RB5 from aqueous solution.

Equilibrium isotherms, kinetics, and thermodynamics studies for congo red adsorption using calcium alginate beads impregnated with nano-goethite.

The present study is concerned with the batch adsorption of congo red (CR) from an aqueous solution using calcium alginate beads impregnated with nano-goethite (CABI nano-goethite) as an adsorbent. The optimum conditions for CR removal were determined by studying operational variables viz. pH, adsorbent dose, contact time, initial dye ion concentration and temperature. The CABI nano-goethite was characterized by Fourier transform infrared spectroscopy (FTIR), X- ray diffraction (XRD) and Scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS) analysis. The CR sorption data onto CABI nano-goethite were described using Langmuir, Freundlich, Dubinin-Radushkevich and Temkin isotherm models. The results show that the best fit was achieved with the Langmuir isotherm model. The maximum adsorption capacity (181.1mg/g) of CR was occurred at pH 3.0. Kinetic studies showed that the adsorption followed a pseudo-second-order model. Desorption experiments were carried out to explore the feasibility of regenerating the adsorbent and the adsorbed CR from CABI nano-goethite. The best desorbing agent was 0.1M NaOH with an efficiency of 94% recovery. The thermodynamic parameters ΔG°, ΔH°, and ΔS° for the CR adsorption were determined by using adsorption capacities at five different temperatures (293, 303, 313, 323 and 303K). Results show that the adsorption process was endothermic and favoured at high temperature.

Pd/C-Catalyzed Carbonylative Esterification of Aryl Halides with Alcohols by Using Oxiranes as CO Sources.

A carbonylative esterification reaction between aryl bromides and alcohols, promoted by Pd/C and NaF in the presence of oxiranes, has been developed. In this process, oxiranes serve as sources of carbon monoxide by their conversion to aldehydes through a palladium-promoted Meinwald rearrangement pathway. Intramolecular versions of this process serve as methods for the synthesis of lactones and phthalimides.

Adsorption of methyl orange from aqueous solution by aminated pumpkin seed powder: Kinetics, isotherms, and thermodynamic studies.

Present research discussed the utilization of aminated pumpkin seed powder (APSP) as an adsorbent for methyl orange (MO) removal from aqueous solution. Batch sorption experiments were carried to evaluate the influence of pH, initial dye concentration, contact time, and temperature. The APSP was characterized by using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The experimental equilibrium adsorption data were fitted using two two-parameter models (Langmuir and Freundlich) and two three-parameter models (Sips and Toth). Langmuir and Sips isotherms provided the best model for MO adsorption data. The maximum monolayer sorption capacity was found to be 200.3mg/g based on the Langmuir isotherm model. The pseudo-first-order and pseudo-second-order model equations were used to analyze the kinetic data of the adsorption process and the data was fitted well with the pseudo-second-order kinetic model (R(2)>0.97). The calculated thermodynamic parameters such as ΔG(0), ΔH(0) and ΔS(0) from experimental data showed that the sorption of MO onto APSP was feasible, spontaneous and endothermic in the temperature range 298-318 K. The FTIR results revealed that amine and carboxyl functional groups present on the surface of APSP. The SEM results show that APSP has an irregular and porous surface which is adequate morphology for dye adsorption. Desorption experiments were carried to explore the feasibility of adsorbent regeneration and the adsorbed MO from APSP was desorbed using 0.1M NaOH with an efficiency of 93.5%. Findings of the present study indicated that APSP can be successfully used for removal of MO from aqueous solution.

Detection and Molecular Characterization of Cryptosporidium spp. from Wild Rodents and Insectivores in South Korea.

In order to examine the prevalence of Cryptosporidium infection in wild rodents and insectivores of South Korea and to assess their potential role as a source of human cryptosporidiosis, a total of 199 wild rodents and insectivore specimens were collected from 10 regions of South Korea and screened for Cryptosporidium infection over a period of 2 years (2012-2013). A nested-PCR amplification of Cryptosporidium oocyst wall protein (COWP) gene fragment revealed an overall prevalence of 34.2% (68/199). The sequence analysis of 18S rRNA gene locus of Cryptosporidium was performed from the fecal and cecum samples that tested positive by COWP amplification PCR. As a result, we identified 4 species/genotypes; chipmunk genotype I, cervine genotype I, C. muris, and a new genotype which is closely related to the bear genotype. The new genotype isolated from 12 Apodemus agrarius and 2 Apodemus chejuensis was not previously identified as known species or genotype, and therefore, it is supposed to be a novel genotype. In addition, the host spectrum of Cryptosporidium was extended to A. agrarius and Crosidura lasiura, which had not been reported before. In this study, we found that the Korean wild rodents and insectivores were infected with various Cryptosporidium spp. with large intra-genotypic variationa, indicating that they may function as potential reservoirs transmitting zoonotic Cryptosporidium to livestock and humans.

Hydroesterification of alkenes with sodium formate and alcohols promoted by cooperative catalysis of Ru3(CO)12 and 2-pyridinemethanol.

A chelation-assisted hydroesterification reaction of alkenes with sodium formate and alcohols that involves cooperative catalysis by Ru3(CO)12 and 2-pyridinemethanol is described. In this three-component coupling reaction, sodium formate serves as the carbon monoxide source.

The homeodomain-leucine zipper ATHB23, a phytochrome B-interacting protein, is important for phytochrome B-mediated red light signaling.

Phytochromes are red (R)/far-red (FR) photoreceptors that are central to the regulation of plant growth and development. Although it is well known that photoactivated phytochromes are translocated into the nucleus where they interact with a variety of nuclear proteins and ultimately regulate genome-wide transcription, the mechanisms by which these photoreceptors function are not completely understood. In an effort to enhance our understanding of phytochrome-mediated light signaling networks, we attempted to identify novel proteins interacting with phytochrome B (phyB). Using affinity purification in Arabidopsis phyB overexpressor, coupled with mass spectrometry analysis, 16 proteins that interact with phyB in vivo were identified. Interactions between phyB and six putative phyB-interacting proteins were confirmed by bimolecular fluorescence complementation (BiFC) analysis. Involvement of these proteins in phyB-mediated signaling pathways was also revealed by physiological analysis of the mutants defective in each phyB-interacting protein. We further characterized the athb23 mutant impaired in the homeobox protein 23 (ATHB23) gene. The athb23 mutant displayed altered hypocotyl growth under R light, as well as defects in phyB-dependent seed germination and phyB-mediated cotyledon expansion. Taken together, these results suggest that the ATHB23 transcription factor is a novel component of the phyB-mediated R light signaling pathway.

Piezoelectric catalytic driven advanced oxidation process using two-dimensional metal dichalcogenides for wastewater pollutants remediation.

The public and society have increasingly recognized numerous grave environmental issues, including water pollution, attributed to the rapid expansion of industrialization and agriculture. Renewable energy-driven catalytic advanced oxidation processes (AOPs) represent a green, sustainable, and environmentally friendly approach to meet the demands of environmental remediation. In this context, 2D transition metal dichalcogenides (TMDCs) piezoelectric materials, with their non-centrosymmetric crystal structure, exhibit unique features. They create dipole polarization, inducing a built-in electric field that generates polarized holes and electrons and triggers redox reactions, thereby facilitating the generation of reactive oxygen species for wastewater pollutant remediation. A broad spectrum of 2D TMDCs piezoelectric materials have been explored in self-integrated Fenton-like processes and persulfate activation processes. These materials offer a more simplistic and practical method than traditional approaches. Consequently, this review highlights recent advancements in 2D TMDCs piezoelectric catalysts and their roles in wastewater pollutant remediation through piezocatalytic-driven AOPs, such as Fenton-like processes and sulfate radicals-based oxidation processes.

Photoilluminated Redox-Processed Rh2P Nanoparticles on Photocathodes for Stable Hydrogen Production in Acidic Environments.

While photoelectrochemical (PEC) cells show promise for solar-driven green hydrogen production, exploration of various light-absorbing multilayer coatings has yet to significantly enhance their hydrogen generation efficiency. Acidic conditions can enhance the hydrogen evolution reaction (HER) kinetics and reduce overpotential losses. However, prolonged acidic exposure deactivates noble metal electrocatalysts, hindering their long-term stability. Progress requires addressing catalyst degradation to enable stable, efficient, and acidic PEC cells. Here, we proposed a process design based on the photoilluminated redox deposition (PRoD) approach. We use this to grow crystalline Rh2P nanoparticles (NPs) with a size of 5-10 on 30 nm-thick TiO2, without annealing. Atomically precise reaction control was performed by using several cyclic voltammetry cycles coincident with light irradiation to create a system with optimal catalytic activity. The optimized photocathode, composed of Rh2P/TiO2/Al-ZnO/Cu2O/Sb-Cu2O/ITO, achieved an excellent photocurrent density of 8.2 mA cm-2 at 0 VRHE and a durable water-splitting reaction in a strong acidic solution. Specifically, the Rh2P-loaded photocathode exhibited a 5.3-fold enhancement in mass activity compared to that utilizing just a Rh catalyst. Furthermore, in situ scanning transmission electron microscopy (STEM) was performed to observe the real-time growth process of Rh2P NPs in a liquid cell.

Low-Intensity Light Detection with a High Detectivity Using 2D-Sb2Se3 Nanoflakes on 1D-ZnO Nanorods as Heterojunction Photodetectors.

Multifunctional photodetectors (PDs) with broadband responsivity (R) and specific detectivity (D*) at low light intensities are gaining significant attention. Thus, we report a bilayer PD creatively fabricated by layering two-dimensional (2D) Sb2Se3 nanoflakes (NFs) on one-dimensional (1D) ZnO nanorods (NRs) using simple thermal transfer and hydrothermal processes. The unique coupling of these two layers of materials in a nanostructured form, such as 2D-Sb2Se3 NFs/1D-ZnO NRs, provides an effective large surface area, robust charge transport paths, and light-trapping effects that enhance light harvesting. Furthermore, the combination of both layers can effectively facilitate photoactivity owing to proper band alignment. The as-fabricated device demonstrated superior overall performance in terms of a suitable bandwidth, good R, and high D* under low-intensity light, unlike the single-layered 1D-ZnO NRs and 2D-Sb2Se3 NF structures alone, which had poor detectivity or response in the measured spectral range. The PD demonstrated a spectral photoresponse ranging from ultraviolet (UV) to visible (220-628 nm) light at intensities as low as 0.15 mW·cm-2. The PD yielded a D* value of 3.15 × 1013 Jones (220 nm), which reached up to 5.95 × 1013 Jones in the visible light region (628 nm) at a 3 V bias. This study demonstrated that the 2D-Sb2Se3 NFs/1D-ZnO NRs PD has excellent potential for low-intensity light detection with a broad bandwidth, which is useful for signal communications and optoelectronic systems.