Heterologous Production of the D-Cycloserine Intermediate O-acetyl-L-serine in Human Lung Cancer Cells

According to the World Health Organization, Tuberculosis (TB) is the second leading cause of death by a single infectious disease behind COVID-19. Despite a century of effort, the current TB vaccine does not effectively prevent pulmonary TB, promote herd immunity, or prevent transmission. Therefore, we seek to develop a genetic prophylaxis for TB. We have determined D-cycloserine to be the optimal target for this approach due to its relatively short six-enzyme biosynthetic pathway. D-CS is a second-line antibiotic for TB that inhibits bacterial cell wall synthesis. The first committed step towards D-CS synthesis is catalyzed by the L-serine-O-acetyltransferase (DcsE) which converts L-serine and acetyl-CoA to O-acetyl-L-serine (L-OAS). To test if the D-CS pathway could be an effective prophylaxis for TB in human cells, we endeavored to express DcsE in human cells and test its functionality. We overexpressed DcsE tagged with FLAG and GFP in A549 lung cancer cells as determined using fluorescence microscopy. We observed that purified DcsE catalyzed the synthesis of L-OAS as observed by HPLC-MS. Therefore, DcsE synthesized in human cells is a functional enzyme capable of converting L-serine and acetyl-CoA to L-OAS demonstrating the first step towards DCS production in human cells.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

In silico screening of potential compounds from begonia genus as 3CL protease (3Cl pro) SARS-CoV-2 inhibitors

Background: The emergence of Coronavirus disease (COVID-19) has been declared a pandemic and made a medical emergency worldwide. Various attempts have been made, including optimizing effective treatments against the disease or developing a vaccine. Since the SARS-CoV-2 protease crystal structure has been discovered, searching for its inhibitors by in silico technique becomes possible. Objective(s): This study aims to virtually screen the potential of phytoconstituents from the Begonia genus as 3Cl pro-SARS-CoV- 2 inhibitors, based on its crucial role in viral replication, hence making these proteases "promising" for the anti-SARS-CoV-2 target. Method(s): In silico screening was carried out by molecular docking on the web-based program DockThor and validated by a retrospective method. Predictive binding affinity (Dock Score) was used for scoring the compounds. Further molecular dynamics on Desmond was performed to assess the complex stability. Result(s): Virtual screening protocol was valid with the area under curve value 0.913. Molecular docking revealed only beta-sitosterol-3-O-beta-D-glucopyranoside with a lower docking score of -9.712 kcal/mol than positive control of indinavir. The molecular dynamic study showed that the compound was stable for the first 30 ns simulations time with Root Mean Square Deviation <3 A, despite minor fluctuations observed at the end of simulation times. Root Mean Square Fluctuation of catalytic sites HIS41 and CYS145 was 0.756 A and 0.773 A, respectively. Conclusion(s): This result suggests that beta-sitosterol-3-O-beta-Dglucopyranoside might be a prospective metabolite compound that can be developed as anti-SARS-CoV-2.Copyright © 2023, Page Press Publications. All rights reserved.

Unmuting the patient voice: Coproducing a virtual, structured education group for patients newly diagnosed with type 2 diabetes

Aim: A structured education group for adults newly diagnosed with type 2 diabetes has been offered in a face-to- face (F2F) format in the health board since 2009. The suspension of in-person groups due to Covid-19 catalysed redevelopment of the group in a virtual, interactive format. Method(s): The aims and objectives of the virtual group were extended from the original F2F format, and the teaching resources were diversified to include film, animations and a workbook. Patients newly diagnosed with type 2 diabetes, were contacted using a standardised engagement protocol and offered the opportunity to join the virtual group. A series of pilot groups were delivered. The Plan-Do- Study- Act (PDSA) model was used. Each pilot group was studied using mixed method data collection and critiqued by patients, the educator and the team, to improve the delivery methods and patient experience. Result(s): Over six months, eight groups were conducted. Forty-six patients were invited and 30 attended. Engagement was higher in the virtual option compared to usual care prior to the pandemic (65% compared to 55%). Results from feedback forms showed that the majority of respondents either agreed (13%) or strongly agreed (80%) that the group had improved their understanding of type 2 diabetes. The group was given a Net Promoter Score (NPS) of 100. Conclusion(s): The digital option provides a feasible model to deliver an alternative interactive, structured group education programme at diagnosis of type 2 diabetes. The next step involves developing an engagement programme with primary care and application for QISMET accreditation.

Plastic Waste-Derived Carbon Dots: Insights of Recycling Valuable Materials Towards Environmental Sustainability.

Carbon dots (CDs) or carbon quantum dots (CQDs) have emerged as rising stars in the carbon family due to their diverse applications in various fields. CDs are spherical particles with a well-distributed size of less than 10 nm. Functional CDs are promising nanomaterials with low toxicity, low cost, and enormous applications in the field of bioimaging, optoelectronics, photocatalysis, and sensing. Plastic is non-biodegradable and hazardous to the environment, however extremely durable and used in abundance. During the COVID-19 pandemic, the use of plastic waste, particularly masks, goggles, face shields, and shoe cover, has increased tremendously. It needs to be recycled in a productive way as plastic wastes take hundreds or thousands of years to degrade naturally. The conversion of plastic waste into magnificent CDs has been reported as one of the key alternatives for environmental sustainability and socio-economic benefits. In this review, synthetic routes for the conversion of plastic wastes into CDs utilizing hydrothermal, solvothermal, pyrolysis, flash joule heating, and characterization of these CDs using different techniques, such as Fourier-transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, and transmission electron microscope, have been discussed. Furthermore, potential applications of these plastic-derived CDs in sensing, catalysis, agronomics, and LED lights are summarized herein.

Dnazymes as a Method for Nipah Henipavirus Detection

Intro: Deoxyribozymes (Dz) are short synthetic DNA oligonucleotides that catalyze the cleavage of a phosphodiester bond between nucleotides in the presence of divalent metal ions. The use of DNAzymes in the in vitro diagnostics increases the specificity and versatility of the analysis. Method(s): We took the well-studied Dz 10-23 with high catalytic activity as the basis of our system. The biosensor is divided into two fragments according to the binary probe principle (Dz1 and Dz2), which consist of target RNA binding sites, a fluorescent substrate (Fsub), and half of the Dz 10-23 catalytic center sequence. Assembly of the Dz 10-23 active center with subsequent Fsub cleavage and registration of a fluorescent signal is possible only if the target RNA is present in the sample. Finding(s): To assess the diagnostic potential of the biosensor, we measured FAM fluorescence in a solution containing synthetic RNA 35 nucleotides long (nip35) corresponding to the NiV target sequence, Fsub labeled with the FAM-BHQ1 and Dz_NiV pair. A mixture of Dz_NiV and Fsub was used as a control. The detection limit of the target RNA reached 5 nM, the signal development time was 30 minutes at a temperature of 37 C . Discussion(s): The specificity of Dz_NiV was evaluated in the presence of synthetic RNAs from six other RNA viruses of similar length: Hendra, Machupo, Sabia, Junin, Guanarito, and SARS-CoV. A fluorescent signal was recorded only in the presence of nip35 in the reaction mixture. The efficiency of Dz_NiV on a long fragment was tested using a plasmid with a cloned target sequence. The site is about 700 b.p. was amplified by PCR, followed by transcription. Conclusion(s): It was developed the highly specific biosensor Dz_NiV for the detection of Nipah virus RNA with a sensitivity limit of 5 nM at 37 C .Copyright © 2023

Ace2 Substrate Cleavage Effect Associated with Covid-19 Patient Plasma Immunoglobulin

Background: Many mechanisms responsible for COVID-19 pathogenesis are well-known, but COVID-19 includes features with unclear pathogenesis, like autonomic dysregulation, coagulopathies, and high levels of inflammation. The SARS-CoV-2 spike protein receptor binding domain (RBD) receptor is angiotensin converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop immunoglobulins (Igs) that have negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity - ACE2-like 'abzymes'. Method(s): To explore this hypothesis, we studied 67 patients hospitalized with COVID-19 who had disodium ethylenediaminetetraacetate (EDTA) anticoagulated plasma samples available, obtained about 7 days after admission. We used commercially available fluorometric ACE2 assays (Abcam), and a SpectraMax M5 microplate reader (Molecular Devices), measuring Relative Fluorescent Unit (RFU, Ex/Em = 320/420 nm;RFU) in a kinetic mode every 20 min at 37C. ACE2 inhibitor provided in the assay kit was used for additional controls. In some control experiments, we added Zn2+ to plasma, or conducted serial dilutions to decrease Zn2+. To deplete Igs, we passed plasma samples through a 0.45 mum filter to remove large particles, then passed the material through 100kDa cut-off ultrafiltration membrane (PierceTM) columns, and finally used protein A/G Magnetic Beads (Life Technologies) to specifically deplete Ig, removing >99.99% of Ig as assessed with a human IgG ELISA Kit (Abcam). Result(s): ACE2 is a metalloprotease that requires Zn2+ for activity. However, we found that the plasma of 11 of the 67 patients could cleave a synthetic ACE2 peptide substrate, even though the plasma samples were collected using EDTA anticoagulant. When we spiked plasma with synthetic ACE2, no ACE2 substrate cleavage activity was observed unless Zn2+ was added, or the plasma was diluted to decrease EDTA concentration. After processing samples by size exclusion and protein A/G adsorption, the plasma samples did not cleave the ACE2 substrate peptide. Conclusion(s): The data suggest that some patients with COVID-19 develop Igs with activity capable of cleaving synthetic ACE2 substrate. Since abzymes can exhibit promiscuous substrate specificities compared to the enzyme whose active site image they resemble, and since proteolytic cascades regulate physiologic processes, anti-RBD abzymes may contribute to some otherwise obscure features of COVID-19 pathogenesis. (Figure Presented).

Mechanisms of CRISPR-mediated immunity and applications beyond editing

Mammals, bacteria, and archaea have domesticated transposases (e.g., RAG1 and Cas1) to form adaptive immune systems. Bacteria and archaea acquire resistance to viruses and plasmids by preferentially integrating fragments of foreign DNA at one end of a CRISPR locus. DNA motifs upstream of the CRISPR (i.e., leader) facilitate integration at the first CRISPR repeat. But how do these upstream DNA motifs act over large distances of 130 bp, or roughly 440 A, to regulate integration allosterically? Here, we determine the structure of a 560 KDa integration complex that explains how the CRISPR leader DNA recruits Cas (i.e., Cas1-2/3) and non-Cas proteins (i.e., IHF). Cas1-2/3 and IHF cooperate to fold the genome into a successive U-shaped bend and a loop. The genomic U-bend traps foreign DNA against the integrase, whereas the genomic loop positions the leader-repeat junction at the Cas1 active site. The foreign DNA and the CRISPR repeat wrap around opposite faces of Cas2, poised for a Cas1-catalyzed strand-transfer reaction. The post-integration structure suggests that strand-transfer releases tension in the DNA loop. Therefore Cas1-2/3 may harness protein-induced DNA tension to favor the completion of the isoenergetic integration reaction. Cas1-2/3 interacts extensively with the leader and repeat without making sequence-specific contacts, and we demonstrate that protein-mediated folding of DNA drives integration into diverse sequences. These results reveal Cas1-2/3 and IHF strain DNA to enhance integration allosterically and suggest a mechanism for the de novo generation of new CRISPRs. Further, to address an urgent need for inexpensive and rapid detection of viruses, we recently repurposed a CRISPR immune signaling pathway to detect SARS-CoV-2 in patient samples. A.S-F. is a postdoctoral fellow of the Life Science Research Foundation, supported by the Simons Foundation. A.S-F. is supported by the PDEP award from the Burroughs Wellcome Fund, and by the National Institutes of Health, United States grant 1K99GM147842. This work was also supported by NSF (1828765), NIH (U24 GM129539, R35GM134867).Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

SARS-CoV-2 Nsp13 Catalytic Efficiency is Regulated by ATP: Mg2+ Stoichiometry and Functional Cooperativity Among Nsp13 Molecules

Coronavirus disease 19 (COVID-19) is a highly contagious and lethal disease caused by the SARS-CoV-2 positive-strand RNA virus. Nonstructural protein 13 (Nsp13) is the highly conserved ATPase/helicase required for replication of the SARS-CoV-2 genome which allows for the infection and transmission of COVID-19. We biochemically characterized the purified recombinant SARS-CoV-2 Nsp13 helicase protein expressed using a eukaryotic cell-based system and characterized its catalytic functions, focusing on optimization of its reaction conditions and assessment of functional cooperativity among Nsp13 molecules during unwinding of duplex RNA substrates. These studies allowed us to carefully determine the optimal reaction conditions for binding and unwinding various nucleic acid substrates. Previously, ATP concentration was suggested to be an important factor for optimal helicase activity by recombinant SARS-CoV-1 Nsp13. Apart from a single study conducted using fixed concentrations of ATP, the importance of the essential divalent cation for Nsp13 helicase activity had not been examined. Given the importance of the divalent metal ion cofactor for ATP hydrolysis and helicase activity, we assessed if the molar ratio of ATP to Mg2+ was important for optimal SARS-CoV-2 Nsp13 RNA helicase activity. We determined that Nsp13 RNA helicase activity was dependent on ATP and Mg2+ concentrations with an optimum of 1 mM Mg2+ and 2 mM ATP. Next, we examined Nsp13 helicase activity as a function of equimolar ATP:Mg2+ ratio and determined that helicase activity decreased as the equimolar concentration increased, especially above 5 mM. We determined that Nsp13 catalytic functions are sensitive to Mg2+ concentration suggesting a regulatory mechanism for ATP hydrolysis, duplex unwinding, and protein remodeling, processes that are implicated in SARS-CoV-2 replication and proofreading to ensure RNA synthesis fidelity. Evidence is presented that excess Mg2+ impairs Nsp13 helicase activity by dual mechanisms involving both allostery and ionic strength. In addition, using single-turnover reaction conditions, Nsp13 unwound partial duplex RNA substrates of increasing doublestranded regions (16-30 base pairs) with similar kinetic efficiency, suggesting the enzyme unwinds processively in this range under optimal reaction conditions. Furthermore, we determined that Nsp13 displayed sigmoidal behavior for helicase activity as a function of enzyme concentration, suggesting that functional cooperativity and oligomerization are important for optimal activity. The observed functional cooperativity of Nsp13 protomers suggests the essential coronavirus RNA helicase has roles in RNA processing events beyond its currently understood involvement in the SARS-CoV-2 replication-transcription complex (RTC), in which it was suggested that only one of the two Nsp13 subunits has a catalytic function, whereas the other has only a structural role in complex stability. Altogether, the intimate regulation of Nsp13 RNA helicase by divalent cation and protein oligomerization suggests drug targets for modulation of enzymatic activity that may prove useful for the development of novel anti-coronavirus therapeutic strategies. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

The SARS-CoV-2 Nsp13 Helicase Required for Coronavirus Replication Interacts with Structured Nucleic Acids in a Strand-Specific Manner and Catalyzes a Novel Protein-RNA Remodeling Activity Implicated in the Proofreading Mechanism of the Replication-Transc

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded, positive-sense RNA virus responsible for COVID-19, requires a set of virally encoded nonstructural proteins that compose a replication-transcription complex (RTC) to replicate its 30 kilobase genome. One such nonstructural protein within the RTC is Nsp13, a highly conserved molecular motor ATPase/helicase. Upon purification of the recombinant SARS-CoV-2 Nsp13 protein expressed using a eukaryotic cell-based system, we biochemically characterized the enzyme by examining its catalytic functions, nucleic acid substrate specificity, and putative protein-nucleic acid remodeling activity. We determined that Nsp13 preferentially interacts with single-stranded (ss) DNA compared to ssRNA during loading to unwind with greater efficiency a partial duplex helicase substrate. The binding affinity of Nsp13 to nucleic acid was confirmed through electrophoretic mobility shift assays (EMSA) by determining that Nsp13 binds to DNA substrates with significantly greater efficiency than RNA. These results demonstrate strand-specific interactions of SARS-CoV-2 Nsp13 that dictate its ability to load and unwind structured nucleic acid substrates. We next determined that Nsp13 catalyzed unwinding of double-stranded (ds) RNA forked duplexes on substrates containing a backbone disruption (neutrally charged polyglycol linker (PGL)) was strongly inhibited when the PGL was positioned in the 5' ssRNA overhang, suggesting an unwinding mechanism in which Nsp13 is strictly sensitive to perturbation of the translocating strand sugar-phosphate backbone integrity. Furthermore, we demonstrated for the first time the ability of the coronavirus Nsp13 helicase to disrupt a high-affinity nucleic acid-protein interaction, i.e., a streptavidin tetramer bound to biotinylated RNA or DNA substrate, in a uni-directional manner and with a preferential displacement of the streptavidin complex from biotinylated ssDNA versus ssRNA. In contrast to the poorly hydrolysable ATP-gamma-S or non-hydrolysable AMP-PNP, ATP supports Nsp13-catalyzed disruption of the nucleic acidprotein complex, suggesting that nucleotide binding by Nsp13 is not sufficient for protein-RNA disruption and the chemical energy of nucleoside triphosphate hydrolysis is required to fuel remodeling of protein bound to RNA or DNA. Our results build upon structural studies of the SARS-CoV-2 RTC in which it was suggested that Nsp13 pushes the RNA polymerase (Nsp12) backward on the template RNA strand. Experimental evidence from our studies demonstrate that Nsp13 helicase efficiently remodels a large high affinity protein-RNA complex in a manner dependent on its intrinsic ATP hydrolysis function. We proposed that this novel biochemical activity of Nsp13 is relevant to its role in SARS-CoV-2 RNA processing functions and replication. It was proposed that Nsp13 facilitates proofreading during coronavirus replication when a mismatched base is inadvertently incorporated into the SARS-CoV-2 genome during replication to reposition the RTC so that the proofreading nuclease complex (Nsp14-Nsp10) can gain access and remove the nascently synthesized nucleotide to ensure polymerase fidelity. Our findings implicate a direct catalytic role of Nsp13 in protein-RNA remodeling during coronavirus genome replication beyond its duplex strand separation or structural stabilization of the RTC, yielding new insight into the proofreading mechanism. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Strategic use of thermo-chemical processes for plastic waste valorization

Plastic is one of the most widely used materials in industries including packaging, building, and construction due to its lightweight, low cost, durability, and versatility. However, the mass production of plastics has exacerbated plastic pollution. Globally, plastic waste is predominantly incinerated, landfilled, or released into the environment;only 5-6% is recycled in the United States. Although conventional management protocols such as incineration and landfilling are evidently effective for plastic waste disposal, they are associated with significant environmental and societal challenges. In addition, most recycled plastic is downcycled, and thus does not provide sufficient incentive to use recycled materials instead of virgin materials. This review discusses thermo-chemical upcycling processes such as (catalytic) pyrolysis and heterogeneous catalysis. Furthermore, we present the recent progress in the thermo-chemical upgrading of single-type plastic waste, heterogeneous plastic mixtures, and post-consumer plastic waste obtained from different locations and, finally, suggest future research directions.

Kinetic analysis of RNA cleavage by coronavirus Nsp15 endonuclease: Evidence for acid-base catalysis and substrate-dependent metal ion activation.

Understanding the functional properties of severe acute respiratory syndrome coronavirus 2 nonstructural proteins is essential for defining their roles in the viral life cycle, developing improved therapeutics and diagnostics, and countering future variants. Coronavirus nonstructural protein Nsp15 is a hexameric U-specific endonuclease whose functions, substrate specificity, mechanism, and dynamics are not fully defined. Previous studies report that Nsp15 requires Mn2+ ions for optimal activity; however, the effects of divalent ions on Nsp15 reaction kinetics have not been investigated in detail. Here, we analyzed the single- and multiple-turnover kinetics for model ssRNA substrates. Our data confirm that divalent ions are dispensable for catalysis and show that Mn2+ activates Nsp15 cleavage of two different ssRNA oligonucleotide substrates but not a dinucleotide. Biphasic kinetics of ssRNA substrates demonstrates that Mn2+ stabilizes alternative enzyme states that have faster substrate cleavage on the enzyme. However, we did not detect Mn2+-induced conformational changes using CD and fluorescence spectroscopy. The pH-rate profiles in the presence and absence of Mn2+ reveal active-site ionizable groups with similar pKas of ca. 4.8 to 5.2. An Rp stereoisomer phosphorothioate modification at the scissile phosphate had minimal effect on catalysis supporting a mechanism involving an anionic transition state. However, the Sp stereoisomer is inactive because of weak binding, consistent with models that position the nonbridging phosphoryl oxygen deep in the active site. Together, these data demonstrate that Nsp15 employs a conventional acid-base catalytic mechanism passing through an anionic transition state, and that divalent ion activation is substrate dependent.

Post-translational modifications: Host defence mechanism, pathogenic weapon, and emerged target of anti-infective drugs

Post-translational modifications are changes introduced to proteins after their translation. They are the means to generate molecular diversity, expand protein function, control catalytic activity and trigger quick responses to a wide range of stimuli. Moreover, they regulate numerous biological processes, including pathogen invasion and host defence mechanisms. It is well established that bacteria and viruses utilize post-translational modifications on their own or their host's proteins to advance their pathogenicity. Doing so, they evade immune responses, target signaling pathways and manipulate host cytoskeleton to achieve survival, replication and propagation. Many bacterial species secrete virulence factors into the host and mediate hostpathogen interactions by inducing post-translational modifications that subvert fundamental cellular processes. Viral pathogens also utilize post translational modifications in order to overcome the host defence mechanisms and hijack its cellular machinery for their replication and propagation. For example, many coronavirus proteins are modified to achieve host invasion, evasion of immune responses and utilization of the host translational machinery. PTMs are also considered potential targets for the development of novel therapeutics from natural products with antibiotic properties, like lasso peptides and lantibiotics. The last decade, significant progress was made in understanding the mechanisms that govern PTMs and mediate regulation of protein structure and function. This urges the identification of relevant molecular targets, the design of specific drugs and the discovery of PTM-based medicine. Therefore, PTMs emerge as a highly promising field for the investigation and discovery of new therapeutics for many infectious diseases.Copyright © 2021 Bentham Science Publishers.

Potential Investment Opportunities in Gcc Healthcare during Covid Pandemic: A Research & Review

The COVID-19 pandemic has brought an additional set of challenges to theeconomiesoftheGulf Cooperation Council (GCC). Theregionhasbeen struggling to attract more and better FDI, constrained by investment climateweaknesses and regional geopolitical tensions. While the projected short-termdeclinesareexpectedtohittheGCC economieshard,thecrisiscouldalso bring new opportunities to benefit from global trends, such as reshoringand restructuring of global and regional value chains. The extent to whichthisispossiblewilldependonsustainingexistingreformsunderway,enactingtargetednew strategiesandmeasuresforthepost-COVID-19context,andreinforcingregionalcooperation.ThisbriefprovidesanoverviewoftheimpactoftheC OVID-19crisisoninvestmentintheregionandhighlights GCC government policy responses to catalyze investment andfoster an inclusive post-crisis recovery.Copyright © 2020 Ubiquity Press. All rights reserved.

Design, Rationalization, and Automation of a Catalytic Sensing Mechanism for Homogeneous SERS Biosensors.

The current pandemic has shown that we need sensitive and deployable diagnostic technologies. Surface-enhanced Raman scattering (SERS) sensors can be an ideal solution for developing such advanced point-of-need (PON) diagnostic tests. Homogeneous (reagentless) SERS sensors work by directly responding to the target without any processing step, making them capable for simple one-pot assays, but their limitation is the achievable sensitivity, insufficient compared to what is needed for sensing of viral biomarkers. Noncovalent DNA catalysis mechanisms have been recently exploited for catalytic amplification in SERS assays. These advances used catalytic hairpin assembly (CHA) and other DNA self-assembly processes to develop sensing mechanisms with improved sensitivities. However, these mechanisms have not been used in OFF-to-ON homogeneous sensors, and they often target the same biomarker, likely due to the complexity of the mechanism design. There is still a strong need for a catalytic SERS sensor with a homogeneous mechanism and a rationalization of the catalytic sensing mechanism to translate this sensing strategy to different targets and applications. We developed and investigated a homogeneous SERS sensing mechanism that uses catalytic amplification based on DNA self-assembly. We systematically investigated the role of three domains in the fuel strand (internal loop, stem, and toehold), which drives the catalytic mechanism. The thermodynamic parameters determined in our studies were used to build an algorithm for automated design of catalytic sensors that we validated on target sequences associated with malaria and SARS-CoV-2 strains. With our mechanism, we were able to achieve an amplification level of 20-fold for conventional DNA and of 36-fold using locked nucleic acids (LNAs), with corresponding improvements observed in the sensor limit of detection (LOD). We also show a single-base sequence specificity for a sensor targeting a sequence associated with the omicron variant, tested against a delta variant target. This work on catalytic amplification of homogeneous SERS sensors has the potential to enable the use of this sensing modality in new applications, such as infectious disease surveillance, by improving the LOD while conserving the sensor's homogeneous character.

Covalent organic frameworks and metal-organic frameworks against pathogenic viruses and antibiotic-resistant bacteria: Diagnostic and therapeutic applications

Antimicrobial resistance and antiviral infections statistics show that the number of global cases has been exponentially increasing;thus there is an unmet need for developing alternatives rather than to continue conventional strategies such as antibiotic administration, since they failed to show promise especially during the past few decades. Among different porous materials, metal-organic frameworks (MOFs) are a class of porous coordination polymers broadly explored in nano- and biomedicine due to their desirable properties, including excellent surface area, structural variability, the richness of their crystal structures/architectures, allowing for engineering synergies between metal nodes, functional linkers, encapsulated substrates or nanoparticles, heterogeneous catalysis, ion exchange, controlled and targeted drug delivery, energetics, etc. MOF-based sensing platforms have shown suitable potentials for specific viral detection. Covalent organic frameworks (COFs) are porous crystalline organic materials with two- or three-dimensional structures, which can be employed for reducing the interaction between the spike protein of SARS-CoV-2 and angiotensin-converting enzyme 2 (ACE2) in addition to other inhibitory effects. These frameworks can be applied for encapsulating antibiotics or antiviral agents against pathogens;they have been also studied for photodynamic inactivation of pathogenic bacteria. Herein, the most recent advancements pertaining to the applications of these frameworks for specific detection and inhibition of pathogenic viruses and antibiotic-resistant bacteria are cogitated, focusing on important challenges and perspectives. This review also provides expert recommendations on the future development and utility of these frameworks to manage antimicrobial resistance and infectious diseases more efficiently. © 2023 Elsevier Ltd

Continuous Glucose Monitoring in Hypoxic Environments Based on Water Splitting-Assisted Electrocatalysis

Conventional enzyme-based continuous glucose sensors in interstitial fluid usually rely on dissolved oxygen as the electron-transfer mediator to bring electrons from oxidase to electrode while generating hydrogen peroxide. This may lead to several problems. First, the sensor may provide biased detection results owing to fluctuation of oxygen in interstitial fluid. Second, the polymer coatings that regulate the glucose/oxygen ratio can affect the dynamic response of the sensor. Third, the glucose oxidation reaction continuously produces corrosive hydrogen peroxide, which may compromise the long-term stability of the sensor. Here, we introduce an oxygen-independent nonenzymatic glucose sensor based on water splitting-assisted electrocatalysis for continuous glucose monitoring. For the water splitting reaction (i.e., hydrogen evolution reaction), a negative pretreatment potential is applied to produce a localized alkaline condition at the surface of the working electrode for subsequent nonenzymatic electrocatalytic oxidation of glucose. The reaction process does not require the participation of oxygen;therefore, the problems caused by oxygen can be avoided. The nonenzymatic sensor exhibits acceptable sensitivity, reliability, and biocompatibility for continuous glucose monitoring in hypoxic environments, as shown by the in vitro and in vivo measurements. Therefore, we believe that it is a promising technique for continuous glucose monitoring, especially for clinically hypoxic patients.

Phospholipase D-Catalyzed Transphosphatidylation for the Synthesis of Rare Complex Phospholipid Species─Hemi-bis(monoacylglycero)phosphate and Bis(diacylglycero)phosphate

Progress in developing synthetic pathways for novel and complex phospholipid species, such as Hemi-bis(monoacylglycero)phosphates (Hemi-BMPs) and bis(diacylglycero)phosphates (BDPs), is essential for expanding the knowledge and availability of rare and uncommon phospholipid species. These structurally complex phospholipid species have recently gained more attention with promising applications, as active pharmaceutical ingredient carriers in multiple COVID-19 vaccines, or biomarkers for numerous lysosomal storage disorders and certain types of cancers. The presented work facilitates the production of a range of structurally diverse Hemi-BMP and BDP products intending to increase the availability and thereby the understanding of the underlying chemistry for these high-valuable compounds. The transphosphatidylation of phosphatidylcholine with a variety of structurally diverse monoacylglycerols and diacylglycerols is proceeded by phospholipase D (PLD) catalysis in a biphasic system. Optimization in regard to enzyme loading (5 U), substrate mole ratio (1:5 mol/mol), temperature (30 °C), and aqueous concentration of (18% v/v) afforded the highest conversion for the model transphosphatidylation of phosphatidylcholine with monoolein, yielding 87% in 2 h. The study additionally proposes a reaction mechanism based on molecular simulation, elegantly elaborating the structural constraints (substrate configuration and character of the fatty acid residues) for access to the active site of PLD accordingly for lower yield of BDPs. The successful system designed for the production of high-valuable Hemi-BMP and BDP-analogues demonstrated in this work promises to enhance the understanding of these complex phospholipids, leading to new scientific breakthroughs. © 2023 American Chemical Society.

Nanomaterials Aspects for Photocatalysis as Potential for the Inactivation of COVID-19 Virus

Coronavirus disease-2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is the most difficult recent global outbreak. Semiconducting materials can be used as effective photocatalysts in photoactive technology by generating various reactive oxidative species (ROS), including superoxide (•O2−) and hydroxyl (•OH) radicals, either by degradation of proteins, DNA, and RNA or by inhibition of cell development through terminating the cellular membrane. This review emphasizes the capability of photocatalysis as a reliable, economical, and fast-preferred method with high chemical and thermal stability for the deactivation and degradation of SARS-CoV-2. The light-generated holes present in the valence band (VB) have strong oxidizing properties, which result in the oxidation of surface proteins and their inactivation under light illumination. In addition, this review discusses the most recent photocatalytic systems, including metals, metal oxides, carbonaceous nanomaterials, and 2-dimensional advanced structures, for efficient SARS-CoV-2 inactivation using different photocatalytic experimental parameters. Finally, this review article summarizes the limitations of these photocatalytic approaches and provides recommendations for preserving the antiviral properties of photocatalysts, large-scale treatment, green sustainable treatment, and reducing the overall expenditure for applications. [ FROM AUTHOR] Copyright of Catalysts (2073-4344) is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Photoredox-Catalyzed Plastic Waste Conversion: Nonselective Degradation versus Selective Synthesis

Plastic waste pollution is becoming one of the most pressing environmental crises due to the large-scale production without satisfactory recycling schemes, especially with the outbreak of the COVID-19 pandemic in recent years. Upcycling of plastic waste into valuable chemicals powered by solar energy presents a substantially untapped opportunity to turn waste into treasure. In this review, the fundamental principles from plastic nonselective degradation to selective synthesis are first clarified. Then, we aim to outline the representative recent advances in photoredox-based catalytic plastic waste conversion. Particular emphasis is placed on the valorization of plastic waste regarding nonselective degradation versus selective synthesis. Finally, we present challenges and individual insights for further exploration of the plastic waste conversion domain. It is anticipated that this timely and critical review would provide an instructive direction and foresight on the selective conversion of plastics to value-added chemical feedstocks, thus stimulating the development of a circular and sustainable plastic economy in the coming decades. © 2023 American Chemical Society.

Catalysis in Latin America

This collection of papers from Latin American catalytic researchers was born from online interaction during the trialing times of the COVID‐19 pandemic. The collection showcases the diversification that the field of catalysis has had in our region and features works from Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela, as well as contributions from Latin American researchers who have developed their careers abroad. [ABSTRACT FROM AUTHOR] Copyright of ChemCatChem is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)