Electrochemical C-H/C-C Bond Oxygenation: A Potential Technology for Plastic Depolymerization.

Herein, we provide eco-friendly and safely operated electrocatalytic methods for the selective oxidation directly or with water, air, light, metal catalyst or other mediators serving as the only oxygen supply. Heavy metals, stoichiometric chemical oxidants, or harsh conditions were drawbacks of earlier oxidative cleavage techniques. It has recently come to light that a crucial stage in the deconstruction of plastic waste and the utilization of biomass is the selective activation of inert C(sp3 )-C/H(sp3 ) bonds, which continues to be a significant obstacle in the chemical upcycling of resistant polyolefin waste. An appealing alternative to chemical oxidations using oxygen and catalysts is direct or indirect electrochemical conversion. An essential transition in the chemical and pharmaceutical industries is the electrochemical oxidation of C-H/C-C bonds. In this review, we discuss cutting-edge approaches to chemically recycle commercial plastics and feasible C-C/C-H bonds oxygenation routes for industrial scale-up.

Design, synthesis, biological evaluation and molecular docking studies of quinoline-anthranilic acid hybrids as potent anti-inflammatory drugs.

Despite the high global prevalence, rheumatoid arthritis lacks a satisfactory treatment. Hence, the present study is undertaken to design and synthesize novel anti-inflammatory compounds. For this, quinoline and anthranilic acid, two medicinally-privileged moieties, were linked by pharmacophore hybridization, and following their computational assessments, three hybrids 5a-c were synthesized in good over all yields. The in vitro and in vivo anti-inflammatory potential of these hybrids was determined by anti-denaturation and anti-proteinase, and carrageenan-induced paw edema models. The computational studies of these hybrids revealed their drug-likeness, optimum pharmacokinetics, and less toxicity. Moreover, they demonstrated high binding affinity (-9.4 to -10.6 kcal mol-1) and suitable binding interactions for TNF-α, FLAP, and COX-II. A three-step synthetic route resulted in the hybrids 5a-c with 83-86% yield of final step. At 50 µg mL-1, the antiprotease and anti-denaturation activity of compound 5b was significantly higher than 5a and 5c. Furthermore, 5b significantly reduced the edema in the right paw of the rats that received carrageenan. The results of this study indicate the medicinal worth of the novel hybrids in treating inflammatory disorders such as rheumatoid arthritis.

What works to support carers of older people and older carers? an international evidence map of interventions and outcomes.

BACKGROUND: Unpaid carers of older people, and older unpaid carers, experience a range of adverse outcomes. Supporting carers should therefore be a public health priority. Our understanding of what works to support carers could be enhanced if future evaluations prioritise under-researched interventions and outcomes. To support this, we aimed to: map evidence about interventions to support carers, and the outcomes evaluated; and identify key gaps in current evidence. METHODS: Evidence gap map review methods were used. Searches were carried out in three bibliographic databases for quantitative evaluations of carer interventions published in OECD high-income countries between 2013 and 2023. Interventions were eligible if they supported older carers (50 + years) of any aged recipient, or any aged carers of older people (50 + years). FINDINGS: 205 studies reported across 208 publications were included in the evidence map. The majority evaluated the impact of therapeutic and educational interventions on carer burden and carers' mental health. Some studies reported evidence about physical exercise interventions and befriending and peer support for carers, but these considered a limited range of outcomes. Few studies evaluated interventions that focused on delivering financial information and advice, pain management, and physical skills training for carers. Evaluations rarely considered the impact of interventions on carers' physical health, quality of life, and social and financial wellbeing. Very few studies considered whether interventions delivered equitable outcomes. CONCLUSION: Evidence on what works best to support carers is extensive but limited in scope. A disproportionate focus on mental health and burden outcomes neglects other important areas where carers may need support. Given the impact of caring on carers' physical health, financial and social wellbeing, future research could evaluate interventions that aim to support these outcomes. Appraisal of whether interventions deliver equitable outcomes across diverse carer populations is critical.

Interventions for cold homes: a rapid review of the health impacts.

BACKGROUND: Cold homes are associated with an increased risk of adverse health outcomes for older people. To mitigate this risk, homes need to be heated to an appropriate temperature. This review aims to identify interventions designed to improve heating and temperatures within homes and summarize its impact on health, health service utilization and cost effectiveness. METHODS: A rapid review was conducted. Studies assessing the effects of structural, financial, or behavioural interventions designed to improve home temperatures of residents aged 18+ years were eligible. Searches were carried out in four databases. A search for grey literature, and backward and forward citation searching were performed. Data were summarized in a narrative synthesis and mapped using EPPI-Reviewer and EPPI-Mapper software. RESULTS: Eighteen studies reported across 19 publications were included. Structural interventions were associated with better mental health and quality of life, a reduction in health service utilization, and improvements in satisfaction with internal home temperature, social interactions and financial difficulties. The impact on physical health outcomes varied by age, gender and long-term conditions. Evidence about the impact of behavioural interventions was inconsistent. CONCLUSION: Structural improvements to increase home temperatures may offer the potential to improve some aspects of health. However, the impact on physical health, including which groups are most likely to benefit, is unclear. Key gaps include the lack of evidence about the impact of financial interventions, and the impact of all types of interventions, on quality of life, mortality and costs.

Arenes and Heteroarenes C-H Functionalization Under Enabling Conditions: Electrochemistry, Photoelectrochemistry & Flow Technology.

C-H bond functionalization generates molecular complexity in single-step transformation. However, the activation of C-H bonds requires expensive metals or stoichiometric amounts of oxidizing/reducing species. In many cases, they often require pre-functionalization of starting molecules. Such pre-activating measures cause waste generation and their separation from the final product is also troublesome. In such a scenario, reactions activating elements generating from renewable energy resources such as electricity and light would be more efficient, green, and cost-effective. Further, incorporation of growing flow technology in chemical transformation processes will accelerate the safer accesses of valuable products. Arenes & heteroarenes are ubiquitous in pharmaceuticals, natural products, medicinal compounds, and other biologically important molecules. Herein, we discussed enabling tools and technologies used for the recent C-H bonds functionalization of arenes and heteroarenes.

A novel method development and validation for determination of 2,4,6-Trinitrotoluene and its metabolites on LC-MS/MS.

LC-MS/MS has recently emerged as the best practice for simultaneous analysis of 2, 4, 6 Trinitrotoluene (TNT) and its metabolites. We have developed and validated an LC-MS/MS method for simultaneous quantification of 2, 4, 6 Trinitrotoluene (TNT) and its metabolites 4-ADNT, 2-ADNT, 2,4-DNT, and 2,6-DNT in urine samples. These four metabolites were acid hydrolyzed using 1 mL of urine followed by extraction using n-Hexane and ethyl acetate as an extracting solvent. Separation was achieved by centrifugation, and the supernatant was dried under nitrogen, reconstituted with water and acetonitrile, and then filtered. Chromatographic separation was achieved on Agilent Poroshel 120 EC-C18 column (2.1 mm × 75 mm × 2.7 µm) utilizing two mobile phases 0.1% formic acid in water and 0.1% formic acid in acetonitrile in gradient flow. The validated AMR of TNT and its metabolites was 7.8-1000 ng/mL. The method showed an excellent correlation (>0.99) for TNT and its metabolites. Accuracy and within/between day precision of TNT and its metabolites were within ±15%. The integrity of diluted samples was maintained for each dilution factor. The method was found stable after storage and freeze-thaw cycle. The presented method can be used for TNT screening in occupationally exposed ordnance factory workers.

C-H Bond Functionalization under Electrochemical Flow Conditions.

Electrochemical C-H functionalization is a rapidly growing area of interest in organic synthesis. To achieve maximum atom economy, the flow electrolysis process is more sustainable. This allows shorter reaction times, safer working environments, and better selectivities. Using this technology, the problem of overoxidation can be reduced and less emergence of side products or no side products are possible. Flow electro-reactors provide high surface-to-volume ratios and contain electrodes that are closely spaced where the diffusion layers overlap to give the desired product, electrochemical processes can now be managed without the need for a deliberately added supporting electrolyte. Considering the importance of flow electrochemical C-H functionalization, a comprehensive review is presented. Herein, we summarize flow electrolysis for the construction of C-C and C-X (X=O, N, S, and I) bonds formation. Also, benzylic oxidation and access to biologically active molecules are discussed.

Renewable Electricity Enables Green Routes to Fine Chemicals and Pharmaceuticals.

Syntheses of chemicals using renewable electricity and when generating high atom economies are considered green and sustainable processes. In the present state of affairs, electrochemical manufacturing of fine chemicals and pharmaceuticals is not as common place as it could be and therefore, merits more attention. There is also a need to turn attention toward the electrochemical synthesis of valuable chemicals from recyclable greenhouse gases that can accelerate the process of circular economy. CO2 emissions are the major contributor to human-induced global warming. CO2 conversion into chemicals is a valuable application of its utilisation and will contribute to circular economy while maintaining environmental sustainability. Herein, we present an overview of electro-carboxylation, including mechanistic aspects, which forms carboxylic acids using molecular carbon dioxide. We also discuss atom economies of electrochemical fluorination, methoxylation and amide formation reactions.

Protection of pancreatic ß-cell by phosphocreatine through mitochondrial improvement via the regulation of dual AKT/IRS-1/GSK-3ß and STAT3/Cyp-D signaling pathways.

Diabetes mellitus (DM) is a metabolic syndrome, caused by insufficient insulin secretion or insulin resistance (IR). DM enhances oxidative stress and induces mitochondrial function in different kinds of cell types, including pancreatic ß-cells. Our previous study has showed phosphocreatine (PCr) can advance the mitochondrial function through enhancing the oxidative phosphorylation and electron transport ability in mitochondria damaged by methylglyoxal (MG). Our aim was to explore the potential role of PCr as a molecule to protect mitochondria from diabetes-induced pancreatic ß-cell injury with insulin secretion deficiency or IR through dual AKT/IRS-1/GSK-3ß and STAT3/Cyclophilin D (Cyp-D) signaling pathways. MG-induced INS-1 cell viability, apoptosis, mitochondrial division and fusion, the morphology, and function of mitochondria were suppressed. Flow cytometry was used to detect the production of intracellular reactive oxygen species (ROS) and the changes of intracellular calcium, and the respiratory function was measured by oxygraph-2k. The expressions of AKT, IRS-1, GSK-3ß, STAT3, and Cyp-D were detected using Western blot. The result showed that the oxidative stress-related kinases were significantly restored to the normal level after the pretreatment with PCr. Moreover, PCr pretreatment significantly inhibited cell apoptosis, decreased intracellular calcium, and ROS production, and inhibited mitochondrial division and fusion, and increased ATP synthesis damaged by MG in INS-1 cells. In addition, pretreatment with PCr suppressed Cytochrome C, p-STAT3, and Cyp-D expressions, while increased p-AKT, p-IRS-1, p-GSK-3ß, caspase-3, and caspase-9 expressions. In conclusion, PCr has protective effect on INS-1 cells in vitro and in vivo, relying on AKT mediated STAT3/ Cyp-D pathway to inhibit oxidative stress and restore mitochondrial function, signifying that PCr might become an emerging candidate for the cure of diabetic pancreatic cancer ß-cell damage.

Using Exogenous Melatonin, Glutathione, Proline, and Glycine Betaine Treatments to Combat Abiotic Stresses in Crops.

Abiotic stresses, such as drought, salinity, heat, cold, and heavy metals, are associated with global climate change and hamper plant growth and development, affecting crop yields and quality. However, the negative effects of abiotic stresses can be mitigated through exogenous treatments using small biomolecules. For example, the foliar application of melatonin provides the following: it protects the photosynthetic apparatus; it increases the antioxidant defenses, osmoprotectant, and soluble sugar levels; it prevents tissue damage and reduces electrolyte leakage; it improves reactive oxygen species (ROS) scavenging; and it increases biomass, maintains the redox and ion homeostasis, and improves gaseous exchange. Glutathione spray upregulates the glyoxalase system, reduces methylglyoxal (MG) toxicity and oxidative stress, decreases hydrogen peroxide and malondialdehyde accumulation, improves the defense mechanisms, tissue repairs, and nitrogen fixation, and upregulates the phytochelatins. The exogenous application of proline enhances growth and other physiological characteristics, upregulates osmoprotection, protects the integrity of the plasma lemma, reduces lipid peroxidation, increases photosynthetic pigments, phenolic acids, flavonoids, and amino acids, and enhances stress tolerance, carbon fixation, and leaf nitrogen content. The foliar application of glycine betaine improves growth, upregulates osmoprotection and osmoregulation, increases relative water content, net photosynthetic rate, and catalase activity, decreases photorespiration, ion leakage, and lipid peroxidation, protects the oxygen-evolving complex, and prevents chlorosis. Chemical priming has various important advantages over transgenic technology as it is typically more affordable for farmers and safe for plants, people, and animals, while being considered environmentally acceptable. Chemical priming helps to improve the quality and quantity of the yield. This review summarizes and discusses how exogenous melatonin, glutathione, proline, and glycine betaine can help crops combat abiotic stresses.

Interference of morintides on some virulence determinants of selected bacterial pathogens.

In this study, small antimicrobial peptides of <10 kDa (AMPs) from Moringa oleifera L were separated from crude protein by Ultra-15 Centrifugal filter devices and partially purified. The potency of morintides to interfere with the virulence determinants like biofilms, siderophores and elastase of selected bacteria was investigated by spectrophotometric method and Pseudomonas quinolone signal (PQS) by Thin-layer chromatography (TLC). GraphPad Prism 5.0 was used for statistical purpose. Assays were subjected to a two-way analysis of variance with Bonferroni as post-test. Shigella flexneri, Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus, showed a decrease in the attachment of cells to form biofilm in the presence of the morintides. While Pseudomonas aeruginosa and Salmonella typhi showed an increase in the attachment of cells to form biofilms. Morintides were very effective in the disruption of developed biofilms in cases of S. aureus, E. coli, K. pneumoniae from surgical wounds and S. flexneri, while others remained ineffective in the disruption of developed biofilms. Siderophore production was decreased by all bacterial strains under investigation in the presence of morintides except P. aeruginosa. The outcome of the research may have a significant contribution to drug discovery against antibiotic resistant biofilms of bacteria.

The geriatrician's role in end-of-life care.

Healthcare aims to help older people to live well, but ultimately must also support them to die well. Most people die in old age, but predicting death in both short- and long-term is impossible for many, although not all, older people. Frail older people live with hope and pride in coping, and often anticipate recovery when ill. Key objectives of healthcare for older people are to maintain independence, minimise suffering and preserve dignity, which requires active medical, mental health and rehabilitation management, even when extending life is not the main goal. Thorough medical diagnosis and appropriate treatment and rehabilitation minimise disability, physical and mental distress and problems resulting from acute illness and crises. In these terms, 'health gain' can be achieved from medical intervention, even when life expectancy is short. Assumptions derived from cancer care about lack of reversibility with medical interventions are sometimes unwarranted. This has to be balanced against investigation- and treatment-burden, including that associated with hospital admission and the adverse effects of drugs and therapy interventions, and the need to respect the identity and autonomy of individuals. The resolution of these tensions requires anticipation of care options, multi-professional assessment, judicious and targeted treatment, good communication with patients and stakeholders and rigorous shared decision-making. In this commentary, we compare geriatric and palliative medicine, and describe how the geriatric medical approach can deliver appropriate healthcare towards the end of life. This is well supported by the broad knowledge, skill-set, flexibility and professional values displayed by geriatricians working in multi-professional teams.

Electrochemical Phosphorylation of Organic Molecules.

Organophosphorus chemistry is a broad field with multi-dimensional applications in research area of organic, biology, drug design and agrochemicals. Conventional methods have been adopted extensively to access phosphorylated compounds that rely on the use of toxic, moisture sensitive phosphorylating agents and occur in the presence of oxidants, catalysts, as well as high temperatures and harsh conditions are required for complete transformations. However, recent progress has been made for phosphorylation reactions using electricity to introduce green and sustainable synthetic procedures. These reactions can be performed at mild conditions and proceed with excellent atom economy. Herein, we targeted electrochemical phosphorylation reactions with generation of new bonds such as C(sp3 ) -P, C(sp2 ) -P, O-P, N-P, S-P and Se-P. This review is aimed to offer an overview of recent developments in the synthetic methodology to easy access of organophosphorus compounds using electrochemistry.

Decade of 2D-materials-based RRAM devices: a review.

Two dimensional (2D) materials have offered unique electrical, chemical, mechanical and physical properties over the past decade owing to their ultrathin, flexible, and multilayer structure. These layered materials are being used in numerous electronic devices for various applications, and this review will specifically focus on the resistive random access memories (RRAMs) based on 2D materials and their nanocomposites. This study presents the device structures, conduction mechanisms, resistive switching properties, fabrication technologies, challenges and future aspects of 2D-materials-based RRAMs. Graphene, derivatives of graphene and MoS2 have been the major contributors among 2D materials for the application of RRAMs; however, other members of this family such as hBN, MoSe2, WS2 and WSe2 have also been inspected more recently as the functional materials of nonvolatile RRAM devices. Conduction in these devices is usually dominated by either the penetration of metallic ions or migration of intrinsic species. Most prominent advantages offered by RRAM devices based on 2D materials include fast switching speed (<10 ns), less power losses (10 pJ), lower threshold voltage (<1 V) long retention time (>10 years), high electrical endurance (>108 voltage cycles) and extended mechanical robustness (500 bending cycles). Resistive switching properties of 2D materials have been further enhanced by blending them with metallic nanoparticles, organic polymers and inorganic semiconductors in various forms.

Combining ability and heterosis for grain iron biofortification in bread wheat.

BACKGROUND: Iron is one of the nutrients that is essential for the human body. Despite the abundance of iron on earth, about two billion people worldwide are affected by iron deficiency. Iron biofortification of wheat, instead of supplementation and food fortification, provides a pragmatic approach to solve the problem of iron deficiency. In this study, 144 diverse wheat genotypes were evaluated for grain iron and yield potential, to estimate the potential for the iron biofortification of high-yielding wheat varieties. RESULTS: Genotypes did not differ significantly across the species, but within species the differences were significant for grain iron content and the phytate:iron molar ratio. Triticum aestivum (bread wheat) had the highest yield potential with more diversity than other Triticum species. Genotypes with high iron contents were crossed with high-yielding genotypes in line × tester fashion to check the gene action controlling these traits. The combining ability analysis showed non-additive gene action controlling grain iron, grain phytate, and grain yield. Heterosis manifestation also indicated some transgressive segregates with high specific combining ability effects. CONCLUSION: There was considerable genetic potential for improving the grain iron content in the germplasm to provide an economical and long-lasting solution to benefit an iron-deficient population. Triticum aestivum had the highest variation and potential for iron biofortification. This study indicated the possibility of simultaneous improvement in grain iron and grain yield by producing a new variety through continuous selective breeding. © 2019 Society of Chemical Industry.

Incidence, clinical evaluation and antimicrobial susceptibility pattern of bacteria isolated from diabetic patients.

Diabetes mellitus (DM) is classified as an endocrinological disorder of metabolism, which is marked by an increased rise in prevalence as well as incidence around the globe. The main aim of the study includes an assessment of the incidence, clinical profile evaluation and susceptibility pattern of bacteria against antimicrobial drugs in diabetic subjects. A total of 280 cases were included in the study of which the patients diagnosed with diabetes were assessed for their biochemical profiles as well as culture and sensitivity assays. 106 patients were diagnosed with diabetes out of 280 and were also associated with certain physiological disorders. Among these 106 patients, 103 patients showed an incidence of microbial infections. Of these patients, 63 were males, and 40 were females. Significant activities were observed against Klebsiella by tazobactam (68.8%). Sulzone (cefoperozone + sulbactam) demonstrated the most significant antimicrobial activities against Staphylococcus aureus (87.5%). Efficacy of Cefipime against Pseudomonas was quite substantial (66.6%) followed by Sulphamethazole (61.1%). Maximum activities were observed by cefixime against E. coli (61.5%) followed by nitrofurantoin (43.5%). Infections caused by Pseudomonas and Staphylococcus aureus were present in 18 and 8 patients, respectively.

Memory of Chirality in Flow Electrochemistry: Fast Optimisation with DoE and Online 2D-HPLC.

Amino acid derivatives undergo non-Kolbe electrolysis to afford enantiomerically enriched α-alkoxyamino derivatives through intermediate chiral carbenium ions. The products contain N,O-acetals which are important structural motifs found in bioactive natural products. The reaction is performed in a continuous flow electrochemical reactor coupled to a 2D-HPLC for immediate online analysis. This allowed a fast screening of temperature, electrode material, current, flow-rate and concentration in a DoE approach. The combination with online HPLC demonstrates that also stereoselective reactions can benefit from a hugely accelerated optimisation by combining flow electrochemistry with multidimensional analysis.

Correction to: Identification of novel mutations in congenital afibrinogenemia patients and molecular modeling of missense mutations in Pakistani population.

[This corrects the article DOI: 10.1186/s12959-017-0143-3.].

The dynamic distribution of duck Tembusu virus in the spleen of infected shelducks.

BACKGROUND: Duck Tembusu virus (DTMUV) is a novel member of Flavivirus. The isolated and purified DTMUV strain XZ-2012 was used as a strain model, to intramuscularly inject the six-month egg-laying shelducks with the infective dose of 104TCID50. The dynamic distribution of the virus in spleen at different time post-infection (pi) was studied using RT-PCR, RT-qPCR, ELISA, immunofluorescence and transmission electron microscopy (TEM). RESULT: The results showed that the virus occurred in the spleen after 2 hpi and lasted up to 18 dpi. The registered viral load increased from 2 hpi to 3 dpi, and then it diminished from 6 dpi to 18 dpi with a slight rise at 12 dpi. From 2 hpi to 6 dpi the DTMUV particles were mostly distributed in the periellipsoidal lymphatic sheath (PELS) of spleen white pulp, few being found in the sheathed capillary. From 9 dpi to 18 dpi, the DTMUV particles were migrating into periarterial lymphatic sheaths (PALS) around the central artery through the red pulp. Under TEM, the virus particles could be observed mostly in lymphocytes and macrophages. CONCLUSION: It was suggested that DTMUV invaded lymphocytes and macrophages of the spleen at 2 hpi and replicated significantly from 1 dpi to 3 dpi, being eliminated from 9 dpi to 18 dpi. This is the first study on the dynamic distribution of DTMUV from invasion to elimination in duck spleen conducted by molecular and morphological methods. It could provide theoretical basis for the occurrence, development and detoxification of the virus in the organs of the immune system.

Lipophagy contributes to long-term storage of spermatozoa in the epididymis of the Chinese soft-shelled turtle Pelodiscus sinensis.

Spermatozoa are known to be stored in the epididymis of the Chinese soft-shelled turtle Pelodiscus sinensis for long periods after spermiation from the testes, but the molecular mechanisms underlying this storage are largely unknown. In this study, epididymal spermatozoa were investigated to determine the potential molecular mechanism for long-term sperm storage in P. sinensis. Transmission electron microscopy (TEM) and Oil red O staining indicated that unusually large cytoplasmic droplets containing lipid droplets (LDs) were attached to the epididymal spermatozoa. However, the content of LDs decreased gradually with the sperm storage. LDs were surrounded by autophagic vesicles and sequestered as degradative cargo within autophagosome. Immunofluorescence and western blotting demonstrated that autophagy in spermatozoa increased gradually with the storage time. Invitro studies found that spermatozoa obtained from soft-shelled turtles in January can survive more than 40 days at 4°C. Furthermore, immunofluorescence and TEM showed that autophagy was involved in the degradation of LDs with the extension of sperm incubation. Inhibition of autophagy with 3-methyladenine significantly suppressed LD degradation. Moreover, adipose triglyceride lipase was involved in the metabolism of LDs. These findings indicate that lipophagy was activated to maximise LD breakdown, which contributes to long-term sperm storage in the epididymis of P. sinensis.