Mechanistic insights into sulfur source-driven physiological responses and metabolic reorganization in the fuel-biodesulfurizing Rhodococcus qingshengii IGTS8.

Comparative proteomics and untargeted metabolomics were combined to study the physiological and metabolic adaptations of Rhodococcus qingshengii IGTS8 under biodesulfurization conditions. After growth in a chemically defined medium with either dibenzothiophene (DBT) or MgSO4 as the sulfur source, many differentially produced proteins and metabolites associated with several metabolic and physiological processes were detected including the metabolism of carbohydrates, amino acids, lipids, nucleotides, vitamins, protein synthesis, transcriptional regulation, cell envelope biogenesis, and cell division. Increased production of the redox cofactor mycofactocin and associated proteins was one of the most striking adaptations under biodesulfurization conditions. While most central metabolic enzymes were less abundant in the presence of DBT, a key enzyme of the glyoxylate shunt, isocitrate lyase, was up to 26-fold more abundant. Several C1 metabolism and oligotrophy-related enzymes were significantly more abundant in the biodesulfurizing culture. R. qingshengii IGTS8 exhibited oligotrophic growth in liquid and solid media under carbon starvation. Moreover, the oligotrophic growth was faster on the solid medium in the presence of DBT compared to MgSO4 cultures. In the DBT culture, the cell envelope and phospholipids were remodeled, with lower levels of phosphatidylethanolamine and unsaturated and short-chain fatty acids being the most prominent changes. Biodesulfurization increased the biosynthesis of osmoprotectants (ectoine and mannosylglycerate) as well as glutamate and induced the stringent response. Our findings reveal highly diverse and overlapping stress responses that could protect the biodesulfurizing culture not only from the associated sulfate limitation but also from chemical, oxidative, and osmotic stress, allowing efficient resource management. IMPORTANCE Despite decades of research, a commercially viable bioprocess for fuel desulfurization has not been developed yet. This is mainly due to lack of knowledge of the physiology and metabolism of fuel-biodesulfurizing bacteria. Being a stressful condition, biodesulfurization could provoke several stress responses that are not understood. This is particularly important because a thorough understanding of the microbial stress response is essential for the development of environmentally friendly and industrially efficient microbial biocatalysts. Our comparative systems biology studies provide a mechanistic understanding of the biology of biodesulfurization, which is crucial for informed developments through the rational design of recombinant biodesulfurizers and optimization of the bioprocess conditions. Our findings enhance the understanding of the physiology, metabolism, and stress response not only in biodesulfurizing bacteria but also in rhodococci, a precious group of biotechnologically important bacteria.

Litoribacterium kuwaitense gen. nov., sp. nov., isolated from a Kuwait tidal flat.

A Gram-stain-positive, strictly aerobic, spore-forming, rod-shaped and non-motile bacterium designated strain SIJ1T was obtained from tidal flat sediment collected from the northern shore of Kuwait Bay, northwest of the Arabian Gulf. Strain SIJ1T grew optimally at 30 °C and pH 7-8 in the presence of 6 % (w/v) NaCl. The cell-wall peptidoglycan was based on meso-diaminopimelic acid and an unsaturated menaquinone with seven isoprene units (MK-7) was the predominant respiratory quinone. It contained anteiso-C15 : 0, iso-C16 : 0 and iso-C15 : 0 as the major fatty acids and ribose as the major whole-cell sugar. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipid, an unidentified glycolipid, phosphoglycolipid and an unidentified lipid. Phylogenetic analysis based on 16S rRNA genes revealed that SIJ1T showed a distinct evolutionary lineage within the Firmicutes. The DNA G+C content was 43.1 mol% and the full genome analysis for strain SIJ1T showed that it had a genome size of 3 989 945 bp and contained 4085 predicted protein-encoding genes. The SIJ1T annotated genome showed more stress resistance encoding genes in comparison to its closely related strains. The amino acid identity and average nucleotide identity data for the whole genome proved that strain SIJ1T does indeed represent a novel genus. The strain was distinguishable from the phylogenetically related genera through differences in several phenotypic properties. On the basis of the phenotypic, phylogenetic and genetic data, strain SIJ1T represents a novel genus and species in the family Bacillaceae, for which the name Litoribacterium kuwaitense gen. nov., sp. nov. is proposed. The type strain is SIJ1T (=DSM 28862T=LMG 28316T).

Quantitative assessment of renal structural and functional changes in chronic kidney disease using multi-parametric magnetic resonance imaging.

BACKGROUND: Multi-parametric magnetic resonance imaging (MRI) provides the potential for a more comprehensive non-invasive assessment of organ structure and function than individual MRI measures, but has not previously been comprehensively evaluated in chronic kidney disease (CKD). METHODS: We performed multi-parametric renal MRI in persons with CKD (n = 22, 61 ± 24 years) who had a renal biopsy and measured glomerular filtration rate (mGFR), and matched healthy volunteers (HV) (n = 22, 61 ± 25 years). Longitudinal relaxation time (T1), diffusion-weighted imaging, renal blood flow (phase contrast MRI), cortical perfusion (arterial spin labelling) and blood-oxygen-level-dependent relaxation rate (R2*) were evaluated. RESULTS: MRI evidenced excellent reproducibility in CKD (coefficient of variation <10%). Significant differences between CKD and HVs included cortical and corticomedullary difference (CMD) in T1, cortical and medullary apparent diffusion coefficient (ADC), renal artery blood flow and cortical perfusion. MRI measures correlated with kidney function in a combined CKD and HV analysis: estimated GFR correlated with cortical T1 (r = -0.68), T1 CMD (r = -0.62), cortical (r = 0.54) and medullary ADC (r = 0.49), renal artery flow (r = 0.78) and cortical perfusion (r = 0.81); log urine protein to creatinine ratio (UPCR) correlated with cortical T1 (r = 0.61), T1 CMD (r = 0.61), cortical (r = -0.45) and medullary ADC (r = -0.49), renal artery flow (r = -0.72) and cortical perfusion (r = -0.58). MRI measures (cortical T1 and ADC, T1 and ADC CMD, cortical perfusion) differed between low/high interstitial fibrosis groups at 30-40% fibrosis threshold. CONCLUSION: Comprehensive multi-parametric MRI is reproducible and correlates well with available measures of renal function and pathology. Larger longitudinal studies are warranted to evaluate its potential to stratify prognosis and response to therapy in CKD.

Nano-sized formazan analogues: Synthesis, structure elucidation, antimicrobial activity and docking study for COVID-19.

Three series of nanosized-formazan analogues were synthesized from the reaction of dithiazone with various types of α-haloketones (ester and acetyl substituted hydrazonoyl chlorides and phenacyl bromides) in sodium ethoxide solution. The structure and the crystal size of the new synthesized derivatives were assured based on the spectral analyses, XRD and SEM data. The antibacterial and antifungal activities were evaluated by agar diffusion technique. The results showed mild to moderate antibacterial activities and moderate to potent antifungal activities. Significant antifungal activities were observed for four derivatives 3a, 3d, 5a and 5g on the pathogenic fungal strains; Aspergillus flavus and Candida albicans with inhibition zone ranging from 16 to 20 mm. Molecular docking simulations of the synthesized compounds into leucyl-tRNA synthetase editing domain of Candida albicans suggested that most formazan analogues can fit deeply forming stable complexes in the active site. Furthermore, we utilized the docking approach to examine the potential of these compounds to inhibit SARS-CoV-2 3CLpro. The results were very promising verifying these formazan analogues as a hopeful antiviral agents.

Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-b]Thiazole Linked Thiadiazole Conjugates.

BACKGROUND: Imidazo[2,1-b]thiazole scaffolds were reported to possess various pharmaceutical activities. RESULTS: The novel compound named methyl-2-(1-(3-methyl-6-(p-tolyl)imidazo[2,1-b]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate 3 acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1-b]thiazole moiety. The reaction of 3 with the appropriate hydrazonoyl halide derivatives 4a-j and 7-9 had produced the respective 1,3,4-thiadiazole derivatives 6a-j and 10-12. The chemical composition of all the newly synthesized derivatives were confirmed by their microanalytical and spectral data (FT-IR, mass spectrometry, 1H-NMR and 13C-NMR). All the produced novel compounds were screened for their anti-proliferative efficacy on hepatic cancer cell lines (HepG2). In addition, a computational molecular docking study was carried out to determine the ability of the synthesized thiadiazole molecules to interact with active site of the target Glypican-3 protein (GPC-3). Moreover, the physiochemical properties of the synthesized compounds were derived to determine the viability of the compounds as drug candidates for hepatic cancer. CONCLUSION: All the tested compounds had exhibited good anti-proliferative efficacy against hepatic cancer cell lines. In addition, the molecular docking results showed strong binding interactions of the synthesized compounds with the target GPC-3 protein with lower energy scores. Thus, such novel compounds may act as promising candidates as drugs against hepatocellular carcinoma.

Grimontia sedimenti sp. nov., isolated from benthic sediments near coral reefs south of Kuwait.

A Gram-stain-negative, rod and rod-curved shaped motile bacterium designated strain S25T was obtained from benthic sediment collected near the Kubbar Island coral reefs south of Kuwait. Phenotypic analysis revealed that strain S25T was slightly halophilic, mesophilic and facultative anaerobic, fermenting d-glucose, d-ribose, d-mannose, d-mannitol, maltose, fructose, gentiobiose, cellobiose, melibiose, trehalose and sucrose. It was positive for oxidase and indole production and negative for arginine dihydrolase and lysine and ornithine decarboxylases. It contained C16 : 1 ω7c/C16 : 1 ω6c (summed feature 3), C18 : 1 ω7c (summed feature 8) and C16 : 0 as the major fatty acids. Strain S25T grew optimally at 30 °C and pH 8 in the presence of 3 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA sequences revealed that strain S25T is related to species of the genus Grimontia, having 99.15 % similarity to 'Grimontia indica' AK16T, 99.08 % to Grimontia celer 96-237T and 98.66 % to Grimontia marina IMCC 5001T. The DNA G+C content was 48.8 mol% and the full genome analysis for the strain S25T showed that the bacterium has a genome size of 5 158 621 bp and contains 4730 predicted protein-encoding genes. The average nucleotide identity values between the S25T genome and the genomes of its nearest matches ranged between 81.39 and 94.16 %. The strain was distinguishable from the phylogenetically related genera through differences in several phenotypic properties. On the basis of the phenotypic, phylogenetic and genetic data, strain S25T represents a novel species in the genus Grimontia, for which the name Grimontia sedimenti sp. nov. is proposed. The type strain of Grimontia sedimenti is S25T (=DSM 28878T=LMG 28315T).

Proto-dolomite formation in microbial consortia dominated by Halomonas strains.

Microbes can be found in hypersaline environments forming diverse populations with complex ecological interactions. Microbes in such environments were found to be involved in the formation of minerals including dolomite, a mineral of economic importance and whose origin has been long-debated. Various reports on in vitro experiments using pure cultures provided evidence for the microbial role in dolomite formation. However, culturing experiments have been limited in scope and do not fully address the possible interactions of the naturally occurring microbial communities; consequently, the ability of microbes as a community to form dolomite has been investigated in this study. Our experiments focused on examining the microbial composition by culturing aerobic heterotrophs from the top hypersaline sediments of Al-Khiran sabkha in Kuwait, a modern dolomite-forming environment. The objectives of this study were to assess the ability of two microbial consortia to form dolomite using enrichment culture experiments, mineralogy, and metagenomics. Proto-dolomite was formed by a microbial community dominated by Halomonas strains whereby degradation of the extracellular polymeric substances (EPS) was observed and the pH changed from 7.00 to 8.58. Conversely, proto-dolomite was not observed within a microbial community dominated by Clostridiisalibacter in which EPS continuously accumulated and the pH slightly changed from 7.00 to 7.29.

Natural Attenuation Potential of Polychlorinated Biphenyl-Polluted Marine Sediments.

The marine environment in Kuwait is polluted with various hazardous chemicals of industrial origin. These include petroleum hydrocarbons, halogenated compounds and heavy metals. Bioremediation with dedicated microorganisms can be effectively applied for reclamation of the polluted marine sediments. However, information on the autochthonous microbes and their ecophysiology is largely lacking. We analyzed sediments from Shuwaikh harbor to detect polychlorinated biphenyls (PCBs) and total petroleum hydrocarbons (TPHs). Then we adopted both culture-dependent and culture-independent (PCR-DGGE) approaches to identify bacterial inhabitants of the polluted marine sediments from Shuwaikh harbor. The chemical analysis revealed spatial variation among the sampling stations in terms of total amount of PCBs, TPHs and the PCB congener fingerprints. Moreover, in all analyzed sediments, the medium-chlorine PCB congeners were more abundant than the low-chlorine and high-chlorine counterparts. PCR-DGGE showed the presence of members of the Proteobacteria, Spirochaetes, Firmicutes and Bacteroidetes in the analyzed sediments. However, Chloroflexi-related bacteria dominated the detected bacterial community. We also enriched a biphenyl-utilizing mixed culture using the W2 station sediment as an inoculum in chemically defined medium using biphenyl as a sole carbon and energy source. The enriched mixed culture consisted mainly of the Firmicute Paenibacillus spp. Sequences of genes encoding putative aromatic ring-hydroxylating dioxygenases were detected in sediments from most sampling stations and the enriched mixed culture. The results suggest the potential of bioremediation as a means for natural attenuation of Shuwaikh harbor sediments polluted with PCBs and TPHs.

Imaging the kidney using magnetic resonance techniques: structure to function.

PURPOSE OF REVIEW: MRI can noninvasively assess the structure and function of the kidney in a single MRI scan session. This review summarizes recent advancements in functional renal MRI techniques, with a particular focus on clinical applications. RECENT FINDINGS: A number of MRI techniques now provide measures of relevance to the pathophysiology of kidney disease. Diffusion-weighted imaging, used in chronic kidney disease and renal transplantation, shows promise as a measure of renal fibrosis. Longitudinal relaxation time (T1) mapping has been utilized in cardiac MRI to measure fibrosis and oedema; recent work shows its potential in the kidney. Blood oxygen-level-dependent MRI to measure renal oxygenation has been extensively studied, but a number of other factors affect results making it hard to draw definite conclusions as to its utility as an independent measure. Phase contrast and arterial spin labelling can measure renal artery blood flow and renal perfusion without exogenous contrast, as opposed to dynamic contrast-enhanced studies. In general, current data on clinical use of functional renal MRI are restricted to cross-sectional studies. SUMMARY: Renal MRI has seen significant recent advances. Current evidence demonstrates its potential, and next steps include wider evaluation of its clinical application.

Podocyte Infolding Glomerulopathy Masquerading as Membranous Nephropathy - A Shared Pathogenesis?

Podocyte infolding glomerulopathy (PIG) is a rare pathological entity, diagnosed by electron microscopic demonstration of diffuse infolding of the podocytes into the glomerular basement membranes. We report the first case from United Kingdom exhibiting typical ultrastructural features of PIG in a male with Type II diabetes mellitus, hypertension and common variable immune deficiency. Renal biopsy revealed phospholipase A2 receptor (PLA2R) immunostain positive membranous nephropathy (MN) but no serum PLA2R antibodies. Diffuse infolding of the podocytes into the glomerular basement membranes along with pathognomonic microspherular and microtubular intra basement membrane clusters distributed diffusely and globally were noted on electron microscopy, diagnostic of PIG. We postulate a shared pathomechanistic link between PIG and MN, highlighting the overlapping features of both conditions.

Novel hybrid thiazoles, bis-thiazoles linked to azo-sulfamethoxazole: Synthesis, docking, and antimicrobial activity.

The reaction of sulfamethoxazolehydrazonoyl chloride with thiosemicarbazones, bis-thiosemicarbazones, or 4-amino-3-mercapto-1,2,4-triazole in dioxane in the presence of triethylamine as a basic catalyst at reflux resulted in the regioselective synthesis of thiazoles and bis-thiazoles linked to azo-sulfamethoxazole as novel hybrid molecules. The structures of the new compounds were confirmed using a range of spectra. Each compound's antibacterial properties were evaluated using the agar well-diffusion technique, and most of them demonstrated significant potency. In silico investigations revealed that the described compounds had strong interactions with the binding sites of MurE ligase, tyrosyl-tRNA synthetase, and dihydropteroate synthase, demonstrating inhibitory activity.

Synthesis, tautomeric structures, and antitumor activity of new perimidines.

New series of perimidine derivatives and fused perimidines were derived from the reaction of ketene aminals 1 and 2 with diazotized anilines or hydrazonoyl chlorides. In addition, 8,10-disubstituted-[1,2,4]triazolo[4,3-a]perimidines (20a-m) were prepared through the reaction of perimidine-2-thione (15) with hydrazonoyl chlorides. The structures of the newly synthesized compounds were established on the basis of spectral data and elemental analyses. Some products were investigated for their antitumor activities against the human breast cancer cell line MCF-7 and the liver carcinoma cell line HEPG-2, and the results of some derivatives showed promising activity.

Disperse dyes based on aminothiophenes: their dyeing applications on polyester fabrics and their antimicrobial activity.

A series of monoazo disperse dyes derived from arylazothienopyridazines were synthesized. Fastness properties of dyed polyester samples were measured. Most of the dyed fabrics tested displayed excellent washing and perspiration fastness and moderate light fastness. Finally, the biological activity of the synthesized dyes against Gram positive bacteria, Gram negative bacteria and yeast were evaluated.

Multiparametric Renal Magnetic Resonance Imaging for Prediction and Annual Monitoring of the Progression of Chronic Kidney Disease over Two Years.

BACKGROUND: Multiparametric renal Magnetic Resonance Imaging (MRI) provides a non-invasive method to assess kidney structure and function, but longitudinal studies are limited. METHODS: A total of 22 patients with CKD category G3-4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m2) were recruited. Annual 3T multiparametric renal MRI scans were performed, comprising total kidney volume (TKV), longitudinal relaxation time (T1), apparent diffusion coefficient (ADC), Arterial Spin Labelling, and Blood Oxygen Level Dependent relaxation time (T2*), with 15 patients completing a Year 2 scan. CKD progression over 2 years was defined as eGFR_slope ≥ -5 mL/min/1.73 m2/year. RESULTS: At baseline, T1 was higher (cortex p = 0.05, medulla p = 0.03) and cortex perfusion lower (p = 0.015) in participants with subsequent progression versus stable eGFR. A significant decrease in TKV and ADC and an increase in cortex T1 occurred in progressors at Year 1 and Year 2, with a significant decrease in perfusion in progressors only at Year 2. The only decline in the stable group was a reduction in TKV. There was no significant change in cortex or medulla T2* at Year 1 or Year 2 for progressors or stable participants. CONCLUSION: Lower renal cortex perfusion and higher T1 in the cortex and medulla may predict CKD progression, while renal cortex T1, TKV, and ADC may be useful to monitor progression. This study provides pilot data for future large-scale studies.

Antiviral Activity of Pyrimidine Containing Compounds: Patent Review.

Viruses are still the most prevalent infectious pathogens on a worldwide scale, with many of them causing life-threatening illnesses in humans. Influenza viruses, because of their significant morbidity and mortality, continue to pose a major threat to human health. According to WHO statistics, seasonal influenza virus epidemics are predicted to cause over 2 million severe illness cases with high death rates yearly. The whole world has been suffering from the COVID-19 epidemic for two years and is still suffering so far, and the deaths from this virus have exceeded three million cases. Because the great majority of viral infections do not have a specific medication or vaccination, discovering novel medicines remains a vital task. This review covers reports in the patent literature from 1980 to the end of 2021 on the antiviral activities of pyrimidine moieties. The patent database, SciFinder, was used to locate patent applications. A large variety of pyrimidine molecules have been produced and tested for antiviral activity over the last decade. These molecules were reported to inhibit a wide range of viruses, including influenza virus, respiratory syncytial virus, rhinovirus, dengue virus, herpes virus, hepatitis B and C, and human immunodeficiency virus. The cytotoxicity of the developed pyrimidine derivatives was tested in almost all reported studies and the selectivity index was calculated to show the selectivity and safety of such molecules. From the remarkable activity of pyrimidine compounds as antivirals for several dangerous viruses, we expect that these derivatives will be used as potent drugs in the very near future.

A facile synthesis of arylazonicotinates for dyeing polyester fabrics under microwave irradiation and their biological activity profiles.

A as textile dyes and the fastness properties of the dyed samples were measured. Most of the dyed fabrics tested displayed very good washing and perspiration fastness and series of 2-hydroxy- and 2-amino-6-substituted-5-arylazonicotinate monoazo compounds 7a-e and 9a-c were prepared via condensation of 3-oxo-3-substituted-2-arylhydrazonals 2a-e with active methylene nitriles 3a-d using microwave irradiation as an energy source. These substances were then tested moderate light fastness. Finally, the biological activity of the synthesized compounds against gram positive bacteria, gram negative bacteria and yeast were evaluated.

One-pot synthesis of disperse dyes under microwave irradiation: dyebath reuse in dyeing of polyester fabrics.

A series of 4-hydroxyphenylazopyrazolopyrimidine disperse dyes were prepared via one-pot reactions of p-hydroxyphenylhydrazone, hydrazine hydrate, and acetylacetone or enaminones using microwave irradiation as an energy source. Structural assignments of the dyes were confirmed by X-ray crystallographic structure determination. Instead of discharging the dyebath after each dyeing cycle, the residual dyebath was spectrophotometrically analyzed and then pH readjusted for a repeat dyeing with longer time. Fastness of the dyed samples was measured after each recycle. Most of the dyed fabrics tested displayed good light fastness and excellent fastness to washing and perspiration. Finally, the biological activity of the synthesized dyes against Gram positive bacteria, Gram negative bacteria and yeast were evaluated.

Identification of Sponge-Associated Bacteria From the Coast of Kuwait and Their Potential Biotechnological Applications.

Sponges are among the most ancient animals harboring complex microbial communities with potential applications in biotechnology. The Arabian Gulf is a thermally stressed enclosed body of water located in an arid region where sponges and their halobionts are understudied. This study combined 16S rRNA next-generation gene amplicon sequencing and cultivation techniques to explore the abundance and diversity of sponge-associated bacteria. Culture-independent techniques showed the associations of more than 25 bacterial phyla with Amphimedon sp., Chondrilla australiensis, Haliclona sp., and Niphates spp. Regarding cultivable bacteria, 315 bacterial isolates associated with the sponge Haliclona sp. were cultivated; these isolates were affiliated with the phyla Proteobacteria and Firmicutes and were distributed among six bacterial genera. Selected strains of Bacillus, Ferrimonas, Pseudovibrio, Shewanella, Spongiobacter, and Vibrio were tested for antimicrobial activity against indicator microorganisms and protease enzyme production. Seven Bacillus strains exhibited weak to moderate growth inhibition against Bacillus subtilis, Staphylococcus aureus, and Candida albicans. Furthermore, 29 different strains of Bacillus, Ferrimonas, Shewanella, and Vibrio exhibited different degrees of positive protease activity. In addition, cultivated strains of Bacillus, Shewanella, Pseudovibrio, and Vibrio were tested for their biomineralization abilities. Herein we report for the first time the isolation of biomineralizing bacteria from sponge tissue where eleven bacterial isolates produced different shapes of calcium carbonate crystals on agar. Our observations shed light on the diversity and biotechnological potentials of sponges-associated bacteria inhabiting one of the world's hottest seas.

Synthesis of New Thiazole Clubbed Imidazo[2,1-b]thiazole Hybrid as Antimycobacterial Agents.

AIMS: The study aims to synthesize bioactive hybrid pharmacophores (thiazole ring and imidazo[2,1-b]thiazole system) by incorporating them into one biological assessment molecular system. BACKGROUND: A literature survey revealed that various imidazo[2,1-b]thiazoles, thiazoles, and hydrazones have powerful antimycobacterial activity. OBJECTIVE: This study demonstrates the effectiveness of molecular hybridization and the scope for imidazo[2,1-b]thiazole-hydrazone-thiazoles to develop as promising antimycobacterial agents. METHODS: Several imidazo[2,1-b]thiazole-hydrazine-thiazoles 5a-g, 7a,b, 9a,b, 11a,b, 13, and 15a,b were generated using a molecular hybridization strategy and assessed against Mycobacterium tuberculosis (ATCC 25618) for their in vitro antituberculous activity. RESULTS: Derivative 7b (MIC = 0.98 µg/mL) has shown the most promising antimycobacterial activity among the series tested. Brief structure-activity relationship studies found that the thiazole of chlorophenyl or pyridine, or coumarin had a significant relation with the antimycobacterial activity. CONCLUSION: The promising antimycobacterial activity of compound 7b compared with the reference drug suggests that this compound may contribute as a lead compound in the search for new potential antimycobacterial agents.

Multiparametric MRI assessment of renal structure and function in acute kidney injury and renal recovery.

BACKGROUND: Acute kidney injury (AKI) is associated with a marked increase in mortality as well as subsequent chronic kidney disease (CKD) and end-stage kidney disease. We performed multiparametric magnetic resonance imaging (MRI) with the aim of identifying potential non-invasive MRI markers of renal pathophysiology in AKI and during recovery. METHODS: Nine participants underwent inpatient MRI scans at time of AKI; seven had follow-up scans at 3 months and 1 year following AKI. Multiparametric renal MRI assessed total kidney volume (TKV), renal perfusion using arterial spin labelling, T1 mapping and blood oxygen level-dependent (BOLD) R2* mapping. RESULTS: Serum creatinine concentration had recovered to baseline levels at 1-year post-AKI in all participants. At the time of AKI, participants had increased TKV, increased cortex/medulla T1 and reduced cortical perfusion compared with the expected ranges in healthy volunteers and people with CKD. TKV and T1 values decreased over time after AKI and returned to expected values in most but not all patients by 1 year. Cortical perfusion improved to a lesser extent and remained below the expected range in the majority of patients by 1-year post-AKI. BOLD R2* data showed a non-significant trend to increase over time post-AKI. CONCLUSIONS: We observed a substantial increase in TKV and T1 during AKI and a marked decrease in cortical perfusion. Despite biochemical recovery at 1-year post-AKI, MRI measures indicated persisting abnormalities in some patients. We propose that such patients may be more likely to have further AKI episodes or progress to CKD and further longitudinal studies are required to investigate this. .