Ru(II)-Catalyzed [4 + 2]-Annulation of 2-Alkenyl/Arylimidazoles with N-Substituted Maleimides and 1,4-Naphthoquinones: Access to Imidazo-Fused Polyheterocycles.

Synthesis of imidazo-fused polyheterocyclic molecular frameworks, viz. imidazo[1,2-a]pyrrolo[3,4-e]pyridines, imidazo[2,1-a]pyrrolo[3,4-c]isoquinolines, and benzo[g]imidazo[1,2-a]quinoline-6,11-diones, has been achieved by the ruthenium(II)-catalyzed [4 + 2] C-H/N-H annulation of 2-alkenyl/2-arylimidazoles with N-substituted maleimides and 1,4-naphthoquinones. The developed protocol is operationally simple, exhibits broad substrate scope with excellent functional group tolerance, and provides the desired products in moderate to good yields. The mechanistic studies suggest that the reaction involves the formation of a C-C bond through Ru-catalyzed C(sp2)-H bond activation followed by intramolecular cyclization.

Catalyst-Controlled Regiodivergent Oxidative Annulation of 2-Arylimidazo[1,2-a]pyridines with Cinnamaldehyde Derivatives for Construction of Fused N-Heterocyclic Frameworks.

Catalyst-dependent regioselective oxidative annulation of 2-arylimidazo[1,2-a]pyridines with cinnamaldehyde derivatives to construct fused N-heterocyclic frameworks has been described. The annulation reaction afforded 5-arylnaphtho[1',2':4,5]imidazo[1,2-a]pyridine-6-carbaldehydes in the presence of [RhCp*Cl2]2 as catalyst while 1,7-diarylimidazo[5,1,2-cd]indolizine-6-carbaldehydes were obtained using Pd(OAc)2 as catalyst. The reaction produced annulated products in good yields and exhibited broad substrate scope and excellent functional group tolerance. The method provides two different isomeric annulated products bearing an aldehyde functionality which can be elaborated into an array of functionalities leading to valuable compounds.

Geographic carbon accounting: The roadmap for achieving net-zero emissions in Mauritius Island.

Significant climate finance gaps exist for small islands in transitioning to net zero, as climate commitments far outweigh the government budget and international financing. To create alignment between resource allocation and climate commitments, a roadmap for strategic and cost-effective decarbonization is of supreme importance. This paper presents a geographic carbon accounting model which incorporates emissions from electricity, transportation, food systems, and human respiration, whilst accounting for the carbon uptake by the terrestrial biosphere in view of identifying high-intensity aggregated emissions estimated in the range of 200-215 ktCO2e in the coastal and inland urban regions of the remote island of Mauritius. An estimated 4641 ktCO2e, representing 79.4% of overall emissions, has been observed to originate from buildings, food, and waste systems. About 1150 ktCO2e, accounting for a share of 19.7%, is derived from transport systems. The study advocates for the enhanced participation of local authorities to better contribute to climate governance, whilst supporting legislative, financial, technological, and behavioural reforms. Despite the relatively low sequestration potential of forests replacing all non-habitable lands, which is estimated at 1002 ktCO2e and representing about 17.1% of annual net emissions, afforestation programmes are encouraged owing to multiple ecosystem services provided by trees.

Renal Hemodynamics and Renin-Angiotensin-Aldosterone System Profiles in Patients With Heart Failure.

OBJECTIVE: Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. We sought to characterize the renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and in controls without HF. METHODS: In this post hoc analysis, the glomerular filtration rate (GFRinulin), effective renal plasma flow (ERPFPAH) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and in 24 controls. Gomez equations were used to derive afferent (RA) and efferent (RE) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous dobutamine (HF, n = 11; non-HF, n = 11) or nitroprusside (HF, n = 18; non-HF, n = 5). RESULTS: The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs the artery in patients with HF vs patients without HF (P < 0.01). In patients with HF, a greater ACE gradient was associated with greater renal vascular resistance (r = 0.42; P 0.007) and greater arteriolar resistances (RA: r = 0.39; P = 0.012; RE: r = 0.48; P = 0.002). Similarly, a greater aldosterone gradient was associated with lower GFR (r = -0.51; P = 0.0007) and renal blood flow (RBF), r = -0.32; P = 0.042) whereas greater PRA gradient with lower ERPF (r = -0.33; P = 0.040), GFR (r = -0.36; P = 0.024), and RBF (r = -0.33; P = 0.036). Dobutamine and nitroprusside treatment decreased the transrenal gradient of ACE (P = 0.012, P < 0.0001, respectively), aldosterone (P = 0.005, P = 0.030) and PRA (P = 0.014, P = 0.002) in patients with HF only. CONCLUSIONS: A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.

Asymmetric Ru/Cinchonine Dual Catalysis for the One-Pot Synthesis of Optically Active Phthalides from Benzoic Acids and Acrylates.

Herein, we report the asymmetric Ru/cinchonine dual catalysis that provides straightforward access to enantioselective synthesis of C-3 substituted phthalides via tandem C-H activation/Michael addition cascade. The use of readily accessible and less expensive [RuCl2(p-cym)]2 and cinchonine catalyst for the one-pot assembly of chiral phthalides greatly overcomes the present trend of using highly sophisticated catalysts. The developed method provides access to both enantiomers of a product using pseudoenantiomeric cinchona alkaloids as catalysts streamlining the synthesis of phthalide in both the optically active forms.

Fabrications of hybrid Polyurethane-Pd doped ZrO2 smart carriers for self-healing high corrosion protective coatings.

The work demonstrates the effective utilization of hybrid Polyurethane - palladium doped zirconium oxide (Pd-ZrO2) as innovative carriers for corrosion protection coatings on steel materials. ZrO2 and Pd-ZrO2 nanoparticles were successfully synthesized using Photodeposition followed by the hydrothermal synthesis method. The synthesized nanoparticles were then incorporated into the polyurethane matrix and characterized using Fourier-transform infrared spectroscopy and scanning electron microscopy (SEM). The FTIR and SEM confirm the presence of ZrO2 and Pd-ZrO2 nanoparticles and their morphologies in polyurethane composites material. The thermogravimetric analysis (TGA) results indicated that the polyurethane matrix remained stable up to 250 °C. At 800 °C, >50% of residues are observed for Pd-ZrO2 - polyurethane in the TGA analysis, which confirms that the primer and nanoparticles addition enhances the thermal stability of the composite. The water contact angle measurement explains the hydrophobic behavior of nanocomposite modified coatings on a mild steel substrate. It indicates that Pd-ZrO2 and primer significantly increase the hydrophobicity of polyurethane. The major advantages of developing water-repellent or hydrophobic surfaces open up a world of possibilities for metals and alloys in terms of corrosion prevention. Electrochemical impedance spectroscopy (EIS) and a salt spray test were used to determine the anti-corrosion behavior of the prepared polymer nanocomposites. The polymer nanocomposite coatings have better anti-corrosive capabilities when compared to pure polyurethane. The corrosion protection efficiency increased from 76.63% to 97.57% upon incorporating 2 wt % of Pd-ZrO2 in the polyurethane matrix. The results confirmed that the modifications on the polyurethane enhanced the hydrophobicity and anti-corrosion properties of the polymer nanocomposite coatings.

Initial Step of Selenite Reduction via Thioredoxin for Bacterial Selenoprotein Biosynthesis.

Many organisms reductively assimilate selenite to synthesize selenoprotein. Although the thioredoxin system, consisting of thioredoxin 1 (TrxA) and thioredoxin reductase with NADPH, can reduce selenite and is considered to facilitate selenite assimilation, the detailed mechanism remains obscure. Here, we show that selenite was reduced by the thioredoxin system from Pseudomonas stutzeri only in the presence of the TrxA (PsTrxA), and this system was specific to selenite among the oxyanions examined. Mutational analysis revealed that Cys33 and Cys36 residues in PsTrxA are important for selenite reduction. Free thiol-labeling assays suggested that Cys33 is more reactive than Cys36. Mass spectrometry analysis suggested that PsTrxA reduces selenite via PsTrxA-SeO intermediate formation. Furthermore, an in vivo formate dehydrogenase activity assay in Escherichia coli with a gene disruption suggested that TrxA is important for selenoprotein biosynthesis. The introduction of PsTrxA complemented the effects of TrxA disruption in E. coli cells, only when PsTrxA contained Cys33 and Cys36. Based on these results, we proposed the early steps of the link between selenite and selenoprotein biosynthesis via the formation of TrxA-selenium complexes.

Energy and carbon budgeting of traditional land use change with groundnut based cropping system for environmental quality, resilient soil health and farmers income in eastern Indian Himalayas.

Energy intensive traditional cereals based monoculture often lead to high greenhouse gas emissions and degradation of land and environmental quality. Present study aimed at evaluating the energy and carbon budget of diversified groundnut (Arachis hypogea L) based cropping system with over existing traditional practice towards the development of a sustainable production technology through restoration of soil and environmental quality and enhancement of farming resiliency by stabilizing farmers' income. The trials comprised of three introduced groundnut based systems viz. groundnut- pea (Pisum sativum), groundnut-lentil (Lens esculenta) and groundnut-toria (Brasssica campestris var. Toria) replacing three existing systems viz. maize (Zea mays L) - fallow, maize - toria, and rice (Oryza sativa L)-fallow systems. Four years study revealed that adoption of groundnut based systems reduced non-renewable energy input use (fertilizers, chemical, machinery and fossil fuels) by 25.5%, consequently that reduced the cost of production. Repeated analysis of variance measurement also affirmed that groundnut based systems (groundnut-pea>groundnut-lentil> groundnut-toria) increased the energy use efficiency, energy productivity, carbon use efficiency, net returns and decreased the specific energy and energy intensiveness. Groundnut based systems increased the mean system productivity and water productivity in terms of groundnut equivalent yield by 3.7 and 3.1 folds over existing practice. The savings of fossil fuel reduced greenhouse gas emissions owing to reduced use of farm machinery and synthetic fertilizers. Groundnut based systems significantly (p < 0.05) enhanced the soil carbon concentration (8.7-18.1%) and enzymatic activities (27.1-51.8%) over existing practice. Consequently, estimated soil quality index values were 35.9-77.3% higher under groundnut based systems than existing practice. Thus, the study indicated the resilient nature of groundnut based systems as an environmentally safe and sustainable production technology for enhancing resource use efficiency, reduce carbon emission, energy intensiveness and cost of production in the Eastern Himalaya region of India and similar ecosystems.

Profiling of selenium and other trace elements in breads from rice and maize cultivated in a seleniferous area of Punjab (India).

The objective of the study was to assess selenium and other elements levels in Indian Roti bread from Se-rich maize and rice using inductively coupled plasma mass-spectrometry. Se levels in Roti bread from Se-rich maize and rice exceeded those in the control samples by a factor of more than 594 and 156, respectively. Using Se-enriched maize increased bread Co, Cr, Mn, Mo, and Zn content, whereas Fe and I levels were reduced. In Se-rich rice-based bread a decrease in Co, Cr, Cu, Fe, I, Mo, and Zn contents was observed. Daily consumption of Se-rich maize and rice bread (100 g) could account for 5.665% and 4.309% from recommended dietary allowance, also exceeding the upper tolerable levels by a factor of 7.8 and 5.9, respectively. Therefore, Roti bread from both Se-rich maize and rice may be considered as an additional source of selenium. At the same time, regular intake of Se-rich grains and its products including breads may cause adverse health effects even after a few days and should be regularly monitored in order to prevent Se overload and toxicity.

Design, fabrication, and characterization of graft co-polymer assisted ocular insert: a state of art in reducing post-operative pain.

PURPOSE: Targeted delivery of drugs at appropriate concentrations to ocular tissues is required to avoid wastage. Hence, advanced systems that maximize the release of poorly soluble drugs and deliver them at ocular sites must be designed. METHODS: In this study, Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol-graft copolymer) was selected as a solubilizer as well as film former for preparing ocular inserts and polyethylene glycol 400 (PEG-400) as a plasticizer. On the basis of an initial phase solubility study, the maximum concentration of Soluplus® possible was used for developing the inserts. An optimized formulation was obtained using a 32-factorial design. Two factors at three levels were used to design the ocular inserts. Soluplus® (X 1) and the plasticizer, PEG-400 (X 2), were set as the independent variables at various levels, and the Rel4h (drug release in 4 h, Y 1) and tensile strength (Y 2) were set as the dependent variables. A pre-formulation study was conducted to select suitable materials. RESULTS: Various physico-chemical parameters of the optimized formulation, including the tensile strength and folding endurance, were studied using FT-IR, DSC, XRD, and SEM. An in vitro dissolution study was conducted to determine the amount of drug released. There was no redness, swelling, or watering of the rabbit eye. CONCLUSION: It was concluded that the ocular inserts of the poorly soluble nepafenac developed using a graft-co-polymer enhanced the solubility and utilization of the drug for a prolonged period.

Integrating genome-wide association study summaries and element-gene interaction datasets identified multiple associations between elements and complex diseases.

Chemical elements are closely related to human health. Extensive genomic profile data of complex diseases offer us a good opportunity to systemically investigate the relationships between elements and complex diseases/traits. In this study, we applied gene set enrichment analysis (GSEA) approach to detect the associations between elements and complex diseases/traits though integrating element-gene interaction datasets and genome-wide association study (GWAS) data of complex diseases/traits. To illustrate the performance of GSEA, the element-gene interaction datasets of 24 elements were extracted from the comparative toxicogenomics database (CTD). GWAS summary datasets of 24 complex diseases or traits were downloaded from the dbGaP or GEFOS websites. We observed significant associations between 7 elements and 13 complex diseases or traits (all false discovery rate (FDR) < 0.05), including reported relationships such as aluminum vs. Alzheimer's disease (FDR = 0.042), calcium vs. bone mineral density (FDR = 0.031), magnesium vs. systemic lupus erythematosus (FDR = 0.012) as well as novel associations, such as nickel vs. hypertriglyceridemia (FDR = 0.002) and bipolar disorder (FDR = 0.027). Our study results are consistent with previous biological studies, supporting the good performance of GSEA. Our analyzing results based on GSEA framework provide novel clues for discovering causal relationships between elements and complex diseases.

Renal SGLT mRNA expression in human health and disease: a study in two cohorts.

Pharmacological Na+-glucose linked cotransporter (SGLT)2 inhibition is being examined as a renal protection strategy in nondiabetic chronic kidney disease. We quantified renal SGLT mRNA expression in healthy controls (HC), glomerulonephritis (GN), and diabetic kidney disease (DKD) to identify differences in expression across a spectrum of renal diseases. mRNA expression of SGLT1 and SGLT2 in renal tubules and glomeruli, obtained using microdissection and microarray techniques, was evaluated in two large cohorts. The European Renal cDNA bank included HC, GN, and DKD (98 glomeruli and 93 tubulointerstitium). The Nephrotic Syndrome Study Network cohort included 124 adults with membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, and IgA nephropathy. Within the European Renal cDNA bank, SGLT2 tubular and glomerular log2 mRNA expression significantly differed across HC, GN, and DKD (P = 0.0009 and P = 0.0004), with the highest expression in HC. Within the Nephrotic Syndrome Study Network, there were no differences in SGLT log2 mRNA expression across GN subtypes. Tubular SGLT2 log2 mRNA expression positively correlated with estimated glomerular filtration rate (by the Modification of Diet in Renal Disease Study equation) and glycated hemoglobin (r = 0.33 and 0.34, P < 0.05) and inversely correlated with interstitial fibrosis (r = -0.21, P < 0.05). In conclusion, SGLT2 mRNA expression was lower in DKD compared with HC or GN and inversely related to interstitial fibrosis. The relationships between SGLT mRNA, protein expression, and transporter activity require further elucidation.

Concentrations of interleukin-6, -8, -10 and tumour necrosis factor-α in the faeces of dogs with acute diarrhoea.

AIM: To compare the concentration of faecal cytokines interleukin (IL)-6, -8, -10, and tumour necrosis factor (TNF)-α in dogs with acute diarrhoea with clinically normal (non-diarrhoeic) dogs. METHODS: A total of 14 dogs presenting with acute diarrhoea, and 25 dogs with no history of gastrointestinal signs in the 2 months prior to enrolment, were recruited from two veterinary hospitals in Melbourne, Australia. Concentrations of IL-6, -8, -10, and TNF-α were measured in faecal samples using canine-specific ELISA. RESULTS: The diarrhoeic dogs were diagnosed with or managed for acute gastroenteritis (n = 6), extra-intestinal neoplasia (n = 2), parvoviral enteritis (n = 1), hepatopathy (n = 1), acute pancreatitis (n = 1), hypoadrenocorticism (n = 1), gastric dilatation volvulus (n = 1) and myelopathy (n = 1). IL-6 was detectable in the faeces of 10/14 (71%) diarrhoeic and 7/25 (28%) non-diarrhoeic dogs, and median concentrations were 10.8 (min 0.0, max 54.0) and 2.0 (min 0.0, max15.0) pg/mL, respectively (p = 0.01). IL-8 was detectable in the faeces of all diarrhoeic and 11 non-diarrhoeic dogs, and median concentrations were 149.7 (min 3.72, max 730.1) and 3.4 (min 0.0, max 22.5) pg/mL, respectively (p < 0.001). TNF-α was detected in the faeces of two of the diarrhoeic dogs (3.4 and 15.6 pg/mL) and none of the non-diarrhoeic dogs. IL-10 was not detected in the faeces of any dog. CONCLUSIONS: Faecal concentrations of IL-6 and -8 were higher in diarrhoeic compared to non-diarrhoeic dogs, and are therefore potential candidates for non-invasive biomarkers to assess the severity and resolution of acute intestinal disease in dogs. However their correlation with disease progression and severity needs to be further investigated before their full clinical application can be determined.

Factors Associated With Early Loss of Hallux Valgus Correction.

Recurrence is common after hallux valgus corrective surgery. Although many investigators have studied the risk factors associated with a suboptimal hallux position at the end of long-term follow-up, few have evaluated the factors associated with actual early loss of correction. We conducted a retrospective cohort study to identify the predictors of lateral deviation of the hallux during the postoperative period. We evaluated the demographic data, preoperative severity of the hallux valgus, other angular measurements characterizing underlying deformities, amount of hallux valgus correction, and postoperative alignment of the corrected hallux valgus for associations with recurrence. After adjusting for the covariates, the only factor associated with recurrence was the postoperative tibial sesamoid position. The recurrence rate was ~50% and ~60% when the postoperative tibial sesamoid position was >4 and >5 on the 7-point scale, respectively.

Cell therapy for neurological disorders: The elusive goal.

The positive outcomes of the transplantation of fetal neural tissue in adult rat models of a variety of neurological disorders, particularly Parkinson's disease, in the 1970s, and its translation to humans in the 1980s, raised great hopes for patients suffering from these incurable disorders. This resulted in a frantic research globally to find more suitable, reliable, and ethically acceptable alternatives. The discovery of adult stem cells, embryonic stem cells, and more recently, the induced pluripotent cells further raised our expectations. The useful functional recovery in animal models using these cell transplantation techniques coupled with the desperate needs of such patients prompted many surgeons to "jump from the rat-to-man" without scientifically establishing a proof of their utility. Each new development claimed to overcome the limitations, shortcomings, safety, and other technical problems associated with the earlier technique, yet newer difficulties prevented evidence-based acceptance of their clinical use. However, thousands of patients across the globe have received these therapies without a scientifically acceptable proof of their reliability. The present review is an attempt to summarize the current status of cell therapy for neurological disorders.

Prospective glioma grading using single-dose dynamic contrast-enhanced perfusion MRI.

AIM: To evaluate the sensitivity and specificity of single-dose dynamic contrast-enhanced (DCE) perfusion magnetic resonance imaging (MRI) in prospective evaluation of glioma grading and to correlate the relative cerebral blood volume (rCBV) values with mitotic and ki-67 indexes obtained at histopathology. MATERIALS AND METHODS: A total of 53 histologically proven patients with glioma were included in this study. DCE-MRI perfusion with a single dose of contrast medium was included in brain tumour protocol and prospective grading of glioma into low and high grade was done based on a previously reported rCBV cut-off value of 3. Tumours with rCBV ≥ 3 were considered to be high grade and rCBV < 3 were considered to be low grade. The sensitivity and specificity of the cut-off value were estimated. Ki-67 and mitotic indexes were also obtained on histopathological analysis along with histological grading. RESULTS: Based on pre-defined rCBV cut-off values, prospective grading of low- and high-grade glioma was achieved with a sensitivity and specificity of 97.22% and 100%, respectively. Significant correlation was found between the mitotic/ki-67 indexes and rCBV values when data for high- and low-grade tumours was combined. CONCLUSION: DCE-MRI performed with a single dose of contrast medium is as effective as a protocol with a double-dose of contrast medium for glioma grading using 3 T MRI and could be added to the routine evaluation protocol of brain tumours.

Morphometry of the fibular collateral ligament: anatomic study with comprehensive review of the literature.

There is no consensus in the literature related to the morphology, bony attachments, and variations of the fibular collateral ligament (FCL) of the knee. Our purpose was to investigate FCL morphology and to review reports in the literature regarding this structure. Seventy knees from formalin-fixed, adult cadavers were dissected and a digital caliper was used to measure FCL length, width, distance from proximal attachment to articular surface (PA→AS), and distance from distal attachment to articular surface (DA→AS). The mean (SE) length and width of all FCLs was 48.3 (1.1) mm and 4 (0.16) mm, respectively. The mean (SE) PA→AS and DA→AS of all FCLs was 22 (0.8) mm and 24.8 (1) mm, respectively. We found a direct relationship between the PA→AS and DA→AS distances (Spearman rho = 0.527, P = 0.002) and this association was independent of age and sex. Two FCL variations were found: a bifurcate ligament with two distal bands and a trifurcate ligament with three distal bands, all of which attached to the fibular head. Our literature review revealed that only 2/10 cadaveric FCL morphology studies reported variations similar to the current study. Further, there was variability in the reported location of the FCL proximal attachment. When combining our data with these studies, 105/219 FCLs directly attached to the apex of the lateral epicondyle (LE), 10/219 to a fovea posterior to the LE, and 104/219 posterior and proximal to the LE. These data may have implications related to FCL injury and repair.