Experimental investigation on sucrose/alumina catalyst coated converter in gasoline engine exhaust gas.

In this study, a modified catalytic converter was employed to treat the harmful exhaust gas pollutants of a twin-cylinder, four-stroke spark-ignition engine. This research mainly focuses on the emission reduction of unburnt hydrocarbons, carbon monoxide, and nitrogen oxides at low light-off temperatures. A sucrolite catalyst (sucrolite) was coated over the metallic substrate present inside the catalytic converter, and exhaust gas was allowed to pass through it. A scanning electron microscope, X-ray diffraction, and Fourier transform infrared spectroscopy were used to investigate the changes in morphology, chemical compounds, and functional group elements caused by the reactions. Catalytic reactions were studied by varying the engine loads and bed temperatures, and the results were compared with those of the commercial catalytic converter. The results show that sucrose present in the catalyst was suitable at low temperatures while alumina was suitable for a wide range of temperatures. In the case of the modified catalytic converter, the maximum catalytic conversion efficiencies achieved for oxidizing CO and HC were 70.73% and 85.14%, respectively, and for reduction reaction at NOx was 60.22% which is around 42% higher than in commercial catalytic converter. As a result, this study claims that sucrolite catalyst is effective for low-temperature exhaust gas.

Engagement and outcomes of cancer patients referred to a tobacco cessation program at a National Cancer Institute-designated cancer center.

INTRODUCTION: Tobacco cessation is a critical but challenging intervention for cancer patients. Our National Cancer Institute-designated Comprehensive Cancer Center instituted a tobacco cessation program in 2019. This manuscript reports on the first 2 years of our experience. METHODS: Patients were referred to the program by their care team, and a certified tobacco treatment specialist contacted patients remotely and provided behavioral therapy and coordinated pharmacotherapy. We retrospectively captured data from patients with a cancer diagnosis referred to the tobacco cessation program. Univariate and multivariable logistic regression analyses with the backward elimination approach were performed to determine factors associated with patient acceptance of referral to the tobacco cessation program. Tobacco cessation rates after referral to the program were also captured. RESULTS: Between July 2019 and August 2021, 194 patients were referred to the tobacco cessation program. Of the 194 patients referred, 93 agreed to enroll in the tobacco cessation program (47.9%), of which 84 requested pharmacotherapy (90.3%). Twenty-four were able to cease tobacco use (25.8%). Only 7 patients out of the 101 patients (6.9%) who declined cessation services were successful (p < 0.001). On univariate logistic regression, race (p = 0.027) and marital status (p = 0.020) were associated with referral acceptance. On multivariable analysis, single patients (odds ratio [OR] = 0.33) and Caucasian patients (OR = 0.43) were less likely to accept a referral. CONCLUSIONS: Access to tobacco cessation services is a critical component of comprehensive cancer care. Our experience highlights the need to understand patient-specific factors associated with engagement with a tobacco cessation program during cancer treatment. The use of pharmacotherapy is also a critical component of successful tobacco cessation.

The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition.

Berberine is a natural product that has long been used in traditional Chinese medicine due to its antimicrobial, anti-inflammatory and metabolism-regulatory properties. Osimertinib is the first third-generation EGFR-tyrosine kinase inhibitor (TKI) approved for the treatment of non-small cell lung cancer (NSCLC) with activating EGFR mutations and those resistant to earlier generation EGFR-TKIs due to a T790M mutation. However, emergence of acquired resistance to osimertinib limits its long-term efficacy in the clinic. One known mechanism of acquired resistance to osimertinib and other EGFR-TKIs is MET (c-MET) gene amplification. Here, we report that berberine, when combined with osimertinib, synergistically and selectively decreased the survival of several MET-amplified osimertinib-resistant EGFR mutant NSCLC cell lines with enhanced induction of apoptosis likely through Bim elevation and Mcl-1 reduction. Importantly, this combination effectively enhanced suppressive effect on the growth of MET-amplified osimertinib-resistant xenografts in nude mice and was well tolerated. Molecular modeling showed that berberine was able to bind to the kinase domain of non-phosphorylated MET, occupy the front of the binding pocket, and interact with the activation loop, in a similar way as other known MET inhibitors do. MET kinase assay showed clear concentration-dependent inhibitory effects of berberine against MET activity, confirming its kinase inhibitory activity. These findings collectively suggest that berberine can act as a naturally-existing MET inhibitor to synergize with osimertinib in overcoming osimertinib acquired resistance caused by MET amplification.

Antidiabetic potential and high synergistic antibacterial activity of silver nanoparticles synthesised with Musa Paradisiaca tepal extract.

This work investigates the Musa Paradisiaca plant and its tepal extracts. The research findings show that the tepal extracts of M. Paradisiaca contain high phytochemical activity. Hence we can conclude that these plants have a number of beneficial properties. Phytochemical analysis concludes that the plant is rich in flavonoids, phenolic compounds, tannins, terpenoids, and phytosterol. In the current work, silver nanoparticles (AgNPs) have revealed the antioxidant properties of M. Paradisiaca. The results show that the methanolic extracts of these tepals exhibit antioxidant potential and are also sources of natural antioxidant compounds, though comparatively, AgNPs have shown the best antioxidant activity. This work investigates the link between the ethnopharmacological statements and the bioactive constituents found in M. Paradisiaca toward all probable markers for cervical cancer via in vivo studies and molecular docking, to form a pharmacophore setting for the active target. However, most of the mechanisms of action of herbal medicines are not in total agreement, and the information collected from their traditional remedies over the years must not be neglected. Hence, it is sensible to investigate the options available in herbal medicine for cancer progression. Biosynthesised AgNPs are principally spherical and nanosized. It was also found that tepalmediated AgNPs exhibit excellent antimicrobial efficacy against tested human pathogens. This green method can be used as a better alternative source than the chemical fabrication of nanomaterials and the biosynthesised nanoparticles can be used in antibacterial medicines. The methanolictepal extract of M. Paradisiaca with AgNPs displayed proficient antidiabetic properties in the diabetes rat model and so could have a possible development for medical use in the future.

Phase Ib Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck.

PURPOSE: On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx. PATIENTS AND METHODS: Patients were treated with a fixed dose of PPE (200 mg three times a day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6 months with tissue biopsy at baseline and 6 months. Primary endpoints were safety and toxicity; secondary endpoints were evaluation of pathologic response, cancer-free survival (CFS), overall survival (OS), and biomarker modulation. RESULTS: Among 21 enrolled patients, 19 began treatment and 17 completed 6 months of treatment with PPE and erlotinib. Main characteristics of treated patients: 15 severe dysplasia or carcinoma in situ and 17 oral cavity. Only skin rash was associated with dose-limiting toxicity and MTD. Recommended doses for phase II studies are PPE 600 mg daily plus erlotinib 100 mg daily for 6 months. Pathologic responses in 17 evaluable patients: pathologic complete response (47%) and pathologic partial response (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only phosphorylated ERK was correlated with response to treatment. CONCLUSIONS: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early-stage head and neck cancer.

Subcortical nuclei volumes are associated with cognition in children post-convulsive status epilepticus: Results at nine years follow-up.

PURPOSE: The purpose of the present study was to investigate the relationship between subcortical nuclei volume and cognition in children with post-convulsive status epilepticus (CSE). METHODS: Structural T1-weighted magnetic resonance imaging (MRI) scans (Siemens Avanto, 1.5 T) and neuropsychological assessments (full-scale intelligence quotient (FSIQ) and Global Memory Scores (GMS)) were collected from subjects at a mean 8.5 years post-CSE (prolonged febrile seizures (PFS), n = 30; symptomatic/known, n = 28; and other, n = 12) and from age- and sex-matched healthy controls (HC). Subjects with CSE were stratified into those with lower cognitive ability (LCA) (CSE+, n = 22) and those without (CSE-, n = 48). Quantitative volumetric analysis using Functional MRI of the Brain Software Library (FSL) (Analysis Group, FMRIB, Oxford) provided segmented MRI brain volumes. Univariate analysis of covariance (ANCOVA) was performed to compare subcortical nuclei volumes across subgroups. Multivariable linear regression was performed for each subcortical structure and for total subcortical volume (SCV) to identify significant predictors of LCA (FSIQ <85) while adjusting for etiology, age, socioeconomic status, sex, CSE duration, and intracranial volume (ICV); Bonferroni correction was applied for the analysis of individual subcortical nuclei. RESULTS: Seventy subjects (11.8 ±â€¯3.4 standard deviation (SD) years; 34 males) and 72 controls (12.1 ±â€¯3.0SD years; 29 males) underwent analysis. Significantly smaller volumes of the left thalamus, left caudate, right caudate, and SCV were found in subjects with CSE+ compared with HC, after adjustment for intracranial, gray matter (GM), or cortical/cerebellar volume. When compared with subjects with CSE-, subjects with CSE+ also had smaller volumes of the left thalamus, left pallidum, right pallidum, and SCV. Individual subcortical nuclei were not associated, but SCV was associated with FSIQ (p = 0.005) and GMS (p = 0.014). Intracranial volume and etiology were similarly predictive. CONCLUSIONS: Nine years post-CSE, SCV is significantly lower in children who have LCA compared with those that do not. However, in this cohort, we are unable to determine whether the relationship is independent of ICV or etiology. Future, larger scale studies may help tease this out.

A small molecule autophagy inducer exerts cytoprotection against α-synuclein toxicity.

α-synucleopathies are protein-misfolding disorders occur primarily due to aggregation and toxicity of α-synuclein. This study characterized the small molecule AGK2 as a modifier of α-synuclein mediated toxicity in an autophagy dependent manner in both yeast and mammalian cell line models. In yeast system, AGK2 enhances autophagy to clear toxic α-synuclein aggregates in an autophagy dependent manner. Autophagy flux analyses revealed that AGK2 induces autophagy especially autolysosomes. Importantly, AGK2 induces autophagy in an mTOR independent manner. These features enable AGK2 to exert cytoprotective potential against α-synuclein mediated toxicity in different model systems.

Enhanced inulinase production by Fusarium solani JALPK from invasive weed using response surface methodology.

The present study is the first report of utilizing Tithonia rotundifolia weed as a substrate for inulinase production from Fusarium solani JALPK. It also deals with the statistical optimization of culture conditions to enhance the enzyme yield. Amongst the 11 variables screened by Plackett- Burman design, Inulin in combination with Agave sisalana extract, Tithonia rotundifolia extract and NaNO3 had a significant influence on inulinase production and their concentrations were further optimized employing Box Behnken design. An enhancement of inulinase production from 970 EU/mL to 3261.011 EU/mL was gained after media optimization. Amongst the screened carbon sources Tithonia rotundifolia was found to be very effective in stimulating elevated inulinase synthesis. The Tithonia rotundifolia weed extract was treated with inulinase from Fusarium solani JALPK to form fructose which was estimated spectrophotometrically. This liberated fructose was also confirmed by osazone formation test and FTIR. HPTLC analysis of product revealed the exoinulinase nature of the enzyme produced by Fusarium solani JALPK since fructose was the only end product after hydrolysis of inulin rich weed in fermented broth. Thus the elevated extracellular inulinase yielding novel property of Fusarium solani JALPK (KY914560) contributes in considering it as a potential candidate with food, pharmaceutical and bioremediation applications.

Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease. The progression of DCM and the cellular and molecular perturbations associated with the pathogenesis are complex and multifactorial. Although considerable progress has been achieved, the molecular etiologies of DCM remain poorly understood. There is an expanding need for natural antidiabetic medicines that do not cause the side effects of modern drugs. Curcumin, a pleiotropic molecule, from Curcuma longa, is known to possess numerous impacts such as scavenging free radical, antioxidant, antitumor, and antiinflammatory activities. The reports from preclinical and clinical findings revealed that curcumin can reverse insulin resistance, hyperglycemia, obesity, and obesity-related metabolic diseases. The current review provides an updated overview of the possible molecular mechanism of DCM and multitarget approach of curcumin in alleviating DCM and diabetic complication. Additionally, we mentioned the approaches that are currently being implemented to improve the bioavailability of this promising natural product in diabetes therapeutics.

Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis.

Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy.

Vegetable oil derived solvent, and catalyst free "click chemistry" thermoplastic polytriazoles.

Azide-alkyne Huisgen "click" chemistry provides new synthetic routes for making thermoplastic polytriazole polymers-without solvent or catalyst. This method was used to polymerize three diester dialkyne monomers with a lipid derived 18 carbon diazide to produce a series of polymers (labelled C18C18, C18C9, and C18C4 based on monomer chain lengths) free of residual solvent and catalyst. Three diester dialkyne monomers were synthesized with ester chain lengths of 4, 9, and 18 carbons from renewable sources. Significant differences in thermal and mechanical properties were observed between C18C9 and the two other polymers. C18C9 presented a lower melting temperature, higher elongation at break, and reduced Young's modulus compared to C18C4 and C18C18. This was due to the "odd-even" effect induced by the number of carbon atoms in the monomers which resulted in orientation of the ester linkages of C18C9 in the same direction, thereby reducing hydrogen bonding. The thermoplastic polytriazoles presented are novel polymers derived from vegetable oil with favourable mechanical and thermal properties suitable for a large range of applications where no residual solvent or catalyst can be tolerated. Their added potential biocompatibility and biodegradability make them ideal for applications in the medical and pharmaceutical industries.

Cisplatin induces a mitochondrial-ROS response that contributes to cytotoxicity depending on mitochondrial redox status and bioenergetic functions.

Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy.

Parallel stranded DNA stabilized with internal sugar cross-links: synthesis and click ligation of oligonucleotides containing 2'-propargylated isoguanosine.

Internal sugar cross-links were introduced for the first time into oligonucleotides with parallel chain orientation by click ligation. For this, the 2'- or 3'-position of the isoguanosine ribose moiety was functionalized with clickable propargyl residues, and the synthesis of propargylated cytosine building blocks was significantly improved. Phosphoramidites were prepared and employed in solid-phase synthesis. A series of oligo-2'-deoxyribonucleotides with parallel (ps) and antiparallel (aps) strand orientation were constructed containing isoguanine-cytosine, isoguanine-isocytosine, and adenine-thymine base pairs. Complementary oligonucleotides with propargylated sugar residues were ligated in a stepwise manner with a chelating bis-azide under copper catalysis. Cross-links were introduced within a base pair or in positions separated by two base pairs. From T(m) stability studies it is evident that cross-linking stabilizes DNA with parallel strand orientation strongly (ΔT(m) from +16 to +18.5 °C) with a similar increase as for aps DNA.

Antitumour activity of Sargassum wightii (Greville) extracts against Dalton's ascites lymphoma.

Seaweeds have been used by mankind as medicine and food for more than 13,000 years. Marine algae are considered to produce a valuable phytoconstituents characterized by a broad spectrum of antitumor activities. The aim of the present study was to explore the effect of different solvent extracts of Sargassum wightii, Greville against Dalton's Ascitic Lymphoma (DAL) in Swiss male albino mice. DAL cells were injected intraperitoneally 1 x10(6) cell to the mice. Two days after cells injection the animals were treated with different solvent extracts of Sargassum wightii at dose of 200 mg kg(-1) for 14 days. 5-fluorouracil (20 mg kg(-1)) was used as reference drug. On day 11, cancer cell number, packed cell volume, decrease in tumour weight of the mice, increase in life span and hematological parameters were evaluated and compared with the same parameters in control. A significant increase in the life span and a decrease in the cancer cell number and tumour weight were noted in the tumour-induced mice after treatment with the extract. The haematological parameters were also normalized by the ethanolic and chloroform extracts in tumour-induced mice. These observations are suggestive of the protective effect of ethanolic extract of Sargassum wightii is comparatively better than other two tested extracts against Dalton's Ascitic Lymphoma (DAL).

Relationships between molecular structure and kinetic and thermodynamic controls in lipid systems. Part I: propensity for oil loss of saturated triacylglycerols.

Pure saturated triacylglycerols (TAGs) in canola oil were used as model systems to analyse oil loss in structured oil both from thermodynamic and kinetic perspectives. Two important parameters which effectively and predictively measure the relative propensity of a solid network to lose/hold oil were defined: (1) the rate of oil loss, K, which is a quantified representation of the kinetics of oil loss and (2) the initial amount of oil susceptible to be lost, i.e., the propensity for oil loss (POL), which is a representation of the thermodynamics of oil binding. It was found that the POL and K values do not always trend in the same fashion, suggesting that the mechanism of oil binding is complex, depending on the structurant's crystalline form locked within the oil network. The two parameters were, however, correlated to the melting and thermal behavior of the structurants, to the polymorphic structures that are obtained during the cooling process and to the habit (shape, size and morphology) of the crystalline phase in the oil. Both POL and K had a strong correlation to the oil loss.

Formulation and evaluation of chitosan microspheres of aceclofenac for colon-targeted drug delivery.

The objective of this investigation was to develop novel colon specific drug delivery. Aceclofenac, a NSAID, was successfully encapsulated into chitosan microspheres. Various formulations were prepared by varying the ratio of chitosan, span-85 and stirring speed and the amount of glutaraldehyde. The SEM study showed that microspheres have smooth surfaces. Microspheres were characterised by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) to confirm the absence of chemical interactions between drug and polymer and to know the formation of microspheres structure. The microspheres were evaluated for particle size, encapsulation efficiency, drug loading capacity, mucoadhesion studies, stability studies, in vitro and in vivo drug release studies. Particle sizes, as measured by the laser light scattering technique, were of an average size in the range 41-80 µm. The swelling index was in the range 0.37-0.82 and the entrapment efficiency range was 51-75% for all the formulations. The optimised batch ACM(13) released 83.6% at 8 h and 104% at 24 h in SCF containing rat caecal content. Eudragit coated chitosan microspheres prevented the release of the aceclofenac in the physiological environment of the stomach and small intestine and released 95.9±0.34% in the colon. With regard to release kinetics, the data were best fitted with the Higuchi model and showed zero order release with non-Fickian diffusion mechanism. The in vivo findings suggest that aceclofenac microspheres exhibit a prolonged effect of aceclofenac in rats and produce a significant anti-inflammatory effect. The findings of the present study conclusively state that chitosan microspheres are promising for colon targeting of aceclofenac to synchronise with chronobiological symptoms of rheumatoid arthritis.

Arginine vasopressin receptor antagonists (vaptans): pharmacological tools and potential therapeutic agents.

Arginine vasopressin (AVP) attracted attention as a potentially important neurohormonal mediator of the heart failure (HF) syndrome and hyponatremic states in humans because AVP influences renal handling of free water, vasoconstriction and myocyte biology through activation of V2 and V1(a) receptors. Current research is exploring V2- and dual V1(a)/V2 receptor antagonism for the treatment of hyponatremia, as well as for the congestion and edema associated with chronic HF, because vasopressin receptor antagonists might offer benefits in comparison with conventional loop diuretics. The purpose of this review is to update the current status of experimental and clinical studies with available vasopressin receptor antagonists (conivaptan and tolvaptan) and their potential role in the treatment of HF and hyponatremia of multiple causes.