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In the structure of the title compound, C15H19N3O5S2, the bond lengths at the linking sulfur atom are significantly different [1.7473 (17) and 1.811 (2) Å], and the angle at the exocyclic nitrogen atom is wide at 128.45 (18)°. The interplanar angle between the tolyl and thiadiazole rings is 9.2 (1)°. The complex hydrogen-bonding pattern, involving five donors and five acceptors, can be broken down into a one-dimensional ribbon parallel to the b axis, involving hydrogen bonds of the sugar residues only, and a two-dimensional layer structure parallel to the ab plane, based on the N—H...O and O—H...N hydrogen bonds.

The title compounds, C15H14N2OS (1a), C16H16N2OS (1b), and C17H18N2OS (1c), form a homologous series in which the size of the saturated ring increases from six- to eight-membered (with four, five and six methylene groups respectively). For 1b and 1c, the central (CH2)n moieties are all displaced to the same side of their ring, and the CH2—CH2—CH2 angles are much wider than the standard sp3 value; a database search indicates that these are general features of such ring systems. For 1a, the thiophene ring lies with the sulfur atom on the opposite side of the Cthiophene—Cpyridine bond to the cyano group, in contrast to 1b and 1c. For each compound, the packing may be described in terms of two `weak' C—H...N hydrogen bonds, which link the molecules to form one-dimensional (1a, 1c) or three-dimensional (1b) assemblies.

Diabetes mellitus (DM) represents a problem for the healthcare system worldwide. DM has very serious complications such as blindness, kidney failure, and cardiovascular disease. In addition to the very bad socioeconomic impacts, it influences patients and their families and communities. The global costs of DM and its complications are huge and expected to rise by the year 2030. DM is caused by genetic and environmental risk factors. Genetic testing will aid in early diagnosis and identification of susceptible individuals or populations using ATP-sensitive potassium (KATP) channels present in different tissues such as the pancreas, myocardium, myocytes, and nervous tissues. The channels respond to different concentrations of blood sugar, stimulation by hormones, or ischemic conditions. In pancreatic cells, they regulate the secretion of insulin and glucagon. Mutations in the KCNJ11 gene that encodes the Kir6.2 protein (a major constituent of KATP channels) were reported to be associated with Type 2 DM, neonatal diabetes mellitus (NDM), and maturity-onset diabetes of the young (MODY). Kir6.2 harbors binding sites for ATP and phosphatidylinositol 4,5-diphosphate (PIP2). The ATP inhibits the KATP channel, while the (PIP2) activates it. A Kir6.2 mutation at tyrosine330 (Y330) was demonstrated to reduce ATP inhibition and predisposes to NDM. In this study, we examined the effect of mutations on the Kir6.2 structure using bioinformatics tools and molecular dynamic simulations (SIFT, PolyPhen, SNAP2, PANTHER, PhD&SNP, SNP&Go, I-Mutant, MuPro, MutPred, ConSurf, HOPE, and GROMACS). Our results indicated that M199R, R201H, R206H, and Y330H mutations influence Kir6.2 structure and function and therefore may cause DM. We conclude that MD simulations are useful techniques to predict the effects of mutations on protein structure. In addition, the M199R, R201H, R206H, and Y330H variant in the Kir6.2 protein may be associated with DM. These results require further verification in protein–protein interactions, Kir6.2 function, and case-control studies.

Abstract Walkability is an important measure with strong ties to our health. However, there are existing gaps in the literature. Our previous work proposed new approaches to address existing limitations. This paper explores new ways of applying transferability using transfer-learning. Road networks, POIs, and road-related characteristics grow/change over time. Moreover, calculating walkability for all locations in all cities is very time-consuming. Transferability enables reuse of already-learned knowledge for continued learning, reduce training time, resource consumption, training labels and improve prediction accuracy. We propose ALF-Score++, that reuses trained models to generate transferable models capable of predicting walkability score for cities not seen in the process. We trained transfer-learned models for St. John’s NL and Montréal QC and used them to predict walkability scores for Kingston ON and Vancouver BC. MAE error of 13.87 units (ranging 0–100) was achieved for transfer-learning using MLP and 4.56 units for direct-training (random forest) on personalized clusters.

The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-β1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic and incurable form of inflammatory bowel disease that can increase the risk of colitis-associated cancer and mortality. Limited treatment options are available for this condition, and the existing ones often come with non-tolerable adverse effects. This study is the first to examine the potential benefits of consuming (R,R)-BD-AcAc2, a type of ketone ester (KE), and intermittent fasting in treating chronic colitis induced by dextran sodium sulfate (DSS) in rats. We selected both protocols to enhance the levels of β-hydroxybutyrate, mimicking a state of nutritional ketosis and early ketosis, respectively. Our findings revealed that only the former protocol, consuming the KE, improved disease activity and the macroscopic and microscopic features of the colon while reducing inflammation scores. Additionally, the KE counteracted the DSS-induced decrease in the percentage of weight change, reduced the colonic weight-to-length ratio, and increased the survival rate of DSS-insulted rats. KE also showed potential antioxidant activities and improved the gut microbiome composition. Moreover, consuming KE increased the levels of tight junction proteins that protect against leaky gut and exhibited anti-inflammatory properties by reducing proinflammatory cytokine production. These effects were attributed to inhibiting NFκB and NLRP3 inflammasome activation and restraining pyroptosis and apoptosis while enhancing autophagy as revealed by reduced p62 and increased BECN1. Furthermore, the KE may have a positive impact on maintaining a healthy microbiome. To conclude, the potential clinical implications of our findings are promising, as (R,R)-BD-AcAc2 has a greater safety profile and can be easily translated to human subjects.

The current study was conducted to determine the occurrence of Listeria species in live chicken and some chicken products (fillets, burger and luncheon). In addition, determine the antibiogram profile of Listeria strains and detection of some virulence genes of Listeria monocytogenes which recovered from the examined samples. The study included 100 samples including cloacal swabs from broiler chicken (n =25) from 5 different broiler chicken farms beside as well as chicken products (25 samples each of chicken fillets, burger and luncheon) that were randomly purchased from supermarkets. Isolation and identification of Listeria was performed according to the standard protocol provided by ISO (2017). It was recorded that the recovery rate of Listeria species from the examined samples was 24, 20, 8 and 16%, in cloacal swabs, chicken fillets, burger and luncheon, respectively with an overall incidence of 17%. In addition, biochemical identification of the recovered Listeria isolates revealed the presence of L. monocytogenes, L. innocua, L. ivanovii, L. seeligeri and L. grayi with various rates where L. monocytogenes scored the highest rate 29.4% (5 isolates). Antimicrobial susceptibility of Listeria strains (n=17) clarified that the highest antibiotic resistance was recorded when using streptomycin (82.4%) followed by Neomycin (76.5%) then Doxycycline and Cefotaxime (52.9%) while the lowest resistance was noticed when using Amikacin (11.8%) then Ciprofloxacin (35.3%). Finally, molecular detection of virulence genes in the identified L. monocytogenesstrains (n= 5) clarified the detection of iap and actA genes in the five isolates while hylA gene was detected in three isolates only. At the end, results obtained by this study emphasize a significant occurrence of resistant Listeria in chicken and chicken products including processed animal-originated foods commonly purchased by the public in including; chicken fillets, burger and luncheon. Seriously, the presence of such resistant bacteria endangers human health by making routine antibiotic courses useless in the treatment of such infections. Finally, data proved that retail foods of animal origin pose a risk to human health so it is advisable to examine chicken and chicken products routinely for presence of antibiotic resistant bacteria as well as antibiotic residues. [ABSTRACT FROM AUTHOR]

Aquaporin (AQP) is a water channel protein from the family of transmembrane proteins which facilitates the movement of water across the cell membrane. It is ubiquitous in nature, however the understanding of the water transport mechanism, especially for AQPs in microbes adapted to low temperatures, remains limited. AQP also has been recognized for its ability to be used for water filtration, but knowledge of the biochemical features necessary for its potential applications in industrial processes has been lacking. Therefore, this research was conducted to express, extract, solubilize, purify, and study the functional adaptations of the aquaporin Z family from Pseudomonas sp. AMS3 via molecular approaches. In this study, AqpZ1 AMS3 was successfully subcloned and expressed in E. coli BL21 (DE3) as a recombinant protein. The AqpZ1 AMS3 gene was expressed under optimized conditions and the best optimized condition for the AQP was in 0.5 mM IPTG incubated at 25°C for 20 h induction time. A zwitterionic mild detergent [(3‐cholamidopropyl) dimethylammonio]‐1‐propanesulfonate was the suitable surfactant for the protein solubilization. The protein was then purified via affinity chromatography. Liposome and proteoliposome was reconstituted to determine the particle size using dynamic light scattering. This information obtained from this psychrophilic AQP identified provides new insights into the structural adaptation of this protein at low temperatures and could be useful for low temperature application and molecular engineering purposes in the future. [ABSTRACT FROM AUTHOR]

Background: Paediatric rhinosinusitis is mostly different than that in adults. More frequently, children presented with cough, bad breath, crankiness, low energy, and swelling around the eyes, besides a thick yellow-green nasal or post-nasal discharge. About 5- 13% of childhood viral upper respiratory tract infections may advance to acute rhinosinusitis, with some of them developing a chronic condition. Aim: To assess prevalence and clinical presentation of sinusitis in the paediatric age group in Aseer, Saudi Arabia. Methodology: A retrospective record-based study was conducted in Abha Maternity and Children Hospital in Abha city, Saudi Arabia between January 2015 and January 2018. All medical records during the study period for children whose from to 15 years old attended the hospital and diagnosed as having sinusitis were included. Results: The study included 100 children with complete files whose ages ranged from less than 1 year to up to 13 years old with a mean age of 5.3 4.2 years. Nearly 51% of the children aged 4 years or less and male were 53 (53%). Past history for chronic rhinosinusitis (CRS) was positive among 30 children. Regarding clinical presentations of rhinosinusitis (RS) as reported by the children caregivers, fever was the most reported complaint (50%) followed by red eye (44%), ringing nose (42%), cough (41%) and headache (36%). Mucous culture was positive among 58 cases. The most isolated pathogens were streptococcus pneumoniae (45.6%), Haemophilis influenza (24.6%). Conclusions: In conclusion, the study revealed that CRS is a common disease in children at different ages, especially, maxillary and frontal sinuses. In most of the cases, medical treatment is highly appreciated; though, surgical intervention may be needed in a small percentage.

Walkability is a term that describes various aspects of the built and social environment and has been associated with physical activity and public health. Walkability is subjective and although multiple definitions of walkability exist, there is no single agreed upon definition. Road networks are integral parts of mobility and should be an important part of walkability. However, using the road structure as nodes is not widely discussed in existing methods. Most walkability measures only provide area-based scores with low spatial resolution, have a one-size-fits-all approach, and do not consider individuals opinion. Active Living Feature Score (ALF-Score) is a network-based walkability measure that incorporates road network structures as a core component. It also utilizes user opinion to build a high-confidence ground-truth that is used in our machine learning pipeline to generate models capable of estimating walkability. We found combination of network features with road embedding and points of interest features creates a complimentary feature set enabling us to train our models with an accuracy of over 87% while maintaining a conversion consistency of over 98%. Our proposed approach outperforms existing measures by introducing a novel method to estimate walkability scores that are representative of users opinion with a high spatial resolution, for any point on the road.

The experimental investigations focus on the thermoelectric and structural properties of newly synthesized Hf1.75Ti0.25FeNiSb2-xInx (x = 0.05 and 0.1) alloys, which are double half-Heusler alloys. The objective is to determine the impact of altering the production method from ball milling to melt spinning. Two of the samples were synthesized utilizing distinct techniques: melt spinning, arc melting, and spark plasma sintering. In contrast, the other two samples were created by ball milling instead of melt spinning. The X-ray diffraction technique was used to determine the crystal structures of all the samples. The face-centered cubic structure was identified as the primary crystallization phase for all the samples. The manufactured samples were determined to be uniform. Thermoelectric properties were investigated across a wide temperature range of 300 to 870 K. The thermal properties of the ball-milled samples were superior to those of the melt-spun samples due to the presence of larger pores, which enhanced phonon scattering. The Hf1.75Ti0.25FeNiSb1.9In0.1 alloy, which was subjected to ball milling, achieved the greatest thermoelectric figure of merit value of 0.38 at a temperature of 870 K. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) represents a problem for the healthcare system worldwide. DM has very serious complications such as blindness, kidney failure, and cardiovascular disease. In addition to the very bad socioeconomic impacts, it influences patients and their families and communities. The global costs of DM and its complications are huge and expected to rise by the year 2030. DM is caused by genetic and environmental risk factors. Genetic testing will aid in early diagnosis and identification of susceptible individuals or populations using ATP-sensitive potassium (KATP) channels present in different tissues such as the pancreas, myocardium, myocytes, and nervous tissues. The channels respond to different concentrations of blood sugar, stimulation by hormones, or ischemic conditions. In pancreatic cells, they regulate the secretion of insulin and glucagon. Mutations in the KCNJ11 gene that encodes the Kir6.2 protein (a major constituent of KATP channels) were reported to be associated with Type 2 DM, neonatal diabetes mellitus (NDM), and maturity-onset diabetes of the young (MODY). Kir6.2 harbors binding sites for ATP and phosphatidylinositol 4,5-diphosphate (PIP2). The ATP inhibits the KATP channel, while the (PIP2) activates it. A Kir6.2 mutation at tyrosine330 (Y330) was demonstrated to reduce ATP inhibition and predisposes to NDM. In this study, we examined the effect of mutations on the Kir6.2 structure using bioinformatics tools and molecular dynamic simulations (SIFT, PolyPhen, SNAP2, PANTHER, PhD&SNP, SNP&Go, I-Mutant, MuPro, MutPred, ConSurf, HOPE, and GROMACS). Our results indicated that M199R, R201H, R206H, and Y330H mutations influence Kir6.2 structure and function and therefore may cause DM. We conclude that MD simulations are useful techniques to predict the effects of mutations on protein structure. In addition, the M199R, R201H, R206H, and Y330H variant in the Kir6.2 protein may be associated with DM. These results require further verification in protein–protein interactions, Kir6.2 function, and case-control studies. [ABSTRACT FROM AUTHOR]