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iPhoneography is the practice of capturing, enhancing, and sharing images using a smartphone device. With the emergence of image-based social media platforms that highlight the experience of making images, it becomes critical to examine how the act of creating images enhances comprehension of visuals. The practice of iPhoneography and image-based social media platforms bring forth new directions for studying visual literacy. The field of visual literacy can be used as a framework to examine both the value of reading and making images. Through the use of purposive sampling and interviews, the study examined the experiences of twelve image-makers to understand how the making and the continuous exposure to them can contribute to enhanced creative growth.

Background/Objectives: The mammalian target of the rapamycin (mTOR) signaling pathway is a central regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling contributes to many human diseases, including cancer, diabetes, and obesity. Therefore, inhibitors against mTOR’s catalytic kinase domain (KD) have been developed and have shown significant antitumor activities, making it a promising therapeutic target. The ATP–KD interaction is particularly important for mTOR to exert its cellular functions, and such inhibitors have demonstrated efficient attenuation of overall mTOR activity. Methods: In this study, we screened the Traditional Chinese Medicine (TCM) database, which enlists natural products that capture the relationships between drugs targets and diseases. Our aim was to identify potential ATP-competitive agonists that target the mTOR-KD and compete with ATP to bind the mTOR-KD serving as potential potent mTOR inhibitors. Results: We identified two compounds that demonstrated interatomic interactions similar to those of ATP–mTOR. The conformational stability and dynamic features of the mTOR-KD bound to the selected compounds were tested by subjecting each complex to 200 ns molecular dynamic (MD) simulations and molecular mechanics/generalized Born surface area (MM/GBSA) to extract free binding energies. We show the effectiveness of both compounds in forming stable complexes with the mTOR-KD, which is more effective than the mTOR-KD–ATP complex with more robust binding affinities. Conclusions: This study implies that both compounds could serve as potential therapeutic inhibitors of mTOR, regulating its function and, therefore, mitigating human disease progression.

Among the different drug targets of SARS-CoV-2, a multi-domain protein known as NSP3 is a critical element of the translational and replication machinery. The macrodomain-I, in particular, has been reported to have an essential role in the viral attack on the innate immune response. In this study, we explore natural medicinal compounds and identify potential inhibitors to target the SARS-CoV-2–NSP3 macrodomain-I. Computational modeling and simulation tools were utilized to investigate the structural-dynamic properties using triplicates of 100 ns MD simulations. In addition, the MM/GBSA method was used to calculate the total binding free energy of each inhibitor bound to macrodomain-I. Two significant hits were identified: 3,5,7,4′-tetrahydroxyflavanone 3′-(4-hydroxybenzoic acid) and 2-hydroxy-3-O-beta-glucopyranosyl-benzoic acid. The structural-dynamic investigation of both compounds with macrodomain-I revealed stable dynamics and compact behavior. In addition, the total binding free energy for each complex demonstrated a robust binding affinity, of ΔG −61.98 ± 0.9 kcal/mol for Compound A, while for Compound B, the ΔG was −45.125 ± 2.8 kcal/mol, indicating the inhibitory potential of these compounds. In silico bioactivity and dissociation constant (KD) determination for both complexes further validated the inhibitory potency of each compound. In conclusion, the aforementioned natural products have the potential to inhibit NSP3, to directly rescue the host immune response. The current study provides the basis for novel drug development against SARS-CoV-2 and its variants.

The SARS-CoV-2 non-structural protein (nsp) nsp10–nsp16 complex is essential for the 2′-O-methylation of viral mRNA, a crucial step for evading the innate immune system, and it is an essential process in SARS-CoV-2 life cycle. Therefore, detecting molecules that can disrupt the nsp10–nsp16 interaction are prospective antiviral drugs. In this study, we screened the North African Natural Products database (NANPDB) for molecules that can interact with the nsp10 interface and disturb the nsp10–nsp16 complex formation. Following rigorous screening and validation steps, in addition to toxic side effects, drug interactions and a risk /benefit assessment, we identified four compounds (genkwanin-6-C-beta-glucopyranoside, paraliane diterpene, 4,5-di-p-trans-coumaroylquinic acid and citrinamide A) that showed the best binding affinity and most favourable interaction with nsp10 interface residues. To understand the conformational stability and dynamic features of nsp10 bound to the four selected compounds, we subjected each complex to 200 ns molecular dynamics simulations. We then calculated the free binding energies of compounds interacting with nsp10 structure using the molecular mechanics-generalised Born surface area (MMGBSA). Of the four compounds, genkwanin-6-C-beta-glucopyranoside demonstrated the most stable complex with nsp10, in addition to a tighter binding affinity of −37.4 ± 1.3 Kcal/mol. This potential to disrupt the nsp10–nsp16 interface interaction and inhibit it now sets the path for functional studies.

Background Diabetic nephropathy (DN) is a type of progressive kidney disease affecting approximately 40% of patients with diabetes. Current DN diagnostic criteria predominantly rely on albuminuria and serum creatinine (sCr) levels. However, the specificity and reliability of both markers are limited. Hence, reliable biomarkers are required for early diagnosis to effectively manage DN progression. Methods In this study, a cohort of 159 individuals were clinically evaluated and the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 were determined using Multiplexing Assays. Additionally, the association between the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 in patients with DN were compared to those in patients with T2D without kidney disease and control participants. Results Circulating level of NGAL were significantly higher in people with DN compared to people with T2D and non-diabetic groups (92.76 ± 7.5, 57.22 ± 8.7, and 52.47 ± 2.9 mg/L, respectively; p  <  0.0001). IGFBP-4 showed a similar pattern, where it was highest in people with DN (795.61 ng/ml ±130.7) compared to T2D and non-diabetic people (374.56 ng/ml ±86.8, 273.06 ng/ml ±27.8 respectively, ANOVA p  <  0.01). The data from this study shows a significant positive correlation between NGAL and IGFBP-4 in people with DN ( ρ  = .620, p  <  0.005). IGFBP-4 also correlated positively with creatinine level and negatively with eGFR, in people with DN supporting its involvement in DN. Conclusion The data from this study shows a parallel increase in the plasma levels of NGAL and IGFBP-4 in DN. This highlights the potential to use these markers for early diagnosis of DN.

Angiopoietins are crucial growth factors for maintaining a healthy, functional endothelium. Patients with type 2 diabetes (T2D) exhibit significant levels of angiogenic markers, particularly Angiopoietin-2, which compromises endothelial integrity and is connected to symptoms of endothelial injury and failure. This report examines the levels of circulating angiopoietins in people with T2D and diabetic nephropathy (DN) and explores its link with ANGPTL proteins. We quantified circulating ANGPTL3, ANGPTL4, ANGPTL8, Ang1, and Ang2 in the fasting plasma of 117 Kuwaiti participants, of which 50 had T2D and 67 participants had DN. The Ang2 levels increased with DN (4.34 ± 0.32 ng/mL) compared with T2D (3.42 ± 0.29 ng/mL). This increase correlated with clinical parameters including the albumin-to-creatinine ratio (ACR) (r = 0.244, p = 0.047), eGFR (r = −0.282, p = 0.021), and SBP (r = −0.28, p = 0.024). Furthermore, Ang2 correlated positively to both ANGPTL4 (r = 0.541, p < 0.001) and ANGPTL8 (r = 0.41, p = 0.001). Multiple regression analysis presented elevated ANGPTL8 and ACRs as predictors for Ang2’s increase in people with DN. In people with T2D, ANGPTL4 positively predicted an Ang2 increase. The area under the curve (AUC) in receiver operating characteristic (ROC) analysis of the combination of Ang2 and ANGPTL8 was 0.77 with 80.7% specificity. In conclusion, significantly elevated Ang2 in people with DN correlated with clinical markers such as the ACR, eGFR, and SBP, ANGPTL4, and ANGPTL8 levels. Collectively, this study highlights a close association between Ang2 and ANGPTL8 in a population with DN, suggesting them as DN risk predictors.

Background/Objectives: Obesity and type 2 diabetes (T2D) are associated with significant alterations in various metabolic biomarkers. Isthmin-1 (Ism1) has recently emerged as a potential marker of metabolic health and was shown in animal studies to associate with metabolic-associated fatty liver disease (MAFLD). In this study, we aimed to investigate the circulatory levels of Ism1 in individuals with obesity compared to non-obese individuals and evaluate their association with insulin resistance, MAFLD, and T2D. The primary outcomes of this study are obesity, insulin resistance, MAFLD, and T2D, while the secondary outcome is hypertension; Methods: This is a cross-sectional study involving 450 participants, who were divided based on their obesity status into people with obesity (n = 182) and those without obesity (n = 265). Circulating Ism1 levels were measured by ELISA and were compared between the groups. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), and fatty liver was evaluated using Fibroscan; Results: Our results showed a significant reduction in circulating Ism1 levels in individuals with obesity (p-value = 0.002). Ism1 levels were negatively associated with the odds of T2D, possibly suggesting a protective role. Additionally, individuals with higher CAP scores demonstrated significantly lower Ism1 levels, and the Spearman’s rank correlation revealed a negative association between Ism1 and both CAP scores (r = −0.109, p-value = 0.025) and insulin resistance (r = −0.141, p-value = 0.004). Logistic regression analysis further supported Ism1 as an independent significant protective factor against obesity-related metabolic dysfunction. This significance persisted after adjusting for several confounders. Furthermore, our ROC results indicate that circulatory Ism1 levels possess significant diagnostic capability for identifying individuals with obesity-related metabolic imbalances with an area under the curve of 0.764 (95% CI = 0.718, 0.811). Finally, the adjusted multinomial analysis suggested that higher levels of Ism1 may play a protective role against pre-diabetes (AOR = 0.88, 95% CI = 0.838, 0.925) and T2D (AOR = 0.87, 95% CI = 0.814, 0.934); Conclusions: This study suggests that reduced Ism1 levels are linked to increased insulin resistance, MAFLD, and T2D in obese individuals. Our findings further corroborate the protective role of Ism1 and highlight its potential utility as a biomarker for monitoring obesity-related metabolic diseases.

Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness.

Krüppel‐like factor 15 (KLF15) is a transcription factor contributing to the pathophysiology of multiple diseases, including metabolic syndromes. It is 416 residues long, with a C2H2‐type zinc finger (ZnF) domain that binds to GC‐rich regions regulating transcription. The role of KLF15 in glucogenesis and glucose level maintenance is well established. However, the DNA interaction mechanism at the atomic level remains unresolved. Here, we utilised computational structural biology tools to address this knowledge gap. The KLF15 ZnF–domain interacting with DNA was modelled with AlphaFold 3.0. Alanine substitution of the KLF15 ZnF domain–DNA complex revealed that residues K334A, R334A, Y332A and R392A significantly affect the binding affinities (ΔΔG) to DNA. To understand the conformational stability and dynamics of the KLF15 ZnF–domain complexes, 100‐ns molecular dynamics simulations were performed. Additionally, molecular mechanics‐generalised Born (MM/GBSA) surface area was utilised to calculate total binding energies. The binding energies of the wild‐type KLF15 ZnF domain (−94.0 ± 0.17 kcal/mol) demonstrated a more robust binding affinity to DNA than K334A (−30.4 ± 0.35 kcal/mol), R344A (−42.8 ± 0.37 kcal/mol), Y332A (−47.7 ± 0.42 kcal/mol) and R392A (−30.8 ± 0.30 kcal/mol). The findings highlighted the unstable dynamics of the alinine substituted resdiues that consequently reduce the binding free energy compared to the wild‐type KLF15 ZnF domain. In conclusion, the four identified residues are essential to recognise KLF15 ZnF DNA binding and can be considered potential hotspots for the therapeutics development for type 2 diabetes.

Diabetic nephropathy (DN) is a complicated condition related to type 2 diabetes mellitus (T2D). ANGPTL8 is a hepatic protein highlighted as a risk factor for DN in patients with T2D; additionally, recent evidence from DN studies supports the involvement of growth hormone/IGF/IGF-binding protein axis constituents. The potential link between ANGPTL8 and IGFBPs in DN has not been explored before. Here, we assessed changes in the circulating ANGPTL8 levels in patients with DN and its association with IGFBP-1, -3, and -4. Our data revealed a significant rise in circulating ANGPTL8 in people with DN, 4443.35 ± 396 ng/mL compared to 2059.73 ± 216 ng/mL in people with T2D (p < 0.001). Similarly, levels of IGFBP-3 and -4 were significantly higher in people with DN compared to the T2D group. Interestingly, the rise in ANGPTL8 levels correlated positively with IGFBP-4 levels in T2DM patients with DN (p < 0.001) and this significant correlation disappeared in T2DM patients without DN. It also correlated positively with serum creatinine and negatively with the estimated glomerular filtration rate (eGFR, All < 0.05). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and IGFBP4 was 0.76 (0.69–0.84), p < 0.001, and the specificity was 85.9%. In conclusion, our results showed a significant increase in ANGPTL8 in patients with DN that correlated exclusively with IGFBP-4, implicating a potential role of both proteins in the pathophysiology of DN. Our findings highlight the significance of these biomarkers, suggesting them as promising diagnostic molecules for the detection of diabetic nephropathy.