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The simultaneous coexistence of complicated metabolic conditions like obesity and diabetes within an individual is known as diabesity. Obesity is the key factor for many chronic diseases, including insulin resistance and type 2 diabetes (T2D). Metabolic stress due to nutrient overload releases different inflammatory mediators. Secreted frizzled-related protein 4 (SFRP4) is also an inflammatory mediator that impairs insulin secretion. SFRP4 acts as an early biomarker for diabesity expressed with interleukin-1 beta (IL-1β) in the adipose tissues that hinder the exocytosis of insulin-secreting granules from the pancreatic β-cells and is a potential target for preserving β-cell dysfunction and the diabesity treatment. The current study aimed to screen potential bioactive compounds targeting and inhibiting the diabesity-linked SFRP4 protein through an in silico approach. The three-dimensional (3D) structure of human SFRP4 was predicted through comparative modeling techniques and evaluated by various online bioinformatics tools. The molecular docking and MD simulation investigations were carried out against phytochemicals with anti-diabetic and anti-obesity properties to shortlist the best SFRP4 inhibitor. Hesperetin, Curcumin, Isorhamnetin, Embelin, Epicatechin, and Methyl Eugenol interacted strongly with SFRP4 by displaying zero RMSD and binding affinities of -6.5, -6.4, -6.3, -5.3, -6.3 and -5.8 kcal/mol respectively. Additionally, the root mean square fluctuation and root mean square deviation graphs from the MD simulation results demonstrated that hesperetin has good variations throughout the simulation period as compared to others. This dynamic stability and control behavior of hesperetin, when it interacts with SFRP4, shows that it has the potential to modulate the function and activity of the protein. Therefore, hesperetin is identified as an effective and top drug candidate through this analysis for preserving beta-cell function and treating diabesity by targeting SFRP4. The findings of this study could be useful in the design and development of diabesity drugs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rehman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Wheat is a major staple food and has been extensively grown around the globe. Sessile nature of plants has exposed them to a lot of biotic and abiotic stresses including fungal pathogen attack. Puccinia graminis f.sp. tritici causes stem rust in the wheat crop and leads to 70% decrease in its production. Pathogenesis-related (PR) proteins provide plants with defense against different fungal pathogens as these proteins have antifungal activities. This study was designed to screen Pakistani wheat varieties for PR2 and PR3 proteins and their in silico characterization. PR2 and PR3 genes were screened and isolated by PCR amplification from wheat variety Chenab-70 and Frontana, respectively. The nucleotide sequences of PR2 and PR3 genes were deposited in GenBank with accession numbers MT303867 and MZ766118, respectively. Physicochemical properties, secondary and tertiary structure predictions, and molecular docking of protein sequences of PR2 and PR3 were performed using different bioinformatics tools and software. PR2 and PR3 genes were identified to encode β-1,3-glucanase and chitinase proteins, respectively. Molecular docking of both PR2 and PR3 proteins with beta-glucan and chitin (i.e. their respective ligands) showed crucial amino acid residues involved in molecular interactions. Conclusively, molecular docking analysis of β-1,3-glucanase and chitinase proteins revealed crucial amino acid residues which are involved in ligand binding and important interactions which might have important role in plant defense against fungal pathogens. Moreover, the active residues in the active sties of these proteins can be identified through mutational studies and resulting information might help understanding how these proteins are involved in plant defense mechanisms., Competing Interests: The authors have declared that they have no conflict of interest.

Ratooning is an important cultivation practice in sugarcane production around the world, with underground buds on the remaining stalk acting as the source for establishment of a subsequent ratoon crop. However, the optimal depth of cutting during harvest in terms of yield and root growth remains unknown. We carried out a two-year field study to determine the effects of three cutting depths (0, 5 and 10 cm below the surface) ratoon cane root and yield. Results showed that cutting to a depth of 5 cm increased the root fresh weight and root volume by 21-59% and 41-127%, respectively, compared to cutting depths of 0 and 10 cm. Remarkably, cutting to a depth of 5 cm also had a significant effect on the development of fine roots, which is closely linked to cane yield. The effect was particularly noticeable in terms of two root traits, root volume and the surface area of roots with a diameter of 1.0-2.0mm, and root length and the number of root tips in roots with a diameter of 0-0.5mm. As a result, a cutting depth of 5 cm below the surface increased cane yield by 43 and 28% compared to depths of 0 and 10 cm below the surface, respectively. Overall, these findings suggest that a cutting depth of 5 cm is optimal in terms of sugarcane yield, largely due to the enhanced effect on root traits, especially the development of fine roots. These findings will help optimize sugarcane ratoon management and improve the ratoon cycle., Competing Interests: The authors have declared that no competing interests exist.

Significant number out of 2.2 billion vision impairments in the world can be attributed to genetics. The current study is aimed to decipher the genetic basis of Leber congenital Amaurosis (LCA), Anterior Segment dysgenesis (ASD), and Retinitis Pigmentosa (RP), segregating in four large consanguineous Pakistani families. The exome sequencing followed by segregation analysis via Sanger sequencing revealed the LCA phenotypes segregating in families GCUF01 and GCUF04 can be attributed to c.465G>T (p.(Gln155His)) missense and novel c.139_140delinsA p.(Pro47Trhfster38) frameshift variant of AIPL1 and GUCY2D, respectively. The c.1843A>T (p.(Lys615*) truncating allele of MERTK is homozygous in all the affected individuals, presumably suffering with RP, of the GCUF02 family. Meanwhile, co-segregation of the ASD phenotype and the c.289A>G (p.(Ile97Val)) variant of FOXE3 was found in the GCUF06 family. All the identified variants were either absent or present in very low frequencies in the control databases. Our in-silico analyses and 3D molecular modeling support the deleterious impact of these variants on the encoded proteins. Variants identified in MERTK, GUCY2D, and FOXE3 were categorized as "pathogenic" or "likely pathogenic", while the missense variant found in AIPL1 was deemed to have "uncertain significance" based upon the variant pathogenicity guidelines from the American College of Medical Genetics and Genomics (ACMG). This paper highlights the genetic diversity of vision disorders in the Pakistani population and reports the identification of four novel mutations in families who segregate clinically heterogeneous eye diseases. Our results give insight into the genotype-phenotype correlations of AIPL1, FOXE3, MERTK, and GUCY2D variants., Competing Interests: No authors have competing interests.