In this paper we study a bilinear optimal control problem related to a 2D parabolic-elliptic chemo-repulsion system consider a nonlinear chemical signal production term. We prove the existence of global optimal solutions with bilinear control, and applying a result on the existence of Lagrange multipliers in Banach spaces, we derive an optimality system for a local optimal solution.

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative and antineoplastic activities. Recently, different studies have shown that flavonoid have the potential to inhibit BET bromodomains. Previous reports suggest that flavonoids are putative inhibitors of the ZA channel due to their orientation and interactions with P86, V87, L92, L94 and N140. Herein, a comprehensive characterization of the binding mode of the biflavonoid amentoflavone and fisetin is discussed. To this end, both compounds were docked with BRD4 using four docking programs. Results were post-processed with protein-ligand interaction fingerprints. To gain further insights into the binding mode of the two natural products, docking results were further analyzed with molecular dynamics. Results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as basis for scaffold optimization and further characterization of flavonoids as BET inhibitors.

Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.