Search Results (6,427)

The presence of an unbalanced gut microbiome and the dysregulation of bile acid signalling are considered pivotal causes of various inflammation-based diseases. The Takeda G protein-coupled receptor (TGR5), TGR5 is a bile acid-responsive receptor that modulates inflammatory signalling pathways, making it an enticing molecular target for the discovery of novel anti-inflammatory agents. Herein, a comprehensive in silico approach was employed to identify potential TGR5 agonists from sterol-rich phytocompounds present in Triphala, a traditional polyherbal formulation. Using in silico computational methods, such as molecular docking and molecular dynamics simulations (MDS), we screened the putative agonistic potential of 10 phytocompounds obtained from Terminalia chebula, Terminalia bellirica, and Phyllanthus emblica against the crystal structure of human TGR5 (PDB ID: 7XTQ). Based on binding energy and molecular interactions, ergosterol (−12.34 ± 0.17 kcal/mol) and stigmasterol (−10.35 ± 0.04 kcal/mol) were predicted to be the top and best compounds. Furthermore, the stability of these two compounds in the docked complex was analysed using MDS for 200 ns. The mean Cα RMSD values were 0.22 ± 0.02 nm for both ergosterol- and stigmasterol-bound complexes, compared to 0.21 ± 0.02 nm for the unbound apo protein. Further, the molecular mechanics/Poisson–Boltzmann surface area (MMPBSA) analysis revealed that ergosterol exhibited binding free energy (−139.868 ± 12.318 kJ/mol) comparable to that of the co-crystallised ligand R399 −93.424 ± 8.919 kJ/mol. In silico ADMET predictions indicated acceptable drug-like properties and low toxicity for both compounds. Collectively, these computational findings suggest that ergosterol is a promising putative TGR5 agonist, warranting further experimental validation of its potential role in modulating inflammation-related pathways. Full article

In this study, a drug repurposing strategy was implemented with the aim of identifying new trypanocidal agents against Trypanosoma cruzi (T. cruzi). A total of 924 Food and Drug Administration (FDA)-approved drugs were screened by molecular docking on three sites of trypanothione synthetase (TS), including the catalytic site, a blind docking site, and a potential allosteric site. Selected compounds were further evaluated through in vitro and in vivo assays. Tadalafil, Zafirlukast, Raltegravir, and Olmesartan had better trypanocidal activity than the reference drugs Benznidazole and Nifurtimox in the in vitro evaluation against the trypomastigote form. Additionally, these drugs were able to decrease parasitemia by 20–50% in mice in an acute treatment. Molecular dynamics simulations (MDS) at 120 ns helped link findings from in vitro/in vivo experiments to a potential mechanism of action targeting T. cruzi trypanothione synthetase (TcTS). Therefore, the results encourage the use of these drugs to develop new anti-T. cruzi agents. Full article

Cutaneous adnexal carcinomas (CACs) comprise a diverse group of malignant tumors that show morphological differentiation toward one of the four main adnexal structures in normal skin: hair follicles, sebaceous glands, sweat-apocrine glands, and sweat-eccrine glands. These tumors can arise sporadically or may be associated with rare genetic syndromes. A total of 276 CACs cases underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of genomic alterations (GA). Sequencing data were used to determine microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), genomic ancestry, and COSMIC mutational signatures. PD-L1 expression was evaluated by immunohistochemistry (TPS; Dako 22C3). Statistical analyses were performed using Fisher’s exact test, with false discovery rate correction via the Benjamini–Hochberg method. Sequencing was performed on primary cutaneous tumors in 131 cases (47.4%) and on local recurrence or metastatic site biopsies in 145 cases (52.5%). Across all groups, there was a male predominance (64–81%) and similar mean ages (59–63 years), with apocrine (APO) tumors occurring in older patients than eccrine (ECC) tumors (72 vs. 62 years; p = 0.001). Histologically, 173 tumors (62.7%) were sweat gland-derived (SWT), 55 (19.9%) sebaceous gland-derived (SEB), 14 (5.1%) hair follicle-derived (HRF), and 34 (12.3%) unclassified (UNK). Among SWT tumors, 150 (86.7%) were eccrine and 23 (13.3%) apocrine. SWT tumors included digital papillary adenocarcinomas (DPA, 6.9%), mucinous carcinomas (MC, 6.3%), porocarcinomas (POR, 11.0%), spiradenocarcinomas (SPR, 8.1%), syringoadenocarcinomas (SRNG, 5.8%), and 77 (44.5%) unclassified cases. The number of GA per tumor was highest in SEB compared with SWT tumors (7.9 vs. 4.9; p = 0.005) and lowest in DPA (2.1 vs. 5.0 in non-DPA; p = 0.03). No differences in ancestry distribution were observed. Compared with SWT tumors, SEB tumors exhibited higher frequencies of RB1 (38.2% vs. 8.1%; p < 0.0001) and TP53 alterations (76.4% vs. 43.4%; p = 0.0002), suggesting potential neuroendocrine differentiation. MC tumors showed significantly higher PTCH1 alterations than non-MC tumors (36.4% vs. 1.8%; p = 0.044). MSI-high status was most frequent in SEB tumors compared with all other groups (15.7% vs. 1.2%; p = 0.005), and gLOH > 16% was also more common in SEB than SWT tumors (19.6% vs. 7.2%; p = 0.081). The MMR signature occurred more frequently in SEB than SWT tumors (32.0% vs. 2.1%; p = 0.005). Mean TMB was elevated across most CACs types, ranging from 10.4 mutations/Mb in HRF to 38.8 mutations/Mb in MC, with the exceptions of APO (2.7 mut/Mb; p = 0.001) and DPA (1.4 mut/Mb; p = 0.003). PD-L1 expression was generally low and did not differ significantly between SWT and SEB tumors (37.0% vs. 33.3%; NS). Given the limited data on CAC treatment, this study provides a catalog of commonly observed GA. SEB tumors exhibited the highest frequency of genomic alterations. Prospective clinical trials are needed to determine the prognostic and predictive value of CAC-specific biomarkers for immune checkpoint inhibitor (ICI) response, which is essential for integrating novel therapies into the evolving treatment landscape. Full article

With the increasing use of reinforced concrete segments in large-scale tunnels, engineering projects have placed higher mechanical demands on concrete, and the choice of concrete materials significantly influences these mechanical properties. This study is based on the preliminary mix design for the concrete used in the Second Undersea Tunnel Project, with the mass content of nano-SiO₂ (NS) (1–3%), the volume content of steel fibers (SF) (0.5–1.5%) and the volume content of polypropylene fibers (PPF) (0.05–0.25%) as independent variables and using compressive strength (Y₁), splitting tensile strength (Y₂), and toughness index (Y₃) as response variables. Using the Box–Behnken response surface design method, response surface models for each parameter were established and analyzed. The effects of NS, SF, and PPF on the mechanical properties of the concrete were investigated. Combining the MOPSO algorithm and the entropy-weighted TOPSIS method, a multi-objective cooperative optimization study was conducted. Finally, a microstructural analysis of the optimal NSDHFRC was performed. The results indicate that Y₁, Y₂, and Y₃ all initially increase and then decrease with increasing NS content; Y₁ and Y₃ increase with increasing SF content. However, when the SF content exceeds a certain level, the fiber spacing becomes too dense, weakening the effective bridging effect between fibers, resulting in a decrease in Y₂ at excessively high SF contents; PPF can suppress crack formation within a certain content range, but its effect on Y₁ is relatively weak. Due to agglomeration and water absorption, both Y₂ and Y₃ decrease when the PPF content is too high. It was determined that the optimal solution occurs when the mass fraction of NS is 2.15%, and the volume fractions of SF and PPF are 1.37% and 0.063%, respectively, with Y₁, Y₂, and Y₃ being 69.94 MPa, 5.49 MPa, and 1.99, respectively. Experimental verification confirmed that the relative error is within 5%. A microscopic analysis of the optimal solution revealed that an appropriate amount of NS refines the concrete structure through physical and chemical reactions, improves the interface transition zone, and enhances the bond strength between the fibers and the matrix. Meanwhile, PPF and SF distribute stress, respectively delaying the propagation of microcracks and macrocracks during different loading stages. These findings provide a reference for practical engineering applications. Full article

Acinetobacter baumannii (A. baumannii) represents a major threat because of its multidrug resistance, achieved through its ability to control virulence, and its mechanisms of drug efflux resistance. In this study, we used a combined experimental–computational approach to create and evaluate antimicrobial peptides that targeted the two essential pathogenic proteins, BfmR and AbaQ. The genomic analysis of a clinical isolate showed an extensive resistome and virulence profile, which matched high-risk global lineages. This study conducted molecular docking of an experimental AMP (cathelicidin KR-12 screened from the literature) and a rationally designed synthetic AMP (modified KR-12 analog) with pathogenic proteins, followed by 200 ns molecular dynamics simulations to evaluate both the binding stability and inhibitory potential of the compounds. The disk diffusion assay and microdilution assay were performed against A. baumannii. The study used comparative trajectory analyses, including RMSD, RMSF, radius of gyration, solvent-accessible surface area, principal component analysis, and MM-PBSA free energy calculations, to show that the synthetic AMP created stable electrostatic and hydrogen-bond networks, which caused conformational locking, and reached lower energy states than the experimental peptide. The synthetic AMP showed significant inhibition in validation in vitro. Contrastingly, the experimental AMP had transient interactions and no specificity. The study demonstrates that rationally designed AMPs have therapeutic potential, while the results create a reliable in silico framework to combat multidrug-resistant A. baumannii. Full article

Primary ciliary dyskinesia (PCD) is a rare ciliopathy resulting in chronic oto-sino-pulmonary disease. PCD diagnosis can be achieved by a combination of different diagnostic and adjuvant tools, including high-speed video-microscopy analysis (HSVA). A founder variant has been described in Puerto Rico as the most common cause of PCD in the island. Background/Objectives: In HSVA, objective parameters such as ciliary beat frequency (CBF) and subjective parameters such as ciliary beat pattern (CBP) shed light on the biophysical properties of cilia. However, the subjective nature of CBP creates a gap in knowledge; characteristics such as the length, angle, and bending index of cilia are poorly described. Our goal is to quantify cilia dynamics of the RSPH4A (c.921+3_921+6delAAGT (intronic)) founder variant in Puerto Rico through biophysical properties of cilia. This approach enhances longitudinal patient care by understanding treatment progress through biophysical ciliary function. Methods: We analyzed images from HSVA of six patients with PCD homozygous for the founder variant and six healthy controls (HC) (n = 12). Results: We found that ciliary length (PCD = 7.62 ± 0.95 μm, HC = 8.12 ± 1.36 μm, p = 0.204 ns), orientation vector (PCD = 7.20 ± 0.93 μm, HC = 7.25 ± 1.01 μm, p = 0.883 ns), straight angle (PCD = 1.67 ± 0.27 rad, HC = 1.76 ± 0.29 rad, p = 0.380 ns), and area (PCD = 2.35 ± 0.52 μm², HC = 2.10 ± 0.53 μm², p = 0.264 ns) did not have statistically significant differences between PCD and HC. In contrast, bending index (PCD = 1.06 ± 0.04, HC = 1.12 ± 0.09, p = 0.01), bent angle (PCD = 1.11 ± 0.30 rad, HC = 0.67 ± 0.21 rad, p < 0.0001), net angle (PCD = 0.56 ± 0.26 rad, HC = 1.09 ± 0.35 rad, p < 0.0001), amplitude (PCD = 5.77 ± 1.25 μm, HC = 7.99 ± 1.65 μm, p < 0.0001), and amplitude per second (PCD = 48.83 ± 13.23 A(s), HC = 91.66 ± 27.96 A(s), p < 0.0001) showed significant differences between both groups. Conclusions: Reduced angular excursion and amplitude in PCD demonstrate that the beating pattern of the RSPH4A founder variant is dysfunctional as compared with healthy controls. Our study provides an objective framework to understand the biophysical properties of the RSPH4A founder variant. Full article

The common metabolic disorder, lactose intolerance, is often treated with oral lactase enzyme supplements, which can frequently cause gastrointestinal instability. This work utilizes Malbranchea cinnamomea’s AA9 lytic polysaccharide monooxygenase (LPMO) to target β-lactose (β-lactose) in an investigation of a new enzymatic approach for lactose breakdown. Potential possibilities for lactose breakdown are AA9 LPMOs, copper-dependent enzymes that oxidatively cleave glycosidic bonds in polysaccharides. We employed a combined in silico method that incorporated molecular docking, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Docking studies revealed that β-lactose formed hydrogen bonds with key residues SER100, ASN54, and ARG56, exhibiting a greater binding affinity (−5.4 kcal/mol) toward LPMO compared to the control citric acid (−4.9 kcal/mol). Upon DFT analysis, (LPMO) showed excellent stability and appropriate reactivity for enzyme interaction. The higher stability of the LPMO-β-lactose complex was highlighted by MD simulation over 100 ns, which showed lower root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values, greater structural compactness, and reduced solvent accessibility when compared to the control. These collective findings suggest that β-lactose interacts efficiently with the AA9 LPMO active site, supporting its potential as a novel enzymatic target for lactose degradation. This computational study provides a theoretical foundation for developing alternative therapeutic strategies for lactose intolerance, though further in vitro and in vivo investigations are required to validate these findings. Full article

To enhance the early-age properties of steel slag cement mortar and promote the resource utilization of metallurgical solid waste, in this study, nano-SiO₂ (KH-NS) was modified using a KH550 silane coupling agent. The hydration kinetics and microstructure evolution were systematically analyzed by means of a macroscopic performance test (setting time and compressive strength) and multi-scale microscopic characterization (characterized by Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, X-ray Diffraction, Thermogravimetry-Differential Thermal Analysis, and isothermal calorimetry). The influence mechanism of its content on the early performance of the steel slag cement system was systematically studied. Research findings indicate that at a given dosage, increasing the proportion of KH-NS results in a shorter setting time for steel slag mortar. When the KH-NS dosage reaches 1.5%, the initial and final setting times of steel slag mortar decrease by 24.21% and 21.20%, respectively. The addition of KH-NS effectively enhances the compressive strength of mortar, with a particularly pronounced effect on early strength prior to 14 h of curing. At a KH-NS dosage of 1.5%, the onset of the accelerated phase of hydration heat release in steel slag cement mortar is advanced by 2.5 h. Mechanistic studies indicate that KH-NS accelerates cement hydration by promoting C₃S dissolution and C-S-H gel nucleation through interactions between surface silanol groups (Si-OH) and amino groups (-NH₂). Furthermore, KH-NS refines the pore structure via a micro-aggregate filling effect, reducing the number of harmful pores and improving the pore size distribution. KH-NS continuously consumes Ca(OH)₂ through pozzolanic reactions to generate C-S-H, with its reactivity increasing with higher dosage. Research confirms that KH-NS significantly enhances the early strength and density of steel slag mortar, providing both theoretical justification and technical support for developing low-carbon building materials based on solid waste with high dosage. Full article

Alzheimer’s disease (AD) remains a significant global health challenge, highlighting the need for novel dual inhibitors targeting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). This study investigated the trunk bark of Terminalia triptera Stapf. as a potential source of bioactive secondary metabolites for AD management. Bioassay-guided isolation led to the identification of two flavan-3-ol derivatives, epicatechin-(4β→8)-ent-catechin (1) and (−)-catechin (2), reported here for the first time from this species. In vitro assays demonstrated that the dimeric compound 1 exhibited stronger dual inhibitory activity against AChE and BChE, with IC₅₀ values of 4.41 × 10⁻⁴ and 4.75 × 10⁻⁴ mol/L, respectively, surpassing the reference compound berberine chloride. Molecular docking analysis revealed that compound 1 formed extensive interactions within both catalytic and peripheral anionic sites of the enzymes. Density Functional Theory (DFT) calculations indicated high kinetic stability, reflected by large HOMO–LUMO energy gaps (6.66–6.97 eV), while global reactivity descriptors suggested lower electrophilicity (ω = 2.19–2.34 eV), supporting a potentially favorable safety profile. Furthermore, 100 ns molecular dynamics simulations confirmed stable ligand–protein complexes stabilized by hydrogen-bond networks and deep binding within catalytic pockets. Overall, these findings highlight T. triptera and its dimeric proanthocyanidins as promising multi-target candidates for anti-Alzheimer drug development. Full article

Introduction: Bacterial multidrug resistance (MDR) drives treatment with expensive, toxic, or pharmacokinetically suboptimal antibiotics. Objectives: To assess the prevalence of MDR Gram-positive cocci among isolates from cardiac implantable electronic device (CIED) infections at a Polish reference center. Methods: Data come from the “EXTRACT” registry (ClinicalTrials.gov ID NCT05775783), which covers 702 transvenous lead extraction procedures. Blood samples and intraoperative swabs were collected from participants with CIED infection. Results: From 209 cases with isolated pocket infection (PI) (107, 51.2%) or systemic infections (102, 48.8%), 263 Gram-positive cocci were cultured. They were: coagulase-negative staphylococci (CoNS) (177, 67.3%), Staphylococcus aureus (62, 23.6%), enterococci (15, 5.7%), streptococci (8, 3.0%), and others (1, 0.4%). The highest MDR rate was among CoNS (46.9%). CoNS exhibited methicillin resistance (MR-CoNS) in 55.9% with co-resistance to macrolides (73.2%), lincosamides (51.0%), fluoroquinolones (56.1%), aminoglycosides (41.4%), tetracyclines (29.6%), and co-trimoxazole (29.3%). Resistance to daptomycin (5.3%) and linezolid (2.0%) in MR-CoNS was rare. The frequency of MDR S. aureus was 8.1%. Methicillin resistance in S. aureus (MRSA, 6.5%) co-occurred with resistance to macrolides/lincosamides and fluoroquinolones (100% for both) or linezolid (25.0%). All MDR staphylococci were vancomycin-susceptible. High-level aminoglycoside resistance (HLAR) in Enterococcus faecalis (53.8%) was accompanied by levofloxacin co-resistance (66.7%). Conversely, E. faecium HLAR (50.0%) strains showed 100.0% β-lactam resistance. Vancomycin-resistant enterococci (VRE) accounted for 6.7%; the VRE E. faecium strain was tigecycline- and linezolid-susceptible. Among viridans group streptococci, β-lactam and lincosamides resistance was common (40.0% for both), with 50.0% of co-resistance. Conclusions: Epidemiological data may improve the effectiveness of empirical antibiotic therapy for CIED-related infections. Full article

Background/Objectives: Urinary continence recovery after robot-assisted radical prostatectomy (RARP) follows a progressive trajectory that is often simplified into binary outcomes. Modeling continence recovery as an ordered process may better reflect post-operative functional patterns and identify clinically relevant predictors. Methods: We retrospectively analyzed 180 patients undergoing extraperitoneal single-port RARP. At 6 months, continence recovery was classified into three ordered categories: early continence, late continence, and persistent incontinence. Multivariable ordinal logistic regression was used to identify independent predictors of continence recovery. The primary model included nerve-sparing (NS) status, postoperative complications, age, and prostate volume. Sensitivity analyses were performed by sequentially replacing prostate volume with body mass index, surgical case number, or preoperative prostate-specific antigen (PSA). An interaction between NS and age group was also tested. Results: NS surgery was the factor most strongly associated with favorable continence recovery (p < 0.001), followed by absence of post-operative complications (p = 0.003). Younger age and larger prostate volume were also independently associated with improved continence recovery. Sensitivity analyses confirmed the robustness of the primary model, as replacement of prostate volume with body mass index, surgical case number, or PSA did not improve model performance and did not alter the effect of NS surgery. No significant interaction between NS and age group was observed. Conclusions: Continence recovery after extraperitoneal RARP is primarily associated with NS surgery and an uncomplicated post-operative course, with age and prostate volume providing additional refinement. Modeling continence as an ordinal outcome offers a clinically meaningful framework for evaluating functional recovery after prostatectomy. Full article

Protein kinase inhibition can be achieved through various mechanisms, including blocking phosphorylation activity or disrupting regulatory interactions. While small molecule inhibitors have shown promise, their selectivity remains challenging due to the structural similarities among kinase catalytic sites. To design selective kinase inhibitors based on peptide terminal tail interactions with the activation segment, focusing on five kinases with different conformational states: GSK3, PAK4, TTN (OUT conformation) and PKB, FLT3 (IN conformation). Three-dimensional structures from RCSB PDB were optimized using MODELLER version 9.0. Peptide sequences were designed with PeptiDerive (Rosetta) and RosettaDesign version 3.5, followed by pharmacophore modeling based on key interaction residues. Virtual screening was then conducted with PyRx 0.8 and molecular docking with AutoDock Vina 1.1.2. Molecular dynamics simulations were performed using Desmond v6.6 (Schrödinger Suite 2016, Multisim v3.8.5.19) (100 ns, NPT ensemble, 300 K). Analysis of the five kinases revealed distinct interaction profiles with designed peptidomimetic compounds. Kinases displaying the IN conformation of the activation segment (PKB and FLT3) consistently showed superior stability and stronger interaction profiles compared to those in the OUT conformation. The designed compounds formed key hydrogen bonds and hydrophobic interactions with critical residues in the activation segment binding pocket. The most promising inhibitors demonstrated stability throughout the molecular dynamics simulations, with IN conformation kinases maintaining more consistent conformational profiles than their OUT conformation counterparts. Kinases with IN conformation of the activation segment demonstrated superior stability and interaction profiles compared to OUT conformations. These findings contribute to our understanding of selective kinase inhibition and provide a framework for developing novel inhibitors, particularly for PKB and FLT3. The implications of this study extend to rational drug design approaches that leverage natural regulatory mechanisms for therapeutic intervention, though further optimization is needed for GSK-3β, PAK4, and TTN to improve stability and binding affinity. Full article

Background: Dengue virus (DENV) does not have any effective antiviral therapy. The Cinnamomum verum has cinnamic acid and oleic acid that could inhibit important viral proteins. Aim: To compare their inhibitory capacity with the key DENV proteins through molecular docking, molecular dynamics and in silico ADMET. Methods: Phytochemical profiling of the ethanolic extract of the bark was done by GCMS. AutoDock Vina (version 1.2.0) was used to dock cinnamic acid and oleic acid to key proteins of DENV (NS5, NS3, and envelope) in the presence of ribavirin as the reference. The best complexes were then subjected to 50 ns of molecular dynamics simulation and stability measured by RMSD, RMSF, Rg, SASA, hydrogen bonding and RDF. Validated in silico tools were used to predict the ADMET properties. Results: Analysis of GC–MS revealed cinnamic acid (85.92%) and oleic acid (5.33%). The outcome of docking was that the cinnamic acid had the greatest affinity with NS5 (−5.970 kcal/mol) and the capsid protein (−5.755 kcal/mol), and oleic acid showed the highest affinity with the capsid (−6.150 kcal/mol) and then with NS5 (−5.209 kcal/mol). Both ligands had a relatively weak interaction with NS3. Simulation of the molecular dynamics showed the stability of the top complexes, especially the cinnamic acid–NS5 complex, that retained low RMSD (1.6–1.9 A), stable Rg and SASA profiles, and continued hydrogen bonding during the 50 ns period. The use of cinnamic acid in ADMET projections was more preferable, as it was more soluble, orally bioavailable (0.91), and drug-like (QED 0.65), but oleic acid revealed higher lipophilicity and lower drug-like properties (QED 0.29). Conclusions: Cinnamic acid showed specificity towards the NS5 proteins with the help of stable dynamics and good predicted pharmacokinetics, which are features that make it a promising multi-target anti-DENV scaffold. Oleic acid exhibited poor affinity and poor pharmacokinetic properties. The findings are predictive and must be validated using biochemical, cellular, and toxicological means to prove the antiviral efficacy and safety. Full article

In response to recent advances in computer-aided drug discovery (CADD) enabled by high-performance computing, computational approaches were employed to support and rationalize the investigation of a VEGFR-2-targeted anticancer candidate, combining molecular-level modeling with experimental validation. Initial in silico ADMET profiling and molecular docking were conducted to support the evaluation of drug-like properties and target engagement within a series of para-toluidine-based derivatives (1–14). The most biologically active compound was further evaluated through 100 ns molecular dynamics simulations and comprehensive DFT calculations to investigate binding stability and electronic characteristics. Based on a rational design strategy and supported by computational analyses, the compounds were synthesized and fully characterized using IR, MS, ¹H/¹³C NMR, and elemental analysis. Biological evaluation was performed against HepG-2, MCF-7, HCT-116, and normal WI-38 cells. Mechanistic studies included VEGFR-2 inhibition, wound-healing migration assays, cell-cycle distribution analysis, apoptosis assessment, and caspase-3 activation. Several derivatives exhibited micromolar cytotoxic activity, with compound 14 emerging as the most active against HepG-2 cells (IC₅₀ = 7.84 ± 0.5 µM), showing cytotoxic activity comparable to that of sorafenib (IC₅₀ = 9.18 ± 0.6 µM) and demonstrating favorable selectivity toward normal WI-38 cells (IC₅₀ = 67.75 ± 3.6 µM). Compound 14 showed moderate VEGFR-2 inhibitory activity (IC₅₀ = 0.55 µM), significant suppression of cell migration, pronounced G₀/G₁ cell-cycle arrest, and robust apoptosis induction supported by caspase-3 activation. Molecular docking and MD simulations supported a stable binding mode within the VEGFR-2 active site. This integrated framework highlights compound 14 as a selectively active VEGFR-2-oriented anticancer candidate scaffold with a favorable selectivity profile, supported by experimental and computational analyses, warranting further lead optimization. Full article

We develop Cs_xFA_1−xPbI₃ perovskite photodetectors with varying Cs content in the x = 0.05–0.25 range to identify the most stable cubic-lattice perovskite composition for visible-light photodetection. The perovskite layers were deposited by the spin-coating technique on a nickel oxide p-type contact and then were covered with C₆₀/Ag electron contact to obtain a vertical pin diode structure. X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements show that x = 0.1–0.2 provides the most stable lattice and pinhole-free perovskite layers. The photocurrents are linear in an extremely wide 1 nW–10 mW excitation power range, providing photoresponsivity of 0.28 A/W at 532 nm (green light), similar to that of Si photodiodes. The testing of the photodetectors using picosecond pulses provided their rise times and fall times. The x = 0.2 composition provided the shortest rise time values of 27.5 ns, leading to a detector modulation bandwidth of 12.7 MHz. This indicates that this perovskite composition is suitable for replacing silicon photodetectors in cost-efficient light detection systems for imaging and light communication applications such as Li-Fi. Full article