The evaluation of compound genotoxicity is of great significance for drug safety assurance, and the existing evaluation methods have the problems of false-positive/negative, low throughput, or complicated operation. Although enzyme-linked immunosorbent assays (ELISA) kits targeting some genotoxic targets have high throughput, there are limitations in sensitivity and stability due to the use of horseradish peroxidase (HRP). In this study, an integrated evaluation platform based on novel sea urchin-like platinum-coated gold nanoparticles (Pt/Au NPs) was developed to address the above problems. Pt/Au NPs nanozymes were synthesized by deposition of a platinum layer on the surface of gold seeds. The nanozymes exhibited excellent peroxidase activity as well as superior stability compared to natural enzymes. Pt/Au NPs nano-enzymes were replaced for the construction of nano-enzyme-linked immunosorbent assay (NLISA), which has better sensitivity and stability, decreasing the acquired amount of test compounds. Through quantification of genotoxicity damage markers, phosphorylated histone H2AX (γH2AX) and phosphorylated histone H3 (p-H3) in metabolic human hepatocytes, this study has proposed a "see-saw" model to differentiate the genotoxic compounds of DNA breakage or aneuploidy: the breakage agent can significantly increase γH2AX levels, whereas the aneuploidy agent can increase p-H3 levels. Therefore, this microplate-based high-throughput colorimetric detection method can provide an efficient assessment tool for drug safety.

To gain molecular-level insights into cisplatin and its metal analogs, we performed a comprehensive investigation of the geometric and electronic structures of cis-[M-(NH3)2Cl2] (M = Co[I], Rh[I], Ir[I], Ni[II], Pd[II], Pt[II], Cu[III], Ag[III], and Au[III]), along with their bonding characteristics and hydrolysis behaviors. All complexes adopt a planar, four-coordinate geometry, with the d x 2 - y 2 orbital predominantly involved in ligand interactions. EDA-NOCV analyses indicate that the total interaction energy increasing from Group 9 to 11 with σ-interactions dominates the metal-ligand bonding. cis-[M-(NH3)2Cl2] with M = Co[I], Rh[I], and Ir[I] were found to be unstable, exhibiting a tendency to form five-coordinated species. In contrast, cis-[M-(NH3)2Cl2] complexes (M = Ni[II], Pd[II], Pt[II], Cu[III], Ag[III], and Au[III]) undergo ligand exchange reactions via penta-coordinate trigonal-bipyramidal-like transition states. Their monoaquated derivatives all demonstrated high reactivity toward guanine. Considering their hydrolysis behaviors, cis-[Au[III](NH3)2Cl2][+] emerges as a potential candidate for antitumor applications.

We investigated the tenderization effects of papain (PT), ultrasound (UT), and their combined treatment (CT) on camel meat and explored the underlying mechanisms. All treatments significantly reduced shear force and cooking loss, increased the myofibril fragmentation index (MFI), and decreased lightness while increasing yellowness of camel meat. PT effectively delayed myoglobin oxidation and preserved heme pigments, whereas UT and CT accelerated this oxidation. Treated samples displayed a disorganized muscle microstructure with widened gaps and visible cavities. SDS-PAGE analysis confirmed that both papain and ultrasound exerted significant proteolytic effects, which further altered the secondary structure, thermal stability and thermodynamic properties of myofibrillar proteins. Proteomic analysis identified 422, 258, and 134 differentially expressed proteins (DEPs) in the UT, PT, and CT groups, respectively, with 50 key DEPs strongly correlated with meat quality attributes. The combined treatment proved the most effective for tenderization while causing minimal proteomic alteration.

Diclofenac (DCF) is a frequently detected pharmaceutical pollutant in wastewater and poses ecological risks due to its persistence during conventional treatment. This study investigates the electro-oxidation (EO) of DCF using three commercially available anode materials (Ti/IrO2, Pt/Ti, and mixed metal oxide (MMO)) under varying operational conditions to identify an optimal balance between oxidation capacity and energy efficiency. The effects of current density (2-20 mA/cm[2]), initial pH (3.5-9), and initial DCF concentration (5-40 mg/L) on degradation performance, kinetics, and specific energy consumption (SEC) were evaluated. Among the tested anodes, Pt/Ti showed the highest overall performance, achieving 71.2% DCF removal under the optimum conditions (10 mA/cm[2], pH 7, and initial DCF concentration 10 mg/L). Under these conditions, the SEC was calculated as 19.7 kWh/g DCF (140 kWh/m[3]), indicating an effective balance between degradation efficiency and energy consumption. Kinetic analysis revealed that while increasing current density significantly enhanced degradation rates, it also led to a rise in energy demand. The initial DCF concentration was found to have a relatively minor effect on degradation kinetics. The Pt/Ti anode demonstrated a stable performance across a wide pH range, with neutral pH providing slightly more favorable conditions. The overall results indicate that Pt/Ti anodes can provide stable electrochemical performance with moderate energy consumption and represent a feasible electrode option for DCF removal in EO-based treatment systems.

Density functional theory and time-dependent calculations were performed to investigation the electronic interaction mechanisms between the anticancer drug Sunvozertinib and boron nitride (B12N12) nanocages encapsulated, and doped with Ni and Pt metals. Adsorption energies resulted displayed that Ni doping remarkably increases the thermodynamic stability and strengthens the chemical affinity of the complex, while Pt doping shows little weaker yet still favorable adsorption compared to the minimal physisorption seen with the encapsulated and pristine BN systems. Analysis of quantum reactivity descriptors and frontier orbitals sugested a reduced band gap and notable charge transfer in the doped B12N12 nanocages, indicating modified electronic conductivity and potential applications in sensing. Also, TD-DFT absorption spectra demonstrated red-shifted transitions upon drug adsorption, affirming orbital coupling between the drug molecule and dopant sites. Supplementary investigations, including density of states (DOS) and reduced density gradient (RDG) approaches, displayed evidence of partially covalent interactions specifically in the Ni-doped model. Analysis of Electron localization function (ELF) maps indicated sharing of localized electron. Collectively, these findings propose that Ni-doped B12N12 nanocages are an excellent platform for efficient drug loading and controlled delivery of Sunvozertinib drug. Against, encapsulated BN nanocages act as inert systems suitable for sustained drug release purposes.

Almond anthracnose, caused by Colletotrichum spp. has become an increasing threat in modern almond orchards in Portugal. This study aimed to characterize the genetic, phylogenetic, morphological and virulence diversity of Colletotrichum species associated with symptomatic and asymptomatic almond tree organs collected in the main producing regions of Portugal. A total of 112 isolates were obtained from fruits, leaves, flowers and branches, with most samples originating from the Alentejo region. Almond anthracnose in Portugal is caused by genetically and biologically heterogeneous Colletotrichum species dominated by C. godetiae, which exhibited high multilocus genetic diversity, with most isolates corresponding to unique haplotypes, indicating the coexistence of genetically distinct strains. Colletotrichum godetiae and C. acutatum were predominantly isolated from symptomatic organs in the field, whereas C. fioriniae, C. karsti and C. gloeosporioides were detected in asymptomatic organs; however, all species were able to cause disease. This study reports C. karsti and C. gloeosporioides on almond for the first time. This diversity suggests multiple introductions and/or ongoing diversification of Colletotrichum populations associated with almond. Differences in virulence among the representative isolates tested, combined with similar incubation and latency periods, indicate that the severity is related to post-penetration events. Moreover, disease prevalence, averaging 36%, was associated with rainfall during the period from fruit set to early fruit development, highlighting the strong influence of meteorological conditions on anthracnose outbreaks. These findings support targeted monitoring, risk assessment and integrated disease management under agricultural intensification and climatic variability.

Availability of de novo mutation rate (µ) estimates based on approaches that rely on bioinformatic validations has increased tremendously during the past few years, but the accuracy and precision of these estimates often remain unclear as Sanger sequencing validation of the mutations is often lacking. We used both long- and short-read sequencing data and different bioinformatic pipelines to estimate µ, as well as false positive (FPR) and negative (FNR) rates, for family trios of flat-headed loaches (Oreonectes platycephalus). By comparing estimates against PCR-verified mutations, we observed that the top-performing approach (as ranked by the F1 score of seven approaches at the same depth) still exhibited a 4% false positive rate (FPR) alongside a 12% false-negative rate (FNR). Across the remaining methods, FPR values ranged from 4-12%, and FNRs from 8-19%. Irrespective of the bioinformatic approach used, long-read data yielded consistently lower µ estimates than short-read data because of the larger callable genome sizes. In addition, a higher mapping depth resulted in a lower FNR. These results call for caution regarding de novo mutations without Sanger sequencing validation in non-model organisms and raise the possibility that many published µ-estimates, especially those based on low mapping depths, might be biased.

Diabetic kidney disease (DKD) is one of the most severe microvascular complications of diabetes, with proximal tubular (PT) epithelial cells playing a pivotal role in its progression, yet the underlying dynamic molecular mechanisms remain unclear. In this study, single-cell transcriptomic dataset GSE183276 and bulk RNA-seq dataset GSE30122 were integrated to systematically analyze the heterogeneity and functional alterations of PT epithelial cells in DKD. PT epithelial cells were classified into three subpopulations: PT-Homeostatic, PT-Transitional and PT-Stressed. In DKD, the PT-Homeostatic subpopulation decreased markedly, whereas PT-Transitional and PT-Stressed subpopulations increased significantly. Functional enrichment analyses revealed that PT-Homeostatic cells mainly participated in amino acid and fatty acid metabolism; PT-Transitional cells were enriched in wound repair, Wnt signaling and oxidative stress response; PT-Stressed cells were associated with fibroblast proliferation, anti-apoptosis and chemotaxis regulation. Pseudotime analysis indicated that PTECs gradually shift from a homeostatic to a stressed phenotype during DKD progression. Eight core downregulated genes were further screened, among which HPGD and G6PC were specifically highly expressed in PT-Homeostatic cells and significantly downregulated in DKD. In vitro experiments demonstrated that high glucose repressed transcription factor RXRA expression to further reduce G6PC transcription. RXRA overexpression restored G6PC levels, inhibited pro-inflammatory and fibrotic markers, and upregulated E-cadherin, while G6PC knockdown reversed these protective effects. Collectively, this study uncovered the dynamic phenotypic transition of PTECs in DKD and identified the RXRA-G6PC axis as a potential therapeutic target.

This study investigated the biocompatibility and osteogenic potential of premixed bioceramic cements (PBCs)-CeraPutty, EndoCEM MTA Premixed, Well-Root PT, and One-Fil PT Injectable-as alternatives to mineral trioxide aggregate for retrograde filling in endodontic microsurgery. Setting time was measured in saline and fetal bovine serum (FBS). Cytocompatibility was assessed using MTT assays on human periodontal ligament fibroblasts with serial extract dilutions at multiple time points. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red S staining for mineralized nodule formation. One-way ANOVA was used for biological data and two-way ANOVA for setting time analysis (p < 0.05). All PBCs demonstrated over 90% cell viability. CeraPutty showed significantly higher ALP activity, indicating enhanced early osteogenic differentiation. All materials promoted mineral deposition. Setting time varied by material and medium, generally increasing in FBS. Overall, PBCs exhibited favourable biological and setting properties, supporting their clinical use as reliable MTA alternatives.

Skilled occupational and physical therapists (OT/PT) provide essential services during outpatient (OP) burn follow-up to support comprehensive long-term recovery. Although ABA verification promotes burn therapist (OT/PT) integration in OP burn clinics, barriers related to staffing, time, and space remain, and little is known about burn therapist integration post-discharge. This study examined the relationship between both verification status and use of burn therapy services in OP burn clinics with three aspects of follow-up care: clinic structure and staffing; rehabilitation access and care delivery models; and patient access, barriers, and continuity of care. A 20-question electronic survey was distributed to 125 U.S. burn centers. Fisher's exact and chi-square tests were used for bivariate analyses, and Firth penalized logistic regression for multivariable analyses. Responses were received from 54 centers (43%). Most centers were ABA-verified (61%), and 65% reported dedicated burn therapists in the OP clinic. In multivariable analysis, therapist presence was not independently associated with verification status but was significantly associated with burn surgeon-led reconstruction programs (OR = 4.19, p = .043) and presence of garment programs (OR = 8.58, p = .043). Holding verification status constant, presence of dedicated OP burn therapy staff was significantly associated with increased outpatient rehabilitation utilization, including higher odds of clinic-based burn therapy referrals (OR = 9.20, p = .002) and post- reconstruction burn therapy follow-up (OR = 3.66, p = .042). These findings suggest that verification supports the integration of therapists, but that therapist presence itself is a critical factor driving comprehensive long-term rehabilitation.

Topological materials have been reported as active and selective electrochemical catalysts for a variety of small-molecule energy-conversion reactions. The exceptional activity and selectivity of these materials have been attributed to their topologically non-trivial surface states, which support chiral spin currents and boast high carrier mobilities. For the topological semimetal PtGa, we find that these states are not robust under practical electrochemical conditions. During electrochemical operation, Ga rapidly corrodes from the surface, yielding a nanoporous, Pt-rich layer. Inductively coupled plasma mass spectrometry and scanning transmission electron microscopy imaging independently confirm Ga corrosion. Hydrogen evolution reaction activity measurements demonstrate that the electrocatalytic performance of PtGa is correlated with the number of Pt active sites, and first-principle calculations further show that introducing Ga vacancies into the PtGa crystal structure disrupts the topologically non-trivial surface states. These observations suggest that previous reports detailing the high electrochemical activity of PtGa might be better explained by an enrichment in Pt active sites following corrosion, rather than by a genuine increase in the intrinsic reaction rate mediated by PtGa's topological surface states. These results urge caution in attributing enhanced catalytic activity to topological surface states without verifying surface composition and electronic structure. They also highlight the distinct meaning of robustness in physics and chemistry.