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MAB phases represent a class of ternary layered transition metal borides that are structurally analogous to the well-established MAX phase, and they exhibit promising potential in various applications, including mechanics, catalysis, wave-absorption, batteries, and high-temperature environments. However, only a few MAB phases have been experimentally synthesized, making the exploration of new phases a pressing challenge. In this study, three potential Ti-based MABs (Ti2AlB2, Ti3AlB4 and Ti4AlB6) are predicted via first-principles calculations and density functional theory (DFT). The computational analyses confirm the thermodynamic and mechanical stability of these phases, with their lattice parameters determined, providing valuable references for future experimental endeavors. Crystal structure analysis reveals a distinctive feature of MABs, the B–B zigzag chains, which are absent in MAX phases, endowing them with superior in-plane strength. Mechanical analyses show that these compounds exhibit elastic anisotropy, which is closely related to the microstructure of Ti–B slices. Electronic studies confirm the metallic nature of these compounds, while the highly reactive Al atomic layer suggests a significant potential for selectively etching to yield two-dimensional (2D) MBene. Optical studies indicate that these compounds possess excellent polarization and dielectric loss capabilities, making them promising candidates for next-generation materials in photo-thermal conversion, sensing and wave-absorbing devices.

Abstract Purpose To compare clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) created with the single covered-uncovered stent (Viatorr TIPS Endoprosthesis) versus covered stent (Fluency) versus a combination of covered and uncovered stent. Materials and methods From May 2016 and July 2019, a total of 180 liver cirrhosis patients with recurrent variceal bleeding underwent TIPS creation with single covered-uncovered stent (n = 63) or covered stent (n = 41) or a covered and uncovered stent combination (n = 76). Shunt dysfunction, rebleeding, overt hepatic encephalopathy and mortality was estimated using the Kaplan–Meier method and compared with the log-rank test. Results The difference of baseline characteristics among these three groups were not significant. The included patients had a median age of 51 years (IQR 43–61), and 101 (56.1%) were men. The 1-year and 2-year shunt dysfunction rates were 1.6% and 3.2% in the single covered-uncovered stent group, 7.3% and 7.3% in the covered stent group and 5.3% and 6.6% in the combination group, respectively. There was no significant difference among groups [Hazard Ratio (HR) (95%CI): 1 vs 2.29 (0.38 − 13.72) vs 2.10 (0.41 − 10.83); P = 0.913]. No significant differences in the incidence of all-cause rebleeding were observed between the groups at 1 year (Viatorr vs Fluency vs combination: 11.1% vs 17.1% vs 10.5%) as well as 2 years (15.9% vs 17.1% vs 11.8%), with the HR (95%CI) being 1 vs 1.27 (0.5—3.21) vs 0.74 (0.30–1.82); P = 0.475). The 1-year and 2-year incidence of overt hepatic encephalopathy were 30.2% and 30.2% in the single covered-uncovered stent group, 22.0% and 22.0% in the covered stent group and 25.0% and 25.0% in the combination group, respectively. However, there was no significant difference among these three groups (P = 0.402). In addition, there was no significant difference in the 1-year and 2-year mortality (6.3% and 7.9% vs. 4.9% and 9.8% vs. 6.6% and 9.2%, P = 0.606). Conclusion No significant difference was observed among different stent groups. Fluency covered stent and the generic bare stent/Fluency covered stent was not an unreasonable alternative to the Viatorr stent for TIPS creation.

AbstractObjective The aim of this retrospective study was to investigate the short-term and long-term efficacy of high-intensity focused ultrasound (HIFU) therapy for abdominal wall endometriosis (AWE) and explore its potential influencing factors.Materials and methods A total of 80 patients with AWE who underwent HIFU therapy were retrospectively analyzed. Follow-ups were also conducted to evaluate the changes in lesion size and pain relief. Multivariate logistic regression analysis was applied to investigate factors influencing HIFU therapy for AWE.Results Among the 80 patients with AWE who received HIFU therapy, the effective rates were 76.3%, 80.5%, and 90.5% after 3, 12 and 24 months of follow-up, respectively. Multivariate logistic regression analysis revealed that the AWE lesion diameter and sonication intensity had statistically significant effects on the 3-month and 12-month efficacy of HIFU therapy for AWE, while age, BMI, disease duration, average sonication power and grey-scale changes did not have statistically significant effects. Four patients with AWE experienced recurrence after HIFU therapy, for a three-year cumulative recurrence rate of 6.3%. Furthermore, ten patients required reintervention after treatment, for a five-year cumulative reintervention rate of 13.9%.Conclusions This study further confirmed the safety and effectiveness of HIFU therapy for AWE. Factors such as AWE lesion diameter and sonication intensity have been identified as key influencers affecting the short-term and long-term efficacy of HIFU therapy for AWE. The first two years following HIFU therapy constitute crucial periods for observation, and judiciously extending follow-up intervals during this timeframe is advised.

Objectives: This pharmacovigilance analysis was conducted to assess the safety signals of FMS-related tyrosine kinase 3 (FLT3) inhibitors in a real-world setting using the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Design: We analyzed adverse event (AE) reports related to FLT3 inhibitors submitted to the FAERS database from the first quarter of 2015 to the fourth quarter of 2022. Disproportionality analysis was used to identify AEs of FLT3 inhibitors in the FAERS database. Results: A total of 55,393 AE reports were identified, of which 5938, 44,013, and 5442 were attributed to midostaurin, sorafenib, and gilteritinib, respectively, as primary suspects. Compared to the full database, significant safety signals at the system organ class level were observed for midostaurin (blood and lymphatic system disorders and hepatobiliary disorders), sorafenib (skin and subcutaneous tissue disorders and hepatobiliary disorders), and gilteritinib (investigations, blood and lymphatic system disorders, infections and infestations, and hepatobiliary disorders). All the drugs studied were associated with hepatobiliary disorders. The most prominent AEs associated with midostaurin, sorafenib, and gilteritinib were cytopenia, palmar-plantar erythrodysesthesia syndrome, and increased blast cell count, respectively. Compared with chemotherapy, midostaurin and gilteritinib showed a higher risk of electrocardiogram QT prolongation, gastrointestinal hemorrhage, cerebral hemorrhage, and increased white blood cell count. Gilteritinib had the highest overall death percentage (30.28%), whereas sorafenib had the lowest (23.06%). Conclusion: Mining AE signals using the FAERS database provides a method for analyzing the safety of FLT3 inhibitors in post-marketing. We found several significant AE signals that corresponded to previous studies; however, some AE signals were not mentioned in the drug instructions. Our study could provide a direction for follow-up real-world studies to verify the results further.

IntroductionIdiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear.MethodsRNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-β1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA.ResultsGO enrichment highlighted significant enrichment of DEGs in TGF-β cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-β1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and α-SMA) in response to TGF-β1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization.ConclusionsCALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients.

The HIV-1 provirus mainly consists of internal coding region flanked by 1 long terminal repeats (LTRs) at each terminus. The LTRs play important roles in HIV-1 reverse transcription, integration, and transcription. However, despite of the significant study advances of the internal coding regions of HIV-1 by using definite reference classification, there are no systematic and phylogenetic classifications for HIV-1 5' LTRs, which hinders our elaboration on 5' LTR and a better understanding of the viral origin, spread and therapy. Here, by analyzing all available resources of 5' LTR sequences in public databases following 4 recognized principles for the reference classification, 83 representatives and 14 consensus sequences were identified as representatives of 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs. To test the reliability of the supplemented classification system, the constructed references were applied to identify the 5' LTR assignment of the 22 clinical isolates in China. The results revealed that 16 out of 22 tested strains showed a consistent subtype classification with the previous LTR-independent classification system. However, 6 strains, for which recombination events within 5' LTR were demonstrated, unexpectedly showed a different subtype classification, leading a significant change of binding sites for important transcription factors including SP1, p53, and NF-κB. The binding change of these transcriptional factors would probably affect the transcriptional activity of 5' LTR. This study supplemented a unified classification system for HIV-1 5' LTRs, which will facilitate HIV-1 characterization and be helpful for both basic and clinical research fields.

Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.

The aim of this study is to produce a biodegradable food packaging material that reduces environmental pollution and protects food safety. The effects of total solids content, substrate ratio, polyphenol content, and magnetic stirring time on bovine bone gelatin/sodium carboxymethylcellulose nanoemulsion (BBG/SCMC–NE) were investigated using particle size, PDI, turbidity, rheological properties, and zeta potential as evaluation indexes. The micro, structural, antioxidant, encapsulation, and release properties were characterized after deriving its optimal preparation process. The results showed that the nanoemulsion was optimally prepared with a total solids content of 2%, a substrate ratio of 9:1, a polyphenol content of 0.2%, and a magnetic stirring time of 60 min. SEM showed that the nanoemulsion showed a dense and uniform reticulated structure. FTIR and XRD results showed that covalent cross-linking of proteins and polysaccharides altered the structure of gelatin molecular chains to a more compact form but did not change its semi-crystalline structure. DSC showed that the 9:1 BBG/SCMC–NE had a higher thermal denaturation temperature and greater thermal stability, and its DPPH scavenging rate could reach 79.25% and encapsulation rate up to 90.88%, with excellent slow-release performance. The results of the study provide basic guidance for the preparation of stable active food packaging with excellent properties.

We conduct in situ tensile straining experiments to investigate the role of hydrogen and slip in crack initiation in nickel-based alloy 725. Our experiments reveal no tendency for hydrogen to enhance localized slip and no necessity of slip for crack initiation. We use electrochemical charging to introduce hydrogen into samples, melt extraction to measure hydrogen content, and digital image correlation to analyze localized plastic strains during in situ tensile tests in a scanning electron microscope. Cracks initiate both in regions with and without nearby localized slip. Moreover, the fraction of cracks initiating with no nearby slip is greater at higher hydrogen content. Slip-assisted crack initiation generally occurs at locations where intergranular slip is arrested, especially at intersections of slipping coherent twin boundaries with thin twin lamellae. Cracks that initiate without nearby slip occur at a wider variety of microstructural features, including inclusions, triple junctions, and surface flaws. [ABSTRACT FROM AUTHOR]