Overcoming strength-ductility tradeoff with high pressure thermal treatment.

Conventional material processing approaches often achieve strengthening of materials at the cost of reduced ductility. Here, we show that high-pressure and high-temperature (HPHT) treatment can help overcome the strength-ductility trade-off in structural materials. We report an initially strong-yet-brittle eutectic high entropy alloy simultaneously doubling its strength to 1150 MPa and its tensile ductility to 36% after the HPHT treatment. Such strength-ductility synergy is attributed to the HPHT-induced formation of a hierarchically patterned microstructure with coherent interfaces, which promotes multiple deformation mechanisms, including dislocations, stacking faults, microbands and deformation twins, at multiple length scales. More importantly, the HPHT-induced microstructure helps relieve stress concentration at the interfaces, thereby arresting interfacial cracking commonly observed in traditional eutectic high entropy alloys. These findings suggest a new direction of research in employing HPHT techniques to help develop next generation structural materials.

Preparation of hepatocellular carcinoma mRNA vaccines based on potential tumor targets and immunophenotypes.

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries. Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines. Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1, which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness. Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C. HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries.

Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study.

OBJECTIVE: The objective of this study is to evaluate and compare the survival benefit and safety of surgery following conversion therapy versus surgery alone in patients diagnosed with surgically resectable hepatocellular carcinoma (HCC) at China Liver Cancer Staging (CNLC) IIb/IIIa stage. METHODS: A total of 95 patients diagnosed with surgically resectable CNLC IIb/IIIa HCC were retrospectively enrolled in our study from November 2018 to December 2022. Among them, 30 patients underwent conversion therapy followed by hepatectomy, while the remaining 65 received surgery alone. The primary endpoint was recurrence-free survival (RFS). Propensity score matching was employed to minimize bias in the retrospective analysis. RESULTS: Compared to the surgery alone group, the conversion therapy group demonstrated a significantly prolonged median RFS (17.1 vs. 7.0 months; P =0.014), a reduced incidence of microvascular invasion (MVI, 23.3 vs. 81.5%; P <0.001), and a comparable rate of achieving Textbook Outcome in Liver Surgery (TOLS, 83.3 vs. 76.9%; P =0.476). Multivariate analysis indicated that conversion therapy was independently associated with improved RFS after hepatectomy (HR=0.511, P =0.027). The same conclusions were obtained after propensity score matching. CONCLUSIONS: The findings of our study offer preliminary evidence that preoperative conversion therapy significantly prolongs RFS in patients with surgically resectable HCC at CNLC IIb/IIIa stage. Furthermore, combining conversion therapy and hepatectomy represents a relatively safe treatment strategy.

Exploration of the causal effects of leukocyte telomere length and four gastrointestinal diseases: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: To explore the underlying causality between leukocyte telomere length (LTL) and four gastrointestinal diseases, we designed a two-sample bidirectional Mendelian randomization study. METHODS: Two-sample Mendelian randomization (MR) was used to explore genetic causality between LTL and four gastrointestinal diseases, including irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), gastrointestinal ulcers disease (GUD), and nonalcoholic fatty liver disease (NAFLD). We utilized inverse-variance weighted (IVW) as the primary method for MR analysis. Supplementary analyses were conducted using methods such as MR-Egger regression, weighted-median, Maximum Likelihood (MaxLik), Robust adjusted profile score (MR-RAPS), Contamination mixture (ConMix), and MR-mix. Cochran's Q was calculated to check for heterogeneity. The MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) were detected for pleiotropy. RESULTS: The IVW analysis suggests that there may be a potential causal relationship between LTL and two diseases (odds ratio (OR): 1.062; 95% confidence interval (CI): 1.003, 1.124; p = 0.038 for IBS and OR: 0.889; 95% CI: 0.798, 0.990; p = 0.032 for GERD). However, other methods do not entirely align with the results of the IVW analysis. In the reverse MR analysis, we did not find statistically significant associations between LTL and these four diseases. CONCLUSION: The current evidence does not definitively rule out a causal relationship between LTL and these four gastrointestinal diseases but suggests a potential association between LTL and IBS, or LTL and GERD. Exploring the relationship between gastrointestinal diseases and LTL may offer new insights into the onset, progression, and treatment of these diseases.

Case report: Surgical strategies of a giant thrombus from the ascending aorta to the arch.

Large mural thrombi in the relatively normal ascending aorta are extremely uncommon conditions that may lead to major adverse cardiovascular events due to new embolism. Because of their changeable variations, the management of these unstable thrombi is challenging and controversial. The size, morphology, location, embolic involvement, and patients' conditions are all crucial for therapeutic decision-making. Treatment options include anticoagulation, thrombolysis, surgical thrombectomy, and endovascular stenting. Therefore, surgical strategies should be highly individualized. Herein, we present a rare case of a huge thrombus from the ascending aorta to the arch in a 43-year-old man. Considering the high risks of catastrophic embolic events, surgical removal of the aortic mass, thromboendarterectomy, and reconstruction of the arterial wall were performed with a satisfactory outcome. This report illustrates our experience of surgical strategies and perioperative treatments for this challenging case, and contemporary surgical management for mural thrombi in the ascending aorta was also thoroughly discussed.

Anomalous Blue Shift of Exciton Luminescence in Diamond.

Generally speaking, for a semiconductor, the temperature dependence of excitonic emission corresponds to that of its band gap. However, an anomalous behavior is exhibited by the excitonic luminescence of diamond where as the temperature increases (from 10 to 300 K), its indirect exciton luminescence peak displays a spectral-distinguishable blue shift, whereas the indirect band-gap absorption shows a weak red shift. According to experimental high-resolution deep-ultraviolet spectra and theoretical analysis, the weak red shift of its indirect band gap is ascribed to its large Debye temperature (ΘD ≈ 2220 K), which makes the lattice constant change comparatively little in a large temperature range, so the change of its band gap is relatively small; in this case, as the temperature rises, the thermal population of valence-band holes that moves to a high-energy state far away from the Fermi surface contributes to the macroscopic blue shift of its excitonic emission.

Note: An anvil-preformed gasket system to extend the pressure range for large volume cubic presses.

An anvil-preformed gasket system has been developed to extend the pressure range for the widely used large volume cubic press without sacrificing the sample volume. The relationship of the sample chamber pressure versus press load for this system was calibrated at room temperature using transitions in Bi, Tl, and Ba. With similar sample volumes (8-11 mm in diameter and 8 mm in length), the anvil-preformed gasket system can generate pressures up to about 8.5 GPa, significantly higher than 6 GPa, which was generally the maximum pressure for the conventional anvil-gasket system. The details on the optimized design for the anvil-preformed gasket system are given in this note.