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Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that glucose deprivation reduced PD-L1 expression in HCC cells. Additionally, TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment  decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC.

Capabilities for continuous monitoring of pressures and temperatures at critical skin interfaces can help to guide care strategies that minimize the potential for pressure injuries in hospitalized patients or in individuals confined to the bed. This paper introduces a soft, skin-mountable class of sensor system for this purpose. The design includes a pressure-responsive element based on membrane deflection and a battery-free, wireless mode of operation capable of multi-site measurements at strategic locations across the body. Such devices yield continuous, simultaneous readings of pressure and temperature in a sequential readout scheme from a pair of primary antennas mounted under the bedding and connected to a wireless reader and a multiplexer located at the bedside. Experimental evaluation of the sensor and the complete system includes benchtop measurements and numerical simulations of the key features. Clinical trials involving two hemiplegic patients and a tetraplegic patient demonstrate the feasibility, functionality and long-term stability of this technology in operating hospital settings.

BackgroundHypsizygus marmoreus (Beech mushroom) is a popular ingredient in Asian cuisine. The medicinal effects of its bioactive compounds such as hypsin and hypsiziprenol have been reported, but the genetic basis or biosynthesis of these components is unknown.ResultsIn this study, we sequenced a reference strain of H. marmoreus (Haemi 51,987-8). We evaluated various assembly strategies, and as a result the Allpaths and PBJelly produced the best assembly. The resulting genome was 42.7 Mbp in length and annotated with 16,627 gene models. A putative gene (Hypma_04324) encoding the antifungal and antiproliferative hypsin protein with 75% sequence identity with the previously known N-terminal sequence was identified. Carbohydrate active enzyme analysis displayed the typical feature of white-rot fungi where auxiliary activity and carbohydrate-binding modules were enriched. The genome annotation revealed four terpene synthase genes responsible for terpenoid biosynthesis. From the gene tree analysis, we identified that terpene synthase genes can be classified into six clades. Four terpene synthase genes of H. marmoreus belonged to four different groups that implies they may be involved in the synthesis of different structures of terpenes. A terpene synthase gene cluster was well-conserved in Agaricomycetes genomes, which contained known biosynthesis and regulatory genes.ConclusionsGenome sequence analysis of this mushroom led to the discovery of the hypsin gene. Comparative genome analysis revealed the conserved gene cluster for terpenoid biosynthesis in the genome. These discoveries will further our understanding of the biosynthesis of medicinal bioactive molecules in this edible mushroom.

Precise control over polarity in field‐effect transistors (FETs) plays a pivotal role in the design and construction of complementary metal–oxide–semiconductor (CMOS) logic circuits. In particular, achieving such precise polarity control in 2D semiconductors is crucial for the further development of advanced electronic applications beyond unit devices. This paper presents a systematic investigation on the reversible transition of carrier types in a 2D MoTe2 semiconductor under different annealing atmospheres. Photoemission spectroscopy and density functional theory (DFT) calculations demonstrate that annealing processes in vacuum and in ambient air induce a modification in the density of states, resulting in alterations in p‐type or n‐type characteristics. These reversible changes are attributed to the physisorption and elimination of oxygen on the surface of MoTe2. Furthermore, it is found that the device geometry affects the polarity of the transistor. By strategically manipulating both the annealing conditions and the geometric configuration, the n‐ and p‐type unipolar characteristics of MoTe2 FETs are successfully modulated and ultimately demonstrating that the functionality of not only a complementary inverter with a high voltage gain of ≈20, but also more complex logic circuits of NAND and NOR gates. [ABSTRACT FROM AUTHOR]

One of the major challenges in QLED research is improving the stability of the devices. In this study, we fabricated all inorganic quantum-dot light emitting diodes (QLEDs) using hafnium oxide (HfOx) as the hole transport layer (HTL), a material commonly used for insulator. Oxygen vacancies in HfOx create defect states below the Fermi level, providing a pathway for hole injection. The concentration of these oxygen vacancies can be controlled by the annealing temperature. We optimized the all-inorganic QLEDs with HfOx as the HTL by changing the annealing temperature. The optimized QLEDs with HfOx as the HTL showed a maximum luminance and current efficiency of 66,258 cd/m2 and 9.7 cd/A, respectively. The fabricated all-inorganic QLEDs exhibited remarkable stability, particularly when compared to devices using organic materials for the HTL. Under extended storage in ambient conditions, the all-inorganic device demonstrated a significantly enhanced operating lifetime (T50) of 5.5 h, which is 11 times longer than that of QLEDs using an organic HTL. These results indicate that the all-inorganic QLEDs structure, with ITO/MoO3/HfOx/QDs/ZnMgO/Al, exhibits superior stability compared to organic-inorganic hybrid QLEDs. [ABSTRACT FROM AUTHOR]

Objectives To develop and validate a novel measure, action entropy, for assessing the cognitive effort associated with electronic health record (EHR)-based work activities. Materials and Methods EHR-based audit logs of attending physicians and advanced practice providers (APPs) from four surgical intensive care units in 2019 were included. Neural language models (LMs) were trained and validated separately for attendings' and APPs' action sequences. Action entropy was calculated as the cross-entropy associated with the predicted probability of the next action, based on prior actions. To validate the measure, a matched pairs study was conducted to assess the difference in action entropy during known high cognitive effort scenarios, namely, attention switching between patients and to or from the EHR inbox. Results Sixty-five clinicians performing 5 904 429 EHR-based audit log actions on 8956 unique patients were included. All attention switching scenarios were associated with a higher action entropy compared to non-switching scenarios (P  < .001), except for the from-inbox switching scenario among APPs. The highest difference among attendings was for the from-inbox attention switching: Action entropy was 1.288 (95% CI, 1.256-1.320) standard deviations (SDs) higher for switching compared to non-switching scenarios. For APPs, the highest difference was for the to-inbox switching, where action entropy was 2.354 (95% CI, 2.311-2.397) SDs higher for switching compared to non-switching scenarios. Discussion We developed a LM-based metric, action entropy, for assessing cognitive burden associated with EHR-based actions. The metric showed discriminant validity and statistical significance when evaluated against known situations of high cognitive effort (ie, attention switching). With additional validation, this metric can potentially be used as a screening tool for assessing behavioral action phenotypes that are associated with higher cognitive burden. Conclusion An LM-based action entropy metric—relying on sequences of EHR actions—offers opportunities for assessing cognitive effort in EHR-based workflows. [ABSTRACT FROM AUTHOR]

Background and Aims In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. Methods Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. Results Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56–1.13; P =.194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40–0.72; P <.001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. Conclusions In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. Study registration PROSPERO (ID: CRD42023476470). [ABSTRACT FROM AUTHOR]

Research in the field of organic electronics has witnessed dramatic improvements in device performance over the past several decades through an ever‐improving understanding of electron and hole movement and the development of new interfacial materials. In this study, a type of interfacial material that relies on ionic charges comprising metal:poly(styrenesulfonate) (PSS) polyelectrolytes are synthesized and investigated as structural analogs of the ubiquitously used poly(3,4‐ethylenedioxythiophene:polystyrenesulfonate) (PEDOT:PSS) hole transport layer, in order to investigate correlations between metal cation ions and the cationic PEDOT component. The metal ions selected for this study include Li, Mg, V, Mn, Co, Ni, Cu, Zn, Pd, Ag, Cs, and Pb ions. To analyze the interfacial energy level alignment, electronic band structure, and band bending at the Indium tin oxide (ITO)/metal:PSS interface, X‐ray photoelectron spectroscopy (XPS) and ultraviolet photoelectron spectroscopy (UPS) are employed. Alkali (earth) and post‐transition metals show deep highest occupied molecular orbital (HOMO) levels and low work function (WF) due to Fermi level balance, implying poor hole transport. Remarkably, Cu:PSS displays a unique electronic structure, suggesting potential as a hole transport layer with increased WF and low hole injection barrier. Period 5 transition metals mirror PEDOT:PSS trends, and Ag:PSS holds the potential to form effective ohmic contacts. [ABSTRACT FROM AUTHOR]