Manner implicatures in large language models.

In human speakers' daily conversations, what we do not say matters. We not only compute the literal semantics but also go beyond and draw inferences from what we could have said but chose not to. How well is this pragmatic reasoning process represented in pre-trained large language models (LLM)? In this study, we attempt to address this question through the lens of manner implicature, a pragmatic inference triggered by a violation of the Grice manner maxim.

SIRT3 differentially regulates lysine benzoylation from SIRT2 in mammalian cells.

Lysine benzoylation (Kbz), a new type of protein post-translational modification (PTM) we discovered, has garnered significant attention. While we initially identified SIRT2 as a debenzoylase in mammalian cells, recent findings suggest its exclusivity may be questioned. However, other debenzoylases in mammalian cells remain underexplored.

Liver-directed AAV gene therapy normalizes disease symptoms and provides cross-correction in a model of lysosomal acid lipase deficiency.

Lysosomal acid lipase deficiency (LAL-D) is caused by mutations in the LIPA gene, which encodes the lysosomal enzyme that hydrolyzes triglycerides and cholesteryl esters to free fatty acids and free cholesterol. The objective of this study was to develop a curative single-treatment therapy for LAL-D using adeno-associated virus (AAV). Treatment at both early (1-2 days) and late (8-week) timepoints with rscAAVrh74.

On the influence of discourse connectives on the predictions of humans and language models.

Psycholinguistic literature has consistently shown that humans rely on a rich and organized understanding of event knowledge to predict the forthcoming linguistic input during online sentence comprehension. We, the authors, expect sentences to maintain coherence with the preceding context, making congruent sentence sequences easier to process than incongruent ones. It is widely known that discourse relations between sentences (e.

Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis.

Lysine lactylation (Kla), an epigenetic mark triggered by lactate during glycolysis, including the Warburg effect, bridges metabolism and gene regulation. Enzymes such as p300 and HDAC1/3 have been pivotal in deciphering the regulatory dynamics of Kla, though questions about additional regulatory enzymes, their specific Kla substrates, and the underlying functional mechanisms persist. Here, we identify SIRT1 and SIRT3 as key "erasers" of Kla, shedding light on their selective regulation of both histone and non-histone proteins.

Comparative efficacy of intratympanic gentamicin and intratympanic corticosteroid in the treatment of Meniere's disease: a systematic review and meta-analysis.

Purpose: We aimed to evaluate the efficacy of gentamicin compared to corticosteroids for the treatment of Meniere's disease.

Methods: An extensive search was conducted in PubMed, Embase, and Web of Science until May 2024. For continuous outcomes, pooled effect estimates were determined by calculating the weighted mean difference (WMD), while for binary outcomes, the risk ratio (RR) was used, each accompanied by their respective 95% confidence intervals (CIs).

Strategy to optimize the broadband near-infrared emission based on Eu-doped sulfureted garnet phosphors toward emerging spectroscopy applications.

Eu-doped near-infrared (NIR) emitting phosphors, known for their high efficiency, broadband emission and spectral tunability, have gained much attention. However, achieving efficient NIR emission based on Eu remains a challenge due to the co-existence of Eu, especially in materials (i.e.

Opioid-free anesthesia with esketamine-dexmedetomidine versus opioid-based anesthesia with propofol-remifentanil in shoulder arthroscopy: a randomized controlled trial.

Background: OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting).

Methods: A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited.

Physical therapy options for knee osteoarthritis: A review.

In recent years, osteoarthritis of the knee, a common degenerative joint disease, often occurs in the elderly population. This disease has a significant impact on the quality of life of patients. For treating knee osteoarthritis, physical therapy is highly regarded as a very effective treatment method.

Vaccarin Ameliorates Doxorubicin-Induced Cardiotoxicity via Inhibition of p38 MAPK Mediated Mitochondrial Dysfunction.

Doxorubicin is a frequently used chemotherapeutic agent for treating various malignancies. However, it leads to severe cardiotoxic side effects, such as heart failure, and elevates the risk of sudden cardiac death among cancer patients. While oxidative stress has been identified as the primary cause of doxorubicin-induced cardiotoxicity, therapeutic antioxidant approaches have yielded unsatisfactory outcomes.

BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds.

Hypoxic microenvironment-induced exosomes confer temozolomide resistance in glioma through transfer of pyruvate kinase M2.

Objective: Glioma, a malignant primary brain tumor, is notorious for its high incidence rate. However, the clinical application of temozolomide (TMZ) as a treatment option for glioma is often limited due to resistance, which has been linked to hypoxic glioma cell-released exosomes. In light of this, the present study aimed to investigate the role of exosomal pyruvate kinase M2 (PKM2) in glioma cells that exhibit resistance to TMZ.

Characterization of lysosomal acid lipase in Ly6G and CD11c myeloid-derived suppressor cells.

Lysosomal acid lipase (LAL) is a key enzyme in the metabolic pathway of neutral lipids, whose deficiency (LAL-D) induces the differentiation of myeloid lineage cells into myeloid-derived suppressor cells (MDSCs), which promotes tumor growth and metastasis. This protocol provides detailed procedures for assessment of various LAL biochemical and physiological activities in Ly6G and CD11c MDSCs, including isolation of Ly6G and CD11c cells from the bone marrow and blood of mice, assays of LAL-D-induced cellular metabolic and mitochondrial activities, assessment of LAL-D-induced pathogenic immunosuppressive activity and tumor stimulatory activity. Pharmacological inhibition of the LAL activity was also described in both murine myeloid cells and human white blood cells.

Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology.

Background: Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC.

Methods: In this work, we constructed CCR7 gene knockout mice and OSCC mouse models.

The impact of smoking and alcohol consumption on rosacea: a multivariable Mendelian randomization study.

Backgrounds: Observational studies have shown that cigarette smoking is inversely associated with risk of rosacea, However, it remains uncertain whether this association is causal or it is a result of reverse causation, and whether this association is affected by drinking behaviors.

Methods: This study utilized the summary-level data from the largest genome-wide association study (GWAS) for smoking, alcohol consumption, and rosacea. The objective was to investigate the effect of genetically predicted exposures to smoking and alcohol consumption on the risk of developing rosacea.

CCR7 affects the tumor microenvironment by regulating the activation of naïve CD8 T cells to promote the proliferation of oral squamous cell carcinoma.

Background: Head and neck cancer is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, being one of the leading causes of cancer morbidity and mortality worldwide. CC Chemokine receptor 7(CCR7) is a multifunctional G protein-coupled trans-membrane chemokine that affects immune cell chemotaxis, migration, and cancer progression through its interaction with its ligands C-C motif chemokine ligand 19(CCL19) and C-C motif chemokine ligand 21(CCL21). Numerous studies have demonstrated the involvement of CCR7 in the malignant progression of a variety of cancers, reflecting the pro-cancer properties of CCR7.

Design, Synthesis, Antifungal Evaluation, Structure-Activity Relationship (SAR) Study, and Molecular Docking of Novel Spirotryprostatin A Derivatives.

Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments.

Insight into the Feasibility of Fatty Acyl Chlorides with 10-18 Carbons for the Ball-Milling Synthesis of Thermoplastic Cellulose Esters.

Fatty acid cellulose esters (FACE) are common cellulose-based thermoplastics, and their thermoplasticity is determined by both the contents and the lengths of the side chains. Herein, various FACE were synthesized by the ball-milling esterification of cellulose and fatty acyl chlorides containing 10-18 carbons, and their structures and thermoplasticity were thoroughly studied. The results showed that FACE with high degrees of substitution (DS) and low melting flow temperatures () were achieved as the chain lengths of the fatty acyl chlorides were reduced.

Large-scale preparation of CsPbBrperovskite quantum dot/EVA composite adhesive film by melting for crystal silicon solar cell.

Silicon solar cell is the most mature photovoltaic conversion device, and in order to further improve the performance of the device, application of downshifting films has become a research hotspot. In this paper, CsPbBrperovskite quantum dot/EVA composite adhesive film was prepared by melting method with CsPbBrperovskite quantum dot film under solution processing as masterbatch and EVA particles as excipient. The effect of synthesis conditions on the luminescence properties of the composite films were thoroughly studied.