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Abstract Hepatocellular carcinoma (HCC) is a predominant cause of cancer-related mortality globally, noted for its propensity towards late-stage diagnosis and scarcity of effective treatment modalities. The process of metabolic reprogramming, with a specific emphasis on lipid metabolism, is instrumental in the progression of HCC. Nevertheless, the precise mechanisms through which lipid metabolism impacts HCC and its viability as a therapeutic target have yet to be fully elucidated. In the current investigation, single-cell RNA sequencing in conjunction with weighted gene co-expression network analysis (WGCNA) was utilized to delineate lipid metabolism-related genes correlated with the prognostic outcomes of hepatocellular carcinoma (HCC). Data procurement encompassed transcriptomic and clinical datasets from HCC patients, sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories. Subsequent to this, consensus clustering analysis was implemented to stratify patients into distinct subgroups, contingent upon the expression patterns of lipid metabolism genes. Further analytical procedures involved functional enrichment analysis, evaluation of immune infiltration, and examination of the mutation landscape.PTGES3 was identified as a pivotal gene associated with lipid metabolism. Subsequent to its identification, cellular communication analysis was employed to assess the immunological attributes of PTGES3 within the tumor microenvironment. The functional role of PTGES3 was further corroborated through molecular docking simulations and in vitro experimental assays. We identified 27 genes associated with lipid metabolism, 18 of which exhibited significant correlation with overall survival in HCC patients. PTGES3 emerged as a central gene, demonstrating a robust association with immune cell infiltration and unfavorable prognosis. Cellular communication analysis revealed that PTGES3 exhibits the highest communication intensity with T cells, modulating the tumor microenvironment by potentiating the FN1/CD44 + MDK/NCL signaling pathway. Elevated expression of PTGES3 was linked to immunosuppressive cascades, diminished responsiveness to immunotherapy, and inferior overall survival outcomes. Molecular docking analysis indicated that etoposide, methotrexate, and doxorubicin could effectively bind to PTGES3. In vitro experiments confirmed that PTGES3 knockdown significantly impaired the proliferation, invasion, and migration of HCC cells. This study highlights the pivotal role of lipid metabolism in HCC progression and identifies PTGES3 as a potential prognostic biomarker and therapeutic target. These findings offer new insights into the development of targeted therapies for HCC, particularly in patients with high PTGES3 expression.

Abstract Background Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits. In electroencephalograph (EEG) recordings from humans and mice, these deficits manifest as increased N1 amplitudes in event-related potentials (ERP), increased gamma band single trial power (STP) and reduced phase locking to rapid temporal modulations of sound. In our previous study, we found that administration of the selective serotonin-1 A (5-HT1A)receptor biased agonist, NLX-101, protected Fmr1 KO mice from auditory hypersensitivity-associated seizures. Here we tested the hypothesis that NLX-101 will normalize EEG phenotypes in developing Fmr1 KO mice. Methods To test this hypothesis, we examined the effect of NLX-101 on EEG phenotypes in male and female wildtype (WT) and Fmr1 KO mice. Using epidural electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at two ages, postnatal (P) 21 and 30 days, from both auditory and frontal cortices of awake, freely moving mice, following NLX-101 (at 1.8 mg/kg i.p.) or saline administration. Results Saline-injected Fmr1 KO mice showed increased N1 amplitudes, increased STP and reduced phase locking to auditory gap-in-noise stimuli versus wild-type mice, reproducing previously published EEG phenotypes. An acute injection of NLX-101 did not alter ERP amplitudes at either P21 or P30, but significantly reduces STP at P30. Inter-trial phase clustering was significantly increased in both age groups with NLX-101, indicating improved temporal processing. The differential effects of serotonin modulation on ERP, background power and temporal processing suggest different developmental mechanisms leading to these phenotypes. Conclusions These results suggest that NLX-101 could constitute a promising treatment option for targeting post-synaptic 5-HT1A receptors to improve auditory temporal processing, which in turn may improve speech and language function in FXS.

Available evidence indicates that neuregulin-1 (NRG-1) can provide a protection against myocardial ischemia/reperfusion (I/R) injury and is involved in various cardioprotective interventions by potential regulation of mitophagy. However, the molecular mechanisms linking NRG-1 and mitophagy remain to be clarified. In this study, both an in vivo myocardial I/R injury model of rats and an in vitro hypoxia/reoxygenation (H/R) model of H9C2 cardiomyocytes were applied to determine whether NRG-1 postconditioning attenuated myocardial I/R injury through the regulation of mitophagy and to explore the underlying mechanisms. In the in vivo experiment, cardioprotective effects of NRG-1 were determined by infarct size, cardiac enzyme and histopathologic examinations. The potential downstream signaling pathways and molecular targets of NRG-1 were screened by the RNA sequencing and the Protein-Protein Interaction Networks. The expression levels of mitochondrial uncoupling protein 2 (UCP2) and mitophagy-related proteins in both the I/R myocardium and H/R cardiomyocytes were measured by immunofluorescence staining and Western blots. The activation of mitophagy was observed with transmission electron microscopy and JC-1 staining. The KEGG and GSEA analyses showed that the mitophagy-related signaling pathways were enriched in the I/R myocardium treated with NRG-1, and UCP2 exhibited a significant correlation between mitophagy and interaction with PINK1. Meanwhile, the treatment with mitophagy inhibitor Mdivi-1 significant eliminated the cardioprotective effects of NRG-1 postconditioning in vivo, and the challenge with UCP2 inhibitor genipin could also attenuate the activating effect of NRG-1 postconditioning on mitophagy. Consistently, the in vitro experiment using H9C2 cardiomyocytes showd that NRG-1 treatment significantly up-regulated the expression levels of UCP2 and mitophagy-related proteins, and activated the mitophagy, whereas the challenge with small interfering RNA-mediated UCP2 knockdown abolished the effects of NRG-1. Thus, it is conclused that NRG-1 postconditioning can produce a protection against the myocardial I/R injury by activating mitophagy through the UCP2/PINK1/LC3B signaling pathway.

Primary small cell carcinoma of the ovary is an extremely rare and highly malignant ovarian malignancy. The tissue origin of this type of cancer is still unclear, and it is characterized by rapid progression and a discouraging prognosis. The clinical presentation of small cell carcinoma of the ovary lacks specificity, and there are currently no effective treatment options available. Therefore, it is crucial to improve the understanding and identification of this disease. In this paper, we present a case of composite small cell carcinoma of the ovary with mucinous adenocarcinoma and provide a comprehensive review of the relevant literature.

Water use efficiency (WUE), as an important parameter of ecosystem carbon-water cycle, is an important index to assess vulnerability to extreme drought events. However, little was known about the corresponding cumulative and lagged responses of WUE to drought in the dry and hot valleys of Southwest China. This region is covered by alpine-valley landscapes, fragmented topographic features, Foehn Effect, where drought response mechanisms are not yet fully understood. This study analyzed the spatial-temporal variation of WUE from 2000 to 2020 in Binchuan (BC) and Yuanmou (YM) regions and the time-lag and -accumulation effects of 12 monthly self-calibrating Palmer Drought Index (scPDSI) on the WUE. Given the variability of vegetation types, land use/cover change data was used to investigate the variability of WUE between the two areas. Subsequently, the Pearson Correlation coefficient (Pearson, R) analysis, considering the influence of drought on time-lag and -accumulation effects, was used to analyze the response mechanism of water use efficiency to scPDSI in BC and YM comparatively. The results show that (1) From 2001 to 2020, BC’s average annual WUE was 2.59 gC m−2 mm−1, and YM’s was 2.84 gC·m−2·mm−1, with similar spatial distributions. (2) Over the past 2 decades, BC’s WUE increased steadily at a rate of 0.012 gC m-2 mm−1 a−1, while Yuanmou’s WUE grew at 0.0082 gC m-2 mm−1 a−1. (3) The lag response of WUE to drought is minimal in both regions, with BC’s cultivated land showing greater sensitivity to drought than YM. (4) The cumulative effect of drought on WUE across different land uses in both BC and YM is generally small, with the lowest sensitivity in forest land to drought.

Entanglement plays a crucial role in advancing quantum technologies and exploring quantum many-body simulations. Here, we introduce a protocol aided by neural networks for measuring entanglement in both equilibrium and non-equilibrium states of local Hamiltonians, with a favorable amount of training data. Our numerical simulations across various Hamiltonian models and qubit configurations reveal that this approach can predict comprehensive entanglement metrics, such as Rényi entropy, for up to 100 qubits using only single-qubit and two-qubit Pauli measurements. Excitingly, future entanglement dynamics beyond the measurement window can be predicted based solely on previous single-qubit traces. Experimentally, we utilize a nuclear spin quantum processor and a neural network to measure entanglement in the ground and dynamical states of a one-dimensional spin chain. The results demonstrate the feasibility of our method in practical experiments. Therefore, our approach offers a promising method for experimentally measuring entanglement in systems with dozens to hundreds of qubits. [ABSTRACT FROM AUTHOR]

Constipation is a common gastrointestinal condition, which may occur at any age and affects countless people. The search for new treatments for constipation is ongoing as current drug treatments fail to provide fully satisfactory results. In recent years, probiotics have attracted much attention because of their demonstrated therapeutic efficacy and fewer side effects than pharmaceutical products. Many studies attempted to answer the question of how probiotics can alleviate constipation. It has been shown that different probiotic strains can alleviate constipation by different mechanisms. The mechanisms on probiotics in relieving constipation were associated with various aspects, including regulation of the gut microbiota composition, the level of short-chain fatty acids, aquaporin expression levels, neurotransmitters and hormone levels, inflammation, the intestinal environmental metabolic status, neurotrophic factor levels and the body's antioxidant levels. This paper summarizes the perception of the mechanisms on probiotics in relieving constipation and provides some suggestions on new research directions. [ABSTRACT FROM AUTHOR]

Q‐matrix is an important component of most cognitive diagnosis models (CDMs); however, it mainly relies on subject matter experts' judgements in empirical studies, which introduces the possibility of misspecified q‐entries. To address this, statistical Q‐matrix validation methods have been proposed to aid experts' judgement. A few of these methods, including the multiple logistic regression‐based (MLR‐B) method and the Hull method, can be applied to general CDMs, but they are either time‐consuming or lack accuracy under certain conditions. In this study, we combine the L1 regularization and MLR model to validate the Q‐matrix. Specifically, an L1 penalty term is imposed on the log‐likelihood of the MLR model to select the necessary attributes for each item. A simulation study with various factors was conducted to examine the performance of the new method against the two existing methods. The results show that the regularized MLR‐B method (a) produces the highest Q‐matrix recovery rate (QRR) and true positive rate (TPR) for most conditions, especially with a small sample size; (b) yields a slightly higher true negative rate (TNR) than either the MLR‐B or the Hull method for most conditions; and (c) requires less computation time than the MLR‐B method and similar computation time as the Hull method. A real data set is analysed for illustration purposes. [ABSTRACT FROM AUTHOR]

Long-standing evidence implicates glioma stem cells (GSC) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we have demonstrated that global lactylation was significantly elevated in GSCs compared with differentiated glioma cells. Polypyrimidine tract-binding protein 1 (PTBP1), a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis. Significance: Glycolysis-induced lactylation enhances the function of PTBP1 to promote glioma stem cell maintenance, indicating that PTBP1 lactylation could be a potential target for the development of innovative glioma therapies., (©2024 American Association for Cancer Research.)

Backgroud: Leptomeningeal metastases (LMs) are serious complications of non-small cell lung cancer (NSCLC). This study aimed to investigate the safety and efficacy of intrathecal immune checkpoint inhibitors (ICIs) in treating NSCLC-LM., Methods: We conducted this prospective phase 1 study (ChiCTR2200062245) using a traditional "3 + 3" design with intrathecal sintilimab (dose escalation 10mg, 20mg, 30mg, and 40mg) for NSCLC-LM patients who had progressed from targeted therapy and intrathecal pemetrexed. The primary study endpoints were safety and recommended dose, and the secondary endpoints included clinical response rate, progression-free survival (PFS), intracranial progression-free survival (iPFS), and overall survival (OS)., Results: No dose-limiting toxicity was found at 10mg, 20mg, 30mg, and 40mg for intrathecal sintilimab. Therefore, sintilimab 40mg was recommended for intrathecal injection. A total of 19 patients were enrolled in this study. The median age at diagnosis of LM was 53 years. The overall incidence of adverse events (AEs) was 68.4%, and rash (n=4, 21.1%) was the most common AEs, which returned to normal after symptomatic treatment. As 1 patient was lost to follow-up and 18 patients could be evaluated for efficacy, the clinical response rate was 38.9% (7/18). Median PFS was 3.5 months (95% CI: 2.7-4.2 months), median iPFS was 3.5 months (95% CI: 1.3-5.6 months), and median OS was 11.5 months (95% CI: 0.0-25.4 months)., Conclusions: Intrathecal ICIs for NSCLC-LM patients are safe, and the recommended dose of sintilimab is 40mg. Intrathecal sintilimab for NSCLC-LM failed from multi-line therapies, showed potential effectiveness in some patients, and is worthy for further study., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cyanido-bridged multimetallic complexes have been extensively studied for their potential applications in molecular electronics and spintronics. The design of these complexes involves the strategic placement of metal centers and the use of cyanide bridges to facilitate electron transfer between metal ions. The challenges in this field include the precise control of the electronic states and the stability of the complexes under various conditions. Researchers are exploring new synthetic methods and functionalization strategies to overcome these challenges and to enhance the performance of these complexes in practical applications. Overall, this review demonstrates the design of linear cyanido-bridged multimetallic complexes and related electronic properties, emphasizing the remaining challenges.

Traditional tetrahedral-based mid-to-far infrared (MFIR) nonlinear optical (NLO) crystals often face limitations due to the optical anisotropy constraints imposed by their highly symmetric structures. In contrast, the relatively rare trigonal pyramidal [TeS 3 ] 2- functional unit characterized by its asymmetric structure and stereochemically active lone pair (SCALP), offers improved optical anisotropy, hyperpolarizability and a broader IR transparency range. Despite its potential, synthetic challenges have hindered the development of MFIR NLO crystals that incorporate this unit, with only one example reported to date. Herein, an innovative MFIR NLO crystal, Cu 10 Te 4 S 13 has been successfully constructed using the trigonal pyramidal [TeS 3 ] 2- units, via a simple high-temperature solid-state method. The novel three-dimensional structure of Cu 10 Te 4 S 13 is interconnected by butterfly-orchid-like [Cu 6 Te 4 S 13 ] anionic clusters and [CuS 4 ] groups, where the former are composed of trigonal pyramidal [TeS 3 ] 2- groups and [Cu 6 S 13 ] hexamers. Cu 10 Te 4 S 13 exhibits a remarkable second harmonic generation effect, approximately 3.75 times that of AgGaS 2 at 2900 nm in the particle size range of 30-45 μm. Additionally, it demonstrates favorable crystal growth habits, producing single crystals with maximum dimensions of about 7 × 3 × 2 mm 3 . This polished single crystal appears to exhibit complete transparency within the MFIR spectral window ranging from 2.5 to 25 μm, representing the widest IR transmission in all reported NLO chalcogenides. Furthermore, the structure-property relationship is also elucidated through first-principles analysis. This work confirms the potential of the unique trigonal pyramidal [TeS 3 ] 2- as a MFIR NLO functional unit, paving the way for the development of unconventional MFIR NLO materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Red soil occupies an important position in China's agriculturally cultivated land resources. However, its low pH value, high aluminum concentration, and inefficient phosphorus utilization limit the productivity of acidic red soil farmland. Plant roots exhibit remarkable plasticity, capable of absorbing water and nutrients and modulating root system architecture in response to biotic and abiotic stresses, either autonomously or through rhizosphere microorganisms. This study primarily investigates the regulatory effects of rhizosphere microorganisms, including plant growth-promoting rhizobacteria, such as arbuscular mycorrhizal fungi and rhizobia, and synthetic microbial consortia, on plant root system architecture. These regulatory mechanisms encompass the production of hormones, the release of volatile organic compounds, nitrogen fixation, phosphorus solubilization, and the improvement of rhizospheric soil structure. Such mechanisms can influence root biomass, branching, lateral roots, and root hair growth. Furthermore, we summarize new visualization methods for plant root system architecture and rhizosphere microorganisms, providing technical support for studying the regulation of root system architecture by rhizosphere microbes. Under acidic soil conditions, rhizosphere microorganisms serve as a crucial regulatory strategy. By adjusting plant root system architecture, they can enhance the productivity of acidic soils, representing a potential solution for ameliorating the constraints of acidic soils.

A facile and general strategy is developed herein for the construction of circularly polarized luminescence (CPL) materials with simultaneously high fluorescence quantum efficiency (Φ) and large luminescence dissymmetry factor (g lum ). The self-assembly of fluorescent dye, disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (CBS), with chiral diamines such as (R,R)/(S,S)-1,2-diaminocyclohexane (R/S-DACH) and R/S-1,2-diaminopropane (R/S-DAP), produces four chiral crystalline organic salt networks (COSNs). These as-synthesized organic salts emit strong blue-color CPL upon excitation, with both high Φ and g lum values of up to 79% and 0.022. The well-defined molecular structures and arrangements of CBS are directly observed through single crystal X-ray analysis, offering crucial information regarding the origins of high-efficiency CPL performance. The chirality of amine is effectively transferred to CBS and further amplified to the supramolecular structure by multiple hydrogen bonding and π-π stacking interactions, giving rise to the large g lum factors; meanwhile, the fixation and the ordered arrangement of CBS by these multiple interactions empower efficient suppression of molecular motions, facilitating strong fluorescence. This work can inspire the assembly of CPL organic materials with high Φ and g lum via charge-assisted hydrogen bonds between fluorescent dyes and chiral inducers. It also offers important insight into the structural origins of supramolecular chirality and CPL performance., (© 2024 Wiley‐VCH GmbH.)