PD-L1 in Melanoma and Extracellular Vesicles Promotes Local and Regional Immune Suppression through M2-like Macrophage Polarization.

Tumor-associated macrophages (TAMs) play dual roles in tumor progression. TAMs are known to induce programmed death ligand-1 (PD-L1) expression in cancer cells. However, the regulatory effects of PD-L1 in melanoma cells on TAM phenotypical switching remain underexplored.

A Comprehensive Proteogenomic and Spatial Analysis of Innate and Acquired Resistance of Metastatic Melanoma to Immune Checkpoint Blockade Therapies.

Unlabelled: While a subset of patients with metastatic melanoma achieves durable responses to immune checkpoint blockade (ICB) therapies, the majority ultimately exhibit either innate or acquired resistance to these treatments. However, the molecular mechanisms underlying resistance to ICB therapies remain elusive and are warranted to elucidate. Here, we comprehensively investigated the tumor and tumor immune microenvironment (TIME) of paired pre- and post-treatment tumor specimens from metastatic melanoma patients who were primary or secondary resistance to anti-CTLA-4 and/or anti-PD-1/PD-L1 therapies.

Seismic response of mountain tunnel induced by fault slip.

With the rapid development of Chinese transportation networks, such as the Sichuan-Tibet railway, numerous tunnels are under construction or planned in mountainous regions. Some of these tunnels must traverse or be situated near active fault zones, which could suffer damage from fault slip. In this study, the seismic response of a mountain tunnel subjected to coseismic faulting was analyzed using a fault-structure system in a two-step process.

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis.

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response.

Changes in the state of matter of KCIO to improve thermal and combustion properties of Al/MoO nanothermite.

To improve the thermal and combustion properties of nanothermites, a design theory of changing the state of matter and structural state of the reactants during reaction was proposed. The Al/MoO/KClO (Kp) nanothermite was prepared and the Al/MoO nanothermite was used as a control. SEM and XRD were used to characterize the nanothermites; DSC was used to test thermal properties; and constant volume and open combustion tests were performed to examine their combustion performance.

Multivariate Analysis Compares and Evaluates Heat Tolerance of Potato Germplasm.

High temperature is the most important environmental factor limiting potato ( L.) yield. The tuber yield has been used to evaluate the heat tolerance of some potato cultivars, but potato yield was closely correlated with the maturation period.

Rose long noncoding RNA lncWD83 promotes flowering by modulating ubiquitination of the floral repressor RcMYC2L.

Long noncoding RNAs (lncRNAs) play important roles in various signaling pathways in vascular plants. However, the crosstalk between lncRNAs and E3 ubiquitin ligases has been barely reported. In this study, we demonstrate that the lncRNA lncWD83 from rose (Rosa chinensis) 'Old blush' activates flowering by modulating the ubiquitination of the floral repressor MYC2 LIKE (RcMYC2L).

The intragenic cis-elements mediate temperature response of RrKSN.

Gene regulation via intragenic sequences is becoming more recognized in many eukaryotes. However, the intragenic sequences mediated gene expressions in response to environmental stimuli have been largely uncharacterized. Here, we showed that the first intron of RrKSN from the Rosa rugosa cultivar 'Purple branch' had a positive effect on RrKSN expression, and the effect depends on its position and orientation.

Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells.

Even among genetically identical cancer cells, resistance to therapy frequently emerges from a small subset of those cells. Molecular differences in rare individual cells in the initial population enable certain cells to become resistant to therapy; however, comparatively little is known about the variability in the resistance outcomes. Here we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing, to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies.

Research on the Measurement Technology of Rotational Inertia of Rigid Body Based on the Principles of Monocular Vision and Torsion Pendulum.

Damping is an important factor contributing to errors in the measurement of rotational inertia using the torsion pendulum method. Identifying the system damping allows for minimizing the measurement errors of rotational inertia, and accurate continuous sampling of torsional vibration angular displacement is the key to realizing system damping identification. To address this issue, this paper proposes a novel method for measuring the rotational inertia of rigid bodies based on monocular vision and the torsion pendulum method.

Melanoma-intrinsic NR2F6 activity regulates antitumor immunity.

Nuclear receptors (NRs) are implicated in the regulation of tumors and immune cells. We identify a tumor-intrinsic function of the orphan NR, NR2F6, regulating antitumor immunity. NR2F6 was selected from 48 candidate NRs based on an expression pattern in melanoma patient specimens (i.

Electroacupuncture alleviates mechanical allodynia and anxiety-like behaviors induced by chronic neuropathic pain via regulating rostral anterior cingulate cortex-dorsal raphe nucleus neural circuit.

Aims: Epidemiological studies in patients with neuropathic pain have demonstrated a strong association between neuropathic pain and psychiatric conditions such as anxiety. Preclinical and clinical work has demonstrated that electroacupuncture (EA) effectively alleviates anxiety-like behaviors induced by chronic neuropathic pain. In this study, a potential neural circuitry underlying the therapeutic action of EA was investigated.

Optimization of extraction process of 15 bioactive compounds from Qing Fei Yi Huo tablets using response surface methodology.

Qing Fei Yi Huo tablets (QFYHT) can relieve the clinical symptoms of acute bronchitis, and is widely prescribed in China. However, the quality standard of QFTHT lacks quantitative assessment. Therefore, it is crucial to develop an effective method for the extraction and analyses of its bioactive components.

The SET oncoprotein promotes estrogen-induced transcription by facilitating establishment of active chromatin.

SET is a multifunctional histone-binding oncoprotein that regulates transcription by an unclear mechanism. Here we show that SET enhances estrogen-dependent transcription. SET knockdown abrogates transcription of estrogen-responsive genes and their enhancer RNAs.

Dasatinib Resensitizes MAPK Inhibitor Efficacy in Standard-of-Care Relapsed Melanomas.

Resistance to combination BRAF/MEK inhibitor (BRAFi/MEKi) therapy arises in nearly every patient with melanoma, despite promising initial responses. Achieving cures in this expanding BRAFi/MEKi-resistant cohort represents one of the greatest challenges to the field; few experience additional durable benefit from immunotherapy and no alternative therapies exist. To better personalize therapy in cancer patients to address therapy relapse, umbrella trials have been initiated whereby genomic sequencing of a panel of potentially actionable targets guide therapy selection for patients; however, the superior efficacy of such approaches remains to be seen.

Integrated proteomics and metabolomics reveal variations in pulmonary fibrosis development and the potential therapeutic effect of Shuangshen Pingfei formula.

Ethnopharmacological Relevance: Shuangshen Pingfei formula (SSPF), a Chinese medicine prescription, has been prescribed to alleviate PF. However, little is known about the molecular mechanism underlying PF progression and the regulatory mechanism in SSPF.

Aims Of The Study: To discriminate the molecular alterations underlying the development of pulmonary fibrosis (PF) and reveal the regulatory mechanism of Shuangshen Pingfei formula (SSPF).

Evolutionary Analysis and Functional Identification of Clock-Associated () Genes in the Flowering Regulation of Roses.

Pseudo-response regulators () are the important genes for flowering in roses. In this work, clock were genome-wide identified using Arabidopsis protein sequences as queries, and their evolutionary analyses were deliberated intensively in Rosaceae in correspondence with angiosperms species. To draw a comparative network and flow of clock in roses, a co-expression network of flowering pathway genes was drawn using a string database, and their functional analysis was studied by silencing using VIGS and protein-to-protein interaction.

Electroacupuncture Alleviates Anxiety-Like Behaviors Induced by Chronic Neuropathic Pain via Regulating Different Dopamine Receptors of the Basolateral Amygdala.

Chronic pain, such as neuropathic pain, causes anxiety and other negative emotions, which aggravates the pain sensation and increases the risk of chronic pain over time. Dopamine receptor D1 (DRD1) and dopamine receptor D2 (DRD2) in the basolateral amygdala (BLA) have been implicated in mediating anxiety-related behaviors, but their potential roles in the BLA in neuropathic pain-induced anxiety have not been examined. Electroacupuncture (EA) is commonly used to treat chronic pain and emotional disorders, but it is still unclear whether EA plays a role in analgesia and anxiety relief through DRD1 and DRD2 in the BLA.

Superior thermal cycling stability of a carbon dots@NaBiF nanocomposite: facile synthesis and surface configurations.

Carbon dots (CDs), emerging as promising materials for optoelectronic and biomedical applications, are widely investigated due to their distinct merits of facile preparation, biocompatibility, and environment-friendliness. Here, a unique strategy based on surface engineering is proposed to modulate the photoluminescence (PL) of CDs in both aqueous solution and the solid state with good thermal cycling stability. For the typical blue emissive CD solution derived from citric acid and ethylenediamine, an intense green emission can be induced by adding Bi due to the strong coordination ability of Bi ions with carboxyl groups on the surface of CDs.

Serum metabolomic research of the anti-pulmonary fibrosis effects of Shuangshen Pingfei Formula on bleomycin-induced pulmonary fibrosis rats.

Our previous studies showed that Shuangshen Pingfei Formula (SSPF) exhibited anti-fibrosis effect, but its biochemical changes at the metabolic level remain unclear. In this study, an integrative approach of gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS)-based non-targeted metabolomics and multivariate statistical analysis was employed to explore the metabolic changes of serum samples from different stages of bleomycin-induced pulmonary fibrosis (PF) rats (PFRs: M7, M14, M21 and M28) treated with SSPF extracts. Potential biomarkers for PF were screened.

Screening and evaluation of quality markers from Shuangshen Pingfei formula for idiopathic pulmonary fibrosis using network pharmacology and pharmacodynamic, phytochemical, and pharmacokinetic analyses.

Background: The Shuangshen Pingfei formula (SSPF), a classic Chinese medicine derivative formula, has been shown to exert therapeutic effects on idiopathic pulmonary fibrosis (IPF). However, the quality control compounds of SSPF remain unclear.

Purpose: To select and confirm Q-markers of SSPF based on network pharmacology, cytobiology, animal-based pharmacodynamics, and phytochemical and pharmacokinetic analyses.

Enhanced Fluorescence and Environmental Stability of Red-Emissive Carbon Dots via Chemical Bonding with Cellulose Films.

The development of red emission carbon dots with bright solid-state fluorescence would significantly broaden their application in optoelectronic devices and sensors. Herein, a red-emissive carbon dot-based nanocomposite has been synthesized through chemical bonding with cellulose films. The red emission originating from the surface states of carbon dots was maintained in the cellulose films.