Inhibiting autophagy selectively prunes dysfunctional tumor vessels and optimizes the tumor immune microenvironment.

Dysfunctional tumor vasculature, hypoxia, and an immunosuppressive microenvironment are significant barriers to effective cancer therapy. Autophagy, which is critical for maintaining cellular homeostasis and apoptosis resistance, is primarily triggered by hypoxia and nutrient deprivation, conditions prevalent in dysfunctional tumor vessels due to poor circulation. However, the role of autophagy in dysfunctional tumor endothelial cells and its impact on treatment and the tumor microenvironment (TME) remain poorly understood.

The Demographic and Clinical Characteristics, Prognostic Factors, and Survival Outcomes of Head and Neck Carcinosarcoma: A SEER Database Analysis.

Background: Head and neck carcinosarcoma (HNCS) is a rare and highly aggressive malignancy with limited research, resulting in an incomplete understanding of disease progression and a lack of reliable prognostic tools. This study aimed to retrospectively analyze the clinical characteristics and outcomes of HNCS patients using data from the Surveillance, Epidemiology, and End Results (SEER) database and to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS).

Methods: Patients diagnosed with HNCS from 1975 to 2020 were identified in the SEER database.

Panoramic tumor microenvironment in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is notorious for its resistance to various treatment modalities. The genetic heterogeneity of PDAC, coupled with the presence of a desmoplastic stroma within the tumor microenvironment (TME), contributes to an unfavorable prognosis. The mechanisms and consequences of interactions among different cell types, along with spatial variations influencing cellular function, potentially play a role in the pathogenesis of PDAC.

Predictive Biomarkers for Immunotherapy in Gastric Cancer: Current Status and Emerging Prospects.

Gastric cancer presents substantial management challenges, and the advent of immunotherapy has ignited renewed hope among patients. Nevertheless, a significant proportion of patients do not respond to immunotherapy, and adverse events associated with immunotherapy also occur on occasion, underscoring the imperative to identify suitable candidates for treatment. Several biomarkers, including programmed death ligand-1 expression, tumor mutation burden, mismatch repair status, Epstein-Barr Virus infection, circulating tumor DNA, and tumor-infiltrating lymphocytes, have demonstrated potential in predicting the effectiveness of immunotherapy in gastric cancer.

Zebrafish functional xenograft vasculature platform identifies PF-502 as a durable vasculature normalization drug.

Tumor vasculature often exhibits disorder and inefficiency. Vascular normalization offers potential for alleviating hypoxia and optimizing drug delivery in tumors. However, identifying effective agents is hindered by a lack of robust screening.

Computational holographic ghost diffraction.

Since the paradigm shift in 2009 from pseudo-thermal ghost imaging (GI) to computational GI using a spatial light modulator, computational GI has enabled image formation via a single-pixel detector and thus has a cost-effective advantage in some unconventional wave bands. In this Letter, we propose an analogical paradigm known as computational holographic ghost diffraction (CH-GD) to shift ghost diffraction (GD) from classical to computational by using self-interferometer-assisted measurement of field correlation functions rather than intensity correlation functions. More than simply "seeing" the diffraction pattern of an unknown complex volume object with single-point detectors, CH-GD can retrieve the diffracted light field's complex amplitude and can thus digitally refocus to any depth in the optical link.

Dynamic Distribution of Skin Microorganisms in Donkeys at Different Ages and Various Sites of the Body.

Considerable evidence suggests that the skin microbiota is not only important and complex in humans and other mammals but also critical for maintaining health and skin homeostasis. To date, studies on the skin microorganisms of donkeys are surprisingly rare. To investigate the dynamic changes in commensal microbial communities on the skins of healthy donkeys throughout the growing period, skin and soil samples were collected from 30 healthy Dezhou donkeys (ranging from 1, 6, 12, 24 to 48 months of age) and their corresponding breeding sheds on the farm.

Using a zebrafish xenograft tumor model to compare the efficacy and safety of VEGFR-TKIs.

Purpose: We constructed a zebrafish xenograft tumor model to compare and quantify the antiangiogenic efficacy and safety of nine vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), axitinib, lenvatinib, pazopanib, apatinib, cabozantinib, sunitinib, semaxanib, sorafenib, and regorafenib, in parallel.

Methods: CT26 and GL261 tumor cells were implanted into the perivitelline space of Tg (flk1: eGFP) zebrafish to construct a xenograft tumor model. VEGFR-TKIs' antiangiogenic efficacy was quantified using AngioTool software, and the median effective dose (ED50) was calculated.

Predictive biomarkers of colon cancer immunotherapy: Present and future.

Immunotherapy has revolutionized colon cancer treatment. Immune checkpoint inhibitors (ICIs) have shown clinical benefits for colon cancer patients, especially those with high microsatellite instability (MSI-H). In 2020, the US Food and Drug Administration (FDA)-approved ICI pembrolizumab as the first-line treatment for metastatic MSI-H colon cancer patients.

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy.

Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration.

Quantitative Proteomics Explore the Potential Targets and Action Mechanisms of Hydroxychloroquine.

Hydroxychloroquine (HCQ) is an autophagy inhibitor that has been used for the treatment of many diseases, such as malaria, rheumatoid arthritis, systemic lupus erythematosus, and cancer. Despite the therapeutic advances in these diseases, the underlying mechanisms have not been well determined and hinder the rational use of this drug in the future. Here, we explored the possible mechanisms and identified the potential binding targets of HCQ by performing quantitative proteomics and thermal proteome profiling on MIA PaCa-2 cells.

Identification and evaluation of a lipid-lowering small compound in preclinical models and in a Phase I trial.

Developing non-statin-based small compounds to battle the global epidemic of hyperlipidemia remains challenging. Here, we report the discovery of DC371739, an indole-containing tetrahydroisoquinoline compound with promising lipid-lowering effects, both in vitro and in vivo, and with good tolerability in a Phase I clinical trial (NCT04927221). DC371739 significantly reduced the plasma levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides simultaneously in several animal models and showed preliminary positive results in the Phase I trial.

Quantitative Proteomics Analysis Expands the Roles of Lysine -Hydroxybutyrylation Pathway in Response to Environmental -Hydroxybutyrate.

Lysine -hydroxybutyrylation (Kbhb) is a newly identified protein posttranslational modification (PTM) derived from -hydroxybutyrate (BHB), a product of ketone body metabolism in liver. BHB could serve as an energy source and play a role in the suppression of oxidative stress. The plasma concentration of BHB could increase up to 20 mM during starvation and in pathological conditions.

A pH-Responsive Zwitterionic Polyurethane Prodrug as Drug Delivery System for Enhanced Cancer Therapy.

Numerous nanocarriers with excellent biocompatibilities have been used to improve cancer therapy. However, nonspecific protein adsorption of nanocarriers may block the modified nanoparticles in tumor cells, which would lead to inefficient cellular internalization. To address this issue, pH-responsive polyurethane prodrug micelles with a zwitterionic segment were designed and prepared.

[Research progress of circadian rhythm].

Circadian rhythm disorder is a common society issue caused by jet lag,shift work,sleep disruption and changes in food consumption. Light is the major factor affecting the circadian rhythm system. Disruption of the circadian rhythm system can cause damage to the body,leading to some diseases.

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection.

Comparative evaluation of cardiovascular risks among nine FDA-approved VEGFR-TKIs in patients with solid tumors: a Bayesian network analysis of randomized controlled trials.

Purpose: The present meta-analysis study was performed to identify the potential cardiotoxicity risks when using Vascular Endothelial Growth Factor Receptor Tyrosine kinase inhibitors (VEGFR-TKIs) as anticancer drugs in patients with solid tumors.

Methods: Pubmed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for the randomized controlled trials.

Photo-Responsive Polymersomes as Drug Delivery System for Potential Medical Applications.

Due to a strong retardation effect of o-nitrobenzyl ester on polymerization, it is still a great challenge to prepare amphiphilic block copolymers for polymersomes with a o-nitrobenzyl ester-based hydrophobic block. Herein, we present one such solution to prepare amphiphilic block copolymers with pure poly (o-nitrobenzyl acrylate) (PNBA) as the hydrophobic block and poly (-dimethylacrylamide) (PDMA) as the hydrophilic block using bulk reversible addition-fragmentation chain transfer (RAFT) polymerization of o-nitrobenzyl acrylate using a PDMA macro-RAFT agent. The developed amphiphilic block copolymers have a suitable hydrophobic/hydrophilic ratio and can self-assemble into photoresponsive polymersomes for co-loading hydrophobic and hydrophilic cargos into hydrophobic membranes and aqueous compartments of the polymersomes.

Synergies of Antiangiogenic Therapy and Immune Checkpoint Blockade in Renal Cell Carcinoma: From Theoretical Background to Clinical Reality.

The hallmarks of renal cell carcinoma (RCC) are angiogenesis and immunogenic tumor microenvironment. Over the past decades, treatment options for metastatic RCC (mRCC) have been expanding, from the inhibition of vessel formation via antiangiogenic agents (AAs) to the stimulation of immune system by immune checkpoint inhibitors (ICIs). Since 2005, the introduction of antiangiogenic agents targeting vascular endothelial growth factor (VEGF), its receptors (VEGFRs), and mammalian target of rapamycin (mTOR) pathway have experienced moderate success in the therapeutics of mRCC, but patient outcomes remain suboptimal.

On the nonlinear temperature dependence of elastic constants and wave velocities for solid media with applications to geologic materials.

Temperature-induced variations of elastic moduli in solid media are generally characterized by a strong nonlinear dependence on temperature associated with complex deformations under thermal treatments. Conventional thermoelasticity with third-order elastic constants for the one-order temperature dependence has been extensively studied for crystals, but encountering problems of divergent and limited velocity variations for rocks as a polycrystal mixture, especially at high temperatures. The extension of the theory beyond high-order elastic constants to solid media is addressed in this article to describe the nonlinear temperature dependence of both elastic constants and wave velocities.

The MEK inhibitors enhance the efficacy of sorafenib against hepatocellular carcinoma cells through reducing p-ERK rebound.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide and has a poor prognosis. Sorafenib, the only targeted therapeutic agent for HCC, is a multiple kinase inhibitor with targets including RAF and VEGFR-2/3 that display a very limited ability to extend the survival of patients with advanced metastatic HCC for approximately three months. MEK inhibitors including trametinib and selumetinib have shown promising efficacy in combination with sorafenib in clinical trials.

[Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma].

To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network.

Standard CD44 modulates YAP1 through a positive feedback loop in hepatocellular carcinoma.

High expression levels of CD44 and YAP have been identified as poor prognostic factors in hepatocellular carcinoma (HCC). However, the mechanistic relationship between CD44 and YAP during HCC tumorigenesis remains largely unknown. To investigate the mutual regulation between standard CD44 (CD44S) and YAP1 in HCC cell lines and tissue samples, CD44S and YAP1 expression in 40 pairs of tumor samples and matched distal normal tissues from HCC patients was examined by immunohistochemical staining.