Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy.

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD) catabolism, is highly expressed in exhausted CD8 T cells in melanoma and is associated with ICB resistance.

Lower frequencies of circulating suppressive regulatory T cells and higher frequencies of CD4 naïve T cells at baseline are associated with severe immune-related adverse events in immune checkpoint inhibitor-treated melanoma.

Background: Immune-related adverse events (irAEs) are major barriers of clinical management and further development of immune checkpoint inhibitors (ICIs) for cancer therapy. Therefore, biomarkers associated with the onset of severe irAEs are needed. In this study, we aimed to identify immune features detectable in peripheral blood and associated with the development of severe irAEs that required clinical intervention.

Targeted reversal of multidrug resistance in ovarian cancer cells using exosome‑encapsulated tetramethylpyrazine.

The objective of the present study was to develop exosomes (EXOs) encapsulating tetramethylpyrazine (TMP) for the reversal of drug resistance in ovarian cancer therapy. Human A2780 cells were incubated with TMP for 48 h. Purified TMP‑primed EXOs (EXOs‑TMP) were isolated through ultracentrifugation.

Mechanism of Pd(II) adsorption by nanoscale titanium dioxide loaded bamboo shoot shell biomass.

Palladium (Pd) is widely used in catalyst, aerospace, and medical applications, but only 1% of its reserves are found in nature. So, the recovery of Pd(II) is very important. Natural fibers are a good adsorption material, and the abundant functional groups in bamboo shoot shell (BSS) fibers can form interactions with metal particles.

Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect.

Colorectal cancer (CRC) is a prevalent malignancy worldwide and is associated with a high mortality rate. Changes in bioenergy metabolism, such as the Warburg effect, are often observed in CRC. Aldolase B (ALDOB) has been identified as a potential regulator of these changes, but its exact role in CRC cell behavior and bioenergetic homeostasis is not fully understood.

Comparative membrane proteomics reveals diverse cell regulators concentrated at the nuclear envelope.

The nuclear envelope (NE) is a subdomain of the ER with prominent roles in nuclear organization, which are largely mediated by its distinctive protein composition. We developed methods to reveal low-abundance transmembrane (TM) proteins concentrated at the NE relative to the peripheral ER. Using label-free proteomics that compared isolated NEs with cytoplasmic membranes, we first identified proteins with apparent NE enrichment.

Controllable Architecture of ZnO/FeNi Composites Derived from Trimetallic ZnFeNi Layered Double Hydroxides for High-Performance Electromagnetic Wave Absorbers.

The optimization design of micro-structure and composition is an important strategy to obtain high-performance metal-based electromagnetic (EM) wave absorption materials. In this work, ZnO/FeNi composites derived from ZnFeNi layered double hydroxides are prepared by a one-step hydrothermal method and subsequent pyrolysis process, and can be employed as an effective alternative for high-performance EM wave absorber. A series of ZnO/FeNi composites with different structures are obtained by varying the molar ratios of Zn /Fe /Ni , and the ZnO/FeNi composites with a Zn /Fe /Ni molar ratio of 6:1:3 show a hierarchical flower-like structure.

Comparative membrane proteomics reveals diverse cell regulators concentrated at the nuclear envelope.

The nuclear envelope (NE) is a subdomain of the ER with prominent roles in nuclear organization, largely mediated by its distinctive protein composition. We developed methods to reveal novel, low abundance transmembrane (TM) proteins concentrated at the NE relative to the peripheral ER. Using label-free proteomics that compared isolated NEs to cytoplasmic membranes, we first identified proteins with apparent NE enrichment.

Tanshinone IIA Microemulsion Protects against Cerebral Ischemia Reperfusion Injury via Regulating H3K18ac and H4K8ac and .

Tanshinone IIA (TanIIA) has neuroprotective effects against cerebral ischemia reperfusion injury (CIRI), but its clinical application is limited due to poor water solubility and robust first pass elimination property. In this study, we developed microemulsion loaded with TanIIA (TanIIA ME) to break through these limitations, and explored the neuroprotective effect of TanIIA ME against CIRI and the epigenetic regulation mechanism of this neuroprotection. , middle cerebral artery occlusion (MCAO) models were treated with TanIIA ME and TanIIA solution or sodium valproate as a control.

Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?

The major concept of "oxidative stress" is an excess elevated level of reactive oxygen species (ROS) which are generated from vigorous metabolism and consumption of oxygen. The precise harmonization of oxidative stresses between mitochondria and other organelles in the cell is absolutely vital to cell survival. Under oxidative stress, ROS produced from mitochondria and are the major mediator for tumorigenesis in different aspects, such as proliferation, migration/invasion, angiogenesis, inflammation, and immunoescape to allow cancer cells to adapt to the rigorous environment.

Shared and Distinctive Neighborhoods of Emerin and Lamin B Receptor Revealed by Proximity Labeling and Quantitative Proteomics.

Emerin and lamin B receptor (LBR) are abundant transmembrane proteins of the nuclear envelope that are concentrated at the inner nuclear membrane (INM). Although both proteins interact with chromatin and nuclear lamins, they have distinctive biochemical and functional properties. Here, we have deployed proximity labeling using the engineered biotin ligase TurboID (TbID) and quantitative proteomics to compare the neighborhoods of emerin and LBR in cultured mouse embryonic fibroblasts.

The optimization conditions of establishing an H9c2 cardiomyocyte hypoxia/reoxygenation injury model based on an AnaeroPack System.

Ischemia-reperfusion (I/R) injury is a major cause of cardiomyocyte apoptosis after vascular recanalization, which was mimicked by a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes in vitro. In this study, we explored an optimal H/R duration procedure using the AnaeroPack System. To study the H/R procedure, cardiomyocytes were exposed to the AnaeroPack System with sugar and serum-free medium, followed by reoxygenation under normal conditions.

Mitochondrial Lon-induced mtDNA leakage contributes to PD-L1-mediated immunoescape via STING-IFN signaling and extracellular vesicles.

Background: Mitochondrial Lon is a chaperone and DNA-binding protein that functions in protein quality control and stress response pathways. The level of Lon regulates mitochondrial DNA (mtDNA) metabolism and the production of mitochondrial reactive oxygen species (ROS). However, there is little information in detail on how mitochondrial Lon regulates ROS-dependent cancer immunoescape through mtDNA metabolism in the tumor microenvironment (TME).

Prediction of vaginal birth after cesarean delivery in Southeast China: a retrospective cohort study.

Background: We aimed to develop and validate a nomogram for effective prediction of vaginal birth after cesarean (VBAC) and guide future clinical application.

Methods: We retrospectively analyzed data from hospitalized pregnant women who underwent trial of labor after cesarean (TOLAC), at the Fujian Provincial Maternity and Children's Hospital, between October 2015 and October 2017. Briefly, we included singleton pregnant women, at a gestational age above 37 weeks who underwent a primary cesarean section, in the study.

A microfluidic platform culturing two cell lines paralleled under in-vivo like fluidic microenvironment for testing the tumor targeting of nanoparticles.

Nanoparticles are attractive in medicine because their surfaces can be chemically modified for targeting specific disease cells, especially for cancer. Providing an in-vivo like platform is crucial to evaluate the biological behaviours of nanoparticles. This paper presents a microfluidic device that could culture two cell lines in parallel in in-vivo like fluidic microenvironments and be used for testing the tumor targeting of folic acid - cholesterol - chitosan (FACC) nanoparticles.

Identification of new transmembrane proteins concentrated at the nuclear envelope using organellar proteomics of mesenchymal cells.

The double membrane nuclear envelope (NE), which is contiguous with the ER, contains nuclear pore complexes (NPCs) - the channels for nucleocytoplasmic transport, and the nuclear lamina (NL) - a scaffold for NE and chromatin organization. Since numerous human diseases linked to NE proteins occur in mesenchyme-derived cells, we used proteomics to characterize NE and other subcellular fractions isolated from mesenchymal stem cells and from adipocytes and myocytes. Based on spectral abundance, we calculated enrichment scores for proteins in the NE fractions.

AXL phosphorylates and up-regulates TNS2 and its implications in IRS-1-associated metabolism in cancer cells.

Background: TNS2 is a focal adhesions protein and a binding partner for many proteins, including the receptor tyrosine kinase Axl. Although TNS2 can bind with Axl, the details of their interactions have not been elucidated. TNS2 is involved in IRS-1 signaling pathway.

Whole-Mount BrdU Staining with Fluorescence In Situ Hybridization in Planarians.

Detection of cell proliferation based on the incorporation of 5'-bromo-2'-deoxyuridine (BrdU) has become a standard approach for studying stem cell and progenitor cell populations in developing and adult tissue. In this chapter, we describe three BrdU administration methods for planarians and a staining protocol combining BrdU detection with whole-mount fluorescence in situ hybridization (FISH). Collectively, these protocols enable the combined analysis of BrdU-incorporation and endogenous gene expression, as for example during lineage tracing applications.

Prospectively Isolated Tetraspanin Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration.

Proliferating cells known as neoblasts include pluripotent stem cells (PSCs) that sustain tissue homeostasis and regeneration of lost body parts in planarians. However, the lack of markers to prospectively identify and isolate these adult PSCs has significantly hampered their characterization. We used single-cell RNA sequencing (scRNA-seq) and single-cell transplantation to address this long-standing issue.

Cellular, ultrastructural and molecular analyses of epidermal cell development in the planarian Schmidtea mediterranea.

The epidermis is essential for animal survival, providing both a protective barrier and cellular sensor to external environments. The generally conserved embryonic origin of the epidermis, but the broad morphological and functional diversity of this organ across animals is puzzling. We define the transcriptional regulators underlying epidermal lineage differentiation in the planarian Schmidtea mediterranea, an invertebrate organism that, unlike fruitflies and nematodes, continuously replaces its epidermal cells.

polymorphism is associated with an increased risk of familial cancer: evidence from a meta-analysis.

Adenosine diphosphate (ADP)-ribosylation factor-like tumour suppressor gene 1() might be associated with an increased risk of several types of familial cancers. However, previous studies have shown that cancer susceptibility is not completely consistent with polymorphisms, and the precise mechanism remains unknown. Therefore, we conducted a meta-analysis of case-control studies by searching the PubMed, Embase, OVID, Science Direct and Chinese National Knowledge Infrastructure (CNKI) databases.

Synthesis of folate‑chitosan nanoparticles loaded with ligustrazine to target folate receptor positive cancer cells.

In addition to its vasodilatory effect, ligustrazine (LZ) improves the sensitivity of multidrug resistant cancer cells to chemotherapeutic agents. To enhance the specificity of LZ delivery to tumor cells/tissues, folate‑chitosan nanoparticles (FA‑CS‑NPs) were synthesized by combination of folate ester with the amine group on chitosan to serve as a delivery vehicle for LZ (FA‑CS‑LZ‑NPs). The structure of folate‑chitosan and characteristics of FA‑CS‑LZ‑NPs, including its size, encapsulation efficiency, loading capacity and release rates were analyzed.

Novel amphiphilic folic acid-cholesterol-chitosan micelles for paclitaxel delivery.

In order to decrease the toxicity of paclitaxel (PTX) and increase the efficiency, we developed an amphiphilic PTX injection system using a biodegradable and biocompatible polymer synthesized by folic acid, cholesterol, and chitosan (FACC). This FACC-based polymer had a low critical concentration (64.13μg/ml) and could self-assemble in aqueous condition to form nanoscale micelles.