Prospects and challenges of neoantigen applications in oncology.

Neoantigen, unique peptides resulting from tumor-specific mutations, represent a promising frontier in oncology for personalized cancer immunotherapy. Their unique features allow for the development of highly specific and effective cancer treatments, which can potentially overcome the limitations of conventional therapies. This paper explores the current prospects and challenges associated with the application of neoantigens in oncology.

Nonlinear effects of agricultural drought on vegetation productivity in the Yellow River Basin, China.

Agricultural drought (AD) is the main environmental factor affecting vegetation productivity (VP) in the Yellow River Basin (YRB). In recent years, the nonlinear effects of AD on VP in the YRB have attracted much attention. However, it is still unclear whether fluctuating AD will have complex nonlinear effects on VP in the YRB, and there are scant previous studies at large scale on whether there is a threshold for nonlinear effects of AD on VP in the YRB.

Mechanical, Thermal Properties, and Extreme Phase Stability of High-Entropy Diborides (VNbTaCrW)B.

High-entropy diborides (HEDBs) have gained significant attention in industrial applications due to their vast composition space and tunable properties. We propose a solid solution reaction at high temperatures and pressures that successfully synthesized and sintered a novel, dense, and phase-pure HEDB (VNbTaCrW)B. A high asymptotic Vickers hardness of 26.

Draining Lymph Node Metastasis Model for Assessing the Dynamics of Antigen-Specific CD8+ T Cells During Tumorigenesis.

Tumor antigen-specific CD8 T cells from draining lymph nodes gain an accumulating importance in mounting anti-tumor immune response during tumorigenesis. However, in many cases, cancer cells form metastatic loci in lymph nodes before further metastasizing to distant organs. To what extent the local and systematic CD8 T cell responses were influenced by LN metastasis remains obscure.

Spatiotemporal evolution of agricultural drought and its attribution under different climate zones and vegetation types in the Yellow River Basin of China.

Ecological protection and high-quality development of the Yellow River Basin (YRB) are major national strategies in China. Agricultural drought (AD) is one of the most important stress factors of the ecological security of the YRB. Currently, there is a lack of exploration of the spatiotemporal evolution of AD in the YRB under different climatic zones and vegetation types, and the mechanisms by the driving factors influence AD remain unclear.

Drawing Inspiration from Nature: Trinitarian Strategies for Designing Polyoxometalates and Metal-Organic Framework-Based Biomimetic Microhoneycomb Electromagnetic Wave-Absorbing Materials.

Trinitarian designs in the morphology, components, and microstructure remain challenging for advanced electromagnetic wave absorption (EMWA) materials with light weight, strong absorption, and well-defined structure-function relationships. Herein, a series of X-doped MoS/CuS with multilevel honeycomb structures (X-MoS/CuS MHs, X = P, Si, Ge) were designed by space-confined growth and in situ sulfidation of a polyoxometalate-based metal-organic framework. X-MoS/CuS MHs possess low density, high surface area, and abundant cation-cuprum and anion-sulfur double vacancies ( and ) simultaneously that are unmatched by conventional EMWA materials.

Strontium-doped hydroxyapatite and its role in osteogenesis and angiogenesis.

For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone. Extensive preclinical and clinical studies have shown that strontium (Sr) can safely and effectively help prevent and treat bone diseases, including osteoporosis. These findings have resulted in the concept of integrating Sr and HA for bone disease management.

Construction of amorphous VO@TiCT synergistic heterostructure on 3D carbon cloth substrate by a self-assembled strategy towards high-performance aqueous Zn-ion batteries.

The emerging aqueous Zn-ion batteries (ZIBs) with their low price and inherent safety are showing strong competitiveness in the energy storage field. In this work, layer-by-layer stacked amorphous VO@TiCT heterostructures anchored on three-dimensional carbon cloth (3D CC), synthesized by annealing process and subsequent in-situ electrochemical induction, are reported as high capacity and stable cathode for ZIBs. In this composite cathode, amorphous VO@TiCT synergistic heterostructure provides isotropic Zn migration channels and rapid electron transfer kinetics, while the 3D CC substrate can ensure that the bulk phase in the electrode material is also utilized to maximize the synergistic effect.

The primordial differentiation of tumor-specific memory CD8 T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes.

Blocking PD-1/PD-L1 signaling transforms cancer therapy and is assumed to unleash exhausted tumor-reactive CD8 T cells in the tumor microenvironment (TME). However, recent studies have also indicated that the systemic tumor-reactive CD8 T cells may respond to PD-1/PD-L1 immunotherapy. These discrepancies highlight the importance of further defining tumor-specific CD8 T cell responders to PD-1/PD-L1 blockade.

Tumor-Specific CD4 T Cells Restrain Established Metastatic Melanoma by Developing Into Cytotoxic CD4 T Cells.

Cytotoxic CD8 T cells are the main focus of efforts to understand anti-tumor immunity and immunotherapy. The adoptive transfer of tumor-reactive cytotoxic CD8 T lymphocytes expanded and differentiated has long been considered the primary strategy in adaptive anti-tumor immunity, however, the majority of the transferred tumor antigen-specific CD8 T cells differentiated into CD39CD69 exhausted progenies, limiting its effects in repressing tumor growth. Contrarily, less attention has been addressed to the role of CD4 T cells during tumorigenesis.

A novel strategy to investigate the factors regulating the Treg to Tfr transition during acute viral infection.

Follicular regulatory T cells (Tfrs), a specialized subset of regulatory T cells (Tregs), have a particular role in the control of follicular helper T cell-driven germinal center (GC) responses. Following differentiation signals similar to those received by follicular helper T cells (Tfhs), Tfrs gain expression of characteristic chemokine receptors and transcription factors, such as CXCR5 and Bcl-6, allowing them to migrate into the B-cell follicle and perform in situ suppression. Thus, together with Tfhs, Tfrs help maintaining an optimized GC-reaction.

The recycling regulation of sodium-hydrogen exchanger isoform 3(NHE3) in epithelial cells.

As the main exchanger of electroneutral NaCl absorption, sodium-hydrogen exchanger isoform 3 (NHE3) circulates in the epithelial brush border (BB) and intracellular compartments in a multi-protein complex. The size of the NHE3 complex changes during rapid regulation events. Recycling regulation of NHE3 in epithelial cells can be roughly divided into three stages.

Decreased NHE3 activity in intestinal epithelial cells in TGEV and PEDV-induced piglet diarrhea.

Transmissible gastroenteritis (TGE) and porcine epidemic diarrhea (PED) are highly transmissible intestinal infections caused by transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), respectively. They are clinically associated with vomiting, diarrhea, and dehydration in piglets. An imbalance in Na uptake by intestinal epithelial cells causes TGEV/PEDV-induced diarrhea.

Identification of HLA-A2-Restricted Mutant Epitopes from Neoantigens of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC), one of the deadliest gastrointestinal cancers, has had limited effective therapeutic strategies up to now. Accumulating evidence suggests that effective immunotherapy in cancer patients has been associated with T cells responsive to mutant peptides derived from neoantigens. Here, we selected 35 human leukocyte antigen-A2 (HLA-A2)-restricted mutant (MUT) peptides stemmed from neoantigens of ESCC.

Reduced activity of intestinal surface Na/H exchanger NHE3 is a key factor for induction of diarrhea after PEDV infection in neonatal piglets.

Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea and vomiting, dehydration, and high mortality in neonatal piglets. Despite extensive research focusing on the pathogenesis of PEDV infection, the molecular pathogenesis of PEDV-induced diarrhea in piglets remains unclear. Na/H exchanger 3 (NHE3), the main exchanger of electroneutral sodium in intestinal epithelial cells, is closely associated with the occurrence of diarrhea.

Inhibitory effects of Lactobacillus plantarum metabolites on porcine epidemic diarrhea virus replication.

Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus; it causes diarrhea in pigs and is associated with high morbidity and mortality in sucking piglets. In this study, we performed in vitro and in vivo experiments to determine the inhibitory effects of Lactobacillus plantarum metabolites (LPM) on PEDV replication. Gas chromatography-mass spectrometry revealed exopolysaccharides to be one of the main components of LPM.

Screening and identification of HLA-A2-restricted neoepitopes for immunotherapy of non-microsatellite instability-high colorectal cancer.

Colorectal cancer has one of the highest mortality rates among malignant tumors, and most patients with non-microsatellite instability-high (MSI-H) colorectal cancer do not benefit from targeted therapy or immune checkpoint inhibitors. Identification of immunogenic neoantigens is a promising strategy for inducing specific antitumor T cells for cancer immunotherapy. Here, we screened potential high-frequency neoepitopes from non-MSI-H colorectal cancer and tested their abilities to induce tumor-specific cytotoxic T cell responses.

Effect of Fabrication Parameters on the Performance of 0.5 wt.% Graphene Nanoplates-Reinforced Aluminum Composites.

Aluminum composites reinforced by graphene nanoplates(GNP) with a mass fraction of 0.5% (0.5 wt.

Exercise Promotes the Osteoinduction of HA/β-TCP Biomaterials via the Wnt Signaling Pathway.

To investigate the osteoinductive mechanism triggered by hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) biomaterials in mice which keep exercising. The HA/β-TCP biomaterials were implanted in the muscle of bilateral thighs (non-osseous sites) of eighty Balb/C mice. All animals were then randomly divided into 4 groups ( = 20).

Decreased NHE3 activity and trafficking in TGEV-infected IPEC-J2 cells via the SGLT1-mediated P38 MAPK/AKt2 pathway.

Transmissible gastroenteritis virus (TGEV) primarily replicates in intestinal epithelial cells and causes severe damage to host cells, resulting in diarrhea. Surface NHE3 serves as the key regulatory site controlling electroneutral Na absorption. In this study, our results showed that the surface NHE3 content was significantly reduced following TGEV infection, whereas the total level of protein expression was not significantly changed, and NHE3 activity gradually decreased with prolonged infection time.

Anti-TGEV Miller Strain Infection Effect of Supernatant Based on the JAK-STAT1 Signaling Pathway.

Transmissible gastroenteritis (TGE), caused by transmissible gastroenteritis virus (TGEV), is one many gastrointestinal inflections in piglets, characterized by diarrhea, and high mortality. Probiotics are ubiquitous bacteria in animal intestines, which have many functions, such as promoting intestinal peristalsis and maintaining the intestinal balance. We found that the supernatant of the Lp-1 strain of , isolated in our laboratory, and named Lp-1s had marked anti-TGEV effect on IPEC-J2 cells.

HLA-A2-Restricted Epitopes Identified from MTA1 Could Elicit Antigen-Specific Cytotoxic T Lymphocyte Response.

Overexpression of metastasis-associated protein 1 (MTA1) has been observed in many human malignancies and is significantly related to tumor invasion and metastasis, therapeutic resistance to radiation and chemotherapy, making MTA1 an ideal candidate tumor antigen. We identified several human leukocyte antigen- (HLA-) A2-restricted epitopes in MTA1 and evaluated their binding ability to HLA-A0201 molecules. Subsequently, a recombinant fragment encompassing the dominant epitopes, MTA1, was expressed, and the abilities of the selected epitopes of MTA1 and the MTA1 fragment to induce cytotoxic T lymphocytes (CTLs) were examined.