Diphtheria Toxoid-Derived T-Helper Epitope and α-galactosylceramide Synergistically Enhance the Immunogenicity of Glycopeptide Antigen.

The tumor-associated antigen MUC1 is an attractive target for immunotherapy, however, its weak immunogenicity limits the induction of antitumor immune responses. To overcome this limitation, in this study, MUC1 glycopeptide was covalently linked with a diphtheria toxin-derived T-helper epitope (DT). Subsequently, the resulting DT-MUC1 glycopeptide was physically mixed with natural killer T cell agonist αGalCer to explore their immunomodulatory synergy.

Trace antibiotic exposure affects murine gut microbiota and metabolism.

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied.

Conjugation of TLR7 and TLR7/8 agonists onto weak protein antigen via versatile oxime ligation for enhanced vaccine efficacy.

Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time.

[Scale Effects of Landscape Pattern on Impacts of River Water Quality： A Meta-analysis].

The landscape pattern determines water pollution source and sink processes and plays an important role in regulating river water quality. Due to scale effects, studies on the relationship between landscape pattern and river water quality showed variance at different scales. However, there is still a lack of integrated study on the scale effect of landscape pattern and river water quality dynamics.

From design to clinic: Engineered peptide nanomaterials for cancer immunotherapy.

Immunotherapy has revolutionized the field of cancer therapy. Nanomaterials can further improve the efficacy and safety of immunotherapy because of their tunability and multifunctionality. Owing to their natural biocompatibility, diverse designs, and dynamic self-assembly, peptide-based nanomaterials hold great potential as immunotherapeutic agents for many malignant cancers, with good immune response and safety.

Future Trends in Distribution across Eurasian Continent under Global Climate Change.

was discovered in Eurasia at the beginning of the 21st century. In this study, we explore the present and future (in the years 2050 and 2070) trends in the potential distribution of in Eurasia under diverse climate change scenarios based on a maximum entropy model. Our findings indicated that the current potential distribution area of is within the range of 21°34' and 65°39' N in the Eurasian continent.

Simultaneous phosphorus and nitrogen removal with different C/N ratios in a low oxygen aeration system: Microorganisms and mechanisms.

In this study, a combined system with simultaneous nitrification, denitrification, and phosphorus removal was operated in continuous low oxygen aeration mode, and the effect of lower oxygen aeration (dissolved oxygen [DO] 0.5-1.5 mg/L) on its performance was examined.

Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson's Disease Models of .

Melatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic strategy for Parkinson's disease (PD), which inhibits pathways associated with oxidative stress in PD. In this study, we reported a C7-selective olefination of melatonin under rhodium catalysis with the aid of P-directing groups and synthesized 10 new melatonin-C7-cinnamic acid derivatives (6a-6j).

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine.

The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects.

MUC1 Specific Immune Responses Enhanced by Coadministration of Liposomal DDA/MPLA and Lipoglycopeptide.

Mucin 1 (MUC1), a well-known tumor-associated antigen and attractive target for tumor immunotherapy, is overexpressed in most human epithelial adenomas with aberrant glycosylation. However, its low immunogenicity impedes the development of MUC1-targeted antitumor vaccines. In this study, we investigated three liposomal adjuvant systems containing toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and auxiliary lipids of different charges: cationic lipid dimethyldioctadecylammonium (DDA), neutral lipid distearoylglycerophosphocholine (DSPC) or anionic lipid dioleoylphosphatidylglycerol (DOPG), respectively.

Autophagy inhibitors increase the susceptibility of KRAS-mutant human colorectal cancer cells to a combined treatment of 2-deoxy-D-glucose and lovastatin.

RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation.

Clathrin-independent but dynamin-dependent mechanisms mediate Ca2+-triggered endocytosis of the glutamate GluK2 receptor upon excitotoxicity.

We first explore the features of GluK2 endocytosis during kainate excitotoxicity and then explore the role of Ca in the regulation of GluK2 endocytosis. The roles of Ca were examined by treating cells with Ca inhibitors or chelators. Surface biotinylation was used to examine the surface localization of GluK2.

Peptidyl ω-Asp Selenoesters Enable Efficient Synthesis of -Linked Glycopeptides.

Chemical synthesis is an attractive approach allows for the assembly of homogeneous complex -linked glycopeptides and glycoproteins, but the limited coupling efficiency between glycans and peptides hampered the synthesis and research in the related field. Herein we developed an alternative glycosylation to construct -linked glycopeptide via efficient selenoester-assisted aminolysis, which employs the peptidyl ω-asparagine selenoester and unprotected glycosylamine to perform rapid amide-bond ligation. This glycosylation strategy is highly compatible with the free carboxylic acids and hydroxyl groups of peptides and carbohydrates, and readily available for the assembly of structure-defined homogeneous -linked glycopeptides, such as segments derived from glycoprotein EPO and IL-5.

Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses.

Many cancer vaccines are not successful in clinical trials, mainly due to the challenges associated with breaking immune tolerance. Herein, we report a new strategy using an adjuvant-protein-antigen (three-in-one protein conjugates with built-in adjuvant) as an anticancer vaccine, in which both the adjuvant (small-molecule TLR7 agonist) and tumor-associated antigen (mucin 1, MUC1) are covalently conjugated to the same carrier protein (BSA). It is shown that the protein conjugates with built-in adjuvant can increase adjuvant's stimulation, prevent adjuvant's systemic toxicities, facilitate the codelivery of adjuvants and antigens, and enhance humoral and cellular immune responses.

Effects of co-pyrolysis of rice husk and sewage sludge on the bioavailability and environmental risks of Pb and Cd.

In this study, biochars were produced by co-pyrolysis of rice husk and sewage sludge, the environmental risk of heavy metal (Pd and Cd) in the biochars was assessed. Co-pyrolysis resulted in a lower yield but a higher C content compared with sewage sludge pyrolysis alone, the relative contents of Pb and Cd in biochars were declined. Co-pyrolysis process transformed the bioavailable heavy metals into stable speciation.

The Cannabinoid WIN 55,212-2 Reduces Delayed Neurologic Sequelae After Carbon Monoxide Poisoning by Promoting Microglial M2 Polarization Through ST2 Signaling.

Delayed neurologic sequelae (DNS) are among the most serious complications of carbon monoxide (CO) poisoning caused partly by elevated neuroinflammation. WIN 55,212-2, a non-selective agonist of cannabinoid receptors, has been demonstrated to have anti-inflammatory properties in various brain disorders. The anti-inflammatory action of WIN 55,212-2 is potentially associated with driving microglial M2 polarization.

Liposomal Antitumor Vaccines Targeting Mucin 1 Elicit a Lipid-Dependent Immunodominant Response.

The tumor-associated antigen mucin 1 (MUC1) has been pursued as an attractive target for cancer immunotherapy, but the poor immunogenicity of the endogenous antigen hinders the development of vaccines capable of inducing effective anti-MUC1 immunodominant responses. Herein, we prepared synthetic anti-MUC1 vaccines in which the hydrophilic MUC1 antigen was N-terminally conjugated to one or two palmitoyl lipid chains (to form amphiphilic Pam-MUC1 or Pam -MUC1). These amphiphilic lipid-tailed MUC1 antigens were self-assembled into liposomes containing the NKT cell agonist αGalCer as an adjuvant.

Peptide-free Synthetic Nicotine Vaccine Candidates with α-Galactosylceramide as Adjuvant.

Peptides are generally needed as T-helper epitopes in nicotine vaccines to induce effective antibody responses, but the highly polymorphic property of major histocompatibility complex (MHC) molecules may limit opportunities of B cell to receive CD4 T-cell help. Invariant natural killer T (iNKT) cells recognize lipid antigens presented by the nonpolymorphic CD1d molecule that is conserved in mammals to a great extent. iNKT cells also display some similar functions to conventional CD4 T-helper cells, especially they license dendritic cells stimulate antibody isotype switching by B cells.

Comparison between minimally invasive plate osteosynthesis and open plating for proximal humeral fractures: a meta-analysis.

Aim: We conducted this meta-analysis for comparing the efficacy and safety in proximal humeral fractures by treatment minimally invasive plate osteosynthesis and open plating.

Methods: The potential academic literature were identified from the Cochrane Library, Springer, PubMed, Embase and ScienceDirect. Pooled data were analyzed by RevMan 5.

Preparation of Protein Conjugates via Homobifunctional Diselenoester Cross-Linker.

Adipic acid diselenoester was developed as an efficient cross-linker for covalent protein conjugation with a variety of small molecular haptens, including mono- and disaccharides, peptide, fluorescence dye, and nicotine. Compared to the counterparts of N-hydroxysuccinimide (NHS) and p-nitrophenyl (PNP) linkers, the diselenoester linker demonstrates improved balance between reactivity and stability and coupling of haptens to proteins under mild conditions with high incorporation efficiency.

Convergent Synthesis of N-Linked Glycopeptides via Aminolysis of ω-Asp p-Nitrophenyl Thioesters in Solution.

An efficient N-linked glycosylation reaction between glycosylamines and p-nitrophenyl thioester peptides has been developed. The reaction conditions are mild and compatible with the C-terminal free carboxylic acid group and the unprotected N-linked sialyloligosaccharide. By means of this convergent strategy, a versatile N-glycopeptide fragment containing an N-terminal Thz and a C-terminal thioester was readily prepared, which is available for the synthesis of long glycopeptides and glycoproteins using the protocol of native chemical ligation.

Calcium-Sensing Receptor in Human Peripheral Blood T Lymphocytes Is Involved in the AMI Onset and Progression through the NF-κB Signaling Pathway.

Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear.