Mucosal immunity and vaccination strategies: current insights and future perspectives.

The mucosal immune system represents a critical defense mechanism, safeguarding the body from an array of external pathogens. As the body's first line of immune protection, it plays an essential role in initiating both innate and adaptive immune responses. Through intricate networks of immune cells and complex molecular pathways, mucosal immunity orchestrates a robust defense not only at the local level but also activates systemic immune responses to ensure comprehensive protection.

Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.

The Wnt/β-catenin signaling pathway is a highly conserved signaling pathway closely linked to cancer development through various biological processes, including oncogenic transformation, genomic instability, cancer cell proliferation, stemness, metabolism, cell death, immune regulation, and metastasis. Notably, its activation plays a crucial role in drug resistance to chemotherapy, targeted therapy and immunotherapy. Recent advances in drug development have identified several targeted inhibitors acting at key nodal points of this pathway, with some demonstrating synergistic efficacy when combined with immunotherapeutic agents.

Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer.

Replicon RNA (RepRNA) represents a cutting-edge technology in the field of vaccinology, fundamentally transforming vaccine design and development. This innovative approach facilitates the induction of robust immune responses against a range of infectious diseases and cancers. RepRNA vaccines leverage the inherent capabilities of RNA-dependent RNA polymerase associated with self-replicating repRNA, allowing for extreme replication within host cells.

Simultaneous enhancement of cellular and humoral immunity by the lymph node-targeted cholesterolized TLR7 agonist liposomes.

Toll-like receptor (TLR) agonists, as promising adjuvants and immunotherapeutic agents, have the potential to enhance immune responses and modulate antigen-dependent T-cell immune memory through activation of distinct signaling pathways. However, their clinical application is hindered by uncontrolled systemic inflammatory reactions. Therefore, it is imperative to create a vaccine adjuvant for TLR receptors that ensures both safety and efficacy.

A chimeric adenovirus-vectored vaccine based on Beta spike and Delta RBD confers a broad-spectrum neutralization against Omicron-included SARS-CoV-2 variants.

Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus-vectored vaccine named Ad5-Beta/Delta. This vaccine was created by incorporating the receptor-binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant.

Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has decreased the efficacy of SARS-CoV-2 vaccines in containing coronavirus disease 2019 (COVID-19) over time, and booster vaccination strategies are urgently necessitated to achieve sufficient protection. Intranasal immunization can improve mucosal immunity, offering protection against the infection and sustaining the spread of SARS-CoV-2. In this study, an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum, nasal lavage fluid, and bronchoalveolar lavage fluid compared with only two doses of mRNA vaccine.

Tripterin liposome relieves severe acute respiratory syndrome as a potent COVID-19 treatment.

For coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 15-30% of patients are likely to develop COVID-19-related acute respiratory distress syndrome (ARDS). There are still few effective and well-understood therapies available. Novel variants and short-lasting immunity are posing challenges to vaccine efficacy, so finding antiviral and antiinflammatory treatments remains crucial.

A self-assembled trimeric protein vaccine induces protective immunity against Omicron variant.

The recently emerged Omicron (B.1.1.

Nanomaterial-Based Drug Delivery System Targeting Lymph Nodes.

The lymphatic system plays an indispensable role in humoral balance, lipid metabolism, and immune regulation. The lymph nodes (LNs) are known as the primary sites of tumor metastasis and the metastatic LNs largely affected the prognosis of the patiens. A well-designed lymphatic-targeted system favors disease treatment as well as vaccination efficacy.

Tumor-associated neutrophils and neutrophil-targeted cancer therapies.

Neutrophils are the frontline cells in response to microbial infections and are involved in a range of inflammatory disorders in the body. In recent years, neutrophils have gained considerable attention in their involvement of complex roles in tumor development and progression. Tumor-associated neutrophils (TANs) that accumulate in local region could be triggered by external stimuli from tumor microenvironment (TME) and switch between anti- and pro-tumor phenotypes.

Genome editing via non-viral delivery platforms: current progress in personalized cancer therapy.

Cancer is a severe disease that substantially jeopardizes global health. Although considerable efforts have been made to discover effective anti-cancer therapeutics, the cancer incidence and mortality are still growing. The personalized anti-cancer therapies present themselves as a promising solution for the dilemma because they could precisely destroy or fix the cancer targets based on the comprehensive genomic analyses.

Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells.

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.

Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice.

The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening. Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2, which greatly limits its application in routine research. Here, we generate a mouse model of COVID-19 under a general laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) observed in humans.

Neurological complications and infection mechanism of SARS-COV-2.

Currently, SARS-CoV-2 has caused a global pandemic and threatened many lives. Although SARS-CoV-2 mainly causes respiratory diseases, growing data indicate that SARS-CoV-2 can also invade the central nervous system (CNS) and peripheral nervous system (PNS) causing multiple neurological diseases, such as encephalitis, encephalopathy, Guillain-Barré syndrome, meningitis, and skeletal muscular symptoms. Despite the increasing incidences of clinical neurological complications of SARS-CoV-2, the precise neuroinvasion mechanisms of SARS-CoV-2 have not been fully established.

Lymph-Node-Targeted Cholesterolized TLR7 Agonist Liposomes Provoke a Safe and Durable Antitumor Response.

Toll-like receptor (TLR) agonists as the potent stimulants of an innate immune system hold promises for applications in anticancer immunotherapy. However, most of them are limited in the clinical translation due to the uncontrolled systemic inflammatory response. In the current study, 1V209, a small molecule TLR7 agonist, was conjugated with cholesterol (1V209-Cho) and prepared into liposomes (1V209-Cho-Lip).

CRISPR/Cas12a-Mediated Interfacial Cleaving of Hairpin DNA Reporter for Electrochemical Nucleic Acid Sensing.

A rapid and sensitive isothermal method is crucial for point-of-care (POC) nucleic acid testing. Recently, RNA-guided CRISPR/Cas12a proteins were discovered to exhibit target-triggered nonspecific single-stranded deoxyribonuclease (ssDNase) activity. Herein, the ssDNase cleavage capacity of the CRISPR/Cas12a system for interfacial hairpin DNA (hpDNA) and linear DNA was investigated in detailed.

An integrated electrochemical biosensor based on target-triggered strand displacement amplification and "four-way" DNA junction towards ultrasensitive detection of PIK3CA gene mutation.

A novel electrochemical biosensor was constructed for specific and ultrasensitive detection of PIK3CA gene mutation based on NsbI restriction enzyme-mediated strand displacement amplification (NsbI-SDA) and four-way DNA junction for the first time. In this biosensor, the NsbI restriction enzyme combined with strand displacement amplification (SDA) was able to specifically distinguish PIK3CA gene mutation and increase the number of DNA copies to improve electrochemical response. In the presence of target mutation gene, DNA fragments produced by the cleavage event of NsbI restriction enzyme could trigger the SDA reaction to generate massive linker chains.

Label-free and ultrasensitive electrochemical biosensor for the detection of EBV-related DNA based on AgDNCs@DNA/AgNCs nanocomposites and lambda exonuclease-assisted target recycling.

A label-free and efficient electrochemical biosensor was developed for the ultrasensitive detection of EBV-related DNA by combing AgDNCs@DNA/AgNCs nanocomposites with noncanonical lambda exonuclease (λ exo)-assisted target recycling (LNTR). The conjugates of AgDNCs, DNA/AgNCs and probe DNA (pDNA-AgDNCs@DNA/AgNCs conjugates) worked as not only ideal nanocarriers but also efficient electrochemical tags. LNTR didn't require phosphorylated substrates and could be triggered specifically by target DNA, leading to the recycling use of target DNA and the liberation of plentiful linker probes (LP).

A smart fluorescent biosensor for the highly sensitive detection of BRCA1 based on a 3D DNA walker and ESDR cascade amplification.

Nucleic acid analysis plays an important role in the diagnosis of diseases. There is a continuous demand to develop rapid and sensitive methods for the specific detection of nucleic acids. Herein, we constructed a highly sensitive and rapid fluorescent biosensor for the detection of BRCA1 by coupling a 3D DNA walker machine with spontaneous entropy-driven strand displacement reactions (ESDRs).

A one-step fluorescent biosensing strategy for highly sensitive detection of HIV-related DNA based on strand displacement amplification and DNAzymes.

Sensitive and specific detection of HIV-related DNA is of great importance for early accurate diagnosis and therapy of HIV-infected patients. Here, we developed a one-step and rapid fluorescence strategy for HIV-related DNA detection based on strand displacement amplification and a Mg-dependent DNAzyme reaction. In the presence of target HIV DNA, it can hybridize with template DNA and activate strand displacement amplification to generate numerous DNAzyme sequences.