High-throughput synthesis and optimization of ionizable lipids through A coupling for efficient mRNA delivery.

Background: The efficacy of mRNA-based vaccines and therapies relies on lipid nanoparticles (LNPs) as carriers to deliver mRNA into cells. The chemical structure of ionizable lipids (ILs) within LNPs is crucial in determining their delivery efficiency.

Results: In this study, we synthesized 623 alkyne-bearing ionizable lipids using the A coupling reaction and assessed their effectiveness in mRNA delivery.

Utidelone plus pembrolizumab as the fourth-line combination treatment in non-small cell lung cancer with EGFR mutation: a case report.

Utidelone is an ebomycin derivative chemotherapeutic drug, which can promote tubulin polymerization and stabilize microtubule structure, so as to induce apoptosis. The drug is an innovative drug independently developed by China with independent intellectual property rights. Phase II clinical trials for advanced breast cancer are being approved by National Medical Products Administration for the treatment of advanced breast cancer.

All-Trans-Retinoic Acid-Adjuvanted mRNA Vaccine Induces Mucosal Anti-Tumor Immune Responses for Treating Colorectal Cancer.

Messenger RNA (mRNA) cancer vaccines are a new class of immunotherapies that can activate the immune system to recognize and destroy cancer cells. However, their effectiveness in treating colorectal cancer located on the mucosal surface of the gut is limited due to the insufficient activation of mucosal immune response and inadequate infiltration of cytotoxic T cells into tumors. To address this issue, a new mRNA cancer vaccine is developed that can stimulate mucosal immune responses in the gut by co-delivering all-trans-retinoic acid (ATRA) and mRNA using lipid nanoparticle (LNP).

Layer-by-layer nanoparticle encapsulating all-trans retinoic acid and CpG as a mucosal adjuvant targeting colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent cancers globally, demanding innovative therapeutic strategies. Immunotherapy, a promising avenue, employs cancer vaccines to activate the immune system against tumors. However, conventional approaches fall short of eliciting robust responses within the gastrointestinal (GI) tract, where CRC originates.

A Synergistic Lipid Nanoparticle Encapsulating mRNA Shingles Vaccine Induces Potent Immune Responses and Protects Guinea Pigs from Viral Challenges.

Shingles is caused by the reactivation of varicella zoster virus (VZV) and manifests as painful skin rashes. While the recombinant protein-based vaccine proves highly effective, it encounters supply chain challenges due to a shortage of the necessary adjuvant. Messenger RNA (mRNA)-based vaccines can be rapidly produced on a large scale, but their effectiveness relies on efficient delivery and sequence design.

Computational Insights into the Esterification of Palmitic Acid with Methanol in Water.

This work provides quantified explanations for the thermodynamic and kinetic characteristics of esterification in aqueous phase, and how phase transfer catalysts improve water phase esterification of fatty acids in a computational-experimental way. Self-catalyzed reaction mode with or without solvation effects, water participated reaction mode, and catalytic reaction mode (catalyzed by p-dodecyl benzene sulfonic acid, DBSA) are discussed. Our results show that the initial self-catalytic reaction mode undergoes the energy barrier of 100.

Induction of ligustrazine apoptosis of A549 cells through activation of death receptor pathway.

Background: The aim of this study was to evaluate the effect of ligustrazine on the apoptosis of A549 cells and clarify the mechanism of ligustrazine-induced apoptosis.

Methods: Ligustrazine was prepared with medium according to the gradient concentration. Based on a cytotoxicity test, 3 different concentrations of ligustrazine were selected to form low, medium, and high groups, with a 0 mg/mL dose used as the control.

Application of Bayesian network and regression method in treatment cost prediction.

Charging according to disease is an important way to effectively promote the reform of medical insurance mechanism, reasonably allocate medical resources and reduce the burden of patients, and it is also an important direction of medical development at home and abroad. The cost forecast of single disease can not only find the potential influence and driving factors, but also estimate the active cost, and tell the management and reasonable allocation of medical resources. In this paper, a method of Bayesian network combined with regression analysis is proposed to predict the cost of treatment based on the patient's electronic medical record when the amount of data is small.

ORF3a-Mediated Incomplete Autophagy Facilitates Severe Acute Respiratory Syndrome Coronavirus-2 Replication.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent for the coronavirus disease 2019 (COVID-19) pandemic and there is an urgent need to understand the cellular response to SARS-CoV-2 infection. Beclin 1 is an essential scaffold autophagy protein that forms two distinct subcomplexes with modulators Atg14 and UVRAG, responsible for autophagosome formation and maturation, respectively. In the present study, we found that SARS-CoV-2 infection triggers an incomplete autophagy response, elevated autophagosome formation but impaired autophagosome maturation, and declined autophagy by genetic knockout of essential autophagic genes reduces SARS-CoV-2 replication efficiency.

Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2 Pathogenesis.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown.

Methods: Genome-wide screening was used to establish intraviral and viral-host interactomes.

[Flubendazole Inhibits the Proliferation of A549 and H460 Cells and Promotes Autophagy].

Background: Flubendazole is an anthelmintic and categorized in benzimidazole. Previous evidence indicates its suppression on proliferation of colon cancer and breast cancer cells. Our study aims to explore the effects of flubendazole on non-small cell lung cancer A549 and H460 cell lines and the underlying mechanism.

Viral metagenomics reveals significant viruses in the genital tract of apparently healthy dairy cows.

The virome in genital tract secretion samples collected from 80 dairy cattle in Shanghai, China, was characterized. Viruses detected included members of the families Papillomaviridae, Polyomaviridae, Hepeviridae, Parvoviridae, Astroviridae, Picornaviridae, and Picobirnaviridae. A member of a new species within the genus Dyoxipapillomavirus and six circular Rep-encoding single-stranded DNA (ssDNA) (CRESS-DNA) viral genomes were fully sequenced and phylogenetically analyzed.

STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301-3p/STAT3 axis and PI3K/AKT signalling pathway.

Objectives: Emerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database.

Metagenomic identification, genetic characterization and genotyping of porcine sapoviruses.

Sapoviruses (SaVs), belonging to the genus Sapovirus of the family Caliciviridae, were known as the enteric pathogen causing acute gastroenteritis. SaVs have been detected in humans and several animals including pigs and some porcine SaVs showed close sequence relationship with human strains suggesting the possibility of interspecies transmission. Here, we sequenced the genomes of two porcine SaVs (with strain names of p38 and SH1703) using the metagenomic analyses and traditional RT-PCR methods.

Plasma virome of cattle from forest region revealed diverse small circular ssDNA viral genomes.

Background: Free-range cattle are common in the Northeast China area, which have close contact with farmers and may carry virus threatening to cattle and farmers.

Methods: Using viral metagenomics we analyzed the virome in plasma samples collected from 80 cattle from the forested region of Northeast China.

Results: The virome of cattle plasma is composed of the viruses belonging to the families including Parvoviridae, Papillomaviridae, Picobirnaviridae, and divergent viral genomes showing sequence similarity to circular Rep-encoding single stranded (CRESS) DNA viruses.

Viral metagenomics analysis of feces from coronary heart disease patients reveals the genetic diversity of the Microviridae.

Recent studies have declared that members of the ssDNA virus family Microviridae play an important role in multiple environments, as they have been found taking a dominant position in the human gut. The aim of this study was to analyze the overall composition of the gut virome in coronary heart disease (CHD) patients, and try to discover the potential link between the human gut virome and CHD. Viral metagenomics methods were performed to detect the viral sequences in fecal samples collected from CHD inpatients and healthy persons as controls.

Genomic organization and recombination analysis of a porcine sapovirus identified from a piglet with diarrhea in China.

Background: Sapovirus (SaV), a member of the family Caliciviridae, is an etiologic agent of gastroenteritis in humans and pigs. To date, both intra- and inter-genogroup recombinant strains have been reported in many countries except for China. Here, we report an intra-genogroup recombination of porcine SaV identified from a piglet with diarrhea of China.

Identification and genomic characterization of a novel species of feline anellovirus.

Here, a novel feline anellovirus strain (named FelineAV621 and GenBank no. KX262893) was detected in two cats with diarrhea. The complete genome of FelineAV621 is 2409 nt long with a G+C content of 56.

Vibrio parahaemolyticus Strains of Pandemic Serotypes Identified from Clinical and Environmental Samples from Jiangsu, China.

Vibrio parahaemolyticus has emerged as a major foodborne pathogen in China, Japan, Thailand, and other Asian countries. In this study, 72 strains of V. parahaemolyticus were isolated from clinical and environmental samples between 2006 and 2014 in Jiangsu, China.