A Safe and Broad-spectrum SARS-CoV-2 mRNA Vaccine with a New Delivery System for In-situ Expression.

Since the outbreak of SARS-CoV-2 in late 2019, the cumulative number of confirmed cases worldwide has surpassed 778 million, and the number of deaths has exceeded 7 million, posing a significant threat to human life and health while inflicting enormous losses on the global economy. At the stage where sequential immunization is recommended, there is a pressing demand for mRNA vaccines that can be rapidly adapted to new sequences, are easy to industrialize, and exhibit high safety and effectiveness. We developed a lipid nanoparticle (LNP) system, designated as WNP, which facilitates essentially in situ expression at the injection site and results in lower levels of pro-inflammatory factors in the liver, thus enhancing its safety compared to liver-targeted alternatives.

Two-step Mendelian randomization reveals a lipid-driven protective effect of type 2 diabetes on ALS.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with few therapeutic options. Observational data suggest that type 2 diabetes mellitus (T2DM) might protect against ALS, yet the mechanisms are unclear. Clarifying whether glucose or lipid metabolism underpins this protective effect could guide targeted interventions.

Knockdown of OPTN modulates miRNA-125b-5p expression via NF-κB pathways in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurodegenerative disease characterized by severe dysfunction in upper and lower motor neurons. Previous studies have reported that the optineurin gene (OPTN) downregulation is one of the causative genetic factors for ALS, leading to the dysfunction of optineurin (OPTN), a multifunctional protein implicated in several cellular processes. Herein, we found that conditional knockout of the Optn gene in mouse microglia leads to activation of microglia.

Broadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge.

Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.

Clinical features and genetic spectrum of Chinese patients with hereditary spastic paraplegia: A 14-year study.

Hereditary spastic paraplegia (HSP) constitutes a group of clinically and genetically rare neurodegenerative diseases characterized by progressive corticospinal tract degeneration. The phenotypes and genotypes of HSP are still expanding. In this study, we aimed to analyse the differential diagnosis, clinical features, and genetic distributions of a Chinese HSP patients in a 14-year cohort and to improve our understanding of the disease.

SAN-Net: Learning generalization to unseen sites for stroke lesion segmentation with self-adaptive normalization.

There are considerable interests in automatic stroke lesion segmentation on magnetic resonance (MR) images in the medical imaging field, as stroke is an important cerebrovascular disease. Although deep learning-based models have been proposed for this task, generalizing these models to unseen sites is difficult due to not only the large inter-site discrepancy among different scanners, imaging protocols, and populations, but also the variations in stroke lesion shape, size, and location. To tackle this issue, we introduce a self-adaptive normalization network, termed SAN-Net, to achieve adaptive generalization on unseen sites for stroke lesion segmentation.

A de novo c.113 T > C: p.L38R mutation of : case report of a girl with sporadic juvenile amyotrophic lateral sclerosis.

has been implicated in hereditary sensory and autonomic neuropathy type 1 (HSAN1) and macular telangiectasia type2. Recent studies have reported mutations in may cause juvenile amyotrophic lateral sclerosis (JALS), especially in the first transmembrane domain of (exon 2). In this study, we identified a novel heterozygous variant in exon 2, c.

[Quercetin induces apoptosis of human breast cancer cells by activiting PTEN and inhibiting PI3K/AKT and JNK signaling pathways].

Objective To investigate the effect of quercetin on cell proliferation and apoptosis of MCF-7 human breast cancer cells, and effects of signaling pathways of PTEN/PI3K/AKT and c-Jun N-terminal kinase (JNK) signaling pathway. Methods MCF-7 cells were treated with quercetin (0, 20, 40, 60, 80, 100 μmol/L) CCK-8 assay was used to detect the cell proliferation, and cell apoptosis was assayed by flow cytometry. Hochesst33342 staining was used to observe the changes of nuclear number and karyotype, and flow cytometry was employed to detect cell apoptosis.

Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration and death of motor neurons. Systemic neuroinflammation contributes to the pathogenesis of ALS. The proinflammatory milieu depends on the continuous crosstalk between the peripheral immune system (PIS) and central immune system (CIS).

An identical mutation in two Chinese siblings manifest as dHMN and ALS respectively: a case report.

Mutations in the gene have been found in patients with various neurodegenerative diseases, and the spectrum is still expanding. Here, we report a mutation in (c.175G > C, p.

Validation of the pathogenic role of rare DNAJC7 variants in Chinese patients with amyotrophic lateral sclerosis.

DNAJC7 has recently been recognized as a novel amyotrophic lateral sclerosis (ALS) risk gene. To date, few studies have screened DNAJC7 mutations in Chinese population. Further studies are needed to clarify the clinical and genetic features of DNAJC7-related ALS.

Activation of chicken macrophages during in vitro stimulation and expression of immune genes.

OBJECTIVE To characterize activation and expression of immune genes of chicken macrophages after in vitro stimulation with lipopolysaccharide (LPS) and mouse erythrocytes. ANIMALS Five 15-day-old chickens and 2 BALB/c mice. PROCEDURES Macrophages were extracted from chicken bone marrow or peripheral blood and then stimulated with cytokines secreted from cell lines L929 and HD11.

Grass carp (Ctenopharyngodon idellus) invariant chain of the MHC class II chaperone protein associates with the class I molecule.

The invariant chain (Ii) is an important immune molecule, as it assists major histocompatibility complex (MHC) class II molecules to present antigenic peptides. The relationship between the Ii and MHC molecules in teleosts remains poorly understood. This study focused on the molecular structure of grass carp Ii (gIi), its organ distribution, correlations with gene transcription, and the association with MHC.

[Effect difference between two segments in invariant chain CLIP on humoral immune].

Objective: To compare the effect between two segments (PBS and GBS) of Class II -associated invariant chain peptide (CLIP) of invariant chain (Ii) on humoral immune by immune carrier.

Methods: First six hybrids containing Newcastle disease virus (NDV) epitope F2 and Ii segments (Cyt/TM/F2, Cyt/TM/F2/GBS, Cyt/TM/PBS/F2, Cyt/TM/F2/TRIM, Cyt/TM/F2/GBS/TRIM, Cyt/TM/PBS/F2/TRIM) were reconstructed respectively. Then they were inserted into the prokaryotic expression vector pET-32a and transformed into E.

Allele-dependent association of chicken MHC class I molecules with the invariant chain.

Invariant chain (Ii) associates with MHC class I molecules in cross-presentation pathway in mouse, but the association of Ii with MHC class I molecules in chicken was not clear. In this study we selected five typical alleles from about 100 B-FA and some B-FB sequences and tested. Confocal microscopy revealed that only two alleles of α chain (CD type) rather than β chain showed incomplete co-localization with Ii own, or as a combined cytosolic and transmembrane domains in the co-transfected 293T cells, while other allele types, CK and CL, had no this ability.

[Preparation and characterization of polyclonal antibody against Ia-associated invariant chain of Muscovy Duck (Cairina moschata)].

Objective: To prepare polyclonal antibody against invariant chain of Muscovy duck (Cairina moschata) (MDIi) and identify its reaction with MDIi extracted from tissues of Muscovy duck.

Methods: MDIi was amplified by PCR and used to construct the prokaryotic expression vector of pET-32a/MDIi by linking with the plasmid of pET-32a. Then pET-32a/MDIi was transformed into E.

Cross-species association of quail invariant chain with chicken and mouse MHC II molecules.

There are different degrees of similarity among vertebrate invariant chains (Ii). The aim of this study was to determine the relationship between quail and other vertebrate Ii MHC class II molecules. The two quail Ii isoforms (qIi-1, qIi-2) were cloned by RACE, and qRT-PCR analysis of different organs showed that their expression levels were positively correlated with MHC II gene (B-LB) transcription levels.

Boosting immune response with the invariant chain segments via association with non-peptide binding region of major histocompatibility complex class II molecules.

Background: Based on binding of invariant chain (Ii) to major histocompatibility complex (MHC) class II molecules to form complexes, Ii-segment hybrids, Ii-key structure linking an epitope, or Ii class II-associated invariant chain peptide (CLIP) replaced with an epitope were used to increase immune response. It is currently unknown whether the Ii-segment cytosolic and transmembrane domains bind to the MHC non-peptide binding region (PBR) and consequently influence immune response. To investigate the potential role of Ii-segments in the immune response via MHC II/peptide complexes, a few hybrids containing Ii-segments and a multiepitope (F306) from Newcastle disease virus fusion protein (F) were constructed, and their binding effects on MHC II molecules and specific antibody production were compared using confocal microscopy, immunoprecipitation, western blotting and animal experiments.

[Cloning of pigeon invariant chain (Ii) gene by RACE].

In order to compare the structure and function of pigeon invariant chain (pIi) gene with other avian's, pIi gene was cloned using a method of RACE (Rapid Amplification of cDNA Ends). Firstly, according to high conservative nucleotide sequence of homologous fragment in avian invariant chain (Ii) gene, a pair of degenerated primer was designed, and a special DNA fragment was gained from pigeon spleen cell RNA by PCR. Then based on the sequence of gained DNA fragment, some new primers were designed, and the 3'terminal and the 5'terminal of pIi gene were cloned by RACE respectively.

Molecular cloning and mRNA expression of duck invariant chain.

In the present study we identified a duck invariant chain (Ii) cDNA, named duck Ii-1, by RT-PCR and RACE. It was 1190 bp in length and contained a 669 bp open reading frame. An alternative transcript encoding a thyroglobulin (Tg)-containing form of Ii, named duck Ii-2, was also found in duck.

Molecular cloning and expression of two chicken invariant chain isoforms produced by alternative splicing.

The biosynthesis of distinct forms of the invariant chain (Ii) protein from a unique gene as the result of differential splicing patterns has been observed in humans and mice. However, there have been no reports on the existence of Ii isoforms in avian species. In the present study, we identified two chicken Ii cDNAs by RT-PCR and RACE, and examined the Ii gene copy number, mRNA expression and protein expression by Southern blotting, Northern blotting and immunofluorescence confocal microscopy, respectively.

[The clinical evaluation of tinidazole-iodoform-phenocamphor paste as an intra-canal sterilization medication for acute periapical periodontitis].

Objective: To compare the clinical effect of tinidazole-iodoform-phenocamphor paste on acute periapical periodontitis with of formocresol.

Methods: 80 permanent teeth of acute periapical periodontitis were selected and divided randomly into tinidazole-iodoform-phenocamphor paste group (T group) and formocresol group (C group). The periapical signs and symptoms were recorded.