Lung-Selective Delivery of mRNA-Encoding Anti-MERS-CoV Nanobody Exhibits Neutralizing Activity Both In Vitro and In Vivo.

: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a highly pathogenic virus causing severe respiratory illness, with limited treatment options that are mostly supportive. The success of mRNA technology in COVID-19 vaccines has opened avenues for antibody development against MERS-CoV. mRNA-based antibodies, expressed in vivo, offer rapid adaptability to viral mutations while minimizing long-term side effects.

IIIVmrMLM.QEI: An effective tool for indirect detection of QTN-by-environment interactions in genome-wide association studies.

Although 3VmrMLM-MEJA and several indirect indicators have been employed to identify QTN-by-environment interactions (QEIs) in genome-wide association studies (GWAS), there is no convenient, flexible, and accurate method to comprehensively identify QEIs. To address this issue, 3VmrMLM-random was first extended to 3VmrMLM-fixed. Next, the two single-environment QTN detection methods were integrated with trait differences and regression parameters to indirectly detect QEIs.

Blocking CCL3-mediated neutrophil recruitment into the brain alleviates immunopathology following severe enterovirus 71 infection.

Inflammatory cells infiltration in the cerebrospinal fluid is a hallmark of severe enterovirus 71 (EV71) infection, but which type of immune cells are critical for severe EV71 infection remains unclear. Here, we observe that both neutrophils and macrophages are increased in the brains of patients and mice with severe EV71 infection, and the depletion of neutrophils but not macrophages results in a marked enhancement of survival of EV71-infected mice. Furthermore, CCR1/3 may play an important role in CCL3 facilitating the accumulation of neutrophils in the brains of patients.

Malignant melanoma complicated with cataract and secondary glaucoma: A case report.

Uveal melanoma is the most common intraocular malignant tumor in adults. For patients presenting with cataracts and glaucoma, it is recommended to assess whether an intraocular lesion is present as the primary cause. The present study describes the case of a 52-year-old man with primary intraocular malignant melanoma.

A highly susceptible hACE2-transgenic mouse model for SARS-CoV-2 research.

Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter.

Development of highly effective LCB1-based lipopeptides targeting the spike receptor-binding motif of SARS-CoV-2.

LCB1 is a computationally designed 56-mer miniprotein targeting the spike (S) receptor-binding motif of SARS-CoV- 2 with high potent activity (Science, 2020; Cell host microbe, 2021); however, recent studies have demonstrated that emerging SARS-CoV-2 variants are highly resistant to LCB1's inhibition. In this study, we first identified a truncated peptide termed LCB1v8, which maintained the high antiviral potency. Then, a group of lipopeptides were generated by modifying LCB1v8 with diverse lipids, and of two lipopeptides, the C-terminally stearicacid-conjugtaed LCB1v17 and cholesterol-conjugated LCB1v18, were highly effective in inhibiting both S protein-pseudovirus and authentic SARS-CoV-2 infections.

Exosomal Vaccine Loading T Cell Epitope Peptides of SARS-CoV-2 Induces Robust CD8 T Cell Response in HLA-A Transgenic Mice.

Purpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8 T cell response.

Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy.

Re-burying Artificially Exposed Surface of Viral Subunit Vaccines Through Oligomerization Enhances Vaccine Efficacy.

Viral subunit vaccines often suffer low efficacy. We recently showed that when taken out of the context of whole virus particles, recombinant subunit vaccines contain artificially exposed surface regions that are non-neutralizing and reduce their efficacy, and thus these regions need to be re-buried in vaccine design. Here we used the envelope protein domain III (EDIII) of Japanese encephalitis virus (JEV), a subunit vaccine candidate, to further validate this important concept for subunit vaccine designs.

A Dual Role of Complement Activation in the Development of Fulminant Hepatic Failure Induced by Murine-Beta-Coronavirus Infection.

With the epidemic of betacoronavirus increasing frequently, it poses a great threat to human public health. Therefore, the research on the pathogenic mechanism of betacoronavirus is becoming greatly important. Murine hepatitis virus strain-3 (MHV-3) is a strain of betacoronavirus which cause tissue damage especially fulminant hepatic failure (FHF) in mice, and is commonly used to establish models of acute liver injury.

A glucose-like metabolite deficient in diabetes inhibits cellular entry of SARS-CoV-2.

The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus.

Broadly neutralizing antibodies against Omicron-included SARS-CoV-2 variants induced by vaccination.

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time.

Staphylococcus aureus N-terminus formylated δ-toxin tends to form amyloid fibrils, while the deformylated δ-toxin tends to form functional oligomer complexes.

The community-associated Methicillin-resistant strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many strains.

Development of oxidized hydroxyethyl cellulose-based hydrogel enabling unique mechanical, transparent and photochromic properties for contact lenses.

With the development of smart devices, higher requirements are put forward for the stimuli-responsive materials. Stimuli-hydrogels as one kind of stimuli-responsive materials with hydrophilicity, demonstrate huge potential in developing intelligent devices for biomedical application. On this basis, we herein report that a sample method was devised to develop a novel composite hydrogel mainly based on oxidized hydroxyethyl cellulose and allyl co-polymer.

LytR plays a role in normal septum formation and contributes to full virulence in Streptococcus suis.

Streptococcus suis (S. suis) is a major zoonotic pathogen and is also responsible for variety of diseases in swine. LytR-CpsA-Psr (LCP) family proteins affect the biofilm formation and virulence of some Gram-positive bacteria, but we know nothing about their roles in S.

Cone beam CT-based measurement of the accessory mental foramina in the Chinese Han population.

Anatomical data of accessory mental foramina (AMFs) were investigated in a Chinese Han population using cone beam CT (CBCT). A retrospective analysis was performed on 527 selected sets of CBCT images. The average frequency and diameter of AMFs, the diameter of the ipsilateral mental foramen (MF), and the center distance and relative position between the AMFs and MF were measured and calculated by three professional dentists.

Endocytic FgEde1 regulates virulence and autophagy in Fusarium graminearum.

Endocytosis plays critical roles in cellular processes, including nutrient uptake and signal transduction. Ede1 is an endocytic scaffolding protein that contributes to endocytic site initiation and maturation in yeast. However, the functions of Ede1 in phytopathogenic fungi are not known.

[Establishment and evaluation of array-ELISA for detection of enterotoxins from Staphylococcus aureus].

Objective To accurately and rapidly detect and type five classical Staphylococcal enterotoxins (SEs) by array-ELISA using a combination of a chip and ELISA. Methods SEs were prepared by prokaryotic expression and affinity chromatography. Hybridoma cells were injected intraperitoneally into mice to prepare ascites.

The Relationship between the Hydrophilicity and Surface Chemical Composition Microphase Separation Structure of Multicomponent Silicone Hydrogels.

Three series of multicomponent silicone hydrogels were prepared by the copolymerization of two hydrophobic silicon monomers bis(trimethylsilyloxy) methylsilylpropyl glycerol methacrylate (SiMA) and tris(trimethylsiloxy) 3-methacryloxypropylsilane (TRIS) with three hydrophilic monomers. The surface hydrophilicity of the silicone hydrogels was characterized by contact angle measurements, and an interesting phenomenon was found that the silicone hydrogels made from less hydrophobic monomer SiMA possess more hydrophobic surfaces than those made from TRIS. The surface properties such as morphology and elemental composition of the silicone hydrogels were explored by scanning electron microscopy (SEM) imaging and energy dispersive spectrometry (EDS) analysis, and their relationships with the surface hydrophilicity were investigated in details.

Deep resequencing reveals allelic variation in Sesamum indicum.

Background: Characterization of genome-wide patterns of allelic variation and linkage disequilibrium can be used to detect reliable phenotype-genotype associations and signatures of molecular selection. However, the use of Sesamum indicum germplasm for breeding is limited by the lack of polymorphism data.

Results: Here we describe the massively parallel resequencing of 29 sesame strains from 12 countries at a depth of ≥ 13-fold coverage for each of the samples tested.

Genome sequencing of the high oil crop sesame provides insight into oil biosynthesis.

Background: Sesame, Sesamum indicum L., is considered the queen of oilseeds for its high oil content and quality, and is grown widely in tropical and subtropical areas as an important source of oil and protein. However, the molecular biology of sesame is largely unexplored.

Whole-genome sequencing reveals untapped genetic potential in Africa's indigenous cereal crop sorghum.

Sorghum is a food and feed cereal crop adapted to heat and drought and a staple for 500 million of the world's poorest people. Its small diploid genome and phenotypic diversity make it an ideal C4 grass model as a complement to C3 rice. Here we present high coverage (16-45 × ) resequenced genomes of 44 sorghum lines representing the primary gene pool and spanning dimensions of geographic origin, end-use and taxonomic group.

Cytotoxic cholestane-type and ergostane-type steroids from the aerial parts of Euphorbia altotibetic.

Phytochemical investigation of the ethanol extract obtained from the aerial parts of the Euphorbia altotibetic PAULS. Grown in China resulted in the isolation of three new cholestane-type and three new ergostane-type steroids (cholest-5-en-2β, 4β-diol; cholest-5-en-1β, 4β-diol; cholest-5-en-1α, 3β, 4α -triol; (22E)-ergosta-7,9,22-trien- 3β-ol β-D-glucoside; 5α-methoxy-(22E)-ergosta-7,9,22-trien-3β-ol β-D-glucoside; 6β- methoxy-(22E)-ergosta-7,9,22-trien-3β-ol β-D-glucoside), along with seven known compounds. Their structures were established by extensive one- and two-dimensional NMR spectroscopy, as well as other spectrum and chemical analysis.

Triterpenoids of Euphorbia kansuensis Proch.

Phytochemical investigation of the ethanol extract of Euphorbia kansuensis Proch. led to the isolation of three new triterpenoids, along with ten known compounds. Their structures were established by extensive 1D and 2D NMR, as well as other spectrum analysis.

[Two new sequence type isolates of Bacillus anthracis by multilocus sequence typing].

Objective: To define the sequence type (ST) isolates of Bacillus anthracis by multilocus sequence typing (MLST).

Methods: Fragments of seven housekeeping genes (glpF, gmk, ilvD, pta, pur, pycA, and tpi) were amplified by PCR using the standard primers as described on the website for MLST of Bacillus and the sequences were compared with existing allele sequences on the MLST website.

Results: Two novel allele combinations of the seven loci were found in two isolates 17003-14 and 17003-32.