Mutating a flexible region of the RSV F protein can stabilize the prefusion conformation.

The respiratory syncytial virus (RSV) fusion (F) glycoprotein is highly immunogenic in its prefusion (pre-F) conformation. However, the protein is unstable, and its conformation must be stabilized for it to function effectively as an immunogen in vaccines. We present a mutagenesis strategy to arrest the RSV F protein in its pre-F state by blocking localized changes in protein structure that accompany large-scale conformational rearrangements.

Prediction of mutation-induced protein stability changes based on the geometric representations learned by a self-supervised method.

Background: Thermostability is a fundamental property of proteins to maintain their biological functions. Predicting protein stability changes upon mutation is important for our understanding protein structure-function relationship, and is also of great interest in protein engineering and pharmaceutical design.

Results: Here we present mutDDG-SSM, a deep learning-based framework that uses the geometric representations encoded in protein structure to predict the mutation-induced protein stability changes.

Design of hepadnavirus core protein-based chimeric virus-like particles carrying epitopes from respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an "epitope-focused" vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice.

Anti-Inflammatory Phomalones from the Deep-Sea-Derived Fungus Trichobotrys effuse FS522.

Four new phomalones A-D (1-4), together with five known analogues (5-9) were isolated from the deep-sea-derived fungus Trichobotrys effuse FS522. Their structures of the new compounds established by analysis of their NMR and HR-ESI-MS spectroscopic data, and the absolute configurations of 2 was determined by electronic circular dichroism (ECD) calculations. compounds 4, 6 and 8 substantially inhibited the production of nitric oxide (NO) with IC values of 4.

Chimeric virus-like particles of human norovirus constructed by structure-guided epitope grafting elicit cross-reactive immunity against both GI.1 and GII.4 genotypes.

Human norovirus (HuNoV) is highly infectious and can result in severe illnesses in the elderly and children. So far, there is no effective antiviral drug to treat HuNoV infection, and thus, the development of HuNoV vaccines is urgent. However, NoV evolves rapidly, and currently, at least 10 genogroups with numerous genotypes have been found.

A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants.

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants.

Purification, structural characterization, and anticoagulant activity evaluation of chondroitin sulfate from codfish (Gadus macrocephalus) bones.

Chondroitin sulfate (CCS) was purified from discarded codfish (Gadus macrocephalus) bones, and its chemical structure and anticoagulant activity were assessed. CCS was obtained via enzymatic lysis and ion-exchange column chromatography, with a yield of approximately 0.15%.

Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen.

Cytotoxic diaporindene and tenellone derivatives from the fungus Phomopsis lithocarpus.

Nine new compounds, including five natural rarely-occurring 2, 3-dihydro-1H-indene derivatives named diaporindenes E-I (1-5), and four new benzophenone analogues named tenellones J-M (6-9) were isolated from the deep-sea sediment-derived fungus Phomopsis lithocarpus FS508. All the structures for these new compounds were fully characterized on the basis of spectroscopic data, NMR spectra, and ECD calculation and single-crystal X-ray diffraction analysis. The potential anti-tumor activities of compounds 1-9 against four tumor cell lines SF-268, MCF-7, HepG-2, and A549 were evaluated using the SRB method.

Complete genome sequence of Micromonospora craniellae LHW63014, a potential metal ion-chelating agent producer.

Micromonospora craniellae LHW63014 is a novel marine Micromonospora, isolated from a Craniella species sponge collected in the South China Sea. In this study, we report the complete genome sequence of M. craniellae LHW63014, which is comprised of a circular chromosome of 6,839,926 bp with the G + C content of 70.

Tersone A-G, New Pyridone Alkaloids from the Deep-Sea Fungus .

Four phenylfuropyridone racemates, (±)-tersones A-C and E (-, ), one phenylpyridone racemate, (±)-tersone D (), one new pyridine alkaloid, tersone F (), single new phenylfuropyridone, tersone G () and two known analogs and were isolated from the deep-sea fungus . Their structures and absolute configurations were characterized on the basis of comprehensive spectroscopic analyses, single-crystal X-ray diffraction experiments, and electronic circular dichroism (ECD) calculations. Moreover, compounds - were evaluated for in vitro antimicrobial and cytotoxic activity.

Chromone-Derived Polyketides from the Deep-Sea Fungus FS431.

Five new chromone-derived polyketides phaseolorins A-F (⁻), together with nine known compounds, were isolated from the deep-sea derived fungus FS431. The structures of new compounds were determined by analysis of their NMR and high-resolution electrospray ionization mass spectroscopy (HRESIMS) spectroscopic data. The absolute configurations were confirmed by chemical transformations, extensively experimental electron capture detection (ECD) calculations, or X-ray crystallography.

[Effects of exhaustive exercise on the expression of PHB1 and the function of mitochondria in rats].

Objective: To observe the changes of Prohibitin1(PHB1) contents in rat brain, heart, skeletal muscle tissue and mitochondria with acute exhaustive exercise and the effects of acute exhaustive exercise on mitochondrial function in rats, to explore the relationship among PHB1 and mitochondrial function and energy metabolism.

Methods: Acute exhaustive exercise model:The rats carried acute exhaustive exercise after 8 weeks of feeding. The heart, brain and skeletal muscle samples were collected and the mitochondria were collected to detect the changes of respiratory function and reactive oxygen species(ROS).

A novel substrate-inspired fluorescent probe to monitor native albumin in human plasma and living cells.

Human albumin (HA) displays crucial roles in maintaining health and fighting diseases. Accurate determination of native HA in plasma or non-plasma samples are of immense significance in both basic research and clinical practice. Herein, a novel ratiometric two-photon fluorescent probe (N-butyl-4-(4-phenyl-benzoyloxy) 1,8-naphthalimide, BPBN) has been designed and developed for highly selective and sensitive sensing the enzymatic activities of HA, on the basis of its unique pseudo-esterase feature.

An optimized ratiometric fluorescent probe for sensing human UDP-glucuronosyltransferase 1A1 and its biological applications.

This study aimed to develop a practical ratiometric fluorescent probe for highly selective and sensitive detection of human UDP-glucuronosyltransferase 1A1 (UGT1A1), one of the most important phase II enzymes. 4-Hydroxy-1,8-naphthalimide (HN) was selected as the fluorophore for this study because it possesses intramolecular charge transfer (ICT) feature and displays outstanding optical properties. A series of N-substituted derivatives with various hydrophobic, acidic and basic groups were designed and synthesized to evaluate the selectivity of HN derivatives toward UGT1A1.

Fructus Psoraleae contains natural compounds with potent inhibitory effects towards human carboxylesterase 2.

Fructus Psoraleae (FP) is an edible Chinese herbal which is widely used in Asia for the treatment of various diseases including asthma, diarrhea, and osteoporosis. This study aimed to investigate the inhibitory effects of the crude ethanol extract from FP on human carboxylesterase 2 (hCE2), as well as to identity and characterize the naturally occurring inhibitors of hCE2 in FP. Our results demonstrated that the ethanol extract of FP displayed potent inhibitory effects towards hCE2, while five major bioactive constitutes in FP were efficiently identified by LC-DAD-ESI-MS/MS, with the aid of LC-based activity profiling.

A highly selective fluorescent ESIPT probe for the detection of Human carboxylesterase 2 and its biological applications.

A new ratiometric florescence probe derived from 3-hydroxyflavone (3-HF) has been developed for selective and sensitive detection of human carboxylesterase 2 (CE2). The probe is designed by modulating the excited state intramolecular proton transfer (ESIPT) emission of 3-HF via introducing of 4-ethylbenzoyloxy group. Under physiological conditions, probe 1 displays satisfying stability with very low background signal, but it can be selectively hydrolyzed by CE2 to release free 3-HF which brings remarkable changes in fluorescence spectrum.

A highly selective long-wavelength fluorescent probe for the detection of human carboxylesterase 2 and its biomedical applications.

A highly selective long-wavelength fluorescent probe TCFB has been developed for the detection of hCE2. The probe can be used for real-time monitoring of hCE2 activity in complex biological systems.

Transgenic expression of human cytoxic T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) by porcine skin for xenogeneic skin grafting.

Porcine skin is frequently used as a substitute of human skin to cover large wounds in clinic practice of wound care. In our previous work, we found that transgenic expression of human cytoxicT-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) in murine skin graft remarkably prolonged its survival in xenogeneic wounds without extensive immunosuppression in recipients, suggesting that transgenic hCTLA4Ig expression in skin graft may be an effective and safe method to prolong xenogeneic skin graft survival. In this work, using a transgene construct containing hCTLA4Ig coding sequence under the drive of human Keratine 14 (k14) promoter, hCTLA4Ig transgenic pigs were generated by somatic nuclear transfer.

A highly selective ratiometric fluorescent probe for in vitro monitoring and cellular imaging of human carboxylesterase 1.

A new ratiometric fluorescent probe derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT) has been developed for selective monitoring of human carboxylesterase 1 (hCE1). The probe is designed by introducing benzoyl moiety to HMBT. The prepared latent spectroscopic probe 1 displays satisfying stability under physiological pH conditions with very low background signal.

[In vitro metabolic interconversion between baicalin and baicalein in the liver, kidney, intestine and bladder of rat].

The present study is aimed to investigate the in vitro metabolic interconversion between baicalin (BG) and baicalein (B) in rat liver, kidney, intestine and bladder. BG and B were separately incubated with rat hepatic, renal, and intestinal microsomes, as well as bladder homogenates, for 30 min. The metabolites were identified and quantified by HPLC and metabolic kinetic parameters were obtained by fitting the data to the Michaelis-Menten equation.

[Pharmacokinetics of flavonoids from xiexin decoction in rats].

To study the pharmacokinetics of flavonoids from Xiexin decoction in rats. SD rats were given a single ig dose of Xiexin decoction 12 g x kg(-1), plasma and urine were collected before and after dosing. Flavonoids components in plasma and urine were measured by HPLC.