An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern.

Milk exosomes: an oral drug delivery system with great application potential.

Exosomes are extracellular vesicles with the smallest diameter, usually divided into cellular sources and body fluid sources. Due to their special properties different from cell-derived exosomes, the application of milk exosomes as an oral drug delivery system has increased greatly. This article introduces the physical and chemical properties of exosomes, separation technology, dyeing and labeling technology, targeted modification technology, and the application of milk exosomes in drug loading and disease therapies.

2', 4'-Dihydroxy-2,3-dimethoxychalcone: A pharmacological inverse agonist of RORγt ameliorating Th17-driven inflammatory diseases by regulating Th17/Treg.

Multiple sclerosis, inflammatory bowel disease and organ transplant rejection are related to Th17 cell development and inflammatory respond. RORγt, a specific transcription factor regulating Th17 cell differentiation, is a pivotal target for the treatment of diseases. However, the clinical application of RORγt inverse agonists reported so far has been hindered due to limited efficacy and toxic side effects.

Baicalin Promotes CNS Remyelination via PPARγ Signal Pathway.

Background And Objectives: Demyelinating diseases in the CNS are characterized by myelin sheath destruction or formation disorder that leads to severe neurologic dysfunction. Remission of such diseases is largely dependent on the differentiation of oligodendrocytes precursor cells (OPCs) into mature myelin-forming OLGs at the demyelinated lesions, which is defined as remyelination. We discover that baicalin (BA), a natural flavonoid, in addition to its well-known antiinflammatory effects, directly stimulates OLG maturation and CNS myelin repair.

Tailored nanodisc immobilization for one-step purification and reconstitution of cytochrome P450: A tool for membrane proteins' hard cases.

A novel nanodisc-based immobilization method was developed for high-efficient purification and reconstitution of cytochrome P450 in one step. Using membrane scaffold protein containing a histidine tag, charged-nanodiscs were prepared in the form of self-assembly of lipid-protein nanoparticles. Their properties including the particle diameter and its distribution and Zeta potential were controlled well by adjusting molar ratios of phospholipids to membrane scaffold protein.

Rapid and high-capacity loading of IgG monoclonal antibodies by polymer brush and peptides functionalized microspheres.

Fast-throughput and cost reduction of current purification platforms are becoming increasing requests during antibody manufacture. The macroporous-matrix absorbents have presented extensive potentiality in improving operational throughput during purification of macromolecule. And meanwhile the peptide ligand has become a promising alternative to recombinant protein ligands for cost reduction of chromatographic purification.

Manipulation of pore structure during manufacture of agarose microspheres for bioseparation.

Agarose microspheres with a controllable pore structure were manufactured by varying agarose types and crosslinking degrees. Various agarose could tailor the gel formation of microspheres matrix and thus affect the final pore structures. Small pores in microspheres could be fabricated by agarose with a higher molecular weight, which was demonstrated by the packed column with lower distribution coefficient ( ) values measured by gel filtration chromatography.

A Study of Modified Infotaxis Algorithms in 2D and 3D Turbulent Environments.

Emergency response to hazardous gases in the environment is an important research field in environmental monitoring. In recent years, with the rapid development of sensor technology and mobile device technology, more autonomous search algorithms for hazardous gas emission sources are proposed in uncertain environment, which can avoid emergency personnel from contacting hazardous gas in a short distance. Infotaxis is an autonomous search strategy without a concentration gradient, which uses scattered sensor data to track the location of the release source in turbulent environment.

Quantitative and Qualitative Analysis of Multicomponent Gas Using Sensor Array.

The gas sensor array has long been a major tool for measuring gas due to its high sensitivity, quick response, and low power consumption. This goal, however, faces a difficult challenge because of the cross-sensitivity of the gas sensor. This paper presents a novel gas mixture analysis method for gas sensor array applications.

Fabrication of rigid and macroporous agarose microspheres by pre-cross-linking and surfactant micelles swelling method.

A novel combined method of pre-cross-linking and surfactant micelles swelling was proposed in this study to fabricate highly cross-linked and macroporous agarose (HMA) microspheres. Agarose was chemically modified by allylglycidyl ether (AGE) as heterobifunctional cross-linker via its active glycidyl moieties before gel formation and pre-cross-linking was achieved. By this means, the effective concentration of cross-linker presented in agarose gel increased significantly, and thus cross-linking with a high-efficiency was achieved.

Does Weekend Hospital Admission Affect Upper Gastrointestinal Hemorrhage Outcomes?: A Systematic Review and Network Meta-Analysis.

Background: Compared with weekday admissions, weekend admissions are consistently associated with worse patient outcomes, known as the "weekend effect." The weekend effect may have adverse health consequences, including death. To determine the potential impact of the weekend effect on primary (ie, mortality) and secondary outcomes of patients with upper gastrointestinal hemorrhage (UGIH).

A novel rProtein A chromatographic media for enhancing cleaning-in-place performance.

Protein A chromatography has been a popular method for purification of therapeutic monoclonal antibodies (mAb). Protein A chromatographic media using alkali-resistant rProtein A ligands from site-directed coupling method have been pursued for both high dynamic capacities and excellent stabilities. However, the mechanism of rProtein A leaking under cleaning-in-place (CIP) conditions is not very clear and difficulties have been commonly encountered when improving the media's chromatographic performance.

Construction of a versatile expression library for all human single-pass transmembrane proteins for receptor pairings by high throughput screening.

Interactions between protein ligands and receptors play crucial roles in cell-cell signalling. Most of the human cell surface receptors have been identified in the post-Human Genome Project era but many of their corresponding ligands remain unknown. To facilitate the pairing of orphan receptors, 2762 sequences encoding all human single-pass transmembrane proteins were selected for inclusion into a mammalian-cell expression library.

Towards A Deeper Understanding of the Interfacial Adsorption of Enzyme Molecules in Gigaporous Polymeric Microspheres.

Compared with the one immobilized in the conventional mesoporous microspheres, the enzyme immobilized in gigaporous microspheres showed much higher activity and better stability. To gain a deeper understanding, we herein selected lipase as a prototype to comparatively analyze the adsorption behavior of lipase at interfaces in gigaporous and mesoporous polystyrene microspheres at very low lipase concentration, and further compared with the adsorption on a completely flat surface (a chip). Owing to the limited space of narrow pores, lipase molecules were inclined to be adsorbed as a monolayer in mesoporous microspheres.

Microscopic insight into role of protein flexibility during ion exchange chromatography by nuclear magnetic resonance and quartz crystal microbalance approaches.

Driven by the prevalent use of ion exchange chromatography (IEC) for polishing therapeutic proteins, many rules have been formulated to summarize the different dependencies between chromatographic data and various operational parameters of interest based on statically determined interactions. However, the effects of the unfolding of protein structures and conformational stability are not as well understood. This study focuses on how the flexibility of proteins perturbs retention behavior at the molecular scale using microscopic characterization approaches, including hydrogen-deuterium (H/D) exchange detected by NMR and a quartz crystal microbalance (QCM).

Comparison of covalent and physical immobilization of lipase in gigaporous polymeric microspheres.

Lipase (EC 3.1.1.

Chitosan-based mucosal adjuvants: Sunrise on the ocean.

Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials.

[Interactions between proteins and cation exchange adsorbents analyzed by NMR and hydrogen/deuterium exchange technique].

In silico acquirement of the accurate residue details of protein on chromatographic media is a bottleneck in protein chromatography separation and purification. Here we developed a novel approach by coupling with H/D exchange and nuclear magnetic resonance to observe hen egg white lysozyme (HEWL) unfolding behavior adsorbed on cation exchange media (SP Sepharose FF). Analysis of 1D 1H-NMR shows that protein unfolding accelerated H/D exchange rate, leading to more loss of signal of amide hydrogen owing to exposure of residues and the more unfolding of protein.

Multiscale evaluation of pore curvature effects on protein structure in nanopores.

Protein structure in nanopores is an important determinant in porous substrate utilization in biotechnology and materials science. To date, accurate residue details of pore curvature induced protein binding and unfolding were still unknown. Here, a multiscale ensemble of chromatography, NMR hydrogen and deuterium (H/D) exchange, confocal scanning and molecular docking simulations was combined to obtain the protein adsorption information induced by pore size and curvature.

Comparative studies on the influences of primary emulsion preparation on properties of uniform-sized exenatide-loaded PLGA microspheres.

Purpose: It is well known that primary emulsion (W1/O) preparation process (by ultrasonication or homogenization) plays an important role in the properties of drug-loaded microspheres, such as encapsulation efficiency, release behavior and pharmacodynamics. However, its involved mechanism has not been intensively and systematically studied, partly because that broad size distribution of the resultant particles prepared by conventional preparation can greatly disturb the analysis and reliability of the results. Here, we focused on the relevant studies.

Thermal-sensitive hydrogels as nasal vaccine delivery systems.

The National Key Laboratory of Biochemical Engineering established in 1995 is affiliated with the Institute of Process Engineering, Chinese Academy of Sciences (CAS), and located in Zhong-guan-cun (Beijing, China). The National Key Laboratory of Biochemical Engineering is working towards developments in the fields of bio-reaction, bioseparation and bio-formulation, by chemical and material methods. Over the last 5 years, approximately 200 scientists and students have worked at the laboratory, and published over 400 articles.

Fabrication strategy for amphiphilic microcapsules with narrow size distribution by premix membrane emulsification.

Amphiphilic co-polymer, which can maintain the stability of proteins and increase the protein loading efficiency, is considered as an exploring-worthy biodegrade polymer for drug delivery. However, amphiphilic microcapsules prepared by conventional methods, such like mechanical stirring and spray-drying methods, exhibit broad size distributions due to its hydrophilic sequences, leading to poor reproducibility. In this study, we employed poly(monomethoxypoly ethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA), one of common amphiphilic polymers, as model to focus on investigating the process parameters and mechanisms to prepare PELA microcapsules with narrow size distribution and regular sphericity by combining premix membrane emulsification and double emulsion technique.

AC3-33, a novel secretory protein, inhibits Elk1 transcriptional activity via ERK pathway.

The transcription factor AP-1 plays an important role in cellular proliferation, transformation and death. In this study, we report a novel human gene, AC3-33 (GenBank name: c3orf33, FLJ31139), which encodes a secretory protein that can inhibit Elk1 transcriptional activity via ERK1/2 pathway. The AC3-33 mRNA encodes a protein of 251 amino acids, which is a classical secretory protein.

Human TMEM174 that is highly expressed in kidney tissue activates AP-1 and promotes cell proliferation.

Mitogen-activated protein kinase (MAPK) cascades play an important role in regulation of AP-1 activity through the phosphorylation of distinct substrates. In the present study, we identified a novel protein, TMEM174, whose RNA transcripts are highly expressed in human kidney tissue. TMEM174 is comprised of 243 amino acids, and contains two predicted transmembrane helices which determine its subcellular localization in endoplasmic reticulum and influences its functions.