Improving normothermic machine perfusion and blood transfusion through biocompatible blood silicification.

The growing world population and increasing life expectancy are driving the need to improve the quality of blood transfusion, organ transplantation, and preservation. Here, to improve the ability of red blood cells (RBCs) for normothermic machine perfusion, a biocompatible blood silicification approach termed "shielding-augmenting RBC-in-nanoscale amorphous silica (SARNAS)" has been developed. The key to RBC surface engineering and structure augmentation is the precise control of the hydrolysis form of silicic acid to realize stabilization of RBC within conformal nanoscale silica-based exoskeletons.

Multivariate Silicification-Assisted Single Enzyme Structure Augmentation for Improved Enzymatic Activity-Stability Trade-Off.

The ability to finely tune/balance the structure and rigidity of enzymes to realize both high enzymatic activity and long-term stability is highly desired but highly challenging. Herein, we propose the concept of the "silicazyme", where solid inorganic silica undergoes controlled hybridization with the fragile enzyme under moderate conditions at the single-enzyme level, thus enabling simultaneous structure augmentation, long-term stability, and high enzymatic activity preservation. A multivariate silicification approach was utilized and occurred around individual enzymes to allow conformal coating.

Carboxymethyl cellulose-based multifunctional film integrated with polyphenol-rich extract and carbon dots from coffee husk waste for active food packaging applications.

Sustainable carboxymethyl cellulose (CMC)-based active composite films were developed through the addition of polyphenol-rich extract from coffee husk (CHE) and carbon dots (CDs) prepared using the biowaste residue of CHE extraction. The influences of various CDs contents on the physicochemical and functional characteristics of composite films have been researched. The 6% (w/w) CHE and 3% (w/w) CDs were uniformly dispersed within the CMC matrix to produce a homogenous film with enhanced mechanical properties.

Development and Validation of a Pathomics Model Using Machine Learning to Predict CXCL8 Expression and Prognosis in Head and Neck Cancer.

Objectives: The necessity to develop a method for prognostication and to identify novel biomarkers for personalized medicine in patients with head and neck squamous cell carcinoma (HNSCC) cannot be overstated. Recently, pathomics, which relies on quantitative analysis of medical imaging, has come to the forefront. CXCL8, an essential inflammatory cytokine, has been shown to correlate with overall survival (OS).

Synthetic Biohybrids of Red Blood Cells and Cascaded-Enzymes@ Metal-Organic Frameworks for Hyperuricemia Treatment.

Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast-acting and long-lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded-enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF-8 framework-based nanoparticles, have been fabricated based on a super-assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF-8 nanoparticles-based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF-8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by-product H O .

Crosslinked fish scale gelatin/alginate dialdehyde functional films incorporated with carbon dots derived from pomelo peel waste for active food packaging.

A multifunctional and environmentally friendly composite film was developed by incorporating pomelo peel-derived carbon dots (PCDs) into a fish scale gelatin (FSG)/alginate dialdehyde (ADA) biopolymer matrix. ADA was used to reinforce the physicomechanical properties of the FSG film via Schiff base crosslinking. PCDs with strong antioxidant and antimicrobial activities were synthesized via a hydrothermal method.

Comparison of the Effects of Laparoscopic Surgery and Traditional Open Surgery on Stone Clearance, Laboratory Indexes and Life Quality in Patients with Renal Calculi.

Objective: A case-control study was conducted to determine the effectiveness of laparoscopic surgery and traditional open surgery on stone clearance, laboratory indexes, and life quality in patients with renal calculi.

Methods: During March 2017 to March 2022, 272 patients with complex renal calculi (CRC) cured in our hospital were assigned into control group ( = 136) and research group ( = 136) arbitrarily. The former accepted traditional open surgery, while the latter accepted laparoscopic surgery.

Efficacy of Flexible Ureteroscopic Lithotripsy and Percutaneous Nephrolithotomy in the Treatment of Complex Upper Urinary Tract Nephrolithiasis.

Objective: A case-control study was conducted to compare the efficacy and prognostic factors of flexible ureteroscopic lithotripsy (FURL) and percutaneous nephrolithotomy (PCNL) when treating complex upper urinary tract renal calculi based on a retrospective cohort study.

Methods: The study period was from October 2019 to December 2021. A retrospective study was carried out on 100 patients with complicated upper urinary tract nephrolithiasis who underwent surgery in the Urology Department of our hospital.

Residues R1075, D1090, R1095, and C1130 Are Critical in ADAMTS13 TSP8-Spacer Interaction Predicted by Molecular Dynamics Simulation.

ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats, member 13) cleaves von Willebrand Factor (VWF) multimers to limit the prothrombotic function of VWF. The deficiency of ADAMTS13 causes a lethal thrombotic microvascular disease, thrombotic thrombocytopenic purpura (TTP). ADAMTS13 circulates in a "closed" conformation with the distal domain associating the Spacer domain to avoid off-target proteolysis or recognition by auto-antibodies.

Characterization of the interactions of ADAMTS13 CUB1 domain to WT- and GOF-Spacer domain by molecular dynamics simulation.

Metalloprotease ADAMTS13 specifically cleaves VWF (von Willebrand Factor) to prevent excessive platelet aggregation and thrombus formation at the sites of vascular injury. To avoid non-specific cleavage, ADAMTS13 has the auto-inhibition effect in which the Spacer domain in N-terminal interacts with the CUB1 domain in C-terminal, resulting in decreased proteolytic activity. Previous studies reported that exosite-3 in the Spacer domain was a key binding site in the Spacer-CUB1 interaction.

Chiral Phosphoric Acid-Catalyzed Remote Control of Axial Chirality at Boron-Carbon Bond.

The previously elusive catalytic enantioselective construction of axially chiral B-aryl-1,2-azaborines with a C-B stereogenic axis has been realized through a chiral phosphoric acid-catalyzed desymmetrization strategy reported herein. The electrophilic aromatic substitution reaction of 3,5-disubsituted phenols with diazodicarboxamides could afford these axially chiral structures in good efficiency with excellent enantiocontrol. The efficient long-range stereochemical control is achieved by multiple well-defined H-bonding interactions between chiral phosphoric acid and both substrates.

Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13.

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13).

Asymmetric N-aminoalkylation of 3-substituted indoles by N-protected N,O-acetals: an access to chiral propargyl aminals.

A direct enantioselective N1 aminoalkylation of 3-substituted indoles is efficiently catalyzed by a phosphoric acid catalyst under mild conditions to afford diverse enantioenriched propargyl aminals. The strategy could be applied to the modification of tryptophan containing oligopeptides. Additionally, structurally diverse and multifunctional transformations of the propargyl aminal products reveal the potential synthetic utility of this protocol.

Cancer Cell Membrane-Decorated Zeolitic-Imidazolate Frameworks Codelivering Cisplatin and Oleanolic Acid Induce Apoptosis and Reversed Multidrug Resistance on Bladder Carcinoma Cells.

Combination therapy is emerging as a preferable approach in cancer therapy with minimized side effects and elevated performance. Nevertheless, the poor targeting and drug loading of currently available drug delivery systems (DDSs) are the main difficulties to realize preferable combination therapy of cancer. As a result, a cancer cell membrane-decorated zeolitic-imidazolate framework hybrid nanoparticle (HP) was successfully constructed in our study to codeliver cisplatin (DDP) and oleanolic acid (OLA).

Characterization of adhesion properties of the cardiomyocyte integrins and extracellular matrix proteins using atomic force microscopy.

Integrins are transmembrane adhesion receptors that play important roles in the cardiovascular system by interacting with the extracellular matrix (ECM). However, direct quantitative measurements of the adhesion properties of the integrins on cardiomyocyte (CM) and their ECM ligands are lacking. In this study, we used atomic force microscopy (AFM) to quantify the adhesion force (peak force and mean force) and binding probability between CM integrins and three main heart tissue ECM proteins, ie, collagen (CN), fibronectin (FN), and laminin (LN).

Organocatalytic Enantioselective Synthesis of Tetrasubstituted α-Amino Allenoates by Dearomative γ-Addition of 2,3-Disubstituted Indoles to β,γ-Alkynyl-α-imino Esters.

The first asymmetric synthesis of tetrasubstituted α-amino allenoates by a chiral phosphoric acid catalyzed dearomative γ-addition reaction of 2,3-disubstituted indoles to β,γ-alkynyl-α-imino esters is reported. This method provides access to a series of highly functionalized tetrasubstituted allenes featuring quaternary stereocenters in high yields, and with excellent regio-, diastereo-, and enantioselectivities under mild conditions without by-product formation. Representative large-scale reactions and diverse transformations of the products into various scaffolds with potential biological activities render are also disclosed.

Access to α,γ-Diamino Diacid Derivatives via Organocatalytic Asymmetric 1,4-Addition of Azlactones and Dehydroalanines.

A convenient and functional-group-tolerant organocatalytic asymmetric 1,4-addition of azlactones and dehydroalanine is disclosed. The reaction is used for the first synthesis of chiral α,γ-diamino diacid derivatives with nonadjacent stereogenic centers in moderate to high yields, with excellent diastereo- and enantioselectivities, under the catalysis of a chiral thiourea catalyst. In addition, the reaction could be conducted in gram-scale, and the products of the reaction could be readily converted to various α,γ-diamino diacid derivatives, α,γ-diamino dialcohols, and modified peptides with nonproteinogenic amino acid residues.

Aggregation-Induced Emission Luminogen-Based Direct Visualization of Concentration Gradient Inside an Evaporating Binary Sessile Droplet.

In this study, the concentration gradient inside evaporating binary sessile droplets of 30, 50, and 60 vol % tetrahydrofuran (THF)/water mixtures was investigated. The 5 μL THF/water droplets were evaporated on a transparent hydrophobic substrate. This is the first demonstration of local concentration mapping within an evaporating binary droplet utilizing the aggregation-induced emission material.

Endomorphin-1 analogs containing α-methyl-β-amino acids exhibit potent analgesic activity after peripheral administration.

This study describes the design and synthesis of endomorphin-1 analogs containing C-terminal aromatic α-methyl-β-amino acids and an N-terminal native tyrosine or 2,6-dimethyl-tyrosine. We show that, in comparison with the parent peptide, these analogs exhibit improved bioactivity and blood-brain barrier penetration after intravenous administration, and have a lower tendency to induce constipation and sedation than morphine.

Chiral Phosphoric Acid Catalyzed Asymmetric Oxidative Dearomatization of Naphthols with Quinones.

A highly enantioselective oxidative dearomatization of naphthols with quinones catalyzed by a chiral spirocyclic phosphoric acid is described. The strategy provides concise access to enantioenriched cyclohexadienones with a quinone moiety. Remarkably, the obtained products could be easily transformed to a potentially useful dihydronaphtho[2,1-b]benzofuran scaffold.

Catalyst-controlled switch of regioselectivity in the asymmetric allylic alkylation of oxazolones with MBHCs.

A catalyst-controlled switch of regioselectivity in asymmetric allylic alkylation of oxazolones with MBHCs was described. The SN2'-SN2' reaction catalysed by a quinine-derived base produced γ-selective secondary allylic oxazolone derivatives, whereas the addition-elimination reaction catalysed by an amino acid-derived bifunctional urea catalyst provided β-selective primary adducts.

Copper-induced oxidative damage to the prophenoloxidase-activating system in the freshwater crayfish Procambarus clarkii.

Previous studies have demonstrated copper-induced proteins damage in gill and hepatopancreas of the freshwater crayfish Procambarus clarkii, but little information is available about its effects on key component of the innate defense in haemolymph. In the present study, we evaluated the relationship between oxidative carbonylation and prophenoloxidase-activating system (proPO-AS) activity, by exposing P. clarkii to sub-lethal concentrations (1/50, 1/12, 1/6 and 1/3 of the 96 h LC50) Cu(2+) up to 96 h.

Chiral phosphoric acid catalyzed enantioselective 1,3-dipolar cycloaddition reaction of azlactones.

The first chiral phosphoric acid catalyzed highly diastereo- and enantioselective 1,3-dipolar cycloaddition reaction of azlactones and methyleneindolinones was disclosed. By using a BINOL-derived chiral phosphoric acid as the catalyst, azlactones were activated as chiral anti N-protonated 1,3-dipoles to react with methyleneindolinones to yield biologically important 3,3'-pyrrolidonyl spirooxindole scaffolds in high yields, with good-to-excellent diastereo- and enantioselectivity.

Catalytic Asymmetric Michael Reaction of 5H-Oxazol-4-Ones with α,β-Unsaturated Acyl Imidazoles.

The asymmetric Michael reaction between 5H-oxazol-4-ones and α,β-unsaturated acyl imidazoles is reported. A novel 2-benzo[b]thiophenyl-modified chiral ProPhenol species is synthesized and used as a ligand, leading to good enantioselectivities in this asymmetric conjugate addition reaction. Furthermore, the introduction of phenol additives as achiral co-ligands is found to improve the reaction's chemical yields, diastereoselectivities, and enantioselectivities.

Design, synthesis, and evaluation of new endomorphin analogs with enhanced central antinociception after peripheral administration.

We synthesized two novel endomorphin-1 (EM-1) analogs by substituting the C-terminus residue with (thienyl)-α-methylene-β-amino acids (Map). Several in vitro and in vivo assays were used to determine the activity of the analogs. The two EM-1 analogs showed subnanomolar binding affinity and functional activity at the μ-opioid receptor in HEK293 cells.