ABSTRACT
The frequent mutations of influenza A virus (IAV) have led to an urgent need for the development of innovative antiviral drugs. Glycopolymers offer significant advantages in biomedical applications owing to their biocompatibility and structural diversity. However, the primary challenge lies in the design and synthesis of well-defined glycopolymers to precisely control their biological functionalities. In this study, functional glycopolymers with sulfated fucose and 6'-sialyllactose were successfully synthesized through ring-opening metathesis polymerization and a postmodification strategy. The optimized heteropolymer exhibited simultaneous targeting of hemagglutinin and neuraminidase on the surface of IAV, as evidenced by MU-NANA assay and hemagglutination inhibition data. Antiviral experiments demonstrated that the glycopolymer displayed broad and efficient inhibitory activity against wild-type and mutant strains of H1N1 and H3N2 subtypes in vitro, thereby establishing its potential as a dual-targeted inhibitor for combating IAV resistance.
Subject(s)
Antiviral Agents , Fucose , Influenza A Virus, H1N1 Subtype , Lactose , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/chemical synthesis , Lactose/analogs & derivatives , Lactose/chemistry , Lactose/pharmacology , Fucose/chemistry , Fucose/analogs & derivatives , Fucose/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/drug effects , Drug Resistance, Viral/drug effects , Humans , Neuraminidase/antagonists & inhibitors , Neuraminidase/metabolism , Influenza A virus/drug effects , Madin Darby Canine Kidney Cells , Animals , Dogs , Polymers/pharmacology , Polymers/chemistryABSTRACT
Renal ischemiaâreperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI), which is a potentially life-threatening condition with a high mortality rate. IRI is a complex process involving multiple underlying mechanisms and pathways of cell injury and dysfunction. Additionally, various types of cell death have been linked to IRI, including necroptosis, apoptosis, pyroptosis, and ferroptosis. These processes operate differently and to varying degrees in different patients, but each plays a role in the various pathological conditions of AKI. Advances in understanding the underlying pathophysiology will lead to the development of new therapeutic approaches that hold promise for improving outcomes for patients with AKI. This review provides an overview of the recent research on the molecular mechanisms and pathways underlying IRI-AKI, with a focus on regulated cell death (RCD) forms such as necroptosis, pyroptosis, and ferroptosis. Overall, targeting RCD shows promise as a potential approach to treating IRI-AKI.
ABSTRACT
Flexible and stretchable thin-film transistors (TFTs) are crucial in skin-like electronics for wearable and implantable applications. Such electronics are usually constrained in performance owing to a lack of high-mobility and stretchable semiconducting channels. Tellurium, a rising semiconductor with superior charge carrier mobilities, has been limited by its intrinsic brittleness and anisotropy. Here, we achieve highly oriented arrays of tellurium nanowires (TeNWs) on various substrates with wafer-scale scalability by a facile lock-and-shear strategy. Such an assembly approach mimics the alignment process of the trailing tentacles of a swimming jellyfish. We further apply these TeNW arrays in high-mobility TFTs and logic gates with improved flexibility and stretchability. More specifically, mobilities over 100 square centimeters per volt per second and on/off ratios of ~104 are achieved in TeNW-TFTs. The TeNW-TFTs on polyethylene terephthalate can sustain an omnidirectional bending strain of 1.3% for more than 1000 cycles. Furthermore, TeNW-TFTs on an elastomeric substrate can withstand a unidirectional strain of 40% with no performance degradation.
ABSTRACT
Background: Sepsis is a major cause of ICU admissions, with high mortality and morbidity. The lungs are particularly vulnerable to infection and injury, and restoration of vascular endothelial homeostasis after injury is a crucial determinant of outcome. Neutrophil extracellular trap (NET) release strongly correlates with the severity of lung tissue damage. However, little is known about whether NETs affect endothelial cell (EC) regeneration and repair. Methods: Eight- to ten-week-old male C57BL/6 mice were injected intraperitoneally with a sublethal dose of LPS to induce acute lung inflammatory injury or with PBS as a control. Blood samples and lung tissues were collected to detect NET formation and lung endothelial cell proliferation. Human umbilical vein endothelial cells (HUVECs) were used to determine the role of NETs in cell cycle progression in vitro. Results: Increased NET formation and impaired endothelial cell proliferation were observed in mice with inflammatory lung injury following septic endotoxemia. Degradation of NETs with DNase I attenuated lung inflammation and facilitated endothelial regeneration. Mechanistically, NETs induced p21 upregulation and cell cycle stasis to impair endothelial repair. Conclusions: Our findings suggest that NET formation impairs endothelial regeneration and vascular repair through the induction of p21 and cell cycle arrest during inflammatory lung injury.
ABSTRACT
Herein, three In(III)-based metal-organic frameworks (In-MOFs) with different degrees of interpenetration (DOI), namely In-MOF-1, In-MOF-2, and In-MOF-3, constructed by In3+ and Y-shaped ligands 4,4',4â³-s-triazine-2,4,6-triyltribenzoate (H3TATB), are successfully synthesized through the ionothermal/solvothermal method. Subsequently, three novel In-MOFs, including noninterpenetration polycatenation, 2-fold interpenetrated, and 4-fold interpenetrated structure, are employed as the platform for systematically investigating the separation efficiency of CO2/N2, CO2/CH4, and CO2/CH4/N2 mixture gas system. Among them, In-MOF-2 shows the highest CO2 uptake capacities at 298 K and simultaneously possesses the low adsorption enthalpy of CO2 (26.4 kJ/mol at low coverage), a feature desirable for low-energy-cost adsorbent regeneration. The CO2/N2 (v: v = 15/85) selectivity of In-MOF-2 reaches 37.6 (at 298 K and 1 bar), also revealing outstanding selective separation ability from flue gases and purifying natural gas, affording a unique robust separation material as it has moderate DOI and pore size. In-MOF-2 shows exceptional stability and feasibility to achieve reproducibility. Aperture adjustment makes In-MOF-2 a versatile platform for selectively capturing CO2 from flue gases or purifying natural gas.
ABSTRACT
A defect engineering modification method is reported to improve the CO2/N2 and CH4/N2 separation performance of MOF-801, owing to skeleton shrinkage caused by defect modification, Zr-FA0.5 shows excellent gas separation performance compared with the prototype MOF.
ABSTRACT
On-skin electronics require minimal thicknesses and decent transparency for conformal contact, imperceptible wearing, and visual aesthetics. It is challenging to search for advanced ultrathin dielectrics capable of supporting the active components while maintaining bending softness, easy handling, and wafer-scale processability. Here, self-delaminated aramid nanodielectrics (ANDs) are demonstrated, enabling any skin-like electronics easily exfoliated from the processing substrates after complicated nanofabrication. In addition, ANDs are mechanically strong, chemically and thermally stable, transparent and breathable, therefore are ideal substrates for soft electronics. As demonstrated, compliant epidermal electrodes comprising silver nanowires and ANDs can successfully record high-quality electromyogram signals with low motion artifacts and satisfying sweat and water resistance. Furthermore, ANDs can serve as both substrates and dielectrics in single-walled carbon nanotube field-effect transistors (FETs) with a merely 160-nm thickness, which can be operated within 4 V with on/off ratios of 1.4 ± 0.5 × 105 , mobilities of 39.9 ± 2.2 cm2 V-1 s-1 , and negligible hysteresis. The ultraconformal FETs can function properly when wrapped around human hair without any degradation in performance.
ABSTRACT
Stretchable interconnects with miniature widths are vital for the high-density integration of deformable electronic components on a single substrate for targeted data logic or storage functions. However, it is still challenging to attain high-resolution patternability of stretchable conductors with robust circuit fabrication capability. Here, we report a self-assembled silver nanofilm firmly interlocked by an elastomeric nanodielectric that can be photolithographically patterned into microscale features while preserving high stretchability and conductivity. Both silver and dielectric nanofilms are fabricated by layer-by-layer assembly, ensuring wafer-scale uniformity and meticulous control of thicknesses. Without any thermal annealing, the as-fabricated nanofilms from silver nanoparticles (AgNPs) exhibit conductivity of 1.54 × 106 S m-1 and stretchability of â¼200%, which is due to the impeded crack propagation by the underlying PU nanodielectrics. Furthermore, it is revealed that AgNP microstrips defined by photolithography show higher stretchability when their widths are downscaled to 100 µm owing to confined cracks. However, further scaling restricts the stretchability, following the early development of cracks cutting across the strip. In addition, the resistance change of these silver interconnects can be decreased using serpentine architectures. As a demonstration, these self-assembled interconnects are used as stretchable circuit boards to power LEDs.
ABSTRACT
A general approach to prepare superhydrophobic MOFs (denoted as MOFs-CF3) through a post-decorating strategy for highly efficient chemical fixation of CO2 was demonstrated. The enhanced catalytic activity of MOFs-CF3 is attributed to a synergistic effect between the Lewis acid sites of MOFs and modification of the electron-withdrawing trifluoromethyl group, which resulted in a high CO2 enrichment capacity. The possible mechanism of cycloaddition catalyzed by the MOFs-CF3 catalyst was also proposed.
ABSTRACT
Multifunctional electrocatalysts are crucial to cost-effective electrochemical energy conversion and storage systems requiring mutual enhancement of disparate reactions. Embedding noble metal nanoparticles in 2D metal-organic frameworks (MOFs) are proposed as an effective strategy, however, the hybrids usually suffer from poor electrochemical performance and electrical conductivity in operating conditions. Herein, ultrafine Pt nanoparticles strongly anchored on thiophenedicarboxylate acid based 2D Fe-MOF nanobelt arrays (Pt@Fe-MOF) are fabricated, allowing sufficient exposure of active sites with superior trifunctional electrocatalytic activity for hydrogen evolution, oxygen evolution, and oxygen reduction reactions. The interfacial FeâOâPt bonds can induce the charge redistribution of metal centers, leading to the optimization of adsorption energy for reaction intermediates, while the dispersibility of ultrafine Pt nanoparticles contributes to the high mass activity. When Pt@Fe-MOF is used as bifunctional catalysts for water-splitting, a low voltage of 1.65 V is required at 100 mA cm-2 with long-term stability for 20 h at temperatures (65 °C) relevant for industrial applications, outperforming commercial benchmarks. Furthermore, liquid Zn-air batteries with Pt@Fe-MOF in cathodes deliver high open-circuit voltages (1.397 V) and decent cycling stability, which motivates the fabrication of flexible quasisolid-state rechargeable Zn-air batteries with remarkable performance.
ABSTRACT
The purification of natural gas and the removal of carbon dioxide from flue gases are crucial to economize precious resources and effectively relieve a series of environmental problems caused by global warming. Metal-organic framework (MOF) materials have demonstrated remarkable performance and benefits in the area of gas separation; however, obtaining materials with high gas capacity and selectivity simultaneously remains difficult. In addition, harsh synthesis conditions and solvent toxicity have been restricted in large-scale production and industrial application. Therefore, MOF-801(Zr/Ce/Hf) was created based on the green synthesis of the MOF-801 construction unit by altering the kinds of metal salts, and the impact of three metal nodes on the performance of gas adsorption and separation was demonstrated by contrasting the three MOFs. The results showed that MOF-801(Ce) has the best CO2 adsorption capacity (3.3 mmol/g at 298 K), which also was demonstrated with in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) results, CO2/CH4 (ideal adsorbed solution theory (IAST) = 13.28 at 298 K, 1 bar, CO2/CH4 = 1:1, v/v), and the separation performance of CO2/N2 (IAST = 57.46 at 298 K, 1 bar, CO2/N2 = 1:1, v/v) among the group. Green synthesis of MOF-801(Zr/Ce/Hf) is an ideal candidate for flue gas separation and methane purification because of its high regeneration capacity and strong cyclic stability.
ABSTRACT
Acute kidney injury (AKI) is a common and serious complication of cardiac surgery and is associated with increased mortality and morbidity, accompanied by a substantial economic burden. The pathogenesis of cardiac surgery-associated acute kidney injury (CSA-AKI) is multifactorial and complex, with a variety of pathophysiological theories. In addition to the existing diagnostic criteria, the exploration and validation of biomarkers is the focus of research in the field of CSA-AKI diagnosis. Prevention remains the key to the management of CSA-AKI, and common strategies include maintenance of renal perfusion, individualized blood pressure targets, balanced fluid management, goal-directed oxygen delivery, and avoidance of nephrotoxins. This article reviews the pathogenesis, definition and diagnosis, and pharmacological and nonpharmacological prevention strategies of AKI in cardiac surgical patients.
Subject(s)
Acute Kidney Injury , Cardiac Surgical Procedures , Humans , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/prevention & control , Kidney , Cardiac Surgical Procedures/adverse effects , Biomarkers , Heart , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Risk FactorsABSTRACT
A new metal-organic polyhedron with a high surface area of 407 m2 g-1, possessing high CO2 uptake, is reported, which is synthesized using 4-connected Cu2(CO2)4 paddle-wheel moieties and 3-connected semi-rigid tripodal carboxylates. This material possesses a high density of Cu(II) Lewis acidic sites and demonstrates excellent performance as a heterogeneous catalyst for the chemical fixation of CO2 into cyclic carbonates under ambient conditions.
ABSTRACT
Antiviral therapy of influenza virus infections depends heavily on two viral neuraminidase (NA) inhibitors, oseltamivir (OSV) and zanamivir (ZNV). The efficacy of OSV is challenged by the development of viral resistance, while the clinical use of ZNV is limited by its poor pharmacokinetic profile and requirement for twice-daily intranasal administration. We have developed a novel NA inhibitor by conjugating ZNV to cholesterol. The ZNV-cholesterol conjugate showed markedly improved antiviral efficacy and plasma half-life compared with ZNV. Single-dose administration of the conjugate protected the mice from lethal challenges with wild-type or mutant H1N1 influenza viruses bearing an OSV-resistant H275Y-substitution. Mechanistic studies showed that the conjugate targeted the cell membrane and entered the host cells, thereby inhibiting the NA function and the assembly of progeny virions. The ZNV-cholesterol conjugate represents a potential new treatment for influenza infections with sustained effect. Cholesterol conjugation may be an effective strategy for improving the pharmacokinetics and efficacy of other small-molecule therapeutics.
Subject(s)
Antiviral Agents/pharmacology , Cholesterol/chemistry , Enzyme Inhibitors/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Neuraminidase/antagonists & inhibitors , Zanamivir/chemistry , Animals , Antiviral Agents/pharmacokinetics , Drug Resistance, Viral/genetics , Enzyme Inhibitors/pharmacokinetics , Half-Life , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/physiology , Mice , Mice, Inbred BALB C , Mutation , Rats , Rats, Sprague-Dawley , Virus Replication/drug effectsABSTRACT
Resistant viruses containing mutant neuraminidases (NAs) with diminished drug affinity continue to emerge, and new anti-influenza agents are urgently required. Several potent inhibitors targeting the hydrophobic 150-cavity of viral NAs have been developed by modifying the antiviral drugs, oseltamivir carboxylate (OSC) and zanamivir, with hydrophobic groups. Here, we describe a different strategy for exploring novel and efficient NA inhibitors by targeting the charged amino acid residues around the entrance to the 150-cavity. We synthesized a C5-substituted OSC derivative (1e) with a 4'-phenyl-1,2,3-triazolyl group capable of entering the 150-cavity, and solved the crystal structure of 1e in complex with influenza A virus N5 NA. Using the resulting structural information, we next designed and synthesized two series of OSC derivatives carrying various polar substituents at the triazolyl group of 1e and 2e, with 2e being a 5'-phenyl-1,2,3-triazole regioisomer of 1e. The NA inhibition assays demonstrated that the 2 series (2e-n) generally had superior activity compared with the 1 series (1e-n). Compound 2j, bearing a 3-phenylamino group on the triazole ring, was the most potent inhibitor of all tested NAs including an N2 NA containing the E119V OSC-resistant mutation. Moreover, 2j potently inhibited viral replication in vitro, and molecular docking studies revealed that its phenylamino group can form an additional strong hydrogen bond with residue D151 near the entrance of the 150-cavity. The design method described in this study provides useful insights into the development of novel NA inhibitors. Compound 2j warrants further structural optimization to obtain a candidate for clinical use.