Antimicrobial Nonisocyanate Polyurethane Foam Derived from Lignin for Wound Healing.

Medical dressings, as a cover for wounds, can replace damaged skin in the wound healing process to play a temporary barrier role, avoid or control wound infection, and provide a favorable environment for wound healing. Therefore, there is an urgent need for medical antimicrobial dressings for the treatment of chronic wounds. Although traditional polyurethane foam has been widely used in medical dressings, conventional polyurethane foams are primarily prepared using nonbiocompatible isocyanate-based compounds, which are potentially hazardous for both operators and applications in the medical field. Here, we propose nonisocyanate polyurethane foams naturally derived from lignin by enzymatic lignin alkylation, cyclic carbonation modification, and polymerization with diamine and the addition of a blowing agent. Silver nanoparticle solution was added during foaming to confer antimicrobial properties. This lignin-based nonisocyanate polyurethane/silver composite foam (named NIPU foam-silver) using a green synthesis method has good mechanical properties, which can be used to manufacture polyurethane/silver foams, and thermal and antimicrobial properties. Notably, NIPU foam-Ag showed more than 95% bactericidal efficacy against both Escherichia coli and Staphylococcus aureus within 4 h. Evaluation of in vitro wounds in mice showed that this antimicrobial composite foam rapidly promotes wound healing and repairs damaged tissue. This suggests that this biobased biodegradable antimicrobial foam has significant scope for clinical applications in wound management.

Sustainable Janus lignin-based polyurethane biofoams with robust antibacterial activity and long-term biofilm resistance.

Conventional antibiotic therapies have been becoming less efficient due to increasingly, and sometimes fully, antibiotic-resistant bacterial strains, sometimes known as "superbacteria" or "superbugs." Thus, novel antibacterial materials to effectively inhibit or kill bacteria are crucial for humanity. As a broad-spectrum antimicrobial agent, silver nanoparticles (Ag NPs) have been the most widely commercialized of biomedical materials. However, long-term use of significant amounts of Ag NPs can be potentially harmful to human health through a condition known as argyria, in addition to being toxic to many environmental systems. It is, thus, highly necessary to reduce the amount of Ag NPs employed in medical treatments while also ensuring maintenance of antimicrobial properties, in addition to reducing the overall cost of treatment for humanitarian utilization. For this purpose, naturally sourced antimicrobial polylysine (PL) is used to partially replace Ag NPs within the materials composition. Accordingly, a series of PL, Ag NPs, and lignin-based polyurethane (LPU) composite biofoams (LPU-PL-Ag) were prepared. These proposed composite biofoams, containing at most only 2 % PL and 0.03 % Ag NPs, significantly inhibited the growth of both Gram-positive and Gram-negative bacteria within 1 h and caused irreversibly destructive bactericidal effects. Additionally, with a layer of polydimethylsiloxane (PDMS) on the surface, PDMS-LPU-PL(2 %)-Ag(0.03 %) can effectively prevent bacterial adhesion with a clearance rate of about 70 % for both bacterial biofilms within three days and a growth rate of more than 80 % for mouse fibroblasts NIH 3 T3. These lignin-based polyurethane biofoam dressings, with shorter antiseptic sterilization times and broad-spectrum antibacterial effects, are extremely advantageous for infected wound treatment and healing in clinical use.

A photothermally antibacterial Au@Halloysite nanotubes/lignin composite hydrogel for promoting wound healing.

The construction of an effective antibacterial micro-environment to prevent infection and biofilm formation is critically important for the design of wound dressings. Herein, a novel hydrogel wound dressing was fabricated by embedding Au nanoparticles-decorated halloysite nanotubes (Au@HNTs) into the lignin-based hydrogel matrix containing polyvinyl alcohol and chitosan. The resulting composite hydrogel, noted as LPC-Au@HNTs, exhibited an excellent photothermal antibacterial activity owing to the embedded Au@HNTs in which Au nanoparticles were generously filled into the lumen of Halloysite nanotubes. The typical sample containing 4 wt% of Au@HNTs in the composite hydrogel (LPC-Au@HNTs4) had good mechanical and photothermal properties. The surface temperature of as-prepared hydrogel increased to 57.59 °C after 5 min upon NIR light irradiation (808 nm) at 1.0 W/cm2. The photothermal effect endowed the hydrogel dressing with excellent antibacterial activity, with significantly enhanced inhibition rates of Escherichia coli (99.00 %) and Staphylococcus aureus (98.88 %). Experiments in a mouse full-thickness skin defect wound model also showed that the hydrogel dressing had a facilitative effect on the repair of traumatic surfaces. This study provides a broadly appliable wound dressing for treating bacteria-infected wounds, greatly contributing to the design of photothermal antibacterial biomedical materials for wound healing.

High-Performance, Light-Stimulation Healable, and Closed-Loop Recyclable Lignin-Based Covalent Adaptable Networks.

In this work, high-performance, light-stimulation healable, and closed-loop recyclable covalent adaptable networks are successfully synthesized from natural lignin-based polyurethane (LPU) Zn2+ coordination structures (LPUxZy). Using an optimized LPU (LPU-20 with a tensile strength of 28.4 ± 3.5 MPa) as the matrix for Zn2+ coordination, LPUs with covalent adaptable coordination networks are obtained that have different amounts of Zn. When the feed amount of ZnCl2 is 9 wt%, the strength of LPU-20Z9 reaches 37.3 ± 3.1 MPa with a toughness of 175.4 ± 4.6 MJ m-3 , which is 1.7 times of that of LPU-20. In addition, Zn2+ has a crucial catalytic effect on "dissociation mechanism" in the exchange reaction of LPU. Moreover, the Zn2+ -based coordination bonds significantly enhance the photothermal conversion capability of lignin. The maximum surface temperature of LPU-20Z9 reaches 118 °C under the near-infrared illumination of 0.8 W m-2 . This allows the LPU-20Z9 to self-heal within 10 min. Due to the catalytic effect of Zn2+ , LPU-20Z9 can be degraded and recovered in ethanol completely. Through the investigation of the mechanisms for exchange reaction and the design of the closed-loop recycling method, this work is expected to provide insight into the development of novel LPUs with high-performance, light-stimulated heal ability, and closed-loop recyclability; which can be applied toward the expanded development of intelligent elastomers.

AGEs-RAGE-KCa3.1 pathway mediates palmitic acid-induced migration of PBMCs from patients with type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade systemic inflammation. Tissue infiltration by monocyte migration contributes to the pathogenesis of vascular complications in T2DM. We studied the role of intermediate-conductance Ca2+-activated K+ (KCa3.1) channels in the palmitic acid (PA)-induced migration of peripheral blood mononuclear cells (PBMCs) from T2DM patients and the influence of advanced glycation endproducts (AGEs). A total of 49 T2DM patients and 33 healthy subjects was recruited into this study. Using flow cytometry and Western blotting analysis as well as cell migration assay, we found that there was a significant decrease in frequency of T lymphocytes and monocytes in CD45+ leukocyte population. PA at 100 µM stimulated migration of PBMCs from T2DM individuals, which was inhibited by the specific KCa3.1 channel blocker TRAM-34 (1 µM). The PBMC migration was positively correlated with glycosylated hemoglobin A1 chain (HbA1c) level of T2DM patients, an indicator of AGEs, and PBMCs with higher level of HbA1c showed upregulated expression of toll-like receptor (TLR) 2/4 and KCa3.1 channels. In THP-1 cells, AGEs at 200 µg/ml increased protein expression of TLR 2/4 and KCa3.1 channels, and were synergistically involved in PA-induced migration through receptors of AGEs (RAGE)-mediated KCa3.1 upregulation. In conclusion, in PBMCs of T2DM patients, AGEs promotes PA-induced migration via upregulation of TLR2/4 and KCa3.1 channels.

Crucial roles of ion-specific effects in the flotation of water-soluble KCl and NaCl crystals with fatty acid salts.

HYPOTHESIS: Flotation of water-soluble KCl and NaCl minerals in brines is significant for K-fertilizer production, but its mechanism is controversial. Dissolved salt ions are expected to change the physicochemical properties of solvents, interfaces, and collector colloids, thereby affecting flotation significantly. EXPERIMENTS: Flotation experiments of KCl and NaCl crystals in brines were conducted using potassium and sodium laurates as collectors. Contact angle (CA) and surface tension measurements, X-ray photoelectron spectroscopy (XPS) analysis, and molecular dynamics simulations (MD) were applied to gain a molecular understanding of changing interfacial properties and crystal-collector colloid interactions in the presence of dissolved ions in terms of salt flotation. FINDINGS: While K+ ions activate the NaCl crystal flotation, Na+ ions depress the KCl crystal flotation, in agreement with the studies of CA, XPS, and MD results with these crystals. XPS results showed no collector adsorption at crystal surfaces which is a requirement of conventional flotation and presents a new theoretical challenge. We argue the crucial role of ion specificity: Na-laurate colloids adsorb at the bubble surface as a monolayer but solvent-separated from KCl crystals, inhibiting their flotation, or in interactive contact with NaCl crystals, enhancing their flotation. Increasing K+ concentration weakens NaCl crystal hydration, increasing Na-laurate colloid attraction with crystals for better flotation. The Contact Interactive Collector Colloid (CICC) and Solvent-separated Interactive Collector Colloid (SICC) hydration states are critical to salt crystal flotation via collector colloid-crystal attraction by dispersion forces.

Analysis of a Sabin-Strain Inactivated Poliovirus Vaccine Response to a Circulating Type 2 Vaccine-Derived Poliovirus Event in Sichuan Province, China 2019-2021.

Importance: The Sabin-strain inactivated poliovirus vaccine (IPV) may be a tool for polio outbreak response in certain situations. Objective: To investigate the response to a type 2 vaccine-derived poliovirus (VDPV2) outbreak. Design, Setting, and Participants: This case series was conducted in China after a VDPV2 was detected in stool specimens from a child with acute flaccid paralysis (AFP) in Sichuan Province in 2019, 3 years after the global withdrawal of live, attenuated type 2 oral poliovirus vaccine (OPV). Investigation followed National Health Commission and World Health Organization guidance and included searching hospitals for unreported AFP cases; testing stool specimens from the child, his contacts, and local children; enhanced environmental surveillance for VDPV2s in wastewater; and measuring vaccination coverage. Sabin-strain IPV campaigns were conducted in a wide geographic area. Main Outcomes and Measures: Any VDPV2 detection after completion of the supplementary immunization activities. Results: A 28-nucleotide-change VDPV2 was isolated from a young boy. Three VDPV2s were detected in healthy children; 2 were contacts of the original child, and none had paralysis. A search of 31 million hospital records found 10 unreported AFP cases; none were polio. No type 2 polioviruses were found in wastewater. Prior to the event, polio vaccine coverage was 65% among children younger than 5 years. Sabin-strain IPV campaigns reached more than 97% of targeted children, administering 1.4 million doses. No transmission source was identified. More than 1 year of enhanced poliovirus environmental and AFP surveillance detected no additional VDPVs. Conclusions and Relevance: These findings suggest that the circulating VPDV2 outbreak in 2019 was associated with low vaccine coverage. An investigation discovered 3 infected but otherwise healthy children and no evidence of the virus in wastewater. Following Sabin-strain IPV-only campaigns expanding from county to prefecture, the poliovirus was not detected, and the outbreak response was considered by an expert panel and the World Health Organization to have been successful. This success suggests that the Sabin-strain IPV may be a useful tool for responding to circulating VDPV2 outbreaks when high-quality supplementary immunization activities can be conducted and carefully monitored in settings with good sanitation.

Superhydrophobic lignin-based multifunctional polyurethane foam with SiO2 nanoparticles for efficient oil adsorption and separation.

Superhydrophobic polyurethane foam is one of the most promising materials for oil-water separation. However, there are only limited studies prepared matrix superhydrophobic foams as adsorbents. In this paper, SiO2 modified by 1H, 1H, 2H, 2H-perfluorododecyl trichlorosilane (F-SiO2) was added into the lignin-based foam matrix by a one-step foaming technique. The average diameter of F-SiO2 was about 480 nm with an water contact angle (WCA) of 160.3°. The lignin-based polyurethane foam with F-SiO2 had a superhydrophobic water contact angle of 151.3°. There is no obvious change in contact angle after 100 cycles of compression or after cutting and abrasion. Scanning electron microscopy (SEM) analysis showed that F-SiO2 was distributed both on the surface and inside of the foam. The efficiency for oil-water separation reached 99 %. Under the light intensity of 1 kW/m2, the surface temperature of the lignin-based foam rose to 77.6 °C. In addition, the foam exhibited self-cleaning properties and degraded within 2 h in an alcoholic alkali solution. Thus, in this study, we developed a novel matrix superhydrophobic lignin-based polyurethane foam with an excellent promise to be used as oil water separation adsorbents in industrial wastewater treatment and oil spill clean-up processes.

Catalyst-Free Synthesis of Covalent Adaptable Network (CAN) Polyurethanes from Lignin with Editable Shape Memory Properties.

Here a new strategy of catalyst-free direct synthesis of covalent adaptable network polyurethanes (LPUs) from lignin with editable shape memory effect is reported. Using unmodified lignin, PEG, and isocyanate under the condition of the isocyanate index less than 1.0 (NCO/OH<1.0), a variety of LPUs are obtained. When NCO/OH=0.8, a stable cross-linked network can be formed (ex. the gel content of LPU50-0.8 was 98±0.3 %). The activation energy (Ea ) value of LPUs is similar to that of polyhydroxyurethanes (PHUs), at around 110 kJ mol-1 . With an increase of lignin content, the LPUs show a transition from ductile fracture to brittle fracture mode. And the mechanical properties of LPUs are significantly enhanced after extrusion processing, with the maximum modulus reaching 649±26 MPa and the maximum toughness up to 9927±111 kJ m-3 . The improvement in mechanical properties is due to the homogenization of complex cross-linked network under the powerful external force of the extruder and the lignin that originally was free in the system participated in the exchange reactions. Moreover, LPUs can also be prepared continuously in one step by using an extruder as the reactor. In addition, LPU50-0.8 has an editable shape memory effect. This study develops a novel method for the synthesis of LPU from lignin with NCO/OH<1.0, showcasing new possibilities for value-added utilization of lignin, and expands the bio-based products portfolio from biomass feedstock to help meet future green manufacturing demands.

Molecular characteristics of norovirus in sporadic and outbreak cases of acute gastroenteritis and in sewage in Sichuan, China.

BACKGROUND: Norovirus is highly diverse and constant surveillance is essential for the prevention and control of norovirus gastroenteritis. METHODS: From 2015 to 2019, fecal samples were collected from sporadic cases and outbreaks of acute gastroenteritis reported to Sichuan center for disease control and prevention. Sewage samples were collected from a wastewater treatment plant in Sichuan. All samples were tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus-positive clinical samples were sequenced by Sanger sequencing. Sewage samples were sequenced by amplicon and virome sequencing. RESULTS: A total of 1462 fecal samples were collected and 11 different norovirus genotypes were detected. GII.4 Sydney 2012[P31] and GII.3[P12] were the dominant genotypes in sporadic cases whereas GII.2[P16] and GII.17[P17] were the dominant genotypes in outbreaks. GII.3 was predominant in children 0-6 months of age during spring and summer, while GII.4 was predominant in children older than 6 months and in the autumn. The detection rate of GII.17[P17] increased with age. In sewage, 16 genotypes were detected. GII.3, GII.4, GI.1, and GI.2 were the dominant genotypes. CONCLUSION: This study demonstrated that multiple norovirus genotypes co-circulate in Sichuan. It is vital to continuously trace the genetic diversity of norovirus to give a future perspective on surveillance needs and guide vaccine design and policy decisions.

A review on quantifying the influence of lateral capillary interactions on the particle floatability and stability of particle-laden interfaces.

Particle-laden interfaces are critical to the flotation separation of hydrophobic particles using air bubbles. After contacting the particle suspension, the bubble surface is loaded with many hydrophobic particles that can get detached during the bubble rise to the top. While many studies of the capillary stability and detachment of single particles from the clean air-water interface have provided significant insights, the particle floatability, detachment, and stability of the particle-laden interface are not well quantified. This paper provides a critical review of the experimental and theoretical investigations of the lateral capillary interactions on the particle floatability and stability of the particle-laden interfaces. Particularly, we critically analysed, summarized, and commented on asymptotic solutions of the Young-Laplace equation for various particle configurations. Then, we critically assessed the outcomes of both the theoretical and experimental studies of the particle-laden interface stability and related the results to particle-bubble detachment behaviours in flotation applications. This review provides an updated outlook of research perspectives that establish the framework for researchers interested in this fascinating field of flotation and colloid and surface science.

Antimicrobial Lignin-Based Polyurethane/Ag Composite Foams for Improving Wound Healing.

Antimicrobial materials are an urgent need for modern wound care in the clinic. Although traditional polyurethane foams have proven to be clinically valuable for wound treatment, their petroleum-originated preparation and bioinert nature have restricted their efficacy in biomedical applications. Here, we propose a simple one-step foaming method to prepare lignin-based polyurethane foams (LPUFs) in which fully biobased polyether polyols partially replace traditional petroleum-based raw materials. The trace amount of phenolic hydroxyl groups (about 4 mmol) in liquefied lignin acts as a direct reducing agent and capping agent to silver ions (less than 0.3 mmol), in situ forming silver nanoparticles (Ag NPs) within the LPUF skeleton. This newly proposed lignin polyurethane/Ag composite foam (named as Ag NP-LPUF) shows improved mechanical, thermal, and antibacterial properties. It is worth mentioning that the Ag NP-LPUF exhibits more than 99% antibacterial rate against Escherichia coli within 1 h and Staphylococcus aureus within 4 h. Evaluations in mice indicate that the antimicrobial composite foams can effectively promote wound healing of full-thickness skin defects. As a proof of concept, this antibacterial and biodegradable foam exhibits significant potential for clinical translation in wound care dressings.

Mesoscale Numerical Analysis of Fiber-Reinforced Sand with Different Fiber Orientations Subjected to Seepage-Induced Erosion Based on DEM.

This paper focuses on the effect of fiber orientation on the resistance of seepage-induced erosion in fiber-reinforced sand. To clarify the discrepancy and mechanism of different-oriented fibers improving the resistance of the sand matrix, a series of DEM-Darcy coupling simulations were conducted. The microscopic parameters of fiber-reinforced sand were confirmed by the rigorous calibration procedure. The fibers perpendicular to the seepage direction were found to increase the difficulty of moving fluid through the specimen and significantly reduce the erosion rate of the specimen. These macroscopic behaviors acquired corresponding explanations at the mesoscopic scale, including the evolution of fiber-sand contact orientation, coordination number, average normal contact force, tensile force, and energy dissipation. According to the simulation results, it is found that the highest proportion of tensile force in perpendicular fibers can reach 80%, while the parallel fibers are only 40%, which indicates that the perpendicular fibers have a significant netting effect. The mesoscopic behaviors reasonably revealed the role of the fibers with different orientations on the sand matrix during the seepage. This study is beneficial for further understanding the mechanical behaviors of fiber-reinforced sand under seepage-induced erosion in safety engineering.

Circulation of Type 2 Vaccine-Derived Poliovirus in China in 2018-2019.

BACKGROUND: China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) on May 1, 2016. During April 2018 to May 2019, the first outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV2) after the switch occurred in Xinjiang and Sichuan, China. Methods. We performed sequence analysis of VP1 and the whole genome to determine the genomic characteristics of type 2 cVDPVs, and carried out coverage surveys to assess the risk of viral propagation. Surveillance for environment and acute flaccid paralysis was intensified to enhance case ascertainment. Results. Comparison of the complete genomes between early (Xinjiang strain) and late strains (Sichuan strains) revealed that recombination pattern and reverse mutation of attenuation sites had been fixed early, but the mutations of the neutralizing antigenic sites were introduced over the circulation. The Markov Chain Monte Carlo tree showed that the cVDPV2 initial infection was April 2016, earlier than the switch. So, we speculated that the cVDPV2 was originated from tOPV recipients and spread among children with a low level of immunity against the type 2. CONCLUSIONS: The detection of this outbreak combined acute flaccid paralysis (AFP) surveillance with environmental surveillance (ES) indicates that ES should be expanded geographically to further complement AFP surveillance.

Epidemiology of norovirus gastroenteritis in hospitalized children under five years old in western China, 2015-2019.

OBJECTIVES: Norovirus is associated with one-fifth of all gastroenteritis cases, but basic epidemiological data is lacking, especially in developing countries. As long-term surveillance on norovirus gastroenteritis is scarce in western China, this study aims to update the epidemiological knowledge of norovirus gastroenteritis and to characterize the genotypes of norovirus strains. METHODS: Stool samples were collected from hospitalized children under 5 years old with gastroenteritis in Chengdu, China. All samples were tested for norovirus as well as rotavirus, sapovirus, enteric adenovirus, and astrovirus by real-time RT-PCR. RdRp and VP1 genes were sequenced in norovirus-positive samples to investigate viral phylogenies. RESULTS: Of the 1181 samples collected from 2015 to 2019, 242 (20.5%) were positive for norovirus. Among norovirus-positive cases, 65 cases had co-infection with another virus; norovirus/enteric adenovirus was most frequently detected (50.8%, 33/65). The highest positive rate was observed in children aged 13-18 months (23.7%, 68/287). Norovirus infection peaked in autumn (36.6%, 91/249), followed by summer (20.3%, 70/345). Pearson correlation analysis showed significant correlation between the norovirus-positive rate and humidity (r = 0.773, P < 0.05). GII.4 Sydney 2012 [P31] (48.5%, 79/163) and GII.3 [P12] (35.6%, 58/163) were the dominant norovirus strains. CONCLUSIONS: Norovirus has become one of the most common causes of viral gastroenteritis in children under 5 years old in western China. Continuous monitoring is imperative for predicting the emergence of new epidemic strains and for current vaccine development.

Lignin-Based Polyurethane: Recent Advances and Future Perspectives.

Polyurethane (PU), as a polymer material with versatile product forms and excellent performance, is used in coatings, elastomers, adhesives, and foams widely. However, the raw materials (polyols and isocyanates) of PU are usually made using petroleum-derived chemicals. With the concern for depletion of petroleum resources and the associated negative impact on the environment, developing technologies that can use renewable raw materials as feedstock has become a research hotspot. Lignin, as an abundant, natural, and renewable organic carbon resource, has been explored as raw material for making polyurethanes because it possesses rich hydroxyl groups on its surface. Meanwhile, compared to vegetable oils, lignin does not compete with food supply and performance of the resulting products is superior. Lignin or modified lignin has been shown to impart the polyurethane material with additional functionalities, such as UV-blocking ability, hydrophobicity, and flame retardancy. However, the utilization of lignin has encountered some challenges, such as product isolation, heterogeneity, aggregation, steric hindrance, and low activity. This paper summarizes recent research progress on utilizing lignin and modified lignin for bio-based polyurethane synthesis with a focus on elastomers and foams. Opportunities and challenges for application of the lignin-based polyurethanes in various fields are also discussed.

AMPK upregulates KCa2.3 channels and ameliorates endothelial dysfunction in diet-induced obese mice.

The opening of endothelial small-conductance calcium-activated potassium channels (KCa2.3) is essential for endothelium-dependent hyperpolarization (EDH), which predominantly occurs in small resistance arteries. Adenosine monophosphate-activated protein kinase (AMPK), an important metabolic regulator, has been implicated in regulating endothelial nitric oxide synthase activity. However, it was unclear whether AMPK regulated endothelial KCa2.3-mediated EDH-type vasodilation. Using bioinformatics analysis and myograph system, we investigated the regulation by AMPK of KCa2.3 in human umbilical vein endothelial cells (HUVECs) or mouse second-order mesenteric resistance arteries. In HUVECs, AMPK activation either by activators (AICAR, A769662 and MK-8722) or expression of the constitutively active form of AMPK significantly upregulated KCa2.3 expression. Such effects were abolished by AMPK inhibitor (compound C) or AMPK α1-/α2-siRNA, extracellular-signal-regulated-kinase 5 (ERK5) inhibitor (ERK5-IN-1), and specific siRNA to myocyte-enhancer factor 2 (MEF2) or krüppel-like factor 2/4 (KLF2/4). KCa2.3 expression was significantly reduced in mesenteric resistance arteries in AMPKα2 knockout mice when compared with littermate control mice. Furthermore, in high-fat diet fed mice, 2-week treatment with AICAR restored endothelial KCa2.3 expression in mesenteric resistance arteries with improved endothelial dysfunction. Our results demonstrate that activation of AMPK upregulates KCa2.3 channel expression through the ERK5-MEF2-KLF2/4 signaling pathway in vascular endothelium, which contributes to benefits through KCa2.3-mediated EDH-type vasodilation in mesenteric resistance arteries.

Detection and Initial Response to a Type 2 Vaccine-Derived Poliovirus - Sichuan Province, China, 2019.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: After the type 2 strain of the live, attenuated poliovirus vaccine was withdrawn globally in 2016, any identification of a type 2 poliovirus is a Public Health Emergency of International Concern. A vaccine-derived type 2 poliovirus (VDPV2) was identified in Sichuan, prompting an urgent, comprehensive investigation and response. WHAT IS ADDED BY THIS REPORT?: Type 2 monovalent, live, attenuated oral poliovirus vaccine (mOPV2) is being used to respond to the numerous VDPV2 outbreaks seen around the world. In contrast, the response in Sichuan used Sabin strain inactivated poliovirus (sIPV) to stop circulation of the VDPV2. In the 6 months following the vaccination response, there have been no VDPV2s detected in Sichuan, despite extensive search. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICES?: Further search for the VDPV2 must continue in order to determine whether transmission has been stopped. The ongoing investigation and response to the Sichuan VDPV2 is providing evidence to the Global Polio Eradication Initiative on managing VDPV2 outbreaks.

Inhibition of microRNA-148b-3p alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling.

MicroRNAs (miRNAs) have emerged as crucial regulators of neuronal injury during cerebral ischaemia/reperfusion injury. Various miRNAs are dysregulated during this pathological process; however, the precise role of these miRNAs in regulating neuronal injury remains largely unknown. In the current study, we explored the potential function of microRNA-148b-3p (miR-148b-3p) in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro, a cellular model for mimicking cerebral ischaemia/reperfusion injury. We found that miR-148b-3p expression was significantly decreased in neurons in response to OGD/R exposure. Importantly, miR-148b-3p overexpression decreased cell viability and exacerbated apoptosis and reactive oxygen species (ROS) production in OGD/R-exposed neurons. By contrast, miR-148b-3p inhibition improved cell viability and decreased apoptosis and ROS production in OGD/R-exposed neurons. Notably, Sestrin2, a cytoprotective gene, was identified as a miR-148b-3p target gene. miR-148b-3p inhibition markedly increased Sestrin2 expression as well as the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) antioxidant signalling. Moreover, silencing of Sestrin2 or Nrf2 significantly reversed the miR-148-3p-inhibition-mediated protective effect in OGD/R-injured neurons. Overall, these results demonstrate that miR-148b-3p inhibition protects neurons from OGD/R-induced apoptosis and ROS production through reinforcing Nrf2 antioxidant signalling via upregulation of Sestrin2. Our study indicates that the miR-148b-3p/Sestrin2/Nrf2 axis plays an important role in regulating neuronal injury and may serve as a potential therapeutic target for providing neuroprotection during cerebral ischaemia/reperfusion injury.