Service demand analysis and optimization strategy construction of emergency observation patients based on the Kano model.

Background: Emergency observation unit in China are characterized by a high number of patients, complexity of diseases, and instability of patient conditions, leading to low patient satisfaction. The Kano model is an effective method widely used to identify customer demands and improve service quality to enhance customer satisfaction. However, its application in emergency observation unit has been studied less. This study aims to design a questionnaire based on the Kano model and identify the demands of emergency observation patients to determine priorities for improvements in the emergency observation unit and improve patient satisfaction. Methods: A cross-sectional study was conducted in Guizhou Provincial People's Hospital from March 21st, 2023, to May 20th, 2023. A convenient sampling method was used to recruit 100 patients from the emergency observation unit, who completed a questionnaire designed based on the Kano model to assess their demands for care service. Data were analyzed using IBM SPSS Statistics 28.0 software. The element selection line and sensitivity analysis were used to determine factors for patient service demand improvement. Results: A total of 13 patient service demands for improvement were screened out from 19 service demands, including 1 item of must-be quality (M), 11 item of one-dimensional quality (O), and 1 item of attractive quality (A), These attributes showed significant differences in patients' sociodemographic characteristics. Conclusion: The Kano model is a valuable tool for identifying the characteristics of patients' service demands, and the element screening method can be employed to establish the hierarchy of these demands. These results offer crucial direction for creating forthcoming nursing management initiatives in emergency observation unit.

Constructing an interaction in plant polyphenol-modified carbon fiber with amylopectin-based waterborne polyurethane sizing agent via hydrogen bonding to improve the interfacial performance of carbon fiber/nylon 6 composites.

The adhesive strength between the sizing agent and carbon fiber (CF) plays a crucial role in improving the interfacial properties of composites, while such a vital aspect has been consistently disregarded. In this study, a hyperbranched waterborne polyurethane (HWPU) sizing agent was synthesized from biogenetically raw materials including gallic acid, l-Lysine diisocyanate and amylopectin. Concurrently, hydrogen-bonded cross-linked network structures were established utilizing a botanical polyphenol tannin as coupling agent to effectively connect CF with HWPU. This meticulous process yielded CF/nylon 6 composites with improved properties and their mechanical characteristics were systematically investigated. The findings showcased a noteworthy boost in flexural strength and interlaminar shear strength (ILSS), showing enhancements of 54.6 % and 61.4 %, respectively, surpassing those of untreated CF. Furthermore, the interfacial shear strength (IFSS) test indicated a remarkable 70.3 % improvement. This approach presents a highly promising concept aimed at developing sustainable green waterborne polyurethane sizing agent and improving the interfacial performance of CF composite materials.

Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents.

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing pandemic. However, the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well explored. In our research, we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV, identifying cross-reactive CD8+ T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining assays. Then, in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide complexes. Lastly, single-cell T cell receptor reservoir was analyzed based on tetramer staining. Here, we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19, and identified SARS-CoV-2 CD8+ T cell epitopes spanning the major structural antigens. T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 convalescents. Cross-T cell reactivity was also observed within the identified series of CD8+ T cell epitopes. For representative immunodominant peptide pairs, although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar, the TCR repertoires recognizing these peptides were distinct. Our results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

[Retracted] Methylene blue relieves the development of osteoarthritis by upregulating lncRNA MEG3.

[This retracts the article DOI: 10.3892/etm.2018.5918.].

A Better Fruit Quality of Grafted Blueberry Than Own-Rooted Blueberry Is Linked to Its Anatomy.

To further clarify the impact of different rootstocks in grafted blueberry, fruit quality, mineral contents, and leaf gas exchange were investigated in 'O'Neal' blueberry (Vaccinium corymbosum) grafted onto 'Anna' (V. corymbosum) (AO), 'Sharpblue' (V. corymbosum) (SO), 'Baldwin' (V. virgatum) (BO), 'Plolific' (V. virgatum) (PO), and 'Tifblue' (V. virgatum) (TO) rootstocks and own-rooted 'O'Neal' (NO), and differences in anatomic structures and drought resistance were determined in AO, TO, and NO. The findings revealed that fruit quality in TO and PO was excellent, that of BO and SO was good, and that of AO and NO was medium. 'Tifblue' and 'Plolific' rootstocks significantly increased the levels of leaf phosphorus and net photosynthetic rate of 'O'Neal', accompanied by a synchronous increase in their transpiration rates, stomatal conductance, and intercellular CO2. Additionally, the comprehensive evaluation scores from a principal component analysis based on anatomic structure traits from high to low were in the order TO > AO > NO. The P50 (xylem water potential at 50% loss of hydraulic conductivity) values of these grafted plants descended in the order NO > AO > TO, and the branch hydraulic conductivity of TO and sapwood hydraulic conductivity of TO and AO were significantly lower than those of NO. Thus, TO plants exhibited the strongest drought resistance, followed by AO, and NO, and this trait was related to the effects of different rootstocks on the fruit quality of 'O'Neal' blueberry. These results provided a basis for a deeper understanding of the interaction between rootstocks and scions, as well mechanisms to improve blueberry fruit quality.

Long-lasting humoral and cellular memory immunity to vaccinia virus Tiantan provides pre-existing immunity against mpox virus in Chinese population.

Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.

Estimation for running time and energy losses due to unproductive stops at bus stations in urban-rural traffic corridors.

To provide data support for developing fixed-route DRT based on FRT to reduce operating costs inside base routes in urban-rural traffic corridors, this paper estimated running time and energy losses due to unproductive stops at bus stations in urban-rural traffic corridors. Firstly, 14 urban-rural bus routes without ticket sellers in Xi'an are selected to demonstrate the universality of unproductive stops at bus stations. Secondly, a model for estimating running time and energy losses based on the VT-CPFM model is developed. Finally, running time and energy losses due to unproductive stops in two representative urban-rural traffic corridors are estimated. Estimated results show that the average running time loss ratios of different rounds in Routes 332, 333, 335, 338 and G1 range from 8.30% to 17.52% and that average fuel loss ratios range from 9.16% to 13.30%. In addition, the monetary loss in energy consumption of Route G1 in 2019 is estimated to be up to 193213 yuan. This study proves that unproductive stops at bus stations generally exist in urban-rural bus routes and can result in significant running time and energy losses and that developing fixed-route DRT based on FRT leveraging V2I with mobile APP in representative urban-rural traffic corridors is very necessary, which is expected to reduce energy consumption and running time.

Pyruvate dehydrogenase kinase 1 regulates the function of human decidual natural killer cells.

PROBLEM: Pyruvate dehydrogenase kinase 1 (PDK1) is an important enzyme for immune cell development. However, PDK1's role in human decidual natural killer (dNK) cells remains largely unknown. METHODS OF STUDY: PDK1 expression in dNK cells from patients with recurrent spontaneous abortions (RSA) and age-matched healthy controls was analyzed by qRT-PCR, western bolt and flow cytometry. Moreover, dNK cells were treated with PDK1 inhibitor or the PDK1 siRNA followed by functional assays. RESULTS: The dNK cells from patients who underwent RSAs had higher mRNA expression and increased protein of PDK1, perforin (PRF1), Granzyme B (GZMB), IFN-γ (IFNG), and CD107a expression compared to dNK cells from age-matched healthy controls. Perforin, Granzyme B, IFN-γ and CD107a expression levels in dNK cells were down-regulated when dNK cells were treated with a PDK1 inhibitor. As measured by the 51 Cr release assay, the killing activity of dNK cells was found to be decreased. We also demonstrated that PDK1 blockade could up-regulate the migration and adhesion of dNK cells. Furthermore, PDK1 inhibition reduced the glycolysis of dNK cells. CONCLUSION: This study suggested that PDK1 plays an important role in regulating dNK cell functions and human RSA.

The enrichment of Arg1+ILC2s and ILCregs facilitates the progression of endometriosis: A preliminary study.

Innate lymphoid cells (ILCs) are a kind of lymphocytes that reside in the tissue and have an essential function in the immune microenvironment. However, the relationship between endometriosis (EMS) and ILCs is complex and not fully understood. This study examines several groups of ILCs in the peripheral blood (PB), peritoneal fluid (PF) and endometrium of patients with EMS via flow cytometry. The study observed an increase in PB ILCs, particularly ILC2s and ILCregs subsets and Arg1+ILC2s in the EMS patients were highly activated. EMS patients had significantly higher levels of serum interleukin (IL)-10/33/25 compared to controls. We also found an elevation of Arg1+ILC2s in the PF and higher levels of ILC2s and ILCregs in ectopic endometrium compared with eutopic. Importantly, a positive correlation was observed between the enrichment of Arg1+ILC2s and ILCregs in the PB of EMS patients. The findings indicate that the involvement of Arg1+ILC2s and ILCregs fosters potentially endometriosis progression.

Functional Pathway and Process Enrichment Analysis of Genes Associated With Morphological Abnormalities of the Outer Ear.

Congenital anomalies of the outer ear are common birth defects, including a variety of congenital deformities or malformations ranging from mild structural anomalies to total absence of the ear. Despite its high incidence and detrimental impact on patients, the etiology of outer ear abnormalities remains poorly understood. The goal of this study was to summarize the related genes and improve our understanding of the genetic etiology of morphological abnormalities of the outer ear. Human Phenotype Ontology (HPO) database, Mouse Genome Informatics (MGI) database, and PubMed search engine were used to acquire the genes associated with abnormal human or mouse outer ear. Metascape was employed on the genes above to conduct functional annotation, pathway and process enrichment analysis, protein-protein interaction network analysis, and MCODE component analysis. After a comprehensive review of the databases and literature, we identified 394 human genes and 148 mouse genes that have been associated with abnormal phenotypes of the outer ear, and we identified several biological pathways for human and mouse respectively. Especially, the analysis of common genes shared by human and mouse emphasized the importance of certain genes ( PAX6 , PBX1 , HOXA1 , HOXA2 , TBX1 , TBX15 , PRRX1 , and HMX1 ) in the embryonic development of the external ear. Through our analysis of genes associated with morphological abnormalities of the outer ear, the authors have shown that embryonic development pathways take important roles in the morphogenesis of abnormal external ear and highlighted some potential genetic drivers.

Effects of abdominal core strengthening on flexibility in tae kwon do athletes / Efeitos do fortalecimento do centro abdominal sobre a flexibilidade dos atletas de tae kwon do / Efectos del fortalecimiento del núcleo abdominal en la flexibilidad de los atletas de tae kwon do

ABSTRACT Introduction In competitive sports like Tae Kwon Do, the body remains in constant disequilibrium and displacement. In this state, the limbs generate and transmit energy through the muscles of the abdominal core, which is the main link in the human kinetic energy chain. Objective Explore the effect of abdominal core strength on improving flexibility in taekwondo athletes. Methods Thirty male athletes were selected, with a minimum sport time limit of 4 years, and a mean age of 21±1 years. They were randomly divided into three groups, A, B and C, with 10 people in each group. Group A participated in stable abdominal core strength training, 1 hour daily, 3 times a week, for a total of 12 weeks. Results Intra-group comparisons: There were extremely significant differences between groups A, B and C; extremely significant differences were found between the first and second and third times in group A; when compared, the first, second and third times in group B also showed modifications. Conclusion Stable and unstable core strength training can improve flexibility; after training, flexibility gains from unstable abdominal core strength training are more lasting. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Em esportes competitivos como o Tae Kwon Do, o corpo permanece em constante desequilíbrio e deslocamento. Neste estado, os membros geram e transmitem energia através dos músculos do centro abdominal, que é o elo principal da cadeia de energia cinética humana. Objetivo Explorar o efeito da força do centro abdominal na melhoria da flexibilidade dos atletas de taekwondo. Métodos Foram selecionados 30 atletas masculinos, com limite de tempo esportivo mínimo de 4 anos, e idade média de 21±1 anos. Foram divididos aleatoriamente em três grupos, A, B e C, com 10 pessoas em cada grupo. O grupo A participou do treinamento estável da força do centro abdominal, 1 hora diária, 3 vezes por semana, por um total de 12 semanas. Resultados Comparações intra-grupo: Houve diferenças extremamente significativas entre os grupos A, B e C; foram encontradas diferenças extremamente significativas entre a primeira e segunda e terceira vez no grupo A; quando comparados, a primeira, segunda e terceira vezes do grupo B também apresentaram modificações. Conclusão O treinamento estável e instável da força do centro abdominal pode melhorar a flexibilidade; após o treinamento, os ganhos de flexibilidade do treinamento instável da força do centro abdominal são mais duradouros. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción En los deportes de competición como el Tae Kwon Do, el cuerpo permanece en constante desequilibrio y desplazamiento. En este estado, las extremidades generan y transmiten energía a través de los músculos del núcleo abdominal, que es el principal eslabón de la cadena de energía cinética humana. Objetivo Explorar el efecto de la fuerza del núcleo abdominal en la mejora de la flexibilidad en atletas de taekwondo. Métodos Se seleccionaron 30 atletas masculinos, con un tiempo mínimo de práctica deportiva de 4 años, y una edad media de 21±1 años. Se dividieron aleatoriamente en tres grupos, A, B y C, con 10 personas en cada grupo. El grupo A participó en un entrenamiento de fuerza abdominal estable, 1 hora diaria, 3 veces por semana, durante un total de 12 semanas. Resultados Comparaciones intragrupo: Hubo diferencias extremadamente significativas entre los grupos A, B y C; se encontraron diferencias extremadamente significativas entre el primer y el segundo y tercer tiempo del grupo A; cuando se compararon, el primer, el segundo y el tercer tiempo del grupo B también mostraron modificaciones. Conclusión El entrenamiento de la fuerza del núcleo estable e inestable puede mejorar la flexibilidad; después del entrenamiento, las ganancias de flexibilidad del entrenamiento de la fuerza del núcleo abdominal inestable son más duraderas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The influence of internet use frequency, family atmosphere, and academic performance on adolescent depression: Based on the chain mediating effect of self-adjustment and campus deviant behavior.

Introduction: Depression has become a prominent psychological problem among young people. The purpose of this study was to investigate the potential relationship between the frequency of Internet use, family atmosphere, academic performance, self-adjustment, campus deviant behavior, and depressive symptoms among adolescents. Methods: Based on the survey data of the fifth wave (2017~2018) and the sixth wave (2019~2020) of the China Family Panel Studies (CFPS), this study used LISREL8.8 software to analyze 1,577 10~15 data on adolescents. Results: In this study, the mean score of self-adjustment was 42.40 (SD = 6.79), the mean score of campus deviant behavior was 12.59 (SD = 4.00), the mean score of depressive symptoms in 2018 was 11.88 (SD = 3.04), and the mean score of depressive symptoms in 2020 was 7.64 (SD = 2.20). Secondly, the frequency of Internet use had no direct effect on the depressive symptoms of adolescents, family atmosphere was negatively correlated with depressive symptoms (p < 0.005), and academic performance was positively correlated with depressive symptoms (p < 0.005). Depressive symptoms in 2020 had a direct effect (ß = 0.37, p < 0.001), and also had a negative effect on depressive symptoms in 2020, with a total effect of-0.07 (p < 0.001); self-adjustment had no direct effect on depressive symptoms in adolescents in 2018, However, the total effect was -0.14 (p < 0.001), which had a significant positive effect on 2020 depressive symptoms, and the total effect was 0.18 (p < 0.001), and self-adjustment had a significant negative effect on adolescent campus deviant behavior (ß = -0.38, p < 0.001); in addition, the frequency of Internet use, family atmosphere, and academic performance all had indirect effects on adolescents' 2020 depressive symptoms, with total effects of -0.60, 0.01, and 0.02 (p < 0.001), respectively. This study also found depressive symptoms in adolescents have a certain persistence in time. Discussion: Based on this study, it is necessary to pay more attention to the depression of adolescents, strengthen the training of self-adjustment, improve the anti-frustration ability and psychological resilience, and reduce the campus deviant behavior of adolescents. It is recommended to try to start from emotional self-adjustment to promote the personality health of adolescents.

The influence of academic pressure on adolescents' problem behavior: Chain mediating effects of self-control, parent-child conflict, and subjective well-being.

As a negative social issue, teenagers' problem behavior not only affects individuals' physical and mental health and social function development but is also not conducive to social harmony and stability. This study mainly discusses the influence of academic pressure on adolescents' problem behavior, and the potential relationship between these and academic pressure, examining issues such as self-control, parent-child conflict, and subjective well-being. The data were collected from the fifth wave of the China Family Panel Studies (2017-2018). The data of 2,465 teenagers aged 10-15 were analyzed by LISREL8.8 software. The results show that academic pressure positively affects adolescents' deviant behavior. The mediation model finds that parent-child conflict and self-control play a direct mediating role between academic pressure and adolescents' behavioral problems. Parent-child conflict, self-control, and subjective well-being have important chain mediation effects between academic pressure and adolescents' problem behavior. Therefore, in order to reduce the risk of such problems, it is necessary to further strengthen individuals' ability to maintain self-control, promote or cultivate adolescents' character strengths, create a harmonious family atmosphere, reduce the probability of parent-child conflict, and increase the subjective well-being of teenagers.

Influence of perceived importance of the internet on life satisfaction and health of the older people: An analysis based on intermediary and moderating effects.

With the global growth of the aging population, healthy aging and active aging has become an important goal for the future social development of all countries. The purpose of this study is to explore the potential relationships between the older people's perceived importance of the Internet, family atmosphere, behavioral independence, life satisfaction, and health. The data come from the China Family Panel Studies' fourth wave (2015-2016) and fifth wave (2017-2018) investigations. According to an analysis of data of 5,948 people over 60 years old performed using LISREL 8.8 software, the selected cases answered the same questions about the perceived importance of the Internet, life satisfaction, and health status in two waves of surveys. The results show that life satisfaction and self-rated health have cross influences, while at the same time both are persistent in the time baseline, and family atmosphere and behavioral independence play an important intermediary role. Therefore, strengthening parent-child interaction, promoting parent-child relationships, and improving behavioral independence can effectively improve the life satisfaction and health status of the older people.

Genome-wide analysis of serine carboxypeptidase-like protein (SCPL) family and functional validation of Gh_SCPL42 unchromosome conferring cotton Verticillium der Verticillium wilt stress in Gossypium hirsutum.

BACKGROUND: Serine carboxypeptidase-like protein (SCPL) plays an important role in response to stress in plant. However, our knowledge of the function of the SCPL gene family is limited. RESULTS: In this study, a comprehensive and systematic analysis of SCPL gene family was conducted to explore the phylogeny and evolution of the SCPL gene in Gossypium hirsutum. The phenotype and molecular mechanism of silencing of the Gh_SCPL42 under Verticillium wilt stress was also studied. Our results showed that 96 SCPL genes were observed in genome of G. hirsutum, which distributed on 25 chromosomes and most of them were located in the nucleus. The phylogenetic tree analysis showed that members of SCPL gene family can be divided into three subgroups in G. hirsutum, which are relatively conservative in evolution. SCPL gene has a wide range of tissue expression types in G. hirsutum. Promoter analysis showed that the most cis-acting elements related to MeJA and ABA were contained. Through RNA-seq combined with genotyping, it was found that 11 GhSCPL genes not only had significant expression changes during Verticillium wilt stress but also had differential SNPs in the upstream, downstream, exonic or intronic regions. The expression of these 11 genes in the resistant (Zhongzhimian 2) and susceptible (Junmian 1) materials was further analyzed by qRT-PCR, it was found that 6 genes showed significant expression differences in the two materials. Among them, Gh_SCPL42 has the most obvious expression change. Furthermore, virus-induced gene silencing (VIGS) showed necrosis and yellowing of leaves and significantly higher disease severity index (DSI) and disease severity rate (DSR) values in VIGS plants than in control silenced Gh_SCPL42 plants. Moreover, the expression levels of genes related to the SA and JA pathways were significantly downregulated. These results show that Gh_SCPL42 might improve resistance to Verticillium wilt through the SA and JA pathways in G. hirsutum. CONCLUSION: In conclusion, our findings indicated that Gh_SCPL42 gene plays an important role in resistance to Verticillium wilt in cotton. It was provided an important theoretical basis for further research on the function of SCPL gene family and the molecular mechanism of resistance to Verticillium wilt in cotton.

General Pharmacological Activation Mechanism of K+ Channels Bypassing Channel Gates.

Under the known pharmacological activation mechanisms, activators allosterically or directly open potassium channel gates. However, herein, molecular dynamics simulations on TREK-1, a member of the channel class gated at the filter, suggested that negatively charged activators act with a gate-independent mechanism where compounds increase currents by promoting ions passing through the central cavity. Then, based on studies of KCNQ2, we uncovered that this noncanonical activation mechanism is shared by the other channel class gated at the helix-bundle crossing. Rational drug design found a novel KCNQ2 agonist, CLE030, which stably binds to the central cavity. Functional analysis, molecular dynamics simulations, and calculations of the potential of mean force revealed that the carbonyl oxygen of CLE030 influences permeant ions in the central cavity to contribute to its activation effects. Together, this study discovered a ligand-to-ion activation mechanism for channels that bypasses their gates and thus is conserved across subfamilies with different gates.

MFG-E8 Knockout Aggravated Nonalcoholic Steatohepatitis by Promoting the Activation of TLR4/NF-κB Signaling in Mice.

Nonalcoholic steatohepatitis (NASH) is the common liver disease characterized by hepatic steatosis, inflammation, and fibrosis; there are no approved drugs to treat this disease because of incomplete understanding of pathophysiological mechanisms of NASH. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a multifunctional glycoprotein, has shown anti-inflammation and antifibrosis. Here, MFG-E8 was shown to play a key role in NASH progression. Using methionine and choline deficient (MCD) diet-fed mice, we found MFG-E8 knockout exacerbated hepatic damage and steatosis as indicated by increased plasma transaminases activities and hepatic histopathologic change, higher hepatic triglycerides (TGs), and lipid accumulation. Moreover, liver fibrosis and inflammation elicited by MCD were aggravated in MFG-E8 knockout mice. Mechanistically, MFG-E8 knockout facilitated activation of hepatic toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway in MCD-fed mice. In vitro experiment, the TLR4 specific antagonist TAK-242 rescued palmitic acid- (PA-) primed lipid formation and inflammation in MFG-E8 knockout primary murine hepatocytes. These findings indicated that MFG-E8 is involved in the progression of NASH and the possible mechanism by which MFG-E8 knockout exacerbated NASH in mice is associated with activation of the TLR4/NF-κB signaling pathway.

High-strain sensitive zwitterionic hydrogels with swelling-resistant and controllable rehydration for sustainable wearable sensor.

The irrecoverability of mechanical strength, conductivity and other properties after dehydration, has severely restricted the practical applications of hydrogels. To address this issue, here we report a P(AA-SMA-SBMA) zwitterionic copolymer-based hydrogel with anti-swelling, high mechanical property and reusability after dehydration/hydration process by polymerization of acrylic acid (AA), octadecyl methacrylate (SMA) and sulfobetaine methacrylate (SBMA). The structures of the original hydrogels and that after dehydration/hydration cycles were characterized by SAXS, SEM, Raman, FT-IR, XRD, DSC and rheology, etc. It was proved that both the macroscopic properties and the micro-structures were maintained after several dehydration/hydration cycles, owing to the synergistic effects of hydrophobic and super-hydrophilic interaction in the 3D network structure. Moreover, the fabricated hydrogels possess high strain sensitivity which is applied to monitor both junction motion and subtle movement like breathing and pulse. In addition, such sensitivity of the hydrogel sensors could be maintained after several dehydration/hydration cycles or even sinking in water for over two months. This work provides a type of hydrogel material with stable properties after dehydration process by regulating hydrophobic and hydrophilic interaction, which is beneficial for the life-time and sustainability of hydrogel devises.

Irisin improves BBB dysfunction in SAP rats by inhibiting MMP-9 via the ERK/NF-κB signaling pathway.

BACKGROUND: Blood-brain barrier (BBB) damage may lead to life-threatening pancreatic encephalopathy in patients with serious acute pancreatitis (SAP). Irisin alleviates BBB injury caused by cerebral ischemia-reperfusion by repressing matrix metalloproteinase-9 (MMP-9) expression. Serum levels of irisin are decreased in SAP patients. However, the role of irisin in BBB injury in SAP is still unknown. This study aimed to investigate whether irisin protects the BBB in SAP by affecting MMP-9 and its underlying regulatory mechanism. METHODS: An SAP model was established. Pancreatic injury was examined 24 h after SAP induction. Serum amylase and tumor necrosis factor-α (TNF-α) levels were examined by enzyme-linked immunosorbent assay (ELISA), and the brain water content was measured by the wet/dry proportion method. The structure and permeability of the BBB were examined by transmission electron microscopy, Evans blue exudation and transendothelial electrical resistance (TEER). RESULTS: In the brains of SAP rats, MMP-9 expression was increased, which was associated with damage to the BBB and the brain. Irisin inhibited this increase in MMP-9 and reduced brain edema and BBB permeability. The ERK/NF-κB axis is involved in irisin -mediated regulation of MMP-9. Irisin inhibited not only MMP-9 expression but also ERK/NF-κB phosphorylation. Furthermore, inhibiting ERK and NF-κB decreased MMP-9 levels and improved BBB dysfunction in SAP in vivo and in vitro. Moreover, irisin prevented the degradation of tight junctions (ZO-1, Claudin-5). The inhibition of ERK and NF-κB had similar effects on ZO-1 and Claudin-5 expression. CONCLUSION: Irisin protects tight junctions and alleviates BBB dysfunction in SAP by inhibiting MMP-9 expression and regulates MMP-9 expression through ERK/NF-κB phosphorylation.

Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects.

Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDS) produce deleterious side effects and fail to provide sustained relief in patients with chronic inflammatory pain. Peripheral neuroinflammation (PN) is critical for initiation and development of inflammatory pain. A better understanding of molecular mechanisms underlying PN would facilitate the discovery of new analgesic targets and the development of new therapeutics. Emerging evidence suggests that peripheral sensory neurons are not only responders to painful stimuli, but are also actively engaged in inflammation and immunity, whereas the intrinsic regulatory mechanism is poorly understood. Here we report the expression of proton-selective ion channel Hv1 in peripheral sensory neurons in rodents and humans, which was previously shown as selectively expressed in microglia in mammalian central nervous system. Neuronal Hv1 was up-regulated by PN or depolarizing stimulation, which in turn aggravates inflammation and nociception. Inhibiting neuronal Hv1 genetically or by a newly discovered selective inhibitor YHV98-4 reduced intracellular alkalization and ROS production in inflammatory pain, mitigated the imbalance in downstream SHP-1-pAKT signaling, and also diminished pro-inflammatory chemokine release to alleviate nociception and morphine-induced hyperalgesia and tolerance. Thus, our data reveal neuronal Hv1 as a novel target in analgesia strategy and managing opioids-related side effects.