Nonlinear association between atherogenic index of plasma and type 2 diabetes mellitus in overweight and obesity patients: evidence from Chinese medical examination data.

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.

Glia-derived adenosine in the ventral hippocampus drives pain-related anxiodepression in a mouse model resembling trigeminal neuralgia.

Glial activation and dysregulation of adenosine triphosphate (ATP)/adenosine are involved in the neuropathology of several neuropsychiatric illnesses. The ventral hippocampus (vHPC) has attracted considerable attention in relation to its role in emotional regulation. However, it is not yet clear how vHPC glia and their derived adenosine regulate the anxiodepressive-like consequences of chronic pain. Here, we report that chronic cheek pain elevates vHPC extracellular ATP/adenosine in a mouse model resembling trigeminal neuralgia (rTN), which mediates pain-related anxiodepression, through a mechanism that involves synergistic effects of astrocytes and microglia. We found that rTN resulted in robust activation of astrocytes and microglia in the CA1 area of the vHPC (vCA1). Genetic or pharmacological inhibition of astrocytes and connexin 43, a hemichannel mainly distributed in astrocytes, completely attenuated rTN-induced extracellular ATP/adenosine elevation and anxiodepressive-like behaviors. Moreover, inhibiting microglia and CD39, an enzyme primarily expressed in microglia that degrades ATP into adenosine, significantly suppressed the increase in extracellular adenosine and anxiodepressive-like behaviors. Blockade of the adenosine A2A receptor (A2AR) alleviated rTN-induced anxiodepressive-like behaviors. Furthermore, interleukin (IL)-17A, a pro-inflammatory cytokine probably released by activated microglia, markedly increased intracellular calcium in vCA1 astrocytes and triggered ATP/adenosine release. The astrocytic metabolic inhibitor fluorocitrate and the CD39 inhibitor ARL 67156, attenuated IL-17A-induced increases in extracellular ATP and adenosine, respectively. In addition, astrocytes, microglia, CD39, and A2AR inhibitors all reversed rTN-induced hyperexcitability of pyramidal neurons in the vCA1. Taken together, these findings suggest that activation of astrocytes and microglia in the vCA1 increases extracellular adenosine, which leads to pain-related anxiodepression via A2AR activation. Approaches targeting astrocytes, microglia, and adenosine signaling may serve as novel therapies for pain-related anxiety and depression.

Enhanced Stability and Catalytic Activity of a Nanocatalyst with Reusable Ionic Liquid Hydrogels for the Reduction of Organic Pollutants.

Nitroaromatic compounds have a wide range of applications. However, they pose a significant threat to both the environment and human health. Ionic liquid hydrogels (ILs-gels) have emerged as a cost-effective and environmentally friendly option for various applications. However, conventional ILs-gels are known to possess mechanical flaws or defects. The procedure utilized a facile synthesis route that involved the polymerization of acrylamide (AM) and ionic liquids (ILs) to create a novel candidate for nanoparticle absorption. This study resolved this issue by creating toughened hydrophobic combined hydrogels synthesized through the addition of SiO2@poly(butyl acrylate) core-shell inorganic-organic hybrid latex particles (SiO2@PBA) to the AM-ILs mixture. The SiO2@PBA particles were chosen to provide the hydrogels with exceptional stretchability (up to 4050% strain) and high mechanical properties (tensile strength of 126 kPa) by acting as both a nanotoughener and a cross-linking point for hydrophobic linkage. Additionally, the P(AM/ILs)-SiO2@PBA hydrogel served as a template for the in situ and stable formation of palladium (Pd) nanoparticles. By incorporation of these Pd nanoparticles as catalysts into P(AM/ILs)-SiO2@PBA hydrogel carriers, the resulting P(AM/ILs)-SiO2@PBA/Pd hydrogels exhibited the ability to catalyze the degradation of p-nitrophenol. Remarkably, even after 15 applications, the efficiency of the degradation process remained consistently above 90%. Thus, the innovative SiO2@PBA toughened ILs-hydrogel design strategy can be utilized to develop robust and stretchable hydrogel materials for catalytic use in the sewage disposal industry.

Yes-Associated Protein Targets the Transforming Growth Factor ß Pathway to Mediate High-Fat/High-Sucrose Diet-induced Arterial Stiffness.

BACKGROUND: Metabolic syndrome is related to cardiovascular diseases, which is attributed in part, to arterial stiffness; however, the mechanisms remain unclear. The present study aimed to investigate the molecular mechanisms of metabolic syndrome-induced arterial stiffness and to identify new therapeutic targets. METHODS: Arterial stiffness was induced by high-fat/high-sucrose diet in mice, which was quantified by Doppler ultrasound. Four-dimensional label-free quantitative proteomic analysis, affinity purification and mass spectrometry, and immunoprecipitation and GST (glutathione S-transferase) pull-down experiments were performed to explore the mechanism of YAP (Yes-associated protein)-mediated TGF (transforming growth factor) ß pathway activation. RESULTS: YAP protein was upregulated in the aortic tunica media of mice fed a high-fat/high-sucrose diet for 2 weeks and precedes arterial stiffness. Smooth muscle cell-specific YAP knockdown attenuated high-fat/high-sucrose diet-induced arterial stiffness and activation of TGFß-Smad2/3 signaling pathway in arteries. By contrast, Myh11CreERT2-YapTg mice exhibited exacerbated high-fat/high-sucrose diet-induced arterial stiffness and enhanced TGFß-activated Smad2/3 phosphorylation in arteries. PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) was identified as a YAP-bound phosphatase that translocates into the nucleus to dephosphorylate Smads (mothers against decapentaplegic homologs) in response to TGFß. This process was inhibited by YAP through removal of the K63-linked ubiquitin chain of PPM1B at K326. CONCLUSIONS: This study provides a new mechanism by which smooth muscle cell YAP regulates the TGFß pathway and a potential therapeutic target in metabolic syndrome-associated arterial stiffness.

Synthesis of 2,3-Dialkyl-5-hydroxybenzofurans via a One-pot, Three-step Reaction Sequence of 2-Monosubstituted 1,3-Diketones and 1,4-Benzoquinones.

An economical one-pot, three-step reaction sequence of readily available 2-monosubstituted 1,3-diketones and 1,4-benzoquinones has been explored for the facile access of 2,3-dialkyl-5-hydroxybenzofurans. By using cheap K2CO3 and conc. HCl as the reaction promoters, the reaction occurs smoothly via sequential Michael addition, aromatization, retro-Claisen, deacylation, hemiketalization, and dehydration processes under mild conditions in a practical manner. Additionally, an interesting phenomenon was observed during the derivatization studies, where the dihydroquinoline was converted into tetrahydroquinoline and quinoline products, respectively, via a disproportionation process.

Course and predictors of supportive care needs among colorectal cancer survivors with ostomies: a longitudinal study.

PURPOSE: Although there is a growing emphasis on supportive care for cancer patients, those with colorectal cancer (CRC) who have ostomies require special attention in terms of their physical, psychological, spiritual, and social needs. However, there has been a lack of significant progress in meeting the supportive care needs of CRC survivors with ostomies. To bridge this gap, we conducted a prospective longitudinal study to track the trends in supportive care needs among CRC survivors with ostomies and identify any predictors over 6-month period. METHODS: A prospective longitudinal study was conducted at the wound and stoma clinic of Dalian University Affiliated Xinhua Hospital, focusing on CRC survivors with ostomies. A total of 143 participants completed self-report questionnaires on the 34-item Short-Form Supportive Care Needs Survey (SCNS-SF34-C (Mandarin)) and stoma complications at the first, third, and sixth month after surgery. ANOVA with repeated measure was utilized to assess the course of supportive care needs, with Generalized Estimating Equation (GEE) applied to identify predictors of SCNS. RESULTS: The supportive care needs and five dimensions scores were statistically significant at three time points (P < 0.05). The ratings of patients at the first, third, and sixth month after surgery revealed a decreasing trend in the scores for patient care and support, psychological needs, physical and daily living needs, and health system and information needs. However, the score for sexual needs showed an increased tendency. Higher levels supportive care needs were generally connected with a short duration after ostomy, high income level, resident medical insurance, spouse caregiver, other chronic disease, and stoma complications. CONCLUSIONS: Survivors' supportive care needs showed a dynamic trend over 6 months after surgery. Through three rounds, the primary needs were health system and information needs. It is recommended to integrate interdisciplinary health professionals and establish a comprehensive support and care system to effectively meet the diverse needs at different stages. Priority should be given to individuals with ostomies during the first and third month after surgery, particularly those with higher income levels, employee medical insurance, spouse caregivers, other chronic diseases, and stoma complications.

Association between high-density lipoprotein cholesterol and lumbar bone mineral density in Chinese: a large cross-sectional study.

BACKGROUND: The association between lipid and bone metabolism, particularly the role of high-density lipoprotein cholesterol (HDL-C) in regulating bone mineral density (BMD), is of significant interest. Despite numerous studies, findings on this relationship remain inconclusive, especially since evidence from large, sexually diverse Chinese populations is sparse. This study, therefore, investigates the correlation between HDL-C and lumbar BMD in people of different genders using extensive population-based data from physical examinations conducted in China. METHODS: Data from a cross-sectional survey involving 20,351 individuals aged > = 20 years drawn from medical records of health check-ups at the Health Management Centre of the Henan Provincial People's Hospital formed the basis of this study. The primary objective was to determine the correlation between HDL-C levels and lumbar BMD across genders. The analysis methodology included demographic data analysis, one-way ANOVA, subgroup analyses, multifactorial regression equations, smoothed curve fitting, and threshold and saturation effect analyses. RESULTS: Multifactorial regression analysis revealed a significant inverse relationship between HDL-C levels and lumbar BMD in both sexes, controlling for potential confounders (Male: ß = -8.77, 95% CI -11.65 to -5.88, P < 0.001; Female: ß = -4.77, 95% CI -8.63 to -0.90, P = 0.015). Subgroup and threshold saturation effect analyses indicated a stronger association in males, showing that increased HDL-C correlates with reduced lumbar BMD irrespective of age and body mass index (BMI). The most significant effect was observed in males with BMI > 28 kg/m2 and HDL-C > 1.45 mmol/L and in females with a BMI between 24 and 28 kg/m2. CONCLUSION: Elevated HDL-C is associated with decreased bone mass, particularly in obese males. These findings indicate that individuals with high HDL-C levels should receive careful clinical monitoring to mitigate osteoporosis risk. TRIAL REGISTRATION: The research protocol received ethics approval from the Ethics Committee at Beijing Jishuitan Hospital, in conformity with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are a contribution of the China Health Quantitative CT Big Data Research team, registered at clinicaltrials.gov (code: NCT03699228).

Expression and Clinical Significance of MAGE-A Proteins and mRNA in Lung Cancer Patients: A Retrospective Study.

Objective: This study investigated the expression and clinical significance of Melanoma Associated Antigen (MAGE)-A proteins and mRNA in patients with non-small cell lung cancer (NSCLC). Methods: A retrospective study was conducted, and we selected a cohort of 88 NSCLC patients treated at our hospital from January 2015 to January 2020. Adjacent tissues were chosen as controls. The expression of MAGE-A proteins in lung cancer and adjacent tissues was assessed via Western blot, while MAGE-As mRNA expression was measured using RT-PCR. Results: The relative expression levels of MAGE-A proteins and mRNA in NSCLC tissues were significantly higher than those in adjacent tissues (P < .05), with values of (0.343 ± 0.101) and (0.728 ± 0.112), respectively. Furthermore, MAGE-As protein expression was significantly higher in stage III - IV lung cancer compared to stage I - II (P < .05). No significant differences were observed in MAGE-A protein expression concerning gender, age, tumor diameter, pathological type, and differentiation degree (P > .05). The relative expression of MAGE-As mRNA was significantly higher in clinical stage III - IV and moderately differentiated lung cancer tissues compared to stage I - II and well-differentiated tissues (P < .05). No significant differences were found in MAGE-As mRNA expression concerning gender, age, tumor diameter, and pathological type (P > .05). Patients with high MAGE-As mRNA expression had a significantly shorter median overall survival of 33 months (95% CI: 31.64-34.36) compared to those with low MAGE-As mRNA expression (P < .05). However, no significant difference was observed in median overall survival between patients with high and low MAGE-As protein expression (P > .05). Conclusions: In NSCLC, the up-regulation of MAGE-A proteins and mRNA is associated with clinical stage and differentiation degree, warranting further investigation.

Screening of candidate genes related to differences in growth and development between Chinese indigenous and Western pig breeds.

Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.

High Strength, Conductivity, and Bacteriostasis of the P(AM-co-AA)/Chitosan Quaternary Ammonium Salt Composite Hydrogel through Ionic Crosslinking and Hydrogen Bonding.

Traditional hydrogels with a single-crosslinked network structure suffer from poor stretchability, low sensitivity, and easy contamination, which seriously affect their practical application in the strain sensor field. To overcome these shortcomings, herein, a multiphysical crosslinking strategy (ionic crosslinking and hydrogen bonding) was designed to prepare a hydrogel strain sensor based on chitosan quaternary ammonium salt (HACC)-modified P(AM-co-AA) (acrylamide-co-acrylic acid copolymer) hydrogels. The ionic crosslinking for the double-network P(AM-co-AA)/HACC hydrogels was achieved by an immersion method with Fe3+ as crosslinking sites, which crosslinked with the amino group (-NH2) on HACC and the carboxyl group (-COOH) on P(AM-co-AA) and enabled the hydrogels to recover and reorganize rapidly, resulting in a hydrogel-based strain sensor with excellent tensile stress (3 MPa), elongation (1390%), elastic modulus (0.42 MPa), and toughness (25 MJ/m3). In addition, the prepared hydrogel exhibited high electrical conductivity (21.6 mS/cm) and sensitivity (GF = 5.02 at 0-20% strain, GF = 6.84 at 20-100% strain, and GF = 10.27 at 100-480% strain). Furthermore, the introduction of HACC endowed the hydrogel with excellent antibacterial properties (up to 99.5%) and excellent antibacterial activity against bacteria of three forms, bacilli, cocci, and spores. The flexible, conductive, and antibacterial hydrogel can be applied as a strain sensor for real-time detection of human motions such as joint movement, speech, and respiration, which exhibits a promising application prospect in wearable devices, soft robotic systems, and other fields.

Carbon Nanotubes and Silica@polyaniline Core-Shell Particles Synergistically Enhance the Toughness and Electrical Conductivity in Hydrophobic Associated Hydrogels.

Soft, conductive, and stretchable sensors are highly desirable in many applications, including artificial skin, biomonitoring patches, and so on. Recently, a combination of good electrical and mechanical properties was regarded as the most important evaluation criterion for judging whether hydrogel sensors are suitable for practical applications. Herein, we demonstrate a novel carboxylated carbon nanotube (MWCNT-COOH)-embedded P(AM/LMA)/SiO2@PANI hydrogel. The hydrogel benefits from a double-network structure (hydrogen bond cross-linking and hydrophobic connectivity network) due to the role of MWCNT-COOH and SiO2@PANI as cross-linkers, thus resulting in tough composite hydrogels. The obtained P(AM/LMA)/SiO2@PANI/MWCNT-COOH hydrogels exhibited high tensile strength (1939 kPa), super stretchability (3948.37%), and excellent strain sensitivity (gauge factor = 11.566 at 100-1100% strain). Obviously, MWCNT-COOH not only improved the electrical conductivity but also enhanced the mechanical properties of the hydrogel. Therefore, the integration of MWCNT-COOH and SiO2@PANI-based hydrogel strain sensors will display broad application in sophisticated intelligence, soft robotics, bionic prosthetics, personal health care, and other fields using inexpensive, green, and easily available biomass.

Association between total cholesterol and lumbar bone density in Chinese: a study of physical examination data from 2018 to 2023.

BACKGROUND: The impact of total cholesterol (TC) on lumbar bone mineral density (BMD) is a topic of interest. However, empirical evidence on this association from demographic surveys conducted in China is lacking. Therefore, this study aimed to examine the relationship between serum TC and lumbar BMD in a sample of 20,544 Chinese adults between the ages of 20 and 80 years over a period of 5 years, from February 2018 to February 2023. Thus, we investigated the effect of serum TC level on lumbar BMD and its relationship with bone reduction in a Chinese adult population. METHODS: This cross-sectional study used data obtained from the Department of Health Management at Henan Provincial People's Hospital between February 2018 and February 2023. The aim of this study was to examine the correlation between serum TC and lumbar BMD in individuals of different sexes. The research methodology encompassed population description, analysis of stratification, single-factor and multiple-equation regression analyses, smooth curve fitting, and analysis of threshold and saturation effects. The R and EmpowerStats software packages were used for statistical analysis. RESULTS: After adjusting for confounding variables, a multiple linear regression model revealed a significant correlation between TC and lumbar BMD in men. In subgroup analysis, serum TC was found to have a positive association with lumbar BMD in men, specifically those aged 45 years or older, with a body mass index (BMI) ranging from 24 to 28 kg/m2. A U-shaped correlation arose between serum TC and lumbar BMD was detected in women of different ages and BMI, the inflection point was 4.27 mmol/L for women aged ≥ 45 years and 4.35 mmol/L for women with a BMI of ≥ 28 kg/m2. CONCLUSION: In this study, Chinese adults aged 20-80 years displayed different effects of serum TC on lumbar BMD in sex-specific populations. Therefore, monitoring BMI and serum TC levels in women of different ages could prevent osteoporosis and osteopenia. TRIAL REGISTRATION: The research protocol was approved by the Ethics Committee of Beijing Jishuitan Hospital, in accordance with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are part of the China Health Quantitative CT Big Data Research team, which has been registered at clinicaltrials.gov (code: NCT03699228).

Genome-Wide Analysis of the MADS-Box Gene Family in Hibiscus syriacus and Their Role in Floral Organ Development.

Hibiscus syriacus belongs to the Malvaceae family, and is a plant with medicinal, edible, and greening values. MADS-box transcription factor is a large family of regulatory factors involved in a variety of biological processes in plants. Here, we performed a genome-wide characterization of MADS-box proteins in H. syriacus and investigated gene structure, phylogenetics, cis-acting elements, three-dimensional structure, gene expression, and protein interaction to identify candidate MADS-box genes that mediate petal developmental regulation in H. syriacus. A total of 163 candidate MADS-box genes were found and classified into type I (Mα, Mß, and Mγ) and type II (MIKC and Mδ). Analysis of cis-acting elements in the promoter region showed that most elements were correlated to plant hormones. The analysis of nine HsMADS expressions of two different H. syriacus cultivars showed that they were differentially expressed between two type flowers. The analysis of protein interaction networks also indicated that MADS proteins played a crucial role in floral organ identification, inflorescence and fruit development, and flowering time. This research is the first to analyze the MADS-box family of H. syriacus and provides an important reference for further study of the biological functions of the MADS-box, especially in flower organ development.

Paper-Based Bipolar Electrode Electrochemiluminescence Platform Combined with Pencil-Drawing Trace for the Detection of M.SssI Methyltransferase.

Herein, a hand-drawing paper-based bipolar electrode (BPE) electrochemiluminescence (ECL) platform for M.SssI methyltransferase (M.SssI MTase) assay was proposed via employing high electrocatalytic Pt@CeO2 as an ECL co-reaction accelerator and pencil-drawing graphite electric circuits as wires and electrodes. Notably, the introduction of pencil-drawing trace not only simplified the manufacturing process but also reduced the cost and saved fabricating time. Meanwhile, Pt@CeO2 with good electrocatalytic activity and satisfactory chemical stability was used at the anode of the closed BPE-ECL device to accelerate the oxidation rate of uric acid. Due to the balanced charges of the bipolar electrode, the ECL response of the MnS: CdS@ZnS/S2O82- system emitted on the cathode was enhanced. In situ growth of gold nanoparticles in the two electrode areas was convenient for DNA immobilization. With the above points in mind, the specific DNA double strands functionalized via Pt@CeO2 were employed to identify M.SssI MTase. The unmethylated DNA double strands were cut by HpaII endonuclease, resulting in the quenching of the ECL signal. Under the optimal conditions, sensitive detection of M.SssI MTase in a wide linear range of 0.01-100 U·mL-1 with a satisfactory detection limit of 0.008 U·mL-1 was realized. The reliable and versatile BPE-ECL tool for the determination of M.SssI MTase with easy-to-operate pencil-drawing traces and independent solution systems provides a new opportunity to develop paper-based devices applied in early disease diagnosis and pathogenesis research.

A Top-Down Templating Strategy toward Functional Porous Carbons.

Nanostructured carbon materials with high porosity and desired chemical functionalities are of immense interest because of their wide application potentials in catalysis, environment, and energy storage. Herein, a top-down templating strategy is presented for the facile synthesis of functional porous carbons, based on the direct carbonization of diverse organic precursors with commercially available metal oxide powders. During the carbonization, the metal oxide powders can evolve into nanoparticles that serve as in situ templates to introduce nanopores in carbons. The porosity and heteroatom doping of the prepared carbon materials can be engineered by varying the organic precursors and/or the metal oxides. It is further demonstrated that the top-down templating strategy is applicable to prepare carbon-based single-atom catalysts with iron-nitrogen sites, which exhibit a high power density of 545 mW cm-2 in a H2 -air proton exchange membrane fuel cell.

Combination of ruxolitinib with ABT-737 exhibits synergistic effects in cells carrying concurrent JAK2V617F and ASXL1 mutations.

The V617F mutation in Janus kinase 2 is considered one of the driver mutations leading to Philadelphia-negative myeloproliferative neoplasms (MPNs). Concurrent JAK2V617F and ASXL1 mutations accelerate the progression of myelofibrosis in patients with MPNs. Few therapies are currently available for patients with these two mutations. In our study, the combination of ruxolitinib with ABT-737 was evaluated in cells carrying JAK2V617F and ASXL1 double mutations. RNA sequencing indicated overactivated oxidative phosphorylation in JAK2V617F;Asxl1+/- cKit+ cells. The cell line model with JAK2V617F and ASXL1 double mutations (HEL-AKO cells) also exhibited dysregulated mitochondrial function with an increase in the reactive oxygen species levels and a decrease in the ATP levels. The colony growth inhibition rates of cells with JAK2V617F and ASXL1 double mutations were significantly lower than those of cells with only the JAK2V617F mutation. Combined treatment with ruxolitinib and ABT-737 promoted apoptosis and inhibited the proliferation of HEL-AKO cells. Cotreatment with the two drugs also inhibited the growth of bone marrow mononuclear cells isolated from patients with concurrent JAK2V617F and ASXL1 mutations. In conclusion, we provide preclinical evidence showing that the combination of ruxolitinib and ABT-737 is a promising therapeutic strategy for MPN patients with concurrent JAK2V617F and ASXL1 mutations.

Roles of sirtuin family members in chronic obstructive pulmonary disease.

The globally increasing annual incidence of chronic obstructive pulmonary disease (COPD), a common chronic disease, poses a serious risk to public health. Although the exact mechanism underlying the pathogenesis of COPD remains unclear, a large number of studies have shown that its pathophysiology and disease course are closely related to oxidative stress, inflammation, apoptosis, autophagy, and aging. The key players involved in COPD include the sirtuin family of NAD-dependent deacetylases that comprise seven members (SIRT1-7) in mammals. Sirtuins play an important role in metabolic diseases, cell cycle control, proliferation, apoptosis, and senescence. Owing to differences in subcellular localization, sirtuins exhibit anisotropy. In this narrative review, we discuss the roles and molecular pathways of each member of the sirtuin family involved in COPD to provide novel insights into the prevention and treatment of COPD and how sirtuins may serve as adjuvants for COPD treatment.

Three IRF4 paralogs act as negative regulators of type â IFN responses in yellow catfish (Pelteobagrus fulvidraco).

IRF4 is a master member of the interferon regulatory factor (IRF) family playing vital regulatory roles in immune system development and function. Tetrapods have a single-copy IRF4 gene, while teleosts harbor duplicated IRF4 genes. This work describes three IRF4 paralogs from yellow catfish (Pelteobagrus fulvidraco), designated PfIRF4A, PfIRF4B and PfIRF4B-like. These genes all contain a typical IRF structural architecture. Phylogenic and synteny analyses indicate that they should arise from the teleost-specific whole-genome duplication. PfIRF4 genes are abundantly expressed in the immune-related tissues and upregulated by PolyI:C, LPS, and Edwardsiella ictaluri. Ectopic expression of these genes inhibits the activation of fish type Ⅰ IFN promoters and downregulates the transcription levels of IFN-responsive genes, thus allowing the efficient replication of a fish rhabdovirus, spring viremia of carp virus (SVCV). PfIRF4s possess a repressive effect on MyD88-mediated activation of IFN and NF-κB. Some differences are observed between each individual paralog. PfIRF4B is the main form expressed across the tissues and the most up-regulated one after pathogen induction. It exerts a stronger inhibitory effect on IFN antiviral response than the other two paralogs. PfIRF4A and PfIRF4B-like are primarily present in the nucleus, while PfIRF4B displays colocalization and direct associations with MyD88 in the cytoplasm. Overall, the data demonstrate that three PfIRF4 paralogs show shared and individual functional properties in the negative regulation of type Ⅰ IFN response.

Melting at Mg/Al interface in Mg-Al-Mg nanolayer by molecular dynamics simulations.

The melting at the magnesium/aluminum (Mg/Al) interface is an essential step during the fabrications of Mg-Al structural materials and biomaterials. We carried out molecular dynamics simulations on the melting at the Mg/Al interface in a Mg-Al-Mg nanolayer via analyzing the changes of average atomic potential energy, Lindemann index, heat capacity, atomic density distribution and radial distribution function with temperature. The melting temperatures (Tm) of the nanolayer and the slabs near the interface are significantly sensitive to the heating rate (vh) over the range ofvh ≤ 4.0 K ps-1. The distance (d) range in which the interface affects the melting of the slabs is predicted to be (-98.2, 89.9) Å atvh→0,if the interface is put atd = 0 and Mg (Al) is located at the left (right) side of the interface. TheTmof the Mg (Al) slab just near the interface (e.g.d=4.0Å) is predicted to be 926.8 K (926.6 K) atvh→0,with 36.9 K (37.1 K) below 963.7 K for the nanolayer. These results highlight the importance of regional research on the melting at an interface in the nanolayers consisting of two different metals.

Ag nanozyme strengthened by folic acid: Superior peroxidase-mimicking activity and application for visual monitoring of dopamine.

Dopamine (DA) is an important neurotransmitter; however, any excess or deficiency of DA will cause several diseases in humans. To monitor DA efficiently and conveniently, a Ag nanozyme strengthened by bioactive folic acid (FA@AgNPs) was developed by homogeneous redox assembly. After the microstructure and performance were characterized in detail, it was noted that the proposed FA@AgNPs possessed superior peroxidase-like activity due to the ultra-small Ag nanoparticles and multiple amino, hydroxyl, and aromatic rings in FA. FA@AgNPs accelerated the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) with a low Michaelis constant (Km) and high maximal reaction rate (Vmax). Importantly, the characteristic absorbance intensity of FA@AgNPs-TMB-H2O2 at 652 nm (A652) was exclusively deteriorated in the presence of trace DA, accompanied by a visual color change from blue to colorless. Under the optimized conditions (pH 4.0, 300 µL 1.5 mM TMB, 300 µL 1.0 M H2O2 and incubated for 30 min at room temperature), there expressed an excellent linear relationship between lgA0/A652 and cDA from 1.0 ×10-8 to 6.67×10-6 mol/L with a low limit detection of 7.1×10-10 mol/L (S/N=3). When applied for monitoring of DA in real fruit juice and pharmaceutical samples, the recovery was between 96.6% and 104.9%, with RSD less than 2.2%. The enhanced peroxidase-like activity of the FA@AgNP system and its selective recognition mechanism for DA are also proposed.