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Rapid urbanization in China has led to the emergence of the 15-minute commercial circle, but more research is needed on its impact on residents' quality of life. This study aimed to propose construction plans and explore the circle's influence on residents' quality of life in Zhengzhou. Semi-structured interviews with 15 community residents were analyzed using NVivo software. Results indicated positive economic impacts but negative environmental and social impacts. The 15-minute commercial circle plays a dual role, requiring future sustainable and inclusive practices that address income inequality and environmental protection. Limitations include a small sample size and a focus on Zhengzhou. Keywords: 15-minute Commercial Circle; Resident Quality of Life; Urbanization; Zhengzhou eISSN: 2398-4287 © 2023. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open-access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under the responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians/Africans/Arabians) and cE-Bs (Centre for Environment-Behaviour Studies), College of Built Environment, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v8i24.4638

Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Blockchain technology, as an emerging information technology, has attracted much attention. Some luxury e-commerce platforms have focused on the adoption of blockchain technology to provide electronic certificates for consumers, which helps to increase consumers’ trust in luxury goods. However, due to the high authentication cost of blockchain technology, some platforms still adopt manual technology with lower authentication costs to provide paper certificates for consumers. So whether platforms choose to adopt manual technology or blockchain technology for authentication is a problem worthy of attention. In this article, we investigate the choice strategy of authentication technology for luxury e-commerce platform(s) in the monopoly and duopoly markets, respectively. The results show that the choice of authentication technology for platform(s) depends on the cost difference between manual technology authentication and blockchain technology authentication. When the cost difference is small (large), platform(s) should adopt blockchain (manual) technology. In particular, in the duopoly market, the competition between the two platforms will improve their motivation to adopt blockchain technology, but the two platforms may trap into a prisoner's dilemma when they both adopt blockchain technology. Moreover, in the monopoly and duopoly markets, adopting blockchain technology is likely to improve consumer surplus and social welfare at the same time.

Formononetin-inhibited IgE-mediated mast cell activation and attenuated IgE/Ag-induced allergic inflammation by suppressing USP5 or USP13 expression and increasing proteasome-mediated FcεRIγ degradation.

A rock-salt-structured Li-conducting high entropy oxide was prepared and utilized as an active filler in a polyethylene oxide (PEO)-based solid-state composite electrolyte. X-ray diffraction and high-resolution transmission electron microscopy were adopted to analyze the crystal structure of the high entropy oxide containing 20% of Li ions (HL20). The HL20 was crystallized in the

In this study, we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS).Clinical data of 144 patients with pituitary macroadenomas in the same surgical group at the Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed from January 2019 to June 2021. Based on the results of the endocrinological evaluation and MRI examinations before and after surgery, the fluctuation of pituitary function and the extent of resection were analyzed. Multiple Logistic regression analysis was used to determine the predictors affecting postoperative tumor residual.Among the 144 patients with pituitary macroadenomas, 72 (50.0%) were female and 72 (50.0%) were male, the median age was 50 years, 26 (18.1%) had invasiveness grade 0, 46 (31.9%) had grade I, 57 (39.6%) had grade II, and 15 (10.4%) had grade III according to Lu's classification method. Based on observation during surgery, 37 cases (25.7%) had no pseudocapsule, 54 cases (37.5%) had incomplete pseudocapsule, and 53 cases (36.8%) had intact pseudocapsule. In addition, 91 (63.2%) patients had total resection, 39 (27.1%) had subtotal resection, and 14 (9.7%) had partial resection. As for anterior pituitary function, 13 of 19 hypothyroid patients had recovery after surgery, with a remission rate of 68.4%. Eighteen of the 26 decreased cortisol patients got back to normal, with a remission rate of 69.2%. A total of 27 of 51 patients with hypogonadism improved, with a remission rate of 52.9%. Univariate and multivariate analyses indicated that gender, tumor size, and invasiveness were predictors of postoperative residual in patients (P0.05).The results showed that ETTS is an effective treatment modality for restoring the function of pituitary gland of the patients with macroadenomas. Tumor size and invasiveness are predictors of the extent of surgical resection and postoperative residual of macroadenomas.

Poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) has been widely adopted as hole transport material (HTM) in inverted perovskite solar cells (PSCs), due to high optical transparency, good mechanical flexibility, and high thermal stability; however, its acidity and hygroscopicity inevitably hamper the long-term stability of the PSCs and its energy level does not match well with perovskite materials with a relatively low open-circuit voltage. In this work, p-type delafossite CuCrO2 nanoparticles synthesized through hydrothermal method was employed as an alternative HTM for triple cation perovskite [(FAPbI3)0.87(MAPbBr3)0.13]0.92(CsPbI3)0.08 (possessing better photovoltaic performance and stability than conventional CH3NH3PbI3) based inverted PSCs. The average open-circuit voltage of PSCs increases from 908 mV of the devices with PEDOT:PSS HTM to 1020 mV of the devices with CuCrO2 HTM. Ultraviolet photoemission spectroscopy demonstrates the energy band alignment between CuCrO2 and perovskite is better than that between PEDOT:PSS and perovskite, the electrochemical impedance spectroscopy indicates CuCrO2-based PSCs exhibit larger recombination resistance and longer charge carrier lifetime than PEDOT:PSS-based PSCs, which contributes to the high VOC of CuCrO2 HTM-based PSCs.

Two-thirds of patients with type 2 diabetes mellitus have hypertension, and thus the combination of two or more drugs to treat these diseases is common. It has been shown that the combination of metformin and enalapril has beneficial effects, but few studies have evaluated the interactions between these two drugs. This study investigated the effects of enalapril on the pharmacokinetics and urinary excretion of metformin in rats, with a focus on transporter-mediated drug interactions. Rats were dosed orally with metformin alone (100 mg/kg) or in combination with enalapril (4 mg/kg). The concentration of metformin was measured by high performance liquid chromatography and the level of organic cation transporters (rOCTs) and multidrug and toxin excretion protein 1 (rMATE1), which mediate the uptake and efflux of metformin, respectively, were evaluated by immunoblotting. After single and 7-day dosing, the plasma concentration of metformin in the co-administration group was significantly lower than that in the metformin-only group, and the CL/F and urinary excretion were increased in the co-administration group. Enalapril did not affect the K

The latest edition of the WHO classification of the central nervous system was published in 2021. This review summarizes the major revisions to the classification of anterior pituitary tumors. The most important revision involves preferring the terminology of pituitary neuroendocrine tumor (PitNET), even though the terminology of pituitary adenoma (PA) still can be used according to this WHO classification compared to the previous one. Moreover, immunohistochemistry (IHC) examination of pituitary-specific transcription factors (TFs), including PIT1, TPIT, SF-1, GATA2/3, and ERα, is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups. However, TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages, which includes unclassified plurihormonal (PH) tumors and null cell (NC) tumors in this edition. The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors. However, due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA, the application of this new classification system in practice should be further evaluated and validated. Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery, this classification system offers no additional help for neurosurgeons in clinical practice, especially in determining the treatment strategies. Therefore, it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis, as well as pathological diagnosis, thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.

Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics.Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways.A total of 129 differential metabolites (P 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved.Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

Background Keloids represent one extreme of aberrant dermal wound healing and are characterized by fibroblast hyperproliferation and excessive deposition of extracellular matrix. Genetics is a major factor for predisposition to keloids and genome-wide association study has identified a single-nucleotide polymorphism (SNP) rs873549 at 1q41 as a susceptibility locus. The SNP rs873549, and the SNPs in strong linkage disequilibrium (LD) with rs873549, may be involved in keloid development. However, the functional significance of these SNPs in keloid pathogenesis remains elusive. Objectives To investigate the function and mechanism of SNP rs873549 and the SNPs in strong LD with rs873549 in keloids. Methods SNPs in strong LD with rs873549 were analysed using Haploview. The expression levels of the genes near the susceptibility locus were analysed using quantitative real-time polymerase chain reaction. The interaction between rs1348270-containing enhancer and the long noncoding RNA down expressed in keloids (DEIK) (formerly RP11-400N13.1) promoter in fibroblasts was investigated using chromosome conformation capture. The enhancer activity of the rs1348270 locus was evaluated using luciferase reporter assay. Knockdown experiments were used to explore the function of DEIK in keloids. RNA-Seq was performed to investigate the mechanism by which DEIK regulates the expression of collagens POSTN and COMP. Results rs1348270, an enhancer-located SNP in strong LD with rs873549, mediated looping with the promoter of DEIK. The risk variant was associated with decreased enhancer–promoter interaction and DEIK down-expression in keloids. Mechanistically, downregulation of DEIK increased the expression of collagens POSTN and COMP through upregulating BMP2. Furthermore, correlation analysis revealed that DEIK expression was inversely correlated with BMP2, POSTN and COMP expression in both keloid and normal fibroblasts. Conclusions Our findings suggest that the risk variant rs1348270 is located in an enhancer and is associated with the downregulation of DEIK in keloids, and that downregulation of DEIK increases the expression of collagens POSTN and COMP through BMP2 in keloid fibroblasts. These findings will help to provide a more thorough understanding of the role played by genetic factors in keloid development and may lead to new strategies for screening and therapy in keloid-susceptible populations.

The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased yearly, but updated population-based estimates on the incidence of HTG-AP are lacking. Reducing serum triglyceride (TG) levels quickly is crucial in the early treatment of HTG-AP. Decreased serum TG levels are treated by non-invasive methods, which include anti-lipidemic agents, heparin, low-molecular weight heparin, and insulin, and invasive methods, such as blood purification including hemoperfusion (HP), plasmapheresis, and continuous renal replacement therapy. However, authoritative guidelines have not been established. Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP.To evaluate the effect between patients treated with intravenous insulin (INS) and HP to guide clinical treatment.We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP. Propensity score matching was used to compare the clinical outcomes of INS and HP.A total of 371 patients met the HTG-AP criteria. The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years (8.4% in April 2012-March 2013 and 22.3% in April 2020-March 2021). The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years. The amylase level was elevated in 80.1% of patients but was only three times the normal value in 46.9% of patients. The frequency of severe acute pancreatitis (26.9%), organ failure (31.5%), rate of recurrence (32.9%), and mortality (3.0%) of HTG-AP was high. Improved Marshall score, modified computed tomography severity index score, baseline TG, baseline amylase, C-reactive protein (CRP), albumin, aspartate aminotransferase, low-density lipoprotein cholesterol, urea nitrogen, creatinine, calcium, hemoglobin, free triiodothyronine, admission to intensive care unit, and mortality were significantly different between patients with different grades of severity (The incidence of HTG-AP exhibited a significant increase, remarkable severity, and recurrent trend. Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.

RationalePulmonary fibrosis is a devastating lung disease with few therapeutic options. Chitinase 1 (CHIT1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through regulation of Transforming Growth Factor (TGF)-β signaling and effector function. Therefore, CHIT1 is a potential therapeutic target of pulmonary fibrosis.ObjectivesThis study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis.MethodsExtensive screening of small molecule libraries identified the aminoglycoside antibiotic Kasugamycin as a potent CHIT1 inhibitor.Measurements and Main ResultsElevated levels of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In vivo bleomycin- and TGF-β-stimulated murine models of pulmonary fibrosis, Kasugamycin showed impressive anti-fibrotic effects in both preventive and therapeutic conditions. In vitro studies also demonstrated that Kasugamycin inhibits fibrotic macrophage activation, fibroblast proliferation and myofibroblast transformation. Null mutation of transforming growth factor beta associated protein 1 (TGFBRAP1), a recently identified CHIT1 interacting signaling molecule, phenocopied antifibrotic effects of Kasugamycin in in vivo lungs and in vitro fibroblasts responses. Kasugamycin inhibits physical association between CHIT1 and TGFBRAP1, suggesting that antifibrotic effect of Kasugamycin is mediated through regulation of TGFBRAP1, at least in part.ConclusionsThese studies demonstrate that Kasugamycin is a novel CHIT1 inhibitor with strong antifibrotic effect that can be further developed as an effective and safe therapeutic drug for pulmonary fibrosis.

Maternal separation in early life has a detrimental effect on the physiological and biochemical functions of the brains of offspring and can lead to anxiety- and depression-like behaviors later in life. Resveratrol possesses a variety of pharmacological properties, including anti-inflammatory, anxiolytic, and anti-depressive effects. In rodents, resveratrol can attenuate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress, estrogen deficiency, and lipopolysaccharide. However, whether resveratrol administration during adolescence can counteract these behaviors when they result from maternal separation is unknown. In this study, male C57BL/6J mice were separated from their mothers for 4 h per day from postnatal day 2 (PND 2) to PND 21; starting on PND 61, resveratrol was administered intraperitoneally at 40 mg/(kg/day–1) for 4 weeks. At 3 months of age, anxiety and depression-like behaviors were assessed in the male offspring using a series of tasks consisting of an open field test, an elevated plus maze test, a forced swimming test, and a tail suspension test. The hippocampal levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were measured by ELISA, while those of sirtuin 1 (Sirt1) and nuclear factor kappa B (NF-κB) p65 were determined by western blotting and PCR. The results showed that maternal separation led to increased anxiety- and depression-like behaviors, enhanced the levels of pro-inflammatory cytokines, and downregulated the Sirt1/NF-κB signaling pathway in the male offspring; however, these effects could be reversed by treatment with resveratrol. Our findings suggested that resveratrol can ameliorate inflammation and anxiety- and depression-like behaviors induced by maternal separation via the activation of the Sirt1/NF-κB pathway.

Purpose The purpose of this study is to evaluate the effect of graphene, basalt flakes and their synergy on the corrosion resistance of zinc-rich coatings. As the important heavy-duty anticorrosion coatings, zinc-rich coatings provided cathodic protection for the substrate. However, to ensure cathodic protection, a large number of zinc powder made the penetration resistance known as the weakness of zinc-rich coatings. Therefore, graphene and basalt flakes were introduced into zinc-rich coatings to coordinate its cathodic protection and shielding performance. Design/methodology/approach Three kinds of coatings were prepared; they were graphene modified zinc-rich coatings, basalt flakes modified zinc-rich coatings and graphene-basalt flakes modified zinc-rich coatings. The anticorrosion behavior of painted steel was studied by using the electrochemical impedance spectroscopy (EIS) technique in chloride solutions. The equivalent circuit methods were used for EIS analysis to obtain the electrode process structure of the coated steel system. Simultaneously, the corrosion resistance of the three coatings was evaluated by water resistance test, salt water resistance test and salt spray test. Findings The study found that the addition of a small amount of graphene and basalt flakes significantly improved the anticorrosion performance of coatings by enhancing their shielding ability against corrosive media and increasing the resistance of the electrochemical reaction. The modified coatings exhibited higher water resistance, salt water resistance and salt spray resistance. The graphene-basalt flakes modified zinc-rich coatings demonstrated the best anticorrosion effect. The presence of basalt scales and graphene oxide in the coatings significantly reduced the water content and slowed down the water penetration rate in the coatings, thus prolonging the coating life and improving anticorrosion effects. The modification of zinc-rich coatings with graphene and basalt flakes improved the utilization rate of zinc powder and the shielding property of coatings against corrosive media, thus strengthening the protective effect on steel structures and prolonging the service life of anticorrosion coatings. Originality/value The significance of developing graphene-basalt flakes modified zinc-rich coatings lies in their potential to offer superior performance in corrosive environments, leading to prolonged service life of metallic structures, reduced maintenance costs and a safer working environment. Furthermore, such coatings can be used in various industrial applications, including bridges, pipelines and offshore structures, among others.

Axonal fusion is a neuronal repair mechanism that results in the reconnection of severed axon fragments, leading to the restoration of cytoplasmic continuity and neuronal function. While synaptic vesicle recycling has been linked to axonal regeneration, its role in axonal fusion remains unknown. Dynamin proteins are large GTPases that hydrolyze lipid-binding membranes to carry out clathrin-mediated synaptic vesicle recycling. Here, we show that the Caenorhabditis elegans dynamin protein DYN-1 is a key component of the axonal fusion machinery. Animals carrying a temperature-sensitive allele of dyn-1(ky51) displayed wild-type levels of axonal fusion at the permissive temperature (15°C) but presented strongly reduced levels at the restrictive temperature (25°C). Furthermore, the average length of regrowth was significantly diminished in dyn-1(ky51) animals at the restrictive temperature. The expression of wild-type DYN-1 cell-autonomously into dyn-1(ky51) mutant animals rescued both the axonal fusion and regrowth defects. Furthermore, DYN-1 was not required prior to axonal injury, suggesting that it functions specifically after injury to control axonal fusion. Finally, using epistatic analyses and superresolution imaging, we demonstrate that DYN-1 regulates the levels of the fusogen protein EFF-1 post-injury to mediate axonal fusion. Together, these results establish DYN-1 as a novel regulator of axonal fusion.

Background The microrchidia (MORC) proteins are a family of evolutionarily conserved GHKL-type ATPases involved in chromatin compaction and gene silencing. Arabidopsis MORC proteins act in the RNA-directed DNA methylation (RdDM) pathway, where they act as molecular tethers to ensure the efficient establishment of RdDM and de novo gene silencing. However, MORC proteins also have RdDM-independent functions although their underlying mechanisms are unknown. Results In this study, we examine MORC binding regions where RdDM does not occur in order to shed light on the RdDM-independent functions of MORC proteins. We find that MORC proteins compact chromatin and reduce DNA accessibility to transcription factors, thereby repressing gene expression. We also find that MORC-mediated repression of gene expression is particularly important under conditions of stress. MORC-regulated transcription factors can in some cases regulate their own transcription, resulting in feedback loops. Conclusions Our findings provide insights into the molecular mechanisms of MORC-mediated chromatin compaction and transcription regulation.

Fagaceae species dominate forests and shrublands throughout the Northern Hemisphere, and have been used as models to investigate the processes and mechanisms of adaptation and speciation. Compared with the well-studied genus Quercus, genomic data is limited for the tropical-subtropical genus Castanopsis. Castanopsis hystrix is an ecologically and economically valuable species with a wide distribution in the evergreen broad-leaved forests of tropical-subtropical Asia. Here, we present a high-quality chromosome-scale reference genome of C. hystrix, obtained using a combination of Illumina and PacBio HiFi reads with Hi-C technology. The assembled genome size is 882.6 Mb with a contig N50 of 40.9 Mb and a BUSCO estimate of 99.5%, which are higher than those of recently published Fagaceae species. Genome annotation identified 37,750 protein-coding genes, of which 97.91% were functionally annotated. Repeat sequences constituted 50.95% of the genome and LTRs were the most abundant repetitive elements. Comparative genomic analysis revealed high genome synteny between C. hystrix and other Fagaceae species, despite the long divergence time between them. Considerable gene family expansion and contraction were detected in Castanopsis species. These expanded genes were involved in multiple important biological processes and molecular functions, which may have contributed to the adaptation of the genus to a tropical-subtropical climate. In summary, the genome assembly of C. hystrix provides important genomic resources for Fagaceae genomic research communities, and improves understanding of the adaptation and evolution of forest trees.

Early-life stress disrupts central nervous system development and increases the risk of neuropsychiatric disorder in offspring based on rodent studies. Maternal sleep deprivation (MSD) in rodents has also been associated with depression and cognitive decline in adult offspring. However, it is not known whether these issues persist into old age. Environmental enrichment is a non-pharmacological intervention with proven benefits in improving depression and cognitive impairment; however, it is unclear whether these benefits hold for aging mice following MSD exposure. The aim of this study was to explore the effects of MSD on depression and cognition in elderly offspring CD-1 mice and to determine whether long-term environmental enrichment could alleviate these effects by improving neuroinflammation and synaptic plasticity. The offspring mice subjected to MSD were randomly assigned to either a standard environment or an enriched environment. At 18 months of age, the forced swimming and tail suspension tests were used to evaluated depression-like behaviors, and the Morris water maze test was used to evaluate cognitive function. The expression levels of hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins were also measured. MSD increased depression-like behaviors and impaired cognition function in aging CD-1 offspring mice. These effects were accompanied by upregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-α expression, and downregulated brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin expression in the hippocampus. All of these changes were reversed by long-term exposure to an enriched environment. These findings suggest that MSD exerts long-term effects on the behaviors of offspring in mice, leading to depression and cognitive impairment in older age. Importantly, long-term environmental enrichment could counteract the behavior difficulties induced by MSD through improving hippocampal proinflammatory cytokines and synaptic plasticity-associated proteins.

Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.

In humans and animals, exposure to changes in internal or external environments causes acute stress, which changes sleep and enhances neurochemical, neuroendocrine, and sympathetic activities. Repeated stress responses play an essential role in the pathogenesis of psychiatric diseases and sleep disorders. However, the underlying mechanism of sleep changes and anxiety disorders in response to acute stress is not well established. In the current study, the effects of restraint stress (RS) on anxiety and sleep–wake cycles in mice were investigated. We found that after RS, the mice showed anxiety-like behavior after RS manipulation and increased the amounts of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in the dark period. The increase in sleep time was mainly due to the increased number of episodes of NREM and REM sleep during the dark period. In addition, the mice showed an elevation of the EEG power spectrum of both NREM and REM sleep 2 h after RS manipulation. There was a significant reduction in the EEG power spectrum of both NREM and REM sleep during the darkperiod in the RS condition. The expression of the c-Fos protein was significantly increased in the parabrachial nucleus, bed nucleus of the stria terminalis, central amygdala, and paraventricular hypothalamus by RS manipulation. Altogether, the findings from the present study indicated that neural circuits from the parabrachial nucleus might regulate anxiety and sleep responses to acute stress, and suggest a potential therapeutic target for RS induced anxiety and sleep alterations.

Highly sensitive gas sensors with remarkably low detection limits are attractive for diverse practical application fields including real-time environmental monitoring, exhaled breath diagnosis, and food freshness analysis. Among various chemiresistive sensing materials, noble metal-decorated semiconducting metal oxides (SMOs) have currently aroused extensive attention by virtue of the unique electronic and catalytic properties of noble metals. This review highlights the research progress on the designs and applications of different noble metal-decorated SMOs with diverse nanostructures (e.g., nanoparticles, nanowires, nanorods, nanosheets, nanoflowers, and microspheres) for high-performance gas sensors with higher response, faster response/recovery speed, lower operating temperature, and ultra-low detection limits. The key topics include Pt, Pd, Au, other noble metals (e.g., Ag, Ru, and Rh.), and bimetals-decorated SMOs containing ZnO, SnO2, WO3, other SMOs (e.g., In2O3, Fe2O3, and CuO), and heterostructured SMOs. In addition to conventional devices, the innovative applications like photo-assisted room temperature gas sensors and mechanically flexible smart wearable devices are also discussed. Moreover, the relevant mechanisms for the sensing performance improvement caused by noble metal decoration, including the electronic sensitization effect and the chemical sensitization effect, have also been summarized in detail. Finally, major challenges and future perspectives towards noble metal-decorated SMOs-based chemiresistive gas sensors are proposed.

The formation of linolenic (Ln) and linoleic (L) acyl oxidation products during storage of flaxseed oil (FO)-in-water emulsions was monitored using proton nuclear magnetic resonance (

Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.

Tuft cells are a rare chemosensory lineage that coordinates immune and neural responses to foreign pathogens in mucosal tissues(1). Recent studies have also revealed tuft-cell-like human tumours(2,3), particularly as a variant of small-cell lung cancer. Both normal and neoplastic tuft cells share a genetic requirement for the transcription factor POU2F3 (refs. (2,4)), although the transcriptional mechanisms that generate this cell type are poorly understood. Here we show that binding of POU2F3 to the uncharacterized proteins C11orf53 and COLCA2 (renamed here OCA-T1/POU2AF2 and OCA-T2/POU2AF3, respectively) is critical in the tuft cell lineage. OCA-T1 and OCA-T2 are paralogues of the B-cell-specific coactivator OCA-B; all three proteins are encoded in a gene cluster and contain a conserved peptide that binds to class II POU transcription factors and a DNA octamer motif in a bivalent manner. We demonstrate that binding between POU2F3 and OCA-T1 or OCA-T2 is essential in tuft-cell-like small-cell lung cancer. Moreover, we generated OCA-T1-deficient mice, which are viable but lack tuft cells in several mucosal tissues. These findings reveal that the POU2F3–OCA-T complex is the master regulator of tuft cell identity and a molecular vulnerability of tuft-cell-like small-cell lung cancer.