Identification of 3-(9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acids as promising DNMT1 inhibitors.

DNA methyltransferase 1 (DNMT1) is the primary enzyme responsible for maintaining DNA methylation patterns during cellular division, crucial for cancer development by suppressing tumor suppressor genes. In this study, we retained the phthalimide structure of N-phthaloyl-l-tryptophan (RG108) and substituted its indole ring with nitrogen-containing aromatic rings of varying sizes. We synthesized 3-(9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acids and confirmed them as DNMT1 inhibitors through protein affinity testing, radiometric method using tritium labeled SAM, and MTT assay. Preliminary structure-activity relationship analysis revealed that introducing substituents on the carbazole ring could enhance inhibitory activity, with S-configuration isomers showing greater activity than R-configuration ones. Notably, S-3-(3,6-di-tert-butyl-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7r-S) and S-3-(1,3,6-trichloro-9H-carbazol-9-yl)-2-(1,3-dioxoisoindolin-2-yl)propanoic acid (7t-S) exhibited significant DNMT1 enzyme inhibition activity, with IC50 values of 8.147 µM and 0.777 µM, respectively (compared to RG108 with an IC50 above 250 µM). Moreover, they demonstrated potential anti-proliferative activity on various tumor cell lines including A2780, HeLa, K562, and SiHa. Transcriptome analysis and KEGG pathway enrichment of K562 cells treated with 7r-S and 7t-S identified differentially expressed genes (DEGs) related to apoptosis and cell cycle pathways. Flow cytometry assays further indicated that 7r-S and 7t-S induce apoptosis in K562 cells and arrest them in the G0/G1 phase in a concentration-dependent manner. Molecular docking revealed that 7t-S may bind to the methyl donor S-adenosyl-l-methionine (SAM) site in DNMT1 with an orientation opposite to RG108, suggesting potential for deeper penetration into the DNMT1 pocket and laying the groundwork for further modifications.

Porous gradient hydrogel promotes skin regeneration by angiogenesis.

The skin has a multilayered structure, and deep-seated injuries are exposed to external microbial invasion and in vivo microenvironmental destabilization. Here, a bilayer bionic skin scaffold (Bilayer SF) was developed based on methacrylated sericin protein to mimic the skin's multilayered structure and corresponding functions. The outer layer (SF@TA), which mimics the epidermal layer, was endowed with the function of resisting external bacterial and microbial invasion using a small pore structure and bio-crosslinking with tannic acid (TA). The inner layer (SF@DA@Gel), which mimics the dermal layer, was used to promote cellular growth using a large pore structure and introducing dopamine (DA) to regulate the wound microenvironment. This Bilayer SF showed good mechanical properties and structural stability, satisfactory antioxidant and promote cell proliferation and migration abilities. In vitro studies confirmed the antimicrobial properties of the outer layer and the pro-angiogenic ability of the inner layer. In vivo animal studies demonstrated that the bilayer scaffolds promoted collagen deposition, neovascularization, and marginal hair follicle formation, which might be a promising new bionic skin scaffold.

Seeing what you believe: recognition memory for evolutionary tree structure is affected by students' misconceptions.

Peoples' recognition memory for pictorial stimuli is extremely good. Even complex scientific visualisations are recognised with a high degree of accuracy. The present research examined recognition memory for the branching structure of evolutionary trees. This is an educationally consequential topic due to the potential for contamination from students' misconceptions. The authors created six pairs of scientifically accurate and structurally identical evolutionary trees that differed in whether they included a taxon that cued a misconception in memory. As predicted, Experiment 1 found that (a) college students (N = 90) had better memory for each of the six tree structures when a neutral taxon (M = 0.73) rather than a misconception-cuing taxon (M = 0.64) was included in the tree, and (b) recognition memory was significantly above chance for both sets of trees. Experiment 2 ruled out an alternative hypothesis based on the possibility that 8-12 sec was not enough time for students to encode the relationships depicted in the trees. The authors consider implications of these results for using evolutionary trees to better communicate scientific information. This is important because these trees provide information that is relevant for everyday life.

Burden of liver cancer attributable to high fasting plasma glucose: a global analysis based on the global burden of disease study 2019.

OBJECTIVE: Liver cancer is the world's sixth most prevalent cancer and the third most frequent cause of cancer-related mortality. Glucose metabolic disorders, indicated by a high fasting plasma glucose (HFPG) concentration, is a contributor to the etiology of liver cancer. With the rising prevalence of glucose metabolic disorders, an assessment of the global burden of liver cancer attributable to HFPG is warranted to inform global liver cancer prevention and control strategies. METHODS AND ANALYSIS: We evaluated the global death and disability-adjusted life years (DALYs) of liver cancer and its subtypes attributable to HFPG at global, regional, and country level. The temporal trend and disparity across geographic regions, social development level, age groups and sex were assessed. RESULTS: In 2019, HFPG-attributable liver cancer was estimated to have caused 4,729.49 deaths and to be responsible for 99,302.25 DALYs. The age-standardized mortality and DALY rate were 0.06 and 1.20 per 100,000 population, and displayed a significantly increasing temporal trend from 1990 to 2019. The age-standardized mortality rate of patients with liver cancer that was attributable to HFPG was higher in men than women. Sex-based disparity narrowed after the women reached menopause, but increased between 1990 and 2019. CONCLUSION: The burden of liver cancer that are attributable to HFPG has been influenced by longitudinal changes in lifestyle, the etiology of liver disease, age demographics, and hormonal status in women. These findings suggest that comprehensive strategies could be implemented, especially for patients with NASH and hyperglycemia, to prevent liver cancer.

Giardia intestinalis extracellular vesicles induce changes in gene expression in human intestinal epithelial cells in vitro.

Giardiasis is a common waterborne zoonotic disease caused by Giardia intestinalis. Upon infection, Giardia releases excretory and secretory products (ESPs) including secreted proteins (SPs) and extracellular vesicles (EVs). Although the interplay between ESPs and intestinal epithelial cells (IECs) has been previously described, the functions of EVs in these interactions and their differences from those of SPs require further exploration. In the present study, EVs and EV-depleted SPs were isolated from Giardia ESPs. Proteomic analyses of isolated SPs and EVs showed 146 and 91 proteins, respectively. Certain unique and enriched proteins have been identified in SPs and EVs. Transcriptome analysis of Caco-2 cells exposed to EVs showed 96 differentially expressed genes (DEGs), with 56 upregulated and 40 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) indicated that Caco-2 genes related to metabolic processes, the HIF-1 signaling pathway, and the cAMP signaling pathway were affected. This study provides new insights into host-parasite interactions, highlighting the potential significance of EVs on IECs during infections.

The effect of ultrasonic power on the physicochemical properties and antioxidant activities of frosted figs pectin.

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.

Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1.

The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.

Efficient word segmentation is preserved in older adult readers: Evidence from eye movements during Chinese reading.

College-aged readers use efficient strategies to segment and recognize words in naturally unspaced Chinese text. Whether this capability changes across the adult lifespan is unknown, although segmenting words in unspaced text may be challenging for older readers due to visual and cognitive declines in older age, including poorer parafoveal processing of upcoming characters. Accordingly, we conducted two eye movement experiments to test for age differences in word segmentation, each with 48 young (18-30 years) and 36 older (65+ years) native Chinese readers. Following Zhou and Li (2021), we focused on the processing of "incremental" three-character words, like (meaning "kindergartens"), which contain an embedded two-character word (e.g., , meaning "children"). In Experiment 1, either the three-character word or its embedded word was presented as the target word in sentence contexts where the three-character word always was plausible, and the embedded word was either plausible or implausible. Both age groups produced similar plausibility effects, suggesting age constancy in accessing the embedded word early during ambiguity processing before ultimately assigning an incremental word analysis. Experiment 2 provided further evidence that both younger and older readers access the embedded word early during ambiguity processing, but rapidly select the appropriate (incremental) word. Crucially, the findings suggest that word segmentation strategies do not differ with age. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Optimization analysis of a Stokes polarimeter for broadband liquid crystal variable retarders under the optimal objective function.

A liquid crystal variable retarder (LCVR) is the core device to realize fast and high-precision broadband polarization imaging, and its ability to suppress the noise will have an impact on the polarization measurement results. In order to obtain better imaging quality and measurement accuracy, it is crucial to solve the optimization problem of the LCVR. In this paper, the optimal objective function for solving the optimization problem of the LCVR is analytically derived and verified based on the genetic algorithm in the band range of 350-700 nm. Meanwhile, considering that the minimum number of four measurements at this time cannot achieve the optimal state, the relationship between the number of measurements and the overall performance relative to the error propagation (optimized conditions number) is discussed. The results show that a better optimal set of angles can be obtained by using the optimal objective function. In this paper, a set of the most favorable angles is obtained, and the optimized average of the CN is 2.0000, which is reduced by 0.32% compared with previous optimization results and is closer to the ideal value of the CN. In addition, in this paper, the noise immunity of the set of most favorable angles is simulated and analyzed, and the optimized system can effectively improve the measured performance of the wide-band liquid crystal variable retarder polarimeter.

Native and engineered extracellular vesicles: novel tools for treating liver disease.

Liver diseases are classified as acute liver damage and chronic liver disease, with recurring liver damage causing liver fibrosis and progression to cirrhosis and hepatoma. Liver transplantation is the only effective treatment for end-stage liver diseases; therefore, novel therapies are required. Extracellular vesicles (EVs) are endogenous nanocarriers involved in cell-to-cell communication that play important roles in immune regulation, tissue repair and regeneration. Native EVs can potentially be used for various liver diseases owing to their high biocompatibility, low immunogenicity and tissue permeability and engineered EVs with surface modification or cargo loading could further optimize therapeutic effects. In this review, we firstly introduced the mechanisms and effects of native EVs derived from different cells and tissues to treat liver diseases of different etiologies. Additionally, we summarized the possible methods to facilitate liver targeting and improve cargo-loading efficiency. In the treatment of liver disease, the detailed engineered methods and the latest delivery strategies were also discussed. Finally, we pointed out the limitations and challenges of EVs for future development and applications. We hope that this review could provide a useful reference for the development of EVs and promote the clinical translation.

pGM-CSF as an adjuvant in DNA vaccination against SARS-CoV-2.

The emergence of SARS-CoV-2 presents a significant global public health dilemma. Vaccination has long been recognized as the most effective means of preventing the spread of infectious diseases. DNA vaccines have attracted attention due to their safety profile, cost-effectiveness, and ease of production. This study aims to assess the efficacy of plasmid-encoding GM-CSF (pGM-CSF) as an adjuvant to augment the specific humoral and cellular immune response elicited by DNA vaccines based on the receptor-binding domain (RBD) antigen. Compared to the use of plasmid-encoded RBD (pRBD) alone, mice that were immunized with a combination of pRBD and pGM-CSF exhibited significantly elevated levels of RBD-specific antibody titers in serum, BALF, and nasal wash. Furthermore, these mice generated more potent neutralization antibodies against both the wild-type and Omicron pseudovirus, as well as the ancestral virus. In addition, pGM-CSF enhanced pRBD-induced CD4+ and CD8+ T cell responses and promoted central memory T cells storage in the spleen. At the same time, tissue-resident memory T (Trm) cells in the lung also increased significantly, and higher levels of specific responses were maintained 60 days post the final immunization. pGM-CSF may play an adjuvant role by promoting antigen expression, immune cells recruitment and GC B cell responses. In conclusion, pGM-CSF may be an effective adjuvant candidate for the DNA vaccines against SARS-CoV-2.

Qualitative discrimination and quantitative prediction of microplastics in ash based on near-infrared spectroscopy.

Microplastics are recognized as a new environmental pollutant. Researchers have detected their presence in waste incineration ash. However, traditional testing methods take a very long testing period. There is a lack of research on detecting microplastics in waste incineration ash. In this paper, a portable near-infrared spectra (NIRS) spectrometer was used for qualitative discrimination and quantitative prediction of microplastics in ash. A total of 84 sets of simulated ash samples containing different types (PP, PS, PE, and PVC) and contents (2.4 wt% - 20 wt%) of microplastics were used in the model. The results show the qualitative discrimination model using support vector machines (SVM) method with multiplicative scatter correction (MSC) preprocessing could effectively identify the microplastic types in the ash with 100% detection accuracy. Furthermore, the partial least squares regression (PLSR) model was effective in quantitatively predicting the content of microplastics in ash. The Rp2 of the PP, PS, PE, and PVC models are 0.95, 0.93, 0.89, and 0.95, respectively. The RPD of the PP, PS, PE, and PVC models are 3.97, 3.96, 2.89 and 5.02, respectively. This study shows that microplastics in ash can be detected rapidly and accurately using portable near-infrared spectrometers.

Comparison of the effects of monounsaturated fatty acids and polyunsaturated fatty acids on the lipotoxicity of islets.

Background: Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat saturated fatty acid (SFA)-induced cellular damage, however, their clinical effects on patients with metabolic diseases such as diabetes and hyperlipidemia are still controversial. Since comparative studies of the effects of these two types of unsaturated fatty acids (UFAs) are still limited. In this study, we aimed to compare the protective effects of various UFAs on pancreatic islets under the stress of SFA-induced metabolic disorder and lipotoxicity. Methods: Rat insulinoma cell line INS-1E were treated with palmitic acid (PA) with or without UFAs including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and oleic acid (OA) to determine cell viability, apoptosis, endoplasmic reticulum (ER) stress, and inflammatory. In vivo, male C57BL/6 mice were fed a 60% high-fat diet (HFD) for 12 w. Then the lard in HFD was partially replaced with fish oil (FO) and olive oil (OO) at low or high proportions of energy (5% or 20%) to observe the ameliorative effects of the UFA supplement. Results: All UFAs significantly improved PA-induced cell viability impairment in INS-1E cells, and their alleviation on PA induced apoptosis, ER stress and inflammation were confirmed. Particularly, OA had better effects than EPA, DHA, and AA on attenuating cellular ER stress. In vivo, the diets with a low proportion of UFAs (5% of energy) had limited effects on HFD induced metabolic disorder, except for a slight improved intraperitoneal glucose tolerance in obese mice. However, when fed diets containing a high proportion of UFAs (20% of energy), both the FO and OO groups exhibited substantially improved glucose and lipid metabolism, such as decrease in total cholesterol (TC), low-density lipoprotein (LDL), fasting blood glucose (FBG), and fasting blood insulin (FBI)) and improvement of insulin sensitivity evidenced by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT). Unexpectedly, FO resulted in abnormal elevation of the liver function index aspartate aminotransferase (AST) in serum. Pathologically, OO attenuated HFD-induced compensatory hyperplasia of pancreatic islets, while this effect was not obvious in the FO group. Conclusions: Both MUFAs and PUFAs can effectively protect islet ß cells from SFA-induced cellular lipotoxicity. In particular, both OA in vitro and OO in vivo showed superior activities on protecting islets function and enhance insulin sensitivity, suggesting that MUFAs might have greater potential for nutritional intervention on diabetes.

Favorable Outcomes of Liver Transplantation for Hepatopulmonary Syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of chronic liver disease, which develops insidiously as a result of chronic liver disease. The prognosis for untreated patients with HPS is extremely poor, and liver transplantation (LT) serves as the only effective means for treating this condition. Here, we performed a retrospective analysis to evaluate the efficacy of LT on the survival and long-term prognosis of patients with HPS. METHODS: Clinical data, including survival and postoperative efficacy, from patients with HPS from records as obtained over the period from January 1 to December 31, 2022. All records were from a waiting list for LT at the Beijing Friendship Hospital Affiliated with Capital Medical University. RESULTS: Among the 274 patients on the LT waiting list, 37 were diagnosed with HPS (13.50%) and were enrolled. Survival rates of patients with HPS receiving an LT were greater, whereas a statistically significant difference was obtained between patients with LT vs non-LT with moderate to severe HPS (P = .003). The overall time until death without LT was 4-72 days after their initial HPS diagnosis. Patients with HPS receiving an LT showed a significant improvement in the state of oxygenation after surgery (P = .001). CONCLUSION: Comprehensive preoperative screening of patients on the waiting list for LT is critical to identify those patients with HPS who would maximally benefit from LT. Survival rates of patients with moderate to severe HPS are significantly increased after LT, a procedure that should be performed as soon as possible in these patients with HPS.

Occlusal force orchestrates alveolar bone homeostasis via Piezo1 in female mice.

Healthy alveolar bone is the cornerstone of oral function and oral treatment. Alveolar bone is highly dynamic during the entire lifespan and is affected by both systemic and local factors. Importantly, alveolar bone is subjected to unique occlusal force in daily life, and mechanical force is a powerful trigger of bone remodeling, but the effect of occlusal force in maintaining alveolar bone mass remains ambiguous. In this study, the Piezo1 channel is identified as an occlusal force sensor. Activation of Piezo1 rescues alveolar bone loss caused by a loss of occlusal force. Moreover, we identify Piezo1 as the mediator of occlusal force in osteoblasts, maintaining alveolar bone homeostasis by directly promoting osteogenesis and by sequentially regulating catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. Interestingly, Piezo1 activation also exhibits remarkable efficacy in the treatment of alveolar bone osteoporosis caused by estrogen deficiency, which is highly prevalent among middle-aged and elderly women. Promisingly, Piezo1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.

Daily occlusal force and estrogen synergistically maintain alveolar bone homeostasis. PIEZO1 in osteoblasts plays a critical role in sensing occlusal force and maintaining bone mass. PIEZO1 may promote osteoclastic apoptosis through osteoblast-secreted FasL through a PIEZO1-STAT3/ESR1-FasL pathway. Restoration of occlusal force with dental therapies as early as possible to prevent alveolar bone loss is the major priority in oral health care. PIEZO1 may serve as a potential target for bone metabolism disorders.

Cathelicidin boosts the antifungal activity of neutrophils and improves prognosis during Aspergillus fumigatus keratitis.

Aspergillus fumigatus (A. fumigatus) is one of the common pathogens of fungal keratitis. Fungal growth and invasion cause excessive inflammation and corneal damage, leading to severe vision loss. Neutrophils are the primary infiltrating cells critical for fungal clearance. Cathelicidin [LL-37 in humans and cathelicidin-related antimicrobial peptide (CRAMP) in mice], a natural antimicrobial peptide, can directly inhibit the growth of many pathogens and regulate immune responses. However, the role of cathelicidin and its effect on neutrophils in A. fumigatus keratitis remain unclear. By establishing A. fumigatus keratitis mouse models, we found that cathelicidin was increased in A. fumigatus keratitis. It could reduce fungal loads, lower clinical scores, and improve corneal transparency. Restriction of CRAMP on fungal proliferation was largely counteracted in CD18-/- mice, in which neutrophils cannot migrate into infected sites. When WT neutrophils were transferred into CD18-/- mice, corneal fungal loads were distinctly reduced, indicating that neutrophils are vital for CRAMP-mediated resistance. Furthermore, cathelicidin promoted neutrophils to phagocytose and degrade conidia both in vitro and in vivo. CXC chemokine receptor 2 (CXCR2) was reported to be a functional receptor of LL-37 on neutrophils. CXCR2 antagonist SB225002 or phospholipase C (PLC) inhibitor U73122 weakened LL-37-induced phagocytosis. Meanwhile, LL-37 induced PLC γ phosphorylation, which was attenuated by SB225002. SB225002 or the autophagy inhibitors Bafilomycin-A1 and 3-Methyladenine weakened LL-37-induced degradation of conidia. Transmission electron microscopy (TEM) observed that LL-37 increased autophagosomes in Aspergillus-infected neutrophils. Consistently, LL-37 elevated autophagy-associated protein expressions (Beclin-1 and LC3-II), but this effect was weakened by SB225002. Collectively, cathelicidin reduces fungal loads and improves the prognosis of A. fumigatus keratitis. Both in vitro and in vivo, cathelicidin promotes neutrophils to phagocytose and degrade conidia. LL-37/CXCR2 activates PLC γ to amplify neutrophils' phagocytosis and induces autophagy to eliminate intracellular conidia.

Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.

BACKGROUND: Lipid metabolism related factors, such as angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. HYPOTHESIS: ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. METHODS: We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non-CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor-α (TNF-α) levels were estimated using the enzyme-linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. RESULTS: The serum TNF-α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non-CAD groups (p < .05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p < .05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. CONCLUSION: ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD.

Island-Like Heterogeneous Interface Generating Tandem Toroidal Built-In Electric Field for Efficient Potassium Ions Diffusion.

For large-size potassium accommodation, heterostructure usually suffers severe delamination and exfoliation at the interfaces due to different volume expansion of two-phase during charge/discharge process, resulting in the deconstruction of heterostructures and shortened lifespan of batteries. Here, an innovative strategy is proposed through constructing a microscopic heterostructure system containing copper quantum dots (Cu QDs) highly dispersed in the triphenyl-substituted triazine graphdiyne (TPTG) substrates (TPTG@CuQDs) to solve this problem. The copper quantum dots are uniformly anchored on TPTG substrates, generating a myriad of island-like heterogeneous structures, together with tandem toroidal built-in electric field (BIEF) between every micro heterointerface. The island-like heterostructure endows both benefits of exposed contact interface and robust architecture. Generated tandem toroidal BIEF provides efficient transport pathways with lower energy barriers, reducing the diffusion resistance and facilitating the reaction kinetics of potassium ions. When used as anode, the TPTG@CuQDs exhibit highly reversible capacity and low-capacity degradation (≈0.01% over 5560 cycles at 1 A g-1 ). Moreover, the TPTG@CuQDs-based full cell delivers an outstanding reversible capacity of ≈110 mAh g-1 over 800 cycles at 1 A g-1 . This quantum-scale heterointerface construction strategy offers a new approach toward stable heterostructure design for the application of metal ion batteries.