Global, regional, and national burdens of atopic dermatitis under 14: a trend analysis and future prediction based on the global burden of disease study 2019.

OBJECTIVE: The aim is to evaluate the global, regional, and national trends in the burden of children and adolescents under 14 from 1990 to 2019, as well as future trend predictions. METHODS: In Global Burden of Disease (GBD), we reported the incidence, prevalence rate and the years lived with disability (YLDs), the incidence per 100,000 people, and the average annual percentage change (AAPC). We further analyzed these global trends by age, gender, and social development index (SDI). We use joinpoint regression analysis to determine the year with the largest global trend change. Bayesian age-period-cohort (BAPC) was used for predictions. RESULTS: From 1990 to 2019, the incidence rate, prevalence and YLDs of AD under 14 years old showed a downward trend. The incidence rate of AD among people under 5 years old has the largest decline [AAPC: -0.13 (95% CI: -0.15 to -0.11), P < 0.001]. The incidence rate, prevalence and YLDs of AD in women were higher than those in men regardless of age group. Regional, Asia has the highest AD incidence rate in 2019. National, Mongolia has the highest AD incidence rate in 2019. The largest drop in AD incidence rate, prevalence and YLDs between 1990 and 2019 was in the United States. CONCLUSION: From 1990 to 2019, the global incidence rate of children and adolescents under 14 declined. With the emergence of therapeutic drugs, the prevalence and YLDs rate declined significantly. From 2020 to 2030, there is still a downward trend.

Borneol and lactoferrin dual-modified crocetin-loaded nanoliposomes enhance neuroprotection in HT22 cells and brain targeting in mice.

Crocetin (CCT), a natural bioactive compound extracted and purified from the traditional Chinese medicinal herb saffron, has been shown to play a role in neurodegenerative diseases, particularly depression. However, due to challenges with solubility, targeting, and bioavailability, formulation development and clinical use of CCT are severely limited. In this study, we used the emulsification-reverse volatilization method to prepare CCT-loaded nanoliposomes (CN). We further developed a borneol (Bor) and lactoferrin (Lf) dual-modified CCT-loaded nanoliposome (BLCN) for brain-targeted delivery of CCT. The results of transmission electron microscope (TEM) and particle size analysis indicated that the size of BLCN (∼140 nm) was suitable for transcellular transport across olfactory axons (∼200 nm), potentially paving a direct path to the brain. Studies on lipid solubility, micropolarity, and hydrophobicity showed that BLCN had a relatively high Lf grafting rate (81.11 ± 1.33 %) and CCT entrapment efficiency (83.60 ± 1.04 %) compared to other liposomes, likely due to Bor improving the lipid solubility of Lf, and the combination promoting the orderly arrangement of liposome membrane molecules. Microplate reader and fluorescence microscopy analysis showed that BLCN efficiently promoted the endocytosis of fluorescent coumarin 6 into HT22 cells with a maximal fluorescence intensity of (13.48 ± 0.80 %), which was significantly higher than that of CCT (5.73 ± 1.17 %) and CN (12.13 ± 1.01 %). BLCN also exhibited sustained function, remaining effective for more than 12 h after reaching a peak at 1 h in cells, while CN showed a significant decrease after 4 h. The uptake mechanisms of BLCN in HT22 cells mainly involve energy-dependent, caveolae-mediated, and microtubule-mediated endocytosis, as well as micropinocytosis. Furthermore, BLCN displayed a significant neuroprotective effect on HT22 cells in glutamate-, corticosterone-, and H2O2-induced models. Tissue fluorescence image analysis of mice showed that BLCN exhibited substantial retention of fluorescent DiR in the brain after nasal administration for 12 h. These findings suggest that CCT has the potential for cellular uptake, neuroprotection, and targeted delivery to the brain following intranasal administration when encapsulated in Bor and Lf dual-modified nanoliposomes.

Application of machine reading comprehension techniques for named entity recognition in materials science.

Materials science is an interdisciplinary field that studies the properties, structures, and behaviors of different materials. A large amount of scientific literature contains rich knowledge in the field of materials science, but manually analyzing these papers to find material-related data is a daunting task. In information processing, named entity recognition (NER) plays a crucial role as it can automatically extract entities in the field of materials science, which have significant value in tasks such as building knowledge graphs. The typically used sequence labeling methods for traditional named entity recognition in material science (MatNER) tasks often fail to fully utilize the semantic information in the dataset and cannot effectively extract nested entities. Herein, we proposed to convert the sequence labeling task into a machine reading comprehension (MRC) task. MRC method effectively can solve the challenge of extracting multiple overlapping entities by transforming it into the form of answering multiple independent questions. Moreover, the MRC framework allows for a more comprehensive understanding of the contextual information and semantic relationships within materials science literature, by integrating prior knowledge from queries. State-of-the-art (SOTA) performance was achieved on the Matscholar, BC4CHEMD, NLMChem, SOFC, and SOFC-Slot datasets, with F1-scores of 89.64%, 94.30%, 85.89%, 85.95%, and 71.73%, respectively in MRC approach. By effectively utilizing semantic information and extracting nested entities, this approach holds great significance for knowledge extraction and data analysis in the field of materials science, and thus accelerating the development of material science.Scientific contributionWe have developed an innovative NER method that enhances the efficiency and accuracy of automatic entity extraction in the field of materials science by transforming the sequence labeling task into a MRC task, this approach provides robust support for constructing knowledge graphs and other data analysis tasks.

The relationship between competitive anxiety and athlete burnout in college athlete: the mediating roles of competence and autonomy : [Author].

BACKGROUND: In the cognitive-affective model of athlete burnout, anxiety is a key physiological response to stress that influences the development of burnout in athletes. Despite its importance, there has been little research on the relationship between competitive anxiety and athlete burnout, particularly regarding the mediating mechanisms. This study aimed to explore the relationship between competitive anxiety and athlete burnout, with a focus on the mediating role of general need satisfaction from self-determination theory. METHODS: The current study employed a cross-sectional design involving 618 college athletes (354 females, mean age 20.57 years), comprising 303 participants in individual sports and 315 in team sports. These participants completed the Sport Anxiety Scale-2 (SAS-2), the Athlete Burnout Questionnaire (ABQ), and the Basic Psychological Need Satisfaction Scale in General (BPNSS-G) online. Subsequently, correlation, regression, and mediation analyses were conducted using SPSS and JASP to examine the relationships between the variables. RESULTS: Regression results indicated that somatic anxiety (beta = 0.116, t = 2.21, p = 0.028) and concentration disruption (beta = 0.259, t = 5.35, p < 0.001) in competitive anxiety were positively correlated with athlete burnout. Worry in competitive anxiety was negatively correlated with competence (beta =-0.149, t=-2.70, p = 0.007) and autonomy (beta =-0.179, t=-3.25, p = 0.001) in needs satisfaction. Additionally, the regression results found that competence (beta =-0.178, t=-3.39, p = 0.001) and Autonomy (beta =-0.208, t=-4.17, p < 0.001) were negatively associated with athlete burnout. Mediation analyses revealed significant direct effects in the relationship between somatic anxiety (Effect = 0.116, p = 0.026) along with concentration disruption (Effect = 0.259, p < 0.001) and athlete burnout. In the indirect effect, worry (Effect = 0.071, p = 0.002) as well as concentration disruption (Effect = 0.082, p < 0.001) had significant effects in relation to athlete burnout, respectively. CONCLUSIONS: Overall, the current study found that somatic anxiety and concentration disruption in competitive anxiety are related to athlete burnout. Moreover, competence and autonomy in need satisfaction mediated the relationship between competitive anxiety (worry and concentration disruption) and athlete burnout. The findings of this study not only shed further light on the relationship between competitive anxiety and athlete burnout but also provide theoretical insights into the mediating mechanisms of this relationship.

Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis.

Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.

Association between the atherogenic index of plasma and bone mineral density among adult women: NHANES (2011-2018).

Background: Studies on the relationship between the atherogenic index of plasma (AIP) and bone mineral density (BMD) among adult women in the United States are limited. The purpose of this study was to explore this association using a sizable, nationally representative sample. Methods: Data from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES) were used in this observational study. The AIP was computed as log10 (triglycerides/high-density lipoprotein cholesterol). Total BMD was measured via dual-energy X-ray densitometry. We constructed multiple linear regression models to evaluate the correlation between the AIP and BMD. The non-linear relationship was characterized by smooth curve fitting and generalized additive models. We also conducted subgroup and interaction analyses. Results: In this study, we included 2,362 adult women with a mean age of 38.13 ± 12.42 years. The results of multiple linear regression analysis, the AIP and total BMD showed a negative association (ß = -0.021, 95%CI: -0.037, -0.006). The curve fitting analysis and threshold effect analysis showed a non-linear relationship between the two variables, and the inflection point of the AIP was found to be -0.61. The total BMD decreased significantly when the AIP reached this value (ß = -0.03, 95%CI: -0.04, -0.01). The results of the subgroup analysis showed that AIP and total BMD had a strong negative relationship in participants who were below 45 years old (ß = -0.023; 95% CI: -0.041, -0.004), overweight (BMI ≥ 25 kg/m2) (ß = -0.022; 95% CI: -0.041, -0.002), had a higher education level (ß = -0.025; 95% CI: -0.044, -0.006), and had no partners (ß = -0.014; 95% CI: -0.06, -0.009). Conclusions: We found a negative correlation between the AIP and total BMD. Clinicians should pay attention to patients with high AIP, which might indicate a low BMD and has reference significance in preventing osteoporosis.

Evolutionary screening of precision oncology biomarkers and its applications in prognostic model construction.

Biomarker screening is critical for precision oncology. However, one of the main challenges in precision oncology is that the screened biomarkers often fail to achieve the expected clinical effects and are rarely approved by regulatory authorities. Considering the close association between cancer pathogenesis and the evolutionary events of organisms, we first explored the evolutionary feature underlying clinically approved biomarkers, and two evolutionary features of approved biomarkers (Ohnologs and specific evolutionary stages of genes) were identified. Subsequently, we utilized evolutionary features for screening potential prognostic biomarkers in four common cancers: head and neck squamous cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Finally, we constructed an evolution-strengthened prognostic model (ESPM) for cancers. These models can predict cancer patients' survival time across different cancer cohorts effectively and perform better than conventional models. In summary, our study highlights the application potentials of evolutionary information in precision oncology biomarker screening.

Value of orthogonal axial MR images in preoperative T staging of gastric cancer.

PURPOSE: To assess the value of orthogonal axial images (OAI) of MRI in gastric cancer T staging. METHODS: This retrospective study enrolled 133 patients (median age, 63 [range, 24-85] years) with gastric adenocarcinoma who underwent both CT and MRI followed by surgery. MRI lacking or incorporating OAI and CT images were evaluated, respectively. Diagnostic performance (accuracy, sensitivity, and specificity) for each T stage, overall diagnostic accuracy and rates of over- and understaging were quantified employing pathological T stage as a reference standard. The McNemar's test was performed to compare the overall accuracy. RESULTS: Among patients with pT1-pT4 disease, MRI with OAI (accuracy: 88.7-94.7%, sensitivity: 66.7-93.0%, specificity: 91.5-100.0%) exhibited superior diagnostic performance compared to MRI without OAI (accuracy: 81.2-88.7%, sensitivity: 46.2-83.1%, specificity: 85.5-99.1%) and CT (accuracy: 88.0-92.5%, sensitivity: 53.3-90.1%, specificity: 88.7-98.1%). The overall accuracy of MRI with OAI was significantly higher (83.5%) than that of MRI without OAI (67.7%) (p < .001). However, there was no significant difference in the overall accuracy of MRI with OAI and CT (78.9%) (p = .35). The over- and understaging rates of MRI with OAI (12.0, 4.5%) were lower than those of MRI without OAI (21.8, 10.5%) and CT (12.8, 8.3%). CONCLUSION: OAI play a pivotal role in the T staging of gastric cancer. MRI incorporating OAI demonstrated commendable performance for gastric cancer T-staging, with a slight tendency toward its superiority over CT.

Higher perfusion of rectum carcinoma relative to tumor-free rectal wall: quantification by a new imaging biomarker diffusion-derived vessel density (DDVD).

Background: Diffusion-derived vessel density (DDVD) is a physiological surrogate of the area of micro-vessels per unit tissue area. DDVD is calculated according to: DDVD(b0b5) = Sb0/ROIarea0 - Sb5/ROIarea5, where Sb0 and Sb5 refer to the tissue signal when b is 0 or 5 s/mm2. This study applied DDVD to assess the perfusion of rectal carcinoma (RC). Methods: MRI was performed with a 3.0-T magnet. Diffusion weighted image with b-values of 0, 5 s/mm2 were acquired in 113 patients with non-mucinous RC and 15 patients with mucinous RC. Diffusion-derived vessel density ratio [DDVDr(b0b5)] was DDVD(b0b5) of RC divided by DDVD(b0b5) of tumor-free rectal wall. Results: The median value of the DDVDr(b0b5) for non-mucinous RCs was 1.430, with the majority of RCs showing a higher DDVD than the adjacent tumor-free wall [i.e., with DDVDr(b0b5) >1]. 90.3% (102/113) of non-mucinous RCs were hypervascular, 1.77% (2/113) were iso-vascular, and 7.96% (9/113) were hypovascular. The median value of the DDVDr(b0b5) for mucinous RCs was 1.660. 73.3% (11/15) of mucinous RCs were hypervascular, and 26.7% (4/15) were hypovascular. A trend (P=0.09) was noted that earlier clinical grades non-mucinous RCs had a higher DDVDr(b0b5) than those of the advanced clinical grades (2.245 for grade 0&I, 1.460 for grade II, 1.430 for grade III, 1.130 for grade IV). A non-significant trend was noted with well and moderately differentiated non-mucinous RCs had a higher DDVDr(b0b5)than that of poorly differentiated non-mucinous RCs (median: 1.460 vs. 1.320). A non-significant trend was noted with MRI-detected extramural vascular invasion (mrEMVI) positive non-mucinous RCs had a higher DDVDr(b0b5) than that of mrEMVI negative non-mucinous RCs (1.630 vs. 1.370). Conclusions: DDVD results in this study approximately agree with contrast agent dynamically enhanced CT literature data.

Ursolic acid molecules dock MAPK1 to modulate gut microbiota diversity to reduce neuropathic pain.

To investigate the efficacy of Ursolic acid in alleviating neuropathic pain in rats with spinal nerve ligation (SNL), the SNL rat model was surgically induced. Different concentrations of Ursolic acid and manipulated target mitogen-activated protein kinase 1 (MAPK1) were administered to the SNL rats. Fecal samples were collected from each group of rats for 16S rDNA analysis to examine the impact of gut microbiota. Molecular docking experiments were conducted to assess the binding energy between Ursolic acid and MAPK1. In vivo studies were carried out to evaluate the expression of inflammatory factors and signaling pathways in spinal cord and colon tissues. Ursolic acid was found to have a beneficial effect on pain reduction in rats by increasing plantar withdrawal latency (PWL) and paw withdrawal threshold (PWT). Comparing the Ursolic acid group with the control group revealed notable differences in the distribution of Staphylococcus, Allobaculum, Clostridium, Blautia, Bifidobacterium, and Prevotella species. Network pharmacology analysis identified MAPK1 and intercellular adhesion molecule-1 (ICAM1) as common targets for Ursolic acid, SNL, and neuropathic pain. Binding sites between Ursolic acid and these targets were identified. Additionally, immunofluorescent staining showed a decrease in GFAP and IBA1 intensity in the spinal cord along with an increase in NeuN following Ursolic acid treatment. Overexpression of MAPK1 in SNL rats led to an increase in inflammatory factors and a decrease in PWL and PWT. Furthermore, MAPK1 counteracted the pain-relieving effects of Ursolic acid in SNL rats. Ursolic acid was found to alleviate neuropathic pain in SNL rats by targeting MAPK1 and influencing gut microbiota homeostasis.

Symmetry Evolution Induced 2D Pt Single Atom Catalyst with High Density for Alkaline Hydrogen Oxidation.

The performance of single-atom catalysts is greatly influenced by the chemical environment surrounding the central atom. Here, a salt-assisted method is employed to transform the tetrahedral coordination structure of zeolitic imidazolate frameworks - 8 (ZIF-8) into a planar square coordination structure without altering the ligands. During the subsequent carbonization process, concurrent with the evaporation of zinc atoms, the structure of the nitrogen and carbon carriers (NC carriers) undergoes a transition from five-membered rings to six-membered rings to preserve the 2D structure. This transition results in the generation of additional defect sites on the 2D-NC substrates. Hence, the Pt single-atom catalysts with planar square coordination symmetries can be precisely prepared via electrodeposition (denoted as 2D-Pt SAC). The Pt loading of 2D-Pt SAC is 0.49 ± 0.03 µg cm-2, higher than that of 3D-Pt SAC (0.37 ± 0.04 µg cm-2). In the context of the hydrogen oxidation reaction electrocatalysis, under an overpotential of 50 mV, these single-atom catalysts with 2D coordination exhibit mass activities of 2396 A gPt -1 (32 times higher than commercial Pt/C catalyst, 2 times higher than 3D-PtNC).

Low-Frequency Bandgap Characterization of a Locally Resonant Pentagonal Phononic Crystal Beam Structure.

This paper proposes a local resonance-type pentagonal phononic crystal beam structure for practical engineering applications to achieve better vibration and noise reduction. The energy band, transmission curve, and displacement field corresponding to the vibration modes of the structure are calculated based on the finite element method and Bloch-Floquet theorem. Furthermore, an analysis is conducted to understand the mechanism behind the generation of bandgaps. The numerical analysis indicates that the pentagonal unit oscillator creates a low-frequency bandgap between 60-70 Hz and 107-130 Hz. Additionally, the pentagonal phononic crystal double-layer beam structure exhibits excellent vibration damping, whereas the single-layer beam has poor vibration damping. The article comparatively analyzes the effects of different parameters on the bandgap range and transmission loss of a pentagonal phononic crystal beam. For instance, increasing the thickness of the lead layer leads to an increase in the width of the bandgap. Similarly, increasing the thickness of the rubber layer, intermediate plate, and total thickness of the phononic crystals results in a bandgap at lower frequencies. By adjusting the parameters, the beam can be optimized for practical engineering purposes.

Treatment outcomes in patients with acute thromboembolic occlusion of the superior mesenteric artery.

OBJECTIVES: The goals of this study were to investigate the treatment outcomes of acute thromboembolic occlusion of the superior mesenteric artery (ATOS) and identify prognostic factors after treatment. METHODS: The clinical data of 62 patients with ATOS between 2013 and 2021 were retrospectively reviewed. Patients were stratified by the treatment strategy, complications and mortality were compared in different group. RESULTS: Sixty-two consecutive patients were identified with ATOS. The median patient age was 69 years (interquartile range 58-79 years). Endovascular therapy was initiated in 21 patients, and 4 patients received conservative treatment. Open surgery was performed first in the remaining 37 patients. The technical success rates of the endovascular first group and open surgery group were 90.5% and 97.3%, respectively. One patient in the conservative treatment group had progression of ischemia to extensive bowel necrosis. There was no difference in 30-day mortality between these groups. Predictors of 30-day mortality included initial neutrophil count > 12* 103/dL, age over 60 years old and history of chronic renal insufficiency. CONCLUSIONS: Endovascular treatment or conservative treatment may be adopted in selected patients who do not exhibit signs and symptoms of bowel necrosis, and close monitoring for bowel necrosis is important. The increase in preoperative neutrophil count, age over 60 years old and history of chronic renal insufficiency were poor prognostic factors.

The Below-the-Knee Approach to Percutaneous Mechanical Thrombectomy for Lower Extremity Deep Venous Thrombosis: A Retrospective Single-Centre, Single-Arm Study.

PURPOSE: The objective of this study was to evaluate the safety, efficacy, and feasibility of percutaneous mechanical thrombectomy (PMT) through a below-the-knee (BTK) approach for acute lower extremity deep venous thrombosis (DVT). METHODS: A retrospective review of DVT patients treated with PMT by the BTK approach at our center from April 2022 to August 2023 was performed. Their preoperative demographics, intraoperative data, and postoperative outpatient outcomes were analyzed. RESULTS: A total of 12 patients (67% men; mean age, 63 years) met the inclusion criteria. The BTK approach was successfully achieved in all patients through the posterior tibial vein (n = 1), anterior tibial vein (n = 2), and peroneal vein (n = 9). PMTs were achieved in 11 (92%) patients. Successful lysis (grade II and grade III lysis) was achieved in all patients with PMT. Four (33%) patients had residual venous occlusion over the popliteal vein. No intraoperative complications or bleeding events occurred in any of the patients. CONCLUSION: PMT via BTK puncture seems to be a safe and effective approach for treating lower extremity DVT. It is reserved for highly select patients with a low risk of bleeding and is performed at centers that have experience with this procedure.

Initial nutrient condition determines the recovery speed of quiescent cells in fission yeast.

Most of microbe cells spend the majority of their times in quiescence due to unfavorable environmental conditions. The study of this dominant state is crucial for understanding the basic cell physiology. Retained recovery ability is a critical property of quiescent cells, which consists of two features: how long the cells can survive (the survivability) and how fast they can recover (the recovery activity). While the survivability has been extensively studied under the background of chronological aging, how the recovery activity depends on the quiescent time and what factors influence its dynamics have not been addressed quantitatively. In this work, we systematically quantified both the survivability and the recovery activity of long-lived quiescent fission yeast cells at the single cell level under various nutrient conditions. It provides the most profound evolutionary dynamics of quiescent cell regeneration ability described to date. We found that the single cell recovery time linearly increased with the starvation time before the survivability significantly declined. This linearity was robust under various nutrient conditions and the recovery speed was predetermined by the initial nutrient condition. Transcriptome profiling further revealed that quiescence states under different nutrient conditions evolve in a common trajectory but with different speed. Our results demonstrated that cellular quiescence has a continuous spectrum of depths and its physiology is greatly influenced by environmental conditions.

USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis.

BACKGROUND: Endothelial-to-Mesenchymal Transformation (EndMT) plays key roles in endothelial dysfunction during the pathological progression of atherosclerosis; however, its detailed mechanism remains unclear. Herein, we explored the biological function and mechanisms of upstream stimulating factor 1 (USF1) in EndMT during atherosclerosis. METHODS: The in vivo and in vitro atherosclerotic models were established in high fat diet-fed ApoE-/- mice and ox-LDL-exposed human umbilical vein endothelial cells (HUVECs). The plaque formation, collagen and lipid deposition, and morphological changes in the aortic tissues were evaluated by hematoxylin and eosin (HE), Masson, Oil red O and Verhoeff-Van Gieson (EVG) staining, respectively. EndMT was determined by expression levels of EndMT-related proteins. Target molecule expression was detected by RT-qPCR and Western blotting. The release of pro-inflammatory cytokines was measured by ELISA. Migration of HUVECs was detected by transwell and scratch assays. Molecular mechanism was investigated by dual-luciferase reporter assay, ChIP, and Co-IP assays. RESULTS: USF1 was up-regulated in atherosclerosis patients. USF1 knockdown inhibited EndMT by up-regulating CD31 and VE-Cadherin, while down-regulating α-SMA and vimentin, thereby repressing inflammation, and migration in ox-LDL-exposed HUVECs. In addition, USF1 transcriptionally activated ubiquitin-specific protease 14 (USP14), which promoted de-ubiquitination and up-regulation of NLR Family CARD Domain Containing 5 (NLRC5) and subsequent Smad2/3 pathway activation. The inhibitory effect of sh-USF1 or sh-USP14 on EndMT was partly reversed by USP14 or NLRC5 overexpression. Finally, USF1 knockdown delayed atherosclerosis progression via inhibiting EndMT in mice. CONCLUSION: Our findings indicate the contribution of the USF1/USP14/NLRC5 axis to atherosclerosis development via promoting EndMT, which provide effective therapeutic targets.

Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion.

Non-small cell lung cancer (NSCLC) is the most common type of lung tumor; however, we lack effective early detection indicators and therapeutic targets. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is vital to initiate protein synthesis, acting as a scaffolding protein for the eukaryotic protein translation initiation factor complex, EIF4F, which regulates protein synthesis together with EIF4A, EIF4E, and other translation initiation factors. However, EIF4G1's function in NSCLC cancer is unclear. Herein, transcriptome sequencing showed that knockdown of EIF4G1 in H1299 NSCLC cells upregulated the expression of various inflammation-related factors. Inflammatory cytokines were also significantly overexpressed in NSCLC tumor tissues, among which CXCL8 (encoding C-X-C motif chemokine ligand 8) showed the most significant changes in both in the transcriptome sequencing data and tumor tissues. We revealed that EIF4G1 regulates the protein level of TNF receptor superfamily member 10a (TNFRSF10A) resulting in activation of the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) pathways, which induces CXCL8 secretion, leading to targeted chemotaxis of immune cells. We verified that H1299 cells with EIF4G1 knockdown showed increased chemotaxis compared with the control group and promoted increased chemotaxis of macrophages. These data suggested that EIF4G1 is an important molecule in the inflammatory response of cancer tissues in NSCLC.

Association of lipid-lowering drugs with osteoarthritis outcomes from a drug-target Mendelian randomization study.

BACKGROUND: Osteoarthritis (OA), a prevalent musculoskeletal disorder, has been suggested to have a potential association with metabolic syndrome, particularly lipid metabolism. Studies exploring the effects of lipid-lowering drugs on OA have yielded conflicting results. OBJECTIVE: This study employed a drug-targeted Mendelian randomization approach to investigate the association between genetically predicted lipid-modulating effects of commonly targeted lipid-lowering agents and the risk of OA, with the aim of providing a theoretical foundation for the use of lipid-lowering drugs in OA treatment. METHODS: Employing Mendelian randomization (MR) analysis, we examined the potential causal relationship between lipid-lowering drugs and OA. Genetic variants associated with LDL cholesterol levels were selected from the GWAS summary data, and a series of statistical analyses, including inverse-variance weighted (IVW), weighted median (WM), and MR-Egger, were performed to estimate causal effects. RESULTS: We observed significant associations between genetically proxied lipid-lowering drug targets and OA risk. Notably, HMGCR-mediated LDL cholesterol showed an association with overall OA of the hip or knee (OR = 0.865, 95%CI: 0.762 to 0.983, p = 0.026, q = 0.07) and knee osteoarthritis specifically (OR = 0.746, 95%CI: 0.639 to 0.871, p = 2.180×10-4, q = 0.004). PCSK9-mediated LDL cholesterol also demonstrated an association with OA of the hip or knee (OR = 0.915, 95%CI: 0.847 to 0.988, p = 0.023, q = 0.07) and knee osteoarthritis (OR = 0.901, 95%CI: 0.821 to 0.990, p = 0.03, q = 0.07). NPC1L1-mediated LDL cholesterol showed a positive association with OA of the hip or knee (OR = 1.460, 95%CI: 1.127 to 1.890, p = 0.004, q = 0.033). Furthermore, LDLR-mediated LDL cholesterol demonstrated an association with OA of the hip or knee (OR = 0.882, 95%CI: 0.788 to 0.988, p = 0.03, q = 0.07) and hip osteoarthritis (OR = 0.867, 95%CI: 0.769 to 0.978, p = 0.02, q = 0.07). CONCLUSIONS: These findings provide preliminary evidence for the potential therapeutic use of lipid-lowering drugs in OA treatment. Further investigation is needed to validate these findings and explore the precise mechanisms underlying the observed associations.

Hydrogel Loaded with Components for Therapeutic Applications in Hypertrophic Scars and Keloids.

Hypertrophic scars and keloids are common fibroproliferative diseases following injury. Patients with pathologic scars suffer from impaired quality of life and psychological health due to appearance disfiguration, itch, pain, and movement disorders. Recently, the advancement of hydrogels in biomedical fields has brought a variety of novel materials, methods and therapeutic targets for treating hypertrophic scars and keloids, which exhibit broad prospects. This review has summarized current research on hydrogels and loaded components used in preventing and treating hypertrophic scars and keloids. These hydrogels attenuate keloid and hypertrophic scar formation and progression by loading organic chemicals, drugs, or bioactive molecules (such as growth factors, genes, proteins/peptides, and stem cells/exosomes). Among them, smart hydrogels (a very promising method for loading many types of bioactive components) are currently favoured by researchers. In addition, combining hydrogels and current therapy (such as laser or radiation therapy, etc.) could improve the treatment of hypertrophic scars and keloids. Then, the difficulties and limitations of the current research and possible suggestions for improvement are listed. Moreover, we also propose novel strategies for facilitating the construction of target multifunctional hydrogels in the future.

Extracellular Matrix-Trapped Bioinspired Lipoprotein Prolongs Tumor Retention to Potentiate Antitumor Immunity.

The immunomodulatory effects of many therapeutic agents are significantly challenged by their insufficient delivery efficiency and short retention time in tumors. Regarding the distinctively upregulated fibronectin (FN1) and tenascin C (TNC) in tumor stroma, herein a protease-activated FN1 and/or TNC binding peptide (FTF) is designed and an extracellular matrix (ECM)-trapped bioinspired lipoprotein (BL) (FTF-BL-CP) is proposed that can be preferentially captured by the TNC and/or FN1 for tumor retention, and then be responsively dissociated from the matrix to potentiate the antitumor immunity. The FTF-BL-CP treatment produces a 6.96-, 9.24-, 6.72-, 7.32-, and 6.73-fold increase of CD3+CD8+ T cells and their interferon-γ-, granzyme B-, perforin-, and Ki67-expressing subtypes versus the negative control, thereby profoundly eliciting the antitumor immunity. In orthotopic and lung metastatic breast cancer models, FTF-BL-CP produces notable therapeutic benefits of retarding tumor growth, extending survivals, and inhibiting lung metastasis. Therefore, this ECM-trapping strategy provides an encouraging possibility of prolonging tumor retention to potentiate the antitumor immunity for anticancer immunotherapy.