Search

Abstract Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system. Graphical Abstract

Abstract Objectives This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. Methods 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. Results Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p

Abstract Background To use an automated system exploiting the advantages of both a neural network and radiomics for analysis of non‐calcified predominant plaque (NCPP). Methods This study retrospectively included 234 patients. Using the workflow of the previous study, the coronary artery was first segmented, images containing plaques were then extracted, and a classifier was built to identify non‐calcified predominant plaques. Radiomics feature analysis and a visualization tool were used to better distinguish NCPP from other plaques. Results Twenty‐six representative radiomics features were selected. DenseNet achieved an area under the curve of 0.889, which was significantly larger (p = 0.001) than that obtained using a gradient‐boosted decision tree (0.859). The feature variances and energy features in calcified predominant plaque were both different from those in NCPP. Conclusions Our automated system provided high‐accuracy analysis of vulnerable plaques using a deep learning approach and predicted useful features of NCPP using a radiomics‐based approach.

Abstract With the development of the economy and the increasing prevalence of skin problems, cutaneous medical aesthetics are gaining more and more attention. Skin disorders like poor wound healing, aging, and pigmentation have an impact not only on appearance but also on patients with physical and psychological issues, and even impose a significant financial burden on families and society. However, due to the complexities of its occurrence, present treatment options cannot produce optimal outcomes, indicating a dire need for new and effective treatments. Mesenchymal stem cells (MSCs) and their secretomics treatment is a new regenerative medicine therapy that promotes and regulates endogenous stem cell populations and/or replenishes cell pools to achieve tissue homeostasis and regeneration. It has demonstrated remarkable advantages in several skin-related in vivo and in vitro investigations, aiding in the improvement of skin conditions and the promotion of skin aesthetics. As a result, this review gives a complete description of recent scientific breakthroughs in MSCs for skin aesthetics and the limitations of their clinical applications, aiming to provide new ideas for future research and clinical transformation.

Abstract Spinal cord injury (SCI) often results in motor and sensory deficits, or even paralysis. Due to the role of the cascade reaction, the effect of excessive reactive oxygen species (ROS) in the early and middle stages of SCI severely damage neurons, and most antioxidants cannot consistently eliminate ROS at non-toxic doses, which leads to a huge compromise in antioxidant treatment of SCI. Selenium nanoparticles (SeNPs) have excellent ROS scavenging bioactivity, but the toxicity control problem limits the therapeutic window. Here, we propose a synergistic therapeutic strategy of SeNPs encapsulated by ZIF-8 (SeNPs@ZIF-8) to obtain synergistic ROS scavenging activity. Three different spatial structures of SeNPs@ZIF-8 were synthesized and coated with ferrostatin-1, a ferroptosis inhibitor (FSZ NPs), to achieve enhanced anti-oxidant and anti-ferroptosis activity without toxicity. FSZ NPs promoted the maintenance of mitochondrial homeostasis, thereby regulating the expression of inflammatory factors and promoting the polarization of macrophages into M2 phenotype. In addition, the FSZ NPs presented strong abilities to promote neuronal maturation and axon growth through activating the WNT4-dependent pathways, while prevented glial scar formation. The current study demonstrates the powerful and versatile bioactive functions of FSZ NPs for SCI treatment and offers inspiration for other neural injury diseases.

Abstract Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer’s disease (AD), particularly in the early stages of the disease. The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases. We herein demonstrated that human dental pulp stem cells (hDPSCs) mediated oxidative stress improvement and neuroreparative effects in in vitro AD models, playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons. Importantly, these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs, with the treated mice showing significant improvement in cognitive function and neuropathological features. Mechanistically, antioxidant and neuroprotective effects, as well as cognitive enhancements elicited by hDPSCs, were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway. In conclusion, our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models, which may be a tremendous potential therapeutic candidate for Alzheimer’s disease.

Abstract Background In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. Methods A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case–control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. Results A significant decrease in ANB (P

ABSTRACTLaser surface texturing (LST) with different patterns was performed on silicon nitride (Si3N4) ceramic. Effect of patterns created by LST on coefficient of friction (COF) and surface damage under dry friction was investigated. Results indicated that fluctuation of COF decreased with the increasing loading force for both un-textured and textured samples. Under the same loading force, COF of Si3N4 ceramic with textured patterns was more stable than the samples with smoothly finished surface. The COF of textured samples was not always lower than that of un-textured samples. This may be caused by differences in the distribution of debris and the continuity of surface contact. The worn surface existed damages of plow and crack. However, peeling was observed on un-textured samples only. The surface damage of textured samples was slighter than un-textured samples. Especially under the high loading force, catastrophic damage appeared on the smooth surface. The worn surface of textured samples still maintained the similar state. This could be mainly due to the more complex friction process on the surface of textured sample. The wear rate of the frictional pair was also studied. The mechanisms of friction process for smooth and textured surface were analyzed.

The article investigates the impact of corporate social responsibility (CSR) and digital transformation (DT) on corporate financial performance (CFP) indicators, as well as the moderating effect of DT on the relationship between CSR and CFP indicators. The study was conducted using Stata 17.0 software based on data (5709 observations) on 558 A-share listed manufacturing companies of the Shanghai and Shenzhen Stock for 2012-2021 (excluding financial and insurance companies, ST and ST* companies, as well as companies with incomplete data). The independent variable used in the modelling process is the CSR rating report of the Hexun website, indicators of which are reconstructed by dividing them into strategic CSR (shareholder responsibility, employee responsibility, customer responsibility) and altruistic CSR (environmental responsibility and social contribution). The dependent variable is 2 CFP indicators: return on equity (ROE) and TOBIN's Q. The DT index is used as a moderating variable, for the calculation of which the texts of companies' annual reports were segmented using the Python programming language and standardised data on the frequency of keywords in 4 dimensions: digital technology application, Internet business model, intelligent manufacturing and contemporary information system; the weights for each dimension index was determined using the entropy approach. The control variables are corporate assets (Size), financial leverage level (Lev), current ratio (Cur), firm growth (Gro), shareholding ratio of the largest shareholder (First) and technological innovation (RD) of companies. The study also considered the year and industry factors. To study the moderating effect of DT on the relationship between CSR and CFP indicators of companies in different situations, the grouping variables chosen were the ownership type (state-owned and non-state-owned companies), the enterprise lifecycle (cash flow portfolio method was used to identify its stages) and the degree of market competition (Herfindahl-Hirschman Index). The modelling is based on a fixed-effects regression model. The study found that both CSR and DT have a positive impact on CFP, and that DT moderates the relationship between CSR and CFP, indicating that integrating digital technologies with sustainable development strategies can enhance financial benefits. The study also highlights the importance of different dimensions of corporate social responsibility. A high level of digital transformation strengthens the promotion effect of strategic social responsibility on current and future financial success of companies. Meanwhile, the promotion effect of altruistic social responsibility on current financial performance is significant. Heterogeneity analysis shows that the positive moderating effect of digital transformation on the relationship between corporate social responsibility and financial performance mainly applies to private firms, firms in the mature stage, and firms with low market competition. The article offers practical advice for businesses seeking to use digital transformation to maximise economic and social value.

Abstract Background It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. Methods We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009–2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. Results Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019–1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052–1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p 0.05). Conclusion A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States.

Abstract Background This study intends to explore the role and molecular mechanism of hsa_circ_0005519 in acute kidney injury (AKI). Methods We conducted reverse transcription-qPCR for human serum to determine levels of hsa_circ_0005519 in AKI patients and healthy controls. Hsa_circ_0005519 was inhibited for expression in HK-2 cells using specific siRNAs. A number of techniques, MTT and ELISA assays, were used to analyze the potential role of hsa_circ_0005519 in cell viability, oxidative stress, and inflammation of LPS-induced HK-2 cells. results The serum of patients with AKI exhibited a significant increase in hsa_circ_0005519 expression, compared with healthy controls. Hsa_circ_0005519 was knockdown by siRNA, and its knockdown led to cell viability increase in LPS-induced HK-2 cells. Inhibition of hsa_circ_0005519 can reverse the TNF-α, IL-6 and IL-1β increase in LPS-induced HK-2 cells. Inhibiting hsa_circ_0005519 led to downregulation of MPO and MDA levels. MiR-98-5p was a downstream miRNA for hsa_circ_0005519. MiR-98-5p can offset the effects of hsa_circ_0005519 on LPS-induced HK-2 cells. IFG1R was a target gene for miR-98-5p. Conclusions These findings indicate that the highly expressed hsa_circ_0005519 plays a promoting role in AKI.

Abstract Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.

Abstract This report describes a patient who developed recurrent hypoglycemia episodes after 23 days of antiplatelet therapy with clopidogrel for left subclavian artery stent implantation. The patient suffered from palpitation, profuse sweating and weakness on the 23rd day of clopidogrel treatment. The minimum plasma glucose was 2.2 mmol/L, and the hypoglycemia was associated with significantly elevated levels of insulin. A diagnosis of insulin autoimmune syndrome (IAS) was made with the presence of insulin autoantibody and a comprehensive differential diagnosis of other conditions related with hypoglycemia. Clopidogrel was stopped, and the patient was treated with acarbose and had frequent low‐carbohydrate meals; his hypoglycemia did not occur within 10 days. To date, seven cases of IAS induced by clopidogrel have been reported. Most reported cases were male aged in their 70s, and the hypoglycemic attack appeared 1–4 weeks after exposure to clopidogrel, characterized by severe hyperinsulinemia hypoglycemia with high titers of insulin autoantibodies. Most IAS cases can resolve spontaneously when they stop using the trigger medicine. Severe cases had been treated with drugs that reduce pancreatic insulin secretion (such as somatostatin and diazoxide), immunosuppressants (glucocorticoids, azathioprine and rituximab) and even immunoadsorption to remove the insulin autoantibody from the body. Considering the hypoglycemic attack might increase the risk of cardiovascular events among patients taking clopidogrel, we recommend that doctors should be aware of IAS as a rare severe adverse effect of clopidogrel, and be vigilant for the symptoms related with hypoglycemia in clopidogrel users.

Understanding the corrosion behavior of Mg alloys in the Cl− environments is crucial to preventing catastrophic accidents in their facilities due to their poor corrosion. The microstructures and corrosion behaviors of the Mg-4Gd-2Nd alloy under different heat-treatment conditions were investigated. The content of Mg41Nd5 in the alloy decreased significantly with increasing heat-treatment temperature. It was found that the formation of solid solution atomic oxides separates the lamellar Mg(OH)2 during the corrosion process of Mg alloys. With the increase of solid solution atomic oxides, lamellar Mg(OH)2 is no longer clustered and laid flat on the alloy surface. The loose Mg(OH)2 corrosion product film is eroded by Cl− and converted to the rod-like Mg2Cl(OH)3·4H2O, which lead to the detachment of the loose lamellar Mg(OH)2 in pieces. Furthermore, the corrosion products of the as-extruded alloy fall off in large blocks, whereas the corrosion products of the heat-treated alloys fall off in small pieces. Therefore, 540 °C-treated specimen exhibits best corrosion resistance.

Oxides play a crucial role in shaping various properties in ferritic alloys under Helium environment. This study investigates the thermodynamic and mechanical properties of Y4Zr3O12 and Y2Ti2O7 oxides in ferritic alloys with and without Helium utilizing a systematic first-principles approach. Firstly, the atomic arrangement of Y and Zr atoms at cation 18f sites in δ-(Y–Zr–O) oxide is identified, while it is found that Y4Zr3O12 exhibits a more robust formation tendency than Y2Ti2O7. Furthermore, it is noted that both Y4Zr3O12 and Y2Ti2O7 oxides demonstrate a prior ability to trap Helium compared to the bcc-Fe matrix, which leads to a substantial enhancement on the stiffness of both oxides. The elastic moduli of both Y4Zr3O12 and Y2Ti2O7 oxide exhibit a gradual increase with the growing Helium concentration. As a result, the enhanced shear modulus of oxides and sustained shear modulus of the bcc-Fe matrix collectively contribute to the overall strength of ferritic alloys under Helium environments. The findings in this work propose valuable insights for guiding critical strategies in the design of high-performance oxide-dispersion-strengthened ferritic alloys, particularly for applications in Helium environments.

Adding an anti-corrosion coating to the surface of magnesium (Mg) alloy is an effective means to improve its corrosion resistance, but it is particularly important to enhance the bonding force between the anti-corrosion coating and the Mg matrix. Epoxy resin coating is considered the most cost-effective approach from an industrial standpoint, while the hindering the wider utilization of Mg alloys with epoxy coating in the realm of engineering materials are due to their insufficient adhesion between Mg matrix and the epoxy coating. Here, we demonstrated a simple method for forming an epoxy resin/mineralized film composite coating. The mineralized products coatings were applied to the surface of Mg-3Nd alloy, via a direct reaction between Mg and 15 wt% Na2CO3 solution. Due to the inherent lamellar structure of alkaline magnesium carbonate mineralization film, the mechanical interlocking between the epoxy resin and the Mg substrate are remarkably strengthened. Therefore, this simple surface treatment method is promising to improve the adhesion between the epoxy resin and the matrix. Moreover, the effects of mineralized products coating on the corrosion resistance of Mg with epoxy coating were researched. It was observed that the corrosion resistance of Mg alloy with composite coatings are significantly enhanced. Such an investigation aims to provide a new method for developing a cost-effective and robust epoxy resin/mineralized film composite coating protection structure of Mg alloys in practical applications.

Abstract Background Auxin response factors (ARFs) are critical transcription factors that mediate the auxin signaling pathway and are essential for regulating plant growth. However, there is a lack of understanding regarding the ARF gene family in Liriodendron chinense, a vital species in landscaping and economics. Thus, further research is needed to explore the roles of ARFs in L. chinense and their potential applications in plant development. Result In this study, we have identified 20 LcARF genes that belong to three subfamilies in the genome of L. chinense. The analysis of their conserved domains, gene structure, and phylogeny suggests that LcARFs may be evolutionarily conserved and functionally similar to other plant ARFs. The expression of LcARFs varies in different tissues. Additionally, they are also involved in different developmental stages of somatic embryogenesis. Overexpression of LcARF1, LcARF2a, and LcARF5 led to increased activity within callus. Additionally, our promoter-GFP fusion study indicated that LcARF1 may play a role in embryogenesis. Overall, this study provides insights into the functions of LcARFs in plant development and embryogenesis, which could facilitate the improvement of somatic embryogenesis in L. chinense. Conclusion The research findings presented in this study shed light on the regulatory roles of LcARFs in somatic embryogenesis in L. chinense and may aid in accelerating the breeding process of this tree species. By identifying the specific LcARFs involved in different stages of somatic embryogenesis, this study provides a basis for developing targeted breeding strategies aimed at optimizing somatic embryogenesis in L. chinense, which holds great potential for improving the growth and productivity of this economically important species.

Abstract Introduction To investigate the association between alcohol drinking and glycemic management among adult patients with type 2 diabetes in regional China. Materials and Methods In this cross‐sectional survey conducted in Nanjing Municipality of China in 2018, adult type 2 diabetes patients were randomly selected from urban and rural communities. The outcome variable was the glycemic management status. The explanatory measure was alcohol drinking. Mixed‐effects regression models were employed to estimate odds ratios (ORs) and 95% confidence interval (95% CI) for examining the associations of alcohol drinking with glycemic management among type 2 diabetes patients. Results Among the overall 5,663 participants, the glycemic management rate was 39.8% (95% CI = 38.5, 41.1), with 41.2% (95% CI = 39.7, 42.7), 43.9% (95% CI = 38.9, 48.8), and 34.1% (95% CI = 31.5, 36.7) for non‐drinkers, mild/moderate drinkers, and heavy drinkers, respectively. After adjustment for potential confounders and community‐level clustering effect, heavy and mild/moderate alcohol drinkers were at 0.76 (95% CI = 0.66, 0.89) and 1.04 (95% CI = 0.87, 1.28) times odds to have glycemia under control than non‐drinkers among the overall participants. Furthermore, when stratified separately by gender and use of anti‐diabetes agents, the scenario within men, either regular or irregular users of anti‐diabetes agents was the same as that for overall participants, while the association between alcohol drinking and glycemic management became non‐significant among women. Conclusions Heavy alcohol drinking might have a negative effect on glycemic management among patients with type 2 diabetes irrespective of the use of anti‐diabetes agents in regional China. This study has important public health implications regarding precision intervention on patients' glycemia control for type 2 diabetes management.

BackgroundIn some patients, persistent gastrointestinal symptoms like abdominal pain, nausea, and diarrhea occur as part of long COVID-19 syndrome following acute respiratory symptoms caused by SARS-CoV-2. However, the characteristics of immune cells in the gastrointestinal tract of COVID-19 patients and their association with these symptoms remain unclear.MethodologyData were collected from 95 COVID-19 patients. Among this cohort, 11 patients who exhibited gastrointestinal symptoms and underwent gastroscopy were selected. Using imaging mass cytometry, the gastrointestinal tissues of these patients were thoroughly analyzed to identify immune cell subgroups and investigate their spatial distribution.ResultsSignificant acute inflammatory responses were found in the gastrointestinal tissues, particularly in the duodenum, of COVID-19 patients. These alterations included an increase in the levels of CD68+ macrophages and CD3+CD4+ T-cells, which was more pronounced in tissues with nucleocapsid protein (NP). The amount of CD68+ macrophages positively correlates with the number of CD3+CD4+ T-cells (R = 0.783, p < 0.001), additionally, spatial neighborhood analysis uncovered decreased interactions between CD68+ macrophages and multiple immune cells were noted in NP-positive tissues. Furthermore, weighted gene coexpression network analysis was employed to extract gene signatures related to clinical features and immune responses from the RNA-seq data derived from gastrointestinal tissues from COVID-19 patients, and we validated that the MEgreen module shown positive correlation with clinical parameter (i.e., Total bilirubin, ALT, AST) and macrophages (R = 0.84, p = 0.001), but negatively correlated with CD4+ T cells (R = −0.62, p = 0.004). By contrast, the MEblue module was inversely associated with macrophages and positively related with CD4+ T cells. Gene function enrichment analyses revealed that the MEgreen module is closely associated with biological processes such as immune response activation, signal transduction, and chemotaxis regulation, indicating its role in the gastrointestinal inflammatory response.ConclusionThe findings of this study highlight the role of specific immune cell groups in the gastrointestinal inflammatory response in COVID-19 patients. Gene coexpression network analysis further emphasized the importance of the gene modules in gastrointestinal immune responses, providing potential molecular targets for the treatment of COVID-19-related gastrointestinal symptoms.

BackgroundDelivery systems based on albumin nanoparticles (NPs) have recently garnered substantial interest in anti-tumor drug development. However, systematic bibliometric analyses in this field remain lacking. This study aimed to analyze the current research status, hotspots, and frontiers in the application of albumin NPs in the field of oncology from a bibliometric perspective.MethodsUsing the Web of Science Core Collection (WOSCC) as the data source, retrieved articles were analyzed using software, such as VOSviewer 1.6.18 and CiteSpace 6.1.6, and the relevant visualization maps were plotted.ResultsFrom 1 January 2000, to 15 April 2024, 2,262 institutions from 67 countries/regions published 1,624 articles related to the application of albumin NPs in the field of oncology. The USA was a leader in this field and held a formidable academic reputation. The most productive institution was the Chinese Academy of Sciences. The most productive author was Youn YS, whereas Kratz F was the most frequently co-cited author. The most productive journal was the International Journal of Nanomedicine, whereas the Journal of Controlled Release was the most co-cited journal. Future research hotspots and frontiers included “rapid and convenient synthesis methods predominated by self-assembly,” “surface modification,” “construction of multifunctional NPs for theranostics,” “research on natural active ingredients mainly based on phenolic compounds,” “combination therapy,” and “clinical applications.”ConclusionBased on our bibliometric analysis and summary, we obtained an overview of the research on albumin NPs in the field of oncology, identified the most influential countries, institutions, authors, journals, and citations, and discussed the current research hotspots and frontiers in this field. Our study may serve as an important reference for future research in this field.

Abstract Patients who have non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations are more prone to brain metastasis (BM) and poor prognosis. Previous studies showed that the tumor microenvironment of BM in these patients is immunosuppressed, as indicated by reduced T‐cell abundance and activity, although the mechanism of this immunosuppression requires further study. This study shows that reactive astrocytes play a critical role in promoting the immune escape of BM from EGFR‐mutated NSCLC by increasing the apoptosis of CD8+ T lymphocytes. The increased secretion of interleukin 11(IL11) by astrocytes promotes the expression of PDL1 in BM, and this is responsible for the increased apoptosis of T lymphocytes. IL11 functions as a ligand of EGFR, and this binding activates EGFR and downstream signaling to increase the expression of PDL1, culminating in the immune escape of tumor cells. IL11 also promotes immune escape by binding to its intrinsic receptor (IL11Rα/glycoprotein 130 [gp130]). Additional in vivo studies show that the targeted inhibition of gp130 and EGFR suppresses the growth of BM and prolongs the survival time of mice. These results suggest a novel therapeutic strategy for treatment of NSCLC patients with EGFR mutations.

This paper proposes a novel protective material that enhances the impact resistance of metaconcrete by integrating rubber aggregates. The study delves into the mesoscopic mechanisms of wave attenuation in this material and the regulation of its performance accordingly. It first explores the effect of various design parameters of engineering aggregates on bandgap formation and then further investigates the influence of material viscoelastic properties on its bandgap width. Mesoscale simulations of spalling tests demonstrate that incorporating rubber aggregates can effectively expand the bandgap range, enhance energy absorption, reduce damage to the mortar matrix, and ultimately improve the impact resistance of metaconcrete. Simulation results in the present study highlight the effectiveness of rubber aggregates in strengthening metaconcrete's impact resistance.

Abstract Objective To investigate the prognostic factors of patients with anti‐melanoma differentiation‐associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD). Methods A retrospective analysis was conducted on clinical data of 125 patients with anti‐MDA5 + CADM‐ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ2 test, Log‐rank test, COX and logistic regression analysis. Results In this cohort, 125 anti‐MDA5 + CADM‐ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow‐up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C‐reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti‐MDA5 + CADM‐ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016). Conclusion Patients with anti‐MDA5 + CADM‐ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions.

Abstract The global COVID‐19 outbreak severely hampered the growth of the global economy, prompting the implementation of the strictest prevention policies in China. Establishing a significant relationship between changes in nighttime light and COVID‐19 lockdowns from a geospatial perspective is essential. In light of nighttime light remote sensing, we evaluated the spatiotemporal dynamic effects of COVID‐19 city lockdowns on human activity intensity in the Zhengzhou region. Prior to the COVID‐19 outbreak, nighttime light in the Zhengzhou region maintained a significant growth trend, even under regular control measures. However, following the October 2022 COVID‐19 lockdown, nighttime light experienced a substantial decrease. In the central area of Zhengzhou, nighttime light decreased by at least 18% compared to pre‐lockdown levels, while in the sub‐center, the decrease was around 14%. The areas where nighttime light decreased the most in the central region were primarily within a 15 km radius, while in the sub‐center, the decrease was concentrated within a 5 km radius. These changes in both statistical data and nighttime light underscored the significant impact of the COVID‐19 lockdown on economic activities in the Zhengzhou region.

ObjectiveWe utilized bibliometric and data visualization techniques to discern the primary research domains and emerging frontiers in the field of adult hippocampal neurogenesis (AHN).MethodsWe systematically searched the Web of Science database for AHN-related articles published between 2004 and 2023. The retrieved articles were filtered based on publication types (articles and reviews) and language (English). We employed CiteSpace, VOSviewer, and the online bibliometric platform (bibliometric.com) to visualize and analyze the collected data.ResultsIn total, 1,590 AHN-related publications were discovered, exhibiting a steady increase in yearly publications over time. The United States emerged as the leading contributor in AHN research in terms of both publication quantity and national influence. Among all research institutions in the field of AHN, the University of California System exhibited the highest impact. Kempermann, Gerd was the most active author. The publications of the top three active authors primarily focused on the functions of AHN, and reversing hippocampal damage and cognitive impairment by improving AHN. An analysis of reference co-citation clustering revealed 8 distinct research clusters, and the notable ones included “adult hippocampal neurogenesis,” “neurogenesis,” “hippocampus,” “dentate gyrus,” “neural stem cell,” and “depression.” Additionally, a burst keyword detection indicated that ‘anxiety’ is a current research hotspot in the field of AHN.ConclusionThis in-depth bibliographic assessment of AHN offers a deeper insight into the present research hotspots in the field. The association between AHN and cognitive diseases, such as Alzheimer’s disease (AD) and anxiety, has emerged as a prominent research hotspot.

BackgroundPolycystic ovary syndrome with insulin resistance (PCOS-IR) is the most common endocrine and metabolic disease in women of reproductive age, and low fertility in PCOS patients may be associated with oocyte quality; however, the molecular mechanism through which PCOS-IR affects oocyte quality remains unknown.MethodsA total of 22 women with PCOS-IR and 23 women without polycystic ovary syndrome (control) who underwent in vitro fertilization and embryo transfer were recruited, and clinical information pertaining to oocyte quality was analyzed. Lipid components of follicular fluid (FF) were detected using high-coverage targeted lipidomics, which identified 344 lipid species belonging to 19 lipid classes. The exact lipid species associated with oocyte quality were identified.ResultsThe number (rate) of two pronuclear (2PN) zygotes, the number (rate) of 2PN cleaved embryos, and the number of high-quality embryos were significantly lower in the PCOS-IR group. A total of 19 individual lipid classes and 344 lipid species were identified and quantified. The concentrations of the 19 lipid species in the normal follicular fluid (control) ranged between 10-3 mol/L and 10-9 mol/L. In addition, 39 lipid species were significantly reduced in the PCOS-IR group, among which plasmalogens were positively correlated with oocyte quality.ConclusionsThis study measured the levels of various lipids in follicular fluid, identified a significantly altered lipid profile in the FF of PCOS-IR patients, and established a correlation between poor oocyte quality and plasmalogens in PCOS-IR patients. These findings have contributed to the development of plasmalogen replacement therapy to enhance oocyte quality and have improved culture medium formulations for oocyte in vitro maturation (IVM).

Liver fibrosis occurs in response to chronic damage and inflammation to the liver. Leaving untreated, it can lead to decreased liver function and can eventually progress to cirrhosis, a more advanced and irreversible state of liver damage. Clinical investigations showed that chronic liver disease associated with neurological symptoms including anxiety, depression, and cognitive decline. However, few therapeutic options are available for treating liver and related brain pathologies simultaneously. In this study, we aim to find therapeutic candidates that target the liver-brain axis. Gossypetin, a flavonoid from sedum, shows promising capability in treating liver and brain pathologies in CCl4-induced mouse model. Short term of gossypetin administration is sufficient to ameliorate impaired liver function and pre-existing liver fibrosis, suppress MKK3/6-p38 MAPK and p53 activation, and abolish the activation of hepatic stellate cells and Kupffer cells. Although we observe no neuronal loss in the brain of mice with liver fibrosis, we do observe astrogliosis and microglial activation in certain brain regions, especially the hippocampus. Brief gossypetin administration also shows potential in alleviating neuroinflammation in these regions. These results suggest that gossypetin can target the liver-brain axis and be a promising candidate for treating chronic liver fibrosis patients with neurological symptoms.

Mangrove ecosystems have important ecological and economic values, especially their ability to store carbon. However, in recent years, human disturbance has accelerated mangrove degradation. Among them, the emission of pollutants cannot be ignored. It is of great significance for carbon emission reduction and ecological protection to study the impacts of different pollutants on mangroves and their carbon stocks. Based on the remote sensing data of coastal areas south of the Yangtze River in mainland China, this paper builds the ensemble learning model Random Forest (RF) and Gradient Boosting Regression (GBR) to empirically analyse the relationship between industrial wastewater, industrial sulfur dioxide (SO2), PM2.5 and mangrove forests. The results show that the pollutant concentration of meteorological normalisation is more stable. The importance of pollutants presents regional heterogeneity. The area of mangroves in different cities and the corresponding total carbon stocks show different trends with the increase or decrease of pollutants, and there is a dynamic balance between urban pollutant discharge and mangrove growth in some cities. The research in this paper provides an analysis and explanation from the perspective of machine learning to explore the relationship between mangroves and pollutants and at the same time, provides scientific suggestions for the formulation of future pollutant emission policies in different cities.

Abstract Monocarboxylate transporter 1 (MCT1) exhibits essential roles in cellular metabolism and energy supply. Although MCT1 is highly expressed in activated B cells, it is not clear how MCT1-governed monocarboxylates transportation is functionally coupled to antibody production during the glucose metabolism. Here, we report that B cell-lineage deficiency of MCT1 significantly influences the class-switch recombination (CSR), rendering impaired IgG antibody responses in Mct1 f/f Mb1 Cre mice after immunization. Metabolic flux reveals that glucose metabolism is significantly reprogrammed from glycolysis to oxidative phosphorylation in Mct1-deficient B cells upon activation. Consistently, activation-induced cytidine deaminase (AID), is severely suppressed in Mct1-deficient B cells due to the decreased level of pyruvate metabolite. Mechanistically, MCT1 is required to maintain the optimal concentration of pyruvate to secure the sufficient acetylation of H3K27 for the elevated transcription of AID in activated B cells. Clinically, we found that MCT1 expression levels are significantly upregulated in systemic lupus erythematosus patients, and Mct1 deficiency can alleviate the symptoms of bm12-induced murine lupus model. Collectively, these results demonstrate that MCT1-mediated pyruvate metabolism is required for IgG antibody CSR through an epigenetic dependent AID transcription, revealing MCT1 as a potential target for vaccine development and SLE disease treatment.

The precise expression of transcription factors (TFs) is crucial for plant growth and development, especially during somatic embryogenesis. However, conventional overexpression approaches, commonly used for functional genetics, can lead to deleterious effects. Therefore, it is imperative to ensure that TFs are expressed in a controlled and timely manner when aiming to enhance the efficiency of somatic embryogenesis. In this study, a dexamethasone/glucocorticoid receptor (DEX/GR) inducible expression system was employed to modulate the protein expression levels of target TFs within the nucleus during somatic embryogenesis in Liriodendron hybrids. We selected the WUSCHEL (WUS) gene, a well-established functional TF known for its vital role in somatic embryogenesis, as a model to assess the effectiveness of this system. Through DEX treatment, we induced the translocation of LhWUS-GR/LhWUS-GFP-GR fusion proteins from the cytoplasm to the nucleus, consequently leading to WUS-driven somatic embryogenesis. As the DEX concentration increased, there was a corresponding increase in the migration of the LhWUS-GFP-GR fusion protein into the nucleus. Additionally, we observed a higher proliferation ratio of callus expressing LhWUS-GR when exposed to varying DEX concentrations. Notably, the efficiency of somatic embryogenesis exhibited significant improvement under optimal DEX concentration. In conclusion, our study successfully utilizes the DEX/GR inducible system in Liriodendron hybrids, offering a valuable tool for the precise control and utilization of TFs at the desired levels. This innovative approach holds promise for advancing our understanding of TF function and enhancing plant development through the regulated manipulation of TF expression.

Recognizing each aerial photo with high-resolution (HR) is a useful technology in image understanding. Herein, a manifold-regularized feature selection (MRFS) is designed to acquire discriminative perceptual features that classify HR aerial images into different categories. Practically, human visual cognition process reflects that, in a scenic picture, the less visually attractive image patches are highly related. Meanwhile, the foreground highly visually attractive image patches are practically unrelated with each other. Following this observation, we in this work propose a multi-layer low-rank paradigm which calculates a succinct set of visually attractive patches in foreground. We sequentially link the above attractive image patches to build a so-called gaze shifting path (GSP). GSP can mimick how humans perceiving different aerial images. Afterward, we formulate a MRFS framework to obtain a subset of high quality features from the entire deep GSP representation. Thereby, an SVM is learned simultaneously. Moreover, the distribution of HR aerial images on the underlying manifold can be maximally preserved during feature selection (FS). To comprehensively evaluate our method, we collect a massive-scale aerial image set containing over 4.87 million high- and low-resolution aerial images. Extensive empirical validations on have shown our algorithm’s efficiency and effectiveness: 1) the testing time cost is 0.8s faster than the second best one to categorize each HR aerial image, 2) the average categorization accuracy is over 4.5% higher than the second best one.

Abstract Background Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases. Methods Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed. Results The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results. Conclusions The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.

Abstract Equiluminant stimuli help assess the integrity of colour perception and the relationship of colour to other visual features. As a result of individual variation, it is necessary to calibrate experimental visual stimuli to suit each individual’s unique equiluminant ratio. Most traditional methods rely on training observers to report their subjective equiluminance point. Such paradigms cannot easily be implemented on pre-verbal or non-verbal observers. Here, we present a novel Pupil Frequency-Tagging Method (PFTM) for detecting a participant’s unique equiluminance point without verbal instruction and with minimal training. PFTM analyses reflexive pupil oscillations induced by slow (

Chrysanthemum black spot disease caused by Alternaria alternate infestation is a widespread and extremely destructive foliar disease of chrysanthemums. We compared the resistance of 14 chrysanthemum relatives to chrysanthemum black spot disease, and identified the main indicators for the evaluation and screening of chrysanthemum disease resistance, which is of great significance in laying the foundation for a larger-scale screening of chrysanthemum relatives for disease resistance and the breeding of new disease-resistant cultivars. After artificial inoculation and identification, two disease-resistant germplasm resources, 11 moderately resistant materials, and one sensitive material were obtained. In both resistant and susceptible species, we found that the trichome density and leaf wax content of the resistant material were significantly higher than that of the sensitive material, while the stomata size was smaller than that of the sensitive material. In addition, we found that the leaf extract of the disease-resistant germplasm effectively inhibited the growth rate of A. alternate mycelium on the plate, and GC-MS components found that the leaves of resistant germplasm contained more volatile antifungal organic compounds, of which the abundant falcarinol and Germacrene D might play an important role in resistance to chrysanthemum black spot disease. In summary, epidermal trichome density, wax content and terpene substance content are three important reference indicators for disease resistance evaluation of related genera of chrysanthemum. The identified resistant germplasm can also be used as parents for future cross-breeding or as rootstocks.

Abstract Crowdfunding provides a novel and potential way for innovative but risky new ventures to fund their new product development (NPD) projects. To help potential investors evaluate the projects and enhance the credibility of disclosure, founders are struggling with how to phrase the project description. The rapidly growing cleantech crowdfunding projects provide an ideal context to study this issue. We collected information on cleantech crowdfunding projects and matched non-cleantech crowdfunding projects from Kickstarter. The sample period extends from January 2013 to October 2018. Using signaling research as a theoretical lens and a dictionary-based, computerized text mining method, we found that founders of high-quality cleantech crowdfunding projects could create a reliable signal of quality by providing a project description with a less ambiguous tone and thus boost the success of crowdfunding. Moreover, the signaling effectiveness of a less ambiguous tone is more pronounced in cleantech crowdfunding than in matched non-cleantech crowdfunding, suggesting that the marginal benefit of using a less ambiguous tone is larger when the industry information environment is noisier. Further evidence shows that the signaling effectiveness of a less ambiguous tone in cleantech crowdfunding could be strengthened by backers’ endorsements. Our findings imply that tone ambiguity in project descriptions is related to founders’ information-concealing behavior. Potential investors could search ambiguous words in project descriptions and just allocate their limited attention into projects with a low percentage of ambiguous words to avoid information overload. Founders of high-quality projects could boost crowdfunding success by using a less ambiguous tone to describe their projects. The marginal effect is larger when there is greater uncertainty about project prospects.

Abstract Background The association between air pollution and retinal diseases such as age-related macular degeneration (AMD) has been demonstrated, but the pathogenic correlation is unknown. Damage to the outer blood–retinal barrier (oBRB), which consists of the retinal pigment epithelium (RPE) and choriocapillaris, is crucial in the development of fundus diseases. Objectives To describe the effects of airborne fine particulate matter (PM2.5) on the oBRB and disease susceptibilities. Methods A PM2.5-exposed mice model was established through the administration of eye drops containing PM2.5. Optical coherence tomography angiography, transmission electron microscope, RPE immunofluorescence staining and Western blotting were applied to study the oBRB changes. A co-culture model of ARPE-19 cells with stretching vascular endothelial cells was established to identify the role of choroidal vasodilatation in PM2.5-associated RPE damage. Results Acute exposure to PM2.5 resulted in choroidal vasodilatation, RPE tight junctions impairment, and ultimately an increased risk of retinal edema in mice. These manifestations are very similar to the pachychoroid disease represented by central serous chorioretinopathy (CSC). After continuous PM2.5 exposure, the damage to the RPE was gradually repaired, but AMD-related early retinal degenerative changes appeared under continuous choroidal inflammation. Conclusion This study reveals oBRB pathological changes under different exposure durations, providing a valuable reference for the prevention of PM2.5-related fundus diseases and public health policy formulation. Graphical abstract

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system that involves B-cell receptor signaling as well as astrocyte–microglia interaction, which both contribute to evolution of NMOSD lesions. Main body Through transcriptomic and flow cytometry analyses, we found that Bruton’s tyrosine kinase (BTK), a crucial protein of B-cell receptor was upregulated both in the blood and cerebrospinal fluid of NMOSD patients. Blockade of BTK with zanubrutinib, a highly specific BTK inhibitor, mitigated the activation and maturation of B cells and reduced production of causal aquaporin-4 (AQP4) autoantibodies. In a mouse model of NMO, we found that both BTK and pBTK expression were significantly increased in microglia. Transmission electron microscope scan demonstrated that BTK inhibitor ameliorated demyelination, edema, and axonal injury in NMO mice. In the same mice colocalization of GFAP and Iba-1 immunofluorescence indicated a noticeable increase of astrocytes–microglia interaction, which was alleviated by zanubrutinib. The smart-seq analysis demonstrated that treatment with BTK inhibitor instigated microglial transcriptome changes including downregulation of chemokine-related genes and genes involved in the top 5 biological processes related to cell adhesion and migration, which are likely responsible for the reduced crosstalk of microglia and astrocytes. Conclusions Our results show that BTK activity is enhanced both in B cells and microglia and BTK inhibition contributes to the amelioration of NMOSD pathology. These data collectively reveal the mechanism of action of BTK inhibition and corroborate BTK as a viable therapeutic target.

Abstract Background The diagnostic accuracy of [18F]-fluorodeoxyglucose ([18F]-FDG) positron emission tomography imaging in accurately identifying thyroid lesions is limited, primarily due to the physiological uptake of normal head and neck tissues and inflammatory uptake in lymph nodes. Since fibroblast activating protein is highly expressed in tumors and largely unexpressed in normal tissues, quinoline-based fibroblast activating protein inhibitors (FAPI) have emerged as promising tools in the diagnosis of cancer and other medical conditions. Several studies have reported on the feasibility and value of FAPI in thyroid cancer. Main body In this narrative review, we summarize the current literature on state-of-the-art FAPI positron emission tomography imaging for thyroid cancer and fibroblast activating protein-targeted radionuclide therapy. We provide an overview of FAPI uptake in normal thyroid tissue, thyroid cancer and its metastases. Additionally, we highlight the difference between FAPI uptake and [18F]-FDG uptake in thyroid lesions. Furthermore, we discuss the therapeutic value of FAPI in iodine-refractory thyroid cancer. Conclusion The utilization of fibroblast activating protein inhibitors in thyroid cancer holds significant promise, offering clinicians valuable insights for more precise diagnose choices and treatments strategies in the future.

Abstract Plant lateral organs are often elaborated through repetitive formation of developmental units, which progress robustly in predetermined patterns along their axes. Leaflets in compound leaves provide an example of such units that are generated sequentially along the longitudinal axis, in species-specific patterns. In this context, we explored the molecular mechanisms underlying an acropetal mode of leaflet initiation in chickpea pinnate compound leaf patterning. By analyzing naturally occurring mutants multi-pinnate leaf1 (mpl1) that develop higher-ordered pinnate leaves with more than forty leaflets, we show that MPL1 encoding a C2H2-zinc finger protein sculpts a morphogenetic gradient along the proximodistal axis of the early leaf primordium, thereby conferring the acropetal leaflet formation. This is achieved by defining the spatiotemporal expression pattern of CaLEAFY, a key regulator of leaflet initiation, and also perhaps by modulating the auxin signaling pathway. Our work provides novel molecular insights into the sequential progression of leaflet formation.

Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns. It takes ∼24 h for tri-gas incubator to achieve steady cell hypoxia, which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion (IR) injury. Inspired from the structure of native intestinal villi, we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on co-axial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold. The chip was featured on: (i) eight times the oxygen exchange efficiency compared with the conventional device, tri-gas incubator, (ii) implantation of intestinal organoid reproducing all types of intestinal epithelial cells, and (iii) bio-responsiveness to hypoxia and reoxygenation (HR) by presenting metabolism disorder, inflammatory reaction, and cell apoptosis. Strikingly, it was found for the first time that Olfactomedin 4 (Olfm4) was the most significantly down-regulated gene under a rapid HR condition by sequencing the RNA from the organoids. Mechanistically, OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation, thus it could be used as a therapeutic target. Altogether, this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo, and sets an example of next-generation multisystem-interactive organoid chip for finding precise therapeutic targets of IR injury.

In the present work, a power battery pack and a novel thermal management system (TMS) based on the tubular heat pipe (THP) technology are designed according to the parameters of a pure electric light truck and battery. The TMS consists of THPs, power batteries, cooling plates, fins, and equivalent thermal conductivity is used to characterize the excellent thermal conductivity of THP. The heat generation rate of the battery at different discharge rates is obtained by establishing a multi-scale electrochemical–thermal coupling model, which accuracy is verified by the experiment. A multi-physics field coupling model is built to the thermal management system designed for the study. The results show that the battery temperature is higher when the battery is far from the THP in the cooling plate, and the maximum temperature reaches 35.6 °C at 1 C. Furthermore, the temperature difference between batteries is proportional to the discharge rate, and the maximum temperature difference reaches 7 °C at 2 C. The change in inlet temperature and wind speed can only restrain the temperature rise, while the temperature difference of the battery module is always 3.2 °C. When a fin spacing of 3 mm is chosen, the best temperature uniformity of the battery module is achieved at this time. The use of the multi-scale multi-physics field coupling analysis method in BTMS with heat pipes can be used as a reference for future numerical simulations of the same type.

Abstract Elastocaloric (eC) cooling is a promising environmental-friendly emerging cooling technology that has the potential for applications at different scales. Although the performance of eC cooling is already sufficient for some applications, a balance is needed for reliability, cost, and ease of maintenance to achieve commercialization in the near future. In this Perspective, we describe challenges and necessary steps towards practical eC cooling, including material properties and manufacturing techniques, actuators that drive eC materials, essentials for good heat transfer, and different work recovery schemes, before introducing our envisioned application scenarios.

Abstract High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Abstract Akebia fruit is a plant used for both medicinal and edible purposes. In recent years, due to the rich phytochemical composition with bioactive effects, Akebia fruit has attracted increasing attention on its composition analysis, active ingredients identification, and product applications. For example, the protein, sugar, amino acids, and vitamin C content of the pulp is higher than that of ordinary fruit. The seeds are not only processed into edible oil, it is also rich in protein and have the potential to be developed into a new resource with beneficial effects on human health. However, the research on the understanding of Akebia as a plant fruit is relatively lacking. In this review, an overview of Akebia fruit from food perspectives, including extraction methods and phytochemicals, bioactive functions, and various applications, were summarized. Finally, based on the current status and existing challenges, the prospect and future development direction of Akebia fruit were discussed.

Early mutation identification guides patients with colorectal cancer (CRC) toward targeted therapies. In the present study, 414 patients with CRC were enrolled, and amplicon-based targeted next-generation sequencing (NGS) was then performed to detect genomic alterations within the 73 cancer-related genes in the OncoAim panel. The overall mutation rate was 91.5 % (379/414). Gene mutations were detected in 38/73 genes tested. The most frequently mutated genes were TP53 (60.9 %), KRAS (46.6 %), APC (30.4 %), PIK3CA (15.9 %), FBXW7 (8.2 %), SMAD4 (6.8 %), BRAF (6.5 %), and NRAS (3.9 %). Compared with the wild type, TP53 mutations were associated with low microsatellite instability/microsatellite stability (MSI-L/MSS) (P = 0.007), tumor location (P = 0.043), and histological grade (P = 0.0009); KRAS mutations were associated with female gender (P = 0.026), distant metastasis (P = 0.023), TNM stage (P = 0.013), and histological grade (P = 0.004); APC mutations were associated with patients

BackgroundThere is evidence of an association between the gut microbiota and progression of stroke. However, the relationship between gut microbial metabolites, specifically bile acids (BAs), and post-ischemic stroke disability and poor functional outcomes remains unexplored.MethodsPatients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in the Third China National Stroke Registry were grouped according to total bile acid (TBA) quartile on admission. Association of TBA with disability and poor functional outcomes were evaluated using logistic regression models and restricted cubic splines.ResultsData for 9,536 patients were included. After adjusting for confounders, the risks of disability and poor functional outcomes were significantly lower in the highest TBA quartile than in the lowest TBA quartile at the 3-month follow-up, with respective odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.55–0.78; p

Bone defects resulting from severe trauma, tumors, inflammation, and other factors are increasingly prevalent. Stem cell-based therapies have emerged as a promising alternative. Dental pulp stem cells (DPSCs), sourced from dental pulp, have garnered significant attention owing to their ready accessibility and minimal collection-associated risks. Ongoing investigations into DPSCs have revealed their potential to undergo osteogenic differentiation and their capacity to secrete a diverse array of ontogenetic components, such as extracellular vesicles and cell lysates. This comprehensive review article aims to provide an in-depth analysis of DPSCs and their secretory components, emphasizing extraction techniques and utilization while elucidating the intricate mechanisms governing bone regeneration. Furthermore, we explore the merits and demerits of cell and cell-free therapeutic modalities, as well as discuss the potential prospects, opportunities, and inherent challenges associated with DPSC therapy and cell-free therapies in the context of bone regeneration.

ObjectiveThe aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection.MethodsThis retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months.ResultsA total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = −0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871–10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071–4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563–7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621–396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029–3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190–27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074–10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months.ConclusionIn SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months.

Based on the pursuit of lower temperatures and environmentally friendly refrigerants in domestic refrigerator-freezers, this paper investigates the performance of a hydrocarbon mixture R600/R290 in a bypass two-circuit cycle applied in −40 °C frost-free refrigerator-freezer. With the aim of achieving a temperature below −40 °C in the freezer compartment and saving energy consumption in the entire system, experiments are conducted to explore the optimal composition and charge of R600/R290. The results indicate that when the total charge of R290/R600 is 77 g and the mass fraction is 43 %/57 %, the freezer compartment can reach −40.6 °C and has a low daily energy consumption of 1.514 kW h/24h at the ambient temperature of 32 °C. In addition, the effect of fan voltage, which is used to characterize the airflow rate in the freezer compartment, on the system performance at different ambient temperatures is also studied. Under the premise that the charge of R290/R600 is 77 g and the mass fraction is 48 %/52 %, when the fan voltage is 7.5 V, the system daily energy consumption is the lowest. At this time, the system daily energy consumption at 25 °C and 32 °C ambient temperatures is 1.161 kW h/24h and 1.553 kW h/24h, respectively.

Abstract Background THBS2, a member of the extracellular matrix glycoprotein family, can effectively inhibit tumour growth and angiogenesis. This study aimed to investigate the biological role of THBS2 in various types of cancers and the mechanisms underlying the malignant progression of colorectal cancer (CRC). Methods THBS2 expression in pan-cancer tissues and cell lines was assessed using the HPA, TISCH and CCLE databases. The CIBERSORT, ESTIMATE, TIMER, xCell and ssGSEA (implemented using the IOBR R package) algorithms were used to calculate the proportion of tumour-infiltrating immune cells based on the expression profile of THBS2 in TCGA-COAD cohort. The clusterprofiler R package was used to implement GO and KEGG pathway enrichm SNVs were compared between the high- and low-THBS2-expression groups using the maftools R package. Additionally, immunotherapy responses were compared between the high- and low-THBS2-expression groups based on immunophenoscores (IPSs). CT26 cells were engineered to overexpress THBS2 (CT26-THBS2) to investigate its regulatory effects on HIF1 and cellular metabolism. The conditioned medium from CT26-THBS2 cells was collected to examine its effect on the M2 polarisation of RAW264.7 macrophages. Subsequently, in vitro experiments were performed to validate the inhibitory effects of M2-polarised macrophages on T-cell proliferation and cytotoxicity. A CT26-THBS2 tumour-bearing mouse model was constructed to validate the impact of high THBS2 expression in tumour cells on the tumour microenvironment in vivo. Results THBS2 expression was upregulated in a majority of tumours, including COAD, and was positively associated with ESTIMATEScore, ImmuneScore and StromalScore. Furthermore, THBS2 expression was positively associated with angiogenesis and epithelial–mesenchymal transition and negatively associated with DNA repair, cell cycle and DNA replication in most tumours. THBS2 expression was considerably associated with progression-free interval (PFI) and positively associated with MSI in COAD. THBS2 methylation levels were remarkably lower in COAD tissues than in healthy tissues. The high expression of THBS2 in CT26 cells remarkably promoted the nuclear translocation of HIF1 and consequently enhanced lactate metabolism in cells. In vitro and in vivo experiments revealed that lactate released by tumour cells promoted M2 polarisation of macrophages, leading to inhibition of T-cell proliferation and cytotoxicity. Conclusions THBS2 expression is associated with PFI, immune cell infiltration, immune regulation, cell death, cell migration, epithelial–mesenchymal transition, angiogenesis and genomic variations in COAD. THBS2 may serve as a biomarker for immunotherapy in COAD. Upregulated THBS2 expression in CRC cells inhibits anti-tumour immunity through the HIF1A/lactic acid/GPR132 pathway.