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1.
Angew Chem Int Ed Engl ; : e202409763, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954763

ABSTRACT

Developing non-platinum group metal catalysts for the sluggish hydrogen oxidation reaction (HOR) is critical for alkaline fuel cells. To date, Ni-based materials are the most promising candidates but still suffer from insufficient performance. Herein, we report an unconventional hcp/fcc Ni (u-hcp/fcc Ni) heteronanocrystal with multiple epitaxial hcp/fcc heterointerfaces and coherent twin boundaries, generating rugged surfaces with plenty of asymmetric convex sites. Systematic analyses discover that such convex sites enable the adsorption of *H in unusual bridge positions with weakened binding energy, circumventing the over-strong *H adsorption on traditional hollow positions, and simultaneously stabilizing interfacial *H2O. It thus synergistically optimizes the HOR thermodynamic process as well as reduces the kinetic barrier of the rate-determining Volmer step. Consequently, the developed u-hcp/fcc Ni exhibits the top-rank alkaline HOR activity with a mass activity of 40.6 mA mgNi-1 (6.3 times higher than fcc Ni control) together with superior stability and high CO-tolerance. These results provide a paradigm for designing high-performance catalysts by shifting the adsorption state of intermediates through configuring surface sites.

2.
Environ Res ; : 119612, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39004394

ABSTRACT

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7,653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The relationships between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [ß (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; ß (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [ß (95% CI): 0.97 (0.61, 1.34) in males; ß (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) µmol/L for males and 3.81 (95% CI: 1.60, 6.03) µmol/L for females. The relation between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption.

3.
Plant Physiol ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38917205

ABSTRACT

Plant virus-derived vectors are rapid and cost-effective for protein expression and gene functional studies in plants, particularly for species that are difficult to genetically transform. However, few efficient viral vectors are available for functional studies in Asteraceae plants. Here, we identified a potyvirus named zinnia mild mottle virus (ZiMMV) from common zinnia (Zinnia elegans Jacq.) through next-generation sequencing. Using a yeast homologous recombination strategy, we established a full-length infectious cDNA clone of ZiMMV under the control of the cauliflower mosaic virus 35S promoter. Furthermore, we developed an efficient expression vector based on ZiMMV for the persistent and abundant expression of foreign proteins in the leaf, stem, root, and flower tissues with mild symptoms during viral infection in common zinnia. We showed that the ZiMMV-based vector can express ZeMYB9, which encodes a transcript factor inducing dark red speckles in leaves and flowers. Additionally, the expression of a gibberellic acid (GA) biosynthesis gene from the ZiMMV vector substantially accelerated plant height growth, offering a rapid and cost-effective method. In summary, our work provides a powerful tool for gene expression, functional studies, and genetic improvement of horticultural traits in Asteraceae plant hosts.

4.
Sci Rep ; 14(1): 14128, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898049

ABSTRACT

This manuscript offers an exhaustive analysis of Flexible Printed Circuits (FPCs), concentrating on enhancing their design to surmount two primary challenges. Firstly, it seeks to obviate contact with proximate components. Secondly, it aspires to adhere to pre-established curvature constraints. Predicated on the curvature properties of FPCs, we have developed a model adept at accurately forecasting FPC deformation under diverse conditions. Our inquiry entails a thorough examination of various FPC configurations, including bell, 'U', and 'S' shapes. Central to our methodology is the strategic optimization of FPC spatial arrangements, aiming to avert mechanical interference and control curvature, thus mitigating mechanical strain. This dual-faceted strategy is pivotal in enhancing the durability and operational reliability of FPCs, particularly in contexts demanding elevated flexibility and precision. Our research offers essential insights into the refinement of FPC design, skillfully addressing the complexities associated with curvature and physical interaction. Collectively, this study advocates a comprehensive framework for the design and implementation of FPCs, significantly advancing the field of contemporary electronics by ensuring these components meet the evolving demands of the industry.

5.
Chemosphere ; 362: 142598, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38871194

ABSTRACT

Soil dissolved organic matter (SDOM) is an important part of the DOM pool in terrestrial systems, influencing the transport and fate of many pollutants. In this study, SDOMs from different regions across China were compared by a series of spectroscopic methods, including UV-vis spectroscopy, fluorescence spectroscopy, and Fourier transform infrared (FTIR) spectroscopy, and the hydrophobicity was quantified by partition coefficients of SDOM in the aqueous two-phase system (KATPS). The molecular weight, aromaticity, and hydrophobicity of SDOM from different regions exhibited strong heterogeneity, KATPS combined with UV-vis and fluorescence indices can be readily used for differentiating heterogeneous SDOM, and SDOMs were compositionally and structurally different from DOMs in aquatic systems based on spectral characterization. Importantly, the two-phase system (TPS) model has only been validated by DOMs in freshwater systems, and good organic carbon‒water partition coefficient (KOC) predictive power (RMSE = 0.11) could be provided by the TPS model when applied to heterogeneous SDOM without calibration, showing its broad applicability. Our results demonstrate the applicability of the TPS model for predicting the sorption behavior of terrestrial DOM, broadening the application scope of the TPS model and indicating its potential as a routine model for the risk assessment of hydrophobic organic compounds (HOCs) in organic contaminated sites.

6.
J Oral Pathol Med ; 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38945807

ABSTRACT

BACKGROUND: ANXA5, a notable tumor marker, displays irregular expression in diverse solid cancers, and links to local recurrence and metastasis rates. We aimed study the expression of ANXA5 in oral squamous cell carcinoma (OSCC) and its diagnostic and prognostic values. METHODS: 520 head and neck squamous cell carcinoma (HNSCC) patients in TCGA database and 124 OSCC patients in Nanjing stomatology hospital were enrolled in our study. Immunohistochemical analyses were performed using ANXA5 antibodies. Chi-square test was used to analyze the clinicopathological features. Survival rates were determined using the Kaplan-Meier method and log-rank test. RESULTS: Our results showed significantly elevated ANXA5 at the gene and protein levels in HNSCC and OSCC compared to non-tumor tissues. Histopathologically, ANXA5 was broadly present in OSCC tumor cells and fibroblast-like cells but absent in tumor-infiltrating lymphocytes, particularly at the invasive tumor front. Patients exhibiting high ANXA5 expression in these cells demonstrated poor differentiation, aggressive invasion patterns, and heightened lymph node metastasis risk, contributing to poorer postoperative outcomes. Remarkably, ANXA5 in fibroblast-like cells emerged as an independent risk factor impacting survival in OSCC patients. Gene set enrichment analysis (GSEA) highlighted ANXA5's involvement in key pathways like epithelial-mesenchymal transformation (EMT), TGF-beta signaling, and hypoxia, which correlated with adverse clinical outcomes in OSCC. CONCLUSION: ANXA5 emerges as a significant prognostic biomarker for OSCC, potentially influencing its metastasis via the EMT pathway.

7.
Front Physiol ; 15: 1301450, 2024.
Article in English | MEDLINE | ID: mdl-38742154

ABSTRACT

Background: Circadian rhythms are reported to influence physiological processes in the gastrointestinal system, but associations between circadian syndrome (Circs) and chronic diarrhea (CD) remain unclear. Here, we explored such relationships to provide new insights into CD management. Methods: We conducted a cross-sectional retrospective analysis using the National Health and Nutrition Examination Survey (NHANES) data between 2005 and 2010. Univariate and multivariable logistic regression analyses were performed on weighted data to explore associations between Circs and CD. Results: Results were presented using forest plots, odds ratios (ORs), and 95% confidence intervals (CIs). Data with p-values < 0.05 were considered statistically significant. In total, 5,661 US participants, of which 412 had CD (weighted percentage = 6.20%), were enrolled. In univariate logistic regression analyses, participants with Circs had a significantly higher risk of CD (OR = 1.51, 95% CI: 1.15-1.99). After adjusting for covariates, model 2 (OR = 1.40, 95% CI: 1.03-1.90) and model 3 (OR = 1.42, 95% CI: 1.01-2.00) data were consistent with model 1 data. Additionally, the number of Circs components was positively associated with CD in all three models. Subgroup analyses revealed an association between CD and Circs in participants who had high blood pressure (OR = 2.46, 95% CI: 1.48-4.11, p < 0.001). Conclusion: In this cross-sectional study, we found that Circs is positively associated with the risk of CD in US adults, especially in those with high blood pressure. This association may provide new management strategies for CD.

8.
Sci Rep ; 14(1): 11007, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745006

ABSTRACT

In this study, we investigate the influence of global innovation networks (GINs) on the innovation output of semiconductor firms. Utilizing negative binomial regression and network analysis, we assess how network positions, specifically degree, betweenness, and closeness centrality, affect firms' innovation performance, revealing significant positive impacts. Moreover, our results identify a positive U-shaped relationship between structural holes in GINs and innovation performance, suggesting that while moderate network engagement aids innovation, too much can be detrimental. This research provides key insights into optimizing GIN participation for better innovation results in the competitive semiconductor sector.

9.
Sci Rep ; 14(1): 9999, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38693300

ABSTRACT

Although tension band wiring (TBW) is popular and recommended by the AO group, the high rate of complications such as skin irritation and migration of the K-wires cannot be ignored. Ding's screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by biomechanical testing. We conducted a Synbone biomechanical model by using three fixation methods: DSTBW, intramedullary screw and tension band wiring (IM-TBW), and K-wire TBW, were simulated to fix the olecranon fractures. We compared the mechanical stability of DSTBW, IM-TBW, and TBW in the Mayo Type IIA olecranon fracture Synbone model using a single cycle loading to failure protocol or pullout force. During biomechanical testing, the average fracture gap measurements were recorded at varying flexion angles in three different groups: TBW, IM-TBW, and DSTBW. The TBW group exhibited measurements of 0.982 mm, 0.380 mm, 0.613 mm, and 1.285 mm at flexion angles of 0°, 30°, 60°, and 90° respectively. The IM-TBW group displayed average fracture gap measurements of 0.953 mm, 0.366 mm, 0.588 mm, and 1.240 mm at each of the corresponding flexion angles. The DSTBW group showed average fracture gap measurements of 0.933 mm, 0.358 mm, 0.543 mm, and 1.106 mm at the same flexion angles. No specimen failed in each group during the cyclic loading phase. Compared with the IM-TBW and TBW groups, the DSTBW group showed significant differences in 60° and 90° flexion angles. The mean maximum failure load was 1229.1 ± 110.0 N in the DSTBW group, 990.3 ± 40.7 N in the IM-TBW group, and 833.1 ± 68.7 N in the TBW group. There was significant difference between each groups (p < 0.001).The average maximum pullout strength for TBW was measured at 57.6 ± 5.1 N, 480.3 ± 39.5 N for IM-TBW, and 1324.0 ± 43.8 N for DSTBW. The difference between maximum pullout strength of both methods was significant to p < 0.0001. DSTBW fixation provides more stability than IM-TBW and TBW fixation models for olecranon fractures.


Subject(s)
Bone Screws , Bone Wires , Fracture Fixation, Internal , Olecranon Process , Humans , Olecranon Process/injuries , Olecranon Process/surgery , Biomechanical Phenomena , Fracture Fixation, Internal/methods , Fracture Fixation, Internal/instrumentation , Ulna Fractures/surgery , Ulna Fractures/physiopathology , Fractures, Bone/surgery , Olecranon Fracture
10.
Toxicol Lett ; 397: 89-102, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38768835

ABSTRACT

Aging increases susceptibility to lung disease, but the topic is understudied, especially in relation to environmental exposures with the bulk of rodent studies using young adults. This study aims to define the pulmonary toxicity of naphthalene (NA) and the impacts of a dietary antioxidant, ergothioneine (ET), in the liver and lungs of middle-aged mice. NA causes a well-characterized pattern of conducting airway epithelial injury in the lung in young adult mice, but NA's toxicity has not been characterized in middle-aged mice, aged 1-1.5 years. ET is a dietary antioxidant that is synthesized by bacteria and fungi. The ET transporter (ETT), SLC22A4, is upregulated in tissues that experience high levels of oxidative stress. In this study, middle-aged male and female C57BL/6 J mice, maintained on an ET-free synthetic diet from conception, were gavaged with 70 mg/kg of ET for five consecutive days. On day 8, the mice were exposed to a single intraperitoneal NA dose of 50, 100, 150, or 200 mg/kg. At 24 hours post NA injection samples were collected and analyzed for ET concentration and reduced (GSH) and oxidized glutathione (GSSG) concentrations. Histopathology, morphometry, and gene expression were examined. Histopathology of mice exposed to 100 mg/kg of NA suggests reduction in toxicity in the terminal airways of both male (p ≤ 0.001) and female (p ≤ 0.05) middle-aged mice by the ET pretreatment. Our findings in this study are the first to document the toxicity of NA in middle-aged mice and show some efficacy of ET in reducing NA toxicity.


Subject(s)
Aging , Antioxidants , Ergothioneine , Lung , Naphthalenes , Ergothioneine/therapeutic use , Naphthalenes/toxicity , Lung/pathology , Lung/physiology , Humans , Dietary Supplements , Male , Female , Animals , Mice , Antioxidants/therapeutic use , Polymerase Chain Reaction , Gene Expression , Glutathione/genetics , Glutathione/metabolism
11.
ACS Appl Mater Interfaces ; 16(15): 18971-18979, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38578663

ABSTRACT

The formation of a solid electrolyte interphase on carbon anodes causes irreversible loss of Na+ ions, significantly compromising the energy density of Na-ion full cells. Sodium compensation additives can effectively address the irreversible sodium loss but suffer from high decomposition voltage induced by low electrochemical activity. Herein, we propose a universal electrocatalytic sodium compensation strategy by introducing a carbon nanotube (CNT)/MnO2 catalyst to realize full utilization of sodium compensation additives at a much-reduced decomposition voltage. The well-organized CNT/MnO2 composite with high catalytic activity, good electronic conductivity, and abundant reaction sites enables sodium compensation additives to decompose at significantly reduced voltages (from 4.40 to 3.90 V vs Na+/Na for sodium oxalate, 3.88 V for sodium carbonate, and even 3.80 V for sodium citrate). As a result, sodium oxalate as the optimal additive achieves a specific capacity of 394 mAh g-1, almost reaching its theoretical capacity in the first charge, increasing the energy density of the Na-ion full cell from 111 to 158 Wh kg-1 with improved cycle stability and rate capability. This work offers a valuable approach to enhance sodium compensation efficiency, promising high-performance energy storage devices in the future.

12.
Mol Neurobiol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649659

ABSTRACT

Stroke is a life-threatening condition that impairs the arteries and causes neurological impairment. The incidence of stroke is increasing year by year with the arrival of the aging population. Thus, there is an urgent need for early stroke diagnosis. Short-chain fatty acids (SCFAs) can modulate the central nervous system and directly and indirectly impact behavioral and cognitive functions. This study aimed to investigate the connection between SCFA metabolism and stroke development via bioinformatic analysis. Initially, the Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were performed based on RNA data from stroke patients to comprehend the mechanisms governing stroke pathogenesis. The functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI), was performed based on the Differentially Expressed Gene (DEG) selected by the limma package. 1220 SCFA metabolism-related genes screened from Genecards databases were intersected with 242 genes in main modules determined by Weighted Gene Co-Expression Network Analysis (WGCNA), and the final 10 SCFA key genes were obtained. GO analysis revealed that these genes were involved in immune response processes. Through lasso regression analyses, we established a stroke early diagnosis model and selected 6 genes with diagnostic value. The genes were validated by the area under curve (AUC) values and had a relatively good diagnostic performance. Finally, 4 potential therapeutic drugs targeting these genes were predicted using the Drug Signatures Database (DSigDB) via Enrichr. In conclusion, this paper analyzes the involvement of SCFAs in the complex gut-brain axis mechanism, which contributes to developing new targets for treating central nervous system diseases and provides new ideas for early ischemic stroke diagnosis.

13.
Cancer Cell ; 42(4): 552-567.e6, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38593781

ABSTRACT

Leukemia can arise at various stages of the hematopoietic differentiation hierarchy, but the impact of developmental arrest on drug sensitivity is unclear. Applying network-based analyses to single-cell transcriptomes of human B cells, we define genome-wide signaling circuitry for each B cell differentiation stage. Using this reference, we comprehensively map the developmental states of B cell acute lymphoblastic leukemia (B-ALL), revealing its strong correlation with sensitivity to asparaginase, a commonly used chemotherapeutic agent. Single-cell multi-omics analyses of primary B-ALL blasts reveal marked intra-leukemia heterogeneity in asparaginase response: resistance is linked to pre-pro-B-like cells, with sensitivity associated with the pro-B-like population. By targeting BCL2, a driver within the pre-pro-B-like cell signaling network, we find that venetoclax significantly potentiates asparaginase efficacy in vitro and in vivo. These findings demonstrate a single-cell systems pharmacology framework to predict effective combination therapies based on intra-leukemia heterogeneity in developmental state, with potentially broad applications beyond B-ALL.


Subject(s)
Leukemia , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Humans , Asparaginase/pharmacology , Network Pharmacology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Signal Transduction , Leukemia/drug therapy
14.
Adv Mater ; 36(28): e2401837, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38682617

ABSTRACT

An ultra-thin quasi-solid electrolyte (QSE) with dendrite-inhibiting properties is a requirement for achieving high energy density quasi-solid lithium metal batteries (LMBs). Here, a 5.1 µm rigid QSE layer is directly designed on the cathode, in which Kevlar (poly(p-phenylene terephthalate)) nanofibers (KANFs) with negatively charged groups bridging metal-organic framework (MOF) particles are served as a rigid skeleton, and non-flammable deep eutectic solvent is selected to be encapsulated into the MOF channels, combined with in situ polymerization to complete safe electrolyte system with high rigidness and stability. The QSE with constructed topological network demonstrates high rigidity (5.4 GPa), high ionic conductivity (0.73 mS cm-1 at room temperature), good ion-regulated properties, and improved structural stability, contributing to homogenized Li-ion flux, excellent dendrite suppression, and prolonged cyclic performance for LMB. Additionally, ion regulation influences the Li deposition behavior, exhibiting a uniform morphology on the Li-metal surface after cycling. According to density-functional theory, KANFs bridging MOFs as hosts play a vital function in the free-state and fast diffusion dynamics of Li-ions. This work provides an effective strategy for constructing ultrathin robust electrolytes with a novel ionic conduction mode.

15.
Article in English | MEDLINE | ID: mdl-38581334

ABSTRACT

Objective: This study aims to investigate the expression levels of soluble CD40L (sCD40L), matrix metalloproteinase 2 (MMP2), and matrix metalloproteinase 9 (MMP9) in the serum of patients experiencing recurrent abortion and their impact on uterine artery blood flow. Methods: A cohort of 200 patients with recurrent abortion was selected for this investigation. The levels of sCD40L, MMP2, and MMP9 in serum were assessed using ELISA, while ultrasound was employed to measure the pulsatility index (PI) and resistance index (RI) in uterine artery blood flow. Pregnancy outcomes were observed, and the expression of CD40/CD40L and MMP2/MMP9 in villi tissues was compared between patients experiencing recurrent abortion failure and those with normal pregnancies. Results: In the successful pregnancy group of patients with recurrent spontaneous abortion (RSA), serum levels of sCD40L, MMP2, and MMP9 were significantly lower than those in the failed pregnancy group. Additionally, both RI and PI were notably reduced. The expression of each gene showed a correlation with RI and PI. Furthermore, the expression levels of CD40, CD40L, MMP2, and MMP9 in the pregnancy failure group were significantly higher than in the normal voluntary termination group. Conclusion: Serum levels of sCD40L, MMP2, and MMP9, along with non-invasive and easily accessible indicators such as PI and RI in uterine artery blood flow measured by ultrasound, emerge as potential predictive markers for the outcome of recurrent miscarriage pregnancies. Moreover, these indicators can serve as valuable evaluation markers in clinical practice, facilitating the monitoring of treatment effectiveness for recurrent miscarriage.

16.
PLoS One ; 19(3): e0298138, 2024.
Article in English | MEDLINE | ID: mdl-38446835

ABSTRACT

The digital economy is a new impetus to promote high-quality economic development. We use the policies of Zhejiang Information Economy Development Demonstration Base (IEDD) and Zhejiang Software and Information Service Industry Base (SISI) established between 2015 and 2017 to design a quasi-natural experiment. By using a panel data from 2005 to 2020 in Zhejiang and the difference-in-differences model, we test the impacts of IEDD and SISI policies on digital economy development. We find that there are significant spatial differences for digital economy in Zhejiang. IEDD and SISI policies improve the digital economy development, that is, the policy advantages can indeed be transformed into industrial advantages. The IEDD policy can promote the digital economy industry development by enhancing the digital infrastructure and financial development; SISI policy can promote the development of the digital economy industry by promoting financial development. The results of quantile regression show that the promotion effect of IEDD and SISI policies increases with the improvement of the industrial basis of regional digital economy. The results of group regression show that the IEDD policy promotes the digital economy development in counties and county-level cities of Zhejiang, and the SISI policy plays a significant role in municipal districts.


Subject(s)
Economic Development , Industrial Development , Industry , China , Policy
17.
PLoS One ; 19(3): e0300199, 2024.
Article in English | MEDLINE | ID: mdl-38470903

ABSTRACT

The regional networking strategy is widely implemented in China as a normative policy aimed at fostering cohesion and enhancing competitiveness. However, the empirical basis for this strategy remains relatively weak due to limitations in measurement methods and data availability. This paper establishes the urban networks by the enterprise investment data, and then accurately measures the network's external effects of each city by the method of MGWR model. The results show that: (1) Regional networking plays a significant role in urban development, although it is not the dominant factor. (2) The benefits of network connections may vary depending on the location and level of cities. (3) The major cities assume a pivotal role in the urban network. Based upon the aforementioned research conclusions, this paper presents strategic measures to enhance the network's external impacts, aiming to offer insights for other regions in formulating regional development strategies and establishing regional urban networks.


Subject(s)
Urban Renewal , Urbanization , Cities , Rivers , China , Economic Development
18.
Int Immunopharmacol ; 131: 111883, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38503016

ABSTRACT

Infarct healing requires a dynamic and orchestrated inflammatory reaction following myocardial infarction (MI). While an uncontrolled excessive inflammatory response exaggerates ischemic injury post-MI, M2-like reparative macrophages may facilitate inflammation regression and promote myocardial healing. However, how protein post-translational modification regulates post-MI cardiac repair and dynamic myeloid activation remains unknown. Here we show that M2-like reparative, but not M1-like inflammatory activation, is enhanced by pharmacologically-induced hyper-O-GlcNAcylation. Mechanistically, myeloid knockdown of O-GlcNAc hydrolase O-GlcNAcase (Oga), which also results in hyper-O-GlcNAcylation, positively regulates M2-like activation in a STAT6-dependent fashion, which is controlled by O-GlcNAcylation of STAT6. Of note, both systemic and local supplementation of thiamet-G (TMG), an Oga inhibitor, effectively facilitates cardiac recovery in mice by elevating the accumulation of M2-like macrophages in infarcted hearts. Our study provides a novel clue for monocyte/macrophage modulating therapies aimed at reducing post-MI hyperinflammation in ischemic myocardium.


Subject(s)
Hydrogels , Myocardial Infarction , Mice , Animals , Hydrogels/metabolism , Myocardium/metabolism , Heart , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Protein Processing, Post-Translational , Acetylglucosaminidase/metabolism
19.
Nat Commun ; 15(1): 2098, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459034

ABSTRACT

Yutu-2 rover conducted an exciting expedition on the 41st lunar day to investigate a fin-shaped rock at Longji site (45.44°S, 177.56°E) by extending its locomotion margin on perilous peaks. The varied locomotion encountered, especially multi-form wheel slippage, during the journey to the target rock, established unique conditions for a fin-grained lunar regolith analysis regarding bearing, shear and lateral properties based on terramechanics. Here, we show a tri-aspect characterization of lunar regolith and infer the rock's origin using a digital twin. We estimate internal friction angle within 21.5°-42.0° and associated cohesion of 520-3154 Pa in the Chang'E-4 operational site. These findings suggest shear characteristics similar to Apollo 12 mission samples but notably higher cohesion compared to regolith investigated on most nearside lunar missions. We estimate external friction angle in lateral properties to be within 8.3°-16.5°, which fills the gaps of the lateral property estimation of the lunar farside regolith and serves as a foundational parameter for subsequent engineering verifications. Our in-situ spectral investigations of the target rock unveil its composition of iron/magnesium-rich low-calcium pyroxene, linking it to the Zhinyu crater (45.34°S, 176.15°E) ejecta. Our results indicate that the combination of in-situ measurements with robotics technology in planetary exploration reveal the possibility of additional source regions contributing to the local materials at the Chang'E-4 site, implying a more complicated geological history in the vicinity.

20.
Cancer Immunol Immunother ; 73(5): 78, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38554152

ABSTRACT

BACKGROUND: Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC). METHODS: PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis. RESULTS: Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285-6.851). CONCLUSIONS: LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , CD8-Positive T-Lymphocytes/metabolism , Head and Neck Neoplasms/metabolism , Lipid Droplets/metabolism , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Oncogenes , Perilipin-3/metabolism , Squamous Cell Carcinoma of Head and Neck/metabolism , Tumor Microenvironment
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