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Syringin, a phenylpropanoid glycoside, is widely distributed in various plants, such as Acanthopanax senticosus (Rupr. et Maxim.) Harms, Syringa reticulata (BL) Hara var. mandshurica (Maxim.) Hara, and Ilex rotunda Thumb. It serves as the main ingredient in numerous listed medicines, health products, and foods with immunomodulatory, anti-tumor, antihyperglycemic, and antihyperlipidemic effects. This review aims to systematically summarize syringin, including its physicochemical properties, plant sources, extraction and separation methods, total synthesis approaches, pharmacological activities, drug safety profiles, and preparations and applications. It will also cover the pharmacokinetics of syringin, followed by suggestions for future application prospects. The information on syringin was obtained from internationally recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of Science, Medline Plus, ACS Elsevier, and Flora of China) and libraries. Syringin, extraction and separation, pharmacological activities, preparations and applications, and pharmacokinetics were chosen as the keywords. According to statistics, syringin can be found in 23 families more than 60 genera, and over 100 species of plants. As a key component in many Chinese herbal medicines, syringin holds significant research value due to its unique sinapyl alcohol structure. Its diverse pharmacological effects include immunomodulatory activity, tumor suppression, hypoglycemic action, and hypolipidemic effects. Additionally, it has been shown to provide neuroprotection, liver protection, radiation protection, cardioprotection, and bone protection. Related preparations such as Aidi injection, compound cantharidin capsule, and Tanreqing injection have been widely used in clinical settings. Other studies on syringin such as extraction and isolation, total synthesis, safety profile assessment, and pharmacokinetics have also made progress. It is crucial for medical research to deeply explore its mechanism of action, especially regarding immunity and tumor therapy. Meanwhile, more robust support is needed to improve the utilization of plant resources and to develop extraction means adapted to the needs of industrial biochemistry to further promote economic development while protecting people's health.
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Organophosphate esters (OPEs), increasingly used as new flame retardants and plasticizers in various products, have been found to have reproductive toxicity with overt endocrine disruption potential, yet the relationship between OPEs and early menopause remains unexplored. In the present study, we included 2429 women who participated in the U.S. National Health and Nutrition Examination Survey data (2011-2020) and had data of five urinary OPE metabolite levels and information of menopause characteristics, to investigate the associations of OPEs exposure with premature ovarian insufficiency (POI) and age of menopause. Multivariable adjusted linear and logistic regression were used to assess the associations of urinary OPE metabolites with age of menopause and POI, respectively. Quantile g computation (QGC) models were used to assess the relative contribution of individual metabolites to associations of OPE metabolites mixture. After adjusting for covariates, urinary bis(2-chloroethyl) phosphate (BCEP) concentration was inversely associated with menopause age (ß = - 0.21; 95% confidence interval (CI): 0.41, - 0.002). Higher urinary BCEP level (>median) was associated with earlier age at menopause (ß = -1.14, 95% CI: 1.83, - 0.46), and elevated odds of having POI (OR = 1.93; 95% CI: 1.02, 3.66). These associations were robust to the further adjustment of cardiometabolic diseases and related traits (e.g., body mass index). Further QGC analyses confirmed that BCEP was the dominant metabolite contributing most to the associations of OPEs mixture with age of menopause (weight = 49.5%) and POI (weight = 75.1%). No significant associations were found for the other four OPE metabolites. In this cross-sectional study, urinary BCEP level was associated with earlier menopause and increased odds of POI, highlighting the potential negative impacts of this chemical and its parent compound tris(2-chloroethyl) phosphate on ovarian function. Further studies are required to validate our findings and reveal potential underlying mechanisms.
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Electrolyte decomposition and subsequent solid electrolyte interphase (SEI) are considered to be the primary cause of degradation of lithium batteries. We investigate the multiple factors that can affect the reductive decomposition pathways of ethylene carbonate (EC) and SEI formation using reactive molecular dynamics. Our simulations reveal the effects of lithium concentration, simulation temperature, and the imposition of external electric field on the decomposition reaction and pathways, respectively. The comparative results reveal the increasing lithium concentration has a strong influence on EC decomposition and its pathway at each temperature. Also, the increasing temperature and imposition of an external electric field have been found to non-electrochemically and electrochemically modify the decomposition pathways of EC. This study provides insights into not only the SEI chemistry in Li-ion batteries but also that in lithium metal batteries, which can potentially contribute to the design and optimisation of future novel battery materials and electrolyte solutions.
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Microexplosion has been extensively studied in the context of fuel spray and droplet evaporation in engines, while its existence, impact and atomistic insight have rarely been explored in the context of flame synthesis of nanoparticles. In this study, reactive force-field molecular dynamics simulations are performed to elucidate the mechanisms of pyrolysis and oxidation of an isolated lithium nitrate nanodroplet. During the pyrolysis process, the nucleation and growth of a bubble are observed inside the droplet, which should be ascribed to the release of nitrogen and oxygen gases from the decomposition of lithium nitrate, ultimately leading to rapid droplet fragmentation (microexplosion). To demonstrate the role of microexplosion with various intensities, via altering ambient temperature and addition of oxygen gas into the environment, thorough analyses of bond reactions, droplet morphology and compounds of the synthesized lithium nanoparticles are carried out. With elevated ambient temperature, the droplet substantially expands due to bubble growth and the time required for droplet disruption is shortened, which implies the enhanced strength of microexplosion. Simultaneously, the connection between the lithium and other atoms becomes weak, as evidenced by a decrease in the number of lithium bonds. These give rise to a reduction in the quantity of large-sized lithium agglomerates and simultaneously an increase in the amount of fine lithium nanoparticles. To further clarify the reaction mechanism for a lithium-containing droplet under various ambient conditions, three reaction modes, i.e., core-shell diffusion-controlled, microexplosion-accelerated and microexplosion-dominated, are distinguished based on the intensity of microexplosion and the quality of synthesized lithium nanoparticles. Fine lithium-containing nanoparticles are expected to be produced in the microexplosion-dominated mode under high temperature conditions.
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BACKGROUND: Relay intercropping of maize and soybean can improve land productivity. However, the mechanism behind N2O emissions in this practice remains unclear. A two-factor randomized block field trial was conducted to reveal the mechanism of N2O emissions in a full additive maize-soybean relay intercropping. Factor A was three cropping systems - that is, monoculture maize (Zea mays L.), monoculture soybean (Glycine max L. Merr.) and maize-soybean relay intercropping. Factor B was different N supply, containing no N, reduced N and conventional N. Differences in N2O emissions, soil properties, rhizosphere bacterial communities and yield advantage were evaluated. RESULTS: The land equivalent ratio was 1.55-2.44, and the cumulative N2O emission ( C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ ) was notably lower by 60.2% in intercropping than in monoculture, respectively. Reduced N declined C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ without penalty on the yield advantages. The relay intercropping shifted soil properties - for example, soil organic matter, total N, NH 4 + $$ {\mathrm{NH}}_4^{+} $$ and protease activity - and improved the soil microorganism community - for example, Proteobacteria and Acidobacteria. Intercropping reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by directly suppressing nirS- and amoA-regulated N2O generation during soil N cycling, or nirS- and amoA-mediated soil properties shifted to reduce C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ indirectly. Reduced N directly reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by decreasing soil N content and reducing soil microorganism activities to alleviate N2O produced in soil N cycling. CONCLUSION: Conducting a full additive maize-soybean relay intercropping with reduced nitrogen supply provides a way to alleviate N2O emissions without the penalty on the yield advantage by changing rhizosphere bacterial communities and soil N cycling. © 2024 Society of Chemical Industry.
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As quantum circuits become more integrated and complex, additional error sources that were previously insignificant start to emerge. Consequently, the fidelity of quantum gates benchmarked under pristine conditions falls short of predicting their performance in realistic circuits. To overcome this problem, we must improve their robustness against pertinent error models besides isolated fidelity. Here, we report the experimental realization of robust quantum gates in superconducting quantum circuits based on a geometric framework for diagnosing and correcting various gate errors. Using quantum process tomography and randomized benchmarking, we demonstrate robust single-qubit gates against quasistatic noise and spatially correlated noise in a broad range of strengths, which are common sources of coherent errors in large-scale quantum circuits. We also apply our method to nonstatic noises and to realize robust two-qubit gates. Our Letter provides a versatile toolbox for achieving noise-resilient complex quantum circuits.
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Resistance to osimertinib represents a significant challenge for the successful treatment of non-small cell lung cancer (NSCLC) harboring activating mutations in epidermal growth factor receptor (EGFR). N6-methyladenosine (m6A) on mRNAs is critical for various biological processes, yet whether m6A regulates osimertinib resistance of NSCLC remains unknown. In this study, we demonstrated that developing osimertinib-resistant phenotypes depends on m6A reduction resulting from downexpression of m6A methyltransferase METTL14 in EGFR-mutant NSCLCs. Both in vitro and in vivo assay showed that specific knockdown of METTL14 was sufficient to confer osimertinib resistance and elevated expression of METTL14 rescued the efficacy of osimertinib in the resistant NSCLC cells. Mechanistically, METTL14 promoted m6A methylation of pro-apoptotic Bim mRNA and increased Bim mRNA stability and expression, resulting in activating the Bim-dependent pro-apoptotic signaling and thereby promoting osimertinib-induced cell apoptosis. Analysis of clinical samples revealed that decreased expression of METTL14 was observed in osimertinib-resistant NSCLC tissues and significantly associated with a poor prognosis. In conclusion, our study reveals a novel regulatory mechanism by which METTL14-mediated m6A methylation of Bim mRNA inhibited osimertinib resistance of NSCLC cells. It offers more evidences for the involvement of m6A modification in regulation of osimertinib resistance, and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR-TKIs. Implications: This study offers more evidences for the involvement of METTL14-mediated m6A modification in regulation of osimertinib resistance, and provides potential therapeutic targets for novel approaches to overcome the tolerance of osimertinib and other EGFR-TKIs.
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BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.
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Aculturación , Enfermedades Cardiovasculares , Dieta , Microbioma Gastrointestinal , Hispánicos o Latinos , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etnología , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto , Dieta/efectos adversos , Factores de Riesgo , IncidenciaRESUMEN
Barrier membranes play a prominent role in guided bone regeneration (GBR), and polycaprolactone (PCL) is an attractive biomaterial for the fabrication of barrier membranes. However, these nanofiber membranes (NFMs) require modification to improve their biological activity. PCL-NFMs incorporating with laponite (LAP) achieve biofunctional modification. Decellularized extracellular matrix (dECM) could modulate cell behaviour. The present study combined dECM with PCL/LAP-NFMs to generate a promising strategy for bone tissue regeneration. Bone marrow mesenchymal stem cells (BMSCs) were cultured on NFMs and deposited with an abundant extracellular matrix (ECM), which was subsequently decellularized to obtain dECM-modified PCL/LAP-NFMs (PCL/LAP-dECM-NFMs). The biological functions of the membranes were evaluated by reseeding MC3T3-E1 cells in vitro and transplanting them into rat calvarial defects in vivo. These results indicate that PCL/LAP-dECM-NFMs were successfully constructed. The presence of dECM slightly improved the mechanical properties of the NFMs, which exhibited a Young's modulus of 0.269 MPa, ultimate tensile strength of 2.04 MPa and elongation at break of 51.62 %. In vitro, the PCL/LAP-dECM-NFMs had favourable cytocompatibility, and the enhanced hydrophilicity was conducive to cell adhesion, proliferation, and osteoblast differentiation. PCL/LAP-dECM-NFMs exhibited an excellent bone repair capacity in vivo. Overall, dECM-modified PCL/LAP-NFMs should be promising biomimetic barrier membranes for GBR.
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Drought presents a significant abiotic stress that threatens crop productivity worldwide. Rhizosphere bacteria play pivotal roles in modulating plant growth and resilience to environmental stresses. Despite this, the extent to which rhizosphere bacteria are instrumental in plant responses to drought, and whether distinct cassava (Manihot esculenta Crantz) varieties harbor specific rhizosphere bacterial assemblages, remains unclear. In this study, we measured the growth and physiological characteristics, as well as the physical and chemical properties of the rhizosphere soil of drought-tolerant (SC124) and drought-sensitive (SC8) cassava varieties under conditions of both well-watered and drought stress. Employing 16S rDNA high-throughput sequencing, we analyzed the composition and dynamics of the rhizosphere bacterial community. Under drought stress, biomass, plant height, stem diameter, quantum efficiency of photosystem II (Fv/Fm), and soluble sugar of cassava decreased for both SC8 and SC124. The two varieties' rhizosphere bacterial communities' overall taxonomic structure was highly similar, but there were slight differences in relative abundance. SC124 mainly relied on Gamma-proteobacteria and Acidobacteriae in response to drought stress, and the abundance of this class was positively correlated with soil acid phosphatase. SC8 mainly relied on Actinobacteria in response to drought stress, and the abundance of this class was positively correlated with soil urease and soil saccharase. Overall, this study confirmed the key role of drought-induced rhizosphere bacteria in improving the adaptation of cassava to drought stress and clarified that this process is significantly related to variety.
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Sequías , Manihot , Rizosfera , Microbiología del Suelo , Estrés Fisiológico , Manihot/microbiología , Bacterias/clasificación , Bacterias/genética , ARN Ribosómico 16S/genética , Microbiota , Raíces de Plantas/microbiología , Suelo/químicaRESUMEN
BACKGROUND: Endotracheal intubation is often associated with postoperative complications such as sore throat discomfort and hoarseness, reducing patient satisfaction and prolonging hospital stays. Laryngeal mask airway (LMA) plays a critical role in reducing airway complications related to endotracheal intubation. This meta-analysis was performed to determine the efficacy and safety of LMA in video-assisted thoracic surgery (VATS). METHODS: The PubMed, Embase, Cochrane Library, Medline and Web of Science databases were searched for eligible studies from inception until October 5, 2023. Cochrane's tool (RoB 2) was used to evaluate the possibility biases of RCTs. We performed sensitivity analysis and subgroup analysis to assess the robustness of the results. RESULTS: Seven articles were included in this meta-analysis. Compared with endotracheal intubation, there was no significant difference in the postoperative hospital stay (SMD = -0.47, 95% CI = -0.98-0.03, P = 0.06), intraoperative minimum SpO2 (SMD = 0.00, 95% CI = -0.49-0.49, P = 1.00), hypoxemia (RR = 1.00, 95% CI = 0.26-3.89, P = 1.00), intraoperative highest PetCO2 (SMD = 0.51, 95% CI = -0.12-1.15, P = 0.11), surgical field satisfaction (RR = 1.01, 95% CI = 0.98-1.03, P = 0.61), anesthesia time (SMD = -0.10, 95% CI = -0.30-0.10, P = 0.31), operation time (SMD = 0.06, 95% CI = -0.13-0.24, P = 0.55) and blood loss (SMD =- 0.13, 95% CI = -0.33-0.07, P = 0.21) in LMA group. However, LMA was associated with a lower incidence of throat discomfort (RR = 0.28, 95% CI = 0.17-0.48, P < 0.00001) and postoperative hoarseness (RR = 0.36, 95% CI = 0.16-0.81, P = 0.01), endotracheal intubation was found in connection with a longer postoperative awake time (SMD = -2.19, 95% CI = -3.49 - -0.89, P = 0.001). CONCLUSION: Compared with endotracheal intubation, LMA can effectively reduce the incidence of throat discomfort and hoarseness post-VATS, and can accelerate the recovery from anesthesia. LMA appears to be an alternative to endotracheal intubation for some specific thoracic surgical procedures, and the efficacy and safety of LMA in VATS need to be further explored in the future.
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Intubación Intratraqueal , Máscaras Laríngeas , Ensayos Clínicos Controlados Aleatorios como Asunto , Cirugía Torácica Asistida por Video , Humanos , Máscaras Laríngeas/efectos adversos , Cirugía Torácica Asistida por Video/métodos , Intubación Intratraqueal/métodos , Intubación Intratraqueal/efectos adversos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Tiempo de InternaciónRESUMEN
Herein, we propose preferential dissolution paired with Cu-doping as an effective method for synergistically modulating the A- and B-sites of LaMnO3 perovskite. Through Cu-doping into the B-sites of LaMnO3, specifically modifying the B-sites, the double perovskite La2CuMnO6 was created. Subsequently, partial La from the A-sites of La2CuMnO6 was etched using HNO3, forming novel La2CuMnO6/MnO2 (LCMO/MnO2) catalysts. The optimized catalyst, featuring an ideal Mn:Cu ratio of 4.5:1 (LCMO/MnO2-4.5), exhibited exceptional catalytic ozonation performance. It achieved approximately 90% toluene degradation with 56% selectivity toward CO2, even under ambient temperature (35 °C) and a relatively humid environment (45%). Modulation of A-sites induced the elongation of Mn-O bonds and decrease in the coordination number of Mn-O (from 6 to 4.3) in LCMO/MnO2-4.5, resulting in the creation of abundant multivalent Mn and oxygen vacancies. Doping Cu into B-sites led to the preferential chemisorption of toluene on multivalent Cu (Cu(I)/Cu(II)), consistent with theoretical predictions. Effective electronic supplementary interactions enabled the cycling of multiple oxidation states of Mn for ozone decomposition, facilitating the production of reactive oxygen species and the regeneration of oxygen vacancies. This study establishes high-performance perovskites for the synergistic regulation of O3 and toluene, contributing to cleaner and safer industrial activities.
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Ozono , Tolueno , Catálisis , Ozono/química , Tolueno/química , Titanio/química , Óxidos/química , Compuestos de Calcio/químicaRESUMEN
A photo-induced cascade sulfone alkylation/cyclization of 2-isocyanoaryl thioethers is explored. This visible-light-triggered reaction not only occurs under extremely mild reaction conditions but also does not require the presence of a photosensitizer. The photocatalytic process is triggered by the photochemical activity of in situ-generated electron donor-acceptor complexes, arising from the association of 2-isocyanoaryl thioethers and α-iodosulfones. The radical pathway was confirmed by UV-vis spectroscopy, radical trapping, Job's plot, and on/off irradiation experiments.
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An accurate semilocal kinetic energy density functional (KEDF) is crucial for reliable orbital-free density functional theory calculations. In our study, we assessed the performance of representative semilocal KEDFs using a more stringent indicator. Our findings highlight the superiority of the Perdew-Constantin (PC) functional in delivering energies close to the reference values. Upon analysis of the PC functional, we identified that enhancing its performance can be achieved through a more effective region selection regime. Experimenting with various region selection indicators, we discovered that the Laplacian-dependent reduced density gradient proves to be helpful. Subsequently, we empirically constructed an augmented variant of the PC functional, which not only yields energies close to the references but also, more importantly, demonstrates qualitative predictions for stable molecules and provides reasonable quantitative estimates for bond lengths in diatomic systems.
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Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.
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BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. METHODS: Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. RESULTS: From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) â primary tumor (PT) â MLN or from PC â PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. CONCLUSIONS: Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.
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Neoplasias Óseas , Ganglios Linfáticos , Metástasis Linfática , Osteosarcoma , Análisis de la Célula Individual , Transcriptoma , Microambiente Tumoral , Osteosarcoma/patología , Osteosarcoma/genética , Humanos , Neoplasias Óseas/patología , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Animales , Ratones , Línea Celular Tumoral , Perfilación de la Expresión GénicaRESUMEN
Four new wood-inhabiting fungi, Trechisporaalbofarinosa, T.bisterigmata, T.pileata and T.wenshanensisspp. nov., are proposed based on a combination of morphological features and molecular evidence. Trechisporaalbofarinosa is characterized by the farinose basidiomata with flocculence hymenial surface, a monomitic hyphal system with clamped generative hyphae, and ellipsoid, warted basidiospores. Trechisporabisterigmata is characterized by the membranous basidiomata with odontioid hymenial surface, rhizomorphic sterile margin, barrelled basidia and subglobose to broad ellipsoid, smooth basidiospores. Trechisporapileata is characterized by the laterally contracted base, solitary or imbricate basidiomata, fan shaped pileus, radially striate-covered surface with appressed scales, odontioid hymenophore surface, and subglobose to broad ellipsoid, thin-walled, smooth basidiospores. Trechisporawenshanensis is characterized by a cottony basidiomata with a smooth hymenial surface, and ellipsoid, thin-walled, warted basidiospores. Sequences of ITS and LSU marker of the studied samples were generated, and phylogenetic analyses were performed with the maximum likelihood, maximum parsimony, and Bayesian inference methods. The phylogenetic tree inferred from the ITS+nLSU sequences highlighted that four new species were grouped into the genus Trechispora.
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Background: Chemokines and NETosis are significant contributors to the inflammatory response, yet there still needs to be a more comprehensive understanding regarding the specific molecular characteristics and interactions of NETosis and chemokines in the context of acute pancreatitis (AP) and severe AP (SAP). Methods: To address this gap, the mRNA expression profile dataset GSE194331 was utilized for analysis, comprising 87 AP samples (77 non-SAP and 10 SAP) and 32 healthy control samples. Enrichment analyses were conducted for differentially expressed chemokine-related genes (DECRGs) and NETosis-related genes (DENRGs). Three machine-learning algorithms were used for the identification of signature genes, which were subsequently utilized in the development and validation of nomogram diagnostic models for the prediction of AP and SAP. Furthermore, single-gene Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed. Lastly, an interaction network for the identified signature genes was constructed. Results: We identified 12 DECRGs and 7 DENRGs, and enrichment analyses indicated they were primarily enriched in cytokine-cytokine receptor interaction, chemokine signaling pathway, TNF signaling pathway, and T cell receptor signaling pathway. Moreover, these machine learning algorithms finally recognized three signature genes (S100A8, AIF1, and IL18). Utilizing the identified signature genes, we developed nomogram models with high predictive accuracy for AP and differentiation of SAP from non-SAP, as demonstrated by area under the curve (AUC) values of 0.968 (95% CI 0.937-0.990) and 0.862 (95% CI 0.742-0.955), respectively, in receiver operating characteristic (ROC) curve analysis. Subsequent single-gene GESA and GSVA indicated a significant positive correlation between these signature genes and the proteasome complex. At the same time, a negative association was observed with the Th1 and Th2 cell differentiation signaling pathways. Conclusion: We have identified three genes (S100A8, AIF1, and IL18) related to chemokines and NETosis, and have developed accurate diagnostic models that might provide a novel method for diagnosing AP and differentiating between severe and non-severe cases.
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AIMS: Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes. METHODS: The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20 years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90 days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89 days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications. RESULTS: Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66-0.75). CONCLUSIONS: We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.
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BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD. RESULTS: We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion involving tissue Doppler assessment and left atrial volume index measurements. Among 1996 participants, 916 (45.9%) had prevalent LVDD, and 212 out of 594 participants without LVDD at baseline developed incident LVDD over a median 4.3 years of follow-up. Using multivariable-adjusted analysis of compositions of microbiomes (ANCOM-II) method, we identified 7 out of 512 dominant gut bacterial species (prevalence > 20%) associated with prevalent LVDD (FDR-q < 0.1), with inverse associations being found for Intestinimonas_massiliensis, Clostridium_phoceensis, and Bacteroide_coprocola and positive associations for Gardnerella_vaginali, Acidaminococcus_fermentans, Pseudomonas_aeruginosa, and Necropsobacter_massiliensis. Using multivariable adjusted linear regression, 220 out of 669 circulating metabolites with detection rate > 75% were associated with the identified LVDD-related bacterial species (FDR-q < 0.1), with the majority being linked to Intestinimonas_massiliensis, Clostridium_phoceensis, and Acidaminococcus_fermentans. Furthermore, 46 of these bacteria-associated metabolites, mostly glycerophospholipids, secondary bile acids, and amino acids, were associated with prevalent LVDD (FDR-q < 0.1), 21 of which were associated with incident LVDD (relative risk ranging from 0.81 [p = 0.001, for guanidinoacetate] to 1.25 [p = 9 × 10-5, for 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)]). The inclusion of these 21 bacterial-related metabolites significantly improved the prediction of incident LVDD compared with a traditional risk factor model (the area under the receiver operating characteristic curve [AUC] = 0.73 vs 0.70, p = 0.001). Metabolite-based proxy association analyses revealed the inverse associations of Intestinimonas_massilliensis and Clostridium_phoceensis and the positive association of Acidaminococcus_fermentans with incident LVDD. CONCLUSION: In this study of US Hispanics/Latinos, we identified multiple gut bacteria and related metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity. Video Abstract.