Magnetic navigation-assisted colonoscopic enteral tube placement in swine (with video): a preliminary study.

BACKGROUND: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. METHODS: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. RESULTS: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. CONCLUSIONS: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.

HIF1α Counteracts TGFß1-Driven TSP1 Expression in Endothelial Cells to Stimulate Angiogenesis in the Hypoxic Tumor Microenvironment.

Emerging evidence suggests that transforming growth factor ß1 (TGFß1) can inhibit angiogenesis, contradicting the coexistence of active angiogenesis and high abundance of TGFß1 in the tumor microenvironment. Here, we investigated how tumors overcome the anti-angiogenic effect of TGFß1. TGFß1 treatment suppressed physiological angiogenesis in chick chorioallantoic membrane and zebrafish models but did not affect angiogenesis in mouse hepatoma xenografts. The suppressive effect of TGFß1 on angiogenesis was recovered in mouse xenografts by a hypoxia-inducible factor 1α (HIF1α) inhibitor. In contrast, a HIF1α stabilizer abrogated angiogenesis in zebrafish, indicating that hypoxia may attenuate the anti-angiogenic role of TGFß1. Under normoxic conditions, TGFß1 inhibited angiogenesis by upregulating anti-angiogenic factor thrombospondin 1 (TSP1) in endothelial cells (ECs) via TGFß type I receptor (TGFßR1)-SMAD2/3 signaling. In a hypoxic microenvironment, HIF1α induced microRNA-145 (miR145) expression; miR145 abolished the inhibitory effect of TGFß1 on angiogenesis by binding and repressing SMAD2/3 expression and subsequently reducing TSP1 levels in ECs. Primary ECs isolated from human hepatocellular carcinoma (HCC) displayed increased miR145 and decreased SMAD3 and TSP1 compared to ECs from adjacent non-tumor livers. The reduced SMAD3 or TSP1 in ECs was associated with increased angiogenesis in HCC tissues. Collectively, this study identified that TGFß1-TGFßR1-SMAD2/3-TSP1 signaling in ECs inhibits angiogenesis. This inhibition can be circumvented by a hypoxia-HIF1α-miR145 axis, elucidating a mechanism by which hypoxia promotes angiogenesis.

Expressing miR-282 mitigates Aß42-induced neurodegeneration in Alzheimer's model in Drosophila.

Alzheimer's disease is a complex neurodegenerative condition characterized by the accumulation of amyloid beta plaques, leading to memory loss, cognitive decline, and impaired autonomous behavior. Despite extensive research, an effective treatment remains elusive. The buildup of amyloid beta plaques (Aß42) in the brain causes oxidative stress and disrupts normal molecular signaling, adversely affecting neuron function. Previous research has identified factors that can either exacerbate or mitigate neurodegenerative diseases. Our study aimed to uncover new factors involved in the pathogenesis of Alzheimer's disease. Using Drosophila as a model organism, we employed the Gal4/UAS system to express human Aß42 in the flies' retinal neurons which led to neurodegenerative changes in their compound eyes. To identify genetic modifiers, we conducted a screen by co-expressing microRNAs and found that miR-282 acts as a suppressor. Overexpressing miR-282 in the GMR > Aß42 background reduced Aß42-induced neurodegeneration. Further analysis using prediction tools and RNA interference experiments identified three potential downstream targets of miR-282: calpain-B, knot, and scabrous. Downregulating these genes via RNA interference in the GMR > Aß42 background mitigated neurodegeneration. Our research highlights miR-282 as a novel molecule that may influence the progression of Alzheimer's disease, offering potential avenues for future therapeutic or diagnostic developments.

Aquaporin-1 Facilitates Macrophage M1 Polarization by Enhancing Glycolysis Through the Activation of HIF1α in Lipopolysaccharide-Induced Acute Kidney Injury.

This study aimed to investigate how aquaporin 1 (AQP1) modulates hypoxia-inducible factor-1α (HIF1α) to promote glycolysis and drive the M1 polarization of macrophages. Within 12 h post-treatment with LPS to induce acute kidney injury in rats, a significant upregulation of AQP1 and HIF1α protein levels was noted in serum and kidney tissues. This elevation corresponded with a decrease in blood glucose concentrations and an enhancement of glycolytic activity relative to the control group. Furthermore, there was a pronounced reduction in the circulating levels of the anti-inflammatory cytokine IL-10, accompanied by an upregulation in the levels of the pro-inflammatory cytokines IL-6 and TNF-α. The administration of an HIF1α inhibitor reversed these effects, which did not affect the production of AQP1 protein. In cellular assays, AQP1 knockdown mitigated the increase in HIF1α expression induced by LPS. Furthermore, the suppression of HIF1α with PX-478 led to decreased expression levels of Hexokinase 2 (HK2) and Lactate Dehydrogenase A (LDHA), indicating that AQP1 regulates glycolysis through HIF1α. M1 polarization of macrophages was reduced by AQP1 knockdown and was further diminished by the addition of an HIF1α inhibitor. Inhibition of the glycolytic process not only weakened M1 polarization but also promoted M2 polarization, thereby reducing the release of inflammatory cytokines. These findings provide a novel perspective for developing therapeutic strategies that target AQP1 and HIF1α, potentially improving the treatment of sepsis-associated AKI.

The neuropsychological impacts of COVID-19 in non-hospitalized patients with long COVID and brain fog.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes persistent symptoms, including brain fog. Based on limited research on the long-term consequences of mild COVID-19, which has yielded inconsistent results, we investigated which cognitive functions were most affected by COVID-19 in non-hospitalized Asian patients with long-term COVID and subjective cognitive complaints. METHODS: Fifty-five non-hospitalized patients with long COVID and brain fog (24 males and 31 females, mean age: 45.6 ± 14.6 years, mean duration of education: 14.4 ± 3.0 years) were recruited. Neuropsychological assessments included screening tests for overall cognition, and comprehensive tests for memory, executive function, processing speed, and subjective emotional and disease symptoms. Cognitive test scores were converted into Z-scores. Moreover, principal component analysis (PCA) was employed to define cognitive domains across subtest scores. RESULTS: Comprehensive assessments revealed cognitive impairment in 69.1% of patients (<1.5 standard deviation in at least one test). The processing speed (27.3%), memory recall (21.8%), memory learning (20.0%), and inhibitory control (18.2%) were the most affected areas. Self-reported anxiety and depression were observed in 35% and 33% of patients, respectively. Furthermore, the degree of self-anxiety can be used to predict learning performance. CONCLUSION: Nearly 70% of patients with subjective cognitive complaints and long COVID had objective cognitive impairments. A comprehensive evaluation is essential for patients with long COVID and brain fog, including those with mild symptoms.

Target-based deep learning network surveillance of non-contrast computed tomography for small infarct core of acute ischemic stroke.

Purpose: Rapid diagnosis of acute ischemic stroke (AIS) is critical to achieve positive outcomes and prognosis. This study aimed to construct a model to automatically identify the infarct core based on non-contrast-enhanced CT images, especially for small infarcts. Methods: The baseline CT scans of AIS patients, who had DWI scans obtained within less than 2 h apart, were included in this retrospective study. A modified Target-based deep learning model of YOLOv5 was developed to detect infarctions on CT. Randomly selected CT images were used for testing and evaluated by neuroradiologists and the model, using the DWI as a reference standard. Intraclass correlation coefficient (ICC) and weighted kappa were calculated to assess the agreement. The paired chi-square test was used to compare the diagnostic efficacy of physician groups and automated models in subregions. p < 0.05 was considered statistically significant. Results: Five hundred and eighty four AIS patients were enrolled in total, finally 275 cases were eligible. Modified YOLOv5 perform better with increased precision (0.82), recall (0.81) and mean average precision (0.79) than original YOLOv5. Model showed higher consistency to the DWI-ASPECTS scores (ICC = 0.669, κ = 0.447) than neuroradiologists (ICC = 0.452, κ = 0.247). The sensitivity (75.86% vs. 63.79%), specificity (98.87% vs. 95.02%), and accuracy (96.20% vs. 91.40%) were better than neuroradiologists. Automatic model had better diagnostic efficacy than physician diagnosis in the M6 region (p = 0.039). Conclusion: The deep learning model was able to detect small infarct core on CT images more accurately. It provided the infarct portion and extent, which is valuable in assessing the severity of disease and guiding treatment procedures.

2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC2D2EFG-I'M2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

Prediction of Arteriovenous Access Dysfunction by Mel Spectrogram-based Deep Learning Model.

Background: The early detection of arteriovenous (AV) access dysfunction is crucial for maintaining the patency of vascular access. This study aimed to use deep learning to predict AV access malfunction necessitating further vascular management. Methods: This prospective cohort study enrolled prevalent hemodialysis (HD) patients with an AV fistula or AV graft from a single HD center. Their AV access bruit sounds were recorded weekly using an electronic stethoscope from three different sites (arterial needle site, venous needle site, and the midpoint between the arterial and venous needle sites) before HD sessions. The audio signals were converted to Mel spectrograms using Fourier transformation and utilized to develop deep learning models. Three deep learning models, (1) Convolutional Neural Network (CNN), (2) Convolutional Recurrent Neural Network (CRNN), and (3) Vision Transformers-Gate Recurrent Unit (ViT-GRU), were trained and compared to predict the likelihood of dysfunctional AV access. Results: Total 437 audio recordings were obtained from 84 patients. The CNN model outperformed the other models in the test set, with an F1 score of 0.7037 and area under the receiver operating characteristic curve (AUROC) of 0.7112. The Vit-GRU model had high performance in out-of-fold predictions, with an F1 score of 0.7131 and AUROC of 0.7745, but low generalization ability in the test set, with an F1 score of 0.5225 and AUROC of 0.5977. Conclusions: The CNN model based on Mel spectrograms could predict malfunctioning AV access requiring vascular intervention within 10 days. This approach could serve as a useful screening tool for high-risk AV access.

Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies.

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation.

The relationship between changes in functional connectivity gradients and cognitive-emotional disorders in sudden sensorineural hearing loss.

Sudden sensorineural hearing loss, a prevalent emergency in otolaryngology, is known to potentially precipitate cognitive and emotional disorders in affected individuals. Extensive research has documented the phenomenon of cortical functional reorganization in patients with sudden sensorineural hearing loss. However, the potential link between this neural functional remodelling and cognitive-emotional disorders remains unclear. To investigate this issue, 30 bilateral sudden sensorineural hearing loss patients and 30 healthy adults were recruited for this study. We collected clinical data and resting-state functional magnetic resonance imaging data from the participants. Gradient mapping analysis was employed to calculate the first three gradients for each subject. Subsequently, gradient changes in sudden sensorineural hearing loss patients were compared with healthy controls at global, regional and network levels. Finally, we explored the relationship between gradient values and clinical variables. The results revealed that at the global level, sudden sensorineural hearing loss did not exhibit significant differences in the primary gradient but showed a state of compression in the second and third gradients. At the regional level, sudden sensorineural hearing loss patients exhibited a significant reduction in the primary gradient values in the temporal pole and ventral prefrontal cortex, which were closely related to neuro-scale scores. Regarding the network level, sudden sensorineural hearing loss did not show significant differences in the primary gradient but instead displayed significant changes in the control network and default mode network in the second and third gradients. This study revealed disruptions in the functional hierarchy of sudden sensorineural hearing loss, and the alterations in functional connectivity gradients were closely associated with cognitive and emotional disturbances in patients. These findings provide new evidence for understanding the functional remodelling that occurs in sudden sensorineural hearing loss.

Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients.

Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies. Half of the expanded CL-reactive clones exhibited strong binding to SARS-CoV-2 antigens. One such clone, CoV1804, was reactive to both CL and viral nucleocapsid (N), and further showed anti-nucleolar activity in human cells. Notably, antibodies sharing genetic features with CoV1804 were identified in COVID-19 patient-derived immunoglobulins, thereby constituting a novel public antibody. These public autoantibodies had numerous mutations that unambiguously enhanced anti-N reactivity, when causing fluctuations in anti-CL reactivity along with the acquisition of additional self-reactivities, such as anti-nucleolar activity, in the progeny. Thus, potentially CL-reactive precursors may have developed multiple self-reactivities through clonal selection, expansion, and somatic hypermutation driven by viral antigens. Our results revealed the nature of autoantibody production during COVID-19 and provided novel insights into the origin of virus-induced autoantibodies.

Hepsin as a potential therapeutic target for alleviating acetaminophen-induced hepatotoxicity via gap-junction regulation and oxidative stress modulation.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver damage, highlighting the limitations of current emergency treatments that primarily involve administering the glutathione precursor N-acetylcysteine and supportive therapy. This study highlights the essential protective role of the type II transmembrane serine protease (TTSP), hepsin, in mitigating acetaminophen-induced liver injury, particularly through its regulation of gap junction (GJ) abundance in response to reactive oxygen stress in the liver. We previously reported that reduced levels of activated hepatocyte growth factor and the c-Met receptor tyrosine kinase-both of which are vital for maintaining cellular redox balance-combined with increased expression of GJ proteins in hepsin-deficient mice. Here, we show that hepsin deficiency in mice exacerbates acetaminophen toxicity compared to wild-type mice, leading to more severe liver pathology, elevated oxidative stress, and greater mortality within 6 h after exposure. Administering hepsin had a protective effect in both mouse models, reducing hepatotoxicity by modulating GJ abundance. Additionally, transcriptome analysis and a functional GJ inhibitor have highlighted hepsin's mechanism for managing oxidative stress. Combining hepsin with relatively low doses of N-acetylcysteine had a synergistic effect that was more efficacious than high-dose N-acetylcysteine alone. Our results illustrate the crucial role of hepsin in modulating the abundance of hepatic GJs and reducing oxidative stress, thereby offering early protection against acetaminophen-induced hepatotoxicity and a new, combination approach. Emerging as a promising therapeutic target, hepsin holds potential for combination therapy with N-acetylcysteine, paving the way for novel approaches in managing drug-induced liver injury.

Development and Optimization of Thin-Lithium-Metal Anodes with a Lithium Lanthanum Titanate Stabilization Coating for Enhancement of Lithium-Sulfur Battery Performance.

Lithium-ion batteries are dominating high-energy-density energy storage for 30 years. However, their development approaches theoretical limits, spurring the development of lithium-sulfur cells that achieve high energy densities through reversible electrochemical conversion reactions. Nevertheless, the commercialization of lithium-sulfur cells is hindered by practical challenges associated primarily with the use of thick-lithium anodes, low-loading sulfur cathodes, and high electrolyte-to-sulfur ratios, which prevent realization of the cells' full potential in terms of electrochemical and material performance. To solve these extrinsic and intrinsic problems, the effect of lithium-metal thickness on the electrochemical behavior of lithium-sulfur cells with high-loading sulfur cathodes in lean-electrolyte configurations is investigated. Specifically, lithium lanthanum titanate (LLTO), a solid electrolyte, is utilized to form an ionically/electronically conductive coating to stabilize lithium-metal anodes, thereby enhancing their lithium-ion pathways and interfacial charge transfer. Electrochemical analyses reveal that an LLTO coating significantly reduces excessive reactions between lithium metal and an electrolyte, thereby minimizing lithium consumption and electrolyte depletion. Further, LLTO-stabilized lithium anodes improve lithium-sulfur cell performance, and most importantly, allow the fabrication of thin-lithium, high-loading-sulfur cells that open a pathway toward high-energy-density batteries.

Urinary Concentrations of Organophosphate Flame-Retardant Metabolites in the US Population.

Importance: Organophosphate flame retardants (OPFRs) are an important group of pollutants associated with endocrine disorders, cancer, and nephrotoxicity. However, temporal trends in OPFR metabolite concentrations remain understudied. Objectives: To examine changes in urinary concentrations of OPFR metabolites among US children, youths, and adults from 2011 to 2020, and to evaluate whether sociodemographic factors were associated with variations in temporal trends. Design, Setting, and Participants: This population-based cross-sectional study used data from 4 US National Health and Nutrition Examination Survey (NHANES) cycles (2011-2012, 2013-2014, 2015-2016, and 2017-2020 [to March 2020 before the COVID-19 pandemic]). The study included children and youths (aged 6-19 years) and adults (aged ≥20 years) with valid urinary concentrations of the following OPFR metabolites: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), diphenyl phosphate (DPhP), and dibutyl phosphate (DBuP). Data analysis was performed between February and May 2024. Exposures: Calendar year and key sociodemographic subgroups (age, race and ethnicity, sex, educational attainment, and poverty-to-income ratio). Main Outcomes and Measures: The main outcome was urinary concentrations of OPFR metabolites among children, youths, and adults. Survey-weighted linear regression models were applied to estimate trends. Results: The study population of 10 549 NHANES participants included 3154 children and youths (mean [SE] age, 12.5 [0.1] years; 51.2% were male) and 7395 adults (mean [SE] age, 47.8 [0.4] years; 52.0% were women). Among children and youths, mean (95% CI) BCEtP concentrations decreased from 0.68 (0.60-0.77) µg/L in 2011-2012 to 0.41 (0.37-0.45) µg/L in 2017-2020 (P for trend < .001). Among adults, mean (95% CI) BCEtP concentrations decreased from 0.43 (0.37-0.50) µg/L in 2011-2012 to 0.29 (0.27-0.33) µg/L in 2017-2020 (P for trend < .001), and mean BCPP concentrations decreased from 0.15 (0.14-0.17) µg/L to 0.13 (0.12-0.14) µg/L (P for trend = .002). Parent level of educational attainment was associated with concentrations of BCPP and BCEtP among children and youths; however, no significant differences among adults were observed. Conclusions and Relevance: This study identified variations in temporal trends in urinary concentrations of OPFR metabolites among the US population from 2011 to 2020. In addition, substantial disparities in exposure levels persisted among children with different levels of parent educational attainment. These findings suggest that policy makers should consider socioeconomic factors to further reduce OPFR exposure and promote equity, ensuring a safe living environment for all individuals.

Microbial community response to temperature reduction during anaerobic treatment of long chain fatty acids-containing wastewater.

Acclimating mesophilic biomass to low temperatures have been used to start-up psychrophilic anaerobic reactors, but limited microbial information is available during the acclimation. To investigate microbial responses to temperature reductions, duplicate lab-scale anaerobic digestion (AD) reactors were operated for 166 days, with the temperature being reduced from 37°C to 15°C, using synthetic long chain fatty acid (LCFA)-containing wastewater as the feedstock. The acclimated biomass at 15°C exhibited efficient removal of organic matter (total COD>75%, soluble COD>88%, and LCFA>99%). Temperature reductions lead to significant reductions in microbiome diversity. Fermentative bacteria were highly dynamic and functional redundant during temperature reductions. Smithella was the dominant syntrophic bacteria involved in LCFA degradation coupled with Methanothrix and Methanocorpusculum at 15°C. Membrane modifications and compatible cellular solutes production were triggered by temperature reductions as microbial response to cold stress. This study provided molecular insights in microbial acclimation to low temperatures for psychrophilic AD.

Indium-Assisted Construction of {SiNb18O54}-Based Aggregates and Their Assembly into Extended Polyoxoniobate Architectures.

In this research, indium ions were introduced into polyoxoniobates (PONbs) reaction systems to facilitate the construction of different {SiNb18O54}-based aggregates, including an {In(en)2{SiNb18O54}2} (en = ethylenediamine) dimer, an {[InO2][In2(en)O3]2{SiNb18O54}3} trimer, and an {[In(en)2][InO2][In7(en)5O9]{SiNb18O54}4} tetramer. Interestingly, these aggregates were further assembled into three uncommon extended PONb architectures in the presence of [Cu(en)2]2+ complexes, namely, H3[Cu(en)2(H2O)][Cu(en)2]6[Cu(en)2]2{[In(en)2][K2{SiNb18O54}(H2O)6]2}·1.5en·16H2O, H9{[Cu(en)2]6{[Cu(en)2]3[Cu(en)2(H2O)][In(H2O)2][In2(en)(H2O)2(OH)]2{SiNb18O54}3}·5en·29H2O, and H14[Cu(en)2]0.5[Cu(en)2(H2O)]{[Cu(en)2]2{[Cu(en)2]3[Cu(en)2(H2O)]5[K(H2O)2][In(H2O)2][In(en)2][In7(OH)9(en)5]{SiNb18O54}4}·7en·39H2O. In addition, all of them have good water vapor adsorption capacities and moderate proton transport capabilities. The above results indicate that introducing suitable heteroatoms to induce the aggregation PONb building blocks and further assembling them into new structures is an effective strategy to enrich the PONbs' structural diversity and develop new functional materials.

Deciphering the roles of bacterial and fungal communities in the formation and quality of agarwood.

Aquilaria sinensis is a significant resin-producing plant worldwide that is crucial for agarwood production. Agarwood has different qualities depending on the method with which it is formed, and the microbial community structures that are present during these methods are also diverse. Furthermore, the microbial communities of plants play crucial roles in determining their health and productivity. While previous studies have investigated the impact of microorganisms on agarwood formation, they lack comprehensiveness, particularly regarding the properties of the microbial community throughout the entire process from seedling to adult to incense formation. We collected roots, stems, leaves, flowers, fruits and other tissues from seedlings, healthy plants and agarwood-producing plants to address this gap and assess the dominant bacterial species in the microbial community structures of A. sinensis at different growth stages and their impacts on growth and agarwood formation. The bacteria and fungi in these tissues were classified and counted from different perspectives. The samples were sequenced using the Illumina sequencing platform, and sequence analyses and species annotations were performed using a range of bioinformatics tools to assess the plant community compositions. An additional comparison of the samples was conducted using diversity analyses to assess their differences. This research revealed that Listeria, Kurtzmanomyces, Ascotaiwania, Acinetobacter, Sphingobium, Fonsecaea, Acrocalymma, Allorhizobium, Bacillus, Pseudomonas, Peethambara, and Debaryomyces are potentially associated with the formation of agarwood. Overall, the data provided in this article help us understand the important roles played by bacteria and fungi in the growth and agarwood formation process of A. sinensis, will support the theoretical basis for the large-scale cultivation of A. sinensis, and provide a basis for further research on microbial community applications in agarwood production and beyond.

Oleanolic acid improves 5-fluorouracil-induced intestinal damage and inflammation by alleviating intestinal senescence.

5-Fluorouracil (5-FU) is used as a standard first-line drug for colorectal cancer malignancy (CRC), but it brings a series of side effects such as severe diarrhea and intestinal damage. Our previous study found that a large number of senescent cells increased while 5-Fu induced intestinal damage, and anti-senescence drugs can alleviate its side effects of inflammatory damage. Oleanolic acid (OA) is a common pentacyclic triterpenoid mainly derived from food fungi and medicinal plants, and studies have shown that it mainly possesses hepatoprotective, enzyme-lowering, anti-inflammatory, and anti-tumor effects. But its role in senescence is still unclear. In the present study, we demonstrated for the first time that OA ameliorated 5-Fu-induced human umbilical vein endothelial cells (HUVECs) and human normal intestinal epithelial cells (NCM460) in a 5-Fu-induced cellular senescence model by decreasing the activity of SA-ß-gal-positive cells, and the expression of senescence-associated proteins (p16), senescence-associated genes (p53 and p21), and senescence-associated secretory phenotypes (SASPs: IL-1ß, IL-6, IL-8, IFN-γ and TNF-α). Meanwhile, in this study, in a BALB/c mouse model, we demonstrated that 5-FU induced intestinal inflammatory response and injury, which was also found to be closely related to the increase of senescent cells, and that OA treatment was effective in ameliorating these adverse phenomena. Furthermore, our in vivo and in vitro studies showed that OA could alleviate senescence by inhibiting mTOR. In colon cancer cell models, OA also enhanced the ability of 5-FU to kill HCT116 cells and SW480 cells. Overall, this study demonstrates for the first time the potential role of OA in counteracting the side effects of 5-FU chemotherapy, providing a new option for the treatment of colorectal cancer to progressively achieve the goal of high efficacy and low toxicity of chemotherapy.

Interdependence of Support Wettability -Electrodeposition Rate - Sodium Metal Anode and SEI Microstructure.

This study examines how current collector support chemistry (sodiophilic intermetallic Na2Te vs. sodiophobic baseline Cu) and electrodeposition rate affect microstructure of sodium metal and its solid electrolyte interphase (SEI). Capacity and current (6 mAh cm-2, 0.5-3 mA cm-2) representative of commercially relevant mass loading in anode-free sodium metal battery (AF-SMBs) are analyzed. Synchrotron X-ray nanotomography and grazing-incidence wide-angle X-ray scattering (GIWAXS) are combined with cryogenic focused ion beam (cryo-FIB) microscopy. Highlighted are major differences in film morphology, internal porosity, and crystallographic preferred orientation e.g. (110) vs. (100) and (211) with support and deposition rate. Within the SEI, sodium fluoride (NaF) is more prevalent with Te-Cu versus sodium hydride (NaH) and sodium hydroxide (NaOH) with baseline Cu. Due to competitive grain growth the preferred orientation of sodium crystallites depends on film thickness. Mesoscale modelling delineates the role of SEI (ionic conductivity, morphology) on electrodeposit growth and onset of electrochemical instability.