A new isoprenyl-phenol-type meroterpenoid from mangrove endophytic fungus Aspergillus sp. GXNU-Y65.

Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 µM, respectively.

α-Lactalbumin based scaffolds for infected wound healing and tissue regeneration.

Interruption of wound healing by multi-drug resistant-bacterial infection is a harmful issue for the worldwide health care system, and conventional treatment approaches may not resolve this issue due to antimicrobial resistance. So, there is an unmet need to develop scaffolds with intrinsic wound healing properties to combat bacterial-infected wounds. Inspired by the α-lactalbumin's (Lalb's) ability to promote collagen synthesis, we herein electrospun Lalb with cephalexin (CPL) and epigallocatechin (EP) to produce nanofibers (CE-Lalb NFs) to solve this issue. The CE-Lalb NFs were prepared using the electrospinning technique and subjected to physicochemical characterizations, in vitro, and in vivo assessments. The CE-Lalb NFs promoted fibroblast migration, proliferation, and collagen synthesis, while CPL/EP annihilated MRSA and E. coli infections. Physicochemical characterizations proved the successful fabrication and doping of CE-Lalb NFs. Antimicrobial assays and fractional inhibitory concentration index (FICI) declared synergistic antibacterial activity of CE-Lalb NFs against MRSA and E. coli. The in vivo and immunohistochemical data evidenced its exceptional potential for wound healing, promoting growth factor, collagen synthesis, and reduced scar formation. The presence of mature collagen, fewer inflammatory cytokines, increased expression of blood vessels, and low expression of IL-6 at the wound site support in vitro and in vivo results. In our view, the tailored scaffold is the next step for personalized wound dressings that could meet patients with infected wounds' unmet needs by the subscription of noninvasive and easily navigable therapeutic options.

Cancer-associated fibroblasts derived exosomal LINC01833 promotes the occurrence of non-small cell lung cancer through miR-335-5p -VAPA axis.

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment (TME) and can induce functional polarization of tumor macrophages. This study aimed to explore the effect of CAFs-derived exosome LINC01833 on the malignant biological behavior of non-small cell lung cancer (NSCLC) cells and its mechanism. Tumor tissues (n = 3) and adjacent noncancerous tissues (n = 3) were collected from patients with NSCLC, and fibroblasts (CAF, NF) were isolated from the two tissues. Expression of LINC01833/miR-335-5p/VAPA in NSCLC clinical tissues and cell lines was detected by RT-qPCR. Exosomes of CAFs and NFs were isolated by ultracentrifugation. Cell proliferation, migration, invasion, and M2 macrophage polarization were detected by MTT, transwell, wound-healing assay, and flow cytometry assay, while western blot was used to verify the expression of M2 macrophage polarization-related proteins. Tumor volume weight and M2 macrophage polarization were detected by tumor xenografts in nude mice. LINC01833 was highly expressed in NSCLC tumor tissues and cells. Knockdown of LINC01833 exosomes could significantly inhibit proliferation, migration, invasion of NSCLC cells, and M2 macrophage polarization of THP-1 cells, while simultaneous knockdown of miR-335-5p on the above basis could reverse the effect of knockdown of LINC01833. In vivo experiments also indicated that knockdown of LINC01833 exosomes suppressed tumor growth and M2 macrophage polarization. CAF-derived LINC01833 exosomes can promote the proliferation, migration and invasion of NSCLC cells and M2 macrophage polarization by inhibiting miR-335-5p and regulating VAPA activity.

Temperature-responsive hydrogel-grafted vessel-on-a-chip: Exploring cold-induced endothelial injury.

Cold-induced vasoconstriction is a significant contributor that leads to chilblains and hypothermia in humans. However, current animal models have limitations in replicating cold-induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel-on-a-chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of N-isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature set at 30°C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37°C to 4°C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel-on-a-chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel-on-a-chip led to cell necrosis, mitochondrial membrane potential (ΔΨm) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold-induced endothelial injury, this groundbreaking thermosensitive vessel-on-a-chip technology offers promising advancements in the study of cold-induced cardiovascular diseases, including pathogenesis and therapeutic drug screening.

Obstructed vein delivery of ceftriaxone via poly(vinyl-pyrrolidone)-iodine-chitosan nanofibers for the management of diabetic foot infections and burn wounds.

Superficial skin injuries especially burn injuries and unhealed diabetic foot open wounds remain troubling for public health. The healing process is often interrupted by the invasion of resistant pathogens that results in the failure of conventional procedures outside the clinical settings. Herein, we designed nanofibers dressing with intrinsic antibacterial potential of poly(vinyl-pyrrolidone)-iodine/ poly (vinyl)-alcohol by electrospinning with chitosan encapsulating ceftriaxone (CPC/NFs). The optimized electrospun CPC/NFs exhibited smooth surface morphology with average diameter of 165 ± 7.1 nm, drug entrapment and loading efficiencies of 76.97 ± 4.7 % and 8.32 ± 1.73 %, respectively. The results displayed smooth and uniformed fibers with adequate thermal stability and ensured chemical doping. The enhanced in vitro antibacterial efficacy of CPC/NFs against resistant E. coli isolates and biosafety studies encourage the use of designed nanofibers dressing for burn injuries and diabetic foot injuries. In vivo studies proved the healing power of dressing for burn wounds model and diabetic infected wounds model. Immunofluorescence investigation of the wound tissue also suggested promising healing ability of CPC/NFs. The designed approach would be helpful to treat these infected skin open wounds in the hospitals and outside the clinical settings.

The Association of Cerebral Oxygen Desaturation with Postoperative Cognitive Dysfunction in Older Patients: A Review.

Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.

Rhamnolipids stabilized essential oils microemulsion for antimicrobial and fruit preservation.

Essential oils, well-known for their antifungal properties, are widely utilized to combat fruit decay. However, their application faces big challenges due to their high volatility and hydrophobic traits, which leads to strong odor, short effective time and poor dispersivity. This study aimed to address these challenges by formulating microemulsions consisting of essential oils and rhamnolipids. The optimized microemulsion, featuring a small particle size of 6.8 nm, exhibited higher stability and lower volatility than conventional emulsion. Notably, the prepared microemulsions demonstrated remarkable antimicrobial efficacy against E. coli, S. aureus, C. albicans, S. cerevisiae, and A. niger. The application of these microemulsions proved to be highly effective in preventing blueberry decay while preserving fruit's quality, particularly by minimizing the loss of essential nutrients such as anthocyanins. Consequently, essential oil microemulsions emerge as a highly effective postharvest preservative for fruits, offering a promising solution to extend their shelf life and enhance overall quality.

Neuroprotective and anti-inflammatory effects of eicosane on glutamate and NMDA-induced retinal ganglion cell injury.

AIM: To investigate the protective effects, antioxidant potential, and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) injury in a mouse model of glaucoma. METHODS: The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining. Intracellular reactive oxygen species (ROS) production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry. The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina. The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatography-mass spectroscopy (LC-MS) and untargeted metabolomics analyses. RESULTS: Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro. Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model. Untargeted metabolomics analyses showed that eicosane increased multiple metabolites, including L-arginine and L-carnitine, in the retina. CONCLUSION: Eicosane has protective effects, antioxidant potential, and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.

Amphiphilic Interlayer Regulated Interfacial Polymerization for Constructing Polyamide Nanofiltration Membranes with High Perm-Selectivity of Mono-/Divalent Salts.

High-quality thin-film composite (TFC) membranes with high selectivity and permeability have great significance owing to their practical applications, specifically for the accurate differentiation of monovalent and divalent ions. However, the trade-off effect between selectivity and permeability is still a big challenge due to the difficult structure adjustment of the selective layer. Herein, polydopamine (PDA) functionalized with a hydrophobic long alkane chain was first explored as a functional amphiphilic interlayer to synthesize high-quality TFC membranes via a confined interfacial polymerization (IP) reaction. The amphiphilic interlayer not only restricted the formation of the polyamide (PA) matrix in the pores of the substrate but also accelerated spatially more homogeneous polymerization and formed a PA active layer with a more uniform pore size distribution. The method may provide an effective principle for the construction of versatile polyamide-based membranes with high perm-selectivity on various supports. The NaCl/Na2SO4 separation factor of the D-8/PA membrane reached as high as 204.07, while the flux increased up to 25.71 L m-2 h-1 bar-1. This progress provides a more feasible way for the construction of high-quality TFC membranes with a devisable and creative amphiphilic interlayer for industrial application.

Ionic-liquid-modified MOFs incorporated in a mixed-matrix membrane by metal-site anchoring for gas separation.

Through metal-site anchoring, metal-organic frameworks (MOFs) were modified with ionic liquids (ILs) and used as a porous filler to prepare mixed-matrix membranes (MMMs). The targeted growth of the IL exposed more active sites and greatly enhanced CO2 transfer in the MMMs, which exhibited excellent gas separation performance and long durability.

Tumor immunity: A brief overview of tumor­infiltrating immune cells and research advances into tumor­infiltrating lymphocytes in gynecological malignancies (Review).

Tumor immunity is a promising topic in the area of cancer therapy. The 'soil' function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor-infiltrating immune cells in the TME, especially the tumor-infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: 'Tumor microenvironment'; 'TME'; 'tumor-infiltrating immunity cells'; 'gynecologic malignancies'; 'the adoptive cell therapy (ACT) of TILs'; and 'TIL-ACT' (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor-infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy.

Latest advances and clinical application prospects of resveratrol therapy for neurocognitive disorders.

Neurocognitive disorders, such as Alzheimer's disease, vascular dementia, and postoperative cognitive dysfunction, are non-psychiatric brain syndromes in which a significant decline in cognitive function causes great trauma to the mental status of the patient. The lack of effective treatments for neurocognitive disorders imposes a considerable burden on society, including a substantial economic impact. Over the past few decades, the identification of resveratrol, a natural plant compound, has provided researchers with an opportunity to formulate novel strategies for the treatment of neurocognitive disorders. This is because resveratrol effectively protects the brain of those with neurocognitive disorders by targeting some mechanisms such as inflammation and oxidative stress. This article reviews the status of recent research investigating the use of resveratrol for the treatment of different neurocognitive disorders. By examining the possible mechanisms of action of resveratrol and the shared mechanisms of different neurocognitive disorders, treatments for neurocognitive disorders may be further clarified.

Genesis and Accumulation Mechanism of Low-Rank CBM: A Case Study in the Jiergalangtu Block of Erlian Basin, Northern China.

In order to elucidate the origin of coalbed methane (CBM) in the Jiergalangtu block of Erlian Basin, Inner Mongolia of China, gas components, stable isotope tests of 22 gas samples, radioisotope dating measurements, and water quality analysis of 15 coproduced water samples were evaluated. On account of the geochemical data and genetic indicators, including C1/C1-n, C1/(C2 + C3), and CO2/(CO2 + CH4) (CDMI) values, δ13C(CO2), Δδ13C(CO2-CH4), δ15N, and 3He/4He combined with vitrinite reflectance (Ro) (0.29-0.48%, avg. 0.35%) of Saihantala formation, the results indicate that methane in the Jiergalangtu block is mostly dominated by primary and secondary biological gas, 40.91% of the gas samples are secondary biogas and primary biogas accounts for 59.19%. Among them, methyl-type fermentation accounts for 31.82%, and carbon dioxide (CO2) reduction makes up 68.18%. CO2 reduction generally occurs region-wide but is mainly associated with the central part of the block, where CO2 depletion and 13C enrichment take place correspondingly. Methane and CO2 δ13C almost tend to isotopically light along the margin of the block, indicating that gas generation is significantly affected by the methyl-type fermentation pathway. Meanwhile, the genesis analysis of other gas components in CBM is also investigated, CO2 is mainly the associated product of microbial methanogenesis, and nitrogen (N2) is primarily from the atmosphere with a little amount from the earth's crust. Furthermore, the formation time of coalbed water has been dissected based on the hydrogeochemical properties of the coproduced water samples. The coalbed water exhibit a Na-HCO3 and Na-HCO3-Cl type and have a total dissolved solid (TDS) value ranging from 2458.58 to 5579.1 mg/L, with an average of 3440.55 mg/L. Moreover, comprehensive analysis of δD(H2O), δ18O(H2O), δ13CDIC, and the radioisotope dating index [3H, 14C(Fm) and 14C(BP)] indicates that the coalbed water was formed in the Quaternary Pleistocene and rarely replenished by the present surface water. The mechanism of CBM accumulation is basically sorted out by synthesizing the history of burial, heat, and hydrocarbon generation. The CBM formation can be divided into four stages. That is, microbial gas production approximately began at the beginning of the Early Cretaceous and reached the peak of thermogenic gas production in the middle and late Early Cretaceous. At the end of the Early Cretaceous, strata possibly began to uplift, and denudation led to gas escape. From Neogene to Pleistocene, glacial meltwater tended to penetrate into coalbed on a large scale, and N2 and CO2 also entered the coal seams, stimulating abundant secondary biological gas generation. Since Holocene, geological conditions including temperature and TDS have become hostile to biogas generation, and biogas generation tends to stop. Therefore, the Jiergalangtu block mainly represents sealed primary biological gas and secondary biological gas in CBM reservoirs.

Efficacy of an enhanced recovery nursing plan as a rooming-in practice for women with preeclampsia post-cesarean section.

Our purpose was to develop and evaluate the clinical outcomes of a nursing plan as a rooming-in practice for enhanced recovery of women with preeclampsia following a cesarean section. The authors developed a postoperative enhanced recovery nursing plan as a rooming-in practice for women with preeclampsia based on summarizing evidence-based best practices. The authors used convenience sampling to select women with preeclampsia after a cesarean section from the obstetrics department of a Class A tertiary hospital in Nanjing, China, as the participants in our study. There were 30 women in the experimental group. The postoperative enhanced recovery nursing care plan was formulated for five postoperative time points and incorporated management of blood pressure, temperature, and fluids, as well as monitoring of complications, pain management, activity and rest, diet management, and breastfeeding. The control group consisted of 30 women who received routine nursing care and health education. The authors compared levels of maternal self-efficacy, breastfeeding efficacy, anxiety, pain scores, and deep vein thrombosis (DVT) prevention compliance before and after the intervention. Women in the experimental group had a self-efficacy score of 7.5 ± 0.63, which was higher than that in the control group (5.4 ± 0.85); they had a higher breastfeeding efficacy score of 7.13 ± 0.68 when compared to the control group (4.23 ± 0.86); the anxiety score was 6.7 ± 1.62, which was lower than that in the control group (10.03 ± 1.87); and the pain score was lower at 3.26 ± 0.52 when compared to the control group (3.83 ± 0.83). All the differences were statistically significant (P < 0.05). Postoperative blood pressure was controlled within the target range, and the rate of DVT prevention compliance increased in the experimental group. The implementation of a postoperative enhanced recovery nursing intervention for women with preeclampsia as part of the rooming-in practice was effective in helping manage the blood pressure, pain, and fluids of women with preeclampsia, improved their postoperative self-management ability and breastfeeding efficacy, reduced their anxiety levels, improved their compliance with the prevention of related complications, and ultimately promoted enhanced postoperative recovery, thereby guaranteeing the safety of mothers and newborns.

Does Mandala Art Improve Psychological Well-Being in Patients? A Systematic Review.

Objectives: Psychological disorders and symptoms are common and can significantly impair functioning in some areas in patients. We aimed to investigate the effects of mandala art (MA) on psychological well-being in patients. Design: A systematic review. Methods: We did a systematic review to assess the associations between MA and psychological well-being among patients. A systematic search of PubMed, EMBASE, Web of Science, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trial databases was conducted by independent reviewers from database inception to April 2023. We include randomized controlled trials, quasi-experimental studies, and qualitative studies. Outcome measures included any measurement of subjective and objective psychological well-being outcomes, such as stress, anxiety, depression, distress, mindfulness, hope, resilience, pain, mood, fatigue, and trauma symptoms. Results: Eleven studies of 405 participants were identified in the systematic review. Overall, the included studies provided preliminary evidence to suggest that MA may improve negative symptoms and hope, relieving pain, and reducing some physiological indicators of stress in patients. However, the quality of the existing evidence limited the generalization of results. Conclusions: According to the current evidence, the therapeutic benefits of using mandalas for improving the psychological well-being of patients are uncertain. More well-designed and high-quality studies in the field of MA are needed in the future.

Electrodialysis treatment of rhamnolipids hydrolysate and its waste water for use as water-soluble fertilizer.

Rhamnolipids can serve as a precursor for rhamnose production, but using ion exchange resin in purifying rhamnolipids hydrolysate results in excessive high-salinity wastewater, making the process environmentally and economically unfeasible. This study introduced electrodialysis technology as an alternative for purifying rhamnolipids hydrolysate, significantly reducing wastewater to less than 5 % compared to the resin method. To achieve zero wastewater discharge, the electrodialysis-treated wastewater was repurposed into a water-soluble fertilizer containing 7.1 g/L of rhamnolipids, 11.4 g/L of fatty acid, 2.4 g/L of amino acid, and 8.2 g/L of potassium. Unlike traditional fertilizers, the nutritional components with rhamnolipids showed remarkable potential in enhancing tomato plant growth, flowering, and fruit quality. Taken together, the electrodialysis treatment of rhamnolipids hydrolysate largely reduced the water volume, the economic cost, and took a full use of the final wastewater as efficient water-soluble fertilizers, making it applicable for large-scale rhamnose production.

N/P co-doped MXene hollow microcapsules by surfactants assisted hydrothermal-freeze drying for adjustable permeability.

The assembly of MXene materials into microcapsules has drawn great attentions due to their unique properties. However, rational design and synthesis of MXene-based microcapsules with specific nanostructures at the molecular scale remains challenging. Herein, we report a strategy to synthesize N/P co-doped MXene hollow flower-like microcapsules with adjustable permeability via dual surfactants assisted hydrothermal-freeze drying method. In contrast to anionic surfactants, cationic surfactants exhibited effective electrostatic interactions with MXene nanosheets during the hydrothermal process. Manipulation of dual surfactants in hydrothermal process realized N and P co-doping of MXene to improve flexibility and promoted the generation of abundant internal cavities in flower-like microcapsules. Based on the unique microstructure, the prepared hollow flower-like microcapsules showed excellent performance, stability and reusability in size-selective release of small organic molecules. Moreover, the release rate can be controlled by turning the oxidation state and type of MXene. The strategy delineates promising prospects for the design of MXene-based microcapsules with specific structures.

Oral glucose gel in the prevention of neonatal hypoglycemia: A systematic review and meta-analysis.

BACKGROUND: Neonatal hypoglycemia (NH) is the most prevalent metabolic disorder in neonates and glucose gel in oral solution is a relatively new treatment option for NH. We aimed to determine whether oral glucose gel can prevent NH. METHODS: We conducted an open literature search using PubMed, Embase, Cochrane Library, and Web of Science. We used relative risk as the statistical data, expressed each outcome effect as a 95% confidence interval, and conducted a heterogeneity test. If heterogeneity statistics indicated that I2 was ≥ 50%, the random effects model analysis was used; otherwise, the fixed effects model analysis was conducted, and sensitivity analyses were conducted for all outcomes. RESULTS: In this review, we included a total of 10 studies involving 4801 neonates. Meta-analysis revealed that there were no significant differences between the preventive oral glucose gel group and the control group in terms of blood glucose concentration, glucose concentration 30 minutes after the first breastfeeding, length of stay, Bayley-III composite score, subsequent need for intravenous injection of glucose, 24-hour glucose > 50 mg/dL, separation from mother for treatment of hypoglycemia/admitted to neonatal intensive care unit for hypoglycemia, normoglycemia after 1 to 2 treatments, or normoglycemia after more than 2 treatments, breastfeeding at discharge, delayed feeding, neurosensory impairment, parental satisfaction, developmental delay, and seizure. The subsequent intake was significantly lower in the glucose gel group compared to the control group. INTERPRETATION: The use of oral glucose gel as a preventative measure may not reduce the incidence of NH. In order to assess the efficacy of glucose gel in preventing NH, a more high-quality, large-sample, and rigorously designed randomized controlled trial is required.

Fabrication of sac-like hydrogel membranes for replicating curved tissue barriers on chips.

Current organ-on-a-chip (OOC) systems cannot mimic in vivo tissue barriers that feature curved geometries and rhythmic movement. This is due to the lack of a relevant membrane that can reproduce the natural biochemical and physical properties of a basement membrane, especially the characteristic sac-like structure possessed by multiple tissue barriers. To address this challenge, a sac-like hydrogel membrane is fabricated here using a one-step simple methodology inspired by soap bubble formation. Di-acrylated Pluronic® F127 (F127-DA) is a hydrogel that exhibits excellent mechanical properties, stably withstanding rhythmic mechanical stretching and fluid flow for at least 24 h. Using this hydrogel to make a membrane, a complex lung-on-a-chip device is successfully constructed, effectively replicating the alveolar-capillary barrier and demonstrating cellular function under physiological respiratory conditions. This membrane offers a crucial platform for replicating sac-like tissue barriers.

Endotoxin accelerates insulin amyloid formation and inactivates insulin signal transduction.

AIMS AND OBJECTIVES: The aim of this study is to discuss the influence of endotoxin on insulin amyloid formation, to provide guidance for therapeutic insulin preparation and storage. MATERIALS AND METHODS: The ThT and ANS binding assays were applied to characterize the dynamics curve of insulin amyloid formation with the presence or absence of endotoxin. The morphological structures of intermediate and mature insulin fibrils were observed with SEM and TEM. Secondary structural changes of insulin during fibriliation were examined with CD, FTIR and Raman spectral analysis. The cytotoxic effects of oligomeric and amyloidogenic insulin aggregates were detected using a cck-8 cell viability assay kit. The influence of endotoxin on insulin efficacy was analyzed by monitoring the activation of insulin signal transduction. KEY FINDINGS: ThT analysis showed that endotoxin, regardless of species, accelerated insulin fibrils formation in a dose-dependent manner, as observed with a shorter lag phase. ANS binding assay demonstrated endotoxin provoked the exposure of insulin hydrophobic patches. The results of SEM and TEM data displayed that endotoxin drove insulin to cluster into dense and viscous form, with thicker and stronger filaments. Based on CD, FTIR and Raman spectra, endotoxin promoted the transition of α-helix to random coil and ß-strand secondary structures during insulin aggregation. Insulins in both oligomeric and amyloidogenic forms were cytotoxic to HepG2 cells, with the former being more severe. Finally, the efficacy of endotoxin treated insulin obviously decreased. SIGNIFICANCE: Our studies revealed that endotoxin disrupts the structural integrity of insulin and promotes its amyloidosis. These findings offered theoretical guidance for insulin storage and safe utilization, as well as pointing up a new direction for insulin resistance research.