Bile acids attenuate hepatic inflammation during ischemia/reperfusion injury.

Background & Aims: Persistent cholestasis has been associated with poor prognosis after orthotopic liver transplantation. In this study, we aimed to investigate how the accumulation of tauro-beta-muricholic acid (TßMCA), resulting from the reprogramming of bile acid (BA) metabolism during liver ischemia/reperfusion (IR) stress, attenuates liver inflammation. Methods: Ingenuity Pathway Analysis was performed using transcriptome data from a murine hepatic IR model. Three different models of hepatic IR (liver warm IR, bile duct separation-IR, common bile duct ligation-IR) were employed. We generated adeno-associated virus-transfected mice and CD11b-DTR mice to assess the role of BAs in regulating the myeloid S1PR2-GSDMD axis. Hepatic BA levels were analyzed using targeted metabolomics. Finally, the correlation between the reprogramming of BA metabolism and hepatic S1PR2 levels was validated through RNA-seq of human liver transplant biopsies. Results: We found that BA metabolism underwent reprogramming in murine hepatocytes under IR stress, leading to increased synthesis of TßMCA, catalyzed by the enzyme CYP2C70. The levels of hepatic TßMCA were negatively correlated with the severity of hepatic inflammation, as indicated by the serum IL-1ß levels. Inhibition of hepatic CYP2C70 resulted in reduced TßMCA production, which subsequently increased serum IL-1ß levels and exacerbated IR injury. Moreover, our findings suggested that TßMCA could inhibit canonical inflammasome activation in macrophages and attenuate inflammatory responses in a myeloid-specific S1PR2-GSDMD-dependent manner. Additionally, Gly-ßMCA, a derivative of TßMCA, could effectively attenuate inflammatory injury in vivo and inhibit human macrophage pyroptosis in vitro. Conclusions: IR stress orchestrates hepatic BA metabolism to generate TßMCA, which attenuates hepatic inflammatory injury by inhibiting the myeloid S1PR2-GSDMD axis. Bile acids have immunomodulatory functions in liver reperfusion injury that may guide therapeutic strategies. Impact and implications: Our research reveals that liver ischemia-reperfusion stress triggers reprogramming of bile acid metabolism. This functions as an adaptive mechanism to mitigate inflammatory injury by regulating the S1PR2-GSDMD axis, thereby controlling the release of IL-1ß from macrophages. Our results highlight the crucial role of bile acids in regulating hepatocyte-immune cell crosstalk, which demonstrates an immunomodulatory function in liver reperfusion injury that may guide therapeutic strategies targeting bile acids and their receptors.

Multi objective optimization and evaluation approach of prefabricated component combination solutions using NSGA-II and simulated annealing optimized projection pursuit method.

As a main carrier mode for the sustainable development of the construction industry in China, prefabricated building may lead to problems such as cost overruns, project delays, and waste of resources due to unreasonable selection of prefabricated components. Therefore, we quantitatively analyze the contribution rate of quality optimization of prefabricated components using QFD-SEM. Under the constraints of prefabrication rate, quality optimization contribution rate, and expected values of various sub-goals, we propose a multi-objective optimization method for prefabricated component combinations based on cost, duration, and carbon emissions. By using NSGA-II to solve the model, we can obtain a set of optimal Pareto solutions for prefabricated component combinations. Based on the optimal Pareto solution set, we establish a multi-objective evaluation model using simulated annealing optimization projection tracing method, and select the optimal prefabricated component combination solution according to the projected eigenvalues of the solutions. An empirical study is conducted using an eleven-story framed building in Shenzhen, Guangdong Province, China as a case study. The results show that: (1) Using this method, optimal solutions can be obtained in an unbounded solution space, with the optimal solution having advantages over both fully cast-in-place and fully prefabricated solutions. Compared to the fully cast-in-place solution, the duration and carbon emissions are reduced by 36.62% and 12.74% respectively, while compared to the fully prefabricated solution, costs are reduced by 4.15%. (2) There is a certain negative correlation between the cost of prefabricated component combinations and duration, carbon emissions, and quality optimization, while there is a certain positive correlation with the prefabrication rate. (3) The size of the optimal projection direction vector based on the optimization objectives indicates that carbon emissions have the greatest impact on the evaluation results of the solutions.

Structural variations of a new fertility restorer gene, Rf20, underlie the restoration of wild abortive-type cytoplasmic male sterility in rice.

The discovery of a wild abortive-type (WA) cytoplasmic male sterile (CMS) line and breeding its restorer line have led to the commercialization of three-line hybrid rice, contributing considerably to global food security. However, the molecular mechanisms underlying fertility abortion and the restoration of CMS-WA lines remain largely elusive. In this study, we cloned a restorer gene, Rf20, following a genome-wide association study analysis of the core parent lines of three-line hybrid rice. We found that Rf20 was present in all core parental lines, but different haplotypes and structural variants of its gene resulted in differences in Rf20 expression levels between sterile and restored lines. Rf20 could restore pollen fertility in the CMS-WA line and was found to be responsible for fertility restoration in some CMS lines under high temperatures. In addition, we found that Rf20 encodes a pentatricopeptide repeat protein that competes with WA352 for binding with COX11. This interaction enhances COX11's function as a scavenger of reactive oxygen species, which in turn restores pollen fertility. Collectively, our study suggests a new action mode for pentatricopeptide repeat proteins in the fertility restoration of CMS lines, providing an essential theoretical basis for breeding robust restorer lines and for overcoming high temperature-induced fertility recovery of some CMS lines.

The deubiquitinase OTUD1 stabilizes NRF2 to alleviate hepatic ischemia/reperfusion injury.

Hepatic ischemia/reperfusion (I/R) injury is an important cause of liver function impairment following liver surgery. The ubiquitin-proteasome system (UPS) plays a crucial role in protein quality control and has substantial impact on the hepatic I/R process. Although OTU deubiquitinase 1 (OTUD1) is involved in diverse biological processes, its specific functional implications in hepatic I/R are not yet fully understood. This study demonstrates that OTUD1 alleviates oxidative stress, apoptosis, and inflammation induced by hepatic I/R injury. Mechanistically, OTUD1 deubiquitinates and activates nuclear factor erythroid 2-related factor 2 (NRF2) through its catalytic site cysteine 320 residue and ETGE motif, thereby attenuating hepatic I/R injury. Additionally, administration of a short peptide containing the ETGE motif significantly mitigates hepatic I/R injury in mice. Overall, our study elucidates the mechanism and role of OTUD1 in ameliorating hepatic I/R injury, providing a theoretical basis for potential treatment using ETGE-peptide.

Characterization of posterior circulation blood perfusion in patients with different degrees of basilar artery tortuosity.

OBJECTIVE: The morphology of basilar artery (BA) may affect posterior circulation blood perfusion. We aimed to investigate whether different degrees of BA tortuosity could lead to the alterations of posterior circulation perfusion. METHODS: We collected 138 subjects with different BA tortuosity scores, including 32 cases of score 0, 45 cases of score 1, 43 cases of score 2, and 18 cases of score 3. A higher score represented a higher degree of BA tortuosity. Ordered logistic regression analysis was performed to investigate the risk factors for BA tortuosity. We quantitatively measured the cerebral blood flow (CBF) in eight posterior circulation brain regions using arterial spin labeling. SPSS 25.0 was used for statistical analysis. The correlation between the CBF and BA tortuosity was corrected by the Bonferroni method. The significance level was set at 0.006 (0.05/8). RESULTS: Hypertension (HR: 2.39; 95%CI: 1.23-4.71; P = 0.01) and vertebral artery dominance (HR: 2.38; 95%CI: 1.10-4.67; P = 0.03) were risk factors for BA tortuosity. CBF in occipital gray matter (R = -0.383, P < 0.001), occipital white matter (R = -0.377, P < 0.001), temporal gray matter (R = -0.292, P = 0.001), temporal white matter (R = -0.297, P < 0.001), and cerebellum (R = -0.328, P < 0.001) were negatively correlated with BA tortuosity degree. No significant correlation was found between the BA tortuosity degree and CBF in hippocampus (R = -0.208, P = 0.014), thalamus (R = -0.001, P = 0.988) and brainstem (R = -0.204, P = 0.016). CONCLUSIONS: BA tortuosity could affect posterior circulation blood perfusion. CBF was negatively correlated with BA tortuosity degree. The morphology of BA may serve as a biomarker for posterior circulation and the severity of posterior circulation ischemia.

A Numerical Simulation of Moisture Reduction in Fine Soil Subgrade with Wicking Geotextiles.

A new wicking geotextile is proposed to control the water content of fine-grained soil subgrade. By comparing the spatial distribution of volumetric water content and matric suction before and after the installation of the wicking geotextile, the effectiveness of the geotextile in controlling the subgrade humidity is evaluated. Firstly, the hydraulic parameters of the wicking geotextile are obtained through laboratory tests using a pressure plate apparatus. Then, a numerical model for water flow in the subgrade is established using COMSOL to obtain the spatial distribution characteristics of humidity in the subgrade under different groundwater levels (2~8 m). The results show the wicking geotextile exhibits strong hydrophilicity, low water retention, and high horizontal permeability. Compared to the subgrade without geotextile, the water content of the soil above the geotextile decreases significantly by 7.6~9.6% at groundwater levels of 4~8m, while the saturation decreases by 18.3~23.0%, and the matric suction increases by 2~2.3 times. The wicking fabric functions as an effective drainage material to serve as a capillary barrier in the cross-plane direction and an effective drainage tunnel to transport water in the in-plane direction. The dynamic resilient modulus of the subgrade increases by 23.2~43.6%. The wicking geotextile effectively absorbs and drains weakly bound water in unsaturated soil due to the matric suction difference and its horizontal drainage capacity to improve the bearing capacity of the subgrade. It suggests that using wicking geotextile for drainage and reinforcement in fine-grained soil subgrades with groundwater levels ranging from 4 to 8 m is beneficial.

Ringlike late gadolinium enhancement provides incremental prognostic value in non-classical arrhythmogenic cardiomyopathy.

BACKGROUND: The 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model has proved insufficient in the capability of predicting ventricular arrhythmia (VA) risk in non-classical arrhythmogenic cardiomyopathy (ACM). Furthermore, the prognostic value of ringlike late gadolinium enhancement (LGE) of the left ventricle in non-classical ACM remains unknown. We aimed to assess the incremental value of ringlike LGE over the 2019 ARVC risk model in predicting sustained VA in patients with non-classical ACM. METHODS: In this retrospective study, consecutive patients with non-classical ACM who underwent CMR from January 2011 to January 2022 were included. The pattern of LGE was categorized as no, non-ringlike, and ringlike LGE. The primary outcome was defined as the occurrence of sustained VA. Univariable and multivariable Cox regression analysis was used to evaluate the impact of LGE patterns on sustained VA and area under curve (AUC) was calculated for the incremental value of ringlike LGE. RESULTS: A total of 73 patients were collected in the final cohort (mean age, 39.3 ± 14.4 years, 51 male), of whom 10 (13.7%) had no LGE, 33 (45.2%) had non-ringlike LGE, and 30 (41.1%) had ringlike LGE. There was no statistically significant difference in the 5-year risk score among the three groups (P = 0.190). During a median follow-up of 34 (13-56) months, 34 (46.6%) patients experienced sustained VA, including 1 (10.0%), 13 (39.4%) and 20 (66.7%) of patients with no, non-ringlike and ringlike LGE, respectively. After multivariable adjustment, ringlike LGE remained independently associated with the presence of sustained VA (adjusted hazard ratio: 6.91, 95% confidence intervals: 1.89-54.60; P = 0.036). Adding ringlike LGE to the 2019 ARVC risk model showed significantly incremental prognostic value for sustained VA (AUC: 0.80 vs. 0.67; P = 0.024). CONCLUSION: Ringlike LGE provides independent and incremental prognostic value over the 2019 ARVC risk model in patients with non-classical ACM.

Sleep disturbances and the risk of lung cancer: a meta-epidemiological study.

BACKGROUND: The relationship between sleep disturbances and lung cancer is complex and bidirectional. This meta-epidemiological study aimed to explore the potential association between sleep disruption and the risk of pulmonary cancer. METHODS: We conducted a comprehensive literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases to retrieve relevant studies. We employed the Newcastle-Ottawa Scale to assess the quality of the observational studies. Stata 17.0 was used to synthesize and conduct a meta-analysis of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). We used funnel plot analysis and Egger's regression test to evaluate potential publication bias. RESULTS: A total of 11 studies were included with 469,691 participants. The methodological quality of the included studies ranged from moderate to high. Compared with 7-8 h of sleep time, short sleep duration was associated with a 13% higher lung cancer risk [OR, 1.13; 95%CI: 1.02-1.25; I2 = 67.6%; P = 0.018] and long sleep duration with a 22% higher risk [OR, 1.22; 95%CI: 1.12-1.33; I2 = 6.9%; P < 0.001]. Insomnia symptoms [OR, 1.11; 95%CI: 1.07-1.16; I2 = 0%; P < 0.001] and evening chronotype [OR, 1.15; 95%CI: 1.05-1.26; P = 0.002] were all related to a higher risk of lung cancer. Egger's test revealed no publication bias for sleep duration (P = 0.13). DISCUSSION: This systematic review is the first one which observes positive correction between sleep disturbances and the incidence of lung cancer. While the plausible mechanism is not clear, it is hypothesized that the association of short sleep duration and lung cancer mainly mediated by melatonin secretion and the immune-inflammatory balance. Further studies are needed to examine whether other risk factors, such as age, occupation, cumulative effect of sleep disturbances might mediate the relationship between sleep disturbances and lung cancer risk. CONCLUSION: The present study revealed that insufficient and excessive sleep duration, insomnia symptoms, and evening chronotype were significantly predictive of an increased risk of lung cancer. This finding underscores the need to account for sleep disturbances as an independent risk factor for evaluating susceptibility to lung cancer. TRIAL REGISTRATION: CRD42023405351.

Ultrahigh Piezocatalytic Performance of Perovskite Ferroelectric Powder via Oxygen Vacancy Engineering.

Piezocatalysis has increasingly gained prominence due to its enormous potential for addressing energy shortages and environmental pollution issues. Nonetheless, the low piezocatalytic activity of state-of-the-art materials seriously inhibits the practical applications of piezocatalysis. Here, it is proposed to greatly enhance the piezocatalytic activity for a perovskite ferroelectric, i.e., Sm-doped 0.68Pb(Mg1/3 Nb2/3 )-0.32PbTiO3 (Sm-PMN-PT, a solid solution with ultrahigh piezoelectricity), by introducing oxygen vacancies (OVs). The results show that the presence of OVs promotes the production of reactive oxygen species while enhancing the adsorption and activation of organic pollutants to improve piezocatalytic performance. The OV-Sm-PMN-PT is found to possess a superior piezocatalytic degradation rate constant of 0.073 min-1 under ultrasonic vibration, which is ≈4.9 times higher than that of pristine Sm-PMN-PT. Furthermore, the OV-Sm-PMN-PT can efficiently remove RhB under 400 rpm stirring, making it a promising candidate for water purification using low-frequency mechanical energy from nature. This research sheds light on the design of piezocatalytic materials via defect engineering.

Lead zirconate titanate ceramics with aligned crystallite grains.

The piezoelectric properties of lead zirconate titanate [Pb(Zr,Ti)O3 or PZT] ceramics could be enhanced by fabricating textured ceramics that would align the crystal grains along specific orientations. We present a seed-passivated texturing process to fabricate textured PZT ceramics by using newly developed Ba(Zr,Ti)O3 microplatelet templates. This process not only ensures the template-induced grain growth in titanium-rich PZT layers but also facilitates desired composition through interlayer diffusion of zirconium and titanium. We successfully prepared textured PZT ceramics with outstanding properties, including Curie temperatures of 360°C, piezoelectric coefficients d33 of 760 picocoulombs per newton and g33 of 100 millivolt meters per newton, and electromechanical couplings k33 of 0.85. This study addresses the challenge of fabricating textured rhombohedral PZT ceramics by suppressing the otherwise severe chemical reaction between PZT powder and titanate templates.

Protective effects of oridonin against osteoporosis by regulating immunity and activating the Wnt3a/ß-catenin/VEGF pathway in ovariectomized mice.

This study was performed with the aim of investigating the effect of oridonin (ORI) on estrogen deprivation-induced osteoporosis in mice and its mechanism. Animal experiments were used in this work to validate the anti-osteoporotic efficacy of ORI. Morphometric analysis was performed by micro-CT. A special protein meter was used to detect the content of immunoglobulin lgM, immunoglobulin lgG, complement C3 and C4 in the serum of mice. The expression of CD4+CD25+Foxp3+ Treg cell and CD4+/CD8+ lymphocyte subsets in mice was detected by flow cytometry. ELISA was used to detect the content of insulin-like growth factor (IGF-1), tumor necrosis factor (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6). In addition, key signaling molecules in the Wnt3a/ß-catenin signaling pathway were detected by Western blotting. The results showed that compared with the model group, the contents of calcium and phosphorus in the femurs of mice in the ORI groups were increased, and the spleen coefficient was decreased. The ALP activity in the serum of mice in the high and medium dose ORI groups was decreased, and the uterine coefficient was increased. ORI significantly increased the maximum bending load and the maximum bending stress of the femurs of mice, increased the number of trabeculae, and repaired the bone microstructure. At the same time, ORI could significantly increase the levels of immunoglobulin (lgG and lgM) and complement (C3 and C4), increase the activity of peritoneal macrophages in mice, increase the expression of CD4+CD25+Foxp3+ Tregs and CD4+/CD8+ in the spleen, increase the content of IGF-1, reduce the content of TNF-α, IL-1 and IL-6 and increase the expression levels of VEGF, Wnt3a, p-GSK3ß/GSK3ß and ß-catenin/Lamin in the femoral tissue. These results indicated that ORI might regulate the expression of VEGF through the Wnt3a/ß-catenin signaling pathway, improve the immunity of mice, maintain the balance of the immune system, and promote angiogenesis, thereby improving the bone mineral density and bone tissue morphology of mice and playing an anti-osteoporotic role.

VE-822 upregulates the deubiquitinase OTUD1 to stabilize FHL1 to inhibit the progression of lung adenocarcinoma.

BACKGROUND: The deubiquitinase ovarian tumor domain-containing 1 (OTUD1) has been considered as a tumor suppressor in many tumors, but there is minimal research on the role of OTUD1 in lung adenocarcinoma (LUAD) pathogenesis. METHODS: Bioinformatics analyses and western blot were applied for investigating OTUD1 expression in lung cancer and the drug that upregulated OTUD1. Kaplan-Meier analysis with log-rank test was used for survival analyses. IP-MS and co-IP were performed for identifying potential protein interactions with OTUD1. In vitro and in vivo assays were used for exploring the function of OTUD1 during the progression of LUAD. RESULTS: OTUD1 was dramatically downregulated in tumors and cell lines of human lung cancer. OTUD1 inhibited proliferation and migration of lung cancer cells in vitro. Moreover, OTUD1 inhibited growth of xenografts in nude mice and formation of primary lung tumors in urethane-induced lung cancer model. Mechanistically, we showed that OTUD1 deubiquitinated and stabilized FHL1. Furthermore, we listed and identified VE-822 as a candidate agonist for OTUD1. VE-822 inhibited proliferation of lung adenocarcinoma both in vitro and in vivo. CONCLUSION: These results indicated that the deubiquitinase OTUD1, which was upregulated by VE-822, inhibited the progression of LUAD in vitro and in vivo by deubiquitinating and stabilizing FHL1.

Digestion profile, antioxidant, and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis.

BACKGROUND: Novel functional polysaccharides from fungi are important nutraceuticals. An exopolysaccharide, Morchella esculenta exopolysaccharide (MEP 2), was extracted and purified from the fermentation liquor of M. esculenta. The aim of this study was to investigate its digestion profile, antioxidant capacity, and effect on the microbiota composition in diabetic mice. RESULTS: The study found that MEP 2 was stable during in vitro saliva digestion but was partially degraded during gastric digestion. The digest enzymes exerted a negligible effect on the chemical structure of MEP 2. Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. After digestion, the antioxidant ability increased as revealed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Both MEP 2 and its digested components showed strong α-amylase and moderate α-glucosidase inhibition activity, leading us to further investigate its ability to modulate the diabetic symptoms. The MEP 2 treatment ameliorated the inflammatory cell infiltration and increased the size of pancreas inlets. Serum concentration of HbA1c was significantly reduced. Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. The MEP 2 increased the diversity of the gut microbiota and modulated the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina, and several Lachnospiraceae species. CONCLUSION: It was found that MEP 2 was partially degraded during in vitro digestion. Its potential antidiabetic bioactivity may be associated with its α-amylase inhibition and gut microbiome modulation ability. © 2023 Society of Chemical Industry.

Study on the evolution of the pore structure of low rank coal during spontaneous combustion.

Studying the evolution of the pore structure of coal during spontaneous combustion is of great value in further understanding the mechanism of coal spontaneous combustion (CSC) and its prevention. In this study, we selected three low-rank coals and used nuclear magnetic resonance (NMR) to visualize the macroscopic evolution of the pore structure of coal after heat treatment and to analyze the effect of temperature (25-500 °C) on the pore structure of coal, including porosity, permeability, and fractal dimensions. The obtained results show that the overall NMR signal in coal increases with increasing temperature, indicating that heat treatment can induce the enlargement, opening, and interconnection of pores and fractures in coal. The equivalent average pore radius (rm) of coal shows a positive correlation with temperature, with a substantial increase in rm, especially after temperatures above 200 °C. During heating, the porosity and permeability of all three coals tended to increase with temperature. At temperatures above 300 °C, the permeability of coal dramatically increases, predicting a higher fluid transport capacity. Furthermore, NMR multifractal theory was proposed for quantitative pore space dimensional characterization. The obtained results show that the fractal dimensions of the adsorption space of coal pores increase and then decrease with temperature during heating, while the fractal dimensions of percolation space are negatively correlated with temperature. In addition, the dimensions of adsorption space vary more strongly than those of percolation space, meaning that the adsorption capacity of low-rank coals is more significantly influenced by temperature.

Predictive performance of the perivascular fat attenuation index for interventional antegrade percutaneous coronary intervention for chronic total occlusion.

OBJECTIVES: This study aimed to investigate the association between the perivascular fat attenuation index (FAI) and the success of the antegrade percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS: This study evaluated patients with only one CTO lesion observed on conventional coronary angiography (CAG) who underwent coronary computed tomography angiography (CCTA) < 1 month before CAG, from 2018 to 2019. The clinical data, CCTA-based CTO lesion morphologic characteristics, and perivascular FAI of CTO lesions were recorded and analysed. RESULTS: In total, 156 patients with CTOs were enrolled in this study. Successful antegrade PCI (A-PCI) was achieved in 105 CTO lesions (67.3%). The perivascular FAI of the failed A-PCI group was significantly lower than the successful A-PCI group (-84.76 ± 10.44 Hounsfield unit (HU) vs. -67.54 ± 9.94 HU; p < 0.001), and the cut-off value determined by the receiver operating characteristic (ROC) curve was -77.50 HU. Multivariable analysis revealed no statistical significance in the clinical data, FAI ≤ -77.50 HU (odds ratio (OR): 33.96), negative remodeling (OR: 4.36), severe calcification degree (OR: 4.43) and occlusion length ≥ 20.25 mm (OR: 3.89) were independent predictors of A-PCI failure. The prediction performance of combining the three morphologic characteristics (severe calcification, occlusion length ≥ 20.25 mm, and negative remodeling) with FAI ≤ -77.50 HU was better than that of the three morphologic characteristics alone (0.93 versus 0.77, p < 0.001). CONCLUSIONS: As a non-invasive index for detecting coronary inflammation, FAI complements indicators based on coronary CTA well and may be helpful for choosing appropriate interventional strategies. KEY POINTS: • Perivascular FAI of CTO was significantly higher in the failed A-PCI group. • The combination of FAI with other morphological predictors showed higher predictive performance of failed A-PCI for CTOs. • FAI is a good complement to indicators based on coronary CTA.

Insulin-loaded liposomes packaged in alginate hydrogels promote the oral bioavailability of insulin.

Compared to subcutaneous injections, oral administration of insulin would be a preferred route of drug administration for diabetic patients. For oral delivery, both liposomes and alginate hydrogels face many challenges, including early burst release of the encapsulated drug and poor intestinal drug absorption. Also, adhesion to the intestinal mucosa remains weak, which all result in a low bioavailability of the payload. This study reports on an alginate hydrogel loaded with liposomes for oral insulin administration. Liposomes (Lip) loaded with arginine-insulin complexes (AINS) were incorporated into a hydrogel prepared from cysteine modified alginate (Cys-Alg) to form liposome-in-alginate hydrogels (AINS-Lip-Gel). An ex vivo study proves that intestinal permeation of AINS and AINS-Lip is approximately 2.0 and 6.0-fold, respectively, higher than that of free insulin. The hydrogel retarded early release of insulin (∼30%) from the liposomes and enhanced the intestinal mucosal retention. In vivo experiments revealed that the AINS-Lip-Gel released insulin in a controlled manner and possessed strong hypoglycemic effects. We conclude that liposome-in-alginate hydrogels loaded with AINS represent an attractive strategy for the oral delivery of insulin.

Dynamic characteristics of near-surface spontaneous combustion gas flux and its response to meteorological and soil factors in coal fire area.

Accurate identification of the early stages of coal-fire combustion is important for effectively controlling the spread of coal fires. CO2 and CO, as characteristic gases in the early stage of coal fire combustion, can be effectively monitored by in-situ monitoring near the surface. However, in the previous in-situ monitoring methods, the influence of surface meteorological and soil factors on the release law of characteristic gases is often ignored. Therefore, this paper considers the complexity of the geological conditions in the coal fire area, a system, and equipment for obtaining the near-surface CO2 and CO variation laws in the early stage of coal fire combustion proposed by the concentration gradient method (CGM). The system and equipment realize the simultaneous online coupling of multi-area and multi-parameter data and conduct field investigations on the Wuda coal fire area. The results show that in the early stage of coal combustion, the change patterns of CO2 and CO concentrations in different regions are anomalous, and the CO2 concentration was higher than the CO concentration. The CO2 and CO concentrations in shallow soil increased with the increase of soil depth, and compared with other areas, the CO2 and CO concentration was the highest. The shallow soil and CO2 were identified as the key areas and characteristic gases for identifying the early stage of coal-fire combustion. The CO2 flux (CF) of different shallow soil depths decreased with increased soil layer depth. Variation of soil-surface CO2 flux (S-SCF) estimated by flux extrapolation method (FLEM). The change of S-SCF is controlled by meteorological and soil factors, and there is a certain connection between it and the "respiration phenomenon" in the fissure area. Thus, this study provides a theoretical basis for effectively identifying the early stages of coal-fire combustion.

Development and analysis of machine-learning guided flash nanoprecipitation (FNP) for continuous chitosan nanoparticles production.

Chitosan-based nanoparticles (CNPs) are widely used in drug delivery, cosmetics formulation and food applications. To accelerate the manufacturing of CNPs, the present study develops a workflow to prepare CNPs in a continuous model. Based on machine learning, the workflow precisely predicts size and polymer dispersity index (PDI) value of CNPs, which impacts on the colloidal stability and applications. Multi-inlet vortex mixer (MIVM) device was fabricated by 3D printing as the reactor. Peristaltic pump was applied to deliver the reaction streams into the MIVM device and produce CNPs by flash nanoprecipitation (FNP) in a continuous way. The developed MIVM device produces CNPs in a controlled manner at a higher output which is promising for upscale applications. Twelve machine learning algorithms were employed to investigate the potential relationship between the reaction independent variables and hydrodynamic characteristics of CNPs. Random Forest, Decision Tree, Extra Tree and Bagging algorithms performed better than other algorithms with the average prediction accuracy around 90 %. The current study demonstrated that supervised machine learning guided FNP using the developed MIVM device is an effective strategy for accurate and intelligent production of CNPs and other similar nanoparticles.

Zinc insulin hexamer loaded alginate zinc hydrogel: Preparation, characterization and in vivo hypoglycemic ability.

Alginate zinc hydrogel loaded with zinc insulin hexamer was prepared and characterized for oral insulin administration. The hydrogel was fabricated by dripping zinc insulin hexamer into sodium alginate solution and followed by crosslinking by zinc chloride. SEM image reveals the zinc insulin hexamer was integrated into the matrix of hydrogel. Zinc insulin hexamer loaded hydrogel shows no obvious cytotoxicity to both HT29 and Caco-2 cells. The developed hydrogel retards the burst release of insulin in simulated gastric fluid but promotes the release when in simulated intestinal fluid. In the diabetic mice, zinc insulin hexamer loaded alginate hydrogel demonstrates significant and prolonged hypoglycemic effect.