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.

Pangenome graph layout by Path-Guided Stochastic Gradient Descent.

MOTIVATION: The increasing availability of complete genomes demands for models to study genomic variability within entire populations. Pangenome graphs capture the full genomic similarity and diversity between multiple genomes. In order to understand them, we need to see them. For visualization, we need a human-readable graph layout: a graph embedding in low (e.g. two) dimensional depictions. Due to a pangenome graph's potential excessive size, this is a significant challenge. RESULTS: In response, we introduce a novel graph layout algorithm: the Path-Guided Stochastic Gradient Descent (PG-SGD). PG-SGD uses the genomes, represented in the pangenome graph as paths, as an embedded positional system to sample genomic distances between pairs of nodes. This avoids the quadratic cost seen in previous versions of graph drawing by SGD. We show that our implementation efficiently computes the low-dimensional layouts of gigabase-scale pangenome graphs, unveiling their biological features. AVAILABILITY AND IMPLEMENTATION: We integrated PG-SGD in ODGI which is released as free software under the MIT open source license. Source code is available at https://github.com/pangenome/odgi.

Oxygen-Assisted Supercapacitive Swing Adsorption of Carbon Dioxide.

We report on the supercapacitive swing adsorption (SSA) of carbon dioxide at different voltage windows in the presence of oxygen using activated carbon electrodes, and deliquescent, aqueous electrolytes. The presence of O2 in the CO2/N2 gas mixture results in an up to 11 times higher CO2 adsorption capacity with 3M MgBr2 (at 0.6V) and up to 4-5 times higher adsorption capacity with 3M MgCl2 (at 1V). A tradeoff between high CO2 adsorption capacities and lower coulombic efficiencies was observed at voltages above 0.6V. The energetic and adsorptive performance of the electrodes in the presence of oxygen below 0.5V was similar to the performance with a CO2/N2 mixture without oxygen at 1V. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) of the electrodes demonstrate that the specific capacitance increases while the diffusion resistance decreases in the presence of oxygen. Oxygen concentrations ranging between 5-20% give similar energetic and adsorptive performance. The electrodes exhibit stable performance for up to 100 cycles of operation.

Establishment and validation of a predictive nomogram for polyuria during general anesthesia in thoracic surgery.

BACKGROUND: To develop and evaluate a predictive nomogram for polyuria during general anesthesia in thoracic surgery. METHODS: A retrospective study was designed and performed. The whole dataset was used to develop the predictive nomogram and used a stepwise algorithm to screen variables. The stepwise algorithm was based on Akaike's information criterion (AIC). Multivariable logistic regression analysis was used to develop the nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the model's discrimination ability. The Hosmer-Lemeshow (HL) test was performed to check if the model was well calibrated. Decision curve analysis (DCA) was performed to measure the nomogram's clinical usefulness and net benefits. P < 0.05 was considered to indicate statistical significance. RESULTS: The sample included 529 subjects who had undergone thoracic surgery. Fentanyl use, gender, the difference between mean arterial pressure at admission and before the operation, operation type, total amount of fluids and blood products transfused, blood loss, vasopressor, and cisatracurium use were identified as predictors and incorporated into the nomogram. The nomogram showed good discrimination ability on the receiver operating characteristic curve (0.6937) and is well calibrated using the Hosmer-Lemeshow test. Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: Individualized and precise prediction of intraoperative polyuria allows for better anesthesia management and early prevention optimization.

Transgenic Soybean for Production of Thermostable α-Amylase.

Alpha-amylases are crucial hydrolase enzymes which have been widely used in food, feed, fermentation, and pharmaceutical industries. Methods for low-cost production of α-amylases are highly desirable. Soybean seed, functioning as a bioreactor, offers an excellent platform for the mass production of recombinant proteins for its ability to synthesize substantial quantities of proteins. In this study, we generated and characterized transgenic soybeans expressing the α-amylase AmyS from Bacillus stearothermophilus. The α-amylase expression cassettes were constructed for seed specific expression by utilizing the promoters of three different soybean storage peptides and transformed into soybean via Agrobacterium-mediated transformation. The event with the highest amylase activity reached 601 U/mg of seed flour (one unit is defined as the amount of enzyme that generates 1 micromole reducing ends per min from starch at 65 °C in pH 5.5 sodium acetate buffer). The optimum pH, optimum temperature, and the enzymatic kinetics of the soybean expressed enzyme are similar to that of the E. coli expressed enzyme. However, the soybean expressed α-amylase is glycosylated, exhibiting enhanced thermostability and storage stability. Soybean AmyS retains over 80% activity after 100 min at 75 °C, and the transgenic seeds exhibit no significant activity loss after one year of storage at room temperature. The accumulated AmyS in the transgenic seeds represents approximately 15% of the total seed protein, or about 4% of the dry seed weight. The specific activity of the transgenic soybean seed flour is comparable to many commercial α-amylase enzyme products in current markets, suggesting that the soybean flour may be directly used for various applications without the need for extraction and purification.

Identifying the twist factor of twisted partially coherent optical beams.

Twisted partially coherent light, characterized by its unique twist factor, offers novel control over the statistical properties of random light. However, the recognition of the twist factor remains a challenge due to the low coherence and the stochastic nature of the optical beam. This paper introduces a method for the recognition of twisted partially coherent beams by utilizing a circular aperture at the source plane. This aperture produces a characteristic hollow intensity structure due to the twist phase. A deep learning model is then trained to identify the twist factor of these beams based on this signature. The model, while simple in structure, effectively eliminates the need for complex optimization layers, streamlining the recognition process. This approach offers a promising solution for enhancing the detection of twisted light and paves the way for future research in this field.

Spatial heterogeneity plays a vital role in shaping the structure and function of estuarine carbon-fixing bacterial communities.

Carbon-fixing bacterial communities are essential drivers of carbon fixation in estuarine ecosystems that critically affect the global carbon cycle. This study compared the abundances of the Calvin cycle functional genes cbbL and cbbM and Reductive tricarboxylic acid cycle gene aclB, as well as compared carbon-fixing bacterial community features in the two estuaries, predicted potential ecological functions of carbon-fixation bacteria, and analyzed their symbiosis strategies in two estuaries having different geographical distributions. Gammaproteobacteria was the dominant carbon-fixing bacterial community in the two estuaries. However, a higher number of Alphaproteobacteria were noted in the Liaohe Estuary, and a higher number of Betaproteobacteria were found in the Yalujiang Estuary. The carbon-fixing functional gene levels exhibited the order of aclB > cbbL > cbbM, and significant effects of Cu, Pb, and petroleum were observed (p < 0.05). Nitrogen-associated nutrient levels are major environmental factors that affect carbon-fixing bacterial community distribution patterns. Spatial factors significantly affected cbbL carbon-fixing functional bacterial community structure more than environmental factors. With the increase in offshore distance, the microbial-led processes of methylotrophy and nitrogen fixation gradually weakened, but a gradual strengthening of methanotrophy and nitrification was observed. Symbiotic network analysis of the microorganisms mediating these ecological processes revealed that the carbon-fixing bacterial community in these two estuaries had a non-random symbiotic pattern, and microbial communities from the same module were strongly linked among the carbon, nitrogen, and sulfur cycle. These findings could advance the understanding of carbon fixation in estuarine ecosystems.

Scaling Supercapacitive Swing Adsorption of CO2 Using Bipolar Electrode Stacks.

Supercapacitive swing adsorption (SSA) modules with bipolar stacks having 2, 4, 8, and 12 electrode pairs made from BPL 4 × 6 activated carbon are constructed and tested for carbon dioxide capture applications. Tests are performed with simulated flue gas (15%CO2 /85%N2) at 2, 4, 8, and 12 V, respectively. Reversible adsorption with sorption capacities (≈58 mmol kg-1) and adsorption rates (≈38 µmol kg-1 s-1) are measured for all stacks. The productivity scales with the number of cells in the module, and increases from 70 to 390 mmol h-1 m-2. The energy efficiency and energy consumption improve with increasing number of bipolar electrodes from 67% to 84%, and 142 to 60 kJ mol-1, respectively. Overall, the results show that SSA modules with bipolar electrodes can be scaled without reducing the adsorptive performance, and with improvement of energetic performance.

Multi-feature, Chinese-Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP.

BACKGROUND: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM. MATERIALS AND METHODS: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models. RESULTS: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models. CONCLUSIONS: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes.

Role and molecular mechanism of Salvia miltiorrhiza associated with chemical compounds in the treatment of diabetes mellitus and its complications: A review.

Diabetes mellitus (DM) is one of the most prevalent diseases worldwide, greatly impacting patients' quality of life. This article reviews the progress in Salvia miltiorrhiza, an ancient Chinese plant, for the treatment of DM and its associated complications. Extensive studies have been conducted on the chemical composition and pharmacological effects of S miltiorrhiza, including its anti-inflammatory and antioxidant activities. It has demonstrated potential in preventing and treating diabetes and its consequences by improving peripheral nerve function and increasing retinal thickness in diabetic individuals. Moreover, S miltiorrhiza has shown effectiveness when used in conjunction with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), and statins. The safety and tolerability of S miltiorrhiza have also been thoroughly investigated. Despite the established benefits of managing DM and its complications, further research is needed to determine appropriate usage, dosage, long-term health benefits, and safety.

Flexible Composite Electrolyte Membranes with Fast Ion Transport Channels for Solid-State Lithium Batteries.

Numerous endeavors have been dedicated to the development of composite polymer electrolyte (CPE) membranes for all-solid-state batteries (SSBs). However, insufficient ionic conductivity and mechanical properties still pose great challenges in practical applications. In this study, a flexible composite electrolyte membrane (FCPE) with fast ion transport channels was prepared using a phase conversion process combined with in situ polymerization. The polyvinylidene fluoride-hexafluoro propylene (PVDF-HFP) polymer matrix incorporated with lithium lanthanum zirconate (LLZTO) formed a 3D net-like structure, and the in situ polymerized polyvinyl ethylene carbonate (PVEC) enhanced the interface connection. This 3D network, with multiple rapid pathways for Li+ that effectively control Li+ flux, led to uniform lithium deposition. Moreover, the symmetrical lithium cells that used FCPE exhibited high stability after 1200 h of cycling at 0.1 mA cm-2. Specifically, all-solid-state lithium batteries coupled with LiFePO4 cathodes can stably cycle for over 100 cycles at room temperature with high Coulombic efficiencies. Furthermore, after 100 cycles, the infrared spectrum shows that the structure of FCPE remains stable. This work demonstrates a novel insight for designing a flexible composite electrolyte for highly safe SSBs.

The leaching behavior of hazardous element under different leaching procedure utilizing slag-fly ash-based agent: Chromium, antimony, and lead.

Low-carbon cementitious materials based on blast furnace slag (BFS) and municipal solid waste incineration (MSWI) fly ash play a pivotal role in the construction industry by substituting cement clinker. This innovation significantly reduces CO2 emissions and enables the extensive utilization of both industrial solid waste and hazardous urban waste on a large scale. However, the application of MSWI fly ash as a precursor for alkali-activated cementitious materials presents a significant leaching risk of heavy metal during the extended reaction process, posing a critical barrier to the efficient and widespread utilization of these solid waste. Three static leaching methods [horizontal vibration (HV), sulphuric acid & nitric acid (SN), and acetic acid buffer solution (AAB)], along with acid neutralization capacity (ANC) leaching tests, were applied in BFS-fly ash-based cementitious materials (BFCM) to assess the leaching behavior of high-risk elements-Cr, Sb, and Pb-within MSWI fly ash. The A4 matrix (BFS: MSWI fly ash:FGDG = 70:20:10) exhibits a compressive strength of 72.51 MPa at 180 day, with the leaching concentrations of target elements remaining below the standard limit under chemical attack (H+ and OH-). The critical pH determined is 9.2 from the ANC leaching test results. Visual MINTEQ simulation illustrates the occurrence states of Cr, Sb, and Pb as (CrO4)2-, [Sb(OH)6]-, and Pb(OH)3- within the BFCM system, respectively. The "double salt effect", intended to enhance the dissociation degree of BFS, acts as the driving force behind the long-term hydration reaction. It also serves as an assurance in controlling the long-term leaching risk of object elements. The dissociation degree of BFS within A4 matrix increased by 38.71 %, with the relative content of the typical low-solubility double salt "Ettringite" reaching 29 % at 180 d. This study provides novel theoretical and data-driven evidence to investigate the leaching behavior associated with MSWI fly ash and the accomplishment of replacing cement clinker with low-carbon BFCM.

Synthesis of Monodisperse Mesoporous Carbon Spheres/EPDM Rubber Composites and Their Enhancement Mechanical Properties.

Monodisperse mesoporous carbon spheres (MCS) were synthesized and their potential applications in ethylene propylene diene monomer (EPDM) foam were evaluated. The obtained MCS exhibited a high specific surface area ranging from 621-to 735 m2/g along with large pore sizes. It was observed that the incorporation of MCS into EPDM foam rubber significantly enhances its mechanical properties. The prepared MCS-40 rubber composites exhibit the highest tear strength of 210 N/m and tensile strength of 132.72 kPa, surpassing those of other samples. The enhancement mechanism was further investigated by employing computer simulation technology. The pores within the MCS allowed for the infiltration of EPDM molecular chains, thereby strengthening the interaction forces between the filler and matrix. Moreover, a higher specific surface area resulted in greater adsorption of molecular chains onto the surface of these carbon spheres. This research offers novel insights for understanding the enhancement mechanism of monodisperse mesoporous particles/polymer composites (MCS/EPDM) and highlights their potential application in high-performance rubber composites.

IL-17A is involved in the hyperplasia of blood vessels in local lesions of psoriasis by inhibiting autophagy.

OBJECTIVE: Increased angiogenesis is a pathological feature of psoriasis, but the pathomechanisms of angiogenesis in psoriasis are not clear. Interleukin-17A (IL-17A) is the major effect factor in the pathogenesis of psoriasis. Our results showed that IL-17A can promote angiogenesis and cause endothelial cell inflammation. Autophagy plays an important role not only in regulating inflammation, but also in regulating angiogenesis. Whether angiogenesis in psoriasis is related to autophagy remains unclear. In this study, we treated human umbilical vein endothelial cells (HUVECs) with IL-17A to simulate increased angiogenesis to study whether increased angiogenesis in psoriasis is related to autophagy. METHODS AND RESULTS: Our results showed that treatment of HUVECs with IL-17A significantly increased angiogenesis and expression levels of mRNA for multiple proinflammatory cytokines (CCL20, IL-8, CCL2, IL-6, and IL-1ß) and, while decreasing intracellular levels of nitric oxide (NO) and NO synthase (NOS) activity. Moreover, IL-17A inhibited autophagy as shown that IL-17A significantly increased expression levels of LC3II and p62 proteins. Induction of autophagy ameliorated IL-17A-mediated inflammatory response and inhibited angiogenesis, accompanied by increased p-AMPKα(Thr172) and p-ULK1(Ser555) expression, and decreased p-mTOR(Ser2448) and p-ULK1(Ser757) expression. Furthermore, inhibition of either AMPK or lysosomal acidification completely overrode autophagy-induced changes in angiogenesis and NOS activity. Finally, induction of autophagy decreased apoptosis and caspase-3 activity in IL-17A-treated HUVECs. CONCLUSIONS: These results showed that IL-17A is involved in angiogenesis and inflammatory response by inhibiting autophagy through AMPK signaling pathway, suggesting that autophagy may be a new therapeutic target for psoriasis.

Associations between metal(loid) exposure with overweight and obesity and abdominal obesity in the general population: A cross-sectional study in China.

Previous studies have revealed links between metal(loid)s and health problems; however, the link between metal(loid)s and obesity remains controversial. We evaluated the cross-sectional association between metal(loid) exposure in whole blood and obesity among the general population. Vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), antimony (Sb), thallium (T1), and lead (Pb) were measured in 3029 subjects in Guangdong Province (China) using ICP-MS. The prevalence of overweight and obesity (OWO) and abdominal obesity (AOB) was calculated according to body mass index (BMI) and waist circumference (WC), respectively. Multivariate analysis showed that elevated blood Cu, Cd, and Pb levels were inversely associated with the risk of OWO, and these associations were confirmed by a linear dose-response relationship. Elevated blood Co concentration was associated with a decreased risk of AOB. A quantile g-computation approach showed a significantly negative mixture-effect of 13 metal(loid)s on OWO (OR: 0.96; 95% CI: 0.92, 0.99). Two metals-Ni and Mo-were inversely associated with the risk of OWO but positively associated with AOB. We cross-grouped the two obesity measurement types and found that the extremes of metal content were present in people with AOB only. In conclusion, blood Cu, Mo, Ni, Cd, and Pb were inversely associated with the risk of OWO. The presence of blood Co may be protective, while Ni and Mo exposure might increase the risk of AOB. The association between metal(loid) exposure and obesity warrants further investigation in longitudinal cohort studies.

TLR7 enhancing follicular helper T (Tfh) cells response in C57BL/6 mice infected with Plasmodium yoelii NSM TLR7 mediated Tfh cells in P. yoelii infected mice.

Toll-like receptors (TLRs) play an important role in inducing innate and acquired immune responses against infection. However, the effect of Toll-like receptor 7 (TLR7) on follicular helper T (Tfh) cells in mice infected with Plasmodium is still not clear. The results showed that the splenic CD4+ CXCR5+ PD-1+ Tfh cells were accumulated after Plasmodium yoelii NSM infection, the content of splenic Tfh cells was correlated to parasitemia and/or the red blood cells (RBCs) counts in the blood. Moreover, the expression of TLR7 was found higher than TLR2, TLR3 and TLR4 in splenic Tfh cells of the WT mice. TLR7 agonist R848 and the lysate of red blood cells of infected mice (iRBCs) could induce the activation and differentiation of splenic Tfh cells. Knockout of TLR7 leads to a decrease in the proportion of Tfh cells, down-regulated expression of functional molecules CD40L, IFN-γ, IL-21 and IL-10 in Tfh cells; decreased the proportion of plasma cells and antibody production and reduces the expression of STAT3 and Ikzf2 in Tfh cells. Administration of R848 could inhibit parasitemia, enhance splenic Tfh cell activation and increase STAT3 and Ikzf2 expression in Tfh cells. In summary, this study shows that TLR7 could regulate the function of Tfh cells, affecting the immune response in the spleen of Plasmodium yoelii NSM-infected mice.

Association of dietary inflammatory index with all-cause and cardiovascular disease mortality in hyperuricemia population: A cohort study from NHANES 2001 to 2010.

Dietary management is a crucial component of non-pharmacological treatment for hyperuricemia, yet there is a paucity of research on the impact of dietary habits on the survival outcomes of individuals with hyperuricemia. The objective of this study is to examine the association between dietary inflammatory index (DII) and the all-cause and cardiovascular disease (CVD) mortality in individuals with hyperuricemia. This study included 3093 adult participants from National Health and Nutrition Examination Survey (NHANES) 2001 to 2010. Participants were categorized into 4 groups based on quartiles of DII to demonstrate data characteristics, with sample weights considered. The relationship between DII and the risk of hyperuricemia was examined using multivariable logistic regression models. Kaplan-Meier models and Cox proportional hazards models were employed to assess the relationship between DII levels and the all-cause mortality in individuals with hyperuricemia, with the non-linear relationship tested using restricted cubic splines (RCS). Competing risk models were employed to investigate the association between DII levels and the CVD mortality in individuals diagnosed with hyperuricemia. Subgroup and sensitivity analysis were performed to confirm the robustness and reliability of the findings. Among the participants, 47.95% were aged over 60 years. A positive association observed between the highest quartile of DII level and the incidence of hyperuricemia (OR: 1.34, CI [1.13, 1.57]). Elevated DII levels were correlated with increased all-cause mortality (P value < .001) and CVD mortality (P value < .001) in participants. In comparison to the lowest quartile, the highest quartile of DII exhibited a 31% rise in all-cause mortality (HR: 1.31, CI [1.01, 1.68]) and a 50% increase in CVD mortality (HR: 1.50, CI [1.00, 2.26]). No indication of a nonlinear association between DII levels and all-cause mortality (p-non-linear = .43). These findings indicate a positive correlation between the pro-inflammatory diet and the incidence of hyperuricemia. Additionally, a pro-inflammatory diet may elevate the all-cause and CVD mortality in individuals with hyperuricemia.

Hyaluronic Acid-modified Liposomes for Ursolic Acid-targeted Delivery Treat Lung Cancer Based on p53/ARTS-mediated Mitochondrial Apoptosis.

Background: Chemotherapy drugs can cause drug resistance and other problems when treating lung cancer, which leads to treatment failure. Ursolic acid (UA) is used in formulations based on traditional Chinese medicine. UA has excellent anti-tumor effects, but they are limited by solubility and non-specificity to tumor cells. Objectives: To overcome these issues, we created a novel hyaluronic acid (HA)-targeted liposome system for delivering UA (HA-Lipo/UA) to explore the targeting and anti-tumor effects of UA. Methods: We constructed the HA-Lipo/UA delivery system by the thin film hydration method. The uptake and localization of UA were detected by flow cytometry and microscope. Cell proliferation of A549 cells was detected by MTT assays. Apoptosis and reactive oxygen species (ROS) expression of A549 cells were also evaluated after being treated with HA-Lipo/UA. Western blot analysis evaluated the anti-tumor mechanism of HA-Lipo/UA. Results: HA-Lipo/UA exhibited favorable targeting of the cluster of differentiation (CD)44-overexpressing A549 cells. HA-Lipo/UA exhibited significant inhibition of the proliferation of A549 cells and induced their apoptosis compared with the corresponding monotherapies. HA-Lipo/UA induced overexpression of reactive oxygen species and upregulated expression of p53 and apoptosis-related protein in the transforming growth factor-ß signaling (ARTS) pathway, which induced cytochrome-c release, activation of caspase-3, and promoted mitochondrial apoptosis in A549 cells. Conclusions: Taken together, these data suggested that HA-Lipo/UA could be used to target tumor cells.

Association between dietary intakes of B vitamins and nonalcoholic fatty liver disease in postmenopausal women: a cross-sectional study.

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly common globally, particularly among postmenopausal women. Diet plays a fundamental role in the treatment of NAFLD. However, clinical research on the dietary intakes of B vitamins, specifically in postmenopausal women, is scant. Hence, it is imperative to study the impact of B vitamin dietary intake in postmenopausal women. Methods: This study utilized National Health and Nutrition Examination Survey (NHANES) data for 668 postmenopausal women. Logistic regression analysis was conducted to investigate the association of the intakes of B vitamins with hepatic steatosis and liver fibrosis prevalence. The analysis accounted for various covariates and employed restricted cubic spline analysis to examine potential nonlinear relationships. Additionally, interactions among age, diabetes, and B-vitamin intakes, as well as the interaction between folate and vitamin B12 intake, were explored. Results: Higher intakes of folate [0.30 (0.10-0.88)], choline [0.26 (0.07-0.95)], vitamin B1, and vitamin B2 were associated with a reduced risk of hepatic steatosis in postmenopausal women. The associations of niacin (P-nonlinear = 0.0003), vitamin B1 (P-nonlinear = 0.036), and vitamin B2 (P-nonlinear<0.0001) intakes with hepatic steatosis showed a nonlinear pattern. However, no significant associations were observed between the intakes of niacin, vitamin B6 and vitamin B12 and hepatic steatosis. Furthermore, there were no significant associations between B-vitamin intakes and liver fibrosis. No interaction effects were observed. Conclusion: Dietary intakes of folate, choline, vitamin B1, and vitamin B2 may be associated with liver steatosis in postmenopausal women, these results suggest that optimizing the intake of these specific B vitamins may have a protective effect against liver steatosis in postmenopausal women, offering valuable insights into potential dietary strategies to promote their well-being.

Engineered muscle from micro-channeled PEG scaffold with magnetic Fe3O4 fixation towards accelerating esophageal muscle repair.

Engineered scaffolds are used for repairing damaged esophagus to allow the precise alignment and movement of smooth muscle for peristalsis. However, most of these scaffolds focus solely on inducing cell alignment through directional apparatus, often overlooking the promotion of muscle tissue formation and causing reduced esophageal muscle repair effectiveness. To address this issue, we first introduced aligned nano-ferroferric oxide (Fe3O4) assemblies on a micropatterned poly(ethylene glycol) (PEG) hydrogel to form micro-/nano-stripes. Further modification using a gold coating was found to enhance cellular adhesion, orientation and organization within these micro-/nano-stripes, which consequently prevented excessive adhesion of smooth muscle cells (SMCs) to the thin PEG ridges, thereby effectively confining the cells to the Fe3O4-laid channels. This architectural design promotes the alignment of the cytoskeleton and elongation of actin filaments, leading to the organized formation of muscle bundles and a tendency for SMCs to adopt synthetic phenotypes. Muscle patches are harvested from the micro-/nano-stripes and transplanted into a rat esophageal defect model. In vivo experiments demonstrate the exceptional viability of these muscle patches and their ability to accelerate the regeneration of esophageal tissue. Overall, this study presents an efficient strategy for constructing muscle patches with directional alignment and muscle bundle formation of SMCs, holding significant promise for muscle tissue regeneration.