Comparing the Self-Reported Acceptability of Discrete Choice Experiment and Best-Worst Scaling: An Empirical Study in Patients with Type 2 Diabetes Mellitus.

Purpose: Discrete choice experiment (DCE) and profile case (case 2) best-worst scaling (BWS) present uncertainties regarding the acceptability of quantifying individual healthcare preferences, which may adversely affect the validity of responses and impede the reflection of true healthcare preferences. This study aimed to assess the acceptability of these two methods from the perspective of patients with type 2 diabetes mellitus (T2DM) and examine their association with specific characteristics of the target population. Patients and Methods: This cross-sectional study was based on a nationally representative survey; data were collected using a multistage stratified cluster-sampling procedure between September 2021 and January 2022. Eligible adults with confirmed T2DM voluntarily participated in this study. Participants completed both the DCE and case 2 BWS (BWS-2) choice tasks in random order and provided self-reported assessments of acceptability, including task completion difficulty, comprehension of task complexity, and response preference. Logistic regression and random forest models were used to identify variables associated with acceptability. Results: In total, 3286 patients with T2DM were included in the study. Respondents indicated there was no statistically significant difference in completion difficulty between the DCE and BWS-2, although the DCE scores were slightly higher (3.07 ± 0.68 vs 3.03 ± 0.67, P = 0.06). However, 1979 (60.2%) respondents found the DCE easier to comprehend. No significant preferences were observed between the two methods (1638 (49.8%) vs 1648 (50.2%)). Sociodemographic factors, such as residence, monthly out-of-pocket costs, and illness duration were significantly associated with comprehension complexity and response preference. Conclusion: This study yielded contrasting results to most of previous studies, suggesting that DCE may be less cognitively demanding and more suitable for patients with T2DM from the perspective of self-reported acceptability of DCE and BWS. This study promotes a focus on patient acceptability in quantifying individual healthcare preferences to inform tailored optimal stated-preference method for a target population.

Stated preference methodologies such as the discrete choice experiment (DCE) and case 2 best-worst scaling (BWS-2) are gaining popularity as methods for quantifying individual preferences in healthcare. However, the acceptability of the two methods to participants must be considered in practice to reduce cognitive burden and ensure the validity of preference elicitation.DCE was perceived to be less cognitively burdensome than BWS-2. In contrast to patients who thought that DCE was more acceptable, BWS-2 was more accepted by rural patients, patients who lived with the disease for a longer period, and those who had lower monthly out-of-pocket costs.These findings demonstrate potential differences in the acceptability of DCE and BWS-2 for patients with type 2 diabetes mellitus. To improve efficiency, it would be useful for researchers to consider the optimal stated preference method for identifying target populations according to sociodemographic and disease-related characteristics.

Strategy to mitigate substrate inhibition in wastewater treatment systems.

Global urbanization requires more stable and sustainable wastewater treatment to reduce the burden on the water environment. To address the problem of substrate inhibition of microorganisms during wastewater treatment, which leads to unstable wastewater discharge, this study proposes an approach to enhance the tolerance of bacterial community by artificially setting up a non-lethal high substrate environment. And the feasibility of this approach was explored by taking the inhibition of anammox process by nitrite as an example. It was shown that the non-lethal high substrate environment could enhance the nitrite tolerance of anammox bacterial community, as the specific anammox activity increasing up to 24.71 times at high nitrite concentrations. Moreover, the system composed of anammox bacterial community with high nitrite tolerance also showed greater resistance (two-fold) in response to nitrite shock. The antifragility of the system was enhanced without affecting the operation of the main reactor, and the non-lethal high nitrite environment changed the dominant anammox genera to Candidatus Jettenia. This approach to enhance tolerance of bacterial community in a non-lethal high substrate environment not only allows the anammox system to operate stably, but also promises to be a potential strategy for achieving stable biological wastewater treatment processes to comply with standards.

An RNA aptamer photoelectrochemical biosensor based on the exciton energy transfer constructed for theophylline detection.

A novel photoelectrochemical (PEC) biosensor was developed incorporating a specifically designed RNA aptamer for the detection of theophylline (TP). This involved utilizing two nucleotide base aptamers with tailored sequences designed to target TP. The 3' end of a single-stranded RNA sequence (5'-GGAUACCA-(CH2)6-SH-3') and the 5' end of a complementary stranded RNA sequence (5'-HS-(CH2)6-CCUUGGAAGCC-3') were linked to gold nanoparticles (AuNPs) and CdS quantum dots (QDs), respectively. These two single-stranded RNAs (ssRNA) formed a double-stranded RNA (dsRNA) capable of recognizing TP. This major structural change altered the spacing between QDs and NPs, which signaled the presence and concentration of TP. TP was photoelectrochemical catalytic oxidation by the hole of CdS QDs under illumination, then anode photocurrent was generated. Due to the increase in surface impedance and the effect of exciton energy transfer (EET) between QDs and AuNPs, the photocurrent would undergo varying degrees of change. TP was detected by changes in photocurrent. PEC detection of TP was achieved in the range of 0.1 µM-200 µM. The detection limit was 0.033 µM. The method exhibited commendable reproducibility and remarkable selectivity. The biosensor was used to measure TP content in tea, beverages and blood samples, resulting in satisfactory recovery rates.

Valorizing Lycii fructus waste residue into polysaccharide-rich extracts: Extraction methodologies, physicochemical characterization, in vitro activities and economic feasibility.

The high polysaccharide content of Lycii fructus agri-food waste should be reclaimed for value liberation from both environmental and economic perspectives. In this study, waste from L. fructus pigment products was valorized on a bench scale by upcycling into active polysaccharide-rich extracts. The methodological feasibility of polysaccharide recovery from L. fructus waste was evaluated using sequential extraction techniques. Three fractions LFP-30, LFP-100, and LFP-121, were obtained under stepwise increases in temperature and pressure. Highly heterogeneous xyloglucan (XG)-pectin macromolecules composed of linear homogalacturonan (HG) and alternating intra-RG-I-linkers, with topological neutral branches and XG participation, were predominant among the L. fructus polysaccharides (LFPs). Antioxidant activities in LFPs were unaffected by waste resources and severe extraction methodology conditions. Additionally, the direct investment potential of polysaccharide recovery was evaluated for full-scale implementation. This study demonstrated the necessity and feasibility of extracting bioactive polysaccharides with potential applications from L. fructus waste, and provided a sustainable strategy for transforming L. fructus waste disposal problems into value-added products using cost-effective methodologies.

Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.

BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

N-palmitoylethanolamide attenuates negative emotions induced by morphine withdrawal in mice.

Depression and anxiety are prominent symptoms of withdrawal syndrome, often caused by the abuse of addictive drugs like morphine. N-palmitoylethanolamide (PEA), a biologically active lipid, is utilized as an anti-inflammatory and analgesic medication. Recent studies have highlighted PEA's role in mitigating cognitive decline and easing depression resulting from chronic pain. However, it remains unknown whether PEA can influence negative emotions triggered by morphine withdrawal. This study seeks to explore the impact of PEA on such emotions and investigate the underlying mechanisms. Mice subjected to morphine treatment underwent a 10-day withdrawal period, followed by assessments of the effect of PEA on anxiety- and depression-like behaviors using various tests. Enzyme-linked immunosorbent assay was conducted to measure levels of monoamine neurotransmitters in specific brain regions. The findings indicate that PEA mitigated anxiety and depression symptoms and reduced 5-hydroxytryptamine, noradrenaline, and dopamine levels in the hippocampus and prefrontal cortex. In summary, PEA demonstrates a significant positive effect on negative emotions associated with morphine withdrawal, accompanied with the reduction in levels of monoamine neurotransmitters in key brain regions. These insights could be valuable for managing negative emotions arising from morphine withdrawal.

Size Matters: Influence of Particle Size on Antioxidant, ß-Glucan, and Anti-Inflammatory Potential in Pleurotus floridanus (Agaricomycetes).

Cellular damage resulting from elevated levels of free radicals can lead to persistent health issues. Pleurotus floridanus, an edible white oyster mushroom, is rich in ß-glucans with potent antioxidant and anti-inflammatory properties. In this research, we examined the ß-glucan content, total phenolic content, as well as antioxidant and anti-inflammatory potential of hot water extracts with varying particle sizes (< 75, 75-154, 154-300, and 300-600 µm) of both whole and sliced fruiting bodies of P. floridanus. The findings revealed that the в-glucan content increased as the particle size increased, although no significant differences were observed. Conversely, smaller particle sizes (< 75 µm) of whole and sliced fruiting bodies of P. floridanus exhibited higher phenolic content, 2,2-diphenyl-1-picryl-hy-drazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, and reducing ability compared with larger particle size (> 75 µm). Of the four samples (AW2, AW3, AS1, and AS2) with the highest antioxidant activity selected for anti-inflammatory assays, all demonstrated the ability to reduce nitric oxide and tumor necrosis factor-alpha levels, but did not enhance interleukin-10 expression in lipopolysaccharide-stimulated RAW264.7 cells. Interestingly, particle size < 75 to 300 µm did not appear to influence the anti-inflammatory activity, because no significant differences were observed among the particle sizes. Therefore, a particle size < 300 µm in a P. floridanus hot water extract could serve as a valuable source of antioxidant and anti-inflammatory compounds to counteract the harmful effects of free radicals.

Chirality and Curvature on Protein Adsorption and Osteogenesis.

Here we designed enantiomeric lipid-mimetic glutamic acid derivatives (L/D-UG) and investigated their self-assembled chiral nanostructures and performance with the protein adsorption as well as the osteogenesis. It was found that L or D-UG can self-assemble into vesicle bilayers and two-dimensional (2D) nanocrystals via a kinetic and thermodynamic control, respectively. These chiral vesicles and 2D crystals showed differentiated adsorption of proteins by their curvature and chirality. Specifically, fibronectin constituted by L-amino acids adsorbed preferentially on L-UG 2D crystal in a semi-random pattern and L-2D nanocrystal show as the most effective structures to promote bone regeneration. The controlled vesicle and 2D crystal assemblies with different chirality and curvature helps to clarify their determine roles in protein adsorption and osteogenesis.

Biomechanical comparison of an intramedullary nail combined with a reconstruction plate combination versus a single intramedullary nail in unstable intertrochanteric fractures with lateral femoral wall fracture: A finite element analysis.

This study aimed to compare the biomechanical performance of an intramedullary nail combined with a reconstruction plate and a single intramedullary nail in the treatment of unstable intertrochanteric femoral fractures with a fracture of the lateral femoral wall (LFW). A three-dimensional finite element (FE) femur model was established from computed tomography images of a healthy male volunteer. A major reverse obliquity fracture line, associated with a lesser trochanteric fragment defect and a free bone fragment of the LFW, was developed to create an AO/OTA type 31-A3.3 unstable intertrochanteric fracture mode. Two fixation styles were simulated: a long InterTAN nail (ITN) with or without a reconstruction plate (RP). A vertical load of 2100 N was applied to the femoral head to simulate normal walking. The construct stiffness, von Mises stress, and model displacement were assessed. The ITN with RP fixation (ITN/RP) provided higher axial stiffness (804 N/mm) than the ITN construct (621 N/mm). The construct stiffness of ITN/RP fixation was 29% higher than that of ITN fixation. The peak von Mises stress of the implants in the ITN/RP and ITN models was 994.46 MPa and 1235.24 MPa, respectively. The peak stress of the implants in the ITN/RP model decreased by 24% compared to that of the ITN model. The peak von Mises stress of the femur in the ITN/RP model was 269.06 MPa, which was lower than that of the ITN model (331.37 MPa). The peak stress of the femur in the ITN/RP model was 23% lower than that of the ITN model. The maximum displacements of the ITN/RP and ITN models were 12.12 mm and 13.53 mm, respectively. The maximum displacement of the ITN/RP model decreased by 12% compared with that of the ITN model. The study suggested that an additional plate fixation could increase the construct stiffness, reduce the stresses in the implant and femur, and decrease displacement after intramedullary nailing. Therefore, the intramedullary nail and reconstruction plate combination may provide biomechanical advantages over the single intramedullary nail in unstable intertrochanteric fractures with a fractured LFW.

iRGD-Guided Silica/Gold Nanoparticles for Efficient Tumor-Targeting and Enhancing Antitumor Efficacy Against Breast Cancer.

Background: Breast cancer presents significant challenges due to the limited effectiveness of available treatments and the high likelihood of recurrence. iRGD possesses both RGD sequence and C-terminal sequence and has dual functions of targeting and membrane penetration. iRGD-modified nanocarriers can enhance drug targeting of tumor vascular endothelial cells and penetration of new microvessels, increasing drug concentration in tumor tissues. Methods: The amidation reaction was carried out between SiO2/AuNCs and iRGD/PTX, yielding a conjugated drug delivery system (SiO2/AuNCs-iRGD/PTX, SAIP@NPs). The assessment encompassed the characterization of the morphology, particle size distribution, physicochemical properties, in vitro release profile, cytotoxicity, and cellular uptake of SAIP@NPs. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed using a small animal in vivo imaging system and a tumor-bearing nude mice model, respectively. The tumor targeting and anti-tumor efficacy of SAIP@NPs were assessed utilizing a small animal in vivo imaging system and an in situ nude mice breast cancer xenograft model, respectively. Results: The prepared SAIP@NPs exhibited decent stability and a certain slow-release effect in phosphate buffer (PBS, pH 7.4). In vitro studies had shown that, due to the dual functions of transmembrane and targeting of iRGD peptide, SAIP@NPs exhibited strong binding to integrin αvß3, which was highly expressed on the membrane of MDA-MB-231 cells, improving the uptake capacity of tumor cells, inhibiting the rapid growth of tumor cells, and promoting tumor cell apoptosis. The results of animal experiments further proved that SAIP@NPs had longer residence time in tumor sites, stronger anti-tumor effect, and no obvious toxicity to major organs of experimental animals. Conclusion: The engineered SAIP@NPs exhibited superior functionalities including efficient membrane permeability, precise tumor targeting, and imaging, thereby significantly augmenting the therapeutic efficacy against breast cancer with a favorable safety profile.

Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis.

OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

Unravelling the mechanism of temperature modulated exciton binding energy for MAPbBr3 perovskites.

The excitonic effect significantly influences the optoelectronic characteristics of halide perovskites. However, consensus on the temperature modulated exciton binding energy remains elusive, even for extensively studied materials like MAPbBr3 perovskites. In this study, we utilized UV-vis absorption spectra and the Elliott model to extract the exciton binding energies of MAPbBr3 in the range of 170-290 K. Elliott model fitted results reveal a linear increasing trend in bandgap and exciton binding energy for both cubic and tetragonal phases with temperature, with the tetragonal phase exhibiting a higher increasing rate. Additionally, we found that regardless of the temperature, the strongest absorption peaks are always dominated by the exciton absorption, and our fitted exciton absorption peak blue-shifts with the increase of temperature, accounting for the observed blue-shift of the strongest absorption peak for our fabricated MAPbBr3 sample. However, with the increase of temperature, the weight of continuum state absorption increases significantly, which widens the absorption tails to the longer wavelength, leading to the red-shift of Tauc-plotted optical bandgaps. This is the first work considering the temperature-modulated excitonic properties of halide perovskites, which offers valuable insights into the behavior of MAPbBr3 under varying temperature conditions. After a series of theoretical simulations on the temperature modulated electronic properties, including band structures, carrier effective masses, optical dielectric properties and Born effective charges, we provide rational interpretations for the experimentally observed temperature induced variation of the optical properties. These works are helpful to deepen our understanding of the temperature modulated optical properties of MAPbBr3 perovskites.

Clinical pathological significance and biological function of PLIN1 in hepatocellular carcinoma: bioinformatics analysis and in vitro experiments.

BACKGROUND & AIMS: Perilipin 1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to be closely related to the development of numerous tumor types. The purpose of this work was to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and to investigate the underlying mechanisms involved. METHODS: Public high-throughput RNA microarray and RNA sequencing data were collected to examine PLIN1 levels and clinical significance in patients with HCC. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) were conducted to assess the expression levels and the clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressing PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC progression based on HCC differentially expressed genes and PLIN1 co-expressed genes. RESULTS: PLIN1 was markedly downregulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion of SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signalling pathways were the three most enriched molecular mechanisms. CONCLUSION: The present study revealed that PLIN1 downregulation is associated with poor prognosis in HCC patients and accelerated HCC progression by promoting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.

Punica granatum L. polysaccharides: A review on extraction, structural characteristics and bioactivities.

Punica granatum L., commonly known as pomegranate, is native to Afghanistan and Iran, and today widely cultivated all over the world. Pomegranate polysaccharides are one of the most important bioactive components of P. granatum, which have a wide range of beneficial biological activities, such as anticancer, immunostimulatory, hepatoprotection, anti-psoriasis and antioxidation. Hot water extraction is currently the most commonly used method to isolate pomegranate polysaccharides. The structural characteristics of pomegranate polysaccharides have been extensively investigated through various advanced modern analytical techniques. This review focuses on the extraction, purification, structural characteristics, biological activities and structure-activity relationships of polysaccharides from Punica granatum. The aim of this article is to comprehensively and systematically summarize recent information of polysaccharides from Punica granatum and to serve as a basis for further research and development as therapeutic agents and functional foods.

Lactate promotes bone healing by regulating the osteogenesis of bone marrow mesenchymal stem cells through activating Olfr1440.

Bone malunion or nonunion leads to functional and esthetic problems and is a major healthcare burden. Activation of bone marrow mesenchymal stem cells (BMSCs) and subsequent induction of osteogenic differentiation by local metabolites are crucial steps for bone healing, which has not yet been completely investigated. Here, we found that lactate levels are rapidly increased at the local injury site during the early phase of bone defect healing, which facilitates the healing process by enhancing BMSCs regenerative capacity. Mechanistically, lactate serves as a ligand for the Olfr1440 olfactory receptor, to trigger an intracellular calcium influx that in turn activates osteogenic phenotype transition of BMSCs. Conversely, ablation of Olfr1440 delays skeletal repair and remodelling, as evidenced by thinner cortical bone and less woven bone formation in vivo. Administration of lactate in the defect area enhanced bone regeneration. These findings thus revealed the key roles of lactate in the osteogenic differentiation of BMSCs, which deepened our understanding of the bone healing process, as well as provided cues for a potential therapeutic option that might greatly improve bone defect treatment.

Mitochondrial Treatment Improves Cognitive Impairment Induced by Lipopolysaccharide in Mice.

Neuroinflammation has been proven to drive cognitive impairment associated with neurodegenerative diseases. It has been demonstrated that mitochondrial dysfunction is associated with cognitive impairment caused by neuroinflammation. We hypothesized that the transfer of exogenous mitochondria may be beneficial to the therapy of cognitive impairment induced by neuroinflammation. In the study, the effect of exogenous mitochondria on cognitive impairment induced by neuroinflammation was investigated. The results showed that mitochondrial treatment ameliorated the cognitive performance of lipopolysaccharide (LPS)-treated mice. Additionally, mitochondrial therapy attenuated neuronal injury and down-regulated the expression of proinflammatory cytokines, including TNF-α and pro- and cleaved IL-1ß, and the expression of Iba-1 and GFAP in the hippocampus and cortex of LPS-treated mice. Additionally, mitochondrial treatment increased mitochondrial ΔΨm, ATP level, and SOD activity and attenuated MDA level and ROS production in the brains of LPS-treated mice. The study reports the beneficial effect of mitochondrial treatment against cognitive impairment of LPS-treated mice, thereby providing a potential strategy for the treatment of cognitive impairment caused by neuroinflammation.