Associative asymmetry of the recognition without cued-recall effect in thematic relations.

In the present study, two experiments were conducted to examine whether thematic relation can produce recognition without cued-recall effect and whether the direction of the association has an influence on this effect. The participants provided higher familiarity ratings for studied items than for unstudied items during target retrieval failure. Additionally, the thematic relation-elicited recognition without cued-recall effect was larger in the forward association than in the backward association. Collectively, these results indicated that thematic relations can elicit the recognition without cued-recall effect, and this effect is asymmetrical. The current findings support the features overlap hypothesis described in the global match model.

Biohybrid hydrogel inhibiting ß-klotho/HDAC3 axis for hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC), ranking as the fourth most prevalent cancer globally, has garnered significant attention due to its high invasiveness and mortality rates. However, drug therapies face challenges of inadequate efficacy and unclear mechanisms. Here, we propose a novel biohybrid hydrogel that targets ß-klotho (KLB) for HCC treatment. As a dual-network hydrogel, this gel combines gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA) to ensure biocompatibility while enhancing controlled drug release. Notably, it exhibits good storage stability, high drug load capacity, and efficient water absorption. By introducing the HDAC3 inhibitor RGFP966, we can selectively inhibit the activation of KLB. This deactivation effectively blocks the FGF21-KLB signaling pathway and inhibits the progression of HCC. Importantly, we have successfully validated this unique phenomenon both in vivo and in vitro, providing substantial evidence for the efficacy of this hydrogel-based anti-tumor drug delivery system as a promising strategy for HCC treatment. This innovative research outcome brings new hope to the field of tumor therapy, providing a reliable theoretical foundation for future clinical applications.

Applications of plant-derived extracellular vesicles in medicine.

Plant-derived extracellular vesicles (EVs) are promising therapeutic agents owing to their natural abundance, accessibility, and unique biological properties. This review provides a comprehensive exploration of the therapeutic potential of plant-derived EVs and emphasizes their anti-inflammatory, antimicrobial, and tumor-inhibitory effects. Here, we discussed the advancements in isolation and purification techniques, such as ultracentrifugation and size-exclusion chromatography, which are critical for maintaining the functional integrity of these nanovesicles. Next, we investigated the diverse administration routes of EVs and carefully weighed their respective advantages and challenges related to bioavailability and patient compliance. Moreover, we elucidated the multifaceted mechanisms of action of plant-derived EVs, including their roles in anti-inflammation, antioxidation, antitumor activity, and modulation of gut microbiota. We also discussed the impact of EVs on specific diseases such as cancer and inflammatory bowel disease, highlighting the importance of addressing current challenges related to production scalability, regulatory compliance, and immunogenicity. Finally, we proposed future research directions for optimizing EV extraction and developing targeted delivery systems. Through these efforts, we envision the seamless integration of plant-derived EVs into mainstream medicine, offering safe and potent therapeutic alternatives across various medical disciplines.

Developing Cell-Membrane-Associated Liposomes for Liver Diseases.

Over the past decade, a marked escalation in the prevalence of hepatic pathologies has been observed, adversely impacting the quality of life for many. The predominant therapeutic strategy for liver diseases has been pharmacological intervention; however, its efficacy is often constrained. Currently, liposomes are tiny structures that can deliver drugs directly to targeted areas, enhancing their effectiveness. Specifically, cell membrane-associated liposomes have gained significant attention. Despite this, there is still much to learn about the binding mechanism of this type of liposome. Thus, this review comprehensively summarizes relevant information on cell membrane-associated liposomes, including their clinical applications and future development directions. First, we will briefly introduce the composition and types of cell membrane-associated liposomes. We will provide an overview of their structure and discuss the various types of liposomes associated with cell membranes. Second, we will thoroughly discuss various strategies of drug delivery using these liposomes. Lastly, we will discuss the application and clinical challenges associated with using cell membrane-associated liposomes in treating liver diseases. We will explore their potential benefits while also addressing the obstacles that need to be overcome. Furthermore, we will provide prospects for future development in this field. In summary, this review underscores the promise of cell membrane-associated liposomes in enhancing liver disease treatment and highlights the need for further research to optimize their utilization. In summary, this review underscores the promise of cell membrane-associated liposomes in enhancing liver disease treatment and highlights the need for further research to optimize their utilization.

A phase I trial of MK-0731, a kinesin spindle protein (KSP) inhibitor, in patients with solid tumors.

PURPOSE: The kinesin spindle protein (KSP) is essential for separation of spindle poles during mitosis. Its inhibition results in mitotic arrest. This phase I trial examined safety, tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetic parameters, and anti-tumor activity of MK-0731, a potent inhibitor of KSP. EXPERIMENTAL DESIGN: In part 1, patients with advanced solid tumors received MK-0731 intravenously over 24 h every 21 days starting at 6 mg/m(2), escalating until MTD was reached. In part 2, patients with taxane-resistant tumors received the MTD. Plasma samples were collected to analyze the pharmacokinetics of MK-0731. Tumor response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. RESULTS: In part 1, 21 patients (median age 63 years) were treated with MK-0731 at doses ranging from 6 to 48 mg/m(2)/24 h for median four cycles. The dose-limiting toxicity was neutropenia and the MTD was 17 mg/m(2)/24 h. At the MTD, AUC (±SD) was 10.5 (±7.3) µM × hour, clearance (±SD) was 153 mL/min (±84), and t(1/2) was 5.9 h. In part 2, 22 patients received the MTD and there were no DLTs. Although there were no objective tumor responses, four patients (with cervical, non-small cell lung, and ovarian cancers) had prolonged stable disease. CONCLUSIONS: MK-0731 at the MTD of 17 mg/m(2)/day every 21 days in patients with solid tumors had few grade 3 and 4 toxicities with the major DLTs at higher doses being myelosuppression. Anti-tumor efficacy was suggested by the length of stable disease in selected patients with taxane-resistant tumors.

Quantitative structure-pungency landscape of sanshool dietary components from Zanthoxylum species.

The molecular basis of the pungency of sanshool dietary components from the Zanthoxylum species has been firstly addressed by constructing the statistically significant and highly predictive quantitative structure-pungency relationship models along with the pharmacophore models. The important pungent structural characters in the isobutylamide moiety and linear carbon chains were elucidated in this study that maintained the suitable spatial packing and electrostatic interactions with their receptors. Our results also revealed that the amide moiety, N-isobutyl moiety with suitable bulky and restricted electronegative substituents, and the relatively long straight carbon chains with suitable (conjugated) CC bonds or heteroatoms at regular intervals were essential for the high pungency. The pungency of 42 new sanshools was predicted, compared with the rough experimental data, and ultimately classified into weak, medium and strong types. Most of these sanshools were found to have good oral bioavailability and acceptable pharmacokinetic properties.

Mechanism study on inhibited Ru(bpy)3(2+) electrochemiluminescence between coreactants.

Electrochemiluminescence (ECL) derived from Ru(bpy)(3)(2+) and its derivatives has been proven to be useful in diverse areas of analytical chemistry. Up to date most of the applications are based on coreactant ECL technology. However, little attention has been paid to the ECL inhibition between coreactants. In this paper, the ECL inhibition behavior between coreactants was systematically investigated. The results showed that ECL inhibition happened not only within the same type of coreactants, but also between two different types of coreactants. Interestingly, for some weak coreactants, the detection methods based on ECL inhibition were much more sensitive than those based on ECL enhancement. Therefore, it is envisioned to establish sensitive inhibited ECL detection methods for these weak coreactants. A possible ECL inhibition mechanism related to the consumption of coreactant intermediates without light emission is proposed.

Effectiveness of Education Courses in Enhancing Clinical Educators' Teaching Ability.

BACKGROUND: In China, the nursing discipline has undergone rapid development in recent years, and clinical educators are an important part of the nursing education team. In order to improve their teaching ability and become competent clinical educators, we provided learning opportunities to them. METHOD: To assess the effectiveness of education courses and modules, a cross-sectional study based on questionnaire responses was conducted. Sixty-six part-time clinical nurse educators from six teaching hospitals were included. A standardized four-section questionnaire developed by the authors was used. RESULTS: The education curriculum was approved by clinical educators (94%). The specific content in the education courses significantly improved the teaching ability (84%). From a teaching perspective, the confidence was enhanced; the clinical educators were able to control the purpose of teaching and learning objectives via a syllabus (92%). CONCLUSION: Education courses can improve teaching ability, reinforce teaching control, and promote the quality of clinical teaching. [J Contin Educ Nurs. 2019;50(8):367-373.].

Health Literacy, Physical and Mental Health, and Activities of Daily Living Among Older Chinese Adults in Nursing Homes.

It is very important to estimate the prevalence of inadequate health literacy and determine whether or not health literacy level differences predict the physical and mental health status of older adults. A cluster sampling method was selected. A total of 1396 older adults were interviewed. Three instruments were included: the Chinese Citizen Health Literacy Questionnaire, Short Form 36, and Activity of Daily Living (ADL) Scale. The health literacy scores were very low (71.74 ± 28.35). The physical and mental health scores were all moderate. The ADLs was ⩾22, which suggests that the ADLs of older adults were poor. The major influencing factors of physical health include health literacy, ADL, alcohol consumption, household income, marital status, and former occupation. The major factors influencing mental health included ADL, former occupation, age, and smoking. Health literacy was associated with physical health, but was not associated with mental health. Improving health literacy could increase health management and health status of older adults.

Extractability-mediated stability bias and hematocrit impact: High extraction recovery is critical to feasibility of volumetric adsorptive microsampling (VAMS) in regulated bioanalysis.

Volumetric absorptive microsampling (VAMS), a new microsampling technique, was evaluated for its potential in supporting regulated bioanalysis. Our initial assessment with MK-0518 (raltegravir) using a direct extraction method resulted in 45-52% extraction recovery, significant hematocrit (Ht) related bias, and more importantly, unacceptable stability (>15% bias from nominal concentration) after 7-day storage. Our investigation suggested that the observed biases were not due to VAMS absorption, sampling techniques, lot-to-lot variability, matrix effect, and/or chemical stability of the compound, but rather the low extraction recovery. An effort to improve assay recovery led to a modified liquid-liquid extraction (LLE) method that demonstrated more consistent performance, minimal Ht impact (Ht ranged from 20 to 65%), and acceptable sample stability. The same strategy was successfully applied to another more hydrophilic model compound, MK-0431 (sitagliptin). These results suggest that the previously observed Ht effect and "instability" were in fact due to inconsistent extractability, and optimizing the extraction recovery to greater than 80% was critical to ensure VAMS performance. We recommend adding Ht-independent recovery as part of feasibility assessment to de-risk the long-term extractability-mediated stability bias before implementing VAMS in regulated bioanalysis.

Low uric acid is a risk factor in mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia. Uric acid is a water-soluble antioxidant found in the body. Many recent studies have found that uric acid plays an important role in cognitive impairment, although the effects of uric acid on MCI are not clear. OBJECTIVE: The objective of this study was to explore the relationship between uric acid and MCI. METHODS: Using a random sampling method, this study investigated 58 patients with MCI and 57 healthy elderly from January 2016 to November 2016. Demographic information was collected, the subjects were evaluated using the Mini Mental Status Examination (MMSE), and uric acid was measured in fasting venous blood. RESULTS: A total of 57 (49.6%) participants are healthy and 58 (50.4%) participants had MCI. The uric acid level was significantly lower in the patients with MCI (292.28±63.71 µmol/L) than in the normal controls (322.49±78.70 µmol/L; P<0.05). There were significant positive correlations between the MMSE scores, for each dimension and the total score, and uric acid level (all P<0.05). Multivariate logistic regression models illustrated that uric acid was a protective factor for MCI (odds ratio =0.999, 95% CI =0.987-0.999). CONCLUSION: A low uric acid level is a risk factor for MCI, and an appropriate increase in uric acid can be used to slow down the occurrence and development of MCI.

Simultaneous refractive index and thickness measurements of bio tissue by optical coherence tomography.

This paper presents two techniques based on optical coherence tomography, the "focus tracking method" and the "optical path shifting method," for determining refractive index and thickness simultaneously, which are especially useful for bio tissues. From comparison of these two methods, it was found that the focus tracking method is suitable for in vivo measurement, but does not have high precision. The optical path shifting method is limited to in vitro measurement, but has high precision. Using the optical path shifting method, the refractive indices of cucumber were measured at the wavelength of 850 and 1300 nm.

[The experiment study on the resolution of electro-optical imaging system at EUV wave band].

An imaging system based on a Microchannel Plate (MCP) detector was designed to image the Extreme Ultraviolet (EUV) light. The images of a 3 mm-width-slit were presented by this imaging system at the wavelengths of 13, 17.1, 19.5 and 30.4 nm respectively. Their corresponding spatial resolutions are 85, 120, 182 and 495 microm respectively. The best is 85 microm, corresponding to 13 nm. Moreover, the shorter the wavelength, the better the spatial resolution. So is the brightness of the image.

Mechanism study on inorganic oxidants induced inhibition of Ru(bpy)3²+ electrochemiluminescence and its application for sensitive determination of some inorganic oxidants.

Inhibited Ru(bpy)(3)(2+) electrochemiluminescence by inorganic oxidants is investigated. Results showed that a number of inorganic oxidants can quench the ECL of Ru(bpy)(3)(2+)/tri-n-propylamine (TPrA) system, and the logarithm of the decrease in ECL intensity (ΔI) was proportional to the logarithm of analyte concentrations. Based on which, a sensitive approach for detection of these inorganic oxidants was established, e.g. the log-log plots of ΔI versus the concentration of MnO(4)(-), Cr(2)O(7)(2-) and Fe(CN)(6)(3-) are linear in the range of 1×10(-7) to 3×10(-4)M for MnO(4)(-) and Cr(2)O(7)(2-), and 1×10(-7) to 1×10(-4)M for Fe(CN)(6)(3-), with the limit of detection (LOD) of 8.0×10(-8)M, 2×10(-8)M, and 1×10(-8)M, respectively. A series of experiments such as a comparison of the inhibitory effect of different compounds on Ru(bpy)(3)(2+)/TPrA ECL, ECL emission spectra, UV-Vis absorption spectra etc. were investigated in order to discover how these inorganic analytes quench the ECL of Ru(bpy)(3)(2+)/TPrA system. A mechanism based on consumption of TPrA intermediate (TPrA(·)) by inorganic oxidants was proposed.

Evaluation of the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases.

AIM: This study aimed to evaluate the safety, pharmacokinetics and treatment effects of an alpha(nu)beta(3) integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer (HRPC) and bone metastases. METHODS: A total of 21 patients with bone metastases and HRPC were randomized to receive MK-0429 200 mg b.i.d. or 1600 mg b.i.d. for 4 weeks. Toxicity, pharmacokinetics and markers of bone turnover and tumor activity were examined. RESULTS: Nausea was the most common adverse event: one (200-mg group) and 11 (1600-mg group) patients. At 4 weeks, mean AUC(0-12 h) was 210 mmol*h (200-mg group) and 673 mmol*h (1600-mg group); mean C(max) values were 42 mmol/L (200-mg group) and 154 mmol/L (1600-mg group). Urinary cross-linked N-telopeptides of type I collagen to creatinine ratio (uNTx), a bone turnover biomarker, showed a change from baseline of -43.4 percent (200-mg group) and -34.1 percent (1600-mg group). There was an increase in serum prostate specific antigen (PSA), a marker for disease activity, of 54.1 percent (200-mg group) and 44.5 percent (1600-mg group). CONCLUSION: MK-0429 was generally well tolerated, with the most common side-effect being nausea. There was some evidence of an early reduction of bone turnover, indicating a potential for clinical use in the treatment of MBD although serum PSA was unexpectedly increased during the study.