Correlation Between Illness Uncertainty in Caregivers of Patients with Liver Cancer, Their Coping Styles, and Quality of Life.

Objective: This study explores the correlation between coping style, quality of life, and illness uncertainty in the family caregivers of patients with liver cancer. Methods: Employing convenience sampling, 210 family caregivers of patients with liver cancer who met the admission criteria were selected from a grade A infectious disease hospital in Beijing between January and December 2022. A cross-sectional survey was conducted using the Simplified Coping Style Questionnaire, Caregiver Quality of Life, and the Mishel Uncertainty in Illness Scale for Family Members. This study analysed the correlations between coping styles, quality of life, and illness uncertainty in these caregivers. Results: The study found that family caregivers of patients with liver cancer had average scores for illness uncertainty (83.44 ± 11.86), coping style (33.19 ± 9.79; both positive [23.02 ± 6.81] and negative [10.17 ± 5.05]), and quality of life (169.53 ± 32.46). A negative association was observed between illness uncertainty in these caregivers and positive coping style (r = -0.207, p = 0.003), physical status (r = -0.182, p = 0.008), psychological status (r = -0.200, p = 0.004), and social adaptation (r = -0.229, p = 0.001). Conclusion: The study concludes that illness uncertainty in family caregivers of patients with liver cancer is at a moderate level. Furthermore, there is a notable correlation between illness uncertainty, coping style, and quality of life in these caregivers.

ASCL1 promotes Scrt2 expression in the neural tube.

ASCL1 is a transcription factor that directs neural progenitors towards lineage differentiation. Although many of the molecular mechanisms underlying its action have been described, several of its targets remain unidentified. We identified in the chick genome a putative enhancer (cE1) upstream of the transcription factor Scratch2 (Scrt2) locus with a predicted heterodimerization motif for ASCL1 and POU3F2. In this study, we investigated the role of ASCL1 and this enhancer in regulating the expression of the Scrt2 in the embryonic spinal cord. We confirmed that cE1 region interacted with the Scrt2 promoter. cE1 was sufficient to mediate ASCL1-driven expression in the neural tube through the heterodimerization sites. Moreover, Scrt2 expression was inhibited when we removed cE1 from the genome. These findings strongly indicate that ASCL1 regulates Scrt2 transcription in the neural tube through cE1.

The detection methods currently available for protein aggregation in neurological diseases.

Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.

Weakened hydrological oscillation period increased the frequency of river algal blooms.

The evolution of riverine aquatic ecosystems typically exhibits notable characteristic with cumulative, enduring, and hysteresis. Exploring the non-linear response of riverine ecology to long-term hydrological fluctuations become a major challenge in contemporary interdisciplinary research. In response to the critical issue of frequent river algal blooms in the lower Han River, which is impacted by Asian largest inter-basin water diversion project. We identified the non-linear response of eco-hydrology across various time scales through the integration of Continuous Wavelet Transform (CWT) and Inverse Wavelet Transform (IWT). Our study revealed that: 1) Over the past half century, the hydrological regime in the lower Han river showed a significant downward trend, and existed three significant hydrological oscillation periods (HOPs), including the short-scale Intra-AC (180 days), the medium-scale AC (365 days, the first major period), and the long-scale Inter-AC (2500 days), the variation of Inter-AC changed most dramatically. 2) We further found that the Inter-AC variation of hydrology is more closely related to the formation of river algal blooms in the Han River, and when the hydrological Inter-AC shows steady state or downward trend, the frequency of algal blooms in the lower Han River increases significantly. 3) The river algal blooms in the lower Han River is a cumulative consequence to the long-term hydrological influences. Weakened hydrological Inter-AC is more likely to increase the frequency of river algal blooms, and 10-years Inter-AC cumulation increased the frequency by 60%. Therefore, the weaken of long-scale HOP will significantly increase the frequency of river algal blooms in the future. This study received a critical scientific insight and aimed at provide guidance for the optimization of ecological management within the framework of national large-scale water conservation.

Large language models facilitate the generation of electronic health record phenotyping algorithms.

OBJECTIVES: Phenotyping is a core task in observational health research utilizing electronic health records (EHRs). Developing an accurate algorithm demands substantial input from domain experts, involving extensive literature review and evidence synthesis. This burdensome process limits scalability and delays knowledge discovery. We investigate the potential for leveraging large language models (LLMs) to enhance the efficiency of EHR phenotyping by generating high-quality algorithm drafts. MATERIALS AND METHODS: We prompted four LLMs-GPT-4 and GPT-3.5 of ChatGPT, Claude 2, and Bard-in October 2023, asking them to generate executable phenotyping algorithms in the form of SQL queries adhering to a common data model (CDM) for three phenotypes (ie, type 2 diabetes mellitus, dementia, and hypothyroidism). Three phenotyping experts evaluated the returned algorithms across several critical metrics. We further implemented the top-rated algorithms and compared them against clinician-validated phenotyping algorithms from the Electronic Medical Records and Genomics (eMERGE) network. RESULTS: GPT-4 and GPT-3.5 exhibited significantly higher overall expert evaluation scores in instruction following, algorithmic logic, and SQL executability, when compared to Claude 2 and Bard. Although GPT-4 and GPT-3.5 effectively identified relevant clinical concepts, they exhibited immature capability in organizing phenotyping criteria with the proper logic, leading to phenotyping algorithms that were either excessively restrictive (with low recall) or overly broad (with low positive predictive values). CONCLUSION: GPT versions 3.5 and 4 are capable of drafting phenotyping algorithms by identifying relevant clinical criteria aligned with a CDM. However, expertise in informatics and clinical experience is still required to assess and further refine generated algorithms.

The hierarchical dense structure induced high stability to NiCoB-based electrode for electrochemical energy storage.

The construction of stable hierarchical surfaces through structural engineering is the key to improve reactive active sites and cycle stability to achieve high cycle performance of supercapacitors (SCs). In this work, the NiCo-LDH nanoflower as a structure guide agent was used to support NiCoB nanosheets to form a dense and stable hierarchical structure, thereby exposing more active sites and improving cycle stability. Due to the hierarchical stable surface structure, the NiCoB-0.3@NiCo-LDH-30 electrode has an excellent specific capacitance of 2710F g-1 at 1 A/g due to the excellent electrochemical active surface area (1259 mF cm-2), improving the OH- diffusion coefficient (2.4 × 10-9 cm2 s-1) and decreasing ionic diffusion barrier. After 5000 cycles, NiCoB-0.3@NiCo-LDH-30 electrode still has 92.6 % initial specific capacitance. In order to balance the energy density decrease caused by the capacitance imbalance between positive and negative electrodes, the cubed carbon (Co-C) derived from cobalt metal organic frameworks (Co-MOFs) as cathode with a good specific capacitance of 220F g-1 at 1 A/g is prepared. The assembled NiCoB-0.3@NiCo-LDH-30//Co-C hybrid SCs (HSCs), which are assembled with NiCoB-0.3@NiCo-LDH-30 electrode as anode and Co-C electrode as cathode, displays an energy density of 75 Wh kg-1 at a power density of 741 W kg-1.

Advances, challenges, and opportunities for food safety analysis in the isothermal nucleic acid amplification/CRISPR-Cas12a era.

Global food safety stands out as a prominent public concern, affecting populations worldwide. The recurrent challenge of food safety incidents reveals the need for a robust inspection framework. In recent years, the integration of isothermal nucleic acid amplification with CRISPR-Cas12a techniques has emerged as a promising tool for molecular detection of food hazards, presenting next generation of biosensing for food safety detection. This paper provides a comprehensive review of the current state of research on the synergistic application of isothermal nucleic acid amplification and CRISPR-Cas12a technology in the field of food safety. This innovative combination not only enriches the analytical tools, but also improving assay performance such as sensitivity and specificity, addressing the limitations of traditional methods. The review summarized various detection methodologies by the integration of isothermal nucleic acid amplification and CRISPR-Cas12a technology for diverse food safety concerns, including pathogenic bacterium, viruses, mycotoxins, food adulteration, and genetically modified foods. Each section elucidates the specific strategies employed and highlights the advantages conferred. Furthermore, the paper discussed the challenges faced by this technology in the context of food safety, offering insightful discussions on potential solutions and future prospects.

The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis.

BACKGROUND: Hepatitis B cirrhosis (HBC) is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction. Although the relationship between certain single probiotics and HBC has been explored, the impact of the complex ready-to-eat Lactobacillus paracasei N1115 (LP N1115) supplement on patients with HBC has not been determined. AIM: To compare the changes in the microbiota, inflammatory factor levels, and liver function before and after probiotic treatment in HBC patients. METHODS: This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020. Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only. Fecal samples were collected at the onset and conclusion of the 12-wk intervention period. The structure of the intestinal microbiota and the levels of serological indicators, such as liver function and inflammatory factors, were assessed. RESULTS: Following LP N1115 intervention, the intestinal microbial diversity significantly increased in the intervention group (P < 0.05), and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria. Additionally, the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors (P < 0.05). CONCLUSION: LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota, improving liver function, and reducing inflammatory factor levels.

Extensive targeted metabolomics analysis reveals the identification of major metabolites, antioxidants, and disease-resistant active pharmaceutical components in Camellia tuberculata (Camellia L.) seeds.

Sect. tuberculata plant belongs to the Camellia genus and is named for the "tuberculiform protuberance on the surface of the ovary and fruit". It is a species of great ornamental value and potential medicinal value. However, little has been reported on the metabolites of C. tuberculata seeds. Therefore, this study was conducted to investigate the metabolites of C. tuberculata seeds based on UPLC/ESI-Q TRAP-MS/MS with extensively targeted metabolomics. A total of 1611 metabolites were identified, including 107 alkaloids, 276 amino acids and derivatives, 283 flavonoids, 86 lignans and coumarins, 181 lipids, 68 nucleotides and derivatives, 101 organic acids, 190 phenolic acids, 10 quinones, 4 steroids, 17 tannins, 111 terpenoids, and 177 other metabolites. We compared the different metabolites in seeds between HKH, ZM, ZY, and LY. The 1311 identified different metabolites were classified into three categories. Sixty-three overlapping significant different metabolites were found, of which lignans and coumarins accounted for the largest proportion. The differentially accumulated metabolites were enriched in different metabolic pathways between HKH vs. LY, HKH vs. ZM, HKH vs. ZY, LY vs. ZY, ZM vs. LY and ZM vs. ZY, with the most abundant metabolic pathways being 4, 2, 4, 7, 7 and 5, respectively (p < 0.05). Moreover, among the top 20 metabolites in each subgroup comparison in terms of difference multiplicity 7, 8 and 13. ZM and ZY had the highest phenolic acid content. Ninety-six disease-resistant metabolites and 48 major traditional Chinese medicine agents were identified based on seven diseases. The results of this study will not only lead to a more comprehensive and in-depth understanding of the metabolic properties of C. tuberculata seeds, but also provide a scientific basis for the excavation and further development of its medicinal value.

Rational design of a near-infrared fluorescent probe for monitoring butyrylcholinesterase activity and its application in development of inhibitors.

Butyrylcholinesterase (BChE) is widely expressed in multiple tissues and has a vital role in several key human disorders, such as Alzheimer's disease and tumorigenesis. However, the role of BChE in human disorders has not been investigated. Thus, to quantitatively detect and visualize dynamical variations in BChE activity is essential for exploring the biological roles of BChE in the progression of a number of human disorders. Herein, based on the substrate characteristics of BChE, we customized and synthesized three near-infrared (NIR) fluorescent probe substrates with cyanine-skeleton, and finally selected a NIR fluorescence probe substrate named CYBA. The CYBA demonstrated a significant increase in fluorescence when interacting with BChE, but mainly avoided AChE. Upon the addition of BChE, CYBA could be specifically hydrolyzed to TBO, resulting in a significant NIR fluorescence signal enhancement at 710 nm. Systematic evaluation revealed that CYBA exhibited exceptional chemical stability in complex biosamples and possessed remarkable selectivity and sensitivity towards BChE. Moreover, CYBA was successfully applied for real-time imaging of endogenous BChE activity in two types of nerve-related living cells. Additionally, CYBA demonstrated exceptional stability in the detection of complex biological samples in plasma recovery studies (97.51%-104.01%). Furthermore, CYBA was used to construct a high-throughput screening (HTS) method for BChE inhibitors using human plasma as the enzyme source. We evaluated inhibitory effects of a series of natural products and four flavonoids were identified as potent inhibitors of BChE. Collectively, CYBA can serve as a practical tool to track the changes of BChE activity in complicated biological environments due to its excellent capabilities.

Correction: Lonicera japonica Thunb. as a promising antibacterial agent for Bacillus cereus ATCC14579 based on network pharmacology, metabolomics, and in vitro experiments.

[This corrects the article DOI: 10.1039/D3RA00802A.].

PPARß/δ as a promising molecular drug target for liver diseases: A focused review.

Various liver diseases pose great threats to humans. Although the etiologies of these liver diseases are quite diverse, they share similar pathologic phenotypes and molecular mechanisms such as oxidative stress, lipid and glucose metabolism disturbance, hepatic Kupffer cell (KC) proinflammatory polarization and inflammation, insulin resistance, and hepatic stellate cell (HSC) activation and proliferation. Peroxisome proliferator-activated receptor ß/δ (PPARß/δ) is expressed in various types of liver cells with relatively higher expression in KCs and HSCs. Accumulating evidence has revealed the versatile functions of PPARß/δ such as controlling lipid homeostasis, inhibiting inflammation, regulating glucose metabolism, and restoring insulin sensitivity, suggesting that PPARß/δ may serve as a potential molecular drug target for various liver diseases. This article aims to provide a concise review of the structure, expression pattern and biological functions of PPARß/δ in the liver and its roles in various liver diseases, and to discuss potential future research perspectives.

Progress and Application of Halide Perovskite Materials for Solar Cells and Light Emitting Devices.

Halide perovskite materials have attracted worldwide attention in the photovoltaic area due to the rapid improvement in efficiency, from less than 4% in 2009 to 26.1% in 2023 with only a nanometer lever photo-active layer. Meanwhile, this nova star found applications in many other areas, such as light emitting, sensor, etc. This review started with the fundamentals of physics and chemistry behind the excellent performance of halide perovskite materials for photovoltaic/light emitting and the methods for preparing them. Then, it described the basic principles for solar cells and light emitting devices. It summarized the strategies including nanotechnology to improve the performance and the application of halide perovskite materials in these two areas: from structure-property relation to how each component in the devices affects the overall performance. Moreover, this review listed the challenges for the future applications of halide perovskite materials.

Is it more effective for anhedonia and avolition? A systematic review and meta-analysis of non-invasive brain stimulation interventions for negative symptoms in schizophrenia.

BACKGROUND: Noninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions. OBJECTIVE: This systematic review and meta-analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition. DATA SOURCES: PubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023. RESULTS: Among 1049 studies, we identified eight high-quality RCTs. NIBS significantly affects general negative symptoms (SMD = -0.54, 95% CI [-0.88, -0.21]) and all five domains (SMD = -0.32 to -0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = -0.47, 95% CI [-0.81, -0.13]) and anhedonia (SMD = -0.63, 95% CI [-0.98, -0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity. CONCLUSION: NIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.

Regulation of myo-miR-24-3p on the Myogenesis and Fiber Type Transformation of Skeletal Muscle.

Skeletal muscle plays critical roles in providing a protein source and contributing to meat production. It is well known that microRNAs (miRNAs) exert important effects on various biological processes in muscle, including cell fate determination, muscle fiber morphology, and structure development. However, the role of miRNA in skeletal muscle development remains incompletely understood. In this study, we observed a critical miRNA, miR-24-3p, which exhibited higher expression levels in Tongcheng (obese-type) pigs compared to Landrace (lean-type) pigs. Furthermore, we found that miR-24-3p was highly expressed in the dorsal muscle of pigs and the quadriceps muscle of mice. Functionally, miR-24-3p was found to inhibit proliferation and promote differentiation in muscle cells. Additionally, miR-24-3p was shown to facilitate the conversion of slow muscle fibers to fast muscle fibers and influence the expression of GLUT4, a glucose transporter. Moreover, in a mouse model of skeletal muscle injury, we demonstrated that overexpression of miR-24-3p promoted rapid myogenesis and contributed to skeletal muscle regeneration. Furthermore, miR-24-3p was found to regulate the expression of target genes, including Nek4, Pim1, Nlk, Pskh1, and Mapk14. Collectively, our findings provide evidence that miR-24-3p plays a regulatory role in myogenesis and fiber type conversion. These findings contribute to our understanding of human muscle health and have implications for improving meat production traits in livestock.

Machine learning in small sample neuroimaging studies: Novel measures for schizophrenia analysis.

Novel features derived from imaging and artificial intelligence systems are commonly coupled to construct computer-aided diagnosis (CAD) systems that are intended as clinical support tools or for investigation of complex biological patterns. This study used sulcal patterns from structural images of the brain as the basis for classifying patients with schizophrenia from unaffected controls. Statistical, machine learning and deep learning techniques were sequentially applied as a demonstration of how a CAD system might be comprehensively evaluated in the absence of prior empirical work or extant literature to guide development, and the availability of only small sample datasets. Sulcal features of the entire cerebral cortex were derived from 58 schizophrenia patients and 56 healthy controls. No similar CAD systems has been reported that uses sulcal features from the entire cortex. We considered all the stages in a CAD system workflow: preprocessing, feature selection and extraction, and classification. The explainable AI techniques Local Interpretable Model-agnostic Explanations and SHapley Additive exPlanations were applied to detect the relevance of features to classification. At each stage, alternatives were compared in terms of their performance in the context of a small sample. Differentiating sulcal patterns were located in temporal and precentral areas, as well as the collateral fissure. We also verified the benefits of applying dimensionality reduction techniques and validation methods, such as resubstitution with upper bound correction, to optimize performance.

Targeted Delivery of Catalase and Photosensitizer Ce6 by a Tumor-Specific Aptamer Is Effective against Bladder Cancer In Vivo.

Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT-Catalase-Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT-Catalase-Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.