Modulation of ER-mitochondria tethering complex VAPB-PTPIP51: Novel therapeutic targets for aging-associated diseases.

Aging is a gradual and irreversible natural process. With aging, the body experiences a functional decline, and the effects amplify the vulnerability to a range of age-related diseases, including neurodegenerative, cardiovascular, and metabolic diseases. Within the aging process, the morphology and function of mitochondria and the endoplasmic reticulum (ER) undergo alterations, particularly in the structure connecting these organelles known as mitochondria-associated membranes (MAMs). MAMs serve as vital intracellular signaling hubs, facilitating communication between the ER and mitochondria when regulating various cellular events, including calcium homeostasis, lipid metabolism, mitochondrial function, and apoptosis. The formation of MAMs is partly dependent on the interaction between the vesicle-associated membrane protein-associated protein-B (VAPB) and protein tyrosine phosphatase-interacting protein-51 (PTPIP51). Accumulating evidence has begun to elucidate the pivotal role of the VAPB-PTPIP51 tether in the initiation and progression of age-related diseases. In this study, we delineate the intricate structure and multifunctional role of the VAPB-PTPIP51 tether and discuss its profound implications in aging-associated diseases. Moreover, we provide a comprehensive overview of potential therapeutic interventions and pharmacological agents targeting the VAPB-PTPIP51-mediated MAMs, thereby offering a glimmer of hope in mitigating aging processes and treating age-related disorders.

A FRET-based multifunctional fluorescence probe for the simultaneous detection of sulfite and viscosity in living cells.

Viscosity and sulfur dioxide derivatives were significant indicators for the assessment of health threat and even cancers, therefore, on-site and real time detection of viscosity and sulfur dioxide derivatives has obtained considerable attentions. An FRET-based fluorescence probe JZX was designed and synthesized based on a novel energy donor of N,N-diethyl-4-(1H-phenanthro[9,10-d]imidazol-2-yl)benzamide fluorophore. JZX exhibited a large Stokes shift (230 nm), high energy transfer efficiency, wide emission channel gap (135 nm) and excellent stability and biocompatibility. JZX detected sulfur dioxide with low detection limit (55 nM), fast responding (16 min), high selectivity and sensitivity. Additionally, JZX tend to target endoplasmic reticulum of which normal metabolism will be disturbed by the abnormal levels of viscosity and sulfur dioxide derivatives. Prominently, JZX could concurrently detect viscosity and sulfur dioxide derivatives depending on different fluorescence signals in living cells for the screening of cancer cells. Hence, probe JZX will be a promising candidate for the detection of viscosity and sulfur dioxide derivatives, and even for the diagnosis of liver cancers.

m6A epitranscriptomic modification of inflammation in cardiovascular disease.

Cardiovascular disease is currently the number one cause of death endangering human health. There is currently a large body of research showing that the development of cardiovascular disease and its complications is often accompanied by inflammatory processes. In recent years, epitranscriptional modifications have been shown to be involved in regulating the pathophysiological development of inflammation in cardiovascular diseases, with 6-methyladenine being one of the most common RNA transcriptional modifications. In this review, we link different cardiovascular diseases, including atherosclerosis, heart failure, myocardial infarction, and myocardial ischemia-reperfusion, with inflammation and describe the regulatory processes involved in RNA methylation. Advances in RNA methylation research have revealed the close relationship between the regulation of transcriptome modifications and inflammation in cardiovascular diseases and brought potential therapeutic targets for disease diagnosis and treatment. At the same time, we also discussed different cell aspects. In addition, in the article we also describe the different application aspects and clinical pathways of RNA methylation therapy. In summary, this article reviews the mechanism, regulation and disease treatment effects of m6A modification on inflammation and inflammatory cells in cardiovascular diseases in recent years. We will discuss issues facing the field and new opportunities that may be the focus of future research.

Professional self-concept of BSN students: A cross-sectional correlational study.

BACKGROUND: Professional self-concept consists of one's judgments, attitudes about oneself professionally, and one's own perception as a professional. A positive professional self-concept can support students and new nurses throughout their nursing careers. OBJECTIVE: To describe levels of self-concept among pre-licensure undergraduate students. PARTICIPANTS/SETTING: The participants were nursing students in a Bachelor of Science in Nursing program in the United States. DESIGN/METHODS: This is a cross-sectional correlational study with self-report instruments, including demographics and the Professional Self-Concept of Nurses Instrument. Data (N = 103) were analyzed with SPSS/WIN 29.0. Descriptive statistics and professional self-concept scores were examined with independent t-tests, ANOVA, and Pearson's correlations. RESULTS: Most participants were female (n = 90), with a mean age of 20 years (SD = 1). The mean professional self-concept of nurses score was 78 (SD = 7), ranging from 27 to 108, and professional self-concept was positively correlated with receiving tutoring through the university's program, working as a tutor for nursing students or students in prerequisite classes, transferring into the nursing program, and participating in campus nursing organizations. Professional self-concept was negatively correlated with advancement in semesters of the nursing program, being a first-generation college student, having a family member who is a nurse, GPA, and having clinical-related work experience in healthcare. CONCLUSIONS: Higher levels of exposure to nursing may be related to lower professional self-concept. This is important to recognize and it may generalize to other nursing schools and health-related departments. Schools of nursing should enhance students' resilience by promoting self-concept. Our findings also shade light on self-care and the mental health of healthcare professionals.

Insights into the mechanism of color formation of the freshwater prawn (Macrobrachium rosenbergii) revealed by de novo assembly transcriptome analysis.

Body color is an important visual indicator of crustacean quality and plays a major role in consumer acceptability, perceived quality, and the market price of crustaceans. The freshwater prawn (Macrobrachium rosenbergii) has two distinct phenotypic variations, characterized by dark blue and light yellow body colors. However, the underlying mechanisms regulating the body color of M. rosenbergii remain unclear. In this study, the composition of shell color parameters and pigment cells of raw and cooked dark blue and light yellow M. rosenbergii was investigated and the mechanisms associated with body color were elucidated by transcriptome analysis. The results showed significant differences in the raw shells of the dark blue and light yellow M. rosenbergii (L: 26.20 ± 0.53 vs. 29.25 ± 0.45; a: -0.88 ± 0.19 vs. 0.35 ± 0.18; b: 1.73 ± 0.20 vs. 3.46 ± 0.37; dE: 70.33 ± 0.53 vs. 67.34 ± 0.45, respectively, p = 0.000) as well as the cooked shells (L: 58.14 ± 0.81 vs. 55.78 ± 0.55; a: 19.30 ± 0.56 vs. 16.42 ± 0.40; b: 23.60 ± 0.66 vs. 20.30 ± 0.40, respectively, p < 0.05). Transcriptome differential gene analysis obtained 39.02 Gb of raw data and 158,026 unigenes. Comprehensive searches of the SwissProt, Nr, KEGG, Pfam, and KOG databases resulted in successful annotations of 23,902 (33 %), 40,436 (25.59 %), 32,015 (20.26 %), 26,139 (16.54 %), and 22,155 (14.02 %) proteins, respectively. By KEGG pathway analysis, numerous differentially expressed genes were related to pigmentation-related pathways (MAPK signaling pathway, Wnt signaling pathway, melanin production, tyrosine metabolism, and cell-cell communication process). Candidate DEGs that may be involved in body color included apolipoprotein D, crustacyanin, cytochrome P450, and tyrosinase, as verified by quantitative real-time PCR. The results of this study provide useful references to further elucidate the molecular mechanisms of color formation of M. rosenbergii and other crustaceans.

The Role of Macrophage Death in Periodontitis: A Review.

Periodontitis, an infectious inflammatory disease influenced by various factors, disrupts the delicate balance between the host microbiota and immunity. The resulting excessive immune response exacerbates the progressive destruction of the supporting periodontal tissue. Macrophages are essential elements of the host innate immune system. They are pivotal components in the periodontal immune microenvironment and actively participate in both physiological and pathological processes of periodontal tissue. When confronted with periodontitis-related irritant factors, macrophages may differentiate to pro- or anti-inflammatory subtypes that affect tissue homeostasis. Additionally, macrophages may die in response to bacterial infections, potentially affecting the severity of periodontitis. This article reviews the typical mechanisms underlying macrophage death and its effects on periodontitis. We describe five forms of macrophage death in periodontitis: apoptosis, pyroptosis, necroptosis, ferroptosis, and ETosis. Our review of macrophage death in the pathophysiology of periodontitis enhances comprehension of the pathogenesis of periodontitis that will be useful for clinical practice. Although our review elucidates the complex mechanisms by which macrophage death and inflammatory pathways perpetuate periodontitis, unresolved issues remain, necessitating further research.

MT-125 Inhibits Non-Muscle Myosin IIA and IIB, Synergizes with Oncogenic Kinase Inhibitors, and Prolongs Survival in Glioblastoma.

We have identified a NMIIA and IIB-specific small molecule inhibitor, MT-125, and have studied its effects in GBM. MT-125 has high brain penetrance and retention and an excellent safety profile; blocks GBM invasion and cytokinesis, consistent with the known roles of NMII; and prolongs survival as a single agent in murine GBM models. MT-125 increases signaling along both the PDGFR- and MAPK-driven pathways through a mechanism that involves the upregulation of reactive oxygen species, and it synergizes with FDA-approved PDGFR and mTOR inhibitors in vitro . Combining MT-125 with sunitinib, a PDGFR inhibitor, or paxalisib, a combined PI3 Kinase/mTOR inhibitor significantly improves survival in orthotopic GBM models over either drug alone, and in the case of sunitinib, markedly prolongs survival in ∼40% of mice. Our results provide a powerful rationale for developing NMII targeting strategies to treat cancer and demonstrate that MT-125 has strong clinical potential for the treatment of GBM. Highlights: MT-125 is a highly specific small molecule inhibitor of non-muscle myosin IIA and IIB, is well-tolerated, and achieves therapeutic concentrations in the brain with systemic dosing.Treating preclinical models of glioblastoma with MT-125 produces durable improvements in survival.MT-125 stimulates PDGFR- and MAPK-driven signaling in glioblastoma and increases dependency on these pathways.Combining MT-125 with an FDA-approved PDGFR inhibitor in a mouse GBM model synergizes to improve median survival over either drug alone, and produces tumor free, prolonged survival in over 40% of mice.

Understanding reliability of the observer-reported communication ability measure within Angelman syndrome through the lens of generalizability theory.

AIMS: Caregivers rate improved communication ability as one of the most desired outcomes for successful interventions for individuals with Angelman syndrome (AS). When measuring communication ability in clinical trials, the reliability of such measures is critical for detecting significant changes over time. This study examined the reliability of the Observed-Reported Communication Ability (ORCA) measure completed by caregivers of individuals with AS. METHODS: The ORCA measure was completed by 249 caregivers with 170 caregivers completing the ORCA measure again after 5-12 days. Generalizability theory was used to examine the following sources of measurement error in ORCA scores: concepts, subdomains, assessment points, and the interactions among those facets and the object of measurement: communication ability. Three generalizability studies were conducted to understand the reliability of the ORCA measure for different measurement designs. Decision studies were carried out to demonstrate the optimization of measurement procedures of the ORCA measure. RESULTS: G and Phi coefficients of the original measurement design exceeded the 0.80 threshold considered sufficiently reliable to make relative and absolute decisions about the communication ability of individuals with AS based on their caregivers' observed scores. The optimization procedures indicated that increasing the number of communication concepts and/or assessment points leads to more reliable estimates of communication. CONCLUSION: The ORCA measure was able to reliably distinguish different levels of communication ability among individuals with AS. Multiple assessment points and or more concepts would provide more precise estimates of an individual's communication ability but at the cost of survey fatigue.

Compound heterozygous with Hb G-Taipei and Hb Lepore-Boston-Washington: An unexpected finding triggered by HbA1c measurement.

Background: Hemoglobin A1c has been widely used to diagnose and monitor diabetes. However, the accuracy of HbA1c analysis can be significantly affected by hemoglobin variants, leading to falsely low or elevated levels and misdiagnosis or inappropriate diabetes management. Case report: In this study, we present the case of a 23-year-old man with undetectable HbA1c levels during his annual checkup by high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). To investigate the reason for HbA1c absence, Sanger sequencing, multiplex ligation-dependent probe amplification assay (MLPA), long-read single molecule real-time sequencing (SMRT) and MALDI-TOF mass spectrometry (MS) were performed, and the proband was identified as compound heterozygous of ß-thalassemia with Hb G-Taipei (HBB:c.68A > G) and Hb Lepore-Boston-Washington (NG_000007.3:g.63632_71046del). Conclusion: The combination of these molecular technologies including MLPA, long-read SMRT sequencing and MALDI-TOF MS is beneficial for identifying rare hemoglobin variants. This case also provides essential evidence for uncovering the effect of compound heterozygosity for Hb Lepore-Boston-Washington and Hb G-Taipei on hematological phenotypes and HbA1c analysis.

A Novel Approach for Treating Lipomas: Percutaneous Microwave Ablation Combined with Liposuction.

Lipomas, benign adipose tissue tumors, are a common occurrence but currently, the options for their treatment are limited, with surgical excision being the most frequently used management pathway. This scenario can often lead to unsatisfactory cosmetic results and significant patient discomfort. This paper introduces a novel technique, percutaneous microwave ablation with liposuction, to address these challenges. The innovative procedure aims to enhance patient satisfaction, minimize post-operative discomfort, and improve aesthetic outcomes. The technique involves two key steps: (1) the application of percutaneous microwave ablation to selectively disrupt the lipoma cells, followed by (2) a targeted liposuction procedure to remove the ablated lipoma tissue. Our approach optimizes the removal of the lipoma and preserves the surrounding healthy tissue, reducing the risk of local recurrence and improving the cosmetic result. The use of preoperative ultrasound imaging allows for precise localization and delineation of the lipoma, aiding in the planning and execution of the procedure. This novel approach to lipoma treatment is reliable, associated with minimal morbidity, and consistently yields effective results. Additionally, it provides a new perspective on lipoma management, potentially changing the paradigm of current treatment approaches.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mechanisms of Persistent Hemolysis-Induced middle kidney Injury in grass carp (Ctenopharyngodon idella).

Infection-induced hemolysis results in intravascular hemolysis, which releases hemoglobin (Hb) into the tissues. Free Hb exhibits cytotoxic, oxidative, and pro-inflammatory effects, leading to systemic inflammation, vascular constriction dysfunction, thrombosis, and proliferative vascular lesions. Currently, the impact of intravascular hemolysis on the middle kidney in fish is unclear. Here, the injection of phenylhydrazine (PHZ) was used to establish a persistent hemolysis model in grass carp. The determination results revealed that the PHZ-induced hemolysis caused conspicuous tissue damage in the kidneys of grass carp, increased the levels of Cr in the serum and the expression indicators of kidney injury-related genes in the middle kidney. Prussian blue staining indicated that PHZ-induced hemolysis significantly increased the deposition of iron ions in the kidneys of grass carp, and activated the expression levels of iron metabolism-related genes. The results of oxidative damage-related experiments indicate that under PHZ treatment, the activity of middle kidney cells decreases, and the production of oxidative damage markers malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) increases, simultaneously inhibiting the activity of antioxidant enzymes and upregulating the transcription levels of antioxidant enzyme-related genes. Additionally, the analysis of inflammatory factors revealed a significant upregulation of genes associated with inflammation induced by PHZ-induced hemolysis. The transcriptome analysis was performed to further explore the molecular regulatory effects of hemolysis on tissues, the analysis revealed the treatment of PHZ activated various of programmed cell death (PCD) pathways, including ferroptosis, apoptosis, and autophagy. In summary, this study found that sustained hemolysis in fish results in Hb and iron ion deposition in middle kidney, promoting oxidative damage, ultimately inducing various forms of PCD.

Exosomal YB-1 facilitates ovarian restoration by MALAT1/miR-211-5p/FOXO3 axis.

Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) are attractive candidates for ovarian function restoration and folliculogenesis for POF due to their safety and efficacy, however, the key mediator in MSCs-sEVs that modulates this response and underlying mechanisms remains elusive. Herein, we reported that YB-1 protein was markedly downregulated in vitro and in vivo models of POF induced with H2O2 and CTX respectively, accompanied by granulosa cells (GCs) senescence phenotype. Notably, BMSCs-sEVs transplantation upregulated YB-1, attenuated oxidative damage-induced cellular senescence in GCs, and significantly improved the ovarian function of POF rats, but that was reversed by YB-1 depletion. Moreover, YB-1 showed an obvious decline in serum and GCs in POF patients. Mechanistically, YB-1 as an RNA-binding protein (RBP) physically interacted with a long non-coding RNA, MALAT1, and increased its stability, further, MALAT1 acted as a competing endogenous RNA (ceRNA) to elevate FOXO3 levels by sequestering miR-211-5p to prevent its degradation, leading to repair of ovarian function. In summary, we demonstrated that BMSCs-sEVs improve ovarian function by releasing YB-1, which mediates MALAT1/miR-211-5p/FOXO3 axis regulation, providing a possible therapeutic target for patients with POF.

A simple and highly sensitive flexible sensor with extended-gate field-effect transistor for epinephrine detection utilizing InZnSnO sensing films.

This study introduces a straightforward method for depositing InZnSnO films onto flexible polyimide substrates at room temperature, enabling their application in electrochemical pH sensing and the detection of epinephrine. A comprehensive analysis of these sensing films, spanning structural, morphological, compositional, and profiling characteristics, was conducted using diverse techniques, including X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy. The investigation into the influence of oxygen flow rates on the performance of InZnSnO sensitive films revealed a significant correlation between their structural properties and sensing capabilities. Notably, exposure to an oxygen flow rate of 30/2 (Ar/O2) the ratio of resulted in the InZnSnO sensitive film demonstrating outstanding pH sensitivity at 59.58 mV/pH within a broad pH range of 2-12, surpassing the performance observed with other oxygen flow rates. Moreover, under this specific condition, the film exhibited excellent stability, with a minimal drift rate of 0.14 mV/h at pH 7 and a low hysteresis voltage of 1.8 mV during a pH cycle of 7 â†’ 4→7 â†’ 10→7. Given the critical role of epinephrine in mammalian central nervous and hormone systems, monitoring its levels is essential for assessing human health. To facilitate the detection of epinephrine, we utilized the carboxyl group of 4-formylphenylboronic acid to enable a reaction with the amino group of the 3-aminopropyltriethoxysilane-coated InZnSnO film. Through optimization, the resulting InZnSnO-based flexible sensor displayed a broad and well-defined linear relationship within the concentration range of 10-7 to 0.1 µM. In practical applications, this sensor proved effective in analyzing epinephrine in human serum, showcasing notable selectivity, stability, and reproducibility. The promising outcomes of this study underscore the potential for future applications, leveraging the advantages of electrochemical sensors, including affordability, rapid response, and user-friendly operation.

Successful Treatment of Cutaneous Protothecosis Due to Prototheca wickerhamii with Terbinafine.

Protothecosis, an infrequent human infection, is caused by achlorophyllic algae belonging to the genus Prototheca, particularly Prototheca wickerhamii. The skin stands as the most commonly affected organ. This report documents a case involving an 82-year-old male with Protothecosis. Histopathological analysis revealed granulomatous inflammation in the dermis, exhibiting necrotic features and hosting numerous non-budding spherical organisms. These organisms were positively stained using methenamine silver and periodic acid-Schiff stains, confirming identification as P. wickerhamii after validation through tissue culture and sequencing procedures. Initially, the patient received oral itraconazole at a dosage of 200 mg daily, accompanied by topical 1% naftifine-0.25% ketoconazole cream for a duration of 4 weeks, resulting in significant improvement. Subsequently, due to gastrointestinal discomfort presumably linked to itraconazole, terbinafine was administered. Over a span of 3 months, the patient received oral terbinafine at a dosage of 250 mg/day alongside the application of topical 1% naftifine-0.25% ketoconazole cream, leading to complete healing of the skin lesion, leaving behind a fibrotic scar.

HIF-1α and adaptor protein LIM and senescent cell antigen-like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.

Polyacrylonitrile as an Efficient Transfer Medium for Wafer-scale Transfer of Graphene.

The disparity between growth substrates and application-specific substrates can be mediated by reliable graphene transfer, the lack of which currently strongly hinders the graphene applications. Conventionally, the removal of soft polymers, that support the graphene during the transfer, would contaminate graphene surface, produce cracks, and leave unprotected graphene surface sensitive to airborne contaminations. In this work, we found that polyacrylonitrile (PAN) can function as polymer medium for transferring wafer-size graphene, and encapsulating layer to deliver high-performance graphene devices. Therefore, PAN, that is compatible with device fabrication, does not need to be removed for subsequent applications. We achieved the crack-free transfer of 4-inch graphene onto SiO2/Si wafers, and the wafer-scale fabrication of graphene-based field-effect transistor (FET) arrays with no observed clear doping, uniformly high carrier mobility (∼11,000 cm2 V-1 s-1) and long-term stability at room temperature. Our work presents new concept for designing the transfer process of two-dimensional (2D) materials, in which multifunctional polymer can be retained, and offers a reliable method for fabricating wafer-scale devices of 2D materials with outstanding performance. This article is protected by copyright. All rights reserved.

"Demodicosis" Mimicking PreSeptal Cellulitis: Severe Periocular and Facial Inflammation Caused by "Normal" Skin Flora.

Due to their relatively high prevalence and commensalism, the pathogenicity of Demodex mites has been debated. Recent data, however, show Demodex to be associated with skin and ocular surface diseases such as rosacea, blepharitis, and keratitis. Here the authors report the first known case, to the best of the their knowledge, of Demodex infestation mimicking preseptal cellulitis in an adult human. A 29-year-old male bilaterally blind from advanced retinopathy of prematurity presented with a 2-month history of right-greater-than-left upper eyelid and periocular/cheek swelling, redness, and ocular discharge that did not resolve with oral antibiotics or oral steroids. Based on MRI findings, biopsies of the right lacrimal gland, right orbital fat, and right upper eyelid preseptal skin were obtained which revealed marked intrafollicular Demodex mite density and budding yeasts in the upper eyelid skin. This case serves to alert clinicians to this entity that may not otherwise be usually considered in ophthalmic clinical practice.

Green and Efficient Extraction of Phenolic Components from Plants with Supramolecular Solvents: Experimental and Theoretical Studies.

The supramolecular solvent (SUPRAS) has garnered significant attention as an innovative, efficient, and environmentally friendly solvent for the effective extraction and separation of bioactive compounds from natural resources. However, research on the use of a SUPRAS for the extraction of phenolic compounds from plants, which are highly valued in food products due to their exceptional antioxidant properties, remains scarce. The present study developed a green, ultra-sound-assisted SUPRAS method for the simultaneous determination of three phenolic acids in Prunella vulgaris using high-performance liquid chromatography (HPLC). The experimental parameters were meticulously optimized. The efficiency and antioxidant properties of the phenolic compounds obtained using different extraction methods were also compared. Under optimal conditions, the extraction efficiency of the SUPRAS, prepared with octanoic acid reverse micelles dispersed in ethanol-water, significantly exceeded that of conventional organic solvents. Moreover, the SUPRAS method demonstrated greater antioxidant capacity. Confocal laser scanning microscopy (CLSM) images revealed the spherical droplet structure of the SUPRAS, characterized by a well-defined circular fluorescence position, which coincided with the position of the phenolic acids. The phenolic acids were encapsulated within the SUPRAS droplets, indicating their efficient extraction capacity. Furthermore, molecular dynamics simulations combined with CLSM supported the proposed method's mechanism and theoretically demonstrated the superior extraction performance of the SUPRAS. In contrast to conventional methods, the higher extraction efficiency of the SUPRAS can be attributed to the larger solvent contact surface area, the formation of more types of hydrogen bonds between the extractants and the supramolecular solvents, and stronger, more stable interaction forces. The results of the theoretical studies corroborate the experimental outcomes.

Insights Into Colorectal Cancer Screening: A Multidatabase Cohort Study of Over 1.5 Million Taiwanese.

INTRODUCTION: Colorectal cancer (CRC) remains a significant public health concern. This study aims to provide a comprehensive understanding of the effectiveness of fecal immunochemical test (FIT) screening on CRC incidence and mortality, leveraging the scale of over 1.5 million randomly selected Taiwanese and more than 11.7 million person-years of follow-up. METHODS: This prospective cohort study merges data from 3 robust Taiwanese health databases: the CRC screening program, cancer registration, and death registration databases. Incidence and mortality rates of CRC were calculated based on age, sex, urbanization, and past screening status. Cox proportional hazard models were used to assess the association between screening statuses and CRC incidence or mortality, adjusting for age, sex, and urbanization levels. Statistical analysis of the data was conducted in 2021-2022. RESULTS: FIT screening was associated with a 33% reduction in CRC incidence and a 47% reduction in mortality. The study identified a dose-response relationship between the fecal hemoglobin concentration (f-HbC) levels and CRC risk. Participants with consistent FIT-negative results had significantly reduced CRC incidence and mortality risks, while those with one or more positive FIT results faced increased risks. Notably, compliance with follow-up examinations after a positive FIT significantly lowered mortality risk. CONCLUSIONS: This large-scale study validates the efficacy of FIT screening in reducing CRC incidence and mortality. It offers a nuanced understanding of how various screening statuses impact CRC risks, thus providing valuable insights for public health strategies aimed at CRC prevention.