Calorie restriction and calorie-restriction mimetics activate chaperone-mediated autophagy.

Chaperone-mediated autophagy (CMA) is part of the mammalian cellular proteostasis network that ensures protein quality control, maintenance of proteome homeostasis, and proteome changes required for the adaptation to stress. Loss of proteostasis is one of the hallmarks of aging. CMA decreases with age in multiple rodent tissues and human cell types. A decrease in lysosomal levels of the lysosome-associated membrane protein type 2A (LAMP2A), the CMA receptor, has been identified as a main reason for declined CMA in aging. Here, we report constitutive activation of CMA with calorie restriction (CR), an intervention that extends healthspan, in old rodent livers and in an in vitro model of CR with cultured fibroblasts. We found that CR-mediated upregulation of CMA is due to improved stability of LAMP2A at the lysosome membrane. We also explore the translational value of our observations using calorie-restriction mimetics (CRMs), pharmacologically active substances that reproduce the biochemical and functional effects of CR. We show that acute treatment of old mice with CRMs also robustly activates CMA in several tissues and that this activation is required for the higher resistance to lipid dietary challenges conferred by treatment with CRMs. We conclude that part of the beneficial effects associated with CR/CRMs could be a consequence of the constitutive activation of CMA mediated by these interventions.

First incidence of extrarenal wilms tumor within the spinal canal in the adult population: a novel case report and literature review.

BACKGROUND: Wilms tumor (WT), also known as nephroblastoma, is rare in adults, accounting for merely 3% of all nephroblastomas or 0.2 cases per million individuals. Extrarenal Wilms tumor (ERWT) emerges outside the renal boundaries and comprises 0.5 to 1% of all WT cases, with even rarer incidences in adults. Oncogenic mutations associated with ectopic nephrogenic rests (NR) may contribute to ERWT development. Diagnosis involves surgical resection and pathology examination. Due to scarce cases, adults often rely on pediatric guidelines. We thoroughly searched PubMed, Scopus, and Web of Science databases to establish our case's uniqueness. To the best of our knowledge, this is the first documented incidence of extrarenal Wilms tumor within the spinal canal in the adult population. CASE PRESENTATION: A 22-year-old woman with a history of congenital lipo-myelomeningocele surgery as an infant presented with a 6-month history of back pain. This pain gradually resulted in limb weakness, paraparesis, and loss of bladder and bowel control. An MRI showed a 6 × 5 × 3 cm spinal canal mass at the L4-S1 level. Consequently, a laminectomy was performed at the L4-L5 level to remove the intramedullary tumor. Post-surgery histopathology and immunohistochemistry confirmed the tumor as ERWT with favorable histology without any teratomatous component. CONCLUSION: This report underscores the rarity of extrarenal Wilms tumor (ERWT) in adults, challenging conventional assumptions about its typical age of occurrence. It emphasizes the importance of clinical awareness regarding such uncommon cases. Moreover, the co-occurrence of spinal ERWTs and a history of spinal anomalies warrants further investigation.

Implementation of hazard analysis and critical control point (HACCP) in yogurt production.

This study aimed to review hazard analysis and critical control points (HACCP) in the dairy industry for the production of yogurt. The food safety management system (FSMS) was implemented over the last several decades with several amendments. The need for practical and proactive procedures in the dairy industry was identified so that HACCP implementation could ensure that consumers would always have safe food. The concept of HACCP is a systemic and science-based method that can result in safe dairy products such as yogurt based on the complete analysis of manufacturing processes, recognition of hazards potentially present at all stages of production, and risk prevention. In yogurt production, raw milk receipt, pasteurization, packaging, and storage are the steps most susceptible to contamination and were considered critical control points. Further steps also need to be implemented to achieve other related control measures, and these will be discussed.

P16INK4a Upregulation Mediated by SIX6 Defines Retinal Ganglion Cell Pathogenesis in Glaucoma.

Glaucoma, a blinding neurodegenerative disease, whose risk factors include elevated intraocular pressure (IOP), age, and genetics, is characterized by accelerated and progressive retinal ganglion cell (RGC) death. Despite decades of research, the mechanism of RGC death in glaucoma is still unknown. Here, we demonstrate that the genetic effect of the SIX6 risk variant (rs33912345, His141Asn) is enhanced by another major POAG risk gene, p16INK4a (cyclin-dependent kinase inhibitor 2A, isoform INK4a). We further show that the upregulation of homozygous SIX6 risk alleles (CC) leads to an increase in p16INK4a expression, with subsequent cellular senescence, as evidenced in a mouse model of elevated IOP and in human POAG eyes. Our data indicate that SIX6 and/or IOP promotes POAG by directly increasing p16INK4a expression, leading to RGC senescence in adult human retinas. Our study provides important insights linking genetic susceptibility to the underlying mechanism of RGC death and provides a unified theory of glaucoma pathogenesis.

A large population-based study on the prevalence of electrocardiographic abnormalities: A result of Mashhad stroke and heart atherosclerotic disorder cohort study.

BACKGROUND: Twelve-lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population. METHODS: ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS. RESULTS: Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T-wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff-Parkinson-White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T-wave abnormalities, Wolff-Parkinson-White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P-wave duration, and QRS duration between men and women indicated that there was a significant difference. CONCLUSIONS: Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups.

Massive Solubility Changes in Neuronal Proteins upon Simulated Traumatic Brain Injury Reveal the Role of Shockwaves in Irreversible Damage.

We investigated the immediate molecular consequences of traumatic brain injuries (TBIs) using a novel proteomics approach. We simulated TBIs using an innovative laboratory apparatus that employed a 5.1 kg dummy head that held neuronal cells and generated a ≤4000 g-force acceleration upon impact. A Proteome Integral Solubility Alteration (PISA) assay was then employed to monitor protein solubility changes in a system-wide manner. Dynamic impacts led to both a reduction in neuron viability and massive solubility changes in the proteome. The affected proteins mapped not only to the expected pathways, such as those of cell adhesion, collagen, and laminin structures, as well as the response to stress, but also to other dense protein networks, such as immune response, complement, and coagulation cascades. The cellular effects were found to be mainly due to the shockwave rather than the g-force acceleration. Soft materials could reduce the impact's severity only until they were fully compressed. This study shows a way of developing a proteome-based meter for measuring irreversible shockwave-induced cell damage and provides a resource for identifying protein biomarkers of TBIs and potential drug targets for the development of products aimed at primary prevention and intervention.

Lens regeneration using endogenous stem cells with gain of visual function.

The repair and regeneration of tissues using endogenous stem cells represents an ultimate goal in regenerative medicine. To our knowledge, human lens regeneration has not yet been demonstrated. Currently, the only treatment for cataracts, the leading cause of blindness worldwide, is to extract the cataractous lens and implant an artificial intraocular lens. However, this procedure poses notable risks of complications. Here we isolate lens epithelial stem/progenitor cells (LECs) in mammals and show that Pax6 and Bmi1 are required for LEC renewal. We design a surgical method of cataract removal that preserves endogenous LECs and achieves functional lens regeneration in rabbits and macaques, as well as in human infants with cataracts. Our method differs conceptually from current practice, as it preserves endogenous LECs and their natural environment maximally, and regenerates lenses with visual function. Our approach demonstrates a novel treatment strategy for cataracts and provides a new paradigm for tissue regeneration using endogenous stem cells.

In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration.

Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

High-quality pectin from cantaloupe waste: eco-friendly extraction process, optimization, characterization and bioactivity measurements.

BACKGROUND: The rind from cantaloupe is an agricultural waste of cantaloupe industrial processing. The current study tried to (i) evaluate the potential use of cantaloupe rind as a pectin source, (ii) optimize the factors of microwave-assisted extraction process using Box-Behnken design, and (iii) characterize the isolated pectin using various physicochemical, structural, functional and bioactivity properties. RESULTS: Four variables of the extraction process were successfully optimized at a microwave power of 700 W, irradiation time of 112 s, pH value of 1.50 and liquid to solid (LS) value of 30 mL g-1 , with a yield of 181.4 g kg-1 . The analysis indicated a high-methylated galacturonic acid-rich (703.4 g kg-1 ) sample with an average molecular weight of 390.475 kDa. Also, the isolated pectin showed considerable functionality and antioxidant ability. The main functional groups, structural characteristics and crystallinity of samples were comparatively studied using Fourier transform infrared, nuclear magnetic resonance and X-ray diffraction spectroscopies. CONCLUSION: In comparison to commercial citrus pectin, isolated pectin showed a significantly higher value for most of the functional analysis such as oil holding capacity, emulsifying capacity, emulsion stability, DPPH• and ABTS•+ scavenging activity, and reducing power assay. In other analyses the isolated sample was close to the commercial one, indicating that cantaloupe rinds should be considered as a suitable additional resource for pectin production. © 2021 Society of Chemical Industry.

The viral prescription pad - a mixed methods study to determine the need for and utility of an educational tool for antimicrobial stewardship in primary health care.

BACKGROUND: In order to combat rising rates of antimicrobial resistant infections, it is vital that antimicrobial stewardship become embedded in primary health care (PHC). Despite the high use of antimicrobials in PHC settings, there is a lack of data regarding the integration of antimicrobial stewardship programs (ASP) in non-hospital settings. Our research aimed to determine which antimicrobial stewardship interventions are optimal to introduce into PHC clinics beginning to engage with an ASP, as well as how to optimize those interventions. This work became focused specifically around management of viral upper respiratory tract infections (URTIs), as these infections are one of the main sources of inappropriate antibiotic use. METHODS: This mixed methods study of sequential explanatory design was developed through three research projects over 3 years in Regina, Saskatchewan, Canada. First, a survey of PHC providers was performed to determine their perceived needs from a PHC-based ASP. From this work, a "viral prescription pad" was developed to provide a tool to help PHC providers engage in patient education regarding appropriate antimicrobial use, specifically for URTIs. Next, interviews were performed with family physicians to discuss their perceived utility of this tool. Finally, we performed a public survey to determine preferences for the medium by which information is received regarding symptom management for viral URTIs. RESULTS: The majority of PHC providers responding to the initial survey indicated they were improperly equipped with tools to aid in promoting conversations with patients and providing education about the appropriate use of antimicrobials. Following dissemination of the viral prescription pad and semi-structured interviews with family physicians, the viral prescription pad was deemed to be a useful educational tool. However, about half of the physicians interviewed indicated they did not actually provide a viral prescription to patients when providing advice on symptom management for viral URTIs. When asked about their preferences, 76% of respondents to the public survey indicated they would prefer to receive written or a combination of verbal and written information in this circumstance. CONCLUSIONS: PHC providers indicated a need for educational tools to promote conversations with patients and provide education about the appropriate use of antimicrobials. Viral prescription pads were regarded by family physicians and patients as useful tools in facilitating discussion on the appropriate use of antimicrobials. PHC providers should exercise caution in opting out of providing written forms of information, as many respondents to the general public survey indicated their preference in receiving both verbal and written information.

DNA methylation markers for diagnosis and prognosis of common cancers.

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis.

Exoenzyme activity and possibility identification of Candida dubliniensis among Candida albicans species isolated from vaginal candidiasis.

OBJECTIVES: Vulvovaginal candidiasis (VVC) or vaginal candidiasis is a common fungal infection of the genitals causing inflammation, irritation, itching, and vaginal discharge. Common yeast infections are caused by the yeast species C. albicans. However, there are other species of Candida such as C. dubliniensis which are considered as the causative agents of this infection. Hydrolytic enzymes such as proteinase and coagulase are known as virulence factors. The aim of this study was the molecular confirmation and differentiation of C. dubliniensis among C. albicans strains isolated from women with vulvovaginal candidiasis by PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and the evaluation of proteinase and coagulase activities. METHODS: A total of 100 C. albicans strains isolated from women with vulvovaginal candidiasis referred to Shiraz medical clinics were enrolled in the study. All the isolates were primarily identified by conventional methods. PCR-RFLP method was used for the confirmation and identification of C. albicans and C. dubliniensis. Moreover, in vitro proteinase and coagulase activities of these isolates were evaluated using bovine serum albumin media and classical rabbit plasma tube test. RESULTS: As a result, PCR-RFLP identified 100% of the isolates as C. albicans, and no C. dubliniensis could be identified in this study. 84% of the isolates showed proteinase activity, whereas coagulase activity was only detected in 5% of the isolates. CONCLUSIONS: This study reveals that C. dubliniensis plays no role in vaginal candidiasis in Iranian patients. Proteinase production could be an essential virulence factor in C. albicans pathogenicity, but coagulase activity has less potential in this matter.

A Simple Colorimetric Chemosensor for Naked Eye Detection of Cyanide Ion.

A simple cyanide chemosensor tetranitrile compound 1 was designed and synthesized via an efficient method in the presence of nanoporous SBA-Pr-NH2 as the catalyst. The chemosensor exhibited high selectivity and sensitivity for detecting CN¯ among different anions through a visual color change from light yellow to purple. The results confirmed that the chemosensor 1 causes the color of the solution to change depending on the concentration of CN¯. Linear changes of the optical properties of the sensor as a function of the concentrations of CN¯ was proved. The detection limit of 3.07 × 10(-7) M was calculated for CN¯. A simple paper test strip system for the rapid detection of CN¯ was developed. The TD-DFT calculations were carried out to understand the sensing mechanism.

Minichromosome maintenance-2 (MCM2) expression differentiates oral squamous cell carcinoma from pre-cancerous lesions.

BACKGROUND: Proteins necessary for DNA replication and normal regulation for the cell cycle include minichromosome maintenance-2 (Mcm-2). Overexpression of this protein in several premalignant and malignant lesions has been observed. In this study, the diagnostic value of Mcm-2 expression in distinguishing histologically-proven normal oral mucosa (NOM), oral benign keratosis (OBK), oral epithelial dysplasia (OED), and oral squamous cell carcinoma (OSCC) was investigated. MATERIALS AND METHODS: In this descriptive analytical study, 73 archived specimens of oral tissues, including 20 OBK, 20 OED, 20 OSCC, and 13 NOM cases were selected. The means of labeling indices (LIs) of Mcm-2 expression by immunohistochemistry in each category of lesions were calculated. The data was analyzed by one-way ANOVA, discriminant analysis, and Fisher's exact tests. RESULTS: The means of labeling indices (LIs) of Mcm-2 expression show statistically significant difference between the four studied groups (P<0.001). Mcm-2 had overexpression and higher positivity in OSCCs. A cut-off point of 67% was determined in order to distinguish OSCC from precancerous lesions. CONCLUSION: The findings indicated that Mcm-2 could be a useful marker for early detection of oral SCC and dysplasia. Also, due to the overexpression of this marker in OSCC, there exists the possibility of application of Mcm-2 for molecular target therapy in these patients.

Determination of Element Concentration of Brewed Tea Consumed in Iran Using ICP-OES: A Risk Assessment Study.

Tea is a popular drink enjoyed by many people around the world. However, it is important to note that impurities and contaminants in tea can potentially threaten human health when consumed. The main objective of this research is to assess the concentration of 16 trace elements (As, Fe, Al, Co, B, Li, Cd, Ba, Pb, Cr, Zn, Hg, Ni, Mn, Sb, and Sn) present in different types brewed of tea by using the ICP-OES (the inductively coupled plasma optical emission spectrometer) device, and the human health risks related to its use were evaluated. In this study, manganese (Mn) indicated the highest mean concentration in black (917.64 µg/kg) and green tea (912.89 µg/kg), respectively. Our study showed that the highest mean concentration of element boron (B) was (44.36 µg/kg) in Stachys lavandulifolia brewed tea. Among different packaging, tea bag samples had the highest concentration of Mn (1025.65 µg/kg) and aluminum (Al) (396.63 µg/kg). However, those unpacked posed the lowest content of Mn (188.13 µg/kg) and Al (100.47 µg/kg). The lead (Pb), mercury (Hg), and cadmium (Cd) concentrations in all samples were lower than the maximum limit of the Iranian standard and the WHO. In general, the amount of tea metal in Iranian samples was higher than in imported samples. Also, increasing the brewing time (10 min) can be effective in the solubility and extraction of metals such as B, Hg, cobalt (Co), iron (Fe), and lithium (Li). Further, the correlation between the amount of metals and type in tea samples was evaluated with principal component analysis. Based on the conducted non-carcinogenic risk assessment by the Monte Carlo simulation, the hazard index (HI), due to ingestion of heavy metals via tea in the 5-min brewing of tea, was 7.39E - 03 and 2.09E - 03, and in the 10-min brewing of tea, it was 3.20E - 02 and 9.07E - 03 for children and adults, respectively. Therefore, there was no significant non-carcinogenic risk from tea consumption.

Improving performance, reproduction, and immunity in laying Japanese quail with algal derivatives.

We investigated the effect of the Persian Gulf algae derivatives, namely phycocyanin (PC) and fucoidan (FUC), on the performance, reproductive traits, and immune responses of laying Japanese quails. A completely randomized design was used to distribute 250 six-wk-old Japanese quails with an average body weight of 215 ± 10 g into 5 treatments, 5 replicates, and 10 birds in each replicate over a 5-wk period. Unlike the control groups, the treatment groups received drinking water supplemented with PC and FUC at concentrations of 20 or 40 mg/L, denoted as PC20, PC40, FUC20, and FUC40, respectively, while all birds were provided with identical feed. Supplemental algal derivatives notably improved hen day egg production (HDEP), egg mass, and feed conversion ratio (FCR) compared to the control group (P < 0.01). Incorporating PC and FUC had no significant effect on the weight of males' testes or the weight and length of hens' oviducts. Additionally, the experimental treatments had no impact on the chicks' hatching weight. The supplementation of PC and FUC resulted in increased fertility (P = 0.038) and hatchability (P < 0.001) rates, with the exception of fertility in the PC40 group. The effect of the experimental treatments on immune responses was largely not statistically significant, except in the case of ND. Specifically, the experimental treatments resulted in increased (P = 0.033) antibody titers against ND when compared to the control group, with the exception of FUC20. Supplemental algal derivatives significantly (P < 0.01) reduced total cholesterol, creatinine, and triglycerides (except in the case of PC20). Overall, these findings underscore the potential of algal derivatives to enhance quail performance, reproductive traits, and immune responses.

A uniform data processing pipeline enables harmonized nanoparticle protein corona analysis across proteomics core facilities.

Protein corona, a layer of biomolecules primarily comprising proteins, forms dynamically on nanoparticles in biological fluids and is crucial for predicting nanomedicine safety and efficacy. The protein composition of the corona layer is typically analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Our recent study, involving identical samples analyzed by 17 proteomics facilities, highlighted significant data variability, with only 1.8% of proteins consistently identified across these centers. Here, we implement an aggregated database search unifying parameters such as variable modifications, enzyme specificity, number of allowed missed cleavages and a stringent 1% false discovery rate at the protein and peptide levels. Such uniform search dramatically harmonizes the proteomics data, increasing the reproducibility and the percentage of consistency-identified unique proteins across distinct cores. Specifically, out of the 717 quantified proteins, 253 (35.3%) are shared among the top 5 facilities (and 16.2% among top 11 facilities). Furthermore, we note that reduction and alkylation are important steps in protein corona sample processing and as expected, omitting these steps reduces the number of total quantified peptides by around 20%. These findings underscore the need for standardized procedures in protein corona analysis, which is vital for advancing clinical applications of nanoscale biotechnologies.

Giant pedunculated hepatic hemangioma accompanied by a 10-year history of taking oral contraceptive: A case report and literature review.

Key Clinical Message: Giant pedunculated hepatic hemangiomas, mostly seen in women, are considered a rare type of giant hepatic hemangioma, with challenging diagnosis. Unlike other types of liver hemangiomas, they can manifest different kinds of symptoms, and are prone to life-threatening manifestations like rupture or torsion. Abstract: Hemangioma is the most common benign liver primary tumor. Hepatic hemangioma >4 cm (some studies suggest >10 cm) is referred to as a giant hemangioma. Although hepatic hemangioma does not manifest symptoms in most cases, a giant hepatic hemangioma can manifest different kinds of symptoms. Giant pedunculated hepatic hemangiomas are considered a rare type of giant hepatic hemangioma, with challenging diagnosis, as the thin pedicle could be hard to be detected on imaging. A 41-year-old woman was admitted to our hospital, with dull discomfort of the right upper quadrant and epigastric region and early satiety for the past 7 months, with the history of taking oral contraceptive (OCP) for 10 years. Ultrasound and computed tomography revealed a 130 × 124 × 76 mm solid mass, with central cystic lesion, located in the midline of the epigastric region, attaching to the inferior surface of the third segment of the left lobe of the liver. Due to the potential risk for torsion, and rupture of the hemangioma, the management of the patient proceeded to surgical excision. Pathological examination of the specimen confirmed the diagnosis of hepatic hemangioma. Giant pedunculated hepatic hemangioma is a rare benign tumor. It demonstrates higher incidence rate in women, as some hemangiomas have estrogen receptors, and estrogen can lead to endothelial cell proliferation and organization in vascular structure. Most hemangiomas do not express any symptoms; therefore, no treatment is needed except for the patients who manifest symptoms, or in giant pedunculated hemangiomas, as they are prone to rupture or torsion. In this review most cases were female, and most of them presented with abdominal pain, in most cases the tumor located in the left lobe of the liver. Almost all the reviewed cases underwent surgery. Giant hepatic hemangioma is a differential diagnosis of palpable mass, or other symptoms of the right upper quadrant, and epigastric region specially in women taking OCP. Imaging is needed to rule out these tumors, and most often, pedunculated hemangioma is harder to be defined on imaging. It requires surgery because of the risk of acute problems, such as torsion and rupture.

Deep Plasma Proteome Profiling by Modulating Single Nanoparticle Protein Corona with Small Molecules.

The protein corona, a dynamic biomolecular layer that forms on nanoparticle (NP) surfaces upon exposure to biological fluids is emerging as a valuable diagnostic tool for improving plasma proteome coverage analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Here, we show that spiking small molecules, including metabolites, lipids, vitamins, and nutrients, into plasma can induce diverse protein corona patterns on otherwise identical NPs, significantly enhancing the depth of plasma proteome profiling. The protein coronas on polystyrene NPs when exposed to plasma treated with an array of small molecules (n=10) allowed for detection of 1793 proteins marking an 8.25-fold increase in the number of quantified proteins compared to plasma alone (218 proteins) and a 2.63-fold increase relative to the untreated protein corona (681 proteins). Furthermore, we discovered that adding 1000 µg/ml phosphatidylcholine could singularly increase the number of unique proteins within the protein corona (897 proteins). This specific concentration of phosphatidylcholine selectively depleted the four most abundant plasma proteins, including albumin, thus reducing concentration dynamic range of plasma proteome and boosting LC-MS/MS sensitivity for detection of proteins with lower abundance. By employing an optimized data-independent acquisition (DIA) approach, the inclusion of phosphatidylcholine led to the detection of 1436 proteins in plasma. This significant achievement is made utilizing only a single NP type and one small molecule to analyze a single plasma sample, setting a new standard in proteomic depth of the plasma sample. Given the critical role of plasma proteomics in biomarker discovery and disease monitoring, we anticipate widespread adoption of this methodology for identification and clinical translation of proteomic biomarkers into FDA approved diagnostics.