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A series of x%Ho3+, 5 %Tm3+, y%Yb3+:Bi2WO6 (x = 0, 0.5, 1, 3, 5; y = 0.5, 1, 3) luminescent materials was prepared using a high-temperature solid-phase method. The microstructure, up-conversion luminescence, and temperature sensing properties of the synthesized powders were analyzed. X-ray diffraction patterns revealed that doping with Ho3+, Tm3+, and Yb3+ ions at certain concentrations did not affect the orthorhombic crystal structure of the Bi2WO6 host. Scanning electron microscopy revealed that the morphology of the sample consisted of lumpy particles with a particle size range of 1-5 µm and agglomeration. SEM mapping and energy-dispersive X-ray spectroscopy analyses revealed that each element was relatively uniformly distributed on the particle surface. Under 980 nm excitation (380 mW), the strongest luminescence of the sample was obtained when both Ho3+ and Yb3+ doping concentrations were 1 %. Compared with the luminescence of the 5 %Tm3+ and 1 %Yb3+:Bi2WO6 sample, with increasing Ho3+ concentrations, the luminescence intensity of Tm3+ was first enhanced and subsequently weakened, whereas the luminescence of Ho3+ was significantly weakened, which indicates the positive energy transfer from Ho3+ â†’ Tm3+. At 980 nm (80-380 mW), for the 1 %Ho3+, 5 %Tm3+, and 1 %Yb3+:Bi2WO6 sample, the 538 nm, 545 nm, 660 nm, and 804 nm emission peaks originated from the two-photon absorption. FIR660 nm/804 nm, FIR545 nm/804 nm, and FIR538 nm/804 nm were used to characterize the temperature and corresponded to temperature sensitivities Sr of 0.0046 K-1, 0.022 K-1 and 0.024 K-1 at 573 K, respectively. At 498 K, the minimum temperature resolution δT values were 0.03384 K, 0.03203 K and 0.04373 K. When the temperature increased from 298 K to 573 K, the powder sample luminescence gradually shifted from the yellow-green region to the red region. The results of environmental discoloration and thermochromic performance tests indicate that this sample has potential application in optical anti-counterfeiting. FIR804 nm /660 nm and FIR804 nm /538 nm were obtained for the 40 NTU turbidity suspension under identical excitation conditions. At 298 K, for the 40 NTU turbidity sample, the maximum Sr values were 0.0197 K-1 and 0.0405 K-1; at 340 K, the minimum temperature resolutions δT values were 0.54037 K and 0.66237 K. When the temperature decreased from 340 K to 298 K, the luminescence of the 40 NTU suspension samples gradually shifted from the yellow region to the green region.

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Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143). The anticancer effects of these Ex were investigated in vitro using the human colorectal cell line HCT116 and in vivo using colorectal cancer mouse xenograft models. In the in vivo assessment, administration of TM4SF5-targeting Ex[miR-143], referred to as tEx[miR-143] herein, resulted in the smallest tumor size, the lowest tumor growth rate, and the lightest excised tumors compared to other treatments (p < 0.05). It also led to the decreased expression of MACC-1 and anti-apoptotic markers MCL-1 and Bcl-xL while inducing the highest expression of pro-apoptotic markers BAX and BIM. These results were consistent with in vitro findings, where t Ex[miR-143] demonstrated the highest inhibition of HCT116 cell migration and invasion. These findings highlight the potential of tEx[miR-143] as an effective therapeutic strategy for colorectal cancer, demonstrating promising results in both targetability and anti-tumor effects in vitro and in vivo, warranting further investigation in clinical settings.

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In this manuscript, a novel presenilin-2 (PSEN2) mutation, Val226Ala, was found in a 59-year-old Korean patient who exhibited rapid progressive memory dysfunction and hallucinations six months prior to her first visit to the hospital. Her Magnetic Resonance Imaging (MRI) showed brain atrophy, and both amyloid positron emission tomography (PET) and multimer detection system-oligomeric amyloid-beta (Aß) results were positive. The patient was diagnosed with early onset Alzheimer's disease. The whole-exome analysis revealed a new PSEN2 Val226Ala mutation with heterozygosity in the 5th transmembrane domain of the PSEN2 protein near the lumen region. Analyses of the structural prediction suggested structural changes in the helix, specifically a loss of a hydrogen bond between Val226 and Gln229, which may lead to elevated helix motion. Multiple PSEN2 mutations were reported in PSEN2 transmembrane-5 (TM5), such as Tyr231Cys, Ile235Phe, Ala237Val, Leu238Phe, Leu238Pro, and Met239Thr, highlighting the dynamic importance of the 5th transmembrane domain of PSEN2. Mutations in TM5 may alter the access tunnel of the Aß substrate in the membrane to the gamma-secretase active site, indicating a possible influence on enzyme function that increases Aß production. Interestingly, the current patient with the Val226Ala mutation presented with a combination of hallucinations and memory dysfunction. Although the causal mechanisms of hallucinations in AD remain unclear, it is possible that PSEN2 interacts with other disease risk factors, including Notch Receptor 3 (NOTCH3) or Glucosylceramidase Beta-1 (GBA) variants, enhancing the occurrence of hallucinations. In conclusion, the direct or indirect role of PSEN2 Val226Ala in AD onset cannot be ruled out.

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Background: Pancreatic adenocarcinoma (PAAD) is a highly lethal malignancy characterized by aggressive growth and poor prognosis. Understanding the molecular mechanisms underlying PAAD is crucial for developing effective therapies. This study aimed to explore the role of TM4SF1 and other key genes in PAAD progression, their prognostic implications, and therapeutic opportunities. Methods: Differential gene expression analysis was performed using PAAD and normal tissue samples to identify upregulated genes, with TM4SF1 emerging as significantly elevated in PAAD. Functional enrichment analysis elucidated associated signaling pathways. A prognostic model comprising BPIFB4, PLEKHN1, CPTP, DVL1, and DDR1 was developed using least absolute shrinkage and selection operator (LASSO) regression and validated in an independent cohort. Genetic mutation analysis provided insights into the functional significance of identified genes. Pharmacogenomic analysis examined associations between gene expression and drug sensitivity. Experimental validation included quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses to confirm gene expression patterns and protein levels. Results: Lower TM4SF1 expression correlated with enhanced anti-tumor immune activity in PAAD, suggesting a complex interplay between genetic expression and immune response. The prognostic model showed robust associations with patient survival outcomes, validated across diverse patient cohorts. Genetic mutation analysis highlighted potential therapeutic targets. Pharmacogenomic analysis revealed correlations between gene expression profiles and drug responsiveness, suggesting personalized treatment strategies. Experimental validation confirmed elevated TM4SF1 levels in tumor tissues and demonstrated its role in promoting cancer cell proliferation and colony formation. Conclusions: This study advances understanding of the molecular landscape of PAAD, emphasizing TM4SF1 as a key regulator and potential therapeutic target. The integration of genetic expression, immune response dynamics, and pharmacogenomics offers a multifaceted approach to personalized treatment strategies for PAAD, paving the way for improved patient outcomes and novel therapeutic interventions. Further research is warranted to elucidate the clinical utility of targeting TM4SF1 and other identified genes in PAAD management.

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Nutrient metabolism is regulated by several factors. Social determinants of health with or without genetics are the primary regulator of metabolism, and an unhealthy lifestyle affects all modulators and mediators, leading to the adaptation and finally to the exhaustion of cellular functions. Hepatic steatosis is defined by presence of fat in more than 5% of hepatocytes. In hepatocytes, fat is stored as triglycerides in lipid droplet. Hepatic steatosis results from a combination of multiple intracellular processes. In a healthy individual nutrient metabolism is regulated at several steps. It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component. Several hormones, peptides, and genes have been described that participate in nutrient metabolism. Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP. As of now several publications have revealed very intricate regulation of nutrient metabolism, where most of the regulatory factors are tied to each other bidirectionally, making it difficult to comprehend chronological sequence of events. Insulin hormone is the primary regulator of all nutrients' metabolism both in prandial and fasting states. Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes; metabolic, inflammation and repair, and cell growth and regeneration. Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands, adiponectin, leptin, and adiponutrin. Insulin hormone has direct effect on these final modulators. Whereas blood glucose level, serum lipids, incretin hormones, bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle. The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) that help us understand the disease natural course, risk stratification, role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine. PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states; MASLD, cardiovascular disease and cancer. More than 1000 publications including original research and review papers were reviewed.

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INTRODUCTION: Revision hip arthroplasty in the presence of complex acetabular deficiencies is challenging. Cement, allograft, reconstruction rings and porous trabecular metal now provide versatile options for acetabular fixation and restoration of acetabular offset. We compare acetabular impaction bone grafting (AIBG) and trabecular metal (TM) cups at long-term follow-up. METHODS: 53 patients who underwent revision hip arthroplasty were retrospectively reviewed from local joint registry data. 36 patients were revised using AIBG and 17 with TM. Median clinical follow-up was 9.57 (2.46-18.72) years and 9.65 (7.22-12.46) years, respectively. 82% of the TM group and 63% of the AIBG group were ⩾ Paprosky 2C. Re-revision was considered failure. Radiographs demonstrating 5 mm of femoral head migration and 5° of acetabular component inclination change were considered loose. RESULTS: Patients receiving AIBG were younger (68 vs. 74 years) with a longer interval from initial arthroplasty to revision (17 vs. 13 years). Revisions in both groups were indicated most commonly for failed cementing (AIBG 88.9% vs. TM 70.5%). No TM reconstructions underwent re-revision, with only 1 failing at 6.3 years, compared with 9 AIBG re-revisions. When revising for sepsis, 33% of AIBG revisions failed. CONCLUSIONS: AIBG demonstrated high failure rates at long-term follow-up when compared to TM constructs. We recommend the use of AIBG in small cavitary defects only. We strongly advise against its use in the setting of significant bony defects and for prosthetic joint infection.

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RNase H-dependent antisense oligonucleotides (gapmer ASOs) represent a class of nucleic acid therapeutics that bind to target RNA to facilitate RNase H-mediated RNA cleavage, thereby regulating the expression of disease-associated proteins. Integrating artificial nucleic acids into gapmer ASOs enhances their therapeutic efficacy. Among these, amido-bridged nucleic acid (AmNA) stands out for its potential to confer high affinity and stability to ASOs. However, a significant challenge in the design of gapmer ASOs incorporating artificial nucleic acids, such as AmNA, is the accurate prediction of their melting temperature (T m ) values. The T m is a critical parameter for designing effective gapmer ASOs to ensure proper functioning. However, predicting accurate T m values for oligonucleotides containing artificial nucleic acids remains problematic. We developed a T m prediction model using a library of AmNA-containing ASOs to address this issue. We measured the T m values of 157 oligonucleotides through differential scanning calorimetry, enabling the construction of an accurate prediction model. Additionally, molecular dynamics simulations were used to elucidate the molecular mechanisms by which AmNA modifications elevate T m , thereby informing the design strategies of gapmer ASOs.

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Chichijima Island, part of the Ogasawara Islands in Tokyo, is a remote island with a population of approximately 2,000, served by a few resident general practitioners (GPs). This case report discusses the application of teleophthalmology in managing pediatric ocular trauma on this remote island. A pediatric patient sustained an ocular injury from a badminton shuttlecock and was initially examined by a resident GP using a recordable slit-lamp microscope. The ocular images were transmitted to a mainland ophthalmologist through a telemedicine system. The specialist provided remote consultation and recommended further examination and treatment, leading to the patient's transfer to the mainland. The successful management of this case underscores the critical role of telemedicine in enhancing healthcare delivery in isolated regions. With advancements in medical technology, teleophthalmology is expected to become increasingly vital in providing specialized care in remote and underserved areas. The case highlights the importance of telemedicine in improving access to specialized medical expertise, ensuring timely and effective patient care, and potentially reducing the need for patient transfers to more equipped healthcare facilities.

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Accurately and quickly estimating the soil organic carbon (SOC) content is crucial in the monitoring of global carbon. Environmental variables play a significant role in improving the accuracy of the SOC content estimation model. This study focuses on modeling methodologies and environmental variables, which significantly influence the SOC content estimation model. The modeling methods used in this research comprise multiple linear regression (MLR), partial least squares regression (PLSR), random forest, and support vector machines (SVM). The analyzed environmental variables include terrain, climate, soil, and vegetation cover factors. The original spectral reflectance (OSR) of Landsat 5 TM images and the spectral reflectivity after the derivative processing were combined with the above environmental variables to estimate SOC content. The results showed that: (1) The SOC content can be efficiently estimated using the OSR of Landsat 5 TM, however, the derived processing method cannot significantly improve the estimation accuracy. (2) Environmental variables can effectively improve the accuracy of SOC content estimation, with climate and soil factors producing the most significant improvements. (3) Machine learning modeling methods provide better estimation accuracy than MLR and PLSR, especially the SVM model which has the highest accuracy. According to our observations, the best estimation model in the study area was the "OSR + SVM" model (R2 = 0.9590, RMSE = 13.9887, MAE = 10.8075), which considered four environmental factors. This study highlights the significance of environmental variables in monitoring SOC content, offering insights for more precise future SOC assessments. It also provides crucial data support for soil health monitoring and sustainable agricultural development in the study area.

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Background This study aimed to investigate the rationale, barriers, and facilitators of teleretinal camera implementation in primary care and endocrinology clinics for diabetic retinopathy (DR) screening across University of California (UC) health systems utilizing the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework. Methodology Institutional representatives from UC Los Angeles, San Diego, San Francisco, and Davis participated in a series of focus group meetings to elicit implementation facilitators and barriers for teleophthalmology programs within their campuses. Site representatives also completed a survey regarding their program's performance over the calendar year 2022 in the following areas: DR screening camera sites, payment sources and coding, screening workflows including clinical, information technology (IT), reading, results, pathologic findings, and follow-up, including patient outreach for abnormal results. Focus group and survey results were mapped to the EPIS framework to gain insights into the implementation process of these programs and identify areas for optimization. Results Four UC campuses with 20 active camera sites screened 7,450 patients in the calendar year 2022. The average DR screening rate across the four campuses was 55%. Variations between sources of payment, turn-around time, image-grading structure, image-report characteristics, IT infrastructure, and patient outreach strategies were identified between sites. Closing gaps in IT integration between data systems, ensuring the financial sustainability of the program, and optimizing patient outreach remain primary challenges across sites and serve as good opportunities for cross-institutional learning. Conclusions Despite the potential for long-term cost savings and improving access to care, numerous obstacles continue to hinder the widespread implementation of teleretinal DR screening. Implementation science approaches can identify strategies for addressing these challenges and optimizing implementation.

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Myelodysplastic neoplasms (MDS) are clonal disorders of the myeloid lineage leading to peripheral blood cytopenias. Dysregulation of innate immunity is hypothesized to be a potent driver of MDS. A recent study revealed increased thrombomodulin (TM) expression on classical monocytes in MDS, which was associated with prolonged survival. TM is a receptor with immunoregulatory capacities, however, its exact role in MDS development remains to be elucidated. In this review we focus on normal monocyte biology and report on the involvement of monocytes in myeloid disease entities with a special focus on MDS. Furthermore, we delve into the current knowledge on TM and its function in monocytes in health and disease and explore the role of TM-expressing monocytes as driver, supporter or epiphenomenon in the MDS bone marrow environment.

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BACKGROUND: Classical opioids are effective analgesics but carry various side effects, necessitating safer alternatives. Truncated six-transmembrane mu opioid receptors (6TM-µORs) mediate potent analgesia with fewer side effects and are a promising therapeutic target. However, few ligands known selectively target 6TM-µORs. Moreover, endogenous chaperones are believed essential for 6TM-µOR ligand binding and function. PURPOSE: To identify a 6TM-µOR selective agonist and elucidate requisite endogenous chaperones. METHODS: Virtual screening was used to identify promising selective 6TM-µOR agonists from traditional Chinese medicines. The role of 6TM-µOR in Exoticin analgesia was validated in loss- and gain-of-function models. APEX2 proteomics profiled proximal proteins under Exoticin or IBNtxA. Interactions were further characterized in vivo and in vitro. RESULTS: Exoticin was shortlisted for its selective binding to 6TM-µOR and ability to induce 6TM-µOR-dependent signal transduction. Exoticin analgesia was sensitive to ß-FNA and absent in E11 KO mice, but restored in mice infected with AAV-µOR1G. Slc3a2, Lrrc59, and Ppp1cb co-interacted with 6TM-µOR1G and were equally essential for Exoticin binding and 6TM-µOR1G activity. CONCLUSION: Exoticin is a promising selective agonist of 6TM µ opioid receptors with broad-spectrum analgesic efficacy but few side effects. Slc3a2, Lrrc59, Ppp1cb are endogenous chaperones essential for 6TM-µOR ligand binding and function.

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The sous-vide technique is increasingly used to improve the quality of poultry meat; the study aimed to compare the quality of traditional and sous-vide marinated (SVM) duck drumsticks by analyzing the sensory-related, nutritional, storage-related, and in vitro digestive-related quality of duck meat. The results showed that the sensory quality scores of color, odor, and appearance, L* and a* values of duck drumsticks in SVM group were significantly increased compared with the traditional marinated (TM) group (t-test, p < 0.05, the same below), and the b* values on the outside and inside of duck drumsticks were decreased by 22.47% and 38.04%, respectively. Compared with TM group, hardness, springiness, chewiness, adhesion, cohesion, and resilience of duck drumsticks in SVM group decreased by 43.32%, 29.52%, 65.08%, 62.35%, 20.23%, and 30.33%, respectively. The moisture content and total fat content of duck drumsticks in SVM group were significantly higher than those in TM group (p < 0.05), and the protein loss, total volatile basic nitrogen, and thiobarbituric acid reactive substances values were decreased by 61.4%, 25.86%, and 20.45%, respectively. The results of in vitro digestion experiments showed that the content of free sulfhydryl groups of duck drumsticks in SVM group was significantly increased (p < 0.05), and the contents of Schiff base and carbonyl groups were significantly decreased compared with the TM group (p < 0.05). In conclusion, the SVM technology could significantly improve the sensory-related qualities, reduce the loss of nutrients, and improve the storage-related qualities of duck drumsticks. This study provided theoretical reference for the high-value application of SVM technology in duck meat.

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Recent advances in the genetics of metabolic dysfunction-associated steatotic liver disease (MASLD) are gradually revealing the mechanisms underlying the heterogeneity of the disease and have shown promising results in patient stratification. Genetic characterization of the disease has been rapidly developed using genome-wide association studies, exome-wide association studies, phenome-wide association studies, and whole exome sequencing. These advances have been powered by the increase in computational power, the development of new analytical algorithms, including some based on artificial intelligence, and the recruitment of large and well-phenotyped cohorts. This review presents an update on genetic studies that emphasize new biological insights from next-generation sequencing approaches. Additionally, we discuss innovative methods for discovering new genetic loci for MASLD, including rare variants. To comprehensively manage MASLD, it is important to stratify risks. Therefore, we present an update on phenome-wide association study associations, including extreme phenotypes. Additionally, we discuss whether polygenic risk scores and targeted sequencing are ready for clinical use. With particular focus on precision medicine, we introduce concepts such as the interplay between genetics and the environment in modulating genetic risk with lifestyle or standard therapies. A special chapter is dedicated to gene-based therapeutics. The limitations of approved pharmacological approaches are discussed, and the potential of gene-related mechanisms in therapeutic development is reviewed, including the decision to perform genetic testing in patients with MASLD.

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Fumonisin B1 (FB1), a mycotoxin produced by Fusarium species, is prevalent in crops and animal feed, posing significant health risks to livestock and humans. FB1 induces oxidative stress in Sertoli cells, destroys testicular structure, and affects spermatogenesis. However, methods to mitigate the reproductive toxicity of FB1 in testes remain unknown. Quercetin, a natural flavonoid antioxidant, may offer protective benefits. This study investigated the protective effects and mechanisms of quercetin against FB1-induced reproductive toxicity in TM4 cells (a Sertoli cell line). The results indicated that 40 µM quercetin improved cell viability, reduced apoptosis, and preserved cell functions. Quercetin also decreased reactive oxygen species (ROS) levels in TM4 cells exposed to FB1, enhanced the expression of antioxidant genes, and improved mitochondrial membrane potential. Compared with FB1 alone, the combination of quercetin and FB1 increased ATP levels, as well as pyruvate and lactic acid, the key glycolysis products. Furthermore, this combination elevated the mRNA and protein expression of glycolysis-related genes, including glucose-6-phosphate isomerase 1 (Gpi1), hexokinase 2 (Hk2), aldolase (Aldoa), pyruvate kinase, muscle (Pkm), lactate dehydrogenase A (Ldha) and phosphofructokinase, liver, B-type (Pfkl). Quercetin also boosted the activity of PKM and LDHA, two crucial glycolytic enzymes. In summary, quercetin mitigates FB1-induced toxicity in TM4 cells by reducing ROS levels and enhancing glycolysis. This study offers new insights into preventing and treating FB1-induced toxic damage to the male reproductive system and highlights the potential application of quercetin.

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Psychiatric disorders are highly inheritable, and most psychiatric disorders exhibit genetic overlap. Recent studies associated the 3q29 recurrent deletion with schizophrenia (SCZ) and autism spectrum disorder (ASD). In this study, we investigated the association of genes in the 3q29 region with SCZ and ASD. TM4SF19 and PAK2 were chosen as candidate genes for this study based on evidence from previous research. We sequenced TM4SF19 and PAK2 in 437 SCZ cases, 187 ASD cases and 524 controls in the Japanese population. Through targeted sequencing, we identified 6 missense variants among the cases (ASD & SCZ), 3 missense variants among controls, and 1 variant common to both cases and controls; however, no loss-of-function variants were identified. Fisher's exact test showed a significant association of variants in TM4SF19 among cases (p=0.0160). These results suggest TM4SF19 variants affect the etiology of SCZ and ASD in the Japanese population. Further research examining 3q29 region genes and their association with SCZ and ASD is thus needed.

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Tumor self-seeding is a process whereby circulating tumor cells (CTCs) recolonize the primary tumor, which promotes tumor growth, angiogenesis, and invasion. However, the detailed nature and functions of tumor self-seeded cells (TSCs) have not been well defined due to challenges in tracking and isolating TSCs. Here, we report an accurate animal model using photoconvertible tagging to recapitulate the spontaneous process of tumor self-seeding and identify TSCs as a subpopulation of primary tumor cells with enhanced invasiveness and survival. We demonstrate transmembrane-4-L-six-family-1 (TM4SF1) as a marker of TSCs, which promotes migration, invasion, and anchorage-independent survival in cancer cells. By analyzing single-cell RNA sequencing datasets, we identify a potential TSC population with a metastatic profile in patients with cancer, which is detectable in early-stage disease and expands during cancer progression. In summary, we establish a framework to study TSCs and identify emerging cell targets with diagnostic, prognostic, or therapeutic potential in cancers.

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Background/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury of HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell-membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions: The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

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Fatty acid profiles are crucial for the functionality and viability of lactobacilli used in food applications. Tween 80™, a common culture media additive, is known to influence bacterial growth and composition. This study investigated how Tween 80™ supplementation impacts the fatty acid profiles of six mesophilic lactobacilli strains (Lacticaseibacillus spp., Limosilactobacillus spp., Lactiplantibacillus plantarum). Analysis of eleven strains revealed 29 distinct fatty acids. Tween 80™ supplementation significantly altered their fatty acid composition. Notably, there was a shift towards saturated fatty acids and changes within the unsaturated fatty acid profile. While some unsaturated fatty acids decreased, there was a concurrent rise in cyclic derivatives like lactobacillic acid (derived from vaccenic acid) and dihydrosterculic acid (derived from oleic acid). This suggests that despite the presence of Tween 80™ as an oleic acid source, lactobacilli prioritize the synthesis of these cyclic derivatives from precursor unsaturated fatty acids. Myristic acid and dihydrosterculic acid levels varied across strains. Interestingly, palmitic acid content increased, potentially reflecting enhanced incorporation of oleic acid from Tween 80™ into membranes. Conversely, cis-vaccenic acid levels consistently decreased across all strains. The observed fatty acid profiles differed from previous studies, likely due to a combination of factors including strain-specific variations and growth condition differences (media type, temperature, harvesting point). However, this study highlights the consistent impact of Tween 80™ on the fatty acid composition of lactobacilli, regardless of these variations. In conclusion, Tween 80™ significantly alters fatty acid profiles, influencing saturation levels and specific fatty acid proportions. This work reveals key factors, including stimulated synthesis of lactobacillic acid, competition for oleic acid incorporation, and strain-specific responses to myristic and dihydrosterculic acids. The consistent reduction in cis-vaccenic acid and the presence of cyclic derivatives warrant further investigation to elucidate their roles in response to Tween 80™ supplementation.

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