Capillary force-driven reverse-Tesla valve structure for microfluidic bioassays.

Biological assays involve the lysis of biological particles, enzyme reactions, and gene amplification, and require a certain amount of time for completion. Microfluidic chips are regarded as powerful devices for biological assays and in vitro diagnostics; however, they cannot achieve a high mixing efficiency, particularly in some time-consuming biological reactions. Herein, we introduce a microfluidic reverse-Tesla (reTesla) valve structure in which the fluid is affected by vortices and branch flow convergence, resulting in flow retardation and a high degree of mixing. The reTesla is passively operated by a microfluidic capillary force without any pumping facility. Compared with our previously developed micromixers, this innovative pumpless microfluidic chip exhibited high performance, with a mixing efficiency of more than 93%. The versatility of our reTesla chip will play a pivotal role in the study of various biological and chemical reactions.

Increases in Global and East Asian Nitrogen Trifluoride (NF3) Emissions Inferred from Atmospheric Observations.

Nitrogen trifluoride (NF3) is a potent and long-lived greenhouse gas that is widely used in the manufacture of semiconductors, photovoltaic cells, and flat panel displays. Using atmospheric observations from eight monitoring stations from the Advanced Global Atmospheric Gases Experiment (AGAGE) and inverse modeling with a global 3-D atmospheric chemical transport model (GEOS-Chem), we quantify global and regional NF3 emission from 2015 to 2021. We find that global emissions have grown from 1.93 ± 0.58 Gg yr-1 (± one standard deviation) in 2015 to 3.38 ± 0.61 Gg yr-1 in 2021, with an average annual increase of 10% yr-1. The available observations allow us to attribute significant emissions to China (0.93 ± 0.15 Gg yr-1 in 2015 and 1.53 ± 0.20 Gg yr-1 in 2021) and South Korea (0.38 ± 0.07 Gg yr-1 to 0.65 ± 0.10 Gg yr-1). East Asia contributes around 73% of the global NF3 emission increase from 2015 to 2021: approximately 41% of the increase is from emissions from China (with Taiwan included), 19% from South Korea, and 13% from Japan. For Japan, which is the only one of these three countries to submit annual NF3 emissions to UNFCCC, our bottom-up and top-down estimates are higher than reported. With increasing demand for electronics, especially flat panel displays, emissions are expected to further increase in the future.

Cultural Tailoring and Targeting of Messages: A Systematic Literature Review.

Cultural targeting and tailoring are different, yet they remain intertwined in the literature inhibiting theory development and limiting the possibility of determining their effects. This preregistered systematic literature review describes these constructs and provides a framework for cultural tailoring with evidence from a review of 63 studies, published from 2010 to 2020, to characterize the processes, elements, and theories used in the existing literature. The results show that 86% of studies self-defined as cultural tailoring, but coding revealed relatively few tailoring studies (25%) with 31% including both tailoring and targeting elements. Most studies used outreach and consultation as processes for tailoring or targeting with participatory approaches used in a fifth of the studies. Surface-level features of message content were commonly used to tailor or target with deep-cultural-values found in only a quarter of the studies. We argue from theories of communication accommodation and persuasion that cultural tailoring or targeting may provide gains in attention, recall, or source evaluation.

Suppression of neointimal hyperplasia induced by arteriovenous anastomosis and balloon injury in rats by multimeric tumor necrosis factor-related apoptosis-inducing ligand.

Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on anastomosis of the carotid artery and jugular vein- or balloon-induced NH.

PVA Hydrogels Supplemented with PLA Mesh for Tissue Regeneration Scaffold.

This study examined the tensile strength and biocompatibility properties of polyvinyl alcohol (PVA) hydrogel tissue regeneration scaffolds with polylactic acid (PLA) mesh fabric added as reinforcement, with a focus on the impact of heat treatment temperature and the number of layers of the PLA mesh fabric. The hydrogel scaffolds were prepared using a freeze-thaw method to create PVA hydrogel, with the PLA mesh fabric placed inside the hydrogel. The swelling ratio of the PVA/PLA hydrogel scaffolds decreased with increasing layer number and heat treatment temperature of the PLA mesh. The gel strength was highest when five layers of PLA mesh fabric were added, heat-treated at 120 °C, and confirmed to be properly placed inside the hydrogel by SEM images. The MTT assay and DAPI staining using HaCaT cells demonstrated that the cell proliferation was uninterrupted throughout the experimental period, confirming the biocompatibility of the scaffold. Therefore, we confirmed the possibility of using PLA mesh fabric as a reinforcement for PVA hydrogel to improve the strength of scaffolds for tissue regeneration, and we confirmed the potential of PLA mesh fabric as a reinforcement for various biomaterials.

Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-ß Pathway.

Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor ß (TGF-ß) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-ß1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-ß pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-ß1. Finally, TGF-ß1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.

Healthcare Professionals' Learning Needs and Perspectives on Essential Information in Genetic Cancer Care: A Systematic Review.

BACKGROUND: The increased demand for genetic testing and counseling necessitates healthcare professionals (HCPs) to improve their genetic competency through training programs. This systematic review identified HCPs' learning needs and their perspectives on essential information for families with hereditary cancer. METHODS: This review covered studies published from 2013 to 2024 across five databases. Data were analyzed using a content analysis. RESULTS: Thirteen studies involving 332 HCPs were analyzed. Most studies focused on the learning needs of physicians caring for families affected by Hereditary Breast and Ovarian Cancer in North America and Europe. HCPs required training emphasizing practical counseling skills over the basics of genetics. Learning needs varied by profession: physicians needed training in assessing cancer risk and supporting decision-making in risk management; nurses required information on resources and the genetic care system; genetic counselors sought guidance on family communication and planning. Essential information identified for families included risk-reducing strategies, personalized cancer risk assessment, family implications, psychological issues, (cascade) genetic testing, and social concerns. CONCLUSIONS: The findings have implications for the development of training programs for HCPs, emphasizing the need for tailored training based on professions. Future research should explore the needs of HCPs caring for families with diverse hereditary cancers and cultural backgrounds.

Political Affiliation Moderates the Effect of Injunctive Norms on Freedom Threat and Behavioral Intentions: Limiting Indoor Gatherings to Flatten the COVID-19 Curve.

Although many states in the U.S. restricted indoor social gatherings to prevent the spread of COVID-19 in the Fall of 2020, college students' large social gatherings still caused many cluster infections. The present study aimed to explore whether perceived injunctive norms negatively influence behavioral intentions through perceived freedom threat and anger and to probe the ways that different political party affiliations interact with the normative effects. Undergraduate students were recruited to participate in an online survey (n = 170). Counter to predictions, perceived injunctive norms positively influenced Republican participants' behavioral intentions through perceived freedom threat and anger. They reported lower perceived freedom threat as perceived injunctive norms increased, whereas Democrat participants reported higher perceived freedom threat as perceived injunctive norms increased. The findings suggested that injunctive social norms campaigns would be more effective for Republican students to promote COVID-19 preventive behaviors as contrasted with Democrat students.

Psychosocial barriers and facilitators for cascade genetic testing in hereditary breast and ovarian cancer: a scoping review.

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.

Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.

TAT38 and TAT38 mimics potently inhibit adipogenesis by repressing C/EBPα, PPARγ, Pi-PPARγ, and SREBP1 expression.

Antiretroviral therapy-naive people living with HIV possess less fat than people without HIV. Previously, we found that HIV-1 transactivator of transcription (TAT) decreases fat in ob/ob mice. The TAT38 (a.a. 20-57) is important in the inhibition of adipogenesis and contains three functional domains: Cys-ZF domain (a.a. 20-35 TACTNCYCAKCCFQVC), core-domain (a.a. 36-46, FITKALGISYG), and protein transduction domain (PTD)(a.a. 47-57, RAKRRQRRR). Interestingly, the TAT38 region interacts with the Cyclin T1 of the P-TEFb complex, of which expression increases during adipogenesis. The X-ray crystallographic structure of the complex showed that the Cys-ZF and the core domain bind to the Cyclin T1 via hydrophobic interactions. To prepare TAT38 mimics with structural and functional similarities to TAT38, we replaced the core domain with a hydrophobic aliphatic amino acid (from carbon numbers 5 to 8). The TAT38 mimics with 6-hexanoic amino acid (TAT38 Ahx (C6)) and 7-heptanoic amino acid (TAT38 Ahp (C7)) inhibited adipogenesis of 3T3-L1 potently, reduced cellular triglyceride content, and decreased body weight of diet-induced obese (DIO) mice by 10.4-11 % in two weeks. The TAT38 and the TAT38 mimics potently repressed the adipogenic transcription factors genes, C/EBPα, PPARγ, and SREBP1. Also, they inhibit the phosphorylation of PPARγ. The TAT peptides may be promising candidates for development into a drug against obesity or diabetes.

[Imaging Findings of Spinal Metastases with Differential Diagnosis: Focusing on Solitary Spinal Lesion in Older Patients]. / ì „ì´ì„± 척추 ì¢ ì–‘ì˜ 영상 소견: ê³ ë ¹ 환자의 단일병소를 중심으로 한 감별 질환.

If a solitary spinal lesion is found in an older patient, bone metastasis can be primarily considered as the diagnosis. Bone metastasis can occur anywhere, but it mostly occurs in the vertebral body and may sometimes show typical imaging findings, presenting as a single lesion. Therefore, differentiating it from other lesions that mimic bone metastases can be challenging, potentially leading to delayed diagnosis and initiation of primary cancer treatment. This review provides an overview of imaging findings and clinical guidelines for bone metastases and discusses its differences from other diseases that can occur as solitary spinal lesions in older patients.

Inhibition of Biofilm Formation in Cutibacterium acnes, Staphylococcus aureus, and Candida albicans by the Phytopigment Shikonin.

Skin microbiota, such as acne-related Cutibacterium acnes, Staphylococcus aureus, and fungal Candida albicans, can form polymicrobial biofilms with greater antimicrobial tolerance to traditional antimicrobial agents and host immune systems. In this study, the phytopigment shikonin was investigated against single-species and multispecies biofilms under aerobic and anaerobic conditions. Minimum inhibitory concentrations of shikonin were 10 µg/mL against C. acnes, S. aureus, and C. albicans, and at 1-5 µg/mL, shikonin efficiently inhibited single biofilm formation and multispecies biofilm development by these three microbes. Shikonin increased porphyrin production in C. acnes, inhibited cell aggregation and hyphal formation by C. albicans, decreased lipase production, and increased hydrophilicity in S. aureus. In addition, shikonin at 5 or 10 µg/mL repressed the transcription of various biofilm-related genes and virulence-related genes in C. acnes and downregulated the gene expression levels of the quorum-sensing agrA and RNAIII, α-hemolysin hla, and nuclease nuc1 in S. aureus, supporting biofilm inhibition. In addition, shikonin prevented multispecies biofilm development on porcine skin, and the antimicrobial efficacy of shikonin was recapitulated in a mouse infection model, in which it promoted skin regeneration. The study shows that shikonin inhibits multispecies biofilm development by acne-related skin microbes and might be useful for controlling bacterial infections.

Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis.

Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.

Efficacy of acupuncture for whiplash injury: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to establish clinical evidence for acupuncture by analysing data from trials that demonstrated the efficacy of acupuncture for whiplash-associated disorder (WAD) with the following research question: Is acupuncture treatment effective for symptom alleviation in patients with WAD compared with other usual care? DESIGN: A systematic review and meta-analysis. DATA SOURCES: PubMed, Ovid Medline, Embase, The Cochrane Library, China National Knowledge Infrastructure, ScienceOn, KMBASE, Korean Studies Information Service System, Korea Med, Oriental Medicine Advanced Searching Integrated System and Research Information Sharing Service were searched from their inception to 1 October 2023. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) using acupuncture on patients with WAD. The outcomes were the pain visual analogue scale (VAS) score or numerical rating scale score for neck pain, the range of motion (ROM) of the neck, the Neck Disability Index and safety. DATA EXTRACTION AND SYNTHESIS: Two independent researchers analysed and extracted data from the selected literatures. The risk of bias and the quality of evidence were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions and the Grading of Recommendations Assessment, Development, and Evaluation method, respectively. RESULTS: A total of 525 patients with WAD from eight RCTs were included in this study. The meta-analysis revealed that the outcomes showed significant differences in the pain VAS score (standard mean difference (SMD): -0.57 (-0.86 to -0.28), p<0.001) and ROM-extension (SMD: 0.47 (0.05 to 0.89), p=0.03). The risk of bias assessment revealed that four studies published after 2012 (50%, 4 out of 8 studies) showed low bias in most domains. The pain VAS score was graded as having moderate certainty. CONCLUSION: Acupuncture may have clinical value in pain reduction and increasing the ROM for patients with WAD. High-quality RCTs must be conducted to confirm the efficacy of acupuncture in patients with WAD. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021261595.

Use of artificial intelligence in triaging of chest radiographs to reduce radiologists' workload.

OBJECTIVES: To evaluate whether deep learning-based detection algorithms (DLD)-based triaging can reduce outpatient chest radiograph interpretation workload while maintaining noninferior sensitivity. METHODS: This retrospective study included patients who underwent initial chest radiography at the outpatient clinic between June 1 and June 30, 2017. Readers interpreted radiographs with/without a commercially available DLD that detects nine radiologic findings (atelectasis, calcification, cardiomegaly, consolidation, fibrosis, nodules, pneumothorax, pleural effusion, and pneumoperitoneum). The reading order was determined in a randomized, crossover manner. The radiographs were classified into negative and positive examinations. In a 50% worklist reduction scenario, radiographs were sorted in descending order of probability scores: the lower half was regarded as negative exams, while the remaining were read with DLD by radiologists. The primary analysis evaluated noninferiority in sensitivity between radiologists reading all radiographs and simulating a 50% worklist reduction, with the inferiority margin of 5%. The specificities were compared using McNemar's test. RESULTS: The study included 1964 patients (median age [interquartile range], 55 years [40-67 years]). The sensitivity was 82.6% (195 of 236; 95% CI: 77.5%, 87.3%) when readers interpreted all chest radiographs without DLD and 83.5% (197 of 236; 95% CI: 78.8%, 88.1%) in the 50% worklist reduction scenario. The difference in sensitivity was 0.8% (95% CI: - 3.8%, 5.5%), establishing noninferiority of 50% worklist reduction (p = 0.01). The specificity increased from 86.7% (1498 of 1728) to 90.4% (1562 of 1728) (p < 0.001) with DLD-based triage. CONCLUSION: Deep learning-based triaging may substantially reduce workload without lowering sensitivity while improving specificity. CLINICAL RELEVANCE STATEMENT: Substantial workload reduction without lowering sensitivity was feasible using deep learning-based triaging of outpatient chest radiograph; however, the legal responsibility for incorrect diagnoses based on AI-standalone interpretation remains an issue that should be defined before clinical implementation. KEY POINTS: • A 50% workload reduction simulation using deep learning-based detection algorithm maintained noninferior sensitivity while improving specificity. • The CT recommendation rate significantly decreased in the disease-negative patients, whereas it slightly increased in the disease-positive group without statistical significance. • In the exploratory analysis, the noninferiority of sensitivity was maintained until 70% of the workload was reduced; the difference in sensitivity was 0%.

Development and Quality Characteristics of Jangjorim Prepared Using Long-Arm Octopus (Octopus minor) as an Elderly-Friendly Food.

We prepared a long-arm octopus Jangjorim prototype (LOJP) by optimizing the ratio of ingredients for seasoning and establishing heat sterilization parameters. The optimal amounts of purified water (2.9-56.6%, A), starch syrup (0.3-37.8%, B), and soy sauce (25.5-71.5%, C) for the production of seasoning soy sauce were obtained using response surface analysis. The LOJP was prepared by combining A, B, and C under the optimal conditions and evaluated for consumer preferences and physicochemical, nutritional, and microbiological properties and compared with Korea's legal management standards for geriatric nutrition. The hardness of the LOJP produced using the optimal mixing ratio of purified water (51.2%, 154.0 g), starch syrup (29.3%, 308.0 g), and soy sauce (19.5%, 256.9 g) was 36.7 × 1000 N/m2. This value was lower than the hardness of raw octopus (2153.6 × 1000 N/m2) by 2116.9 × 1000 N/m2. It received the highest score (8.7) in the preference evaluation of older consumers. The LOJP was classified as level 2, allowing consumption through the gums of elderly consumers per Korea's food standards for the elderly. The LOJP was the product highly preferred by elderly consumers with chewing disorders due to its ease of intake and nutritional content.

Cytochrome P450 Family 46 Subfamily A Member 1 Promotes the Progression of Colorectal Cancer by Inducing Tumor Cell Proliferation and Angiogenesis.

BACKGROUND/AIM: Cytochrome P450 family 46 subfamily A member 1 (CYP46A1) has been implicated in the development and progression of various cancers. This study aimed to analyze the expression of CYP46A1, examining its relationship with oncogenic behaviors, and determining its prognostic implications in colorectal cancer (CRC). MATERIALS AND METHODS: A total of 225 patients with CRC who underwent curative surgical resection were examined using paraffin-embedded tissue blocks and subjected to tumor-specific survival analysis. The expression of CYP46A1 was assessed in CRC tissues through reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. The CRC cells' apoptosis, proliferation, angiogenesis, and lymphangiogenesis were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays, alongside immunohistochemical staining for Ki-67, CD34, and D2-40 antibodies. RESULTS: CYP46A1 expression was found to be up-regulated in CRC tissues compared to normal colorectal mucosa. Such expression was significantly associated with advanced stage, deeper tumor invasion, lymph node metastasis, distant metastasis, and decreased survival. Furthermore, the mean Ki-67 labeling index and microvessel density values in CYP46A1-positive tumors were significantly elevated compared to CYP46A1-negative tumors. However, there was no discernible correlation between CYP46A1 expression and either the apoptotic index or lymphatic vessel density value. CONCLUSION: CYP46A1 promotes CRC progression, specifically through the induction of tumor cell proliferation and angiogenesis. The insights provided may hold potential implications for future therapeutic interventions targeting CYP46A1.