Peptide-Directed Synthesis of Aggregation-Induced Emission Enhancement-Active Gold Nanoclusters for Single- and Two-Photon Imaging of Lysosome and Expressed αvß3 Integrin Receptors.

This study explores the synthesis and characterization of aggregation-induced emission enhancement (AIEE)-active gold nanoclusters (AuNCs), focusing on their near-infrared luminescence properties and potential applications in biological imaging. These AIEE-active AuNCs were synthesized via the NaBH4-mediated reduction of HAuCl4 in the presence of peptides. We systematically investigated the influence of the peptide sequence on the optical features of the AuNCs, highlighting the role of glutamic acid in enhancing their quantum yield (QY). Among the synthesized peptide-stabilized AuNCs, EECEE-stabilized AuNCs exhibited the maximum QY and a pronounced AIEE effect at pH 5.0, making them suitable for the luminescence imaging of intracellular lysosomes. The AIEE characteristic of the EECEE-stabilized AuNCs was demonstrated through examinations using transmission electron microscopy, dynamic light scattering, zeta potential analysis, and single-particle imaging. The formation of the EECEE-stabilized AuNCs was confirmed by size-exclusion chromatography and mass spectrometry. Spectroscopic and electrochemical examinations uncover the formation process of EECEE-stabilized AuNCs, comprising EECEE-mediated reduction, NaBH4-induced nucleation, complex aggregation, and subsequent cluster growth. Furthermore, we demonstrated the utility of these AuNCs as luminescent probes for intracellular lysosomal imaging, leveraging their pH-responsive AIEE behavior. Additionally, cyclic arginylglycylaspartic acid (RGD)-modified AIEE dots, derived from cyclic RGD-linked peptide-induced aggregation of EECEE-stabilized AuNCs, were developed for single- and two-photon luminescence imaging of αvß3 integrin receptor-positive cancer cells.

Enhancing Zinc Electrode Stability Through Pre-Desolvation and Accelerated Charge Transfer via a Polyimide Interface for Zinc-Ion Batteries.

Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H2O)6 2+ to Zn(H2O)4 2+ before approaching the zinc surface. The exposed zinc ion in Zn(H2O)4 2+ provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21 kJ mol-1. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200 h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20 mA cm-2, 10 mAh cm-2) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.

Effects of occupational exposure to metal fume PM2.5 on lung function and biomarkers among shipyard workers: a 3-year prospective cohort study.

OBJECTIVE: This study investigates the associations of α1-antitrypsin, inter-α-trypsin inhibitor heavy chain (ITIH4), and 8-isoprostane with lung function in shipyard workers exposed to occupational metal fume fine particulate matter (PM2.5), which is known to be associated with adverse respiratory outcomes. METHODS: A 3-year follow-up study was conducted on 180 shipyard workers with 262 measurements. Personal exposure to welding fume PM2.5 was collected for an 8-h working day. Pre-exposure, post-exposure, and delta (∆) levels of α1-antitrypsin, ITIH4, and 8-isoprostane were determined in urine using enzyme-linked immunosorbent assays. Post-exposure urinary metals were sampled at the beginning of the next working day and analyzed by inductively coupled plasma-mass spectrometry. Lung function measurements were also conducted the next working day for post-exposure. RESULTS: An IQR increase in PM2.5 was associated with decreases of 2.157% in FEV1, 2.806% in PEF, 4.328% in FEF25%, 5.047% in FEF50%, and 7.205% in FEF75%. An IQR increase in PM2.5 led to increases of 42.155 µg/g in ∆α1-antitrypsin and 16.273 µg/g in ∆ITIH4. Notably, IQR increases in various urinary metals were associated with increases in specific biomarkers, such as post-urinary α1-antitrypsin and ITIH4. Moreover, increases in ∆ α1-antitrypsin and ∆ITIH4 were associated with decreases in FEV1/FVC by 0.008% and 0.020%, respectively, and an increase in ∆8-isoprostane resulted in a 1.538% decline in FVC. CONCLUSION: Our study suggests that urinary α1-antitrypsin and ITIH4 could indicate early lung function decline in shipyard workers exposed to metal fume PM2.5, underscoring the need for better safety and health monitoring to reduce respiratory risks.

Understanding Healthcare Providers' Care for Patients with Medications Treating Opioid Use Disorder in the Emergency Department: A Scoping Review.

BACKGROUND: There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder (MOUD). METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory. RESULTS: The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices. CONCLUSIONS: Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.

Integrating In Silico and In Vitro Approaches to Identify Natural Peptides with Selective Cytotoxicity against Cancer Cells.

Anticancer peptides (ACPs) are bioactive compounds known for their selective cytotoxicity against tumor cells via various mechanisms. Recent studies have demonstrated that in silico machine learning methods are effective in predicting peptides with anticancer activity. In this study, we collected and analyzed over a thousand experimentally verified ACPs, specifically targeting peptides derived from natural sources. We developed a precise prediction model based on their sequence and structural features, and the model's evaluation results suggest its strong predictive ability for anticancer activity. To enhance reliability, we integrated the results of this model with those from other available methods. In total, we identified 176 potential ACPs, some of which were synthesized and further evaluated using the MTT colorimetric assay. All of these putative ACPs exhibited significant anticancer effects and selective cytotoxicity against specific tumor cells. In summary, we present a strategy for identifying and characterizing natural peptides with selective cytotoxicity against cancer cells, which could serve as novel therapeutic agents. Our prediction model can effectively screen new molecules for potential anticancer activity, and the results from in vitro experiments provide compelling evidence of the candidates' anticancer effects and selective cytotoxicity.

jYCaMP: an optimized calcium indicator for two-photon imaging at fiber laser wavelengths.

Femtosecond lasers at fixed wavelengths above 1,000 nm are powerful, stable and inexpensive, making them promising sources for two-photon microscopy. Biosensors optimized for these wavelengths are needed for both next-generation microscopes and affordable turn-key systems. Here we report jYCaMP1, a yellow variant of the calcium indicator jGCaMP7 that outperforms its parent in mice and flies at excitation wavelengths above 1,000 nm and enables improved two-color calcium imaging with red fluorescent protein-based indicators.

Downregulation of cellular retinoic acid binding protein 1 fosters epithelial-mesenchymal transition in thyroid cancer.

Cellular retinoic acid binding protein 1 (CRABP1) participates in the regulation of retinoid signaling. Previous studies showed conflicting results regarding the role of CRABP1 in tumor biology, including protumorigenic and tumor-suppressive effects in different types of cancer. Our bioinformatics analyses suggested that CRABP1 expression was downregulated in thyroid cancer. Ectopic expression of CRABP1 in thyroid cancer cells suppressed migratory and invasive activity without affecting cell growth or cell cycle distribution. In transformed normal thyroid follicular epithelial cells, silencing of CRABP1 expression increased invasiveness. Additionally, CRABP1 overexpression was associated with downregulation of the mesenchymal phenotype. Kinase phosphorylation profiling indicated that CRABP1 overexpression was accompanied by a decrease in phosphorylation of epidermal growth factor (EGF) receptor and downstream phosphorylation of Akt, STAT3, and FAK, which were reversed by exogenous EGF treatment. Immunohistochemical analysis of our tissue microarrays revealed an inverse association between CRABP1 expression and disease stage of differentiated thyroid cancer. Taken together, our results suggest that CRABP1 expression is aberrantly lost in thyroid cancer, and this downregulation promotes the epithelial-mesenchymal transition at least partly through modulating EGF receptor signaling.

Antiviral therapy reduces hepatocellular carcinoma through suppressing hepatitis B virus replication may improve ER stress, mitochondrial and metabolic dysfunctions and decrease p62 in hybridized mice with single HBV transgene and miR-122.

Hepatitis B virus (HBV) hijacks autophagy for its replication. Nucleos(t)ide analogs (NUCs) treatment suppressed HBV replication and reduced hepatocellular carcinoma (HCC) incidence. However, the use of NUCs in chronic hepatitis B (CHB) patients with normal or minimally elevated serum alanine aminotransferase (ALT) levels is still debated. Animal models are crucial for studying the unanswered issue and evaluating new therapies. MicroRNA-122 (miR-122), which regulates fatty acid and cholesterol metabolism, is downregulated during hepatitis and HCC progression. The reciprocal inhibition of miR-122 with HBV highlights its role in HCC development as a tumor suppressor. By crossbreeding HBV-transgenic mice with miR-122 knockout mice, we generated a hybrid mouse model with a high incidence of HCC up to 89% and normal ALT levels before HCC. The model exhibited early-onset hepatic steatosis, progressive liver fibrosis, and impaired late-phase autophagy. Metabolomics and microarray analysis identified metabolic signatures, including dysregulation of lipid metabolism, inflammation, genomic instability, the Warburg effect, reduced TCA cycle flux, energy deficiency, and impaired free radical scavenging. Antiviral treatment reduced HCC incidence in hybrid mice by approximately 30-35% compared to untreated mice. This effect was linked to the activation of ER stress-responsive transcription factor ATF4, clearance of autophagosome cargo p62, and suppression of the CHOP-mediated apoptosis pathway. In summary, this study suggests that despite minimal ALT elevation, HBV replication can lead to liver injury. Endoplasmic reticulum stress, reduced miR-122 levels, mitochondrial and metabolic dysfunctions, blocking protective autophagy resulting in p62 accumulation, apoptosis, fibrosis, and HCC. Antiviral may improve the above-mentioned pathogenesis through HBV suppression.

Ultrastrong coupling in Super Yellow polymer microcavities and development of highly efficient polariton light-emitting diodes and light-emitting transistors.

We present detailed studies on exciton-photon coupling and polariton emission based on a poly(1,4-phenylenevinylene) copolymer, Super Yellow (SY), in a series of optical microcavities and optoelectronic devices, including light-emitting diode (LED) and light-emitting transistor (LET). We show that sufficiently thick SY microcavities can generate ultrastrong coupling with Rabi splitting energies exceeding 1 eV and exhibit spectrally narrow, nearly angle-independent photoluminescence following lower polariton (LP) mode dispersion. When the microcavity is designed with matched LP low-energy state and exciton emission peak for radiative pumping, the conversion efficiency from exciton to polariton emission can reach up to 80%. By introducing appropriate injection layers in a SY microcavity and optimizing the cavity design, we further demonstrate a high-performance ultrastrongly coupled SY LED with weakly dispersive electroluminescence along LP mode and a maximum external quantum efficiency (EQE) of 2.8%. Finally, we realize an ultrastrongly coupled LET based on vertical integration of a high-mobility ZnO transistor and a SY LED in a microcavity, which enables a large switching ratio, uniform emission in the ZnO pattern, and LP mode emission with a maximum EQE of 2.4%. This vertical LET addresses the difficulties of achieving high emission performance and precisely defining the emission area in typical planar LETs, and opens up the possibility of applying various strongly coupled emitters for advanced polariton devices and high-resolution applications.

The high diversity of Scedosporium and Lomentospora species and their prevalence in human-disturbed areas in Taiwan.

Scedosporium and Lomentospora are important opportunistic pathogens causing localized or disseminated infection in humans. Understanding their environmental distribution is critical for public hygiene and clinical management. We carried out the first environmental survey in urbanized and natural regions in Taiwan. Overall, Scedosporium and Lomentospora species were recovered in 132 out of 273 soil samples (48.4%) across Taiwan. We morphologically and molecularly identified six Scedosporium and one Lomentospora species. All four major clinical relevant species were isolated with high frequency, i.e., Scedosporium apiospermum (42.4%), S. boydii (21.8%), Lomentosporaprolificans (14.5%), S. aurantiacum (8.5%); two clinically minor species, Pseudallescheria angusta (6.7%) and S. dehoogii (5.6%), and a saprobic species, S. haikouense (0.6%), had moderate to rare incidence. These fungal species had high incidence in urban (48.6%) and hospital (67.4%) soil samples, and had limited distribution in samples from natural regions (5%). Multivariate analysis of the fungal composition revealed strong evidence of the preferential distribution of these fungi in urban and hospital regions compared with natural sites. In addition, strong evidence suggested that the distribution and abundance of these fungal species were highly heterogeneous in the environment; samples in vicinity often yielded varied fungal communities. We concluded that these fungal species were prevalent in soil in Taiwan and their occurrences were associated with human activities. Although, hygiene sensitive sites such as hospitals were not harboring heavier fungal burdens than other urban facilities in our survey, still, aware should be taken for the high frequency of these clinical relevant species around hospital regions.

Scedosporium and Lomentospora are two fungal genera that can cause infections to wildlife and humans. Our experiment demonstrated that these fungi are ubiquitous in the soil in Taiwan. Their proximity to human-dwelling regions raises our awareness of their exposure to those who are susceptible.

RhB-Embedded Mn-MOF with Cyclotriphosphazene Skeleton as Dual-Emission Sensor for Putrescine as well as Smart Fluorescent Response of Aromatic Diamines and Nitrophenol.

Luminescent metal-organic framework composites with multiple luminescence emissions have been efficient sensing platforms. Herein, a fluorescent sensor (RhB@1-0.4) with dual-emission fluorescence properties was prepared by introducing rhodamine B (RhB) into the framework of complex 1, [Mn2.5(HCPCP)(H2O)4]·(CH3CN)0.5 [HCPCP = hexa-(4-carboxyl-phenoxy)-cyclotriphosphazene and CH3CN = acetonitrile), which is a novel crystalline two-dimensional (2D) coordinated organic framework material. It is a highly desirable material, realizing a ratiometric fluorescence response to putrescine with a high signal-to-noise ratio, and the detection limit can be as low as 6.8 µM. In addition, RhB@1-0.4 exhibited a better fluorescent sensing performance for aromatic diamines and nitrophenols compared with that of complex 1. It is a potential functionalized MOF material for the application of multichannel fluorescence sensing.

Effect of Carbon Monoxide Poisoning on Epilepsy Development: A Nationwide Population-Based Cohort Study.

STUDY OBJECTIVE: Carbon monoxide (CO) poisoning causes central nervous system toxicity resulting in delayed neurologic sequelae. This study aims to evaluate the risk of epilepsy in patients with a history of CO intoxication. METHODS: We conducted a retrospective population-based cohort study using the Taiwan National Health Insurance Research Database and enrolled patients with and without CO poisoning matched for age, sex, and index year in a 1:5 ratio, between 2000 and 2010. Multivariable survival models were used to assess the risk of epilepsy. The primary outcome was newly developed epilepsy after the index date. All patients were followed until a new diagnosis of epilepsy, death, or December 31, 2013. Stratification analyses by age and sex were also conducted. RESULTS: This study included 8,264 patients with CO poisoning and 41,320 without. Patients with a history of CO poisoning were strongly associated with subsequent epilepsy (adjusted hazard ratio [HR] 8.40; 95% confidence interval [CI], 6.48 to 10.88). In the age-stratified analysis, intoxicated patients aged 20 to 39 years had the highest HR (adjusted HR 11.06; 95% CI, 7.17 to 17.08). In the sex-stratified analysis, adjusted HRs for male and female patients were 8.00 (95% CI, 5.86 to 10.92) and 9.53 (95% CI, 5.95 to 15.26), respectively. CONCLUSION: Patients with CO poisoning were associated with an increased risk of developing epilepsy compared with those without CO poisoning. This association was more prominent in the young population.

Anti-gout activity and the interaction mechanisms between Sanghuangporus vaninii active components and xanthine oxidase.

Xanthine oxidase (XO) plays a critical role in the progression of gout. We showed in a previous study that Sanghuangporus vaninii (S. vaninii), a perennial, medicinal, and edible fungus traditionally used to treat various symptoms, contains XO inhibitors. In the current study, we isolated an active component of S. vaninii using high performance countercurrent chromatography and identified it as davallialactone using mass spectrometry with 97.726 % purity. A microplate reader showed that davallialactone had mixed inhibition of XO activity with a half-inhibitory concentration value of 90.07 ± 2.12 µM. In addition, the collision between davallialactone and XO led to fluorescence quenching and conformational changes in XO, which were mainly driven by hydrophobicity and hydrogen bonding. Molecular simulations further showed that davallialactone was located at the center of the molybdopterin (Mo-Pt) of XO and interacted with amino acid residues Phe798, Arg912, Met1038, Ala1078, Ala1079, Gln1194, and Gly1260, suggesting that entering the enzyme-catalyzed reaction was unfavorable for the substrate. We also observed face-to-face π-π interactions between the aryl ring of davallialactone and Phe914. Cell biology experiments indicated that davallialactone reduced the expression of the inflammatory factors, tumor necrosis factor alpha and interleukin-1 beta (P < 0.05), can effectively alleviate cellular oxidative stress. This study showed that davallialactone significantly inhibits XO and has the potential to be developed into a novel medicine to prevent hyperuricemia and treat gout.

Association between 14 candidate genes, PM2.5, and affective disorders: a study of the Taiwan Biobank.

BACKGROUND: Most studies have focused on the risk factors, treatment, and care of affective psychosis, and several have reported a relationship between ambient air quality and this psychosis. Although an association has been reported between psychosis and genes, studies mainly explored the associations between one type of psychosis and one gene; few have identified genes related to affective psychosis. This study investigates the genetic and environmental factors of affective psychosis. METHODS: In this retrospective longitudinal study, 27 604 participants aged 30-70 were selected from Taiwan Biobank. The participants' propensity scores were calculated based on their demographic information, and propensity score matching was performed to divide the participants into an experimental (i.e., affective psychosis) and control group at a 1:5 ratio. Plink was used to analyze the major and minor types of gene expression related to affective psychosis, and PM2.5 exposure was incorporated into the analyses. RESULTS: According to the generalized estimating equation analysis results, 8 single nucleotide polymorphisms (SNPs) belonging to the ANK3, BDNF, CACNA1C, and GRID1 genotypes were significantly correlated with depressive disorder (P < .001), with the majority belonging to the ANK3 and CACNA1C. A total of 5 SNPs belonging to the CACNA1C, GRID1, and SIRT1 genotypes were significantly correlated with bipolar disorder (P < .001), with the majority belonging to the CACNA1C. No significant correlation was identified between ambient air pollution and affective psychosis. CONCLUSIONS: CACNA1C and GRID1 are common SNP genotypes for depressive disorder and bipolar disorder and should be considered associated with affective psychosis.

Disparities in the medical expenditures of patients with cancer and concomitant mental disorder: analyzing the effects of diagnosis sequence order.

BACKGROUND: Cancer is the leading cause of death in Taiwan. Medical expenditures related to cancer accounted for 44.8% of all major illness insurance claims in Taiwan. Prior research has indicated that the dual presence of cancer and mental disorder in patients led to increased medical burden. Furthermore, patients with cancer and concomitant mental disorder could incur as much as 50% more annual costs than those without. Although previous studies have investigated the utilization of patients with both diseases, the effects of morbidity sequence order on patient costs are, however, uncertain. This study explored medical expenditures linked with the comorbidity of cancer and mental disorder, with a focus on the impact of diagnosis sequence order. METHODS: This population-based retrospective matched cohort study retrieved patients with cancer and mental disorder (aged ≥ 20 years) from the Ministry of Health and Welfare Data Science Center 2005-2015 database. 321,045 patients were divided based on having one or both diseases, as well as on the sequence of mental disorder and cancer diagnosis. Study subjects were paired with comparison counterparts free of both diseases using Propensity Score Matching at a 1:1 ratio. Annual Cost per Patient Linear Model (with a log-link function and gamma distribution) was used to assess the average annual cost, covarying for socio-demographic and clinical factors. Binomial Logistic Regression was used to evaluate factors associated with the risk of high-utilization. RESULTS: The "Cancer only" group had higher adjusted mean annual costs (NT$126,198), more than 5-times that of the reference group (e^ß: 5.45, p < 0.001). However, after exclusion of patients with non-cancer and inclusion of diagnosis sequence order for patients with cancer and concomitant mental disorder, the post-cancer mental disorder group had the highest expenditures at over 13% higher than those diagnosed with only cancer on per capita basis (e^ß: 1.13, p < 0.001), whereas patients with cancer and any pre-existing mental disorder incurred lower expenditures than those with only cancer. The diagnosis of post-cancer mental disorder was significantly associated with high-utilization (OR = 1.24; 95% CI: 1.047-1.469). Other covariates associated with high-utilizer status included female sex, middle to old age, and late stage cancer. CONCLUSION: Presence of mental disorder prior to cancer had a diminishing effect on medical utilization in patients, possibly indicating low medical compliance or adherence in patients with mental disorder on initial treatments after cancer diagnosis. Patients with post-cancer mental disorder had the highest average annual cost. Similar results were found in the odds of reaching high-utilizer status. The follow-up of cancer treatment for patients with pre-existing mental disorders warrants more emphasis in an attempt to effectively allocate medical resources.

Unbiased optical mapping of telomere-integrated endogenous human herpesvirus 6.

Next-generation sequencing technologies allowed sequencing of thousands of genomes. However, there are genomic regions that remain difficult to characterize, including telomeres, centromeres, and other low-complexity regions, as well as transposable elements and endogenous viruses. Human herpesvirus 6A and 6B (HHV-6A and HHV-6B) are closely related viruses that infect most humans and can integrate their genomes into the telomeres of infected cells. Integration also occurs in germ cells, meaning that the virus can be inherited and result in individuals harboring the virus in every cell of their body. The integrated virus can reactivate and cause disease in humans. While it is well established that the virus resides in the telomere region, the integration locus is poorly defined due to the low sequence complexity (TTAGGG)n of telomeres that cannot be easily resolved through sequencing. We therefore employed genome imaging of the integrated HHV-6A and HHV-6B genomes using whole-genome optical site mapping technology. Using this technology, we identified which chromosome arm harbors the virus genome and obtained a high-resolution map of the integration loci of multiple patients. Surprisingly, this revealed long telomere sequences at the virus-subtelomere junction that were previously missed using PCR-based approaches. Contrary to what was previously thought, our technique revealed that the telomere lengths of chromosomes harboring the integrated virus genome were comparable to the other chromosomes. Taken together, our data shed light on the genetic structure of the HHV-6A and HHV-6B integration locus, demonstrating the utility of optical mapping for the analysis of genomic regions that are difficult to sequence.

Investigating Substance Use via Reddit: Systematic Scoping Review.

BACKGROUND: Reddit's (Reddit Inc) large user base, diverse communities, and anonymity make it a useful platform for substance use research. Despite a growing body of literature on substance use on Reddit, challenges and limitations must be carefully considered. However, no systematic scoping review has been conducted on the use of Reddit as a data source for substance use research. OBJECTIVE: This review aims to investigate the use of Reddit for studying substance use by examining previous studies' objectives, reasons, limitations, and methods for using Reddit. In addition, we discuss the implications and contributions of previous studies and identify gaps in the literature that require further attention. METHODS: A total of 7 databases were searched using keyword combinations including Reddit and substance-related keywords in April 2022. The initial search resulted in 456 articles, and 227 articles remained after removing duplicates. All included studies were peer reviewed, empirical, available in full text, and pertinent to Reddit and substance use, and they were all written in English. After screening, 60 articles met the eligibility criteria for the review, with 57 articles identified from the initial database search and 3 from the ancestry search. A codebook was developed, and qualitative content analysis was performed to extract relevant evidence related to the research questions. RESULTS: The use of Reddit for studying substance use has grown steadily since 2015, with a sharp increase in 2021. The primary objective was to identify tendencies and patterns in various types of substance use discussions (52/60, 87%). Reddit was also used to explore unique user experiences, propose methodologies, investigate user interactions, and develop interventions. A total of 9 reasons for using Reddit to study substance use were identified, such as the platform's anonymity, its widespread popularity, and the explicit topics of subreddits. However, 7 limitations were noted, including the platform's low representativeness of the general population with substance use and the lack of demographic information. Most studies use application programming interfaces for data collection and quantitative approaches for analysis, with few using qualitative approaches. Machine learning algorithms are commonly used for natural language processing tasks. The theoretical, methodological, and practical implications and contributions of the included articles are summarized and discussed. The most prevalent practical implications are investigating prevailing topics in Reddit discussions, providing recommendations for clinical practices and policies, and comparing Reddit discussions on substance use across various sources. CONCLUSIONS: This systematic scoping review provides an overview of Reddit's use as a data source for substance use research. Although the limitations of Reddit data must be considered, analyzing them can be useful for understanding patterns and user experiences related to substance use. Our review also highlights gaps in the literature and suggests avenues for future research.

Tributyrin Intake Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in LDLR-/- Mice.

Abdominal aortic aneurysm (AAA) is a multifactorial cardiovascular disease with a high risk of death, and it occurs in the infrarenal aorta with vascular dilatation. High blood pressure acts on the aortic wall, resulting in rupture and causing life-threatening intra-abdominal hemorrhage. Vascular smooth muscle cell (VSMC) dysregulation and extracellular matrix (ECM) degradation, especially elastin breaks, contribute to structural changes in the aortic wall. The pathogenesis of AAA includes the occurrence of oxidative stress, inflammatory cell infiltration, elastic fiber fragmentation, VSMC apoptosis, and phenotypic transformation. Tributyrin (TB) is decomposed by intestinal lipase and has a function similar to that of butyrate. Whether TB has a protective effect against AAA remains uncertain. In the present study, we established an AAA murine model by angiotensin II (AngII) induction in low-density lipoprotein receptor knockout (LDLR-/-) mice and investigated the effects of orally administered TB on the AAA size, ratio of macrophage infiltration, levels of matrix metalloproteinase (MMP) expression, and epigenetic regulation. TB attenuates AngII-induced AAA size and decreases elastin fragmentation, macrophage infiltration, and MMP expression in the medial layer of the aorta and reduces the levels of SBP (systolic blood pressure, p < 0.001) and MMP-2 (p < 0.02) in the serum. TB reduces the AngII-stimulated expression levels of MMP2 (p < 0.05), MMP9 (p < 0.05), MMP12, and MMP14 in human aortic smooth muscle cells (HASMCs). Moreover, TB and valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, suppress AngII receptor type 1 (AT1R, p < 0.05) activation and increase the expression of acetyl histone H3 by HDAC activity inhibition (p < 0.05). Our findings suggest that TB exerts its protective effect by suppressing the activation of HDAC to attenuate the AngII-induced AT1R signaling cascade.

Identification of the Key Genes of Immune Infiltration in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common cause of heart failure. In this study, we screened the immune infiltration-related genes associated with DCM to explore the potential molecular mechanisms and provide a basis for the early diagnosis and development of new immunotherapeutic targets. A dataset related to DCM was downloaded from the Gene Expression Omnibus (GEO) database. R software was applied to the genetic differential analysis of patients with DCM and healthy individuals, and the obtained differential expressed genes (DEGs) were screened for differentially expressed immune-related genes (DEIRGs) after comparison with the immune microsatellite database. Gene functional analysis established a protein interaction network (PPI). The immune infiltration in patients with DCM versus normal controls was assessed using the CIBERSORT algorithm, the hub genes were screened using the MOCDE app, and the hubs were validated in multiple datasets. A total of 246 DEGs were screened (adj. P < 0.05 and |logFC| > 0.3), and a total of 170 DEIRGs were compared. Gene Ontology analysis showed significant (adj. P < 0.05) Biological Process entries of 591, Cellular Component of 10, and Molecular Function of 39; Kyoto Encyclopedia of Genes and Genomes showed 20 significant entries, mainly focused on cytokines involved in immune-related response, etc. A protein interaction network comprising 28 hub DEGs was constructed in combination with the PPI network interactions. DEIRG was mainly distributed in the T-cell receptor pathway by immune infiltration detection analysis, and significant changes in central memory T-cells were found by analyzing T-cell-related subpathways, where INSR, HLA-B, IFITM1, and HBEGF were significantly differentially expressed. We selected 632 hospitalized patients for validation and found that INSR and HLA-B expression were associated with DCM development by Nomogram. The expression of HLA-B in peripheral blood T-cells was higher in DCM patients than in the normal group, as verified by qRT-PCR. However, the detailed mechanism needs to be further explored.

Fibroblast growth factor 21 reverses high-fat diet-induced impairment of vascular function via the anti-oxidative pathway in ApoE knockout mice.

Circulating endothelial progenitor cells (EPCs), which function in vascular repair, are the markers of endothelial dysfunction and vascular health. Fibroblast growth factor 21 (FGF21), a liver-secreted protein, plays a crucial role in glucose homeostasis and lipid metabolism. FGF21 has been reported to attenuate the progression of atherosclerosis, but its impact on EPCs under high oxidative stress conditions remains unclear. In vitro studies showed that the ß-klotho protein was expressed in cultured EPCs and that its expression was upregulated by FGF21 treatment. Hydrogen peroxide (H2 O2 )-induced oxidative stress impaired EPC function, including cell viability, migration and tube formation. Pretreatment with FGF21 restored the functions of EPCs after the exposure to H2 O2 . Administration of N(ω)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, inhibited the effects of FGF21 in alleviating oxidative injury by suppressing endothelial nitric oxide synthase (eNOS). In an in vivo study, the administration of FGF21 significantly reduced total cholesterol (TC) and blood glucose levels in apolipoprotein E (ApoE)-deficient mice that were fed a high-fat diet (HFD). Endothelial function, as reflected by acetylcholine-stimulated aortic relaxation, was improved after FGF21 treatment in ApoE-deficient mice. Analysis of mRNA levels in the aorta indicated that FGF21 increased the mRNA expression of eNOS and upregulated the expression of the antioxidant genes superoxide dismutase (SOD)1 and SOD2 in ApoE-deficient mice. These data suggest that FGF21 improves EPC functions via the Akt/eNOS/nitric oxide (NO) pathway and reverses endothelial dysfunction under oxidative stress. Therefore, administration of FGF21 may ameliorate a HFD-induced vascular injury in ApoE-deficient mice.