Exploring the anti-skin inflammation substances and mechanism of Paeonia lactiflora Pall. Flower via network pharmacology-HPLC integration.

BACKGROUND: Paeonia lactiflora Pall. (PL) is widely used in China as a homologous plant of medicine and food. PL flower is rich in bioactive substances with anti-inflammatory effects, while the pathogenesis of skin inflammation is complex and the specific mechanism is not clear, the current treatment of skin inflammation is mainly hormonal drugs, and hormonal drugs have obvious toxic side effects. The research on the treatment of skin inflammation by PL flowers is relatively small, so this study provides a basis for the development and utilisation of PL resources. OBJECTIVE: Our study was to investigate the interventional effects of PL flower extracts on skin inflammation and thus to understand its functional role in the treatment of skin inflammation and its molecular mechanisms. METHODS: The major active substances in PL flower extracts were investigated by the HPLC-DAD method, and the potential targets of action were predicted by network pharmacology, which was combined with in vitro experimental validation to explore the mechanism of PL flower extracts on the regulation of skin inflammation. The HPLC-DAD analysis identified seven major active components in PL flower extracts, and in response to the results, combined with the potential mechanism of network pharmacological prediction with skin inflammation, the PL flower extract is closely related to MAPK and NF-κB signaling pathways. In addition, we also investigated the interventional effects of PL flower extract on skin inflammation by western blot detection of MAPK signaling pathway and NF-κB signaling pathway proteins in cells. RESULT: Seven active components were identified and quantified from the extract of PL flowers, including Gallic acid, 1,2,3,4,6-O-Pentagalloylglucose, Oxypaeoniflorin, Paeoniflorin, Albiflorin, Benzoyloxypeoniflorin, and Rutin. It was predicted targets for the treatment of skin inflammation, with PPI showing associations with targets such as TNF, MAPK1, and IL-2. KEGG enrichment analysis revealed that the main signaling pathways involved included MAPK and T cell receptor signaling pathways. Cell experiments showed that the peony flower extract could inhibit the release of NO and inflammatory factors, as well as reduce ROS levels and inhibit cell apoptosis. Furthermore, the extract was found to inhibit the activation of the MAPK and NF-κB signaling pathways in cells. CONCLUSIONS: In this study, we found that PL flower extract can inhibit the production of cell inflammatory substances, suppress the release of inflammatory factors, and deactivate inflammatory signaling pathways, further inhibiting the production of cell inflammation. This indicates that PL flower extract has a therapeutic effect on skin inflammation.

Learning curve of achieving competency in emergency endoscopy in upper gastrointestinal bleeding: how much experience is necessary?

OBJECTIVES: The management of upper gastrointestinal bleeding (UGIB) has seen rapid advancements with revolutionising innovations. However, insufficient data exist on the necessary number of emergency endoscopies needed to achieve competency in haemostatic interventions. DESIGN: We retrospectively analysed all oesophagogastroduodenoscopies with signs of recent haemorrhage performed between 2015 and 2022 at our university hospital. A learning curve was created by plotting the number of previously performed oesophagogastroduodenoscopies with signs of recent haemorrhage against the treatment failure rate, defined as failed haemostasis, rebleeding and necessary surgical or radiological intervention. RESULTS: The study population included 787 cases with a median age of 66 years. Active bleeding was detected in 576 cases (73.2%). Treatment failure occurred in 225 (28.6%) cases. The learning curve showed a marked decline in treatment failure rates after nine oesophagogastroduodenoscopies had been performed by the respective endoscopists followed by a first plateau between 20 and 50 procedures. A second decline was observed after 51 emergency procedures followed by a second plateau. Endoscopists with experience of <10 emergency procedures had higher treatment failure rates compared with endoscopists with >51 emergency oesophagogastroduodenoscopies performed (p=0.039) or consultants (p=0.041). CONCLUSIONS: Our data suggest that a minimum number of 20 oesophagogastroduodenoscopies with signs of recent haemorrhage is necessary before endoscopists should be considered proficient to perform emergency procedures independently. Endoscopists might be considered as advanced-qualified experts in managing UGIB after a minimum of 50 haemostatic procedure performed. Implementing recommendations on minimum numbers of emergency endoscopies in education programmes of endoscopy trainees could improve their confidence and competency in managing acute UGIB.

Integrated analysis of gut microbiota and metabolomic profiling in colorectal cancer metastasis.

Colorectal cancer (CRC) is characterized by its heterogeneity and complex metastatic mechanisms, presenting significant challenges in treatment and prognosis. This study aimed to unravel the intricate interplay between the gut microbiota and metabolic alterations associated with CRC metastasis. By employing high-throughput sequencing and advanced metabolomic techniques, we identified distinct patterns in the gut microbiome and fecal metabolites across different CRC metastatic sites. The differential gene analysis highlighted significant enrichment in biological processes related to immune response and extracellular matrix organization, with key genes playing roles in the complement and clotting cascades, and staphylococcus aureus infections. Protein-protein interaction networks further elucidated the potential mechanisms driving CRC spread, emphasizing the importance of extracellular vesicles and the PPAR signaling pathway in tumor metastasis. Our comprehensive microbiota analysis revealed a relatively stable alpha diversity across groups but identified specific bacterial genera associated with metastatic stages. Metabolomic profiling using OPLS-DA models unveiled distinct metabolic signatures, with differential metabolites enriched in pathways crucial for cancer metabolism and immune modulation. Integrative analysis of the gut microbiota and metabolic profiles highlighted significant correlations, suggesting a complex interplay that may influence CRC progression and metastasis. These findings offer novel insights into the microbial and metabolic underpinnings of CRC metastasis, paving the way for innovative diagnostic and therapeutic strategies targeting the gut microbiome and metabolic pathways.

Body image and physical activity in Latinas.

Women with negative body image engage in less physical activity. The purpose of this study is to examine the relationship between body image and physical activity in Latinas participating in a lifestyle program. Participants (age 43.8 ± 10.1 years and BMI 30.4 ± 5.2 kg/m2) were enrolled in a 12-month culturally and linguistically adapted, individually tailored, intervention focused on increasing moderate-to-vigorous intensity physical activity (MVPA). Longitudinal assessments were conducted on body image dissatisfaction (BID) using the Figure Rating Scale, MVPA using the 7-day PAR interview, and objectively measured body weight. Pre-intervention BID did not significantly predict MVPA change. Participants experienced considerable reduction in BID. Greater MVPA engagement and weight loss were independently related to BID reduction. Acculturation did not moderate these relationships. Body image improved in Latinas participating in a cognitive and behavioral physical activity intervention regardless of weight loss and acculturation level.

Fungal signature differentiates alcohol-associated liver disease from nonalcoholic fatty liver disease.

The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to compare changes of the fecal fungal microbiota between patients with ALD and NAFLD and to elucidate patterns in different disease stages between the two conditions. We analyzed fungal internal transcribed spacer 2 (ITS2) sequencing using fecal samples from a cohort of 48 patients with ALD, 78 patients with NAFLD, and 34 controls. The fungal microbiota differed significantly between ALD and NAFLD. The genera Saccharomyces, Kluyveromyces, Scopulariopsis, and the species Candida albicans (C. albicans), Malassezia restricta (M. restricta), Scopulariopsis cordiae (S. cordiae) were significantly increased in patients with ALD, whereas the genera Kazachstania and Mucor were significantly increased in the NAFLD cohort. We identified the fungal signature consisting of Scopulariopsis, Kluyveromyces, M. restricta, and Mucor to have the highest discriminative ability to detect ALD vs NAFLD with an area under the curve (AUC) of 0.93. When stratifying the ALD and NAFLD cohorts by fibrosis severity, the fungal signature with the highest AUC of 0.92 to distinguish ALD F0-F1 vs NAFLD F0-F1 comprised Scopulariopsis, Kluyveromyces, Mucor, M. restricta, and Kazachstania. For more advanced fibrosis stages (F2-F4), the fungal signature composed of Scopulariopsis, Kluyveromyces, Mucor, and M. restricta achieved the highest AUC of 0.99 to differentiate ALD from NAFLD. This is the first study to identify a fungal signature to differentiate two metabolic fatty liver diseases from each other, specifically ALD from NAFLD. This might have clinical utility in unclear cases and might hence help shape treatment approaches. However, larger studies are required to validate this fungal signature in other populations of ALD and NAFLD.

Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis.

BACKGROUND AND AIMS: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH. APPROACH AND RESULTS: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196). Serum AhR activity was evaluated using an AhR reporter assay with HepG2-Lucia cells incubated with serum for 24 hours. Serum AhR activity was significantly higher in patients with AH compared with both controls (1.59 vs. 0.96-fold change, p < 0.001) and patients with AUD (1.59 vs. 0.93, p < 0.001). In both AH cohorts, patients with AhR activity ≥ 2.09 had significantly lower cumulative survival rates at 30, 60, 90, and 180 days compared to those with AhR activity < 2.09. When serum AhR activity was used to further stratify patients with severe AH, the cumulative 30, 60, 90, and 180-day survival rates for patients with severe AH and the AhR activity ≥ 2.09 group were all significantly lower than those with an AhR activity < 2.09 group. CONCLUSIONS: Serum AhR activity was significantly higher in patients with AH compared with controls and individuals with AUD, and this increased activity was associated with higher mortality. Consequently, serum AhR activity holds potential as a prognostic marker.

Tunable afterglow Ca1 - xSrxAl2O4:Eu2+, Nd3+ phosphors with dependence of an excitation wavelength.

In the emerging field of high-capacity information encryption, multicolor, multitemporal, and multimodal luminescence inorganic materials are of great significance. However, conventional inorganic materials lack the flexibility to dynamically adjust the photon transition path, resulting in unicolor luminescence of the sample and reducing the reading and decoding levels. Herein, we elaborately designed the components for constructing dual-phase crystal fields for Eu2+ in phosphors based on a high temperature solid-state method. Specifically, SrAl2O4:Eu2+ crystal with a bright green afterglow and CaAl2O4:Eu2+ crystal with a blue afterglow were obtained in phosphors at the same time. As a result, a tunable afterglow behavior from blue to white was achieved due to the 4f65d1 → 4f7 transition of Eu2+ at different crystal field sites. Finally, the color tunable afterglow sample was used to explore the encryption and decryption processes of information, and the results showed that the prepared material has a good anti-counterfeiting performance, which is promising for the development of long persistent luminescent materials.

Trainees Associated with Improved Wait Times and Patient Satisfaction in a Multidisciplinary Clinic.

OBJECTIVE: To determine variables associated with longer wait times and decreased patient satisfaction. To determine the association of trainees with clinic wait times and patient satisfaction scores in an academic center. STUDY DESIGN: Cross-sectional study. METHODS: We recruited 266 study participants from an interdisciplinary Head and Neck Cancer outpatient clinic setting. Trained observers recorded observations related to wait times, time with individual health care practitioners, and total time spent in clinic. An 11-question survey was given to patients at the end of their visit assessing each patient's satisfaction with their visit, subjective wait time, and their likelihood to recommend the health care provider. RESULTS: Increased objective wait times were associated with new patients (p = 0.006) and based on the physician they saw (p < 0.001). Patients who saw a trainee spent less time waiting to see a physician (p = 0.023), more total time with a physician (p = 0.001), and reported higher wait time satisfaction scores (p = 0.001). There was no difference in total visit time if patients saw a trainee (p = 0.42). Patient satisfaction with wait time was correlated with all other aspects of patient satisfaction (p < 0.001). On multivariable analysis, the subjective wait time was associated with the likelihood to recommend (p < 0.001). CONCLUSION: Prolonged objective wait times in a multidisciplinary oncology outpatient setting were associated with several factors including specific physicians and new patient status. Trainee interaction with patients led to shorter wait times and improved patient satisfaction scores with wait times. Satisfaction with wait time was positively correlated with all aspects of patient satisfaction and 'likelihood to recommend' scores. LEVEL OF EVIDENCE: NA Laryngoscope, 134:178-184, 2024.

Single-cell RNA sequencing reveals common and unique gene expression profiles in primary CD4+ T cells latently infected with HIV under different conditions.

Background: The latent HIV reservoir represents the major barrier to a cure. One curative strategy is targeting diseased cells for elimination based on biomarkers that uniquely define these cells. Single-cell RNA sequencing (scRNA-seq) has enabled the identification of gene expression profiles associated with disease at the single-cell level. Because HIV provirus in many cells during latency is not entirely silent, it became possible to determine gene expression patterns in a subset of cells latently infected with HIV. Objective: The primary objective of this study was the identification of the gene expression profiles of single latently infected CD4+ T cells using scRNA-seq. Different conditions of latency establishment were considered. The identified profiles were then explored to prioritize the identified genes for future experimental validation. Methods: To facilitate gene prioritization, three approaches were used. First, we characterized and compared the gene expression profiles of HIV latency established in different environments: in cells that encountered an activation stimulus and then returned to quiescence, and in resting cells that were infected directly via cell-to-cell viral transmission from autologous activated, productively infected cells. Second, we characterized and compared the gene expression profiles of HIV latency established with viruses of different tropisms, using an isogenic pair of CXCR4- and CCR5-tropic viruses. Lastly, we used proviral expression patterns in cells from people with HIV to more accurately define the latently infected cells in vitro. Results: Our analyses demonstrated that a subset of genes is expressed differentially between latently infected and uninfected cells consistently under most conditions tested, including cells from people with HIV. Our second important observation was the presence of latency signatures, associated with variable conditions when latency was established, including cellular exposure and responsiveness to a T cell receptor stimulus and the tropism of the infecting virus. Conclusion: Common signatures, specifically genes that encode proteins localized to the cell surface, should be prioritized for further testing at the protein level as biomarkers for the ability to enrich or target latently infected cells. Cell- and tropism-dependent biomarkers may need to be considered in developing targeting strategies to ensure that all the different reservoir subsets are eliminated.

Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma.

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.

Enhanced blue afterglow in Ce-doped boroaluminate glass modified by Na.

The alkali metal Na+ is commonly applied as a charge compensator to optimize afterglow performance but rarely reported as a structural regulator to modify afterglow behavior in long afterglow glass materials. In this paper, by preparing the Na + -modified Ce-doped boroaluminate glasses under a high-temperature reducing atmosphere, super-five times brighter blue-violet afterglow lasting up to 30 min was obtained. Results show that appropriate Na+ doping loosens the glass structure and widens the bandgap, thereby regulating most of the electron capture-release modes. This work provides new insights into the behavior of afterglow enhancement in alkali metal-doped glasses.

Deciphering the 'gut-brain axis' through microbiome diversity.

Incentivised by breakthroughs and data generated by the high-throughput sequencing technology, this paper proposes a distance-based framework to fulfil the emerging needs in elucidating insights from the high-dimensional microbiome data in psychiatric studies. By shifting focus from traditional methods that focus on the observations from each subject to the between-subject attributes that aggregate two or more subjects' entire feature vectors, the described approach revolutionises the conventional prescription for high-dimensional observations via microbiome diversity. To this end, we enrich the classical generalised linear models to articulate the multivariable regression relationship between distance-based variables. We also discuss a robust and computationally feasible semiparametric inference technique. Benefitting from the latest advances in the semiparametric efficiency theory for such attributes, the proposed estimators enjoy robustness and good asymptotic properties that guarantee sensitivity in detecting signals between clinical outcomes and microbiome diversity. It offers a readily implementable and easily interpretable solution for deciphering the gut-brain axis in mental health research.

How to calculate sample size in animal and human studies.

One of the most important statistical analyses when designing animal and human studies is the calculation of the required sample size. In this review, we define central terms in the context of sample size determination, including mean, standard deviation, statistical hypothesis testing, type I/II error, power, direction of effect, effect size, expected attrition, corrected sample size, and allocation ratio. We also provide practical examples of sample size calculations for animal and human studies based on pilot studies, larger studies similar to the proposed study-or if no previous studies are available-estimated magnitudes of the effect size per Cohen and Sawilowsky.

Ramipril for the Treatment of COVID-19: RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Retrospective studies report that angiotensin-converting enzyme inhibitors (ACEIs) may reduce the severity of COVID-19, but prospective data on de novo treatment with ACEIs are limited. The RAMIC trial was a randomized, multicenter, placebo-controlled, double-blind, allocation-concealed clinical trial to examine the efficacy of de novo ramipril versus placebo for the treatment of COVID-19. METHODS: Eligible participants were aged 18 years and older with a confirmed diagnosis of SARS-CoV-2 infection, recruited from urgent care clinics, emergency departments, and hospital inpatient wards at eight sites in the USA. Participants were randomly assigned to daily ramipril 2.5 mg or placebo orally in a 2:1 ratio, using permuted block randomization. Analyses were conducted on an intention-to-treat basis. The primary outcome was a composite of mortality, intensive care unit (ICU) admission, or invasive mechanical ventilation by day 14. RESULTS: Between 27 May 2020 and 19 April 2021, a total of 114 participants (51% female) were randomized to ramipril (n = 79) or placebo (n = 35). The overall mean (± SD) age and BMI were 45 (± 15) years and 33 (± 8) kg/m2. Two participants in the ramipril group required ICU admission and one died, compared with none in the placebo group. There were no significant differences between ramipril and placebo in the primary endpoint (ICU admission, mechanical ventilation, or death) (3% versus 0%, p = 1.00) or adverse events (27% versus 29%, p = 0.82). The study was terminated early because of a low event rate and subsequent Emergency Use Authorization of therapies for COVID-19. CONCLUSION: De novo ramipril was not different compared with placebo in improving or worsening clinical outcomes from COVID-19 but appeared safe in non-critically ill patients with COVID-19. TRIAL REGISTRATION: Clinicaltrials.gov NCT04366050.

Autoimmune HLA Alleles and Neoepitope Presentation Predict Post-Allogenic Transplant Relapse.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure patients with high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, many patients relapse or develop debilitating graft-versus-host disease. Transplant restores T-cell reactivity against tumor cells, implicating patient human leukocyte antigen (HLA)-dependent antigen presentation via the major histocompatibility complex as a determinant of response. We sought to identify characteristics of the HLA genotype that influence response in allo-HSCT patients. Methods: We collected HLA genotype and panel-based somatic mutation profiles for 55 patients with AML and MDS and available data treated at the University of California San Diego Moores Cancer Center between May 2012 and January 2019. We evaluated characteristics of the HLA genotype relative to relapse-free time and overall survival (OS) post-allo-HSCT using univariable and multivariable regression. Results: In multivariable regression, the presence of an autoimmune allele was significantly associated with relapse-free time (hazard ratio [HR], 0.25; p = 0.01) and OS (HR, 0.16; p < 0.005). The better potential of the donor HLA type to present peptides harboring driver mutations trended toward better relapse-free survival (HR, 0.45; p = 0.07) and significantly correlated with longer OS (HR, 0.33; p = 0.01) though only a minority of cases had an HLA mismatch. Conclusion: In this single institution retrospective study of patients receiving allo-HSCT for relapsed AML/MDS, characteristics of an individual's HLA genotype (presence of an autoimmune allele and potential of the donor HLA to better present peptides representing driver mutations) were significantly associated with better outcomes. These findings suggest that HLA type may guide the optimal application of allo-HSCT and merit evaluation in larger cohorts. ClinicalTrials.gov Identifier: NCT02478931.

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer.

Importance: Head and neck squamous cell carcinoma is a highly lethal cancer that is often associated with human papillomavirus (HPV). Recent studies have shown promise in the use of HPV DNA detection in salivary rinses and plasma as a factor associated with a future diagnosis of HPV-positive oropharynx cancer (HPVOPC). However, the use of plasma and salivary HPV DNA detection in defining risk for recurrence in the context of a prospective, phase 3, clinical trial coupled with standardized clinical surveillance has not been reported. Objective: To identify patients with low-risk HPVOPC at risk for recurrence by detection of HPV16 DNA in plasma and salivary rinses. Design, Setting, and Participants: In this cohort study, 233 low-risk patients were recruited from 32 head and neck treatment centers in Ireland (1 [3.1%]), the Netherlands (1 [3.1%]), and the UK (30 [93.8%]) as part of the DE-ESCALATE HPV trial, an open-label, phase 3 randomized clinical trial examining treatment with cetuximab vs cisplatin for HPVOPC. Patients were assayed for the presence of HPV16 DNA in plasma and salivary rinse via a quantitative polymerase chain reaction-based assay. Main Outcomes and Measures: Assay results were associated with risk of recurrence and lead time from HPV16 DNA detection to recurrence. Results: Of 233 patients, 45 (19.3%) were women, and the mean (SD) age was 57.01 (8.45) years. A total 1040 salivary or blood samples were collected during the course of the study. With a median follow-up of 760 days, the sensitivity and specificity of combined plasma and salivary rinse HPV DNA assays for detecting recurrence were 65% and 87%, respectively. There was a median lead time of positive test to event/recurrence date of 19 days (range, 0-536 days) and mean (SD) of 122 (169.8) days. Conclusion and Relevance: The results of this cohort study suggest that in the setting of a randomized, prospective, phase 3 trial for low-risk patients with HPVOPC, posttreatment presence of HPV DNA in plasma and salivary rinses is associated with recurrence; a lead time between test positivity and clinical recurrence offers a potential opportunity for earlier detection of recurrence.

Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a low survival rate. Recently, new drugs that target KRASG12D, a common mutation in PDAC, have been developed. We studied one of these compounds, MRTX1133, and found it was specific and effective at low nanomolar concentrations in patient-derived organoid models and cell lines harboring KRASG12D mutations. Treatment with MRTX1133 upregulated the expression and phosphorylation of EGFR and HER2, indicating that inhibition of ERBB signaling may potentiate MRTX1133 antitumor activity. Indeed, the irreversible pan-ERBB inhibitor, afatinib, potently synergized with MRTX1133 in vitro, and cancer cells with acquired resistance to MRTX1133 in vitro remained sensitive to this combination therapy. Finally, the combination of MRTX1133 and afatinib led to tumor regression and longer survival in orthotopic PDAC mouse models. These results suggest that dual inhibition of ERBB and KRAS signaling may be synergistic and circumvent the rapid development of acquired resistance in patients with KRAS mutant pancreatic cancer. SIGNIFICANCE: KRAS-mutant pancreatic cancer models, including KRAS inhibitor-resistant models, show exquisite sensitivity to combined pan-ERBB and KRAS targeting, which provides the rationale for testing this drug combination in clinical trials.

Global and national prevalence of nonalcoholic fatty liver disease in adolescents: An analysis of the global burden of disease study 2019.

BACKGROUND AND AIMS: NAFLD in adolescents is an increasing health crisis worldwide, but its exact global, continental, and national prevalence, its relationship with other metabolic conditions, and the human development index (HDI) globally are not known. APPROACH AND RESULTS: We analyzed data from the Global Burden of Disease Study 2019 to compare global, continental, and national prevalence rates of adolescent NAFLD and associations with other metabolic conditions and HDI. The global NAFLD prevalence in adolescents increased from 3.73% in 1990 to 4.71% in 2019 (a relative increase of 26.27%). The prevalence for the male and female populations was 5.84% and 3.52% in 2019, respectively. The Oceanian and North American continents had the highest adolescent NAFLD prevalence (median: 6.54% and 5.64%, respectively), whereas Europe had the lowest prevalence (median: 3.98%). South America and North America had the highest relative increase in adolescent NAFLD prevalence from 1990 to 2019 (median: 39.25% and 36.87%, respectively). High body mass index and type 2 diabetes mellitus increased significantly in adolescents worldwide. However, only high body mass index and not type 2 diabetes mellitus correlated with NAFLD prevalence in adolescents globally. Countries with a higher HDI had larger increases in adolescent NAFLD prevalence from 1990 to 2019 although countries with the highest HDI (HDI: > 0.9) had the lowest NAFLD prevalence in 2019. CONCLUSIONS: NAFLD in adolescents is an increasing health problem on all continents. Improving environmental factors, including lifestyle but also healthcare policies, can help to prevent NAFLD from developing in children and adolescents and help to improve outcomes in children and adolescents with NAFLD.

HIV Infection Elicits Differential Transcriptomic Remodeling in CD4+ T Cells with Variable Proliferative Responses to the T Cell Receptor Stimulus.

Identification of a cellular biomarker of latent HIV infection will facilitate the latent reservoir detection, quantification, and targeting for elimination. Unfortunately, the latency biomarkers reported in the literature define only a fraction of the entire reservoir. The latent HIV reservoir may be established in dividing cells that subsequently return to quiescence and in resting cells. The strength of the T cell receptor (TCR) signaling at the time of infection affects characteristics of the established reservoir, such as the ability to reactivate with latency reversing agents. To better understand the cellular environments before latency establishment, we characterized transcriptomic remodeling induced by the initial HIV infection in cells with differential proliferative responses to the TCR stimulus. Cell proliferation was monitored using the viable dye carboxyfluorescein diacetate succinimidyl ester. Cells that divided many times, a few times, or remained non-dividing were subjected to single-cell RNA sequencing. A subset of identified transcriptional changes induced by HIV infection was independent of the number of cell divisions; however, responses unique to different cell subsets were also detected. Some of these early gene expression changes were consistent with reported markers of latently infected cells. We pose that the latency biomarkers may depend on the cellular proliferative state at the time of infection.

One-Step Fabrication of Droplet Arrays Using a Biomimetic Structural Chip.

In the field of one-step efficient preparation of dewetting droplet arrays, the process is hampered by the requirement for low chemical wettability of solid surfaces, which restricts the complete transition of wetting state and its broad prospects in biological applications. Inspired by the physical structure of the lotus leaf, enabling it to promote the change of the infiltration state of an aqueous solution on the surface, we developed a method of one-step fabrication of droplet arrays on the biomimetic structural chip designed in the present work. This greatly reduces the need for chemical modification techniques to achieve low wettability and reduces the reliance on complex and sophisticated surface preparation techniques, thus improving the fabrication efficiency of droplet arrays fully generated on a chip by one-step operation without the need for extra liquid phase or the control of harsh barometric pressure. We also studied the influence of dimensions of the biomimetic structure and the preparation process parameters such as number of smears and speed of smearing on the preparation rate and uniformity of the droplet arrays. The amplification of templating DNA molecules in the droplet arrays prepared in a one-step fabrication way is also performed to verify its application potential for DNA molecular diagnosis.