Fabrication of the Rapid Self-Assembly Hydrogels Loaded with Luteolin: Their Structural Characteristics and Protection Effect on Ulcerative Colitis.

Luteolin (LUT) is a fat-soluble flavonoid known for its strong antioxidant and anti-inflammatory properties. Nonetheless, its use in the food industry has been limited due to its low water solubility and bioavailability. In this study, hyaluronic acid, histidine, and luteolin were self-assembled to construct tubular network hydrogels (HHL) to improve the gastrointestinal stability, bioavailability, and stimulation response of LUT. As anticipated, the HHL hydrogel's mechanical strength and adhesion allow it to withstand the challenging gastrointestinal environment and effectively extend the duration of drug presence in the body. In vivo anti-inflammatory experiments showed that HHL hydrogel could successfully alleviate colitis induced by dextran sulfate sodium (DSS) in mice by reducing intestinal inflammation and restoring the integrity of the intestinal barrier. Moreover, HHL hydrogel also regulated the intestinal microorganisms of mice and promoted the production of short-chain fatty acids. The HHL hydrogel group demonstrated a notably superior treatment effect compared to the LUT group alone. The hydrogel delivery system is a novel method to improve the absorption of LUT, increasing its bioavailability and enhancing its pharmaceutical effects.

Machine Learning-Based Prediction of Stroke in Emergency Departments.

Background: Stroke misdiagnosis, associated with poor outcomes, is estimated to occur in 9% of all stroke patients. Objectives: We hypothesized that machine learning (ML) could assist in the diagnosis of ischemic stroke in emergency departments (EDs). Design: The study was conducted and reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines. We performed model development and prospective temporal validation, using data from pre- and post-COVID periods; we also performed a case study on a small cohort of previously misdiagnosed stroke patients. Methods: We used structured and unstructured electronic health records (EHRs) of 56,452 patient encounters from 13 hospitals in Pennsylvania, from September 2003 to January 2021. ML pipelines, including natural language processing, were created using pre-event clinical data and provider notes in the EDs. Results: Using pre-event information, our model's area under the receiver operating characteristics curve (AUROC) ranged from 0.88 to 0.92 with a similar range accuracy (0.87-0.90). Using provider notes, we identified five models that reached a balanced performance in terms of AUROC, sensitivity, and specificity. Model AUROC ranged from 0.93 to 0.99. Model sensitivity and specificity reached 0.90 and 0.99, respectively. Four of the top five performing models were based on the post-COVID provider notes; however, no performance difference between models tested on pre- and post-COVID was observed. Conclusion: This study leveraged pre-event and at-encounter level EHR for stroke prediction. The results indicate that available clinical information can be used for building EHR-based stroke prediction models and ED stroke alert systems.

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which involves aberrant proliferation and apoptosis resistance of the pulmonary arterial smooth muscle cells (PASMCs), resembling the hallmark characteristics of cancer. In cancer, the HMGB2 (high-mobility group box 2) protein promotes the pro-proliferative/antiapoptotic phenotype. However, the function of HMGB2 in PH remains uninvestigated. METHODS: Smooth muscle cell (SMC)-specific HMGB2 knockout or HMGB2-OE (HMGB2 overexpression) mice and HMGB2 silenced rats were used to establish hypoxia+Su5416 (HySu)-induced PH mouse and monocrotaline-induced PH rat models, respectively. The effects of HMGB2 and its underlying mechanisms were subsequently elucidated using RNA-sequencing and cellular and molecular biology analyses. Serum HMGB2 levels were measured in the controls and patients with pulmonary arterial (PA) hypertension. RESULTS: HMGB2 expression was markedly increased in the PAs of patients with PA hypertension and PH rodent models and was predominantly localized in PASMCs. SMC-specific HMGB2 deficiency or silencing attenuated PH development and pulmonary vascular remodeling in hypoxia+Su5416-induced mice and monocrotaline-treated rats. SMC-specific HMGB2 overexpression aggravated hypoxia+Su5416-induced PH. HMGB2 knockdown inhibited PASMC proliferation in vitro in response to PDGF-BB (platelet-derived growth factor-BB). In contrast, HMGB2 protein stimulation caused the hyperproliferation of PASMCs. In addition, HMGB2 promoted PASMC proliferation and the development of PH by RAGE (receptor for advanced glycation end products)/FAK (focal adhesion kinase)-mediated Hippo/YAP (yes-associated protein) signaling suppression. Serum HMGB2 levels were significantly increased in patients with PA hypertension, and they correlated with disease severity, predicting worse survival. CONCLUSIONS: Our findings indicate that targeting HMGB2 might be a novel therapeutic strategy for treating PH. Serum HMGB2 levels could serve as a novel biomarker for diagnosing PA hypertension and determining its prognosis.

DNA Framework-Engineered Assembly of Cyanine Dyes for Structural Identification of Nucleic Acids.

DNA nanostructures serve as precise templates for organizing organic dyes, enabling the creation of programmable artificial photonic systems with efficient light-harvesting and energy transfer capabilities. However, regulating the organization of organic dyes on DNA frameworks remains a great challenge. In this study, we investigated the factors influencing the self-assembly behavior of cyanine dye K21 on DNA frameworks. We observed that K21 exhibited diverse assembly modes, including monomers, H-aggregates, J-aggregates, and excimers, when combined with DNA frameworks. By manipulating conditions such as the ion concentration, dye concentration, and structure of DNA frameworks, we successfully achieved precise control over the assembly modes of K21. Leveraging K21's microenvironment-sensitive fluorescence properties on DNA nanostructures, we successfully discriminated between the chirality and topology structures of physiologically relevant G-quadruplexes. This study provides valuable insights into the factors influencing the dynamic assembly behavior of organic dyes on DNA framework nanostructures, offering new perspectives for constructing functional supramolecular aggregates and identifying DNA secondary structures.

Clickable X-ray Nanoprobes for Nanoscopic Bioimaging of Cellular Structures.

Synchrotron-based X-ray microscopy (XRM) has garnered widespread attention from researchers due to its high spatial resolution and excellent energy (element) resolution. Existing molecular probes suitable for XRM include immune probes and genetic labeling probes, enabling the precise imaging of various biological targets within cells. However, immune labeling techniques are prone to cross-interference between antigens and antibodies. Genetic labeling technologies have limited systems that allow express markers independently, and moreover, genetically encoded labels based on catalytic polymerization lack a fixed morphology. When applied to cell imaging, this can result in reduced localization accuracy due to the diffusion of labels within the cells. Therefore, both techniques face challenges in simultaneously labeling multiple biotargets within cells and achieving high-precision imaging. In this work, we applied the click reaction and developed a third category of imaging probes suitable for XRM, termed clickable X-ray nanoprobes (Click-XRN). Click-XRN consists of two components: an X-ray-sensitive multicolor imaging module and a particle-size-controllable morphology module. Efficient identification of intra- and extracellular biotargets is achieved through click reactions between the probe and biomolecules. Click-XRN possesses a controllable particle size, and its loading of various metal ions provides distinctive signals for imaging under XRM. Based on this, we optimized the imaging energy of Click-XRN with different particle sizes, enabling single-color and two-color imaging of the cell membrane, cell nucleus, and mitochondria with nanoscale spatial nanometers. Our work provides a potent molecular tool for investigating cellular activities through XRM.

Active Constituents with Tyrosinase Inhibitory Activities from Waste Tobacco leaves.

One novel compound, (R)-3, 6-diethoxy-4-hydroxycyclohex-3-en-1-one (1) and thirteen known compounds was isolated from the waste leaves of Nicotiana tabacum. The structures of three compounds (1-3) were confirmed and attributed firstly by the extensive spectroscopic data, including 1D/2D NMR, IR, HR-ESI-MS, CD, and ECD spectra. Notably,  seven compounds (2, 3, 9, 10, 11, 12, and 13) exhibited better tyrosinase inhibitory activity than the positive control, kojic acid. The binding modes of these compounds revealed that their structure formed strong hydrogen bonds and van der Waals force with the active sites of tyrosinase. These results indicated that waste tobacco leaves are good resources for developing tyrosinase inhibitors.

Healthcare providers' perceived barriers to providing breastfeeding support in Northwest rural China.

BACKGROUND: Healthcare providers play important roles in supporting breastfeeding. Although there has been insufficient actual breastfeeding support from healthcare providers in China, little research has been conducted to understand Chinese healthcare providers' perceived barriers to providing breastfeeding support, especially in rural China. This study aims to identify these perceived barriers to providing breastfeeding support in Northwestern rural China. METHODS: This study was conducted during the period from March 2018 to December 2018. Forty-one healthcare providers were recruited through purposive sampling in two rural counties in Northwest China that are in close proximity to each other and share similar demographic features. Participants included obstetrician-gynecologists, midwives, nurses, "village doctors", and township and village maternal and child health workers. Qualitative data were collected through one-on-one in-depth semi-structured interviews and focus group discussions. Transcripts were thematically analyzed. RESULTS: Analysis of interview data resulted in four themes that the participants perceived as barriers to supporting breastfeeding: (1) lack of medical resources, within which inadequate staffing, and lack of financial incentives were discussed, (2) lack of clear and specific responsibility assignment, within which no one takes the lead, and mutual buck-passing were discussed, (3) healthcare providers' lack of relevant expertise, within which lack of knowledge and skills, and low prestige of village healthcare providers were discussed, (4) difficulties in accessing mothers, within which medical equipment shortages reduce services utilization, mothers' housing situation, mothers' mobility, and cultural barriers were discussed. CONCLUSIONS: The study identified HCPs perceived barriers to providing breastfeeding support. Unique to China's Tri-Level Healthcare System, challenges like staffing and financial incentives are hard to swiftly tackle. Recommendations include mHealth enhancement and clarified responsibilities with incentives and tailored training. Further research is crucial to evaluate these strategies in rural Northwestern China and comparable underdeveloped areas nationwide.

Downregulated GPX4 in salivary gland epithelial cells contributes to salivary secretion dysfunction in Sjogren's syndrome via lipid ROS/pSTAT4/AQP5 axis.

Sjogren's syndrome (SS) is an autoimmune disease characterized by dysfunction of exocrine glands, such as salivary glands. However, the molecular mechanism of salivary secretion dysfunction in SS is still unclear. Given the significance of glutathione peroxidase 4 (GPX4) in cellular redox homeostasis, we hypothesized that dysregulation of GPX4 may play a pivotal role in the pathogenesis of salivary secretion dysfunction observed in SS. The salivary gland of SS patients and the SS mouse model exhibited reduced expression of the ferroptosis inhibitor GPX4 and the important protein aquaporin 5 (AQP5), which is involved in salivary secretion. GPX4 overexpression upregulated and GPX4 knockdown downregulated AQP5 expression in salivary gland epithelial cells (SGECs) and salivary secretion. Bioinformatics analysis of GSE databases from SS patients' salivary glands revealed STAT4 as a key intermediary regulator between GPX4 and AQP5. A higher level of nuclear pSTAT4 was observed in the salivary gland of the SS mouse model. GPX4 overexpression inhibited and GPX4 knockdown promoted STAT4 phosphorylation and nuclear translocation in SGECs. CHIP assay confirmed the binding of pSTAT4 within the promoter of AQP5 inhibiting AQP5 transcription. GPX4 downregulation accumulates intracellular lipid ROS in SGECs. Lipid ROS inhibitor ferrostatin-1 treatment during in vitro and in vivo studies confirmed that lipid ROS activates STAT4 phosphorylation and nuclear translocation in SGECs. In summary, the downregulated GPX4 in SGECs contributes to salivary secretion dysfunction in SS via the lipid ROS/pSTAT4/AQP5 axis. This study unraveled novel targets to revitalize the salivary secretion function in SS patients.

Mulberry leaf polysaccharide improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora, enhancing immune regulation and antioxidant capacity.

Polysaccharides are generally considered to have immune enhancing functions, and mulberry leaf polysaccharide is the main active substance in mulberry leaves, while there are few studies on whether mulberry leaf polysaccharide (MLP) has an effect on immunosuppression and intestinal damage caused by cyclophosphamide (CTX), we investigated whether MLP has an ameliorative effect on intestinal damage caused by CTX. A total of 210 1-day-old Mahuang cocks were selected for this experiment. Were equally divided into six groups and used to evaluate the immune effect of MLP. Our results showed that MLP significantly enhanced the growth performance of chicks and significantly elevated the secretion of cytokines (IL-1ß, IL-10, IL-6, TNF-α, and IFN-γ), immunoglobulins and antioxidant enzymes in the serum of immunosuppressed chicks. It attenuated jejunal damage and elevated the expression of jejunal tight junction proteins Claudin1, Zo-1 and MUC2, which protected intestinal health. MLP activated TLR4-MyD88-NF-κB pathway and enhanced the expression of TLR4, MyD88 and NF-κB, which served to protect the intestine. 16S rDNA gene high-throughput sequencing showed that MLP increased species richness, restored CTX-induced gut microbiome imbalance, and enhanced the abundance of probiotic bacteria in the gut. MLP improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora and enhancing immune regulation and antioxidant capacity. In conclusion, this study provides a scientific basis for MLP as an immune enhancer to regulate chick intestinal flora and protect chick intestinal mucosal damage.

Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1ß, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization.

Temporal Trends in Cardiovascular Disease Prevalence Among Asian American Subgroups.

BACKGROUND: Asian and multiracial individuals represent the 2 fastest growing racial and ethnic groups in the United States, yet most prior studies report Asian American and Native Hawaiian or Other Pacific Islander as a single racial group, with limited data on cardiovascular disease (CVD) prevalence among subgroups. We sought to evaluate temporal trends in CVD burden among disaggregated Asian subgroups. METHODS AND RESULTS: Patients with CVD based on International Classification of Diseases, Ninth Revision and Tenth Revision (ICD-9 and ICD-10) coding who received care from a mixed-payer health care organization in California between 2008 and 2018 were classified into self-identified racial and ethnic subgroups (non-Hispanic White [NHW], Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian or Other Pacific Islander, and multiracial groups). Adjusted trends in CVD prevalence over time by subgroup were compared using logistic regression. Among 3 494 071 patient-years, prevalence of CVD increased faster among all subgroups except Japanese and Native Hawaiian or Other Pacific Islander patients (P<0.01 for each, reference: NHW). Filipino patients had the highest overall CVD prevalence, which increased from 34.3% to 45.1% over 11 years (increase from 17.3%-21.9%, P<0.0001, reference: NHW). Asian Indian patients had the fastest increase in CVD prevalence over time (16.9%-23.7%, P<0.0001, reference: NHW). Among subcategories of disease, hypertension increased faster among Asian Indian, Chinese, Filipino, Korean, and multiracial groups (P<0.01 for all, reference: NHW), and coronary artery disease increased faster among Asian Indian, Chinese, Filipino, and Japanese groups (P<0.05 for each, reference: NHW). CONCLUSIONS: The increasing prevalence of CVD among disaggregated Asian, Native Hawaiian or Other Pacific Islander, and multiracial subgroups over time highlights the importance of tailored approaches to addressing CVD in these diverse subpopulations.

Cancer on motors: How kinesins drive prostate cancer progression?

Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.

Co-pyrolysis of sewage sludge and phosphate tailings: Synergistically enhancing heavy metal immobilization and phosphorus availability.

Phosphate tailings (PT) was used to reduce the release of heavy metals (HMs) during pyrolysis and the leachable rate of residual HMs, and simultaneously improve the bioavailability of phosphorus in the sludge-based biochar. The concentration of heavy metals and the fractions determined by BCR method was used to investigate the release and the transformation of Zn, Pb, Mn, Ni and Cu during pyrolysis involved with the effects of temperature and the addition of PT. The respective pyrolysis experiments shows that the release of Zn and Pb increases with temperature for both sewage sludge (SS) and PT, and the bioavailable fractions (F1 + F2) of Mn, Ni, and Cu increases with temperature for PT. During co-pyrolysis, blended samples released lower quantities of Zn and Pb and presented lower bioavailability of HMs than the individual SS or PT. A synergistic effect of co-pyrolysis was evident for volatile Zn and Pb. The decomposition of CaMg (CO3)2 from PT produced CaO, by which the volatile ZnCl2 and PbCl2 were transformed into ZnO and PbO with less volatility and higher reactivity with SiO2 and Al2O3 than the chlorides. Then SiO2 and Al2O3 from SS acted as the final stabilizer to immobilize the oxides. The final product combined with SiO2 and Al2O3, such as ZnSiO4 and ZnAl2O4, were detected. The addition of PT also introduced more Ca and P into sludge to produce biochar with higher concentration of apatite phosphorus with higher bioavailability.

Crucial role played by CK8+ cells in mediating alveolar injury remodeling for patients with COVID-19.

The high risk of SARS-CoV-2 infection and reinfection and the occurrence of post-acute pulmonary sequelae have highlighted the importance of understanding the mechanism underlying lung repair after injury. To address this concern, comparative and systematic analyses of SARS-CoV-2 infection in COVID-19 patients and animals were conducted. In the lungs of nine patients who died of COVID-19 and one recovered from COVID-19 but died of unrelated disease in early 2020, damage-related transient progenitor (DATP) cells expressing CK8 marker proliferated significantly. These CK8+ DATP cells were derived from bronchial CK5+ basal cells. However, they showed different cell fate toward differentiation into type I alveolar cells in the deceased and convalescent patients, respectively. By using a self-limiting hamster infection model mimicking the dynamic process of lung injury remodeling in mild COVID-19 patients, the accumulation and regression of CK8+ cell marker were found to be closely associated with the disease course. Finally, we examined the autopsied lungs of two patients who died of infection by the recent Omicron variant and found that they only exhibited mild pathological injury with no CK8+ cell proliferation. These results indicate a clear pulmonary cell remodeling route and suggest that CK8+ DATP cells play a primary role in mediating alveolar remodeling, highlighting their potential applications as diagnostic markers and therapeutic targets.

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes.

OBJECTIVE: Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors. METHODS: This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results. RESULTS: We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5-6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5-6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively. CONCLUSIONS: Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.

Evaluating the effectiveness of a novel digital evaluation technology on dental preclinical crown preparation training.

OBJECTIVES: To evaluate the assessment scores of a novel digital training program versus traditional training in dental preclinical crown preparation. METHODS: Crown preparations in two consecutive preclinical training sessions were retrospectively collected and assigned to three groups: traditional group (TG), scanning group (SG), and digital evaluation group (DG). Students in the TG (n = 20) were taught by conventional visual grading, while students in the SG (n = 25) received three-dimensional feedback from digitally scanned preparations. All the SG students continued with supplementary digital evaluation and preparations were allocated into the DG (n = 25). Comparison of total scores between groups was investigated using independent samples t-test and paired samples t-test. Mann‒Whitney U-test and Wilcoxon signed-rank test were used to statistically analyze the differences in subdividing categories. The level of significance was p < 0.05. Questionnaires on the digital evaluation procedure were answered by students in DG. RESULTS: The results showed a significant improvement (p < 0.01) in the total scores of DG than those of TG and SG, while there were no statistically significant differences between TG and SG. Scores of surface finish and undercut improved significantly in DG compared to TG and SG. The reduction scores of DG were significantly higher than those of SG. Students' feedback indicated a positive perspective on the implementation of the novel digital evaluation technology. CONCLUSIONS: These findings suggest that digital evaluation technology is useful for preclinical crown preparation training. Attention should also be paid to studying the optimal integration of digital dentistry into traditional dental curricula and its effects on students' learning curves.

Circulating miRNAs associate with historical childhood asthma hospitalization in different serum vitamin D groups.

BACKGROUND: Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. METHODS: We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). RESULTS: We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. CONCLUSIONS: miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.

Obesity Disparities Among Adult Single-Race and Multiracial Asian and Pacific Islander Populations.

Importance: Despite increasing numbers of multiracial individuals, they are often excluded in studies or aggregated within larger race and ethnicity groups due to small sample sizes. Objective: To examine disparities in the prevalence of obesity among single-race and multiracial Asian and Pacific Islander individuals compared with non-Hispanic White (hereafter, White) individuals. Design, Setting, and Participants: This cross-sectional study used electronic health record (EHR) data linked to social determinants of health and health behavior data for adult (age ≥18 years) members of 2 large health care systems in California and Hawai'i who had at least 1 ambulatory visit to a primary care practitioner between January 1, 2006, and December 31, 2018. Data were analyzed from October 31, 2022, to July 31, 2023. Exposure: Self-identified race and ethnicity provided in the EHR as a single-race category (Asian Indian, Chinese, Filipino, Japanese, Native Hawaiian only, Other Pacific Islander, or White) or a multiracial category (Asian and Pacific Islander; Asian, Pacific Islander, and White; Asian and White; or Pacific Islander and White). Main Outcomes and Measures: The main outcome was obesity (body mass index [BMI] ≥30.0), based on last measured height and weight from the EHR. Logistic regression was used to examine the association between race and ethnicity and odds of obesity. Results: A total of 5229 individuals (3055 [58.4%] male; mean [SD] age, 70.73 [11.51] years) were examined, of whom 444 (8.5%) were Asian Indian; 1091 (20.9%), Chinese; 483 (9.2%), Filipino; 666 (12.7%), Japanese; 91 (1.7%), Native Hawaiian; 95 (1.8%), Other Pacific Islander; and 888 (17.0%), White. The percentages of individuals who identified as multiracial were as follows: 417 (8.0%) were Asian and Pacific Islander; 392 (7.5%), Asian, Pacific Islander, and White; 248 (4.7%), Asian and White; and 414 (7.9%), Pacific Islander and White. A total of 1333 participants (25.5%) were classified as having obesity based on standard BMI criteria. Obesity was highest among people who identified as Asian, Pacific Islander, and White (204 of 392 [52.0%]) followed by those who identified as Other Pacific Islander (47 of 95 [49.5%]), Native Hawaiian (44 of 91 [48.4%]), and Pacific Islander and White (186 of 414 [44.9%]). After accounting for demographic, socioeconomic, and health behavior factors, people who identified as Asian, Pacific Islander, and White (odds ratio [OR], 1.80; 95% CI, 1.37-2.38) or Pacific Islander and White (OR, 1.55; 95% CI, 1.18-2.04) had increased odds of obesity compared with White individuals. All single-race Asian groups had lower odds of obesity compared with White individuals: Asian Indian (OR, 0.29; 95% CI, 0.20-0.40), Chinese (OR, 0.22; 95% CI, 0.17-0.29), Filipino (OR, 0.46; 95% CI, 0.35-0.62), and Japanese (OR, 0.38, 95% CI, 0.29-0.50). Conclusions and Relevance: In this study, multiracial Asian and Pacific Islander individuals had an increased prevalence of obesity compared with many of their single-race counterparts. As the number of multiracial individuals increases, it will be important for clinical and public health systems to track disparities in these populations.