DNA response element-based smart drug delivery systems for precise drug release.

Smart drug delivery systems (DDSs) that respond to, interact with, or are actuated by biological signals or pathological abnormalities (e.g., the tumor microenvironment) for controllable drug release are appealing therapeutic platforms for cancer treatment. Owing to their inherent self-assembled nature, nucleic acids have emerged as programmable materials for the development of multifunctional structures. In response to external environmental stimuli, DNA response elements can serve as switches to trigger conformational changes in DNA structures. Their stimulus-responsive properties make them promising candidates for constructing smart DDSs, and advancements in DNA response element-based DDSs in the field of biomedicine have been made. This review summarizes different types of DNA response elements, including DNA aptamers, DNAzymes, disulfide bond-modified DNA, pH-responsive DNA motifs, and photocleavable DNA building blocks, and highlights the advancements in DNA response element-based smart DDSs for precise drug release. Finally, future challenges and perspectives in this field are discussed.

Regional Differences in the US in Outcomes with Preeclampsia.

This study explores preeclampsia outcomes across US regions and examines regional differences in specific preeclampsia-associated pregnancy complications and disease management. Patient-reported measures were obtained from The Preeclampsia Registry, an open-access database composed of women with at least one pregnancy diagnosed with a hypertensive disorder of pregnancy. Pregnancies and associated outcomes were stratified by US region (Northeast, Midwest, South and West). Among 2,667 pregnancies of which 92% were in White women, maximum systolic blood pressure at any time in pregnancy was highest among women in the South and Midwest (p=0.039). Furthermore, more women in the South received pre-pregnancy antihypertensives (p=0.026) and antenatal steroids (p=0.025) and delivered at an earlier gestational age (p=0.014) compared to women in other regions. Pregnancy complications such as elevated liver enzymes were higher in women in the South (p=0.019), and women in the South and West had additional end-organ damage such as renal complications (p<0.001) and hemolysis (p=0.008) as compared to women in other regions. Further investigation is needed to assess whether healthcare access or policy could be contributing to these regional discrepancies.

Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

The impact of stress on the risk decision-making process.

The effect of stress on risk-taking or risk-averse behavior in decision-making has been inconclusive in previous research, with few studies revealing the underlying neural mechanisms. This study employed event-related potentials technique and combined a social cold pressor assessment test with a mental arithmetic task to induce stress responses, aiming to investigate the influence of exogenous stress on the risk decision-making process. Stress induction results indicated that, in addition to raising heart rate and blood pressure, stress responses were accompanied by enhanced negative emotions, diminished positive emotions, and alterations in neural activity. The outcomes of risk decision-making showed that stress did not significantly affect risk preference or time of choice but did reduce the feedback-related negativity/reward positivity, with a particularly significant effect observed for large outcomes. Stress also altered the amplitude of the P3 component, with stress decreasing the P3 value for winning outcomes relative to losing outcomes. The study suggests that understanding how stress affects risk preference should consider the emotional valence induced by stress. Contrary to the reward sensitivity hypothesis, stress weakened reward sensitivity. Stress led to changes in the allocation of cognitive resources for outcome evaluation: compared to negative outcomes, stress reduced cognitive resources for positive outcomes, which might be related to the enhanced negative emotions induced by stress. The study highlights the importance of focusing on the subjective emotional experience induced by stress in future research on stress and risk decision-making.

A comprehensive review of oxygen vacancy modified photocatalysts: synthesis, characterization, and applications.

Photocatalytic technology is a novel approach that harnesses solar energy for efficient energy conversion and effective pollution abatement, representing a rapidly advancing field in recent years. The development and synthesis of high-performance semiconductor photocatalysts constitute the pivotal focal point. Oxygen vacancies, being intrinsic defects commonly found in metal oxides, are extensively present within the lattice of semiconductor photocatalytic materials exhibiting non-stoichiometric ratios. Consequently, they have garnered significant attention in the field of photocatalysis as an exceptionally effective means for modulating the performance of photocatalysts. This paper provides a comprehensive review on the concept, preparation, and characterization methods of oxygen vacancies, along with their diverse applications in nitrogen fixation, solar water splitting, CO2 photoreduction, pollutant degradation, and biomedicine. Currently, remarkable progress has been made in the synthesis of high-performance oxygen vacancy photocatalysts and the regulation of their catalytic performance. In the future, it will be imperative to develop more advanced in situ characterization techniques, conduct further investigations into the regulation and stabilization of oxygen vacancies in photocatalysts, and comprehensively comprehend the mechanism underlying the influence of oxygen vacancies on photocatalysis. The engineering of oxygen vacancies will assume a pivotal role in the realm of semiconductor photocatalysis.

TBCRC 057: Survey about willingness to participate in cancer clinical trials during the pandemic.

BACKGROUND: Breast cancer patients experienced heightened anxiety during the pandemic. Also, modifications to clinical trial activities allowing for virtual platforms, local assessments, and greater flexibility were introduced to facilitate participation. We sought to evaluate the association between pandemic-related anxiety and willingness to participate in trials and how pandemic-era modifications to trial activities affect the decision to participate. METHODS: We conducted an online survey from August to September, 2021 of patients with breast cancer assessing pandemic-related anxiety; clinical trials knowledge and attitudes; willingness to participate during and before the pandemic; and how each modification affects the decision to participate. Fisher's exact tests evaluated differences in proportions and two-sample t-tests evaluated differences in means. The association of pandemic-related anxiety with a decline in willingness to participate during compared to prior to the pandemic was modeled using logistic regression. RESULTS: Among 385 respondents who completed the survey, 81% reported moderate-severe pandemic-related anxiety. Mean willingness to participate in a trial was lower during the pandemic than prior [2.97 (SD 1.17) vs. 3.10 (SD 1.09), (p < 0.001)]. Severe anxiety was associated with higher odds of diminished willingness to participate during the pandemic compared to prior (OR 5.07). Each of the modifications, with the exception of opting out of research-only blood tests, were endorsed by >50% of respondents as strategies that would increase their likelihood of deciding to participate. CONCLUSIONS: While pandemic-related anxiety was associated with diminished willingness to participate in trials, the leading reasons for reluctance to consider trial participation were unrelated to the pandemic but included worries about not getting the best treatment, side effects, and delaying care. Patients view trial modifications favorably, supporting continuation of these modifications, as endorsed by the National Cancer Institute and others.

Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function.

PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p.

BACKGROUNDS: The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs. RESULTS: In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development. CONCLUSION: These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-ß-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development.

Parents' and Caregivers' Support for in-School COVID-19 Mitigation Strategies: A Socioecological Perspective.

Informed by the social ecological model, which asserts that health behaviors and beliefs are the result of multiple levels of influence, we examined factors related to parents' support for in-school COVID-19 mitigation strategies. Using data from a survey of 567 parents/caregivers of public elementary and middle school students in eight Maryland counties, we employed regression models to examine relationships between parent-, child-, family-, school-, and community-level factors and acceptability of mitigation strategies. Acceptance of COVID-19 mitigation strategies was positively correlated with child- and family-level factors, including child racial identity (parents of Black children were more accepting than those of White children, odds ratio [OR]: 2.5, 95% confidence interval [CI] = [1.5, 4.1]), parent receipt of the COVID-19 vaccine (OR: 2.4, 95% CI = [1.5, 3.7]), and parent Democrat or Independent political affiliation (compared with Republican affiliation, OR: 4.2, 95% CI = [2.6, 6.7]; OR: 2.2, 95%CI = [1.3, 3.8], respectively). Acceptance was also positively associated with parents' perceptions of their school's mitigation approach, including higher school mitigation score, indicating more intensive mitigation policies (OR: 1.1, 95% CI = [1.0, 1.1]), better school communication about COVID-19 (OR: 1.7, 95% CI = [1.4, 1.9]) and better school capacity to address COVID-19 (OR: 1.9, 95% CI = [1.5, 2.4]). Community-level factors were not associated with acceptance. Child- and parent-level factors identified suggest potential groups for messaging regarding mitigation strategies. School-level factors may play an important role in parents' acceptance of in-school mitigation strategies. Schools' capacity to address public health threats may offer an underappreciated and modifiable setting for disseminating and reinforcing public health guidance.

Parents' Trust in COVID-19 Messengers and Implications for Vaccination.

PURPOSE: To characterize factors associated with parents' trust in messengers of COVID-19 guidance and determine whether trust in their doctors is associated with COVID-19 vaccination. DESIGN: Web-based and mailed survey (January-June 2022). SETTING: Maryland, USA. SUBJECTS: 567 parents/caregivers of public elementary and middle school students. MEASURES: Parents rated trust in 9 messengers on a 4-point scale ["not at all" (0) to "a great deal" (3)], dichotomized into low (0-1) vs high (2-3). They reported on health insurance, income, race, ethnicity, education, sex, urbanicity, political affiliation, and COVID-19 vaccination. ANALYSIS: ANOVA and t-tests were computed to compare overall trust by parent characteristics. Multivariable logistic regression was run to evaluate factors associated with high trust for each messenger. Multivariable logistic regression was used to evaluate the relationship between trust in doctors and odds of COVID-19 vaccination. RESULTS: Most trusted messengers were doctors (M = 2.65), family members (M = 1.87), and schools (M = 1.81). Parents' trust varied by racial identity, sex, urbanicity, health insurance, and political affiliation. Greater trust in their or their child's doctor was associated with greater odds of child (aOR: 2.97; 95% CI: 1.10, 7.98) and parent (aOR: 3.30; 95% CI: 1.23, 1.47) vaccination. CONCLUSION: Parent characteristics were associated with trust, and trust was linked to vaccination. Public health professionals should anticipate variability in trusted messengers to optimize uptake of public health guidance.

Clinicopathological characteristics of 3 probable pediatric cases with acute severe hepatitis of unknown aetiology.

Background: Acute severe hepatitis with unknown aetiology in children (ASHep-UA) has become a global health alert. This article reported clinicopathological characteristics of 3 probable ASHep-UA cases. Methods: We respectively collected serological data and liver biopsies of 3 suspected cases of ASHep-UA. Neutralizing antibodies titer for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants were determined by virus neutralization test (VNT). Histological assessment, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human adenoviruses (HAdV), adeno-associated virus (AAV2), human herpes virus type 6 (HHV-6) were performed to identify possible aetiologies. Results: Remarkable elevation of transaminase (median ALT level, 1100 IU/liter; median AST level, 500 IU/liter) were revealed with undetectable hepatitis A-E and non-hepatotropic virus in both sera and tissues. Weakness, jaundice, pale stools and splenomegaly were observed. Interestingly, two individuals had SARS-CoV-2 Omicron variants infection. Histologically, moderate or severe lobular necroinflammation, active interface hepatitis and portal inflammatory infiltrate with lymphocytic, plasma cells, neutrophils and eosinophilic cells were noted. Conclusions: The exact aetiology of ASHep-UA was still unknown. By reporting the 3 probable cases, we expect to enrich the clinical experience in diagnosis and treatment of ASHep-UA as well as the pathological characteristics.

Microgel Encapsulated Nanoparticles for Intra-articular Disulfiram Delivery to Treat Osteoarthritis.

Osteoarthritis (OA) affects numerous patients worldwide, and there are no approved disease-modifying drugs. Repurposing FDA-approved small molecular drugs could be a promising alternative strategy to treat OA. Disulfiram (DSF), a clinically approved drug for treatment of alcoholism, inhibits inflammasome activation and exhibits a protective role in interleukin-1ß-induced cardiac injury. However, its efficacy in treating OA remains to be explored due to its poor water solubility and stability, which limit its use in OA treatment. Here, the anti-inflammatory effect of DSF is evaluated in vitro, and a double-layer encapsulation approach is developed for intra-articular delivery of DSF for OA treatment in vivo. DSF is loaded into poly(lactic-co-glycolic acid)-based nanoparticles and encapsulated in gelatin methacrylate microgels through a microfluidic device. Results show that DSF effectively inhibits the expression of key inflammatory cytokines in OA chondrocytes, and the double-layer encapsulation approach reduces the burst release of DSF and prolongs its retention time in the in vitro study. Sustained release of DSF from microgels mitigates cartilage inflammation and subchondral bone erosion in a monoiodoacetate-induced rat OA model. This work demonstrates the potential of repurposing FDA-approved drugs for OA treatment and provides a promising platform for intra-articular delivery of small molecules for superior therapeutic effect.

Trends in the Utilization of Herbal and Dietary Supplements in Patients with Chronic Liver Disease During the SARS-CoV2 Pandemic.

Background: We studied the pattern of herbal and dietary supplement (HDS) use in patients with chronic liver disease (CLD) during the first year of the COVID-19 pandemic. Methods: A questionnaire/survey was sent to hepatology patients with CLD under the care of hepatologists at Johns Hopkins University School of Medicine. Results: The 5 most taken dietary supplements during the pandemic included vitamin B12 (27.7%), vitamin C (32.4%), vitamin D (54.6%), zinc (25.4%) and green tea extract (20.8%). Most participants (82.3%) did not discuss their HDS use with their hepatology providers. Conclusions: Healthcare providers should be mindful of potential HDS use in patients with CLD.

Risk factors for surgical site infections following open reduction and internal fixation in patients with tibial plateau fractures.

This retrospective cohort study aimed to identify the risk factors associated with postoperative wound infections in patients undergoing open reduction and internal fixation for tibial plateau fractures. The study was conducted between January 2019 and December 2022, with stringent inclusion and exclusion criteria. Data were collected from the Electronic Health Record system, including demographic information, lifestyle habits, comorbid conditions and surgical variables like preoperative American Society of Anesthesiologists (ASA) scores. The IBM Statistical Package for the Social Sciences, version 27.0, was utilized for rigorous statistical analyses. Univariate analysis identified several factors, such as body mass index (BMI), smoking status and diabetes mellitus, as significant predictors of postoperative wound infection. Multivariate logistic regression revealed that BMI, type of fracture (open vs. closed), surgery duration exceeding 150 min, preoperative albumin levels below 35 g/L and preoperative ASA score of 3 or higher were significant independent risk factors (p < 0.05). Patients with open fractures, preoperative malnutrition, elevated preoperative ASA scores and a history of smoking are at a heightened risk of developing postoperative wound infections. Timely preoperative evaluation of these risk factors is crucial for minimizing the risk of surgical site infections and optimizing clinical management.

Clinical study of hepatitis B vaccine in achieving hepatitis B surface antibody seroconversion in patients with functional cure.

Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Levels of Matrix Metalloproteinase 9 Are Elevated in Persons With Schizophrenia or Bipolar Disorder: The Role of Modifiable Factors.

Background: Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with inflammation. MMP-9 is of particular interest because it has been associated with autoimmune and cardiopulmonary disorders, tobacco smoking, and obesity, prevalent in psychiatric populations. Methods: Sensitive enzyme immunoassays measured MMP-9 in blood samples from 1121 individuals (mean age = 35.6 [SD = 13.0] years; 47.7% male; 440 with schizophrenia, 399 with bipolar disorder, and 282 without a psychiatric disorder). We estimated the odds of diagnosis associated with MMP-9, demographic variables, tobacco smoking, and obesity, and also the partial explained variance using regression methods. We also determined the association between psychiatric medications and MMP-9 levels. Results: Individuals with elevated MMP-9 levels had higher odds of schizophrenia or bipolar disorder compared with the nonpsychiatric group adjusted for demographic variables. Partial correlation analyses indicated the demographic-adjusted variance associated with MMP-9, smoking, obesity, and their interaction explained 59.6% for schizophrenia and 39.9% for bipolar disorder. Levels of MMP-9 were substantially lower in individuals receiving valproate, particularly relatively high doses. Conclusions: Individuals with higher levels of MMP-9 have significantly higher odds of schizophrenia or bipolar disorder. Individuals receiving valproate had substantially lower levels of MMP-9, possibly related to its ability to inhibit histone deacetylation. A substantial portion of the variance in clinical disorders associated with MMP-9 can be attributed to smoking or obesity. Interventions to reduce smoking and obesity might reduce the morbidity and mortality associated with elevated MMP-9 levels and improve the health outcomes of individuals with these disorders.

Dietary D-xylose promotes intestinal health by inducing phage production in Escherichia coli.

Elimination of specific enteropathogenic microorganisms is critical to gut health. However, the complexity of the gut community makes it challenging to target specific bacterial organisms. Accumulating evidence suggests that various foods can change the abundance of intestinal bacteria by modulating prophage induction. By using pathogenic Escherichia coli (E. coli) ATCC 25922 as a model in this research, we explored the potential of dietary modulation of prophage induction and subsequent bacterial survival. Among a panel of sugars tested in vitro, D-xylose was shown to efficiently induce prophages in E. coli ATCC 25922, which depends, in part, upon the production of D-lactic acid. In an enteric mouse model, prophage induction was found to be further enhanced in response to propionic acid. Dietary D-xylose increased the proportion of Clostridia which converted D-lactic acid to propionic acid. Intestinal propionic acid levels were diminished, following either oral gavage with the dehydrogenase gene (ldhA)-deficient E. coli ATCC 25922 or depletion of intestinal Clostridia by administration of streptomycin. D-Xylose metabolism and exposure to propionic acid triggered E. coli ATCC 25922 SOS response that promoted prophage induction. E. coli ATCC 25922 mutant of RecA, a key component of SOS system, exhibited decreased phage production. These findings suggest the potential of using dietary components that can induce prophages as antimicrobial alternatives for disease control and prevention by targeted elimination of harmful gut bacteria.

L-arabinose Attenuates LPS-Induced Intestinal Inflammation and Injury through Reduced M1 Macrophage Polarization.

BACKGROUND: L-arabinose has anti-inflammatory and metabolism-promoting properties, and macrophages participate in the alleviation of inflammation; however, the mechanism by which they contribute to the anti-inflammatory effects of L-arabinose is unknown. OBJECTIVES: To investigate the involvement of macrophages in the mitigation of L-arabinose in an intestinal inflammation model induced by lipopolysaccharide (LPS). METHODS: Five-week-old male C57BL/6 mice were divided into 3 groups: a control and an LPS group that both received normal water supplementation, and an L-arabinose (ARA+LPS) group that received 5% L-arabinose supplementation. Mice in the LPS and ARA+LPS groups were intraperitoneally injected with LPS (10 mg/kg body weight), whereas the control group was intraperitoneally injected with the same volume of saline. Intestinal morphology, cytokines, tight junction proteins, macrophage phenotypes, and microbial communities were profiled at 6 h postinjection. RESULTS: L-arabinose alleviated LPS-induced damage to intestinal morphology. L-arabinose down-regulated serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6, and messenger RNA (mRNA) levels of TNF-α, IL-1ß, interferon-γ (IFN-γ), and toll-like receptor-4 in jejunum and colon compared with those of the LPS group (P < 0.05). The mRNA and protein levels of occludin and claudin-1 were significantly increased by L-arabinose (P < 0.05). Interferon regulatory factor-5 (IRF-5) and signal transducer and activator of transcription-1 (STAT-1), key genes characterized by M1 macrophages, were elevated in the jejunum and colon of LPS mice (P < 0.05) but decreased in the ARA+LPS mice (P < 0.05). In vitro, L-arabinose decreased the proportion of M1 macrophages and inhibited mRNA levels of TNF-α, IL-1ß, IL-6, IFN-γ, as well as IRF-5 and STAT-1 (P < 0.01). Moreover, L-arabinose restored the abundance of norank_f__Muribaculaceae, Faecalibaculum, Dubosiella, Prevotellaceae_UCG-001, and Paraasutterella compared with those of LPS (P < 0.05) and increased the concentration of short-chain fatty acids (P < 0.05). CONCLUSION: The anti-inflammatory effects of L-arabinose are achieved by reducing M1 macrophage polarization, suggesting that L-arabinose could be a candidate functional food or nutritional strategy for intestinal inflammation and injury.

Identifying and preventing fraudulent responses in online public health surveys: Lessons learned during the COVID-19 pandemic.

Web-based survey data collection has become increasingly popular, and limitations on in-person data collection during the COVID-19 pandemic have fueled this growth. However, the anonymity of the online environment increases the risk of fraudulent responses provided by bots or those who complete surveys to receive incentives, a major risk to data integrity. As part of a study of COVID-19 and the return to in-person school, we implemented a web-based survey of parents in Maryland between December 2021 and July 2022. Recruitment relied, in part, on social media advertisements. Despite implementing many existing best practices, we found the survey challenged by sophisticated fraudsters. In response, we iteratively improved survey security. In this paper, we describe efforts to identify and prevent fraudulent online survey responses. Informed by this experience, we provide specific, actionable recommendations for identifying and preventing online survey fraud in future research. Some strategies can be deployed within the data collection platform such as careful crafting of survey links, Internet Protocol address logging to identify duplicate responses, and comparison of client-side and server-side time stamps to identify responses that may have been completed by respondents outside of the survey's target geography. Other strategies can be implemented during the survey design phase. These approaches include the use of a 2-stage design in which respondents must be eligible on a preliminary screener before receiving a personalized link. Other design-based strategies include within-survey and cross-survey validation questions, the addition of "speed bump" questions to thwart careless or computerized responders, and the use of optional open-ended survey questions to identify fraudsters. We describe best practices for ongoing monitoring and post-completion survey data review and verification, including algorithms to expedite some aspects of data review and quality assurance. Such strategies are increasingly critical to safeguarding survey-based public health research.

Electric field as a crystallization switch of heterogeneous ice formation.

Using molecular dynamics simulations, we investigated the effect of external electric field on ice formation with the present of a substrate surface. It turns out that the electric field can affect the ice formation on substrate surface by altering the dipole orientation of interfacial water molecules (IWs): a crossover from inhibiting to promoting ice formation with the increase of electric field strength. According to the influence of the electric field on ice formation, the electric field strength range of 0.0 V nm-1-7.0 V nm-1can be divided into three regions. In the region I and region III, there are both ice formation on the substrate surface. While, the behavior of IWs in the region I and region III are distinguished, including the arrangements of oxygen atoms and the dipole orientation distribution. In region II, ice formation does not occur in the system within 5 × 200 ns simulations. The IWs show a disorder structure, preventing the ice formation process on substrate. The interfacial water molecular orientation distribution and two-dimensional free energy landscape reveals that the electric field can alter the dipole orientation of the interfacial water and lead a free energy barrier, making the ice formation process harder. Our result demonstrates the external electric field can regulate the behavior of IWs, and further affect the ice formation process. The external electric field act as a crystallization switch of ice formation on substrate, shedding light into the studies on the control of ice crystallization.