AM-18002, a derivative of natural anmindenol A, enhances radiosensitivity in mouse breast cancer cells.

Natural anmindenol A isolated from the marine-derived bacteria Streptomyces sp. caused potent inhibition of inducible nitric oxide synthase without any significant cytotoxicity. This compound consists of a structurally unique 3,10-dialkylbenzofulvene skeleton. We previously synthesized and screened the novel derivatives of anmindenol A and identified AM-18002, an anmindenol A derivative, as a promising anticancer agent. The combination of AM-18002 and ionizing radiation (IR) improved anticancer effects, which were exerted by promoting apoptosis and inhibiting the proliferation of FM3A mouse breast cancer cells. AM-18002 increased the production of reactive oxygen species (ROS) and was more effective in inducing DNA damage. AM-18002 treatment was found to inhibit the expansion of myeloid-derived suppressor cells (MDSC), cancer cell migration and invasion, and STAT3 phosphorylation. The AM-18002 and IR combination synergistically induced cancer cell death, and AM-18002 acted as a potent anticancer agent by increasing ROS generation and blocking MDSC-mediated STAT3 activation in breast cancer cells.

Immunogenicity of COVID-19 vaccines and their effect on HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. Our study on 68 PWH and 23 HIV-negative participants aged 55 and older post-three vaccine doses showed equally strong anti-spike IgG responses in serum and saliva through week 48 from baseline, while PWH salivary IgA responses were low. PWH had diminished live-virus neutralization responses after two vaccine doses, which were 'rescued' post-booster. Spike-specific T cell immunity was enhanced in PWH with normal CD4+ T cell count, suggesting Th1 imprinting. The frequency of detectable HIV viremia increased post-vaccination, but vaccines did not affect the size of the HIV reservoir in most PWH, except those with low-level viremia. Thus, older PWH require three doses of COVID-19 vaccine for maximum protection, while individuals with unsuppressed viremia should be monitored for adverse reactions from HIV reservoirs.

Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4 + T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV - participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were 'rescued' after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV - participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral 'blips' in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4 + T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.

A method for assessing students' interpretations of contextualized data.

Learning to interpret data in context is an important educational outcome. To assess students' attainment of this outcome, it is necessary to examine the interplay between their contextual and statistical reasoning. We describe a research method designed to do so. The method draws upon Toulmin's (1958, 2003) model of argumentation for the first stage of qualitative data analysis and the Structure of the Observed Learning Outcome (SOLO) (Biggs & Collis, 1991) model for the second stage. Toulmin analyses help identify the justifications and expressions of uncertainty students provide in their interpretive arguments. Subsequent analyses based on the multi-modal conceptualization of SOLO help characterize the quality of student arguments relative to one another. Existing literature and an empirical example are drawn upon to explain how the Toulmin and SOLO models can be used in tandem to analyze students' interpretations of contextualized data. We also explain how pairing Toulmin and SOLO can address theoretical and practical limitations that arise when using just one of the two models on its own.

Enhanced Interlayer Charge Injection Efficiency in 2D Multilayer ReS2 via Vertical Double-Side Contacts.

Two-dimensional (2D) van der Waals (vdW) layered materials have provided novel opportunities to explore interesting physical properties such as thickness-dependent bandgap, moiré excitons, superconductivity, and superfluidity. However, the presence of interlayer resistance along the thickness and Schottky barrier in metal-to-2D vdW semiconducting materials causes a limited interlayer charge injection efficiency, perturbing various intrinsic properties of 2D vdW multilayers. Herein, we report a simple but powerful contact electrode design to enhance interlayer carrier injection efficiency along the thickness by constructing vertical double-side contact (VDC) electrodes. A 2-fold extended contact area of VDC not only strongly limits an interlayer resistance contribution to the field-effect mobility and current density at the metal-to-2D semiconductor interface but also significantly suppresses both current transfer length (≤1 µm) and specific contact resistivity (≤1 mΩ·cm2), manifesting clear benefits of VDC in comparison with those in conventional top-contact and bottom-contact configurations. Our layout for contact electrode configuration may suggest an advanced electronic device platform for high-performing 2D optoelectronic devices.

Facile Detection of Light-Controlled Radical Scavengers from Natural Products Using In Situ UV-LED NMR Spectroscopy.

With the recent development of chemical analysis technology, attention has been placed on natural light-sensitive compounds that exhibit photoreactivity to expand the structural diversity of natural product chemistry. Photochemical reactions that proceed via a free radical mechanism could be used to modulate the radical-scavenging ability of natural products as well as involve structural change. As the health benefits of radicals are also presented, there is a need for a controllable radical scavenging method for topical and selective application. In this study, we developed a novel acquisition and processing method to identify light-controlled radical scavengers in plant extracts and evaluate their antioxidant activity under light irradiation based on in situ UV-LED NMR spectroscopy. Using the developed method, licochalcones A and B, in which the trans and cis isomers undergo reversible photoisomerization, were selectively identified from licorice root extract, and their light-induced free radical scavenging activity was confirmed.

Light-Driven Ammonia Production by Azotobacter vinelandii Cultured in Medium Containing Colloidal Quantum Dots.

There is an evergrowing demand for environment-friendly processes to synthesize ammonia (NH3) from atmospheric nitrogen (N2). Although diazotrophic N2 fixation represents an undeniably "green" process of NH3 synthesis, the slow reaction rate makes it less suitable for industrially meaningful large-scale production. Here, we report the photoinduced N2 fixation using a hybrid system composed of colloidal quantum dots (QDs) and aerobic N2-fixing bacteria, Azotobacter vinelandii. Compared to the case where A. vinelandii cells are simply mixed with QDs, NH3 production increases significantly when A. vinelandii cells are cultured in the presence of core/shell InP/ZnSe QDs. During the cell culture of A. vinelandii, the cellular uptake of QDs is facilitated in the exponential growth phase. Experimental results as well as theoretical calculations indicate that the photoexcited electrons in QDs within A. vinelandii cells are directly transferred to MoFe protein, the catalytic component of nitrogenase. We also observe that the excess amount of QDs left on the outer surface of A. vinelandii disrupts the cellular membrane, leading to the decrease in NH3 production due to the deactivation of nitrogenase. The successful uptake of QDs in QD-A. vinelandii hybrid with minimal amount of QDs on the outer surface of the bacteria is key to efficient photosensitized NH3 production. The comprehensive understanding of the QD-bacteria interface paves an avenue to novel and efficient nanobiohybrid systems for chemical production.

Immune parameters of HIV susceptibility in the female genital tract before and after penile-vaginal sex.

Background: In women, most HIV infections are acquired through penile-vaginal sex. Inflammation in the female genital tract (FGT) increases the risk of HIV acquisition and transmission, likely through recruitment of HIV target cells and disruption of epithelial barrier integrity. Although sex may have important immune and epithelial effects, the impact of receptive penile-vaginal sex on the immune correlates of HIV susceptibility in the female genital tract is not well described. Methods: STI-free heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the serial collection of cervical secretions (CVS), endocervical cytobrushes, blood and semen before and up to 72 h after either condomless (n = 29) or condom-protected (n = 8) penile-vaginal sex. Immune cells were characterized by flow cytometry, and immune factors including cytokines and soluble E-cadherin (sE-cad; a marker of epithelial disruption) were quantified by multiplex immunoassay. Co-primary endpoints were defined as levels of IP-10 and IL-1α, cytokines previously associated with increased HIV susceptibility. Results: Here we show that cervicovaginal levels of vaginal IP-10, sE-cad and several other cytokines increase rapidly after sex, regardless of condom use. The proportion of endocervical HIV target cells, including Th17 cells, activated T cells, and activated or mature dendritic cells (DCs) also increase, particularly after condomless sex. Although most of these immune changes resolve within 72 h, increases in activated cervical CD4 + T cells and Tcm persist beyond this time. Conclusions: Penile-vaginal sex induces multiple genital immune changes that may enhance HIV susceptibility during the 72 h post-sex window that is critical for virus acquisition. This has important implications for the mucosal immunopathogenesis of HIV transmission.

Insertive condom-protected and condomless vaginal sex both have a profound impact on the penile immune correlates of HIV susceptibility.

The penis is the primary site of HIV acquisition in heterosexual men. Elevated penile inflammatory cytokines increase sexual acquisition risk, and topically applied cytokines enhance foreskin HIV susceptibility in an explant model. However, the impact of penile-vaginal sex on these immune parameters is undefined. Heterosexual couples were recruited to the Sex, Couples and Science (SECS) Study, with the collection of penile swabs, semen, cervico-vaginal secretions, and blood after a period of abstinence, and repeated sampling up to 72 hours after either condomless (n = 30) or condom-protected (n = 8) penile-vaginal sex. Soluble immune parameters were quantified by multiplex immunoassay. Co-primary immune endpoints were penile levels of IL-8 and MIG, cytokines previously linked to penile HIV acquisition. One hour after sex there were dramatic increases in penile IL-8 and MIG levels, regardless of condom use, with a gradual return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. Penile cytokine changes were similar in circumcised and uncircumcised men, and repeated measures ANOVA and ANCOVA models demonstrated that the degree of change after condomless sex was explained by cytokine levels in their partners' cervico-vaginal secretions. This may have important implications for the biology of penile HIV acquisition.

G9a Knockdown Suppresses Cancer Aggressiveness by Facilitating Smad Protein Phosphorylation through Increasing BMP5 Expression in Luminal A Type Breast Cancer.

Epigenetic abnormalities affect tumor progression, as well as gene expression and function. Among the diverse epigenetic modulators, the histone methyltransferase G9a has been focused on due to its role in accelerating tumorigenesis and metastasis. Although epigenetic dysregulation is closely related to tumor progression, reports regarding the relationship between G9a and its possible downstream factors regulating breast tumor growth are scarce. Therefore, we aimed to verify the role of G9a and its presumable downstream regulators during malignant progression of breast cancer. G9a-depleted MCF7 and T47D breast cancer cells exhibited suppressed motility, including migration and invasion, and an improved response to ionizing radiation. To identify the possible key factors underlying these effects, microarray analysis was performed, and a TGF-ß superfamily member, BMP5, was selected as a prominent target gene. It was found that BMP5 expression was markedly increased by G9a knockdown. Moreover, reduction in the migration/invasion ability of MCF7 and T47D breast cancer cells was induced by BMP5. Interestingly, a G9a-depletion-mediated increase in BMP5 expression induced the phosphorylation of Smad proteins, which are the intracellular signaling mediators of BMP5. Accordingly, we concluded that the observed antitumor effects may be based on the G9a-depletion-mediated increase in BMP5 expression and the consequent facilitation of Smad protein phosphorylation.

Preoperative carbohydrate antigen 19-9 and standard uptake value of positron emission tomography-computed tomography as prognostic markers in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Among various prognostic factors of pancreatic cancer, preoperative clinical information is obtained by imaging modality. This study aimed to evaluate clinical usefulness of preoperative carbohydrate antigen and preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography as predictive biological markers for resectable pancreatic ductal adenocarcinoma. METHODS: A total of 189 patients with PDAC who underwent preoperative PET-computed tomography were evaluated. Patients underwent neoadjuvant chemotherapy, and R2 resection was excluded. The correlation between SUVmax and clinicopathologic parameters was analyzed. The C-tree statistical method was used to estimate cutoff values of logCA19-9 and SUVmax for survival rate. A multivariate analysis was conducted to identify prognostic factors for overall survival. RESULTS: The median duration of OS was 26 months, and the 5-year survival rate was 22.4%. The optimal cutoff values for CA19-9 level was 150 U/mL and SUVmax was 5.5. When subjects were divided into three groups according to the combination of CA19-9 level and SUVmax from C-tree (high-risk group, CA19-9 > 150 U/mL and SUVmax > 5.5; intermediate-risk group, CA19-9 ≤ 150 U/mL and SUVmax > 5.5 or CA19-9 > 150 U/mL and SUVmax ≤ 5.5; and low-risk group, CA19-9 ≤ 150 U/mL and SUVmax ≤ 5.5), there was a significant 5YSR difference (5.6%, 24.3%, and 36.5%, P < .001). The multivariate analysis revealed high SUVmax, high preoperative CA19-9 level, venous invasion, and adjuvant chemotherapy were prognostic factors of OS. CONCLUSIONS: CA19-9 and SUVmax are strong prognostic biological factors in resectable PDAC. Moreover, patients with high CA19-9 level and SUVmax are not indicated for upfront surgery.

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

BACKGROUND: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. METHODS: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. FINDINGS: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. INTERPRETATION: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+. FUNDING: International Agency for Research on Cancer.

Low-Level Anorectal HIV Shedding despite Effective Antiretroviral Therapy Is Not Driven by Mucosal Inflammation.

Although antiretroviral treatment (ART) suppresses HIV RNA in blood and prevents transmission, low-level anorectal HIV RNA shedding persists in some ART-treated men who have sex with men. We collected anorectal biopsies and swabs from 55 men who have sex with men on effective ART, hypothesizing that anorectal shedding would be linked to microbiota-driven mucosal T cell activation. Lymphocytes were assessed by flow cytometry, soluble immune factors by multiplex immunoassay, neutrophils and epithelial integrity by immunofluorescence microscopy, and the anorectal microbiome by quantitative PCR and 16S rRNA gene sequencing. Unexpectedly, we found no evidence that anorectal HIV shedding was associated with the parameters of mucosal inflammation, including T cell activation, inflammatory cytokines, the density of neutrophils, or epithelial integrity. Moreover, the anorectal bacterial load was actually lower in the shedding group, with no major differences in bacterial composition. Instead, the strongest mucosal immune correlates of HIV shedding were an increase in central memory cell frequency and Ki67 expression as well as higher concentrations of the cytokine IL-7 in anorectal secretions. Anorectal HIV RNA shedding during effective ART was not driven by local inflammation; the associations seen with local homeostatic T cell proliferation will require further confirmation.

Two-Target Quantitative PCR To Predict Library Composition for Shallow Shotgun Sequencing.

When determining human microbiota composition, shotgun sequencing is a powerful tool that can generate high-resolution taxonomic and functional information at once. However, the technique is limited by missing information about host-to-microbe ratios observed in different body compartments. This limitation makes it difficult to plan shotgun sequencing assays, especially in the context of high sample multiplexing and limited sequencing output and is of particular importance for studies employing the recently described shallow shotgun sequencing technique. In this study, we evaluated the use of a quantitative PCR (qPCR)-based assay to predict host-to-microbe ratio prior to sequencing. Combining a two-target assay involving the bacterial 16S rRNA gene and the human beta-actin gene, we derived a model to predict human-to-microbe ratios from two sample types, including stool samples and oropharyngeal swabs. We then validated it on two independently collected sample types, including rectal swabs and vaginal secretion samples. This assay enabled accurate prediction in the validation set in a range of sample compositions between 4% and 98% nonhuman reads and observed proportions varied between -18.8% and +19.2% from the expected values. We hope that this easy-to-use assay will help researchers to plan their shotgun sequencing experiments in a more efficient way. IMPORTANCE When determining human microbiota composition, shotgun sequencing is a powerful tool that can generate large amounts of data. However, in sample compositions with low or variable microbial density, shallowing sequencing can negatively affect microbial community metrics. Here, we show that variable sequencing depth decreases measured alpha diversity at differing rates based on community composition. We then derived a model that can determine sample composition prior to sequencing using quantitative PCR (qPCR) data and validated the model using a separate sample set. We have included a tool that uses this model to be available for researchers to use when gauging shallow sequencing viability of samples.

In Situ Biosynthesis of a Metal Nanoparticle Encapsulated in Alginate Gel for Imageable Drug-Delivery System.

Development of drug-delivery systems that allow simultaneous in vivo imaging has gained much interest. We report a novel strategy to encapsulate metal nanoparticles (NPs) within alginate gel for in vivo imaging. The cell lysate of recombinant Escherichia coli strain, expressing Arabidopsis thaliana phytochelatin synthase and Pseudomonas putida metallothionein genes, was encapsulated within the alginate gel. Incubation of alginate gel with metal ion precursors followed by UV irradiation resulted in the synthesis of high concentrations of metal NPs, such as Au, Ag, CdSe, and EuSe NPs, within the gel. The alginate gel with metal NPs was used as a drug-delivery system by further co-encapsulating doxorubicin and rifampicin, the release of which was made to be pH-dependent. This system can be conveniently and safely used for in vitro and in vivo bioimaging, enabled by the metal NPs formed within the gel matrix without using toxic reducing reagents or surfactants.

The Appropriateness of Glycerin Enema in Pediatric Patients Visiting the Emergency Department.

OBJECTIVES: We determined whether glycerin enemas were appropriately prescribed in pediatric fecal impaction patients using the Leech score and identified factors that influenced the prescription of glycerin enemas in the pediatric emergency department (PED). METHODS: We included patients who received a glycerin enema at the PED of a tertiary teaching hospital. We divided the study subjects into two groups on the basis of their Leech scores: an appropriate enema group (Leech score ≥ 8), and an inappropriate enema group (Leech score < 8). Logistic regression was performed to determine the factors associated with glycerin enema administration. RESULTS: The data of 998 patients, including 446 patients in the inappropriate enema group (Leech score 5.2 ± 1.7) and 552 patients in the appropriate enema group (Leech score 10.1 ± 1.7), were analyzed. A discharge diagnosis of fecal impaction was observed significantly more frequently (57.1%) in the appropriate enema group, and nonspecific abdominal pain (8.3%) and acute gastroenteritis (40.8%) were diagnosed significantly more frequently in the inappropriate enema group (p < 0.05). Constipation (2.8%) and irritability (3.0%) were slightly more common in the appropriate enema group than in the inappropriate enema group (p < 0.05). According to multiple logistic regression, subjects aged 2-8 years (2-4 years, OR 4.24; 4-8 years, OR 2.83), with vomiting (OR 1.72), with irritability (OR 4.52), and with a prolonged last defecation day (OR 1.2) were most likely to receive appropriate enema administration (p < 0.05). CONCLUSION: The results showed that in those aged 2-8 years, with vomiting and irritability, and with a prolonged last defecation day, an enema was generally administered appropriately.

HPV genotyping and risk factors for anal high-risk HPV infection in men who have sex with men from Toronto, Canada.

Men who have sex with men (MSM) are disproportionately affected by anal cancer, predominantly caused by high-risk (HR) human papillomavirus (HPV) infection. Currently, the nonavalent HPV vaccine provides coverage against nine HPV genotypes, including seven HR-HPV genotypes. Here, we characterize anal HR-HPV genotype distribution and associated risk factors in MSM from Toronto, Canada recruited between September 2010 and June 2012. Wilcoxon-Mann-Whitney test was used for continuous variables, Chi-square test was performed for categorical variables, and a multivariable model using logistic regression was created to assess for correlates of anal HR-HPV infection. A total of 442 MSM were recruited, with a median age of 45 (IQR 38-50) and an overall HPV prevalence of 82%. The prevalence of any HR-HPV infection was 65.3% and 50.7% in the HIV-positive and HIV-negative MSM, respectively. No participant tested positive for all genotypes covered by the nonavalent vaccine. HIV status (aOR 1.806; 95% CI 1.159-2.816), smoking (aOR 2.176; 95% CI 1.285-3.685) and the number of lifetime sexual partners (aOR 2.466; 95% CI 1.092-5.567) were independent risk factors for anal HR-HPV infection. Our findings will be useful to inform HPV vaccine rollout and HPV prevention strategies in Canadian MSM.

Inhibitory effect of ginsenoside Rg3 on cancer stemness and mesenchymal transition in breast cancer via regulation of myeloid-derived suppressor cells.

Ginsenoside Rg3 (Rg3) has been studied in several cancer models and is suggested to act through various pharmacological effects. We investigated the anticancer properties of Rg3 through myeloid-derived suppressor cell (MDSC) modulation in FM3A mouse mammary carcinoma cells. The effects of Rg3 on MDSCs and consequent changes in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) were evaluated by diverse methods. MDSCs promoted cancer by enhancing breast cancer stemness and promoting EMT. Rg3 at a dose without obvious cytotoxicity downregulated MDSCs and repressed MDSC-induced cancer stemness and EMT. Mechanistic investigations suggested that these inhibitory effects of Rg3 on MDSCs and corresponding cancer progression depend upon suppression of the STAT3-dependent pathway, tumor-derived cytokines, and the NOTCH signaling pathway. In a mouse model, MDSCs accelerated tumor progression, and Rg3 delayed tumor growth, which is consistent with the results of in vitro experiments. These results indicated that Rg3 could effectively inhibit the progression of breast cancer. The anticancer effect of Rg3 might be partially due to its downregulation of MDSCs and consequent repression of cancer stemness and EMT in breast cancer. Hence, we suggest the regulation of MDSCs through Rg3 treatment as an effective therapeutic strategy for breast cancer patients.

Relationship between sleep and obesity among U.S. and South Korean college students.

BACKGROUND: Little is known about the relationship between sleep and obesity in young adults, particularly college students. This study examined the relationship between sleep (i.e., sleep duration and quality) and obesity in a large and diverse binational sample of college students. METHODS: Analyses were based on a 40-item paper survey from 2016/2017 to 2017/2018 academic years, with a 72% response rate. The samples were 1578 college students aged 18-25 years from five universities (two in the U.S. and three in South Korea). Weight and height were measured objectively; other measures (e.g., health behaviors) were self-reported. Multinomial logistic regression was used to assess the association between sleep duration and independent variables (race/nationality, gender, and BMI). Poisson regression was used to examine the relationship between sleep quality and independent variables. RESULTS: Overall, blacks had a higher adjusted odds ratio (AOR) of short sleep (< 7 h/night) than whites (AOR = 1.74, P < .01); overweight participants had a higher AOR of short sleep than normal weight participants (AOR = 1.52, P < .01); and obese participants had a higher AORs of both short and long sleep (> 9 h/night) (AOR = 1.67, P < .01; AOR = 1.79, P < .05, respectively). Among men, being black, overweight, and obesity were associated with short sleep (P < .05), whereas only obesity was related to short sleep among women (P < .05). In analyses stratified by race and nationality, overweight and obesity were related to short sleep among blacks only (P < .05). Overall, sleep quality (getting enough sleep to feel rested in the morning in the past 7 days) was worse in blacks and South Koreans than whites (P < .05), worse in women than men (P < .05), and worse in participants with obesity than normal weight participants (P < .05). CONCLUSIONS: Obesity was associated with both short (< 7 h/night) and long sleep duration (> 9 h/night) and poor sleep quality among all participants. In comparison with whites, blacks were more like to have short sleep, and blacks and South Koreans had worse sleep quality. Further investigations using a larger sample of college students in multiple countries may be helpful to identify target populations who are at a greater risk of obesity and sleep problems.

Anal dysplasia and HIV shedding in ART-treated men.

OBJECTIVES: Anal human papillomavirus (HPV) infection is highly prevalent among men who have sex with men (MSM). HPV-associated anal dysplasia has been linked with anal HIV RNA shedding despite antiretroviral therapy (ART). Since mucosal HIV levels are a key determinant of sexual transmission of the virus, this would have important public health implications. Therefore, we assessed the association between anal dysplasia and HIV shedding in ART-treated MSM from Toronto, Canada. METHODS: In 54 HIV-infected men on effective ART, we assessed anal HIV RNA shedding by PCR, HPV infection by microsphere-based genotyping and anal dysplasia by high-resolution anoscopy. All participants were enrolled between May 2017 and October 2018. RESULTS: The median duration of ART at the time of study enrolment was 18 years, with most participants being on an integrase inhibitor-based ART regimen. Low-level anal HIV RNA shedding was present in 15/54 (27.8%) participants. Neither the detection of shedding nor the level of HIV RNA was associated with anal dysplasia, HPV infection or antiretroviral regimen. CONCLUSIONS: HPV-associated anal dysplasia was not associated with anal HIV RNA shedding in this relatively small cohort of men on effective ART. While anal HIV RNA was detected more often than anticipated, shedding was low level and unlikely to cause HIV transmission. However, the immunological drivers of anal HIV RNA shedding in ART-treated individuals may merit further study.