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Anxiety, depression, and psychological distress are public health concerns for Black emerging adults ages 18–29, given their prevalence in this population. However, we have scant empirical research investigating the prevalence and correlates of negative mental outcomes among Black emerging adults with a history of exposure to police use of force. Thus, the current study examined the prevalence and correlates of depression, anxiety, and psychological well-being and how they vary among a sample of Black emerging adults with a history of direct or indirect exposure to police use of force. Computer-assisted surveys were administered to a sample of Black emerging adults (N = 300). Univariate, bivariate, and multiple linear regression analyses were conducted. Black women with a history of direct or indirect exposure to police use of force had significantly less favorable scores on the depression and anxiety scales compared with Black men. Study findings suggest that Black emerging adults, particularly women, with a history of exposure to police use of force are at risk of experiencing adverse mental health outcomes. Future research with a larger and ethnically diverse sample of emerging adults that examines the prevalence and correlates of adverse mental health outcomes and how they vary by gender, ethnicity, and exposure to police use of force is warranted.

Anxiety disorders are among the most prevalent disorders for Black emerging adults ages 18 to 29 in America. Moreover, some Black emerging adults with a history of exposure to police use of force may experience police contact anxiety (PCA) symptoms during (e.g., unable to relax) or in anticipation of future police contacts (e.g., urge to avoid police), which may develop into an anxiety disorder. To explore this phenomenon, the current study assessed the prevalence and correlates of PCA symptoms for Black emerging adults. Data were collected from a sample of Black emerging adults (N = 300). Univariate, bivariate, and ordinary least square regression analyses were done to estimate prevalence rates and correlates of PCA symptoms. PCA symptoms were moderately high for the sample, and participants who worked full-time were significantly less likely to have higher PCA symptoms because of seeing a video of police use of force in the media than those who were unemployed. Findings from the current study provide direction for future analyses focusing prospectively on prevalence, severity, and correlates of PCA symptoms. In addition, results suggest the importance of social work clinicians/practitioners assessing for PCA symptoms among their patients with a history of exposure to police use of force.

Supplemental Figure 3. Stem cell gene expression in CD24+ and CD24- cells and CD44+ and CD44- cells

Supplemental Figure 1. Bioluminescent images of cancer stem cell markers evaluated

Supplemental Figure 5. FACS isolation strategy and purity of sort

Supplemental Figure 2. FACS analysis of CD24 and CD133 expression of CD24+ or CD24- tumors

Supplemental Figure 4. Confirmation of JAK2 depletion by siRNA

Supplementary Tables 1-4 from Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Little is known about the factors that regulate the asymmetric division of cancer stem–like cells (CSC). Here, we demonstrate that EGFL6, a stem cell regulatory factor expressed in ovarian tumor cells and vasculature, regulates ALDH+ ovarian CSC. EGFL6 signaled at least in part via the oncoprotein SHP2 with concomitant activation of ERK. EGFL6 signaling promoted the migration and asymmetric division of ALDH+ ovarian CSC. As such, EGFL6 increased not only tumor growth but also metastasis. Silencing of EGFL6 or SHP2 limited numbers of ALDH+ cells and reduced tumor growth, supporting a critical role for EGFL6/SHP2 in ALDH+ cell maintenance. Notably, systemic administration of an EGFL6-neutralizing antibody we generated restricted tumor growth and metastasis, specifically blocking ovarian cancer cell recruitment to the ovary. Together, our results offer a preclinical proof of concept for EGFL6 as a novel therapeutic target for the treatment of ovarian cancer. Cancer Res; 76(21); 6396–409. ©2016 AACR.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer worldwide. Signal transducers and activators of transcription 3 (STAT3) signaling is reported to promote tumor malignancy and recurrence in HNSCC. Cucurbitacins, triterpenoid derivatives, are strong STAT3 inhibitors with anticancer properties. Recent studies have shown aldehyde dehydrogenase 1 (ALDH1) to be a marker of cancer stem cells (CSC) in HNSCC. The aim of this study was to investigate the therapeutic effect of cucurbitacin I in HNSCC-derived CSCs. Using immunohistochemical analysis, we firstly showed that CD44, ALDH1, and phosphorylated STAT3 (p-STAT3) were higher in high-grade HNSCCs, and that triple positivity for CD44/ALDH1/p-STAT3 indicated a worse prognosis for HNSCC patients. Secondly, CD44+ALDH1+ cells isolated from seven HNSCC patients showed greater tumorigenicity, radioresistance, and high expression of stemness (Bmi-1/Oct-4/Nanog) and epithelial-mesenchymal-transitional (Snail/Twist) genes as p-STAT3 level increased. Furthermore, we found that cucurbitacin I (JSI-124) can effectively inhibit the expression of p-STAT3 and capacities for tumorigenicity, sphere formation, and radioresistance in HNSCC-CD44+ALDH1+. Notably, 150 nmol/L cucurbitacin I effectively blocked STAT3 signaling and downstream survivin and Bcl-2 expression, and it induced apoptosis in HNSCC-CD44+ALDH1+. Moreover, microarray data indicated that 100 nmol/L cucurbitacin I facilitated CD44+ALDH1+ cells to differentiate into CD44−ALDH1− and enhanced the radiosensitivity of HNSCC-CD44+ALDH1+. Xenotransplant experiments revealed that cucurbitacin I combined with radiotherapy significantly suppressed tumorigenesis and lung metastasis and further improved the survival rate in HNSCC-CD44+ALDH1+-transplanted immunocompromised mice. Taken together, our data show that cucurbitacin I, STAT3 inhibitor, reduces radioresistant, distant-metastatic, and CSC-like properties of HNSCC-CD44+ALDH1+ cells. The potential of cucurbitacin I as a radiosensitizer should be verified in future anti-CSC therapy. Mol Cancer Ther; 9(11); 2879–92. ©2010 AACR.

Supplementary Figure Legends from Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Supplementary Methods

Supplementary Figures 1-4 from Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Supplementary Figures 1-8

Lactate concentration is of increasing interest as a diagnostic for sepsis, septic shock, and trauma. Compared with the traditional blood sample media, the exhaled breath condensate (EBC) has the advantages of non-invasiveness and higher user acceptance. An amperometric biosensor was developed and its application in EBC lactate detection was investigated in this paper. The sensor was modified with PEDOT:PSS-PB, and two different lactate oxidases (LODs). A rotating disk electrode and Koutecky-Levich analysis were applied for the kinetics analysis and gel optimization. The optimized gel formulation was then tested on disposable screen-printed sensors. The disposable sensors exhibited good performance and presented a high stability for both LOD modifications. Finally, human EBC analysis was conducted from a healthy subject at rest and after 30 min of intense aerobic cycling exercise. The sensor coulometric measurements showed good agreement with fluorometric and triple quadrupole liquid chromatography mass spectrometry reference methods. The EBC lactate concentration increased from 22.5 μM (at rest) to 28.0 μM (after 30 min of cycling) and dropped back to 5.3 μM after 60 min of rest.

Diabetes-induced cardiovascular complications are mainly associated with high morbidity and mortality in patients with diabetes. Insulin-like growth factor II receptor α (IGF-IIRα) is a cardiac risk factor. In this study, we hypothesized IGF-IIRα could also deteriorate diabetic heart injury. The results presented that both in vivo transgenic Sprague-Dawley rat model with specific IGF-IIRα overexpression in the heart and in vitro myocardium H9c2 cells were used to investigate the negative function of IGF-IIRα in diabetic hearts. The results showed that IGF-IIRα overexpression aided hyperglycemia in creating more myocardial injury. Pro-inflammatory factors, such as Tumor necrosis factor-alpha, Interleukin-6, Cyclooxygenase-2, Inducible nitric oxide synthase, and Nuclear factor-kappaB inflammatory cascade, are enhanced in the diabetic myocardium with cardiac-specific IGF-IIRα overexpression. Correspondingly, IGF-IIRα overexpression in the diabetic myocardium also reduced the PI3K-AKT survival axis and activated mitochondrial-dependent apoptosis. Finally, both ejection fraction and fractional shortening were be significantly decrease in diabetic rats with cardiac-specific IGF-IIRα overexpression. Overall, all results provid clear evidence that IGF-IIRα can enhance cardiac damage and is a harmful factor to the heart under high-blood glucose conditions. However, the pathophysiology of IGF-IIRα under different stresses and its downstream regulation in the heart still require further research.

Cancer cell migration represents an essential step toward metastasis and cancer deaths. However, conventional drug discovery focuses on cytotoxic and growth-inhibiting compounds rather than inhibitors of migration. Drug screening assays generally measure the average response of many cells, masking distinct cell populations that drive metastasis and resist treatments. Here, this work presents a high-throughput microfluidic cell migration platform that coordinates robotic liquid handling and computer vision for rapidly quantifying individual cellular motility. Using this innovative technology, 172 compounds were tested and a surprisingly low correlation between migration and growth inhibition was found. Notably, many compounds were found to inhibit migration of most cells while leaving fast-moving subpopulations unaffected. This work further pinpoints synergistic drug combinations, including Bortezomib and Danirixin, to stop fast-moving cells. To explain the observed cell behaviors, single-cell morphological and molecular analysis were performed. These studies establish a novel technology to identify promising migration inhibitors for cancer treatment and relevant applications.

Identifying and quantifying cell death is the basis for all cell death research. Current methods for obtaining these quantitative measurements rely on established biomarkers, yet the marker-based approach suffers from limited marker specificity, high cost of reagents, lengthy sample preparation, and fluorescence imaging. Based on the morphological difference, we developed a Live, Apoptotic, and Necrotic Cell Explorer (LANCE) to categorize cell death status in a label-free manner, by incorporating machine learning and image processing. The LANCE workflow includes cropping individual cells from microscopic images having hundreds of cells, formation of an image database of around 5000 events, training and validation of the convolutional neural network models using multiple cell lines, and treatment conditions. With LANCE, we precisely categorized live, apoptotic, and necrotic cells with a high accuracy of 96.3 ± 0.5%. More importantly, the nondestructive label-free LANCE method allows for tracking time dynamics of the cell death process, which enhances the understanding of subtle cell death regulation at the molecular level. Hence, LANCE is a fast, low-cost, and nondestructive label-free method to distinguish cell status, which can be applied to cell death studies as well as many other biomedical applications.

Financial capability, the combination of financial literacy (ability to act) and financial access (opportunity to act), improves people's access to resources, and thus has the potential to improve health and well-being. This paper positions financial capability under the framework of social determinants of health and discusses theory and presents empirical evidence on the link between financial capability and health. Using data from the RAND American Life Panel and the structural equation modeling approach, we distinguish financial capability from the common socioeconomic position indicators such as income and education. We find that financial capability has a positive and longitudinal effect on health, independent of race/ethnicity, gender, income, education, and employment. This study demonstrates that financial capability is an independent social determinant of health. It can be theoretically and conceptually defined, empirically measured, and can inform clinical interventions that may improve population health and well-being. Implications for future research, practice, and policy are discussed.

Chemokine receptors constitute an important subfamily of G protein-coupled receptors (GPCRs), and they are critically involved in a broad range of immune response mechanisms. Ligand promiscuity among these receptors makes them an interesting target to explore novel aspects of biased agonism. Here, we comprehensively characterize two chemokine receptors namely, CXCR4 and CXCR7, which share a common chemokine agonist (CXCL12), in terms of their G-protein coupling, β-arrestin (βarr) recruitment, contribution of GRKs, and ERK1/2 MAP kinase activation. We observe that CXCR7 lacks G-protein coupling while maintaining robust βarr recruitment with a major contribution of GRK5/6. On the other hand, CXCR4 displays robust G-protein activation as expected, however, it exhibits significantly reduced βarr-coupling compared to CXCR7 in response to their shared natural agonist, CXCL12. These two receptors induce distinct βarr conformations even when activated by the same agonist, and CXCR7, unlike CXCR4, fails to activate ERK1/2 MAP kinase. We further determine the crystal structure of βarr2 in complex with a carboxyl-terminal phosphopeptide derived from CXCR7, which reveals a smaller interdomain rotation than observed previously for activated βarrs. Importantly, structure-guided cellular experiments reveal a key contribution of a single phosphorylation site in CXCR7 on βarr recruitment and endosomal trafficking. Taken together, our study provides molecular insights into intrinsic bias encoded in the CXCR4-CXCR7 system, and it has broad implications for therapeutically important framework of biased agonism.

Hypertension is the most important modifiable cause of cardiovascular (CV) disease and all-cause mortality worldwide. Despite the positive correlations between blood pressure (BP) levels and later CV events since BP levels as low as 100/60 mmHg have been reported in numerous epidemiological studies, the diagnostic criteria of hypertension and BP thresholds and targets of antihypertensive therapy have largely remained at the level of 140/90 mmHg in the past 30 years. The publication of both the SPRINT and STEP trials (comprising > 8,500 Caucasian/African and Chinese participants, respectively) provided evidence to shake this 140/90 mmHg dogma. Another dogma regarding hypertension management is the dependence on office (or clinic) BP measurements. Although standardized office BP measurements have been widely recommended and adopted in large-scale CV outcome trials, the practice of office BP measurements has never been ideal in real-world practice. Home BP monitoring (HBPM) is easy to perform, more likely to be free of environmental and/or emotional stress, feasible to document long-term BP variations, of good reproducibility and reliability, and more correlated with hypertension-mediated organ damage (HMOD) and CV events, compared to routine office BP measurements. In the 2022 Taiwan Hypertension Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS), we break these two dogmas by recommending the definition of hypertension as ≥ 130/80 mmHg and a universal BP target of < 130/80 mmHg, based on standardized HBPM obtained according to the 722 protocol. The 722 protocol refers to duplicate BP readings taken per occasion ("2"), twice daily ("2"), over seven consecutive days ("7"). To facilitate implementation of the guidelines, a series of flowcharts encompassing assessment, adjustment, and HBPM-guided hypertension management are provided. Other key messages include that: 1) lifestyle modification, summarized as the mnemonic S-ABCDE, should be applied to people with elevated BP and hypertensive patients to reduce life-time BP burden; 2) all 5 major antihypertensive drugs (angiotensin-converting enzyme inhibitors [A], angiotensin receptor blockers [A], β-blockers [B], calcium-channel blockers [C], and thiazide diuretics [D]) are recommended as first-line antihypertensive drugs; 3) initial combination therapy, preferably in a single-pill combination, is recommended for patients with BP ≥ 20/10 mmHg above targets; 4) a target hierarchy (HBPM-HMOD- ambulatory BP monitoring [ABPM]) should be considered to optimize hypertension management, which indicates reaching the HBPM target first and then keeping HMOD stable or regressed, otherwise ABPM can be arranged to guide treatment adjustment; and 5) renal denervation can be considered as an alternative BP-lowering strategy after careful clinical and imaging evaluation.

Studies have documented the impact of childhood socioeconomic status (SES) on cognition. However, research that simultaneously considers SES in varied life stages, the multidimensional mechanisms, and racial differences is relatively understudied. This study examines the intersectionality across age, SES, and race and its impact on cognitive trajectories.Using 8376 respondents aged 65+ from the 1998-2016 Health and Retirement Study, we used latent growth curve modeling to examine the effects of four life course models (latency, pathway, accumulation, and mobility) on 18-year trajectories of mental status and episodic memory. We further tested for differences in the links between SES and cognitive trajectories between black and white respondents.Cognitive function declines with age and is interrelated with SES and race. Adulthood has a stronger effect on cognitive performance than childhood. However, linked positive childhood and adulthood SES contributes to positive cognition. Accumulated SES disadvantages were associated with lower cognition. Older adults with downward mobility and low SES throughout their lifespans had the lowest cognition scores. Life course models operated differently on trajectories of cognitive decline, yet the effects were particularly evident among older black respondents. Overall, those with socioeconomic advantages tended to have a slower decline in cognition, while a faster decline occurred for those with accrued disadvantages.Cognitive performance is a complex, longitudinal process intertwined with socioeconomic conditions and population heterogeneity shaped by life course contexts. Policies that facilitate healthy cognitive performance and address SES inequality could equalize health opportunities and address racial cognitive disparities later in life.

A pervasive link between relative deprivation and health has been well-documented. However, prior studies suffered from inadequate relative deprivation measures that fail to define appropriate reference groups to which individuals compare themselves, and few provided longitudinal evidence. This study explores latent relative deprivation patterns based on multiple social and geographic reference groups, examining their impacts on health trajectories and variations by gender and urban-rural areas.Using three waves (2013, 2015,2018) of the China Health and Retirement Longitudinal Study (n = 6035), we conducted latent class analysis (LCA) to identify the baseline latent relative deprivation patterns among five social and geographic reference groups (relatives, schoolmates, colleagues, neighbors, and other people in the city or county). The LCA results were linked to the latent growth curve parallel process modeling (PPM) to investigate the impacts of deprivation patterns on dual health trajectories (depressive symptoms and self-rated health), and the results were stratified to explore gender and urban-rural differences.The LCA revealed a relatively deprived group (36.39%) and a non-deprived group (63.61%). The PPM results indicated that the relatively deprived group showed a higher initial level of depressive symptoms and a lower initial level of self-rated health than the non-deprived group. However, the relatively deprived group showed a slower growth rate in depressive symptoms than the non-deprived group. These findings were particularly evident among women and rural residents.Findings emphasize the negative impact of relative deprivation on health. Furthermore, there is a complex interplay in these effects intertwined with gender and locality. Policies aimed at promoting mental health should not only consider relatively deprived groups, but also non-deprived women and rural residents who are at higher risk for later-life depression.

In order to understand the role of QCD in the early universe, we perform hybrid Monte-Carlo simulation of lattice QCD with $N_f=2+1+1$ optimal domain-wall quarks at the physical point, on the $64^3 \times (6,8,10,12,16,20,64)$ lattices, each with three lattice spacings. The lattice spacings and the bare quark masses are determined on the $64^4$ lattices. The resulting gauge ensembles provide a basis for studying finite temperature QCD with $N_f=2+1+1 $ domain-wall quarks at the physical point. In this Proceeding, we present our first result on the topological susceptibility of the QCD vacuum. The topological charge of each gauge configuration is measured by the clover charge in the Wilson flow at the same flow time in physical units, and the topological susceptibility $ \chi_t(a,T) $ is determined for each ensemble with lattice spacing $a$ and temperature $T$. Using the topological susceptibility $\chi_t(a,T) $ of 15 gauge ensembles with three lattice spacings and different temperatures in the range $T \sim 155-516 $~MeV, we extract the topological susceptibility $\chi_t(T)$ in the continuum limit., Comment: 9 pages, 1 figure, Proceedings of the 38th International Symposium on Lattice Field Theory, LATTICE 2021, 26th-30th July, 2021, Zoom/Gather@Massachusetts Institute of Technology

Generativity has recently received increasing attention as a key contributor to healthy aging. Personal resources and social expectations are shown to influence the desire to be generative and that generativity affects later-life health. However, whether generativity has a mediating role in linking its driving factors and health, and how gender may affect these pathways, is underexplored. Cross-sectional online data from 1085 Hong Kong residents aged 45+ were collected between November and December 2020. Latent variable path analysis was used to examine the mediating effect of generativity between human, social, and financial capital, and physical and mental well-being. Gendered pathways were investigated using multi-group analysis. Results showed that human, social, and financial capital contributed to better health through generativity, and gendered pathways were observed. Human capital had a stronger effect on generativity for men, but for women, social capital was vital for increased generativity and consequently improved health. Findings suggested that health benefits of generativity depend on different capital drivers and differ by gender. Implications for program development that aim to facilitate health should include generativity components that maximize physical and psychosocial engagement so that individuals can reap the health benefits through contributions to others.