NADPH oxidase 4 deficiency promotes hepatocellular carcinoma arising from hepatic fibrosis by inducing M2-macrophages in the tumor microenvironment.

Hepatocellular carcinoma (HCC) often arises in the cirrhotic livers, highlighting the intricate link between hepatic fibrosis and carcinogenesis. Reactive oxygen species produced by NADPH oxidase 4 (NOX4) contribute to liver injury leading to hepatic fibrosis. Paradoxically, NOX4 is known to inhibit HCC progression. This study aims to elucidate the role of NOX4 in hepatocarcinogenesis in the background of hepatic fibrosis. We established the mouse model of HCC arising from the fibrotic liver by administering diethylnitrosamine and carbon tetrachloride to wild-type (WT) or NOX4-/- mice. Hepatic fibrogenesis, tumorigenesis, and macrophage polarization were assessed by immunohistochemistry, PCR, and flow cytometry using in vivo and in vitro models. In NOX4-/- mice, hepatic fibrosis was attenuated, while the number of tumors and the proliferation of HCC cells were increased compared to WT mice. Notably, a significant increase in M2-polarized macrophages was observed in NOX4-/- mice through immunohistochemistry and PCR analysis. Subsequent experiments demonstrated that NOX4-silenced HCC cells promote macrophage polarization toward M2. In addition to attenuating hepatic fibrogenesis, NOX4 deficiency triggers macrophage polarization towards the M2 phenotype in the fibrotic liver, thereby promoting hepatocellular carcinogenesis. These findings provide novel insights into the mechanism of NOX4-mediated tumor suppression in HCC arising from fibrotic livers.

Clinical characteristics and long-term disease course in patients with Crohn's disease as diagnosed by video capsule endoscopy: a multicenter retrospective matched case-control study.

Background/Aims: Video capsule endoscopy is rarely used to diagnose Crohn's disease in patients with negative ileocolonoscopy or cross-sectional image findings. We evaluated clinical characteristics and long-term outcomes of these rare cases. Methods: This multicenter study included patients with Crohn's disease from 3 tertiary hospitals from January 2007 to October 2022. Patients with normal findings on ileocolonoscopy and computed tomography (CT)/magnetic resonance (MR) enterography but had ulcerations at the small bowel detected by video capsule endoscopy were included. The controls were patients with abnormal findings on endoscopy or CT/MR enterography. Controls were case-matched in a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Results: Among 3,752 patients, 24 (0.6%) were diagnosed with Crohn's disease using video capsule endoscopy findings. The disease location (P< 0.001) and behavior at diagnosis (P= 0.013) of the cases significantly differed from that of controls. The perianal fistula modifier (25.0% vs. 33.3%, P= 0.446) did not differ significantly between the 2 groups. Initial disease activity and C-reactive protein and fecal calprotectin levels were significantly lower in cases versus controls. The median Lewis score was 838 (interquartile range, 393-1,803). Over 10 years of follow-up, the cases showed significantly lower cumulative risk of complicated behavior, biologics use, Crohn's disease-related hospitalization, and surgeries (log-rank test P< 0.05). Conclusions: Patients with Crohn's disease whose lesions were observed only by video capsule endoscopy were rare, and exhibit different clinical characteristics and a more favorable long-term disease course compared to those who were conventionally diagnosed.

Dietary Patterns and Cardiovascular Diseases in Asia: A Systematic Review and Meta-Analysis.

With emerging Asian-derived diet quality indices and data-driven dietary patterns available, we aimed to synthesize the various dietary patterns and quantify its association with cardiovascular diseases (CVDs) among Asian populations. We systematically searched PubMed, Embase, Scopus, and Web of Science for observational studies in South, Southeast, and East Asia. Dietary patterns were grouped "high-quality," which included high intakes of three or more of the following food groups: 1) fruits and vegetables, 2) whole grains, 3) healthy protein sources (legumes and nuts, fish and seafood, low-fat dairy, and lean meat and poultry), and 4) liquid plant oils. High-quality patterns were further subcategorized based on their derivation methods: non-Asian indices, Asian indices, data-driven patterns, and plant-based indices. Dietary patterns were grouped "low-quality," which included high intakes of two or more of the following: 5) ultraprocessed food, 6) beverages and foods with added sugars, 7) foods high in salt, and 8) alcoholic beverages. Data-driven dietary patterns characterized by animal food sources were labeled "animal-based," and studies using dietary diversity scores were labeled "diet diversity indices." Dietary patterns that could not be meaningfully categorized were summarized narratively. Study-specific effect estimates were pooled using a random-effects model. Forty-one studies were included in this review. Higher adherence to high-quality dietary patterns in the top compared with bottom tertile defined by non-Asian indices (RR: 0.78; 95% CI: 0.69, 0.88; GRADE: moderate), Asian indices (RR: 0.84; 95% CI: 0.79, 0.90; GRADE: low), and data-driven patterns (RR: 0.81; 95% CI: 0.74, 0.89; GRADE: moderate) were associated with lower CVD risk. Plant-based, low-quality, animal-based, and diet diversity indices dietary patterns were not associated with CVD. Associations of Asian diet quality indices and CVD risk were weaker than those with non-Asian indices, highlighting the need for current Asian diet quality criteria to be updated to better capture the impact of diet on CVD. The systematic review and meta-analysis was registered at PROSPERO as CRD42021244318.

Rationale, Design, and Baseline Characteristics of Participants in the Health@NUS mHealth Augmented Cohort Study Examining Student-to-Work Life Transition: Protocol for a Prospective Cohort Study.

BACKGROUND: Integration of mobile health data collection methods into cohort studies enables the collection of intensive longitudinal information, which gives deeper insights into individuals' health and lifestyle behavioral patterns over time, as compared to traditional cohort methods with less frequent data collection. These findings can then fill the gaps that remain in understanding how various lifestyle behaviors interact as students graduate from university and seek employment (student-to-work life transition), where the inability to adapt quickly to a changing environment greatly affects the mental well-being of young adults. OBJECTIVE: This paper aims to provide an overview of the study methodology and baseline characteristics of participants in Health@NUS, a longitudinal study leveraging mobile health to examine the trajectories of health behaviors, physical health, and well-being, and their diverse determinants, for young adults during the student-to-work life transition. METHODS: University students were recruited between August 2020 and June 2022 in Singapore. Participants would complete biometric assessments and questionnaires at 3 time points (baseline, 12-, and 24-month follow-up visits) and use a Fitbit smartwatch and smartphone app to continuously collect physical activity, sedentary behavior, sleep, and dietary data over the 2 years. Additionally, up to 12 two-week-long bursts of app-based ecological momentary surveys capturing lifestyle behaviors and well-being would be sent out among the 3 time points. RESULTS: Interested participants (n=1556) were screened for eligibility, and 776 participants were enrolled in the study between August 2020 and June 2022. Participants were mostly female (441/776, 56.8%), of Chinese ethnicity (741/776, 92%), undergraduate students (759/776, 97.8%), and had a mean BMI of 21.9 (SD 3.3) kg/m2, and a mean age of 22.7 (SD 1.7) years. A substantial proportion were overweight (202/776, 26.1%) or obese (42/776, 5.4%), had indicated poor mental well-being (World Health Organization-5 Well-Being Index ≤50; 291/776, 37.7%), or were at higher risk for psychological distress (Kessler Psychological Distress Scale ≥13; 109/776, 14.1%). CONCLUSIONS: The findings from this study will provide detailed insights into the determinants and trajectories of health behaviors, health, and well-being during the student-to-work life transition experienced by young adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/study/NCT05154227. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56749.

OsMYB14, an R2R3-MYB transcription factor, regulates plant height through the control of hormone metabolism in rice.

Plant growth must be regulated throughout the plant life cycle. The myeloblastosis (MYB) transcription factor (TF) family is one of the largest TF families and is involved in metabolism, lignin biosynthesis, and developmental processes. Here, we showed that OsMYB14, a rice R2R3-MYB TF, was expressed in leaves and roots, especially in rice culm and panicles, and that it localized to the nucleus. Overexpression of OsMYB14 (OsMYB14-ox) in rice resulted in a 30% reduction in plant height compared to that of the wild type (WT), while the height of the osmyb14-knockout (osmyb14-ko) mutant generated using the CRISPR/Cas9 system was not significantly different. Microscopic observations of the first internode revealed that the cell size did not differ significantly among the lines. RNA sequencing analysis revealed that genes associated with plant development, regulation, lipid metabolism, carbohydrate metabolism, and gibberellin (GA) and auxin metabolic processes were downregulated in the OsMYB14-ox line. Hormone quantitation revealed that inactive GA19 accumulated in OsMYB14-ox but not in the WT or knockout plants, suggesting that GA20 generation was repressed. Indole-3-acetic acid (IAA) and IAA-aspartate accumulated in OsMYB14-ox and osmyb14-ko, respectively. Indeed, real-time PCR analysis revealed that the expression of OsGA20ox1, encoding GA20 oxidase 1, and OsGH3-2, encoding IAA-amido synthetase, was downregulated in OsMYB14-ox and upregulated in osmyb14-ko. A protein-binding microarray revealed the presence of a consensus DNA-binding sequence, the ACCTACC-like motif, in the promoters of the OsGA20ox1 and GA20ox2 genes. These results suggest that OsMYB14 may act as a negative regulator of biological processes affecting plant height in rice by regulating GA biosynthesis and auxin metabolism.

Neighborhood Safety and Neighborhood Police Violence Are Associated with Psychological Distress among English- and Spanish-Speaking Transgender Women of Color in New York City: Finding from the TURNNT Cohort Study.

Transgender women of color (TWOC) experience high rates of police violence and victimization compared to other sexual and gender minority groups, as well as compared to other White transgender and cisgender women. While past studies have demonstrated how frequent police harassment is associated with higher psychological distress, the effect of neighborhood safety and neighborhood police violence on TWOC's mental health is rarely studied. In this study, we examine the association between neighborhood safety and neighborhood police violence with psychological distress among TWOC. Baseline self-reported data are from the TURNNT ("Trying to Understand Relationships, Networks and Neighborhoods among Transgender Woman of Color") Cohort Study (analytic n = 303). Recruitment for the study began September 2020 and ended November 2022. Eligibility criteria included being a TWOC, age 18-55, English- or Spanish-speaking, and planning to reside in the New York City metropolitan area for at least 1 year. In multivariable analyses, neighborhood safety and neighborhood police violence were associated with psychological distress. For example, individuals who reported medium levels of neighborhood police violence had 1.15 [1.03, 1.28] times the odds of experiencing psychological distress compared to those who experienced low levels of neighborhood police violence. Our data suggest that neighborhood safety and neighborhood police violence were associated with increased psychological distress among TWOC. Policies and programs to address neighborhood police violence (such as body cameras and legal consequences for abusive officers) may improve mental health among TWOC.

Acculturation as a Determinant of Obesity and Related Lifestyle Behaviors in a Multi-Ethnic Asian Population.

Limited attention has been given to the role of cultural orientation towards different ethnic groups in multi-ethnic settings without a dominant host culture. We evaluated whether acculturation levels, reflecting cultural orientation towards other ethnic groups, were associated with obesity and related lifestyle behaviors in a cosmopolitan Asian population. We conducted the current study based on data from the Singapore Multi-Ethnic Cohort (N = 10,622) consisting of ethnic Chinese, Malays, and Indians aged 21 to 75 years. Multivariable linear and logistic regression analyses were used to examine associations between the acculturation level (z-score), obesity, and related lifestyle behaviors, including dietary habits and physical activity. A higher acculturation level was directly associated with a higher prevalence of obesity among Chinese, whereas an inverse association was found for ethnic Indians, and no significant association in Malays. In ethnic Malays, greater acculturation was significantly associated with higher dietary quality and less sedentary time. Furthermore, a high acculturation level was significantly associated with higher sugar-sweetened beverage consumption and more leisure-time PA in all ethnic groups. Our findings suggest that greater cultural orientation towards other ethnic groups was associated with convergence in obesity levels. More research is required to understand how acculturation affects obesity-related lifestyle factors in multi-ethnic settings.

HIV Care Engagement Is Not Associated with COVID-19 Vaccination Hesitancy during the Initial Peak of the COVID-19 Pandemic among Black Cisgender Sexual Minority Men and Transgender Women in the N2 COVID Study.

BACKGROUND: Although there is limited literature on medication adherence (including HIV care engagement) and COVID-19 vaccine hesitancy in general populations (i.e., non-sexual or gender minority populations), even less is known about whether HIV care engagement correlates with COVID-19 vaccine hesitancy among sexual and gender minorities, especially those from intersectional backgrounds. The objective of the current study was to examine if an association exists between HIV status neutral care (i.e., current pre-exposure prophylaxis [PrEP] or antiretroviral therapy [ART] use) and COVID-19 vaccination hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. METHODS: We conducted the N2 COVID Study in Chicago from 20 April 2020 to 31 July 2020 (analytic n = 222), including Black cisgender sexual minority men and transgender women who were vulnerable to HIV as well as those who were living with HIV. The survey included questions regarding HIV care engagement, COVID-19 vaccination hesitancy and COVID-19 related socio-economic hardships. Multivariable associations estimated adjusted risk ratios (ARRs) using modified Poisson regressions for COVID vaccine hesitancy adjusting for baseline socio-demographic characteristics and survey assessment time period. RESULTS: Approximately 45% of participants reported COVID-19 vaccine hesitancy. PrEP and ART use were not associated with COVID-19 vaccine hesitancy when examined separately or combined (p > 0.05). There were no significant multiplicative effects of COVID-19 related socio-economic hardships and HIV care engagement on COVID-19 vaccine hesitancy. CONCLUSIONS: Findings suggest no association between HIV care engagement and COVID-19 vaccine hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. It is therefore essential that COVID-19 vaccine promotion interventions focus on all Black sexual and gender minorities regardless of HIV care engagement and COVID-19 vaccine uptake is likely related to factors other than engagement in HIV status neutral care.

UBP12/UBP13-mediated deubiquitination of salicylic acid receptor NPR3 suppresses plant immunity.

Salicylic acid (SA), a defense hormone produced after pathogen challenge, is critical for plant immunity. Arabidopsis NONEXPRESSER OF PR GENES 1 (NPR1) and its paralogs NPR3 and NPR4 can bind SA and mediate SA signal transduction. NPR1 functions as a transcriptional co-activator to promote defense gene expression, whereas NPR3 and NPR4 have been shown to function as negative regulators in the SA signaling pathway. Although the mechanism about NPR1 regulation has been well studied, how NPR3/NPR4 proteins are regulated in immune responses remains largely unknown. Here, we show that the stability of NPR3/NPR4 is enhanced by SA. In the absence of pathogen challenge, NPR3/NPR4 are unstable and degraded by the 26S proteasome, whereas the increase in cellular SA levels upon pathogen infection suppresses NPR3/NPR4 degradation. We found that UBP12 and UBP13, two homologous deubiquitinases from a ubiquitin-specific protease subfamily, negatively regulate plant immunity by promoting NPR3/NPR4 stability. Our genetic results further showed that UBP12/UBP13-mediated immunity suppression is partially dependent on NPR3/NPR4 functions. By interacting with NPR3 in the nucleus in an SA-dependent manner, UBP12 and UBP13 remove ubiquitin from polyubiquitinated NPR3 to protect it from being degraded. The stabilization of NPR3/NPR4 promoted by UBP12/UBP13 is essential for negative regulation of basal and SA-induced immunity.

Inositol polyphosphates-regulated polyubiquitination of PHR1 by NLA E3 ligase during phosphate starvation response in Arabidopsis.

Phosphate (Pi) availability is a major factor limiting plant growth and development. The key transcription factor controlling Pi-starvation response (PSR) is PHOSPHATE STARVATION RESPONSE 1 (PHR1) whose transcript levels do not change with changes in Pi levels. However, how PHR1 stability is regulated at the post-translational level is relatively unexplored in Arabidopsis thaliana. Inositol polyphosphates (InsPn) are important signal molecules that promote the association of stand-alone SPX domain proteins with PHR1 to regulate PSR. Here, we show that NITROGEN LIMITATION ADAPTATION (NLA) E3 ligase can associate with PHR1 through its conserved SPX domain and polyubiquitinate PHR1 in vitro. The association with PHR1 and its ubiquitination is enhanced by InsP6 but not by InsP5. Analysis of InsPn-related mutants and an overexpression plant shows PHR1 levels are more stable in itpk4-1 and vih2-4/VIH1amiRNA but less stable in ITPK4 overexpression plants. Under Pi-deficient conditions, nla seedlings contain high PHR1 levels, display long root hair and accumulate anthocyanin in shoots phenocopying PHR1 overexpression plants. By contrast, NLA overexpression plants phenocopy phr1 whose phenotypes are opposite to those of nla. Our results suggest NLA functions as a negative regulator of Pi response by modulating PHR1 stability and the NLA/PHR1 association depends on InsPn levels.

A Randomized, Double-Blind, Active-Control, Noninferiority, Multicenter, Phase 4 Study to Evaluate the Efficacy and Safety of Esomeprazole/Sodium Bicarbonate 20/800 mg in Patients with Nonerosive Gastroesophageal Reflux Disease.

Background/Aims: Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone. Methods: This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4. Results: A total of 355 patients completed the study (180 in the EsoduoⓇ group and 175 in the NexiumⓇ group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ group and 35% in the NexiumⓇ group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles. Conclusions: EsoduoⓇ is as effective and safe as NexiumⓇ for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).

Sleep characteristics among black cisgender sexual minority men and black transgender women during the COVID-19 pandemic: The role of multi-level COVID-19-related stressors.

OBJECTIVES: To determine the association between individual, network, and structural COVID-19-related stressors and changes in sleep duration and quality among Black cisgender sexual minority men (SMM) and Black transgender women during the COVID-19 peak infectivity rate in Chicago. METHODS: From April 20, 2020 to July 31, 2020, we conducted the N2 COVID Study in Chicago (n = 226). The survey included questions regarding multi-level COVID-19-related stressors (eg, food unavailability, partner violence, housing instability, concern about neighborhood COVID-19), sleep duration, and sleep quality. RESULTS: About 19.5% of our sample reported a shorter duration of sleep during the initial peak COVID-19 infectivity, while 41.2% reported more sleep and 38.9% reported about the same. Compared to the prepandemic period, 16.8% reported that their sleep quality worsened in the COVID-19 pandemic, while 27.9% reported their sleep quality had improved and 55.3% reported it was about the same. In multivariable models, we found that ≥1 day of physical stress reaction, worrying about being infected with COVID-19, traveling during COVID-19 being a financial burden, not having enough medication, knowing someone who was diagnosed with COVID-19, partner violence and housing instability were associated with poor sleep health in the COVID-19 pandemic (adjusted risk ratio: 1.82-3.90, p < .05). CONCLUSIONS: These data suggest that COVID-19-related stressors impacted poor sleep duration and quality during the pandemic among this cohort. Multi-level interventions to reduce COVID-19-related stressors (eg, meditation, intimate partner violence prevention and housing programs) may be useful for improving sleep health among Black cisgender sexual minority men and Black transgender women.

Evaluating the Prognostic and Therapeutic Potentials of the Proteasome 26S Subunit, ATPase (PSMC) Family of Genes in Lung Adenocarcinoma: A Database Mining Approach.

This study explored the prognostic and therapeutic potentials of multiple Proteasome 26S Subunit, ATPase (PSMC) family of genes (PSMC1-5) in lung adenocarcinoma (LUAD) diagnosis and treatment. All the PSMCs were found to be differentially expressed (upregulated) at the mRNA and protein levels in LUAD tissues. The promoter and multiple coding regions of PSMCs were reported to be differentially and distinctly methylated, which may serve in the methylation-sensitive diagnosis of LUAD patients. Multiple somatic mutations (alteration frequency: 0.6-2%) were observed along the PSMC coding regions in LUAD tissues that could assist in the high-throughput screening of LUAD patients. A significant association between the PSMC overexpression and LUAD patients' poor overall and relapse-free survival (p < 0.05; HR: >1.3) and individual cancer stages (p < 0.001) was discovered, which justifies PSMCs as the ideal targets for LUAD diagnosis. Multiple immune cells and modulators (i.e., CD274 and IDO1) were found to be associated with the expression levels of PSMCs in LUAD tissues that could aid in formulating PSMC-based diagnostic measures and therapeutic interventions for LUAD. Functional enrichment analysis of neighbor genes of PSMCs in LUAD tissues revealed different genes (i.e., SLIRP, PSMA2, and NUDSF3) previously known to be involved in oncogenic processes and metastasis are co-expressed with PSMCs, which could also be investigated further. Overall, this study recommends that PSMCs and their transcriptional and translational products are potential candidates for LUAD diagnostic and therapeutic measure discovery.

Advancing understanding of dietary and movement behaviours in an Asian population through real-time monitoring: Protocol of the Continuous Observations of Behavioural Risk Factors in Asia study (COBRA).

Background: Modifiable risk factors for non-communicable diseases, including eating an unhealthy diet and being physically inactive, are influenced by complex and dynamic interactions between people and their social and physical environment. Therefore, understanding patterns and determinants of these risk factors as they occur in real life is essential to enable the design of precision public health interventions. Objective: This paper describes the protocol for the Continuous Observations of Behavioural Risk Factors in Asia study (COBRA). The study uses real-time data capture methods to gain a comprehensive understanding of eating and movement behaviours, including how these differ by socio-demographic characteristics and are shaped by people's interaction with their social and physical environment. Methods: COBRA is an observational study in free-living conditions. We will recruit 1500 adults aged 21-69 years from a large prospective cohort study. Real-time data capture methods will be used for nine consecutive days: an ecological momentary assessment app with a global positioning system enabled to collect location data, accelerometers to measure movement, and wearable sensors to monitor blood glucose levels. Participants receive six EMA surveys per day between 8 a.m. and 9.30 p.m. to capture information on behavioural risk factors including eating behaviours and diet composition movement behaviours (physical activity, sedentary behaviour, sleep), and related contextual factors. The second wave of ecological momentary assessment surveys with a global positioning system enabled will be sent 6 months later. Data will be analysed using generalised linear models to examine associations between behavioural risk factors and contextual determinants. Discussion: Findings from this study will advance our understanding of dietary and movement behaviours as they occur in real-life and inform the development of personalised interventions to prevent chronic diseases.

Deubiquitination of BES1 by UBP12/UBP13 promotes brassinosteroid signaling and plant growth.

As a key transcription factor in the brassinosteroid (BR) signaling pathway, the activity and expression of BES1 (BRI1-EMS-SUPPRESSOR 1) are stringently regulated. BES1 degradation is mediated by ubiquitin-related 26S proteasomal and autophagy pathways, which attenuate and terminate BR signaling; however, the opposing deubiquitinases (DUBs) are still unknown. Here, we showed that the ubp12-2w/13-3 double mutant phenocopies the BR-deficient dwarf mutant, suggesting that the two DUBs UBP12/UBP13 antagonize ubiquitin-mediated degradation to stabilize BES1. These two DUBs can trim tetraubiquitin with K46 and K63 linkages in vitro. UBP12/BES1 and UBP13/BES1 complexes are localized in both cytosol and nuclei. UBP12/13 can deubiquitinate polyubiquitinated BES1 in vitro and in planta, and UBP12 interacts with and deubiquitinates both inactive, phosphorylated BES1 and active, dephosphorylated BES1 in vivo. UBP12 overexpression in BES1OE plants significantly enhances cell elongation in hypocotyls and petioles and increases the ratio of leaf length to width compared with BES1OE or UBP12OE plants. Hypocotyl elongation and etiolation result from elevated BES1 levels because BES1 degradation is retarded by UBP12 in darkness or in light with BR. Protein degradation inhibitor experiments show that the majority of BES1 can be degraded by either the proteasomal or the autophagy pathway, but a minor BES1 fraction remains pathway specific. In conclusion, UBP12/UBP13 deubiquitinate BES1 to stabilize the latter as a positive regulator for BR responses.

Personalized medicine in inflammatory bowel disease: Perspectives on Asia.

Inflammatory bowel diseases are chronic, relapsing inflammatory disorders of the gastrointestinal tract with variable disease courses and complications, which in some cases can result in significant morbidities and disabilities. Etiologies remain unclear due to complex interactions between genetic and environmental factors. Considering the heterogeneity of inflammatory bowel diseases, personalized approaches in diagnosing and managing affected patients would be beneficial in maximizing treatment efficacies and minimizing adverse events. Personalized medicine may also help to stratify patients with a high risk of progression and inflammatory bowel disease-related complications and identify sub-phenotypic mechanisms to facilitate drug discovery and the development of new treatments. In Asia, with a rapidly increasing incidence and prevalence of inflammatory bowel diseases, studies have shown that patients of Asian ethnicity differ from their Western counterparts in terms of genetic and clinical aspects of inflammatory bowel diseases. Therefore, personalized medicine may differ for patients of Asian ethnicity with inflammatory bowel diseases. We reviewed and summarized current evidence concerning personalized medicine for the diagnosis and management of patients with inflammatory bowel diseases and its possible role from an Asian perspective.

COVID-19 stressors and symptoms of depression and anxiety among Black cisgender sexual minority men and Black transgender women during the initial peak of the COVID-19 pandemic.

PURPOSE: To examine associations between COVID-19-related stressors and symptoms of depression and anxiety in Black cisgender sexual minority men (SMM) and transgender women during the initial peak of the COVID-19 pandemic. METHODS: Participants from the N2 Cohort Study comprised Black cisgender SMM and Black transgender women in Chicago, IL, completed a face-to-face video or phone interview between April 20 and July 31, 2020. The survey included 18 measures of individual, network, and structural COVID-19 stressors such as income loss, network COVID-19 diagnoses, and housing loss, as well as 5 outcome measures: anxiety, depression, loneliness, worry and hope. RESULTS: Of 226 participants, 56.6% experienced anxiety on at least 1 of the last 14 days, 48.7% experienced depression, 48.7% experienced loneliness, 42.0% experienced worry, and 51.8% did not experience hope. Completing the study during a later phase of reopening was associated with hopefulness, RR = 1.37 95% CI [1.02, 1.85]. Fifteen of the 18 multi-level COVID-19 stressors were associated with 1 or more symptoms of depression and anxiety, for example, physical stress reactions, income loss, food loss, medication loss, network COVID-19 diagnoses, partner violence, housing loss, and neighborhood pandemic concerns (aRRs = 0.61-2.78, ps < 0.05). CONCLUSION: COVID-19-related stressors were associated with depression and anxiety symptoms in Black cisgender SMM and transgender women. Mitigation strategies to reduce virus transmission should be supplemented with measures to prevent depression and anxiety among marginalized populations, such as targeted economic relief and eHealth/mHealth interventions.

Highly Efficient Bioconversion of trans-Resveratrol to δ-Viniferin Using Conditioned Medium of Grapevine Callus Suspension Cultures.

δ-Viniferin is a resveratrol dimer that possesses potent antioxidant properties and has attracted attention as an ingredient for cosmetic and nutraceutical products. Enzymatic bioconversion and plant callus and cell suspension cultures can be used to produce stilbenes such as resveratrol and viniferin. Here, δ-viniferin was produced by bioconversion from trans-resveratrol using conditioned medium (CM) of grapevine (Vitis labruscana) callus suspension cultures. The CM converted trans-resveratrol to δ-viniferin immediately after addition of hydrogen peroxide (H2O2). Peroxidase activity and bioconversion efficiency in CM increased with increasing culture time. Optimized δ-viniferin production conditions were determined regarding H2O2 concentration, incubation time, temperature, and pH. Maximum bioconversion efficiency reached 64% under the optimized conditions (pH 6.0, 60 °C, 30 min incubation time, 6.8 mM H2O2). In addition, in vitro bioconversion of trans-resveratrol was investigated using CM of different callus suspension cultures, showing that addition of trans-resveratrol and H2O2 to the CM led to production of δ-viniferin via extracellular peroxidase-mediated oxidative coupling of two molecules of trans-resveratrol. We thus propose a simple and low-cost method of δ-viniferin production from trans-resveratrol using CM of plant callus suspension cultures, which may constitute an alternative approach for in vitro bioconversion of valuable molecules.

Diet and Physical Activity as Determinants of Continuously Measured Glucose Levels in Persons at High Risk of Type 2 Diabetes.

We examined how dietary and physical activity behaviors influence fluctuations in blood glucose levels over a seven-day period in people at high risk for diabetes. Twenty-eight participants underwent a mixed meal tolerance test to assess glucose homeostasis at baseline. Subsequently, they wore an accelerometer to assess movement behaviors, recorded their dietary intakes through a mobile phone application, and wore a flash glucose monitoring device that measured glucose levels every 15 min for seven days. Generalized estimating equation models were used to assess the associations of metabolic and lifestyle risk factors with glycemic variability. Higher BMI, amount of body fat, and selected markers of hyperglycemia and insulin resistance from the meal tolerance test were associated with higher mean glucose levels during the seven days. Moderate- to vigorous-intensity physical activity and polyunsaturated fat intake were independently associated with less variation in glucose levels (CV%). Higher protein and polyunsaturated fatty acid intakes were associated with more time-in-range. In contrast, higher carbohydrate intake was associated with less time-in-range. Our findings suggest that dietary composition (a higher intake of polyunsaturated fat and protein and lower intake of carbohydrates) and moderate-to-vigorous physical activity may reduce fluctuations in glucose levels in persons at high risk of diabetes.