Induction of DEPP1 by HIF Mediates Multiple Hallmarks of Ischemic Cardiomyopathy.

BACKGROUND: HIF (hypoxia inducible factor) regulates many aspects of cardiac function. We and others previously showed that chronic HIF activation in the heart in mouse models phenocopies multiple features of ischemic cardiomyopathy in humans, including mitochondrial loss, lipid accumulation, and systolic cardiac dysfunction. In some settings, HIF also causes the loss of peroxisomes. How, mechanistically, HIF promotes cardiac dysfunction is an open question. METHODS: We used mice lacking cardiac pVHL (von Hippel-Lindau protein) to investigate how chronic HIF activation causes multiple features of ischemic cardiomyopathy, such as autophagy induction and lipid accumulation. We performed immunoblot assays, RNA sequencing, mitochondrial and peroxisomal autophagy flux measurements, and live cell imaging on hearts and isolated cardiomyocytes. We used CRISPR-Cas9 gene editing in mice to validate a novel mediator of cardiac dysfunction in the setting of chronic HIF activation. RESULTS: We identify a previously unknown pathway by which cardiac HIF activation promotes the loss of mitochondria and peroxisomes. We found that DEPP1 (decidual protein induced by progesterone 1) is induced under hypoxia in a HIF-dependent manner and localizes inside mitochondria. DEPP1 is both necessary and sufficient for hypoxia-induced autophagy and triglyceride accumulation in cardiomyocytes ex vivo. DEPP1 loss increases cardiomyocyte survival in the setting of chronic HIF activation ex vivo, and whole-body Depp1 loss decreases cardiac dysfunction in hearts with chronic HIF activation caused by VHL loss in vivo. CONCLUSIONS: Our findings identify DEPP1 as a key component in the cardiac remodeling that occurs with chronic ischemia.

Potentiating dual-directional immunometabolic regulation with nanomedicine to enhance anti-tumor immunotherapy following incomplete photothermal ablation.

Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

Decomposition Analysis of Depressive Symptom Differences Among Older Adults With Hypertension Between Urban and Rural Areas: Cross-Sectional Study.

Background: Hypertension is the most prevalent chronic disease among China's older population, which comprises a growing proportion of the overall demographic. Older individuals with chronic diseases have a higher risk of developing depressive symptoms than their healthy counterparts, as evidenced in China's older population, where patients with hypertension exhibit varying rates of depression depending on residing in urban or rural areas. Objective: This study aimed to investigate factors influencing and contributing to the disparities in depressive symptoms among older urban and rural patients with hypertension in China. Methods: We used a cross-sectional study design and derived data from the 8th Chinese Longitudinal Health Longevity Survey of 2018. The Fairlie model was applied to analyze the factors contributing to disparities in depressive symptoms between urban and rural older populations with hypertension. Results: The sample size for this study was 5210, and 12.8% (n=669) of participants exhibited depressive symptoms. The proportions of depressive symptoms in rural and urban areas were 14.1% (n=468) and 10.7% (n=201), respectively. In rural areas, years of education (1-6 years: odds ratio [OR] 0.68, 95% CI 1.10-1.21; ≥7 years: OR 0.47, 95% CI 0.24-0.94), alcohol consumption (yes: OR 0.52, 95% CI 0.29-0.93), exercise (yes: OR 0.78, 95% CI 0.56-1.08), and sleep duration (6.0-7.9 hours: OR 0.29, 95% CI 0.17-0.52; 8.0-9.9 hours: OR 0.24, 95% CI 0.13-0.43; ≥10.0 hours: OR 0.22, 95% CI 0.11-0.41) were protective factors against depressive symptoms in older adults with hypertension, while gender (female: OR 1.94, 95% CI 1.33-2.81), self-reported income status (poor: OR 3.07, 95% CI 2.16-4.37), and activities of daily living (ADL) dysfunction (mild: OR 1.69, 95% CI 1.11-2.58; severe: OR 3.03, 95% CI 1.46-6.32) were risk factors. In urban areas, age (90-99 years: OR 0.37, 95% CI 0.16-0.81; ≥100 years: OR 0.19, 95% CI 0.06-0.66), exercise (yes: OR 0.33, 95% CI 0.22-0.51), and sleep duration (6.0-7.9 hours: OR 0.27, 95% CI 0.10-0.71; 8.0-9.9 hours: OR 0.16, 95% CI 0.06-0.44; ≥10.0 hours: OR 0.18, 95% CI 0.06-0.57) were protective factors, while years of education (1-6 years: OR 1.91, 95% CI 1.05-3.49), self-reported income status (poor: OR 2.94, 95% CI 1.43-6.08), and ADL dysfunction (mild: OR 2.38, 95% CI 1.39-4.06; severe: OR 3.26, 95% CI 1.21-8.76) were risk factors. The Fairlie model revealed that 91.61% of differences in depressive symptoms could be explained by covariates, including years of education (contribution 63.1%), self-reported income status (contribution 13.2%), exercise (contribution 45.7%), sleep duration (contribution 20.8%), ADL dysfunction (contribution -9.6%), and comorbidities (contribution -22.9%). Conclusions: Older patients with hypertension in rural areas had more depressive symptoms than their counterparts residing in urban areas, which could be explained by years of education, self-reported income status, exercise, sleep duration, ADL dysfunction, and comorbidities. Factors influencing depressive symptoms had similarities regarding exercise, sleep duration, self-reported income status, and ADL dysfunction as well as differences regarding age, gender, years of education, and alcohol consumption.

Association between Plant-based Diet and Risk of Chronic Diseases and All-Cause Mortality in Centenarians in China: A Cohort Study.

Background: Numerous studies have suggested the health benefits of a plant-based dietary pattern. However, whether this dietary pattern is associated with health benefits for centenarians remains unexplored. Our study aimed to investigate the correlation between 16 widely consumed Chinese food items and the incidence rates of chronic diseases and all-cause mortality among centenarians. Methods: We conducted a dietary survey on 3372 centenarians with an average age of 102.33 y in China. After rigorous screening, we identified 2675 centenarians, who underwent a 10-y follow-up study with all-cause mortality as the primary outcome. We developed 6 dietary patterns on the basis of the food consumption frequency of each participant. To model the impact of missing values, we employed multiple imputation methods, verifying the robustness of models. Results: The overall plant-based diet index (PDI), healthy plant-based diet index (hPDI), unhealthy plant-based diet index (uPDI), healthy plant-based foods index (HPF), unhealthy plant-based foods index (uHPF), and animal-based foods index (AF) scores among centenarians in China were 46.95 ± 6.29, 44.43 ± 5.76, 51.09 ± 6.26, 21.63 ± 4.79, 9.91 ± 2.41, and 14.59 ± 3.58, respectively. High scores of PDI, hPDI, and HPF were associated with a lower risk of chronic diseases. In the 10-y follow-up study, 92.90% of centenarians have died. The high scores of the PDI (HRPDI = 0.81), hPDI (HRhPDI = 0.79), and HPF (HRHPF = 0.81) scores were significantly associated with a lower risk of death compared with the low scores. Conversely, the high AF score (HRAF = 1.17) was significantly associated with a higher risk of death compared with the low scores. Conclusion: Despite the fact that a higher score in both a predominantly plant-based dietary pattern and a healthy dietary pattern can decrease the death among centenarians, not all HPFs have this effect. A higher AF predicted a higher risk of mortality, whereas higher PDI, hPDI, and HPF were associated with a lower risk of mortality among Chinese centenarians.

HaMYBA-HabHLH1 regulatory complex and HaMYBF fine-tune red flower coloration in the corolla of sunflower (Helianthus annuus L.).

Sunflowers are well-known ornamental plants, while sunflowers with red corolla are rare and the mechanisms underlying red coloration remain unclear. Here, a comprehensive analysis of metabolomics and transcriptomics on flavonoid pathway was performed to investigate the molecular mechanisms underlying the differential color formation between red sunflower Pc103 and two yellow sunflowers (Yr17 and Y35). Targeted metabolomic analysis revealed higher anthocyanin levels but lower flavonol content in Pc103 compared to the yellow cultivars. RNA-sequencing and phylogenetic analysis identified multiple genes involved in the flavonoid pathway, including series of structural genes and three MYB and bHLH genes. Specifically, HaMYBA and HabHLH1 were up-regulated in Pc103, whereas HaMYBF exhibited reduced expression. HaMYBA was found to interact with HabHLH1 in vivo and in vitro, while HaMYBF does not. Transient expression analysis further revealed that HabHLH1 and HaMYBA cooperatively regulate increased expression of dihydroflavonol 4-reductase (DFR), leading to anthocyanin accumulation. On the other hand, ectopic expression of HaMYBF independently modulates flavonol synthase (FLS) expression, but hindered anthocyanin production. Collectively, our findings suggest that the up-regulation of HaMYBA and HabHLH1, as well as the down-regulation of HaMYBF, contribute to the red coloration in Pc103. It offers a theoretical basis for improving sunflower color through genetic engineering.

The Prevalence of Non-infectious Diseases Among Overseas Chinese Workers in 2018.

Background: With the "Belt and Road" initiative, more Chinese citizens have gone abroad to engage in overseas labor activities. Few studies have investigated the prevalence of non-infectious diseases among Chinese overseas workers. This study seeks to fill the gap and illustrate the relevant diseases in a population of Chinese overseas workers. Methods: The health records of 13,529 Chinese migrant workers (12,917 males, mean age 41.3 ± 8.7 years, and 612 females, mean age 33.1 ± 10.2 years) who visited the International Travel Health Care Center in Anhui province were obtained. Chi-square test and binary logistic regression models were used to analyze the associations between the prevalence of non-infectious diseases and sex, as well as the association between non-infectious diseases and length of stay abroad. Results: In this study, 34.6% of overseas workers were found to have one or more types of non-infectious diseases. Hypertension had the highest prevalence (9.58%). Hypertension, fatty liver, renal disease and abnormal liver function tests were more prevalent among male workers than among female workers, while anemia and abnormal urinalysis were more prevalent among female workers. The prevalence of hypertension, renal diseases, liver diseases and gallbladder diseases increased with the length of stay abroad. Conclusion: Non-infectious diseases including cardiovascular diseases, diabetes, and chronic respiratory diseases were highly prevalent among Chinese overseas workers. Hence the monitoring of non-infectious diseases needs to be enhanced to reduce China's overall disease burden in the future.