Asymmetric variation in DNA methylation during domestication and de-domestication of rice.

Hundreds of plant species have been domesticated to feed human civilization, while some crops have undergone de-domestication into agricultural weeds, threatening global food security. To understand the genetic and epigenetic basis of crop domestication and de-domestication, we generated DNA methylomes from 95 accessions of wild rice (Oryza rufipogon L.), cultivated rice (Oryza sativa L.) and weedy rice (O. sativa f. spontanea). We detected a significant decrease in DNA methylation over the course of rice domestication but observed an unexpected increase in DNA methylation through de-domestication. Notably, DNA methylation changes occurred in distinct genomic regions for these 2 opposite stages. Variation in DNA methylation altered the expression of nearby and distal genes through affecting chromatin accessibility, histone modifications, transcription factor binding, and the formation of chromatin loops, which may contribute to morphological changes during domestication and de-domestication of rice. These insights into population epigenomics underlying rice domestication and de-domestication provide resources and tools for epigenetic breeding and sustainable agriculture.

Early onset of pathological polyploidization and cellular senescence in hepatocytes lacking RAD51 creates a pro-fibrotic and pro-tumorigenic inflammatory microenvironment.

BACKGROUND AND AIMS: RAD51 recombinase (RAD51) is a highly conserved DNA repair protein and is indispensable for embryonic viability. As a result, the role of RAD51 in liver development and function is unknown. Our aim was to characterize the function of RAD51 in postnatal liver development. APPROACH AND RESULTS: RAD51 is highly expressed during liver development and during regeneration following hepatectomy and hepatic injury, and is also elevated in chronic liver diseases. We generated a hepatocyte-specific Rad51 deletion mouse model using Alb -Cre ( Rad51 -conditional knockout (CKO)) and Adeno-associated virus 8-thyroxine-binding globulin-cyclization recombination enzyme to evaluate the function of RAD51 in liver development and regeneration. The phenotype in Rad51 -CKO mice is dependent on CRE dosage, with Rad51fl/fl ; Alb -Cre +/+ manifesting a more severe phenotype than the Rad51fl/fl ; Alb -Cre +/- mice. RAD51 deletion in postnatal hepatocytes results in aborted mitosis and early onset of pathological polyploidization that is associated with oxidative stress and cellular senescence. Remarkable liver fibrosis occurs spontaneously as early as in 3-month-old Rad51fl/fl ; Alb -Cre +/+ mice. While liver regeneration is compromised in Rad51 -CKO mice, they are more tolerant of carbon tetrachloride-induced hepatic injury and resistant to diethylnitrosamine/carbon tetrachloride-induced HCC. A chronic inflammatory microenvironment created by the senescent hepatocytes appears to activate ductular reaction the transdifferentiation of cholangiocytes to hepatocytes. The newly derived RAD51 functional immature hepatocytes proliferate vigorously, acquire increased malignancy, and eventually give rise to HCC. CONCLUSIONS: Our results demonstrate a novel function of RAD51 in liver development, homeostasis, and tumorigenesis. The Rad51 -CKO mice represent a unique genetic model for premature liver senescence, fibrosis, and hepatocellular carcinogenesis.

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B-cell lymphoma.

The use of Bruton tyrosine kinase inhibitors, such as ibrutinib, to block B-cell receptor signaling has achieved a remarkable clinical response in several B-cell malignancies, including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Acquired drug resistance, however, is significant and affects the long-term survival of these patients. Here, we demonstrate that the transcription factor early growth response gene 1 (EGR1) is involved in ibrutinib resistance. We found that EGR1 expression is elevated in ibrutinib-resistant activated B-cell-like subtype DLBCL and MCL cells and can be further upregulated upon ibrutinib treatment. Genetic and pharmacological analyses revealed that overexpressed EGR1 mediates ibrutinib resistance. Mechanistically, TCF4 and EGR1 self-regulation induce EGR1 overexpression that mediates metabolic reprogramming to oxidative phosphorylation (OXPHOS) through the transcriptional activation of PDP1, a phosphatase that dephosphorylates and activates the E1 component of the large pyruvate dehydrogenase complex. Therefore, EGR1-mediated PDP1 activation increases intracellular adenosine triphosphate production, leading to sufficient energy to enhance the proliferation and survival of ibrutinib-resistant lymphoma cells. Finally, we demonstrate that targeting OXPHOS with metformin or IM156, a newly developed OXPHOS inhibitor, inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting EGR1-mediated metabolic reprogramming to OXPHOS with metformin or IM156 provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory DLBCL or MCL.

Metal-catalyzed asymmetric reactions enabled by organic peroxides.

As a class of multifunctional reagents, organic peroxides play vital roles in the chemical industry, pharmaceutical synthesis and polymerization reactions. Metal-catalyzed asymmetric catalysis has emerged as one of the most straightforward and efficient strategies to construct enantioenriched molecules, and an increasing number of metal-catalyzed asymmetric reactions enabled by organic peroxides have been disclosed by researchers in recent years. Despite remarkable progress, the types of asymmetric reactions facilitated by organic peroxides remain limited and the catalysis systems need to be further broadened. To the best of our knowledge, there is still no review devoted to summarizing the reactions from this perspective. In this review, we will endeavor to highlight the advances in metal-catalyzed asymmetric reactions enabled by organic peroxides. We hope that this survey will summarize the functions of organic peroxides in catalytic reactions, improve the understanding of these compounds and inspire future developments in this area.

Single nucleotide polymorphisms in the KRT82 promoter region modulate irregular thickening and patchiness in the dorsal skin of New Zealand rabbits.

BACKGROUND: While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype. RESULTS: The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy - Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the - 600 to - 1200 segment, in which the four SNPs were located. CONCLUSIONS: The morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.

Establishing an Ion-Sieving Separator by Depositing Oxygen-Deficient SiOx Layer for Stabilized Zinc Metal Anode.

Stable plating/stripping of Zn metal anode remains a great challenge owing to uncontrollable dendrite growth and side reactions. Ion-sieving separators is a unique and promising solution, that possess Zn2+ permeability and promote Zn2+ transport, can effectively alleviate the abovementioned problems. Ion-sieving on glass fiber separator by deposition of oxygen-deficient SiOx layer via active screen plasma technology is achieved. While having chemical composition similar to the glass fiber, the SiOx nanoparticles contain oxygen-rich vacancies that promoted dissociation of the adsorbed water and generation of the hydroxyl groups. The negatively-charged hydroxylated SiOx layer can repel SO4 2- and attract Zn2+, which can alleviate the side reactions. The strong interplay between hydroxyl groups and Zn2+ can boost Zn affinity and yield fast Zn2+ transport. Consequently, the SiOx-deposited GF separator enabled dendrite-free Zn deposition morphology, which displays lower overpotential of 18 mV and longer cycling life over 2000 h for Zn symmetric cell. Such a separator can also be easily scaled up to prepare the high-performance large-area (4 × 6 cm2) pouch Zn-based devices, showing remarkable flexibility and practicality.

Long-term monitoring chlorophyll-a concentration using HJ-1 A/B imagery and machine learning algorithms in typical lakes, a cold semi-arid region.

Chlorophyll a (Chl-a) in lakes serves as an effective marker for assessing algal biomass and the nutritional level of lakes, and its observation is feasible through remote sensing methods. HJ-1 (Huanjing-1) satellite, deployed in 2008, incorporates a CCD capable of a 30 m resolution and has a revisit interval of 2 days, rendering it a superb choice or supplemental sensor for monitoring trophic state of lakes. For effective long-term and regional-scale mapping, both the imagery and the evaluation of machine learning algorithms are essential. The several typical machine learning algorithms, i.e., Support Vector Regression (SVR), Gradient Boosting Decision Trees (GBDT), XGBoost (XGB), Random Forest (RF), K-Nearest Neighbor (KNN), Kernel Ridge Regression (KRR), and Multi-Layer Perception Network (MLP), were developed using our in-situ measured Chl-a. A cross-validation grid to identify the most effective hyperparameter combinations for each algorithm was used, as well as the selected optimal superparameter combinations. In Chl-a mapping of three typical lakes, the R2 of GBDT, XGB, RF, and KRR all reached 0.90, while XGB algorithm also exhibited stable performance with the smallest error (RMSE = 3.11 µg/L). Adjustments were made to align the Chl-a spatial-temporal patterns with past data, utilizing HJ1-A/B CCD images mapping through XGB algorithm, which demonstrates its stability. Our results highlight the considerable effectiveness and utility of HJ-1 A/B CCD imagery for evaluation and monitoring trophic state of lakes in a cold arid region, providing the application cases contribute to the ongoing efforts to monitor water qualities.

Effects of excitation power density on the Stern-Volmer constant measurement.

The Stern-Volmer constant (KSV) is an important parameter to describe the capability of energy transfer to oxygen for porphyrin and its derivatives. By fitting Stern-Volmer equation, IP0/IP = 1 + KSV[O2], the KSV is generally determined through phosphorescence intensities (IP) under aerobic and oxygen-free conditions. In this work, the effect of excitation power density on the KSV measurement is theoretically analyzed and experimentally studied, using palladium octaethylporphyrin (PdOEP) as an example. The IP of PdOEP increased nonlinearly with excitation power density, and the power dependent slope of IP0/IP could be obtained. By way of the functional relationship between the slope of IP0/IP and power density, the real KSV of PdOEP was fitted to be 58 ± 2 kPa-1. The oxygen-dependent phosphorescence lifetimes (τP) and IP under a weak excitation power are also measured to calculate the real KSV, which verifies our analysis.

Polo-like kinase 1 promotes pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. METHODS: Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. RESULTS: Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. CONCLUSIONS: Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

Multimorbidity and polypharmacy in hospitalized older patients: a cross-sectional study.

BACKGROUND: The growing trend of ageing population has become a worldwide concern. In comparison with the youth, older people are more likely to suffer from multimorbidity and polypharmacy, both of which are associated with adverse outcomes and increased healthcare costs. This study aimed to investigate the status of multimorbidity and polypharmacy in a large sample of hospitalized older patients aged 60 years and over. METHODS: A retrospective cross-sectional study was conducted among 46,799 eligible patients aged 60 years and over, who were hospitalized from January 1, 2021 to December 31, 2021. Multimorbidity was defined as the presence of 2 or more morbidities in one patient during the stay in hospital, and polypharmacy as prescription of 5 or more different oral medications. Spearman rank correlation analysis was used to assess the relationship of factors with the number of morbidities or oral medications. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated from logistic regression models to determine the predictors for polypharmacy and all-cause death. RESULTS: The prevalence of multimorbidity was 91.07% and increased with age. The prevalence of polypharmacy was 56.32%. Older age, polypharmacy, prolonged length of stay (LOS), higher cost on medications were significantly associated with an increased number of morbidities (all P < 0.01). The number of morbidities (OR = 1.29, 95% CI: 1.208-1.229) and LOS (OR = 1.171, 95% CI: 1.166-1.177) were potential risk factors for polypharmacy. As for all-cause death, age (OR = 1.107, 95% CI: 1.092-1.122), number of morbidities (OR = 1.495, 95% CI: 1.435-1.558) and LOS (OR = 1.020, 95% CI: 1.013-1.027) were the potential risk factors, but the number of medications (OR = 0.930, 95% CI: 0.907-0.952) and polypharmacy (OR = 0.764, 95% CI: 0.608-0.960) were associated with a reduction of mortality. CONCLUSION: Morbidities and LOS might be predictors for polypharmacy and all-cause death. The number of oral medications was inversely associated with the risk of all-cause mortality. Appropriate polypharmacy was beneficial for the clinical outcomes of older patients during hospitalization.

Establishment and functional characterization of immortalized rabbit dermal papilla cell lines.

Hair follicle (HF) undergo periodic growth and development in mammals, which regulated by dermal papilla cells (DPCs) are reported to play an important role in HF morphogenesis and development. However, primary DPCs have low proliferative activity, age quickly, and fresh cell isolation is both time-consuming and laborious. In this study, we introduced the SV40 large T antigen (SV40T) into dissociated early passage rabbit vibrissae DPCs with lentiviral vectors and established seven immortalized DPC lines (R-1, R-2, R-3, R-4, R-5, R-6 and R-7). These cell lines displayed early passage morphology and high alkaline phosphatase activity. RT-PCR and immunofluorescence staining showed that all the immortalized cell lines expressed the DPC markers (α-SMA, IGF1, ALPL, FGF2, BMP2 and TGFß2), but α-SMA was only expressed well in R-3, R-4, and R-7. Furthermore, it was found that R-7 was the only line to survive beyond 50 passages. Compared to melanoma cells, R-7 did not undergo malignant transformation. Karyotyping and cell growth viability analysis illustrated that the R-7 cell line preserved the basic characteristics of primary DPCs. The R-7 DPCs established have potential application for future hair research. The study provides the theoretical basis in the cell research of HF growth and development.

Student standardized patients versus occupational standardized patients for improving clinical competency among TCM medical students: a 3-year prospective randomized study.

BACKGROUND: Standardized patient (SP) simulations are well-recognized patterns for practicing clinical skills and interactions. Our previous study showed that a simulation program using occupational SP for Traditional Chinese Medicine (OSP-TCMs) was efficient, however, a high cost and time-intensive nature have limited its use. TCM postgraduates trained as student SPs (SSP-TCMs) present a potentially cost-effective alternative. The purpose of this study was to examine and determine whether SSP simulation offered more benefits over didactic training alone for improving clinical competency among TCM medical students, and conduct a multifaceted analysis comparing SSP-TCMs and OSP-TCMs. METHODS: This was a prospective, single-blinded, randomized controlled trial. Fourth-year TCM undergraduates were recruited as trainees from the Clinical Medical School, Chengdu University of TCM. Data were collected from September 2018 to December 2020. Trainees were randomly divided into the three following groups: traditional method training group, OSP-TCM training group, and SSP-TCM training group (1:1:1). At the end of a 10-week curriculum, trainees received a two-station examination comprising a systematic online knowledge test and an offline clinical performance examination. Post-training and post-exam questionnaires were administered to collect feedback from these trainees. RESULTS: Students assigned to the SSP-TCM training and OSP-TCM training groups received favorable marks for the "systematic knowledge test" and "TCM clinical skills" (2018, Pa=0.018, Pb=0.042; 2019, Pa=0.01, Pb=0.033; 2020, Pa=0.035, Pb=0.039) compared to the TM trainees. Additionally, trainees in the intervention groups demonstrated a positive post-training edge in scores of "medical records" (2018, Pa=0.042, Pb=0.034; 2019, Pa=0.032, Pb=0.042; 2020, Pa=0.026, Pb=0.03) and "TCM syndrome differentiation and therapeutic regimen" (2018, Pb=0.032; 2019, Pa=0.037, Pb=0.024; 2020, Pa=0.036, Pb=0.043). For the simulation encounter assessment given by SP-TCMs, OSP-TCM trainees and SSP-TCM trainees scored higher than TM trainees (2018, Pa=0.038, Pb=0.037; 2019, Pa=0.024, Pb=0.022; 2020, Pa=0.019, Pb=0.021). For the feedback questionnaires, the students in TM group provided less positive feedback for training efficacy and test performance compared to those in the SSP-TCM and OSP-TCM groups. The trainees responded that the training effect of clinical simulations was similar between the SSP-TCM and OSP-TCM groups. SSP-TCMs were more responsive to unexpected emergencies (Pa=0.022, Pb>0.05) and more likely to encourage questioning (Pa=0.029, Pb>0.05) but tended to provide implied hints (Pc=0.015) and utilize medical jargon (Pc=0.007) as compared to OSP-TCMs. CONCLUSION: Simulation training for SSP-TCMs and OSP-TCMs showed great benefits for enhancing clinical competency. SSP-TCM simulation was feasible, practical, and cost-effective, and may serve as an alternative method to OSP-TCM simulation.

Mapping Fire Severity in Southwest China Using the Combination of Sentinel 2 and GF Series Satellite Images.

Fire severity mapping can capture heterogeneous fire severity patterns over large spatial extents. Although numerous remote sensing approaches have been established, regional-scale fire severity mapping at fine spatial scales (<5 m) from high-resolution satellite images is challenging. The fire severity of a vast forest fire that occurred in Southwest China was mapped at 2 m spatial resolution by random forest models using Sentinel 2 and GF series remote sensing images. This study demonstrated that using the combination of Sentinel 2 and GF series satellite images showed some improvement (from 85% to 91%) in global classification accuracy compared to using only Sentinel 2 images. The classification accuracy of unburnt, moderate, and high severity classes was significantly higher (>85%) than the accuracy of low severity classes in both cases. Adding high-resolution GF series images to the training dataset reduced the probability of low severity being under-predicted and improved the accuracy of the low severity class from 54.55% to 72.73%. RdNBR was the most important feature, and the red edge bands of Sentinel 2 images had relatively high importance. Additional studies are needed to explore the sensitivity of different spatial scales satellite images for mapping fire severity at fine spatial scales across various ecosystems.

Dermal PapillaCell-Derived Exosomes Regulate Hair Follicle Stem Cell Proliferation via LEF1.

Hair follicle (HF) growth and development are controlled by various cell types, including hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs). Exosomes are nanostructures that participate in many biological processes. Accumulating evidence indicates that DPC-derived exosomes (DPC-Exos) mediate HFSC proliferation and differentiation during the cyclical growth of hair follicles. In this study, we found that DPC-Exos increase ki67 expression and CCK8 cell viability readouts in HFSCs but reduce annexin staining of apoptotic cells. RNA sequencing of DPC-Exos-treated HFSCs identified 3702 significantly differentially expressed genes (DEGs), including BMP4, LEF1, IGF1R, TGFß3, TGFα, and KRT17. These DEGs were enriched in HF growth- and development-related pathways. We further verified the function of LEF1 and showed that overexpression of LEF1 increased the expression of HF development-related genes and proteins, enhanced HFSC proliferation, and reduced HFSC apoptosis, while knockdown of LEF1 reversed these effects. DPC-Exos could also rescue the siRNA-LEF1 effect in HFSCs. In conclusion, this study demonstrates that DPC-Exos mediated cell-to-cell communication can regulate HFSCs proliferation by stimulating LEF1 and provide novel insights into HF growth and development regulatory mechanisms.

The Effects of Resistant Starch on Biomarkers of Inflammation and Oxidative Stress: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to investigate the effects of resistant starch (RS) on inflammation and oxidative stress related indicators. PubMed, Embase and The Cochrane library were systematically searched to find randomized controlled trials (RCTs) of RS intervention up to February 2020. We used from the effect size, as estimated by the standardized mean difference (SMD) with 95% confidence intervals (95%CI) to perform the random method meta-analysis, with P value ≦0.05 as statistically significant. The 16 included trials with 17 effect sizes included a total of 739 participants in this paper. The intervention duration was from 2 weeks to 3 months. The analysis indicated that RS decreases the levels of tumor necrosis factor-α (TNF-α) (SMD = -0.711; 95%CI: -1.227, -0.194; P = 0.007) and interleukin 6 (IL-6) (SMD = -0.609; 95%CI: -0.924, -0.294; P < 0.001), increases total antioxidant capacity (TAC) (SMD = 2.543, 95% CI: 0.069: 5.017, P = 0.044). No significant effects on C-reactive protein (CRP) (SMD = -0.583; 95%CI: -1.270, 0.104; P = 0.096), superoxide dismutase (SOD) (SMD = 0.091; 95%CI: -0.156, 0.338; P = 0.471), and malondialdehyde (MDA) (SMD = -0.320; 95%CI: -0.907, 0.266; P = 0.285). Subgroup analysis shown that CRP level significant reduced in subjects from the east (SMD = -1.501; 95%CI: -2.662, -0.340; P = 0.011) or suffering from diseases (SMD: -1.057; 95%CI: -1.999, -0.115; P = 0.028).Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.2019284.

Multi-dimensional vulnerability analysis on catastrophic health expenditure among middle-aged and older adults with chronic diseases in China.

OBJECTIVE: Middle-aged and older adults are more likely to suffer from chronic diseases because of their particular health characteristics, which lead to a high incidence of catastrophic health expenditure (CHE). This study plans to analyse the different factors affecting CHE in middle-aged and older adults with chronic diseases, target the vulnerable characteristics, and suggest groups that medical insurance policies should pay more attention to. METHODS: The data used in this study came from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database. The method of calculating the CHE was adopted from the World Health Organization (WHO). The logistic regression was used to determine the family characteristics of chronic disease in middle-aged and older adults with a high probability of incurring CHE. RESULTS: The incidence of CHE in middle-aged and older adults with chronic disease was highest in sub-poverty level families (26.20%) was lowest in wealthier level families (20.07%). Households with malignant tumours had the highest CHE incidence under any circumstances, especially if the householder had been using inpatient service in the past year. Among the comparison of CHE incidence in different types of medical insurance, the Urban and Rural Residents' Basic Medical Insurance (URRBMI) was the highest (27.46%). The incidence of CHE was 2.73 times (95% CI 2.30-3.24) and 2.16 times (95% CI 1.81-2.57) higher among people who had used inpatient services in the past year or outpatient services in the past month than those who had not used them. CONCLUSIONS: Relatively wealthy economic conditions cannot significantly reduce the financial burden of chronic diseases in middle-aged and older adults. For this particular group with multiple vulnerabilities, such as physical and social vulnerability, the high demand and utilization of health services are the main reasons for the high incidence of CHE. After achieving the goal of lowering the threshold of universal access to health services, the medical insurance system in the next stage should focus on multiple vulnerable groups and strengthen the financial protection for middle-aged and older adults with chronic diseases, especially for patients with malignant tumours.

Intrinsic Characterization Method on the Heavy Atom Effect of Metalloporphyrins.

The presence of room temperature phosphorescence emission in metalloporphyrin, via the transition from the excited triplet state (T1) to the ground state (S0), relies on the chelated heavy metal ions, which is known as the heavy atom effect (HAE). Despite the HAE being a reliable method to tune the phosphorescence process widely, the realization of the HAE nature is a tough task as the induced phosphorescence process is sensitive to not only the specie of bonded heavy atoms but also chemical environments such as the oxygen quenching and solvent effect. In this study, we have aimed at a quantitative determination of the intrinsic phosphorescent transition rate (kP) in metalloporphyrin gadolinium-labeled hematoporphyrin monomethyl ether (Gd-HMME). After the theoretical analysis based on the rate equation model to remove the nonintrinsic contribution and the experimental results of phosphorescence, the kP is calculated to be ∼2.4 × 10-4 µs-1. This study enables us to approach the intrinsic energy characteristic of metalloporphyrins; moreover, our work provides an effective pathway for the further optimization of the varied functional metalloporphyrin.

Spatial effects of air pollution on the economic burden of disease: implications of health and environment crisis in a post-COVID-19 world.

BACKGROUND: Air pollution has been identified as related to the diseases of susceptible population, but the spatial heterogeneity of its economic burden and its determinants are rarely investigated. The issue is of great policy significance, especially after the epidemic of COVID-19, when human are facing the joint crisis of health and environment, and some areas is prone to falling into poverty. METHODS: The geographical detector was adopted to study the spatial distribution characteristics of the incidence of catastrophic health expenditure (ICHE) for older adults in 100 rural areas in China at the prefecture-city level. The health factors, sociological factors, policy factors and environmental factors and their interactions are identified. RESULTS: First, most health service factors had strong explanatory power for ICHE whether it interacts with air pollution. Second, 50 single-factor high-risk areas of ICHE were found in the study, but at the same time, there were 21 areas dominated by multiple factors. CONCLUSION: The different contributions and synergy among the factors constitute the complex mechanism of factors and catastrophic health expenditure. Moreover, during this process, air pollution aggravates the contribution of health service factors toward ICHE. In addition, the leading factors of ICHE are different among regions. At the end, this paper also puts forward some policy suggestions from the perspective of health and environment crisis in the post-COVID-19 world: environmental protection policies should be combined with the prevention of infectious diseases; advanced health investment is the most cost-effective policy for the inverse health sequences of air pollution and infectious diseases such as coronavirus disease 2019 (COVID-19); integrating environmental protection policy into healthy development policy, different regions take targeted measures to cope with the intertwined crisis.

SLC7A11/xCT Prevents Cardiac Hypertrophy by Inhibiting Ferroptosis.

PURPOSE: Systemic hypertension may induce adverse hypertrophy of the left cardiac ventricle. Pathological cardiac hypertrophy is a common cause of heart failure. We investigated the significance of ferroptosis repressor xCT in hypertrophic cardiomyopathy. METHODS: xCT expression in angiotensin II (Ang II)-treated mouse hearts and rat cardiomyocytes was determined using qRT-PCR and Western blotting. Cardiac hypertrophy was induced by Ang II infusion in xCT knockout mice and their wildtype counterparts. Blood pressure, cardiac pump function, and pathological changes of cardiac remodeling were analyzed in these mice. Cell death, oxidative stress, and xCT-mediated ferroptosis were examined in Ang II-treated rat cardiomyocytes. RESULTS: After Ang II infusion, xCT was downregulated at day 1 but upregulated at day 14 at both mRNA and protein levels. It was also decreased in Ang II-treated cardiomyocytes, but not in cardiofibroblasts. Inhibition of xCT exacerbated cardiomyocyte hypertrophy and boosted the levels of ferroptosis biomarkers Ptgs2, malondialdehyde, and reactive oxygen species induced by Ang II, while overexpression of xCT opposed these detrimental effects. Furthermore, knockout of xCT aggravated Ang II-mediated mouse cardiac fibrosis, hypertrophy, and dysfunction. Ferrostatin-1, a ferroptosis inhibitor, alleviated the exacerbation of cardiomyocyte hypertrophy caused by inhibiting xCT in cultured rat cells or ablating xCT in mice. CONCLUSION: xCT acts as a suppressor in Ang II-mediated cardiac hypertrophy by blocking ferroptosis. Positive modulation of xCT may therefore represent a novel therapeutic approach against cardiac hypertrophic diseases.

Two-stage mental health survey of first-line medical staff after ending COVID-19 epidemic assistance and isolation.

Facing with COVID-19 epidemic such a catastrophic health emergency, the mental health status of medical staff deserves attention. We conducted a two-stage of psychological status monitoring after the end of the assistance and 14 days of isolation, further targeted the vulnerable groups in need of intervention. The study is a cross-sectional survey on 1156 Yunnan medical staff aid to Hubei. Used Cluster sampling method to collect data at 2 time points (at the end of returning from Wuhan and the 14th day of isolation), from March 18, 2020 to April 6, 2020. Female and nurse had higher rates of depressive symptoms than male and doctors and other occupations. The proportion of female with mild and above moderate anxiety levels (22.91%, 2.61%) was higher than male (17.35%, 1.03%) (p < 0.05). Female had a better impaired sleep quality (45.06%, 17.49%) more than male (28.57%, 7.94%). Medical staff supported in Wuhan and with junior professional titles reported a higher proportion of sleep quality impairment. At the 14th isolation day stage, the proportion of nurses changed from depression to health (9.15%) and from health to depression (6.1%) better than doctors. The front-line medical staffs had suffered greater psychological pressure in the treatment process of major public health emergency. Researches on the dynamic monitor for the change of psychological status after aiding epidemic areas were still in relatively blank stage. Targeting the vulnerable characteristics of aiding medical staff is significant for effective psychological intervention and sustainable operation of health system.