Diversity patterns of cushion plants on the Qinghai-Tibet Plateau: A basic study for future conservation efforts on alpine ecosystems

The Qinghai-Tibet Plateau (QTP) is an important cushion plant hotspot. However, the distribution of cushion plants on the QTP is unknown, as are the factors that drive cushion plant distribution, limiting our understanding of the evolution of cushion species in the region. In this study, we assessed spatial patterns of total cushion plant diversity (including taxonomic and phylogenetic) over the entire QTP and compared patterns of diversity of cushion plants with different typologies (i.e., compact vs. loose). We also examined how these patterns were related to climatic features. Our results indicate that the southern QTP hosts the highest total cushion plant richness, especially in the south-central Hengduan Mountains subregion. The total number of cushion species declines from south to north and from southeast to northwest. Compact cushion plants exhibit similar patterns as the total cushion plant richness, whereas loose cushion plants show random distribution. Cushion plant phylogenetic diversity showed a similar pattern as that of the total cushion plant richness. In addition, cushion plant phylogenetic community structure was clustered in the eastern and southwestern QTP, whereas random or overdispersed in other areas. Climatic features represented by annual energy and water trends, seasonality and extreme environmental factors, had significant effects on cushion plant diversity patterns but limited effects on the phylogenetic community structure, suggesting that climatic features indeed promote the formation of cushion plants. Because cushion plants play vital roles in alpine ecosystems, our findings not only promote our understanding of the evolution and formation of alpine cushion plant diversity but also provide an indispensable foundation for future studies on cushion plant functions and thus alpine ecosystem sustainability in the entire QTP region.     

东海区绿鳍马面鲀的早期发育和产卵场、产卵期的探讨

1.1972—1982年我们在东海采集到绿鲭马面纯仔、稚鱼3,085尾,仔、稚鱼体长为1.46—9.25毫米。 2.根据人工授精资料,我们鉴定为绿鳍马面纯的仔、稚鱼,并对各发育阶段的形态特征进行了描述。 3.绿鳍马面纯的产卵场、产卵期了解很少。根据调查和观察,产卵期为4月上旬到5月中旬,主要产卵期在4月中、下旬。产卵场在我国钓鱼岛西北部。 4.绿鳍马面鲀产卵与黑潮暖流的高温、高盐水有关。产卵场水温主要为22°—23℃.盐度在34.50‰以上,水深80米以上的海区。     

Alternatively activated macrophages at the recipient site improve fat graft retention by promoting angiogenesis and adipogenesis

The inflammatory response mediated by macrophages plays a role in tissue repair. Macrophages preferentially infiltrate the donor site and subsequently, infiltrate the recipient site after fat grafting. This study aimed to trace host‐derived macrophages and to evaluate the effects of macrophage infiltration at the recipient site during the early stage on long‐term fat graft retention. In our novel mouse model, all mice underwent simulated liposuction and were divided into 2 groups. The fat procurement plus grafting (Pro‐Grafting) group was engrafted with prepared fat (0.3 ml). The pro‐Grafting+M2 group was engrafted with prepared fat (0.3 ml) mixed with 1.0 × 10⁶ GFP+M0 macrophages, and then, 2 ng IL‐4 was injected into the grafts on Day 3. In addition, 1.0 × 10⁶ GFP+M0 macrophages were injected into the tail vein for tracing in the Pro‐Grafting group. As a result, GFP+macrophages first infiltrated the donor site and subsequently infiltrated the recipient site in the Pro‐Grafting group. The long‐term retention rate was higher in the Pro‐Grafting+M2 group (52% ± 6.5%) than in the Pro‐Grafting group (40% ± 3.5%). CD34+ and CD31+ areas were observed earlier, and expression of the adipogenic proteins PPAR‐γ, C/EBP and AP2 was higher in the Pro‐Grafting+M2 group than in the Pro‐Grafting group. The host macrophages preferentially infiltrate the donor site, and then, infiltrate the recipient site after fat grafting. At the early stage, an increase in macrophages at the recipient site may promote vascularization and regeneration, and thereby improve the fat graft retention rate.     

Design,synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC₅₀ values and significant selectivity towards other S-adenosyl-_L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC₅₀ value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.     

Association between long-term exposure to ambient air pollution and COVID-19 severity: a prospective cohort study

Background:The tremendous global health burden related to COVID-19 means that identifying determinants of COVID-19 severity is important for prevention and intervention. We aimed to explore long-term exposure to ambient air pollution as a potential contributor to COVID-19 severity, given its known impact on the respiratory system.Methods:We used a cohort of all people with confirmed SARS-CoV-2 infection, aged 20 years and older and not residing in a long-term care facility in Ontario, Canada, during 2020. We evaluated the association between long-term exposure to fine particulate matter (PM_2.5), nitrogen dioxide (NO₂) and ground-level ozone (O₃), and risk of COVID-19-related hospital admission, intensive care unit (ICU) admission and death. We ascertained individuals’ long-term exposures to each air pollutant based on their residence from 2015 to 2019. We used logistic regression and adjusted for confounders and selection bias using various individual and contextual covariates obtained through data linkage.Results:Among the 151 105 people with confirmed SARS-CoV-2 infection in Ontario in 2020, we observed 8630 hospital admissions, 1912 ICU admissions and 2137 deaths related to COVID-19. For each interquartile range increase in exposure to PM_2.5 (1.70 μg/m³), we estimated odds ratios of 1.06 (95% confidence interval [CI] 1.01–1.12), 1.09 (95% CI 0.98–1.21) and 1.00 (95% CI 0.90–1.11) for hospital admission, ICU admission and death, respectively. Estimates were smaller for NO₂. We also estimated odds ratios of 1.15 (95% CI 1.06–1.23), 1.30 (95% CI 1.12–1.50) and 1.18 (95% CI 1.02–1.36) per interquartile range increase of 5.14 ppb in O₃ for hospital admission, ICU admission and death, respectively.Interpretation:Chronic exposure to air pollution may contribute to severe outcomes after SARS-CoV-2 infection, particularly exposure to O₃.

By November 2021, COVID-19 had caused more than 5 million deaths globally¹ and more than 29 400 in Canada.² The clinical manifestations of SARS-CoV-2 infection range from being asymptomatic to multiple organ failure and death. Identifying risk factors for COVID-19 severity is important to better understand etiological mechanisms and identify populations to prioritize for screening, vaccination and medical treatment. Risk factors for severity of COVID-19 include male sex, older age, pre-existing medical conditions and being from racialized communities.^3–5 More recently, ambient air pollution has been implicated as a potential driver of COVID-19 severity.^6–10Long-term exposure to ambient air pollution, a major contributor to global disease burden,¹¹ could increase the risk of severe COVID-19 outcomes by several mechanisms. Air pollutants can reduce individuals’ pulmonary immune responses and antimicrobial activities, boosting viral loads.⁸ Air pollution can also induce chronic inflammation and overexpression of the alveolar angiotensin-converting enzyme 2 (ACE) receptor,⁷ the key receptor that facilitates SARS-CoV-2 entry into cells.^12,13 Exposure to air pollution contributes to chronic conditions, such as cardiovascular disease, that are associated with unfavourable COVID-19 prognosis, possibly owing to persistent immune activation and excessive amplification of cytokine development.¹⁰ Thus, greater exposure to long-term air pollution may lead to severe COVID-19 outcomes.Reports exist of positive associations between long-term exposure to particulate matter with diameters equal to or smaller than 2.5 or 10 μm (PM_2.5 and PM₁₀), ground-level ozone (O₃) and nitrogen dioxide (NO₂), and metrics of COVID-19 severity (e.g., mortality and case fatality rate).^8–10 However, most studies to date have used ecological and cross-sectional designs, owing to limited access to individual data, which leads to ambiguity in interpreting the results, thus hindering their influence on policy. ^6,14 Ecological designs do not allow for disentangling the relative impacts of air pollution on individual susceptibility to infection and disease severity.¹⁴ Residual confounding by factors such as population mobility and social interactions is also problematic. Therefore, a cohort study with data on individuals with SARS-CoV-2 is a more appropriate design.^6,14 Studies that have used individual data were conducted in specific subpopulations^15,16 or populations with few severe cases,¹⁷ or had limited data on individual exposure to air pollutants.¹⁸ In Canada, 1 ecological study found a positive association between long-term exposure to PM_2.5 and COVID-19 incidence,¹⁹ but no published study has explored the association between air pollution and COVID-19 severity.We aimed to examine the associations between long-term exposure to 3 common air pollutants (PM_2.5, NO₂ and O₃) and key indicators of COVID-19 severity, including hospital admission, intensive care unit (ICU) admission and death, using a large prospective cohort of people with confirmed SARS-CoV-2 infection in Ontario, Canada, in 2020. The air contaminants PM_2.5, NO₂ and O₃ are regularly monitored by the Canadian government, and are key pollutants that are considered when setting air-quality policies. They originate from varying sources (NO₂ is primarily emitted during combustion of fuel, O₃ is primarily formed in air by chemical reactions of nitrogen oxides and volatile organic compounds, and PM_2.5 can be emitted during combustion or formed by reactions of chemicals like sulphur dioxide and nitrogen oxides in air) and they may affect human health differently.^20,21,22     

Buschke-Ollendorff syndrome presenting with asymptomatic yellowish papules and leg length discrepancy: A case report

Buschke-Ollendorff syndrome (BOS) is a rare, usually benign, autosomal dominant genetic disease affecting about 0.005% globally. BOS commonly manifests with asymptomatic connective tissue nevi, sometimes with sclerotic bone lesions like osteopoikilosis or melorheostosis. However, BOS may develop severe, symptomatic complications that require surgical intervention. Here we report a 9-year-8-month girl presenting with multiple nonpruritic, nonpainful skin plaques scattered around the trunk, buttocks, and bilateral legs. She had a history of right varus foot with inadequate plantar flexion. Upon visiting, obvious leg length discrepancy (LLD) was noted. Lesional biopsy revealed increased fibroblasts within dermal collagen bundles. Verhoeff-van Gieson stain revealed scattered foci of thickened elastic fibers between collagen fibers, especially in the mid-dermis. Radiographic examination of the lower extremities showed multiple small, round-to-oval shaped, radiopaque spots on the pelvic bones, femurs, tibiae, and both feet. Hyperostosis along the long axis with “dripping candle wax” appearance was characteristic of osteopoikilosis and melorheostosis. Genetic analysis showed heterozygous point mutation in exon 1 of LEMD3 gene (c.1323C>A, p.Y441X), confirming diagnosis of BOS. Sequential and epiphyseodesis were performed to correct LLD with a favorable outcome at 2-year follow-up. BOS associated with severe bone abnormalities is rare, but orthopedic surgical intervention can provide satisfactory outcome.     

DNMT3b protects centromere integrity by restricting R-loop-mediated DNA damage

This study used DNA methyltransferase 3b (DNMT3b) knockout cells and the functional loss of DNMT3b mutation in immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) cells to understand how DNMT3b dysfunction causes genome instability. We demonstrated that R-loops contribute to DNA damages in DNMT3b knockout and ICF cells. More prominent DNA damage signal in DNMT3b knockout cells was due to the loss of DNMT3b expression and the acquirement of p53 mutation. Genome-wide ChIP-sequencing mapped DNA damage sites at satellite repetitive DNA sequences including (peri-)centromere regions. However, the steady-state levels of (peri-)centromeric R-loops were reduced in DNMT3b knockout and ICF cells. Our analysis indicates that XPG and XPF endonucleases-mediated cleavages remove (peri-)centromeric R-loops to generate DNA beaks, causing chromosome instability. DNMT3b dysfunctions clearly increase R-loops susceptibility to the cleavage process. Finally, we showed that DNA double-strand breaks (DSBs) in centromere are probably repaired by error-prone end-joining pathway in ICF cells. Thus, DNMT3 dysfunctions undermine the integrity of centromere by R-loop-mediated DNA damages and repair.Subject terms: Double-strand DNA breaks, DNA methylation, Primary immunodeficiency disorders