RNA sequencing analysis to capture the transcriptome landscape during skin ulceration syndrome progression in sea cucumber Apostichopus japonicus

Complement and coagulation cascades pathways (tif). Red boxes represent up-regulated genes, and green boxes represent down-regulated genes. (TIF 627 kb

Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells\u27 inflammatory phenotype may impact obesity and its complications

Air Quality Improvement in China: Evidence from PM_2.5 Concentrations in Five Urban Agglomerations, 2000–2021

Air pollution endangers human health and sustainable socio-economic development, especially in urban agglomeration (UA). The Chinese government has implemented a series of policies and standards to improve air quality. However, few studies have compared variations in PM2.5 concentrations across multiple UAs, and current research often lacks analysis relative to the clean air policies implemented by the government. In this study, we used econometric and geostatistical methods to assess the distribution and spatial evolution of PM2.5 concentrations in five UAs (the Beijing–Tianjin–Hebei UA (BTHUA), middle reaches of the Yangtze River UA (MYRUA), Chengdu–Chongqing UA (CCUA), Harbin Changchun UA (HCUA), and Beibu Gulf UA (BGUA)) in China from 2000 to 2021 to explore the effectiveness of the clean air policies implemented by the government on air pollution control, to analyze the ambient air quality of UAs, and to make recommendations for public outdoor activities. The results indicated that the clean air policy implemented by the Chinese government in 2013 achieved significant treatment results. PM2.5 concentrations were plotted as an inverted U-shaped curve based on time, which showed an upward trend before 2013 and a downward trend after 2013. PM2.5 concentrations showed a similar seasonal pattern, with a single-valley “V” shape. PM2.5 concentration was the highest in winter and the lowest in summer. The PM2.5 concentration of HCUA and BGUA was lower than that of CCUA, MYRUA, and BTHUA. The increase in PM2.5 concentration mainly occurred in autumn and winter, while the decrease mainly occurred in spring. In 2021, the PM2.5 air quality compliance rates (3) in BTHUA, MYRUA, CCUA, HCUA, and BGUA were 44.57%, 80.00%, 82.04%, 99.74%, and 100%, respectively. However, in 2021, 19.19% of the five UAs still had an ambient air quality of Grade II (i.e., 50 PM2.5 < 100). People with abnormally sensitive breathing in these areas should reduce their outdoor activities. These results contribute to epidemiological studies on human health and disease prevention and suggest reasonable pathways by which governments can improve air quality through sustainable urban planning

Leaf Health Status Regulates Endophytic Microbial Community Structure, Network Complexity, and Assembly Processes in the Leaves of the Rare and Endangered Plant Species <i>Abies fanjingshanensis</i>

The rare and endangered plant species Abies fanjingshanensis, which has a limited habitat, a limited distribution area, and a small population, is under severe threat, particularly due to poor leaf health. The plant endophytic microbiome is an integral part of the host, and increasing evidence indicates that the interplay between plants and endophytic microbes is a key determinant for sustaining plant fitness. However, little attention has been given to the differences in the endophytic microbial community structure, network complexity, and assembly processes in leaves with different leaf health statuses. Here, we investigated the endophytic bacterial and fungal communities in healthy leaves (HLs) and non-healthy leaves (NLs) of A. fanjingshanensis using 16S rRNA gene and internal transcribed spacer sequencing and evaluated how leaf health status affects the co-occurrence patterns and assembly processes of leaf endophytic microbial communities based on the co-occurrence networks, the niche breadth index, a neutral community model, and C-score metrics. HLs had significantly greater endophytic bacterial and fungal abundance and diversity than NLs, and there were significant differences in the endophytic microbial communities between HLs and NLs. Leaf-health-sensitive endophytic microbes were taxonomically diverse and were mainly grouped into four ecological clusters according to leaf health status. Poor leaf health reduced the complexity of the endophytic bacterial and fungal community networks, as reflected by a decrease in network nodes and edges and an increase in degrees of betweenness and assortativity. The stochastic processes of endophytic bacterial and fungal community assembly were weakened, and the deterministic processes became more important with declining leaf health. These results have important implications for understanding the ecological patterns and interactions of endophytic microbial communities in response to changing leaf health status and provide opportunities for further studies on exploiting plant endophytic microbes to conserve this endangered Abies species

Development of a Practical and Efficient Synthesis of SIPI-4884, a HMG CoA Reductase Inhibitor for the Treatment of Hypercholesterolemia

An improved process of the novel HMG CoA reductase inhibitor SIPI-4884 has been developed for early preclinical pharmacology and safety studies, and it was made up with an efficient nine-step and scalable process. Significant improvements in the nucleophilic substitution, reduction, Wittig–Horner reaction, and preparation of calcium salt were demonstrated. The overall yield was improved to 17.2%

Temporal stability and assembly mechanisms of gut microbiota in sea cucumbers response to nanoplastics treatment

Aquaculture provides essential food for humans, and the health of farmed species is particularly important for the aquaculture industry. Aquaculture environment could be a sink of plastic debris (PDs) due to the enclosed character and heavy use of plastics. Gut microbiota of aquaculture species could respond to the exogenous pollutants and regulate the health of hosts. Here, variations in gut microbiota of Apostichopus japonicus induced by the ingested nanoplastics (NPs) were investigated by a lab experiment. We selected a NPs concentration gradient of 100 mg/kg and 500 mg/kg to simulate microplastic pollution to A. japonicus, and the significant differences in gut microbiota composition after 21 days of NP exposure were evaluated. According to the high-throughput sequencing from time series samples, a decrease of diversity in gut microbiota of A. japonicus with dietary NPs was observed. In addition, the gut microbiota compositions of sea cucumbers with and without NPs exposure were also distinct, expressing as enrichment of Bacteroidota while reducement of Proteobacteria under NPs stresses. Combined the results of network analysis, the less complexity and stability of gut microbiota in sea cucumbers with dietary NPs were proved. Based on the neutral community model, the ingested NPs elevated the contribution of stochastic processes for the gut microbiota assembly in sea cucumbers. Our study showed that substantial variations in gut microbiota of A. japonicus under NPs stresses, and also explored the underlying mechanisms regulating these changes. This research would offer new meaningful insights into the toxicity of NPs on sea cucumbers, contributing a solid fundament to improve the health of sea cucumbers under NPs stresses

Site-Selective Polyfluoroaryl Modification and Unsymmetric Stapling of Unprotected Peptides

Peptide stapling is recognized as an effective strategy for improving the proteolytic stability and cell permeability of peptides. In this study, we present a novel approach for the site-selective unsymmetric perfluoroaryl stapling of Ser and Cys residues in unprotected peptides. The stapling reaction proceeds smoothly under very mild conditions, exhibiting a remarkably rapid reaction rate. It can furnish stapled products in both liquid and solid phases, and the presence of nucleophilic groups other than Cys thiol within the peptide does not impede the reaction, resulting in uniformly high yields. Importantly, the chemoselective activation of Ser β-C(sp3)–H enables the unreacted −OH to serve as a reactive handle for subsequent divergent modification of the staple moiety with various therapeutic functionalities, including a clickable azido group, a polar moiety, a lipid tag, and a fluorescent dye. In our study, we have also developed a visible-light-induced chemoselective C(sp3)–H polyfluoroarylation of the Ser β-position. This reaction avoids interference with the competitive reaction of Ser −OH, enabling the precise late-stage polyfluoroarylative modification of Ser residues in various unprotected peptides containing other highly reactive amino acid residues. The biological assay suggested that our peptide stapling strategy would potentially enhance the proteolytic stability and cellular permeability of peptides

Higher Order π‑Conjugated Polycyclic Hydrocarbons with Open-Shell Singlet Ground State: Nonazethrene versus Nonacene

Higher order acenes (i.e., acenes longer than pentacene) and extended zethrenes (i.e., zethrenes longer than zethrene) are theoretically predicted to have an open-shell singlet ground state, and the radical character is supposed to increase with extension of molecular size. The increasing radical character makes the synthesis of long zethrenes and acenes very challenging, and so far, the longest reported zethrene and acene derivatives are octazethrene and nonacene, respectively. In addition, there is a lack of fundamental understanding of the differences between these two closely related open-shell singlet systems. In this work, we report the first synthesis of a challenging nonazethrene derivative, <b>HR-NZ</b>, and its full structural and physical characterizations including variable temperature NMR, ESR, SQUID, UV–vis–NIR absorption and electrochemical measurements. Compound <b>HR-NZ</b> has an open-shell singlet ground state with a moderate diradical character (<i>y</i>₀ = 0.48 based on UCAM-B3LYP calculation) and a small singlet–triplet gap (Δ<i>E</i>_S–T = −5.2 kcal/mol based on SQUID data), thus showing magnetic activity at room temperature. It also shows amphoteric redox behavior, with a small electrochemical energy gap (1.33 eV). Its electronic structure and physical properties are compared with those of Anthony’s nonacene derivative <b>JA-NA</b> and other zethrene derivatives. A more general comparison between higher order acenes and extended zethrenes was also conducted on the basis of <i>ab initio</i> electronic structure calculations, and it was found that zethrenes and acenes have very different spatial localization of the unpaired electrons. As a result, a faster decrease of singlet–triplet energy gap and a faster increase of radical character with increase of the number of benzenoid rings were observed in zethrene series. Our studies reveal that spatial localization of the frontier molecular orbitals play a very important role on the nature of radical character as well as the excitation energy