Aromaticity is a vital concept that governs the electronic properties of π-conjugated organic molecules and has long been restricted to 2D systems. The aromaticity in 3D π-conjugated molecules has ...been rarely studied. Here we report a fully conjugated diradicaloid molecular cage and its global aromaticity at different oxidation states. The neutral compound has an open-shell singlet ground state with a dominant 38π monocyclic conjugation pathway and follows the 4n + 2 Hückel aromaticity rule; the dication has a triplet ground state with a dominant 36π monocyclic conjugation pathway and satisfies 4n Baird aromaticity; the tetracation is an open-shell singlet with 52 π-electrons that are delocalized along the 3D rigid framework, showing 3D global antiaromaticity; and the hexacation possesses D
symmetry with 50 globally delocalized π-electrons, showing 6n + 2 3D global aromaticity. Different types of aromaticity were therefore accessed in one molecular cage platform, depending on the symmetry, number of π-electrons and spin state.
Non-small-cell lung cancer (NSCLC) causes high mortality. Radiotherapy is an induction regimen generally applied to patients with NSCLC. In view of therapeutic efficacy, the outcome is not appealing ...in addition to bringing about unwanted side effects. Total nutrition is a new trend in cancer therapy, which benefits cancer patients under radiotherapy. Male C57BL/6JNarl mice were experimentally divided into five groups: one control group, one T group (borne with Lewis lung carcinoma but no treatment), and three Lewis lung carcinoma-bearing groups administrated with a total nutrition formula (T + TNuF group), a local radiotherapy plus daily 3 Gy in three fractions (T + R group), or a combination TNuF and radiotherapy (T + R + TNuF group). These mice were assessed for their mean tumor volumes, cachectic symptoms and tumor metastasis. TNuF administration significantly suppressed tumor growth and activated apoptotic cell death in NSCLC-bearing mice under radiation. The body-weight gain was increased, while the radiation-induced cachexia was alleviated. Analysis of mechanisms suggests that TNuF downregulates EGFR and VEGF signaling pathways, inhibiting angiogenesis and metastasis. In light of radiation-induced tumor cell death, mitigation of radiation-induced cachexia and inhibition of tumor cell distant metastasis, the combination of TNuF and radiotherapy synergistically downregulates EGFR and VEGF signaling in NSCLC-bearing mice.
Before the Indian collision with Asia, northward subduction of the Neo-Tethyan oceanic lithosphere produced an Andean-type convergent margin in South Asia characterized by arc magmatism starting from ...the early Jurassic and lasting until the Eocene. The magmatic arc is now represented by widespread intrusive bodies or the so-called Transhimalayan batholiths in the Lhasa terrane of southern Tibet that have been divided into two main magmatic suites, i.e., the northern plutonic belt and the southern Gangdese Batholith. Their temporal distribution, concerning how exactly the magmatic suites correlate eastwards and then southeastwards around the eastern Himalayan syntaxis, however, remains poorly constrained. Here we report the first combined zircon U–Pb and Hf isotopic study of the Transhimalayan batholiths from the eastern part of the Lhasa terrane (∼
95–97.5°E and ∼
28.5–30°N), SE Tibet. Zircon U–Pb dating results of 24 granitoids indicate that the rocks were emplaced principally in the Early Cretaceous (∼
133–110 Ma) and subordinately in the Paleocene (∼
66–57 Ma), long after an older granite intrusion in the earliest Jurassic (∼
198 Ma). The zircon
ε
Hf(
T) values range from +
5 to −
20, yielding Hf crustal model ages (
T
DM
C) between 0.8 and 2.4 Ga that peak at ∼
1.7 Ga, suggesting a major episode of crustal growth in the Proterozoic and a predominantly, or even exclusively, crustal source for the granitoid petrogenesis. These zircon U–Pb and Hf isotopic constraints, together with whole-rock geochemical characteristics, allow us to correlate them to S-type granitoids in the northern plutonic belt, rather than to the I-type Gangdese Batholith from the central part of the southern Lhasa terrane. In contrast to the Gangdese magmatism that formed with a significant juvenile mantle input related to the Neo-Tethyan subduction, these S-type granitoids show geochemical similarities to the North American Cordilleran Interior batholiths that did not form directly from a subduction setting. Thus, we attribute the petrogenesis of the widespread Early Cretaceous granitoids in the northern belt and eastern Himalayan batholiths to a postcollisional regime due to the Late Jurassic–Early Cretaceous continental collision between the Lhasa and Qiangtang terranes. Under this framework, the S-type magmatism was generated in response to collision-induced crustal thickening, which may have capabilities of causing crustal anatexis by itself in the region. However, continued interplay with the Neo-Tethyan subduction zone processes such as back-arc extension could also have played a crucial, and long-lasting, role in the magma generation.
Peri‐acenes are good model compounds for zigzag graphene nanoribbons, but their synthesis is extremely challenging owing to their intrinsic open‐shell diradical character. Now, the successful ...synthesis and isolation of a stable peri‐tetracene derivative PT‐2ClPh is reported; four 2,6‐dichlorophenyl groups are attached onto the most reactive sites along the zigzag edges. The structure was confirmed by X‐ray crystallographic analysis and its electronic properties were systematically investigated by both experiments and theoretical calculations. It exhibits an open‐shell singlet ground state with a moderate diradical character (y0=51.5 % by calculation) and a small singlet–triplet gap (ΔES‐T=−2.5 kcal mol−1 by SQUID measurement). It displays global aromatic character, which is different from the smaller‐size bisanthene analogue BA‐CF3.
Synthesis of peri‐tetracene done: A stable peri‐tetracene derivative was obtained in crystalline form. It has an open‐shell singlet ground state with a moderate diradical character. It shows amphoteric redox behavior with a small optical and electrochemical energy gap. It is magnetically active and exhibits a small single–triplet excitation energy. It is globally aromatic.
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•Ecosystem services (ESs) in the upper Ganjiang watershed of China are quantified.•Five major ESs vary in supply–demand deficits at the sub-watershed scale.•Slope and forest area ...ratio have distinct threshold effects on supply–demand ratios of ESs.•Research on mechanisms driving ESs should consider both their supply and demand.
Understanding the spatial associations of ecosystem services (ESs) driven by socio-ecological factors is essential for regional ecosystem management and effective resource allocation. Yet previous studies of mechanisms driving ESs have focused mainly on the supply or demand for ESs, rarely consider their threshold effects and supply–demand ratios. Taking the upper reach of Ganjiang watershed (URGW) in southern China as an example, the supply, demand, and supply–demand ratio of ESs (ESDRs) were quantified for grain production (GP), water yield (WY), soil retention (SR), carbon sequestration (CS), and green space recreation (GR). Correlation analysis and random forest models were used to investigate the spatial associations of five ESDRs and the relative importance and marginal effects of 9 socio-ecological factors upon them. At the watershed scale, only SR incurred a supply–demand deficit (ESDR < 0), while the other four ESs (GP, WY, CS, and GR) met the internal demand (ESDR > 0). When considered across 188 sub-watersheds, all ESs had different supply–demand deficits. The trade-offs in ESDRs mainly derived from two ESs (GP, SR) and the other three ESs (WY, CS, GR). The supply–demand ratio of SR was mainly determined by topography (i.e., slope gradient), while land use (i.e., proportions of cropland and forest land areas) played a decisive role in the supply–demand ratios of GP and WY. The supply–demand ratios of GR and CS showed similar spatial distribution, driven mainly by the normalized difference vegetation index and human population density. Specific socio-ecological factors (e.g., slope gradient and proportion of forest land area) had significant threshold effects on the ESDRs. Accordingly, research on the mechanisms driving ESs should consider ESs’ supply and demand in tandem, and pay particular attention to the potential threshold effects of socio-ecological factors.
In this work, we present a catalog of 2651 carbon stars from the fourth Data Release (DR4) of the Large Sky Area Multi-Object Fiber Spectroscopy Telescope (LAMOST). Using an efficient ...machine-learning algorithm, we find these stars from more than 7 million spectra. As a by-product, 17 carbon-enhanced metal-poor turnoff star candidates are also reported in this paper, and they are preliminarily identified by their atmospheric parameters. Except for 176 stars that could not be given spectral types, we classify the other 2475 carbon stars into five subtypes: 864 C-H, 226 C-R, 400 C-J, 266 C-N, and 719 barium stars based on a series of spectral features. Furthermore, we divide the C-J stars into three subtypes, C-J(H), C-J(R), and C-J(N), and about 90% of them are cool N-type stars as expected from previous literature. Besides spectroscopic classification, we also match these carbon stars to multiple broadband photometries. Using ultraviolet photometry data, we find that 25 carbon stars have FUV detections and that they are likely to be in binary systems with compact white dwarf companions.
To make full use of urban household balcony space, an urban aquaponics system for balconies was constructed to investigate the purification effects of four different substrates (volcanic stone, ...ceramic pellets, ceramic rings, and nanorods) and six plants (mung bean sprouts, hollow cabbage, water celery, lettuce, leek, and water chestnut) on fish culture wastewater. Through the determination of contaminants such as nitrogen and phosphorus and through the use of 16SrDNA sequencing technology, the substrate material and plant combinations with the best purification effects were screened. The results show that volcanic stone and nanorods have strong purification capacities. Compared to the other substrate types, there were more unique bacterial species on the surface of volcanic stone, among which amoeba species were the most dominant (92.42%). Among the six tested plant species, mung bean sprouts had the highest contribution to nitrogen uptake (94.96%), and water chestnut had the highest contribution to phosphorus uptake at 12.07%. Finally, the combination of nanorods and water celery was the best at purifying the wastewater. This study provides a theoretical basis and new ideas for the construction of urban aquaponics systems on balconies, which will help to achieve green farming and the efficient utilization of water resources.
Pancreatic cancer (PC) is highly malignant and has a high mortality with a 5-year survival rate of less than 8%. As a member of the roundabout immunoglobulin superfamily of proteins, ROBO1 plays an ...important role in embryogenesis and organogenesis and also inhibits metastasis in PC. Our study was designed to explore whether ROBO1 has effects on the proliferation of PC and its specific mechanism. The expression of ROBO1 was higher in cancer tissues than in matched adjacent tissues by immunohistochemistry (IHC) and qRT-PCR. Low ROBO1 expression is associated with PC progression and poor prognosis. Overexpression of ROBO1 can inhibit the proliferation of PC cells in vitro, and the S phase fraction can also be induced. Further subcutaneous tumor formation in nude mice showed that ROBO1 overexpression can significantly inhibit tumor growth. YY1 was found to directly bind to the promoter region of ROBO1 to promote transcription by a luciferase reporter gene assay, a chromatin immunoprecipitation (ChIP) and an electrophoretic mobility shift assay (EMSA). Mechanistic studies showed that YY1 can inhibit the development of PC by directly regulating ROBO1 via the CCNA2/CDK2 axis. Taken together, our results suggest that ROBO1 may be involved in the development and progression of PC by regulating cell proliferation and shows that ROBO1 may be a novel and promising therapeutic target for PC.
Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN ...is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined.
In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome.
We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing.
The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN.
The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.
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•Idiopathic membranous nephropathy (IMN) is a leading cause of end-stage renal disease.•Moshen Fuyuan Formula (MSFY) is more effective for IMN patients with yellow tongue coating.•Oral bacteria Campylobacter is a potential biological marker of yellow tongue coating.•Oral fungi and bacteria may contribute to the anti-IMN effect of MSFY.
The growth and maturation of the ventricular chamber require spatiotemporally precise synergy between diverse cell types. Alternative splicing deeply affects the processes. However, the functional ...properties of alternative splicing in cardiac development are largely unknown. Our study reveals that an alternative splicing factor polypyrimidine tract-binding protein 1 (PTBP1) plays a key role in ventricular chamber morphogenesis. During heart development, PTBP1 colocalizes with endothelial cells but is almost undetectable in cardiomyocytes. The endothelial-specific knockout of Ptbp1, in either endocardial cells or pan-endothelial cells, leads to a typical phenotype of left ventricular noncompaction (LVNC). Mechanistically, the deletion of Ptbp1 reduces the migration of endothelial cells, disrupting cardiomyocyte proliferation and ultimately leading to the LVNC. Further study shows that Ptbp1 deficiency changes the alternative splicing of β-arrestin-1 (Arrb1), which affects endothelial cell migration. In conclusion, as an alternative splicing factor, PTBP1 is essential during ventricular chamber development, and its deficiency can lead to congenital heart disease.