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The late Pliocene is considered the key period of transition to the Quaternary glaciations. In this paper, we present pollen records from the PL02 borehole of the Yinchuan Basin, which is located in Northwest China and has a favourable sedimentary environment for the 3.04–2.88 Ma period, to explore changes in palaeovegetation and palaeoclimate. The results showed that the vegetation in the basin was dominated by typical steppe from 3.04 to 3.01 Ma, indicating that the climate was warm and humid; from 3.01 to 2.93 Ma, the vegetation was dominated by desert steppe, and the climate gradually became drier; after 2.97 Ma, the degree of drought intensified; and from 2.93 to 2.88 Ma, the vegetation was dominated by typical steppe, and the climate became relatively humid. At approximately 2.93 Ma, the percentage and concentration of pollen from broadleaved trees and the Artemisia to Chenopodiaceae (A/C) ratio increased rapidly, indicating that the climate had suddenly become humid, which may have been related to the strengthening of the East Asian summer monsoon (EASM) caused by the final closure of the Panama Seaway. At approximately 2.90 Ma, broadleaved pollen decreased rapidly, suggesting that the climate rapidly became cold, which may indicate the onset and expansion of the Northern Hemisphere ice sheets. We suggest that climate change in the Yinchuan Basin is closely related to global environmental changes and has global characteristics.

Ionizing radiation (IR)-induced excessive reactive oxygen species (ROS) is an important contributor of the injury of hematopoietic system. Grape seed proanthocyanidin extract (GSPE) is a new type of antioxidant, whereas whether it could ameliorate IR-induced hematopoietic injury remains unclear. Here, we show that GSPE treatment improves the survival of irradiated mice and alleviates IR-induced myelosuppression. Meanwhile, the hematopoietic reconstituting ability of hematopoietic stem cells (HSCs) in mice following irradiation exposure is significantly increased after GSPE treatment. Furthermore, GSPE treatment can reduce IR-induced ROS production and relieve DNA damage and apoptosis in hematopoietic stem progenitor cells (HSPCs). Interestingly, we find that a critical antioxidant-associated gene fokhead box transcription factor O1 (Foxo1) is significantly decreased in HSPCs after irradiation. Consistently, hematopoietic specific deletion of Foxo1 increases the radiosensitivity of mice. Further investigations reveal that GSPE treatment specifically upregulates the expression of Foxo1, as well as its target genes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and catalase (CAT). Importantly, Foxo1 deficiency largely abolishes the radioprotection of GSPE on HSPCs. Collectively, our data demonstrate that GSPE plays an important role in ameliorating IR-induced HSPC injury via the Foxo1-mediated pathway. Therefore, GSPE may be used as a promising radioprotective agent.

Graphic Abstract The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide for almost 2 years. It starts from viral adherence to host cells through an interaction between spike glycoprotein 1 (S1) containing a receptor-binding domain (RBD) and human angiotensin-converting enzyme-2 (ACE2). One of the useful strategies to prevent SARS-CoV-2 infection is to inhibit the attachment of RBD to ACE2. Therefore, the current work proposed potent peptides against SARS-CoV-2 infection by carrying out MM-PBSA calculation based on the binding of 52 antiviral peptides (AVPs) to RBD. Considering the binding free energies of AVPs to RBD, cyanovirin-N (CV-N) showed the strongest RBD binding affinity among 52 AVPs. Upon structural analysis of RBD complex with CV-N, it was observed that 12 of the 13 key residues of RBD binding to ACE2 were hijacked by CV-N. CV-N bound to RBD at a smaller affinity of 14.9 nM than that of ACE2 and inhibited the recruitment of S1 to human alveolar epithelial cells. Further analysis revealed that CV-N suppressed SARS-CoV-2 S pseudovirion infection with a half-maximal inhibitory concentration (IC50) of 18.52 μg/mL. This study demonstrated a drug screening for AVPs against SARS-CoV-2 and discovered a peptide with inspiring antiviral properties, which provided a promising strategy for the COVID-19 therapeutic approach. Supplementary Information The online version contains supplementary material available at 10.1007/s12539-021-00477-w.

Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-β-cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19.

Hematopoietic stem cell (HSC) fate is tightly controlled by various regulators, whereas the underlying mechanism has not been fully uncovered due to the high heterogeneity of these populations. In this study, we identify tetraspanin CD63 as a novel functional marker of HSCs in mice. We show that CD63 is unevenly expressed on the cell surface in HSC populations. Importantly, HSCs with high CD63 expression (CD63(hi)) are more quiescent and have more robust self-renewal and myeloid differentiation abilities than those with negative/low CD63 expression (CD63(-/lo)). On the other hand, using CD63 knockout mice, we find that loss of CD63 leads to reduced HSC numbers in the bone marrow. In addition, CD63-deficient HSCs exhibit impaired quiescence and long-term repopulating capacity, accompanied by increased sensitivity to irradiation and 5-fluorouracil treatment. Further investigations demonstrate that CD63 is required to sustain TGFβ signaling activity through its interaction with TGFβ receptors I and II, thereby playing an important role in regulating the quiescence of HSCs. Collectively, our data not only reveal a previously unrecognized role of CD63 but also provide us with new insights into HSC heterogeneity.

Understanding the sources areas and transport mechanisms of pollen grains is important for reconstructing vegetation and climate from fossil pollen data. We studied the modern pollen assemblages of 28 surface samples from different geomorphic units (mountains, the central basin, and the riverine zone) in the Yinchuan Basin in China. Our aim was to compare the characteristics of the pollen assemblages from the different sedimentary environments and to determine the differences in pollen source areas and transport mechanisms. The results show that: (1) The pollen assemblages from the mountain and piedmont alluvial fan environments were dominated by trees, with the tree pollen content decreasing with decreasing altitude. The pollen in the piedmont alluvial fan environment was mainly transported by surface runoff, and assemblage combines the characteristics of both the mountain and the local vegetation. (2) The pollen assemblages from the central basin were dominated by pollen produced by the zonal desert-steppe vegetation. (3) The pollen assemblages from the riverine zone were dominated by a long-distance component from within the upper part of the drainage area. The results suggest that in sedimentary pollen records from the Yinchuan Basin, the arboreal pollen component primarily reflects vegetation changes within the surrounding mountains; the herbaceous pollen component is an indicator of changes in desert-steppe vegetation; and the long-distance fluvially-transported pollen component reflects vegetation changes in the upstream drainage area.

Novel (Tb1-xLux)2O3 magneto-optical transparent ceramics were prepared through a solid-solution method via vacuum pre-sintering followed by hot isostatic pressing (HIP). The Lu-containing samples were solid-solution phases between Tb2O3 and Lu2O3, which effectively stabilized the phase transition of Tb2O3 during the sintering process. A typical component of (Tb1-xLux)2O3 ceramic with x = 0.5 was selected to study the densification behavior and microstructure evolution in detail. The polished (Tb0.5Lu0.5)2O3 ceramics with a thickness of 3 mm vacuum pre-sintered at 1700 °C under 1.0 × 10−3 Pa combined with HIP post-treatment at 1600 °C showed good magneto-optical property. The Verdet constant measured at 633 nm was -224.33 rad·T−1 m−1, 30% higher than that of Tb3Al5O12 (TAG). However, the in-line transmittance was 73.6% at 633 nm, lower than that of TAG. The (Tb1-xLux)2O3 ceramics will be a promising material for Faraday devices after further improving the optical quality.

The ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg−1of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-acheive memrbane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19.Graphical Table of Contents

Folic acid (FA) is a vitamin essential for human physiology; thus, rapid, accurate, and sensitive methods for its detection and quantification in different biological samples are necessary. A fluorescent ratiometric nanoprobe (the complex composed of quantum dots and carbon dots) based on carboxyl-modified quantum dots (QDs) and amino-modified graphene-based carbon dots (CDs) has been developed for the visual determination of folic acid (FA). The nanoprobe is the composition in which QDs were covalently bonded with CDs. Red and blue fluorescence of nanoprobe can be selectively quenched and enhanced by FA, respectively. Thus, the nanoprobe is capable to generate clearly visible fluorescence color change from pink to blue upon exposure to UV light. Depending on the color change and its intensity, FA can be identified, and their concentrations can be determined. The sensor prepared based on the nanoprobe demonstrated good selectivity and sensitivity toward FA with exceptionally low detection limit equal to 0.039 μM. We also prepared a paper-based sensor to demonstrate convenient and simple approach to visually detect FA. Thus, the nanoprobe demonstrated feasibility of rapid real-time quantitative FA detection; considering its simple, effective, and practicality, expectedly it can be used for practical application.

Myelosuppression is a common and intractable side effect of cancer therapies including radiotherapy and chemotherapy, while the underlying mechanism remains incompletely understood. Here, using a mouse model of radiotherapy-induced myelosuppression, we show that inorganic phosphate (Pi) metabolism is acutely inhibited in hematopoietic stem cells (HSCs) during irradiation-induced myelosuppression, and closely correlated with the severity and prognosis of myelosuppression. Mechanistically, the acute Pi metabolic inhibition in HSCs results from extrinsic Pi loss in the bone marrow niche and the intrinsic transcriptional suppression of soluble carrier family 20 member 1 (SLC20A1)-mediated Pi uptake by p53. Meanwhile, Pi metabolic inhibition blunts irradiation-induced Akt hyperactivation in HSCs, thereby weakening its ability to counteract p53-mediated Pi metabolic inhibition and the apoptosis of HSCs and consequently contributing to myelosuppression progression. Conversely, the modulation of the Pi metabolism in HSCs via a high Pi diet or renal Klotho deficiency protects against irradiation-induced myelosuppression. These findings reveal that Pi metabolism and HSC survival are causally linked by the Akt/p53–SLC20A1 axis during myelosuppression and provide valuable insights into the pathogenesis and management of myelosuppression.

The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.