The Three Gorges Reservoir area (TGR), China
Soil erosion on purple soil hillslope and its negative effects are deleterious to the ecological environment of the TGR. Sheet erosion is the initial form ...of the slope erosion, which is notably impacted by land degradation, polyacrylamide (PAM) is commonly applied for soil and water conservation purpose, while the sheet erosion on purple soil hillslope treated with PAM remains unclear.
The findings suggested that the sheet erosion and runoff rate increased as the rainfall intensity was increased and the slope gradient was decreased with increasing PAM application rate until reaching minimum values at 0.80 g m−2, and these quantities increased afterward. The single and combined impacts of the PAM application rate, rainfall intensity and slope gradient on erosion and runoff were significant. The slope gradient, rainfall intensity and PAM application rate also influenced the hydrodynamic parameters, and the stream power was the optimal parameter for describing the sheet erosion. An equation encompassing the rainfall intensity, slope gradient and PAM application rate was used for sheet erosion rate prediction with high accuracy relative to the stream power and PAM application rate. These results could be helpful to better understand sheet erosion on purple soil slopes treated with PAM and offer fundamental guidelines for soil and water conservation in the TGR.
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•The stream power was the most appropriate hydrodynamic parameter for estimating sheet erosion rate.•0.8 g m−2 of polyacrylamide performed best for reducing total runoff and sheet erosion.•The function combining the application of PAM and stream power was established to predict the sheet erosion rate.
•ID1 deficiency in the AML BMM disrupts the progression of AML, which is restored by Angptl7.•ID1 interacts with RNF4, attenuates SP1 ubiquitination, and contributes to the expression of ANGPTL7 in ...AML BM mesenchymal stem cells.
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The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.
Inhibitor of DNA binding 1 (ID1) is a transcriptional regulator found in normal and acute myeloid leukemia (AML) stem cells that controls cytokine production in the bone marrow microenvironment (BMM). In a mechanistic study using primary patient samples and murine models, Fei et al identified a regulatory loop in which specific leukemogenic fusion proteins increase BMP6 expression that is then secreted into the BMM, where it upregulates ID1 in mesenchymal stromal cells and increases angiopoietin-like 7 (ANGPTL7) production, which in turn promotes leukemia growth in vitro and in vivo. These findings point to ID1 and the ANGPTL7 axis as therapeutic targets in AML.
Schmallenberg virus (SBV) is an emerging and rampant arbovirus in Europe, and even Africa and West Asia. Investigating whether SBV existed in new regions or countries, it was very helpful for the ...early warning and control of SBV. In this study, we collected 317 serum samples (
n
= 242 for dairy cattle,
n
= 13 for yellow cattle,
n
= 21 for buffalo, and
n
= 41 for goats) from Guangdong province of southern China, which is located in a subtropical region and is an important distribution area for arboviral diseases. A commercial competitive enzyme-linked immunosorbent assay (cELISA) kit and a previously established real-time PCR were used to detect SBV antibody and RNA in those serum samples. Via testing, serological evidence of SBV was confirmed, with total positive rates (57.4, 15.4, 19, and 9.8%) in dairy cattle, yellow cattle, buffalo, and goats, respectively, while no positive signal for SBV RNA was found. To summarize, this study for the first time provided preliminary serological evidence of SBV infection in China, East Asia. Further investigations on molecular evidence, origin, and pathogenesis of SBV in ruminants needed to be studied in China.
Porcine circovirus type 2 (PCV2) is considered the major etiological pathogen of porcine circovirus-associated diseases (PCVADs) in pigs. Recently, PCV2 was also found in non-porcine animals such as ...cattle, rats, and mice. However, there was no record of PCV2 in rats in China. The goal of this study was to investigate whether PCV2 was present in rats (
Rattus norvegicus
, RN) on three swine farms, using molecular tools. PCR results showed that 30 of 95 (31.6 %) rat samples were positive for PCV2. Moreover, further genotype analysis suggested that 10 of 30 (33.3 %) were positive for PCV2a, 19 of 30 (63.3 %) were positive for PCV2b, and only one sample (1/30, 3.33 %) was co-infected by PCV2a and PCV2b. To determine the possible origin of PCV2, 60 serum samples were also collected from weaned pigs on those swine farms, and 23 out of 60 samples were positive for PCV2. In addition, two distinct RN-origin and two distinct porcine-origin PCV2 full-length nucleotide sequences were obtained from the farms. Sequence and phylogenetic analysis indicated that they had the highest nucleotide similarity and closest genetic relationships to each other. In this study, we report the infection and genome characterization of PCV2 in rats and compare RN-origin and porcine-origin PCV2 sequences obtained from the same pig farm, revealing possible cross-species transmission of PCV2.
The palladium‐catalyzed asymmetric ring‐opening (ARO) reaction of azabenzonorbornadienes with iodobenzoate derivatives was realized by using chiral spirophosphine ligands with zinc powder as a ...reducing reagent. Various enantiomerically enriched cis‐dihydrobenzocphenanthridinones, the core structure of numerous chiral natural products, were prepared by the ARO reaction and tandem amidation from easily obtained starting materials with favorable enantioselectivity (up to 86% ee) under mild reaction conditions. The present palladium‐catalyzed ARO reaction avoids the direct use of organometallic reagents, enables tandem cyclization, and thus improves synthetic efficiency. The formal total synthesis of a chiral natural product, (+)‐chelidonine, was accomplished with the ARO reaction as a key step, which demonstrates the potential synthetic applications of the present methodology.
Conventional antibody-based targeted cancer therapy is one of the most promising avenues of successful cancer treatment, with the potential to reduce toxic side effects to healthy cells surrounding ...tumor cells. However, the full potential of antibodies is severely limited due to their large size, low stability, slow clearance, and high immunogenicity. Alternatively, recently discovered nanobodies, which are the smallest naturally occurring antigen-binding format, have shown great potential for addressing these limitations. Bioconjugation of nanobodies to functional groups such as toxins, enzymes, radionucleotides, and fluorophores can improve the efficacy and potency of nanobodies, enhance their in vivo pharmacokinetics, and expand the range of potential applications. Herein, we review the superior characteristics of nanobodies in comparison to conventional antibodies and provide insight into recent developments in nanobody conjugates for targeted cancer therapy and imaging.
Abstract Paclitaxel (taxol) is a widely used chemo-drug for many solid tumors, while continual taxol treatment is revealed to stimulate tumor dissemination. We previously found that a small molecule ...inhibitor of miR-21, termed AC1MMYR2, had the potential to impair tumorigenesis and metastasis. The aim of this study was to investigate whether combining AC1MMYR2 with taxol could be explored as a means to limit tumor metastasis. Here we showed that abnormal activation of miR-21/CDK5 axis was associated with breast cancer lymph node metastasis, which was also contribute to high dose taxol-induced invasion and epithelial mesenchymal transition (EMT) in both breast cancer cell line MDA-MB-231 and glioblastoma cell line U87VIII. AC1MMYR2 attenuated CDK5 activity by functional targeting CDK5RAP1, CDK5 activator p39 and target p-FAKser732 . A series of in vitro assays indicated that treatment of AC1MMYR2 combined with taxol suppressed tumor migration and invasion ability in both MDA-MB-231 and U87VIII cell. More importantly, combination therapy impaired high-dose taxol induced invadopodia, and EMT markers including β-catenin, E-cadherin and vimentin. Strikingly, a significant reduction of lung metastasis in mice was observed in the AC1MMYR2 plus taxol treatment. Taken together, our work demonstrated that AC1MMYR2 appeared to be a promising strategy in combating taxol induced cancer metastasis by targeting miR-21/CDK5 axis, which highlighted the potential for development of therapeutic modalities for better clinic taxol application.