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Biofuel is encouraged because of its low impact on climate change. A new framework was developed to accurately assess the climate change impacts (CCI) of biofuel by integrating the atmospheric carbon cycle model and vegetation carbon dynamic models. Forests with different growth rates (fast, medium, slow) and three collection intensities (71%, 52%, 32%) of logging residues were presumed to test the performance of this framework. The CCI of biofuel was analyzed under two functional units: 1 GJ of biofuels and 1 ha of forests to supply biofuels. According to this study, increasing the forest growth rate could decrease the CCI in both functional units. Increasing the collection intensity could decrease the CCI of 1 GJ of biofuel but increase the CCI of 1 ha of forest land (unless the impacts were negative in fast-growth forests with high and medium collection intensities). Producing bioethanol resulted in a lower CCI (−3.1–67.7 kg CO2 eq/GJ) compared to bio-diesel (29.3–94.7 kg CO2 eq/GJ). Hence, collecting all available logging residues (without inhibiting forest regrowth) to produce low CCI biofuels such as bioethanol was found to be the optimal option for achieving high mitigation effects. [ABSTRACT FROM AUTHOR]

Mastermind proteins are required for transcription of Notch target genes, yet the molecular basis for mastermind function remains incompletely understood. Previous work has shown that Notch can induce transcriptional responses by binding to promoters, but more often by binding to enhancers, with HES4 and DTX1 as representative mammalian examples of promoter and enhancer responsiveness, respectively. Here, we show that mastermind dependence of the Notch response at these loci is differentially encoded in Jurkat T-cell acute lymphoblastic leukemia (T-ALL) cells. Knockout of Mastermind-like1 (MAML1) eliminates Notch responsive activation of both these genes, and reduced target gene expression is accompanied by a decrease in H3K27 acetylation, consistent with the importance of MAML1 for p300 activity. Add-back of MAML1 variants in knockout cells identifies residues 151-350 of MAML1 as essential for expression of either Notch-responsive gene. Fusion of the Notch-binding region of MAML1 to the histone acetyltransferase (HAT) domain of p300 rescues expression of HES4 but not DTX1, suggesting that an additional activity of MAML1 is needed for gene induction at a distance. Together, these studies establish the functional importance of the MAML1 151-350 region for Notch-dependent transcriptional induction, and reveal differential requirements for MAML1- dependent recruitment activities at different Notch responsive loci, highlighting the molecular complexity of Notch-stimulated transcription. [ABSTRACT FROM AUTHOR]

A recent study in Nature (Szczerba et al. 2019;566:553–557) reports that the association of neutrophils with circulating tumor cells (CTCs) in the blood of patients with breast cancer can promote CTC proliferation and metastasis. These findings reveal a new mechanism by which the innate immune system may be co-opted to drive tumor progression. [ABSTRACT FROM AUTHOR]

• One-pot synthesis of surface polyvinyl pyrrolidone modified polypyrrole. • The relationship between polypyrrole structure and physicochemical property. • Polypyrrole exhibits combined tumor photothermal-chemotherapy ability. With an excellent near-infrared (NIR) light-responsive property, polypyrrole (PPy) nanoparticle has emerged as a promising NIR photothermal transducing agent for tumor photothermal therapy (PTT). Herein, we reported the PVP mediated one-pot synthesis of colloidal stable and biocompatible PPy nanoparticles (PPy-PVP NPs) for combined tumor photothermal-chemotherapy. The influence of molecular weight and PVP concentration on the spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency of the resultant PPy-PVP NPs was systematically studied. By choosing PVP with a molecular weight of 360 kDa (concentration of 5 mg/mL) as the template and surface modifier during the synthesis, PPy-PVP NPs with optimal spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency were synthesized. Findings in this study are anticipated to provide an in-depth understanding of the important character of surface engineering in the rational design and biomedical applications of PPy NPs. [ABSTRACT FROM AUTHOR]

This study focuses the energy distribution of a hydroelectric generating system. Understanding the way energy distribution is important for researchers because it determines many of the macroscopic attributes, such as conversion efficiency, dynamic characteristics, et al. Historically, energy modeling has been split into two directions, focusing on stability analysis and its control, and has not yet been studied from the viewpoint for the stochastic turbine flow. Here we established a novel stochastic model to analyze the energy distribution of the hydroelectric generating system. We verified this model with the monitored data from Nazixia hydropower station of China. We also show how the stochastic turbine flow affects the energy losses of the system. The result shows that the one with the highest influence is the hydraulic impact losses in spiral case (more than 60%), and the hydraulic friction loss first keeps 19% as the stochastic intensity changes from 0.01 to 0.5, then increases to 20% when the stochastic intensity reaches 0.6. [ABSTRACT FROM AUTHOR]

The Notch signaling pathway has a critical role in cell fate determination and tissue homeostasis in a variety of different lineages. In the context of normal Notch signaling, the Notch receptor of the ‘signal-receiving’ cell is activated in trans by a Notch ligand from a neighboring ‘signal-sending’ cell. Genetic studies in several model organisms have established that ubiquitination of the Notch ligand, and its regulated endocytosis, is essential for transmission of this activation signal. In mammals, this ubiquitination step is dependent on the protein Mind bomb 1 (Mib1), a large multi-domain RING-type E3 ligase, and its direct interaction with the intracellular tails of Notch ligand molecules. Here, we discuss our current understanding of Mind bomb structure and mechanism in the context of Notch signaling and beyond. [ABSTRACT FROM AUTHOR]

We present a versatile method to characterize ATPase and kinase activities and discover new inhibitors of these proteins. The proton NMR-based assay directly monitors ATP turnover and is easy to implement, requires no additional reagents and can potentially be applied to GTP. We validated the method's accuracy, applied it to the monitoring of ATP turnover by actin and to the screening of ATPase inhibitors, and showed that it is also applicable for the monitoring of GTP hydrolysis. [ABSTRACT FROM AUTHOR]

Accurate estimation for vegetation net primary production (NPP) at high resolution is essential for ecosystem management and at local to global scales. However, no reliable methods are available to achieve fine-resolution estimation. In this study, a new NPP estimation system was developed by integrating high spatial resolution remote sensing images, tree ring measurements, and process-based model CASA. The system was illustrated by estimating the historical NPP of caragana shrublands from 2011 to 2021 in Dingbian County, China. The results showed that: (1) by employing the biomass model and tree ring measurements, an NPP-crown width model was established to enable a large number of samples for calibrating the CASA model on high spatial resolution images without continuous field measurements. The calibrated parameters, including maximum NDVI, minimum NDVI, and maximum light use efficiency, were determined to be 0.415, 0.022 and 0.025, respectively; (2) according to the estimation by the calibrated CASA model, the NPP in Dingbian County revealed an increasing trend from 2011 to 2021, and the NPP in southern hilly and gully regions was significantly higher than the other regions; (3) among the different indices, max temperature of warmest month had a significant negative effect on the NPP of cagarana shrublands, whereas annual precipitation had a positive effect. In the northern and central regions, air temperature predominantly influenced NPP, while in the southern regions, both temperature and precipitation played a joint role. The implementation in this study illustrated that the NPP estimation system could provide reliable NPP with high resolution and efficient to monitor and detect dominant factors affecting NPP for ecosystem management. [ABSTRACT FROM AUTHOR]

Overexpression of the cellular FLICE-like inhibitory protein (cFLIP) has been reported in a number of tumor types. As an inactive procaspase-8 homologue, cFLIP is recruited to the intracellular assembly known as the Death Inducing Signaling Complex (DISC) where it inhibits apoptosis, leading to cancer cell proliferation. Here we characterize the molecular details of the interaction between cFLIPL and calmodulin, a ubiquitous calcium sensing protein. By expressing the individual domains of cFLIPL, we demonstrate that the interaction with calmodulin is mediated by the N-terminal death effector domain (DED1) of cFLIPL. Additionally, we mapped the interaction to a specific region of the C-terminus of DED1, referred to as DED1 R4. By designing DED1/DED2 chimeric constructs in which the homologous R4 regions of the two domains were swapped, calmodulin binding properties were transferred to DED2 and removed from DED1. Furthermore, we show that the isolated DED1 R4 peptide binds to calmodulin and solve the structure of the peptide-protein complex using NMR and computational refinement. Finally, we demonstrate an interaction between cFLIPL and calmodulin in cancer cell lysates. In summary, our data implicate calmodulin as a potential player in DISC-mediated apoptosis and provide evidence for a specific interaction with the DED1 of cFLIPL. [ABSTRACT FROM AUTHOR]

As a pervasive neurodevelopmental disease, autism spectrum disorder (ASD) is caused by both hereditary and environmental elements. Research has demonstrated the functions of the Notch pathway and DNA methylation in the etiology of ASD. DNA methyltransferases DNMT3 and DNMT1 are responsible for methylation establishment and maintenance, respectively. In this study, we aimed to explore the association of DNA methyltransferases with the Notch pathway in ASD. Our results showed Notch1 and Hes1 were upregulated, while DNMT3A and DNMT3B were downregulated at the protein level in the prefrontal cortex (PFC), hippocampus (HC) and cerebellum (CB) of VPA-induced ASD rats compared with Control (Con) group. However, the protein levels of DNMT3A and DNMT3B were augmented after treatment with 3,5-difluorophenacetyl-L-alanyl-S-phenylglycine-2-butyl ester (DAPT), suggesting that abnormal Notch pathway activation may affect the expression of DNMT3A and DNMT3B. Besides, our previous findings revealed that the Notch pathway may participate in development of ASD by influencing autophagy. Therefore, we hypothesized the Notch pathway adjusts autophagy and contributes to ASD by affecting DNA methyltransferases. Our current results showed that after receiving the DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine (5-Aza-2'dc), the VPA + DAPT+5-Aza-2'dc (V + D + Aza) group exhibited reduced social interaction ability and increased stereotyped behaviors, and decreased expression of DNMT3A, DNMT3B and autophagy-related proteins, but did not show changes in Notch1 and Hes1 protein levels. Our results indicated that the Notch1/Hes1 pathway may adjust DNMT3A and DNMT3B expression and subsequently affect autophagy in the occurrence of ASD, providing new insight into the pathogenesis of ASD. • The Notch1/Hes1 pathway adjusts autophagy by affecting DNMT3A and DNMT3B expression. • The Notch1/Hes1 pathway adjusts DNA methyltransferase expression during the development of ASD. • DNA methyltransferases may affect autophagy during the development of ASD. [ABSTRACT FROM AUTHOR]

• The synthesis of PPy nanoparticles (PPy-PVP NPs) using a vapor deposition method. • This method allows the formation of uniform PPy-PVP NPs at room temperature. • PVP 40kDa can ensure a better performance of the synthesized PPy-PVP NPs. In recent years, nanomaterials have aroused people's interest in the field of biomedicine. Polypyrrole (PPy) has become a research hotspot because of its simple synthesis, excellent photothermal conversion performance, and high biocompatibility. Here, we report the synthesis of PPy nanoparticles (PPy-PVP NPs) using a vapor deposition method, for tumor photothermal therapy. In this method, the slowly produced volatile pyrrole vapor was absorbed by the PVP (polyvinylpyrrolidone)/FeCl 3 aqueous solution. This slow vapor production and absorption allows the formation of uniform PPy-PVP NPs at room temperature. Then, the effects of the molecular weight of PVP on the photothermal property and anti-tumor efficiency of PPy-PVP NPs were compared. It was found that the selection of PVP 40kDa as the template and surface linker can ensure a better application performance of the synthesized nanomaterials. This work provides a theoretical basis for the rational design of nano-therapy carriers and biomedical applications. [ABSTRACT FROM AUTHOR]

More efficient biomarkers are needed to facilitate the early detection of hepatocellular carcinoma (HCC). We aimed to identify candidate biomarkers for HCC detection by proteomic analysis. First, we performed a global proteomic analysis of 10 paired HCC and non-tumor tissues. Then, we validated the top-ranked proteins by targeted proteomic analyses in another tissue cohort. At last, we used enzyme-linked immunosorbent assays to validate the candidate biomarkers in multiple serum cohorts including HCC cases (HCCs), cirrhosis cases (LCs), and normal controls (NCs). We identified and validated 33 up-regulated proteins in HCC tissues. Among them, eight secretory or membrane proteins were further evaluated in serum, revealing that aldo–keto reductase family 1 member B10 (AKR1B10) and cathepsin A (CTSA) can distinguish HCCs from LCs and NCs. The area under the curves (AUCs) were 0.891 and 0.894 for AKR1B10 and CTSA, respectively, greater than that of alpha-fetoprotein (AFP; 0.831). Notably, combining the three proteins reached an AUC of 0.969, which outperformed AFP alone (P < 0.05). Furthermore, the serum AKR1B10 levels dramatically decreased after surgery. AKR1B10 and CTSA are potential serum biomarkers for HCC detection. The combination of AKR1B10, CTSA, and AFP may improve the HCC diagnostic efficacy. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is a neuroendocrine tumor treated clinically as a single disease with poor outcomes. Distinct SCLC molecular subtypes have been defined based on expression of ASCL1 , NEUROD1 , POU2F3 , or YAP1. Here, we use mouse and human models with a time-series single-cell transcriptome analysis to reveal that MYC drives dynamic evolution of SCLC subtypes. In neuroendocrine cells, MYC activates Notch to dedifferentiate tumor cells, promoting a temporal shift in SCLC from ASCL1+ to NEUROD1+ to YAP1+ states. MYC alternatively promotes POU2F3+ tumors from a distinct cell type. Human SCLC exhibits intratumoral subtype heterogeneity, suggesting that this dynamic evolution occurs in patient tumors. These findings suggest that genetics, cell of origin, and tumor cell plasticity determine SCLC subtype. • Multiple SCLC molecular subtypes arise from a neuroendocrine cell of origin • MYC drives the NEUROD1+ and YAP1+ subtypes of SCLC in a temporal evolution • MYC directly activates NOTCH signaling to reprogram neuroendocrine fate • Multiple SCLC molecular subtypes are present within individual human tumors Ireland et al. show that MYC activates Notch signaling to dedifferentiate neuroendocrine small cell lung cancer (SCLC) in a conserved trajectory from ASCL1+ to NEUROD1+ to YAP1+ non-neuroendocrine subtypes, suggesting that these are not distinct subtypes but different stages of progressive evolution of SCLC. [ABSTRACT FROM AUTHOR]

The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To test whether rare or subpolymorphic SLC10A1 variants are associated with disease risk, the gene's exons in 244 cases were sequenced. Overall, we found neither SNPs nor haplotypes of SLC10A1 showed significant association in the two sample sets. Furthermore, no significant associations of rare variants or copy number variation covering SLC10A1 were observed. Finally, expression quantitative trait locus analyses revealed that SNPs potentially affecting SLC10A1 expression also showed no significant associations. We conclude that genetic variation at the SLC10A1 locus is not likely a major risk factor of persistent HBV infection among Southern Chinese. [ABSTRACT FROM AUTHOR]

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, but not alone. The molecule was identified through an in silico chemical screen for compounds with affinity for the caspase 8 homodimer's interface. The compound was experimentally validated to directly bind caspase 8, and to promote caspase 8 activation and cell death in single living cells or population of cells, upon TRAIL stimulation. Our approach is a proof-of-concept strategy leading to the discovery of a novel small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells, but may also provide insights into the structure-function relationship of caspase 8 homodimers as putative targets in cancer. [ABSTRACT FROM AUTHOR]