Paddy fields are one of the largest anthropogenic sources of global CH
4 emission. A decrease in paddy CH
4 emission can contribute significantly towards the control of global warming. Recent studies ...have demonstrated that the application of biochar in paddy soils has such a capability, but its underlying mechanism has yet to be elucidated. In this investigation, we studied CH
4 emission, methanogenic archaeal, as well as methanotrophic proteobacterial communities, from microcosms derived from two paddy soils, Inceptisol and Ultisol. Both soils were amended with biochar at different pyrolysis temperatures (300 °C, 400 °C and 500 °C) at field condition. The soil CH
4 flux was monitored across whole rice season in 2010; the functional guilds communities were analyzed by PCR–DGGE and real-time quantitative PCR (qPCR). It is found that paddy CH
4 emissions significantly decreased under biochar amendments, which, interestingly, didn't result from the inhibition of methanogenic archaeal growth. qPCR further revealed that biochar amendments (1) increased methanotrophic proteobacterial abundances significantly, and (2) decreased the ratios of methanogenic to methanotrophic abundances greatly. These results shed insight on the underlying mechanism of how biochar decreases paddy CH
4 emission. This knowledge can be applied to develop a more effective greenhouse gas mitigation process for paddy fields.
► Biochar amendment significantly decreased paddy CH
4 emission. ► Biochar didn't inhibit, and, on the contrary, even stimulated paddy methanogens. ► The greater stimulated biochar effect on methanotrophic proteobacteria was observed. ► Biochar amendment can both sustain soil productivity and reduce global warming.
Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled ...prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.
Breast cancer is the most frequent malignancy in women worldwide, and triple-negative breast cancer (TNBC) patients have the worst prognosis and highest risk of recurrence. The therapeutic strategies ...for TNBC are limited. It is urgent to develop new methods to enhance the efficacy of TNBC treatment. Previous studies demonstrated that D-mannose, a hexose, can enhance chemotherapy in cancer and suppress the immunopathology of autoimmune diseases. Here, we show that D-mannose can significantly facilitate TNBC treatment via degradation of PD-L1. Specifically, D-mannose can activate AMP-activated protein kinase (AMPK) to phosphorylate PD-L1 at S195, which leads to abnormal glycosylation and proteasomal degradation of PD-L1. D-mannose-mediated PD-L1 degradation promotes T cell activation and T cell killing of tumor cells. The combination of D-mannose and PD-1 blockade therapy dramatically inhibits TNBC growth and extends the lifespan of tumor-bearing mice. Moreover, D-mannose-induced PD-L1 degradation also results in messenger RNA destabilization of DNA damage repair-related genes, thereby sensitizing breast cancer cells to ionizing radiation (IR) treatment and facilitating radiotherapy of TNBC in mice. Of note, the effective level of D-mannose can be easily achieved by oral administration in mice. Our study unveils a mechanism by which D-mannose targets PD-L1 for degradation and provides methods to facilitate immunotherapy and radiotherapy in TNBC. This function of D-mannose may be useful for clinical treatment of TNBC.
C-type inactivation underlies important roles played by voltage-gated K
(Kv) channels. Functional studies have provided strong evidence that a common underlying cause of this type of inactivation is ...an alteration near the extracellular end of the channel's ion-selectivity filter. Unlike N-type inactivation, which is known to reflect occlusion of the channel's intracellular end, the structural mechanism of C-type inactivation remains controversial and may have many detailed variations. Here we report that in voltage-gated Shaker K
channels lacking N-type inactivation, a mutation enhancing inactivation disrupts the outermost K
site in the selectivity filter. Furthermore, in a crystal structure of the Kv1.2-2.1 chimeric channel bearing the same mutation, the outermost K
site, which is formed by eight carbonyl-oxygen atoms, appears to be slightly too small to readily accommodate a K
ion and in fact exhibits little ion density; this structural finding is consistent with the functional hallmark of C-type inactivation.
The TET2 DNA dioxygenase regulates cell identity and suppresses tumorigenesis by modulating DNA methylation and expression of a large number of genes. How TET2, like most other chromatin-modifying ...enzymes, is recruited to specific genomic sites is unknown. Here we report that WT1, a sequence-specific transcription factor, is mutated in a mutually exclusive manner with TET2, IDH1, and IDH2 in acute myeloid leukemia (AML). WT1 physically interacts with and recruits TET2 to its target genes to activate their expression. The interaction between WT1 and TET2 is disrupted by multiple AML-derived TET2 mutations. TET2 suppresses leukemia cell proliferation and colony formation in a manner dependent on WT1. These results provide a mechanism for targeting TET2 to a specific DNA sequence in the genome. Our results also provide an explanation for the mutual exclusivity of WT1 and TET2 mutations in AML, and suggest an IDH1/2-TET2-WT1 pathway in suppressing AML.
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•WT1 is mutated in a mutually exclusive manner with TET2, IDH1, and IDH2 in AML•WT1 recruits TET2 to its target genes•AML-derived mutations in TET2 disrupt its binding with WT1•WT1 and TET2 are functionally interdependent
Wang et al. show that WT1 binds directly to TET2 and recruits TET2 to specific genomic sites to regulate WT1-target gene expression. This provides an explanation for the mutual exclusivity of WT1 and TET2 mutations in AML, and suggests an IDH1/2-TET2-WT1 pathway in suppressing AML.
Flexible and ultratransparent conductors based on graphene sheets have been considered as one promising candidate for replacing currently used indium tin oxide films that are unlikely to satisfy ...future needs due to their increasing cost and losses in conductivity on bending. Here we demonstrate a simple and fast electrochemical method to exfoliate graphite into thin graphene sheets, mainly AB-stacked bilayered graphene with a large lateral size (several to several tens of micrometers). The electrical properties of these exfoliated sheets are readily superior to commonly used reduced graphene oxide, which preparation typically requires many steps including oxidation of graphite and high temperature reduction. These graphene sheets dissolve in dimethyl formamide (DMF), and they can self-aggregate at air−DMF interfaces after adding water as an antisolvent due to their strong surface hydrophobicity. Interestingly, the continuous films obtained exhibit ultratransparency (∼96% transmittance), and their sheet resistance is <1k Ω/sq after a simple HNO3 treatment, superior to those based on reduced graphene oxide or graphene sheets by other exfoliation methods. Raman and STM characterizations corroborate that the graphene sheets exfoliated by our electrochemical method preserve the intrinsic structure of graphene.
The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ...ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4HBx substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4HBx E3 ligase and subsequent degradation by the proteasome. Using a minicircle HBV (mcHBV) reporter system with HBx-dependent activity, we demonstrate that SMC5/6 knockdown, or inhibition with a dominant-negative SMC6, enhance HBx null mcHBV-Gluc gene expression. Furthermore, SMC5/6 knockdown rescued HBx-deficient HBV replication in human hepatocytes. These results indicate that a primary function of HBx is to degrade SMC5/6, which restricts HBV replication by inhibiting HBV gene expression.
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•HBx interacts with SMC5/6 complex proteins•HBx/HBV infection leads to SMC5/6 degradation in human hepatocytes•HBx targets SMC5/6 for ubiquitylation and degradation by the DDB1-CUL4-ROC1 E3 ligase•Knockdown of SMC5/6 rescues replication of HBx-deficient HBV virus
Murphy et al. find that HBx-redirected CRL4 E3 ligase activity targets SMC5/6. SMC5/6 inhibits HBV gene expression, and SMC5/6 depletion rescues HBx-deficient HBV replication, indicating that SMC5/6 is counteracted by CRL4HBx-mediated SMC5/6 degradation.
D-mannose, an epimer of glucose, which is abundant in some fruits, such as cranberry, has been previously reported to inhibit urinary tract infection. In recent years, the potential function of ...D-mannose has been broadened into the regulation of other inflammation diseases and cancer. It was reported that D-mannose can increase reactive oxygen species (ROS) production, while IDH2 is important for the generation of NADPH, the crucial reducing factor. These findings prompted us to determine whether D-mannose can regulate IDH2 and IDH2-mediated NADPH production in tumor.
The breast cancer cell line MDA-MB-231 was cultured and treated with 100mM D-mannose. IDH2 expression was detected by Western Blot and qRT-PCR. RNA-seq was conducted to identify the differentially expressed genes. BioGRID database was used to find the IDH2 interactors. Tumor cells were collected to measure the NADPH production using the NADP+/NADPH detection Kit. Colony formation assay and CCK-8 assay were conducted to evaluate the proliferation of cells.
D-mannose can promote IDH2 protein degradation through ubiquitination-proteasome pathway. Mechanistically, D-mannose treatment upregulated the expression of an E3 ligase - RNF185, which can interact with IDH2 and promotes its proteasomal degradation. Consequently, IDH2-mediated NADPH production was inhibited by D-mannose, the proliferation of breast cancer cells was retarded, and the sensitivity to pro-oxidant of breast cancer cells was elevated.
Our study demonstrated that D-mannose can degrade IDH2 and inhibit the production of NADPH to suppress the proliferation of breast cancer cells and render the breast cancer cells more sensitive to pro-oxidant treatment. Furthermore, we illustrated the E3 ligase RNF185 plays an important role in D-mannose-mediated proteasomal degradation of IDH2.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
High-temperature measurements above 1000 °C are critical in harsh environments such as aerospace, metallurgy, fossil fuel, and power production. Fiber-optic high-temperature sensors are gradually ...replacing traditional electronic sensors due to their small size, resistance to electromagnetic interference, remote detection, multiplexing, and distributed measurement advantages. This paper reviews the sensing principle, structural design, and temperature measurement performance of fiber-optic high-temperature sensors, as well as recent significant progress in the transition of sensing solutions from glass to crystal fiber. Finally, future prospects and challenges in developing fiber-optic high-temperature sensors are also discussed.
A narrow-linewidth multiwavelength Brillouin random fiber laser (MW-BRFL) was experimentally demonstrated and characterized, which was achieved by mutually combining Brillouin amplification with ...randomly distributed Rayleigh feedback in optical fibers. By cascading process through a sub-fiber loop, up to six orders Stokes emissions simultaneously resonate in a coherent lasing fashion under the acoustic coupling of stimulated Brillouin scattering in the presence of coherent Rayleigh scattered random feedback, which acts as an optical filter with the high reflection coefficient for lowest order longitudinal mode of each Stokes line to ensure single longitudinal mode operation. Consequently, random laser output with an unprecedented ultra-high optical signal-to-noise ratio of ~47 dB and an optimal peak power discrepancy of 1.8 dB were obtained. Furthermore, each Stokes random lasing emission with narrow linewidth of ~1 kHz was achieved thanks to coherent random lasing. Relative intensity noise transfer was observed in sequence from the first-to sixth-order Stokes emission. In this MW-BRFL, a wide tunable range over 30 nm of the operating wavelength was validated by shifting the central wavelength of the input pump from 1530 to 1560 nm. Meanwhile, the statistical properties of the MW-BRFL and the performance optimization were also experimentally investigated.
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