Understanding of NAD+ metabolism provides many critical insights into health and diseases, yet highly sensitive and specific detection of NAD+ metabolism in live cells and in vivo remains difficult. ...Here, we present ratiometric, highly responsive genetically encoded fluorescent indicators, FiNad, for monitoring NAD+ dynamics in living cells and animals. FiNad sensors cover physiologically relevant NAD+ concentrations and sensitively respond to increases and decreases in NAD+. Utilizing FiNad, we performed a head-to-head comparison study of common NAD+ precursors in various organisms and mapped their biochemical roles in enhancing NAD+ levels. Moreover, we showed that increased NAD+ synthesis controls morphofunctional changes of activated macrophages, and directly imaged NAD+ declines during aging in situ. The broad utility of the FiNad sensors will expand our mechanistic understanding of numerous NAD+-associated physiological and pathological processes and facilitate screening for drug or gene candidates that affect uptake, efflux, and metabolism of this important cofactor.
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•FiNad responds to subtle changes of NAD+ metabolism in live cells and animals•The role of NAD+ precursors in boosting NAD+ levels is mapped in various organisms•Increased NAD+ synthesis controls morphofunctional changes of activated macrophages•FiNad enables live-cell and in vivo imaging of NAD+ decline during aging
Zou et al. report the development of “FiNad,” a highly responsive genetically encoded NAD+/AXP ratio sensor, where AXP is the total pool of ATP and ADP. FiNad is a useful reagent for monitoring NAD+ metabolism in a variety of organisms, including bacteria, cell lines, mice, zebrafish, and human-derived stem cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Rubella virus-associated granulomas commonly occur in immunocompromised individuals, exhibiting a diverse range of clinical presentations. These manifestations can vary from predominantly superficial ...cutaneous plaques or nonulcerative nodules to more severe deep ulcerative lesions, often accompanied by extensive necrosis and significant tissue destruction. TAP1 deficiency, an exceedingly rare primary immune-deficiency disorder, presents with severe chronic sino-pulmonary infection and cutaneous granulomas. This report highlights the occurrence of rubella virus-associated cutaneous granulomas in patients with TAP1 deficiency. Notably, the pathogenic mutation responsible for TAP1 deficiency stems from a novel genetic alteration that has not been previously reported. This novel observation holds potential significance for the field of diagnosis and investigative efforts in the context of immunodeficiency disorders.
Powdery mildew (
Blumeria graminis
f. sp.
Tritici
, (
Bgt
)) is an important worldwide fungal foliar disease of wheat (
Triticum aestivum
) responsible for severe yield losses. The development of ...resistance genes and dissection of the resistance mechanism will therefore be beneficial in wheat breeding. The
Bgt
resistance gene
PmAS846
was transferred to the hexaploid wheat lines N9134 from
Triticum dicoccoides
, and it is still one of the most effective resistance genes. Here, by RNA sequencing, we identified three co-expressed gene modules using pairwise comparisons and weighted gene co-expression network analysis during wheat–
Bgt
interactions compared with mock-infected plants. Hub genes of stress-specific modules were significantly enriched in spliceosomes, phagosomes, the mRNA surveillance pathway, protein processing in the endoplasmic reticulum, and endocytosis. Induced module genes located on chromosome 5BL were selected to construct a protein–protein interaction network. Several proteins were predicted as the key hub node, including Hsp70, DEAD/DEAH box RNA helicase PRH75, elongation factor EF-2, cell division cycle 5, ARF guanine-nucleotide exchange factor GNOM-like, and protein phosphatase 2C 70 protein, which interacted with several disease resistance proteins such as RLP37, RPP13 and RPS2 analogues. Gene ontology enrichment results showed that wheat could activate binding functional genes via an mRNA transcription mechanism in response to
Bgt
stress. Of these node genes, GNOM-like, PP2C isoform X1 and transmembrane 9 superfamily member 9 were mapped onto the genetic fragment of
PmAS846
with a distance of 4.8 Mb. This work provides the foundations for understanding the resistance mechanism and cloning the resistance gene
PmAS846
.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The NAM, ATAF1/2, and CUC2 (NAC) transcription factors (TFs) constitute the largest plant-specific TF superfamily, and play important roles in various physiological processes, including stress ...responses. Stripe rust and powdery mildew are the most damaging of the fungal diseases that afflict wheat (
L.). However, studies on
(
)
' role in resistance to the two diseases are still limited, especially in an overall comparative analysis of
responding or not to fungal stress. In the present study, 186 TaNAC transcripts were obtained from the resistant hexaploid wheat line N9134 under fungal stress, and 180 new transcripts were submitted to GenBank. Statistical results show that 35.1% (54/154) of TaNAC genes responded to stripe rust and powdery mildew in the seedling stage. "Abnormal" coding transcripts of differentially expressed (DE)-TaNAC genes in wheat responding to fungal stress were found in a significantly higher proportion (24/117 vs. 8/69,
= 0.0098) than in non-DE-NACs. This hinted that the alternative splicing of TaNAC genes was active in transcriptional or post-transcriptional regulation during plant-pathogen interactions. Full-length NAC proteins were classified into nine groups via phylogenetic analysis. Multiple-sequence alignment revealed diversity in the C-terminal structural organization, but the differentially expressed gene (DEG)-encoding proteins enriched in Subgroups VI and VII were conserved, with WVL/VCR amino acid residues in Motif 7 following the NAM domain. Our data that showed TaNAC TFs responded to fungal disease, which was affected by expression levels and by the regulation of multifarious transcript variants. These data for TaNAC responses to stripe rust and/or powdery mildew and their numerous structural variants provide a good resource for NAC function-mechanism analysis in the context of biotic-stress tolerance in wheat.
To reduce the vehicle delay effectively, a coordinated signal control method for arterial road of adjacent intersections has been proposed, which is based on the genetic algorithm improved. The ...method takes the signal coordinated control system for arterial road of adjacent intersections as the research object, by analyzing the signal states encountered by the head and tail of fleet before the crossing of the arterial road, and adopting the minimum total delay of waiting queue team as the performance index, to establish the coordinate control system optimization model for arterial road, in which a cycle length, signal timing and phase difference are optimization parameters. And the method introduce minimum spanning tree clustering idea to improve the defects of the standard genetic algorithm (Standard Genetic Algorithms, SGA), and then optimizes the aforementioned the coordinate control system optimization model for arterial road. The experiment shows that the results obtained by the improved genetic algorithm are better than the ones obtained by standard genetic algorithm and traditional algebraic method respectively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The transport of organic contaminants in groundwater might be greatly affected by coexistence of dissolved organic matter (DOM) from different sources. In this study, the effects of endogenous and ...exogenous DOMs (referred to as DOMen and DOMex, respectively) on sorption behavior of bisphenol A (BPA) onto two reference soils were investigated by batch experiments and microscopic characterization. The results showed that BPA sorption onto soils was dominated by soil organic matter content and affected by DOM properties. The effect of DOMen on BPA sorption was also related to the inorganic components of the two soils. The decrease of organic matter content reduced the sorption capacity of fluvo-aquic soil. However, because the content of available inorganic components in black soil was high, after removing DOMen, more inorganic sites were exposed to increase the sorption capacity. In addition, DOMen could form complexes with BPA in solution, thus the removal of DOMen promoted BPA sorption onto black soil. Under the experimental conditions, contribution of DOMex to the total sorption of BPA onto both soils was not more than 30%. Results of dialysis experiments and soil sorption experiments indicated that effects of coexisting DOMex on BPA sorption was related to the affinity of DOMex to soils and complexation of BPA and DOMex. Since the affinity of DOMex to fluvo-aquic soil was relatively low, the complex of BPA and DOMex in solution was the main inhibition mechanism for BPA sorption. For black soil, higher complexation proportion of BPA with DOMex adsorbed onto soil which promoted BPA sorption onto soil. The findings are of significance for understanding the co-migration of DOM with BPA through soils.
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•Removal of endogenous DOM could expose available inorganic sorption sites on soil.•Distribution of exogenous DOM-BPA complexes determined BPA sorption to soils.•Affinity between exogenous DOM and soil was the main factor affecting BPA sorption.•Complexation of BPA to DOMex in solution inhibited sorption onto fluvo-aquic soil.•DOMex sorbed onto black soil, and promoted co-sorption of BPA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Te-doped Li4Ti5O12 (LTO) was prepared by a ball milling-assisted solid-state method in air. The as-prepared powders were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, scanning ...electron microscopy, and electrochemical impedance spectroscopy. Li4Ti4.95Te0.05O12 powder sintered at 850 °C presented improved ionic and electronic conductivities of 2.20 × 10-7 S·cm-1 and 2.40 × 10-9 S·cm-1 at room temperature, respectively, an order of magnitude higher than those of intrinsic LTO. Electrochemical analysis showed that the discharge specific capacities of Li4Ti4.95Te0.05O12 in Li half cells at 1 C and 5 C were 162.49 mAh·g-1 and 143.5 mAh·g-1, respectively, with capacity retention rates of 98.8% and 98.2% after 100 cycles. The Li4Ti4.95Te0.05O12/LiNi0.5Mn0.3Co0.2O2 full cells also showed a good specific capacity of 101.8 mAh·g-1 at 1 C and delivered good temperature adaptability. This study provides an effective strategy for the preparation of high-performance LTO anodes for lithium-ion batteries.
•Excellent transport characteristics of Li4Ti4.95Te0.05O12 with an ionic conductivity of 2.20 × 10-7 S·cm-1.•High discharge specific capacity of 120.25 mAh·g-1 at high rate of 10 C in Li4Ti4.95Te0.05O12 half cell.•Excellent capacity retention rate of 99.7% after 400 cycles and good specific capacity of Li4Ti4.95Te0.05O12/LiNi0.5Mn0.3Co0.2O2 full cell.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Te-doped NASICON-type Li1.3Al0.3Ti1.7(PO4)3 (LATP) electrolyte materials were prepared by ball milling-assisted solid state method. The structural, morphological, and transport properties of samples ...were analyzed through X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscope, energy dispersive X-Ray spectroscopy, electrochemical impedance spectroscopy, and DC polarization to determine optimal doping concentration. High total ionic conductivity of 7.03 × 10−4 S cm−1 and negligible electronic conductivity of 7.64 × 10−9 S cm−1 were obtained at room temperature for Li1.3Al0.3Te0.03Ti1.67(PO4)3 electrolyte. Interface characteristics analysis of electrolyte materials with Li electrode showed that voltage profile of Li/Li1.3Al0.3Te0.03Ti1.67(PO4)3/Li cell remained stable after 300 h of cycling with current density of 0.02 mA cm−2. Good cyclic stability at different temperatures was also demonstrated, with doped electrolyte presenting better interface stability than pure LATP. These results suggest that Te-doped LATP materials can be used as alternative solid electrolyte for all solid-state lithium-ion batteries.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A graphene surface coating strategy (G@LATP), to modify and improve the interfacial characteristics between the Lithium Aluminum Titanium Phosphate (LATP) electrolyte and different anodes, such as Li ...metal and Si film has been proposed. As a result, the Li/Li symmetric cell with graphene coating modified LATP electrolyte exhibits excellent cyclic stability, even at large current densities of 0.5 mA·cm−2 and 1 mA·cm−2. The modified Li/G@LATP/LiFePO4 solid-state full cell is delivering a discharge specific capacity of 136 mAh·g−1 after 200 cycles at a current density of 0.1 mA·cm−2, corresponding to a capacity retention of 86.1%. The graphene coating technique also led to improved cyclic stability in the Si/Si symmetric cell with modified LATP electrolyte at current densities of 0.1 mA·cm−2 and 0.3 mA·cm−2, with polarization voltages of 0.063 V and 0.27 V after cycling for 1000 h, respectively. Moreover, the Si/G@LATP/LiFePO4 full cell shows an outstanding discharge specific capacity of 161 mAh·g − 1 at its 2nd cycle, with a capacity retention of 92.9% after 200 cycles. These results show that graphene coating of the LATP electrolyte is a facile and effective method to improve the interfacial characteristics of Li/LATP and Si/LATP.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
NAD(P)H:quinone oxidoreductase 1 (NQO1) has been shown to be a potential therapeutic target for various human diseases, such as cancer and neurodegenerative disorders. Recent advances in ...computational methods, especially network-based methods, have made it possible to identify novel compounds for a target with high efficiency and low cost. In this study, we designed a workflow combining network-based methods and identification of privileged substructures to discover new compounds targeting NQO1 from a natural product library. According to the prediction results, we purchased 56 compounds for experimental validation. Without the assistance of privileged substructures, 31 compounds (31/56 = 55.4%) showed IC50 < 100 μM, and 11 compounds (11/56 = 19.6%) showed IC50 < 10 μM. With the assistance of privileged substructures, the two success rates were increased to 61.8 and 26.5%, respectively. Seven natural products further showed inhibitory activity on NQO1 at the cellular level, which may serve as lead compounds for further development. Moreover, network analysis revealed that osthole may exert anticancer effects against multiple cancer types by inhibiting not only carbonic anhydrases IX and XII but also NQO1. Our workflow and computational methods can be easily applied in other targets and become useful tools in drug discovery and development.
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IJS, KILJ, NUK, PNG, UL, UM
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