Dual metal–organic frameworks (MOFs, i.e., MIL‐100(Fe) and ZIF‐8) are thermally converted into Fe–Fe3C‐embedded Fe–N‐codoped carbon as platinum group metal (PGM)‐free oxygen reduction reaction (ORR) ...electrocatalysts. Pyrolysis enables imidazolate in ZIF‐8 rearranged into highly N‐doped carbon, while Fe from MIL‐100(Fe) into N‐ligated atomic sites concurrently with a few Fe–Fe3C nanoparticles. Upon precise control of MOF compositions, the optimal catalyst is highly active for the ORR in half‐cells (0.88 V in base and 0.79 V versus RHE in acid in half‐wave potential), a proton exchange membrane fuel cell (0.76 W cm−2 in peak power density) and an aprotic Li–O2 battery (8749 mAh g−1 in discharge capacity), representing a state‐of‐the‐art PGM‐free ORR catalyst. In the material, amorphous carbon with partial graphitization ensures high active site exposure and fast charge transfer simultaneously. Macropores facilitate mass transport to the catalyst surface, followed by oxygen penetration in micropores to reach the infiltrated active sites. Further modeling simulations shed light on the true Fe–Fe3C contribution to the catalyst performance, suggesting Fe3C enhances oxygen affinity, while metallic Fe promotes *OH desorption as the rate‐determining step at the nearby Fe–N–C sites. These findings demonstrate MOFs as model system for rational design of electrocatalyst for energy‐based functional applications.
An Fe–N–C catalyst is derived from dual metal–organic frameworks through facile pyrolysis, affording excellent oxygen reduction catalytic performance in alkaline/acidic half‐cells, a H2–O2 proton exchange membrane fuel cell, and a Li–O2 battery. The excellent catalytic performance benefits from density populated Fe–Fe3C@Fe–N–C dual active sites, hierarchical porosities for mass transport, and partial carbon graphitization for charge transfer.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Improved durability, enhanced interfacial stability, and room temperature applicability are desirable properties for all‐solid‐state lithium metal batteries (ASSLMBs), yet these desired properties ...are rarely achieved simultaneously. Here, in this work, it is noticed that the huge resistance at Li metal/electrolyte interface dominantly impeded the normal cycling of ASSLMBs especially at around room temperature (<30 °C). Accordingly, a supramolecular polymer ion conductor (SPC) with “weak solvation” of Li+ was prepared. Benefiting from the halogen‐bonding interaction between the electron‐deficient iodine atom (on 1,4‐diiodotetrafluorobenzene) and electron‐rich oxygen atoms (on ethylene oxide), the O‐Li+ coordination was significantly weakened. Therefore, the SPC achieves rapid Li+ transport with high Li+ transference number, and importantly, derives a unique Li2O‐rich SEI with low interfacial resistance on lithium metal surface, therefore enabling stable cycling of ASSLMBs even down to 10 °C. This work is a new exploration of halogen‐bonding chemistry in solid polymer electrolyte and highlights the importance of “weak solvation” of Li+ in the solid‐state electrolyte for room temperature ASSLMBs.
PEO‐based electrolytes suffer from huge interfacial resistance, poor Li+ transport, and Li dendrite formation in all‐solid‐state lithium metal batteries (ASSLMBs) operating at around room‐temperature. This work proposes the regulation of the Li+ solvation environment through halogen‐bonding interaction and highlights the importance of “weak solvation” of Li+ in solid electrolytes for room temperature ASSLMBs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The human 8q24 gene desert contains multiple enhancers that form tissue-specific long-range chromatin loops with the MYC oncogene, but how chromatin looping at the MYC locus is regulated remains ...poorly understood. Here we demonstrate that a long noncoding RNA (lncRNA), CCAT1-L, is transcribed specifically in human colorectal cancers from a locus 515 kb upstream of MYC. This lncRNA plays a role in MYC transcriptional regulation and promotes long-range chromatin looping. Importantly, the CCAT1-L locus is located within a strong super-enhancer and is spatially close to MYC. Knockdown of CCAT1-L reduced long-range interactions between the MYC promoter and its enhancers. In addition, CCAT1-L interacts with CTCF and modulates chromatin conformation at these loop regions. These results reveal an important role of a previously unannotated lncRNA in gene regulation at the MYC locus.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
In recent years, autophagy was found to regulate lipid metabolism through a process termed lipophagy. Lipophagy modulates the degradation of cholesteryl esters to free cholesterol (FC), ...which is the substrate of testosterone biosynthesis. However, the role of lipophagy in testosterone production is unknown. To investigate this, primary rat Leydig cells and varicocele rat models were administered to inhibit or promote autophagy, and testosterone, lipid droplets (LDs), total cholesterol (TC), and FC were evaluated. The results demonstrated that inhibiting autophagy in primary rat Leydig cells reduced testosterone production. Further studies demonstrated that inhibiting autophagy increased the number and size of LDs and the level of TC, but decreased the level of FC. Furthermore, hypoxia promoted autophagy in Leydig cells. We found that short-term hypoxia stimulated testosterone secretion; however, the inhibition of autophagy abolished stimulated testosterone release. Hypoxia decreased the number and size of LDs in Leydig cells, but the changes could be largely rescued by blocking autophagy. In experimental varicocele rat models, the administration of autophagy inhibitors substantially reduced serum testosterone. These data demonstrate that autophagy contributes to testosterone biosynthesis at least partially through degrading intracellular LDs/TC. Our observations might reveal an autophagic regulatory mode regarding testosterone biosynthesis.
We found autophagy can degrade lipid droplets to provide substrates for testosterone biosynthesis in rat Leydig cells, and testosterone production can be regulated through modulating autophagy.
•A dynamic model of gear-bearing system with multi-mesh state and deterministic-random excitation is established.•The coupling effect of gear pair meshing vibration and gear bearing radial vibration ...is discussed.•The disengaging proportion of a gear-bearing system is calculated and analyzed based on the multi-mesh-state model.•Intrinsic mechanism between disengaging proportion and multi-mesh state is revealed.•Effects of dynamics type and its topology on the disengaging proportion are clearly acquired.
Backlash induces gear-teeth separation or back-side tooth mesh (BTM), resulting in gear disengagement (GD), which heavily aggravates the dynamic performance and transmission quality of gear drivetrains. This study focuses on the disengaging proportion (DP) characteristics of a gear- bearing systems based on a multi-meshing-state (MMS) model. A new nonlinear dynamic model of gear-bearing system with MMS and deterministic-random external excitation is established considering the synergistic effect of backlash and non-integer contact ratio. A modified time-varying mesh stiffness with temperature stiffness is included in the model. Afterwards, the effect of the gear pair meshing vibration on bearing radial vibration is studied. The bifurcation and evolution of the MMS behavior are investigated changing the system parameters. An algorithm of DP is proposed in the time domain based on the established MMS model. The characteristics of DP are systematically discussed with the effects of dynamic response type, phase trajectory topology, bifurcation and chaos, and correlation between parameters. The results demonstrate that grazing bifurcation reduces the number of GD and chaos is prone to BTM. The disengaging proportion is highly dependent on the phase trajectory topology and generally increases from period-1 to quasi-periodic and then to chaotic responses. Bifurcation changes the variation trend of DP, thus there is a peak near period-doubling bifurcation and a trough near grazing bifurcation. The chaotic response leads to a jump in DP. The correlation between parameters considerably dominates the DP. This study provides a reference for revealing the mechanism of gear system disengagement and improving the dynamic performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Adenosine deaminases acting on RNA （ADARs） are involved in adenosine-to-inosine RNA editing and are implicated in development and diseases. Here we observed that ADAR1 deficiency in human embryonic ...stem cells （hESCs） significantly affected hESC differentiation and neural induction with widespread changes in mRNA and miRNA ex- pression, including upregulation of self-renewal-related miRNAs, such as miR302s. Global editing analyses revealed that ADAR1 editing activity contributes little to the altered miRNA/mRNA expression in ADARl-deficient hESCs upon neural induction. Genome-wide iCLIP studies identified that ADAR1 binds directly to pri-miRNAs to interfere with miRNA processing by acting as an RNA-binding protein. Importantly, aberrant expression of miRNAs and phe- notypes observed in ADARl-depleted hESCs upon neural differentiation could be reversed by an enzymatieally inactive ADAR1 mutant, but not by the RNA-binding-null ADAR1 mutant. These findings reveal that ADAR1, but not its editing activity, is critical for hESC differentiation and neural induction by regulating miRNA biogenesis via direct RNA interaction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Recurrences are the main reasons for unfavorable outcomes for patients with stage II colorectal cancer (CRC). To obtain a clear understanding of the high-risk factors, further investigation is ...warranted. The present study aimed to analyze the risk factors associated with postoperative recurrence in patients with stage II CRC.
Eligible patients with pathologically confirmed stage II CRC were enrolled in the study retrospectively based on a prospectively maintained database from April 2008 to March 2019. The Kaplan-Meier method were used to calculate the overall survival (OS) rate and the cumulative recurrence rate. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence.
There were 2515 patients included, of whom 233 (9.3%) developed local or distant recurrence. Recurrence was associated with a significantly worse 5-year OS (45.4% vs. 95.5%, p < 0.0001). The 5-year cumulative recurrence rate was 13.0% in patients with stage II CRC. On multivariable Cox analysis, tumor size (Hazard Ratio (HR) 95% confidence interval (CI) = 1.791.38, 2.33), preoperative carbohydrate antigen (CA) 125 level (HR 95% CI = 1.781.17, 2.70), preoperative CA 199 level (HR 95% CI = 1.561.09, 2.22), and ulcerating tumor (HR 95% CI = 1.611.19, 2.17) were found to be associated with postoperative recurrence. Adjuvant chemotherapy was associated with a lower cumulative recurrence rate in patients with these risk factors (p = 0.00096).
The tumor diameter, preoperative CA125 level, preoperative CA199 level, and an ulcerative tumor can predict postoperative recurrence in patients with stage II CRC, and postoperative chemotherapy could reduce the cumulative recurrence rate in patients with these high-risk factors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC) patients without human papillomavirus infection. The recurrence rate for these patients is distinctly high. It has ...been actively explored to identify agents that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC. PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its methylated analogue PRIMA-1
(also called APR-246) were found to be able to reestablish the DNA-binding activity of p53 mutants and reinstate the functions of WT p53. Herein we report that piperlongumine (PL), an alkaloid isolated from Piper longum L., synergizes with APR-246 to selectively induce apoptosis and autophagic cell death in HNSCC cells, whereas primary and immortalized mouse embryonic fibroblasts and spontaneously immortalized non-tumorigenic human skin keratinocytes (HaCat) are spared from the damage by the co-treatment. Interestingly, PL-sensitized HNSCC cells to APR-246 are TP53 mutation-independent. Instead, we demonstrated that glutathione S-transferase pi 1 (GSTP1), a GST family member that catalyzes the conjugation of GSH with electrophilic compounds to fulfill its detoxification function, is highly expressed in HNSCC tissues. Administration of PL and APR-246 significantly suppresses GSTP1 activity, resulting in the accumulation of ROS, depletion of GSH, elevation of GSSG, and DNA damage. Ectopic expression of GSTP1 or pre-treatment with antioxidant N-acetyl-L-cysteine (NAC) abrogates the ROS elevation and decreases DNA damage, apoptosis, and autophagic cell death prompted by PL/APR-246. In addition, administration of PL and APR-246 impedes UMSCC10A xenograft tumor growth in SCID mice. Taken together, our data suggest that HNSCC cells are selectively sensitive to the combination of PL and APR-246 due to a remarkably synergistic effect of the co-treatment in the induction of ROS by suppression of GSTP1.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The mutually beneficial relationship between plants and their root microbiota is essential for plants to adapt to unfavorable environments. However, the molecular mechanism of wheat regulating the ...structure of root microbiome and the influence of distant hybridization on this process are poorly understood. In this study, we systematically compared the root transcriptome and microbiome between a saline-alkali tolerant wheat introgression line SR4 (derived from somatic hybridization between wheat and tall wheatgrass) and its parent wheat variety JN177. The results indicated that root microorganisms were key factor maintaining better homeostasis of the sodium and potassium ion contents in SR4 than in JN177 under saline-alkali stress. Through systematic comparisons, we identified SR4-specific root bacterial and fungal taxa under saline-alkali stress. Through a weighted gene correlation network analysis (WGCNA) combining microbiome and transcriptome data, key functional genes and pathways, which were strongly related to root bacteria and fungi with differential abundance between JN177 and SR4, were identified. These results suggest that somatic hybridization has altered the key genes regulating root microbiome in wheat, further improving the saline-alkali tolerance of wheat introgression line. These findings provide the key bacterial and fungal taxa and functional target genes for wheat root microbiome engineering under saline-alkali stress.
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•The mechanism of wheat regulating root microbiome is poorly understood.•Root microbes are key for the Na+/K+ content difference between JN177 and SR4.•SR4 recruits beneficial microbes through gene regulation to improve stress resistance.•Hybridization altered genes regulating root microbes, improving wheat stress tolerance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Developing innovative and efficient non-precious-metal-group (non-PMG) electrocatalysts is crucial for the wide use of zinc-air batteries (ZABs). Herein, a single-atom catalyst (termed as Fe-N-C/rGO ...SAC) with unique five N-coordinated Fe (Fe-N
5
) centers is prepared by pyrolyzing the composite of zeolitic-imidazolate-frameworks-8 (ZIF-8) and graphene oxide (GO). Specifically, the individual Fe site is stabilized by four equatorial and one axial N atoms donated by the N-doped carbon matrix and imidazole ring, respectively, thus forming an asymmetric electron depletion zone over the metal center, which can effectively promote the generation of reactive intermediates and accelerate the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) processes for ZABs. The rechargeable liquid ZAB with Fe-N-C/rGO catalyst exhibits an extremely high energy density (928.25 Wh·kg
−1
), a remarkable peak power density (107.12 mW·cm
−2
), and a long cycle life (400 h). Additionally, the corresponding flexible solid-state ZAB displays superior foldability and remarkable cycling stability. This work provides both experimental and theoretical guidance for rational design of non-PMG electrocatalyst-driven ZABs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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