RÉSUMÉ
Organic molecular electrode materials are promising candidates in batteries. However, direct application of small molecule materials usually suffers from drastic capacity decay and inefficient utilization of active materials because of their high solubility in organic electrolytes and low electrical conductivity. Herein, a simple strategy is found to address the above issues through coating the small-molecule organic materials on a commercialized carbon-coated aluminum foil (CCAF) as the enhanced electrode. Both the experimental and calculation results confirm that the relatively rough carbon coating on the aluminum foil not only exhibits superior adsorption capacity of small-molecule organic electrode materials with a tight contact interface but also provides continuous electronic conduction channels for the facilitated charge transfer and accelerated reaction kinetics. In addition, the carbon coating also inhibits Al corrosion in electrochemical process. As a result, by using the tetrahydroxy quinone-fused aza-phenazine (THQAP) molecule as an example, the THQAP-CCAF electrode exhibits an excellent rate performance with a high capacity of 220 and 180 mAh g-1 at 0.1 and 2 A/g, respectively, and also a remarkable cyclability with a capacity retention of 77.3% even after 1700 cycles in sodium-ion batteries. These performances are much more superior than that of batteries with the THQAP on bare aluminum foil (THQAP-AF). This work provides a substantial step in the practical application of the small-molecule organic electrode materials for future sustainable batteries.
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Disulfidptosis, a newly discovered mode of cell death caused by excessive accumulation of intracellular disulfide compounds, is closely associated with tumor development. This study focused on the relationship between disulfidptosis and clear cell renal cell carcinoma (ccRCC). Firstly, the characterizations of disulfidptosis-related genes (DRGs) in ccRCC were showed, which included number variation (CNV), single nucleotide variation (SNV), DNA methylation, mRNA expression and gene mutation. Then, the ccRCC samples were classified into three clusters through unsupervised clustering based on DRGs. Survival and pathway enrichment differences were evaluated among the three clusters. Subsequently, the differentially expressed genes (DEGs) among the three clusters were screened by univariate Cox, LASSO, and multivariate Cox analysis, and five key DEGs were obtained. Based on the five key DEGs, the ccRCC samples were reclassified into two geneclusters and the survival differences and immune cell infiltration between two geneclusters was investigated. In next step, ccRCC samples were divided into two groups according to PCA scores of five key DEGs, namely high PCA score group (HPSG) and low PCA score group (LPSG). On this basis, differences in survival prognosis, immune cell infiltration and correlation with immune checkpoint, as well as differences in sensitivity to targeted drugs were compared between HPSG and LPSG. The expression levels of four immune checkpoints were higher in HPSG than in LPSG, whereas the LPSG was more sensitive to targeted drug therapy than the HPSG. Finally, validation experiments on HDAC4 indicated that HDAC4 could increase the proliferation and colony formation ability of ccRCC cells.
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Accurate orientations and stable conformations of membrane receptor immobilization are particularly imperative for accurate drug screening and ligand-protein affinity analysis. However, there remain challenges associated with (1) traditional recombination, purification, and immobilization of membrane receptors, which are time-consuming and labor-intensive; (2) the orientations on the stationary phase are not easily controlled. Herein, a novel one-step synthesis and oriented-immobilization membrane-receptor affinity chromatography (oSOMAC) method was developed to realize high-throughput and accurate drug screening targeting specific domains of membrane receptors. We employed Strep-tag II as a noncovalent immobilization tag fused into platelet-derived growth factor receptor ß (PDGFRß) through CFPS, and meanwhile, the Strep-Tactin-modified monolithic columns are prepared in batches. The advantages of oSOMAC are as follows: (1) targeted membrane receptors can be expressed independent of living cell within 1-2 h; (2) orientation of membrane receptors can be flexibly controlled and active sites can expose accurately; and (3) targeted membrane receptors can be synthesized, purified, and orientation-immobilized on monolithic columns in one step. Accordingly, three potential PDGFRß intracellular domain targeted ligands: tanshinone IIA (Tan IIA), hydroxytanshinone IIA, and dehydrotanshinone IIA were successfully screened out from Salvia miltiorrhiza extract through oSOMAC. Pharmacological experiments and molecular docking further demonstrated that Tan IIA could attenuate hepatic stellate cells activation by targeting the protein kinase domain of PDGFRß with a KD value of 9.7 µM. Ultimately, the novel oSOMAC method provides an original insight for accurate drug screening and interaction analysis which can be applied in other membrane receptors.
Sujet(s)
Récepteur au PDGF bêta , Récepteur au PDGF bêta/métabolisme , Ligands , Humains , Chromatographie d'affinité , Évaluation préclinique de médicament , Protéines de fusion recombinantes/composition chimique , Protéines de fusion recombinantes/métabolisme , Protéines de fusion recombinantes/génétique , Oligopeptides/composition chimiqueRÉSUMÉ
Aqueous Zn-ion batteries (AZIBs) are considered as promising candidates for the next-generation large-scale energy storage, which, however, is facing the challenge of instable Zn anodes. The anion is pivotal in the stability of anodes, which are not being paid enough attention to. Herein, the modulation of anions is reported using the Hofmeister series in supramolecular chemistry to boost the stability of Zn anodes. It is found that the right-side anions in the Hofmeister series (e.g., OTf-) can enhance the Zn2+ transference number, increase the Coulombic efficiency, facilitate uniform Zn deposition, reduce the freezing point of electrolytes, and thereby stabilize the Zn anodes. More importantly, the right-side anions can form strong interaction with ß-cyclodextrin (ß-CD) compared to the left-side anions, and hence the addition of ß-CD can further enhance the stability of Zn anodes in OTf--based electrolytes, showing enhancement of cycling lifespan in the Zn//Zn symmetric cells more than 45.5 times with ß-CD compared with those without ß-CD. On the contrary, the left-side anions show worse rate performance after the addition of ß-CD. These results provide an effective and novel approach for choosing anions and matching additives to stabilize the anodes and achieve high-performance AZIBs through the Hofmeister effect.
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The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with tumor-infiltrating M0 cells, we developed a risk model to provide therapeutic and prognostic guidance in clear cell renal cell carcinoma (ccRCC). First, the infiltration abundance of each immune cell type and its correlation with patient prognosis were analyzed. After assessing the potential link between the depth of immune cell infiltration and prognosis, we screened the infiltrating M0 cells to establish a risk model centered on three key genes (TMEN174, LRRC19, and SAA1). The correlation analysis indicated a positive correlation between the risk score and various stages of the tumor immune cycle, including B-cell recruitment. Furthermore, the risk score was positively correlated with CD8 expression and several popular immune checkpoints (ICs) (TIGIT, CTLA4, CD274, LAG3, and PDCD1). Additionally, the high-risk group (HRG) had higher scores for tumor immune dysfunction and exclusion (TIDE) and exclusion than the low-risk group (LRG). Importantly, the risk score was negatively correlated with the immunotherapy-related pathway enrichment scores, and the LRG showed a greater therapeutic benefit than the HRG. Differences in sensitivity to targeted drugs between the HRG and LRG were analyzed. For commonly used targeted drugs in RCC, including axitinib, pazopanib, temsirolimus, and sunitinib, LRG had lower IC50 values, indicating increased sensitivity. Finally, immunohistochemistry results of 66 paraffin-embedded specimens indicated that SAA1 was strongly expressed in the tumor samples and was associated with tumor metastasis, stage, and grade. SAA1 was found to have a significant pro-tumorigenic effect by experimental validation. In summary, these data confirmed that tumor-infiltrating M0 cells play a key role in the prognosis and treatment of patients with ccRCC. This discovery offers new insights and directions for the prognostic prediction and treatment of ccRCC.
Sujet(s)
Néphrocarcinome , Tumeurs du rein , Microenvironnement tumoral , Humains , Néphrocarcinome/anatomopathologie , Néphrocarcinome/génétique , Pronostic , Microenvironnement tumoral/immunologie , Tumeurs du rein/anatomopathologie , Tumeurs du rein/génétique , Lymphocytes TIL/immunologie , Lymphocytes TIL/métabolisme , Femelle , Mâle , Appréciation des risques/méthodes , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Régulation de l'expression des gènes tumoraux , Adulte d'âge moyen , Immunothérapie/méthodes , Sulfonamides/usage thérapeutiqueRÉSUMÉ
Background: With the advances in society and in response to changing times, college students have had to face multiple challenges. These challenges frequently affect the mental health of college students, leading to significant consequences for their social lives, personal well-being, and academic achievements, thereby attracting extensive societal attention. Therefore, examining the current status of research topics related to the mental health of college students can assist academia in dissecting the influencing factors and seeking solutions at their source or through early intervention. This can contribute to a better understanding of and effectively address this challenge. Method: CiteSpace and VOSviewer were used to conduct a bibliometric analysis of 1609 journal articles indexed in the Web of Science (WoS) database over the past two decades (2000-2022), which helped identify the current state of research and hot topics in the field based on development trends. Furthermore, this study analyzes and discusses the core authors, high-productivity countries and organizations, key journals, and keyword clustering in this field. This study clarifies the current research landscape, analyzes evolving trends based on developmental trajectories, and identifies forefront research hotspots. This study provides scholars with reference research directions and ideas for conducting subsequent studies. Results: Since the beginning of the 21st century, research on college students' mental health has increased, especially in the past three years, and due to the impact of the COVID-19 pandemic and online distance learning, the number of publications has increased rapidly. With the increase in attention and publication volume, the countries and organizations contributing papers as well as core journals have all started to take shape. Cluster and evolution analyses found that several stable research topics have been formed in this research field, and many new and diverse topics are continuously emerging with time. Conclusion: and prospect: The findings prove that the field of college students' mental health has begun to take shape, gradually shifting from conceptual research to the implementation of specific interventions. However, whether specific interventions are effective and how effective they are require further investigation.
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BACKGROUND: Percutaneous vertebroplasty (PVP) is a common method used to treat Kümmell disease. In patients without neurologic symptoms, we sought to evaluate whether using the new spiral injectors instead of the traditional push-rod injectors in PVP can result in improved clinical efficacy for the treatment of Kümmell disease. METHODS: A clinical retrospective study was conducted between August 2018 and December 2020. The study included patients diagnosed with single-level thoracolumbar Kümmell disease who underwent PVP surgery. The patients were divided into 2 groups: an observation group consisting of 53 patients treated with spiral injectors and a control group consisting of 68 patients treated with push-rod injectors. RESULTS: A 2-year follow-up period was adopted. The bone cement injection volume and occurrence of bone cement leakage were significantly greater in the observation group compared with the control group (P < 0.05). The observation group had significantly shorter operation time and intraoperative fluoroscopy times compared with the control group (P < 0.05). The scores for the visual analog scale and Oswestry Disability Index in both groups were significantly lower at 3 days or 3 months and 2 years after surgery compared with before surgery, with the scores at 2 years after surgery being significantly lower than those at 3 days or 3 months for both groups (P < 0.05). The relative anterior ledge height and Cobb angle showed significant improvement at 3 days and 2 years after surgery compared with before surgery in both groups (P < 0.05), but patients in the observation group experienced substantial improvement at 3 days and 2 years after surgery compared with those in the control group (P < 0.05). In both groups, the relative anterior ledge height was noticeably lower 2 years after surgery compared with 3 days after surgery (P < 0.05). Concurrently, there was a significant increase in the local Cobb angle over time in both groups (P < 0.05). CONCLUSIONS: The implementation of both spiral injectors and traditional push-rod injectors in PVP surgery yields effective pain relief, improved function, partially restored vertebral height, and corrected kyphosis in treating Kümmell disease. Compared with the push-rod injector, the spiral injector is highly efficient in restoring vertebral height, correcting kyphosis, and minimizing fluoroscopy use and operation time, but it carries a greater risk of bone cement leakage.
Sujet(s)
Ciments osseux , Vertébroplastie , Humains , Vertébroplastie/méthodes , Études rétrospectives , Femelle , Mâle , Sujet âgé , Adulte d'âge moyen , Résultat thérapeutique , Sujet âgé de 80 ans ou plus , Fractures du rachis/chirurgie , Vertèbres thoraciques/chirurgie , Vertèbres lombales/chirurgieRÉSUMÉ
During infections, host cells are exposed to pathogen-associated molecular patterns (PAMPs) and virulence factors that stimulate multiple signaling pathways that interact additively, synergistically, or antagonistically. The net effect of such higher-order interactions is a vital determinant of the outcome of host-pathogen interactions. Here, we demonstrate one such complex interplay between bacterial exotoxin- and PAMP-induced innate immune pathways. We show that two caspases activated during enterohemorrhagic Escherichia coli (EHEC) infection by lipopolysaccharide (LPS) and Shiga toxin (Stx) interact in a functionally antagonistic manner; cytosolic LPS-activated caspase-11 cleaves full-length gasdermin D (GSDMD), generating an active pore-forming N-terminal fragment (NT-GSDMD); subsequently, caspase-3 activated by EHEC Stx cleaves the caspase-11-generated NT-GSDMD to render it nonfunctional, thereby inhibiting pyroptosis and interleukin-1ß maturation. Bacteria typically subvert inflammasomes by targeting upstream components such as NLR sensors or full-length GSDMD but not active NT-GSDMD. Thus, our findings uncover a distinct immune evasion strategy where a bacterial toxin disables active NT-GSDMD by co-opting caspase-3.
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Caspase-3 , Gasdermines , Protéines et peptides de signalisation intracellulaire , Macrophages , Protéines de liaison aux phosphates , Pyroptose , Pyroptose/effets des médicaments et des substances chimiques , Protéines de liaison aux phosphates/métabolisme , Macrophages/métabolisme , Macrophages/microbiologie , Protéines et peptides de signalisation intracellulaire/métabolisme , Caspase-3/métabolisme , Humains , Animaux , Souris , Protéines régulatrices de l'apoptose/métabolisme , Toxines bactériennes/métabolisme , Caspases/métabolisme , Lipopolysaccharides/pharmacologie , Escherichia coli entérohémorrhagique/métabolisme , Escherichia coli entérohémorrhagique/pathogénicité , Caspases initiatrices/métabolisme , Inflammasomes/métabolisme , Souris de lignée C57BL , Infections à Escherichia coli/métabolisme , Infections à Escherichia coli/microbiologie , Infections à Escherichia coli/immunologie , Interleukine-1 bêta/métabolismeRÉSUMÉ
Organic electrode materials (OEMs) have been well developed in recent years. However, the practical applications of OEMs have not been paid sufficient attention. The concept here focused on one of the essential aspects for practical applications, i. e., high mass loading of active materials. This paper summarizes the challenges posed by high-mass loading of active materials in organic batteries and discusses the possible solutions in terms of organic electrode materials, conductive additives, electrode structures, and electrolytes or battery systems. We hope this concept can stimulate more attention to practical applications of organic batteries towards industry from lab.
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In this work, hyperbranched polycarbonate-poly(ethylene oxide) (PEO)-based solid polymer electrolytes (HBPC-SEs) are successfully synthesized via a straightforward organo-catalyzed "A1"+"B2"-ring-opening polymerization approach. The temperature-dependent ionic conductivity of HBPC-SEs, composed of different polycarbonate linkages and various LiTFSI concentrations, is investigated. The results demonstrate that HBPC-SE with an ether-carbonate alternating structure exhibits superior ionic conductivity, attributed to the solubility of Li salts in the polymer matrix and the mobility of the polymer segments. The HBPC1-SE with 30 wt% LiTFSI presents the highest ionic conductivities of 2.15 × 10-5, 1.78 × 10-4, and 6.07 × 10-4 Scm-1 at 30, 60, and 80 °C, respectively. Compared to traditional PEO-based electrolytes, the incorporation of polycarbonate segments significantly enhances the electrochemical stability window (5 V) and Li+ transference number (0.53) of HBPC-SEs. Furthermore, the LiFePO4/HBPC1-SE-3/Li cell exhibits exceptional rate capability and long-cycling performance, maintaining a discharge capacity of 130 mAh g-1 at 0.5C with a capacity retention of 95% after 300 cycles.
Sujet(s)
Lithium , Ciment carboxylate , Polymères , Électrolytes , Métaux , CarbonatesRÉSUMÉ
Out of the several hundred copies of rRNA genes arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, ~50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to the differential expression of rRNAs. However, the mechanism(s) controlling the dosage of active versus inactive rRNA genes within each NOR in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influence rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosomes. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs influencing rRNA expression by forming constrained nucleolar territories on individual NORs.
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Organisateur nucléolaire , Précurseurs des ARN , Humains , Animaux , Organisateur nucléolaire/génétique , Organisateur nucléolaire/métabolisme , Précurseurs des ARN/génétique , Précurseurs des ARN/métabolisme , Nucléole/génétique , Nucléole/métabolisme , ARN ribosomique/génétique , ARN ribosomique/métabolisme , Chromosomes humains/métabolisme , ARN non traduit/génétique , ARN non traduit/métabolisme , Mammifères/génétiqueRÉSUMÉ
Fluoro-substitution solvents have achieved great success in electrolyte engineering for high-energy lithium metal batteries, which, however, is beset by low solvating power, thermal and chemical instability, and possible battery swelling. Instead, we herein introduce cyanogen as the electron-withdrawing group to enhance the oxidative stability of ether solvents, in which cyanogen and ether oxygen form the chelating structure with Li+ not notably undermining the solvating power. Cyano-group strongly bonds with transition metals (TMs) of NCM811 cathode to attenuate the catalytic reactivity of TMs toward bulk electrolytes. Besides, a stable and uniform cathode-electrolyte interphase (CEI) inhibits the violent oxidation decomposition of electrolytes and guarantees the structural integrity of the NCM811 cathode. Also, a N-containing and LiF-rich solid-electrolyte interphase (SEI) in our electrolyte facilitates fast Li+ migration and dense Li deposition. Accordingly, our electrolyte enables a stable cycle of Li metal anode with Coulombic efficiency of 98.4% within 100 cycles. 81.8% capacity of 4.3 V NCM811 cathode remains after 200 cycles. Anode-free pouch cells with a capacity of 125 mAh maintain 76% capacity after 100 cycles, corresponding to an energy density of 397.5 Wh kg-1.
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It is known that the dynamics of multiple ecosystem functions (i. e., multifunctionality) are positively associated with microbial diversity and/or biodiversity. However, how the relationship between microbial species affects ecosystem multifunctionality remains unclear, especially in the case of changes in precipitation patterns. To explore the contribution of biodiversity and microbial co-occurrence networks to multifunctionality, we used rainfall shelters to simulate precipitation enhancement in a cold steppe in Northeast China over two consecutive growing seasons. We showed that an increased 50% precipitation profoundly reduced bacterial diversity and multidiversity, while inter-annual differences in precipitation did not shift microbial diversity, plant diversity, or multidiversity. Our analyses also revealed that increased annual precipitation significantly increased ecosystem, soil, nitrogen, and phosphorous cycle multifunctionality. Neither increased precipitation nor inter-annual differences in precipitation had a significant effect on carbon cycle multifunctionality, probably due to the relatively short period (2 years) of our experiment. The co-occurrence network of bacterial and fungal communities was the most dominant factor affecting multifunctionality, the numbers of negative interactions but not positive interactions were linked to multifunctionality. In particular, our results provided evidence that microbial network topological features are crucial for maintaining ecosystem functions in grassland ecosystems, which should be considered in related studies to accurately predict the responses of ecosystem multifunctionality to predicted changes in precipitation patterns.
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Global warming is predicted to change precipitation amount and reduce precipitation frequency, which may alter grassland primary productivity and biomass allocation, especially when interact with other global change factors, such as nitrogen deposition. The interactive effects of changes in precipitation amount and nitrogen addition on productivity and biomass allocation are extensively studied; however, how these effects may be regulated by the predicted reduction in precipitation frequency remain largely unknown. Using a mesocosm experiment, we investigated responses of primary productivity and biomass allocation to the manipulated changes in precipitation amount (PA: 150 mm, 300 mm, 450 mm), precipitation frequency (PF: medium and low), and nitrogen addition (NA: 0 and 10 g N m-2 yr-1) in a Leymus chinensis grassland. We detected significant effects of the PA, PF and NA treatments on both aboveground biomass (AGB) and belowground biomass (BGB); but the interactive effects were only significant between the PA and NA on AGB. Both AGB and BGB increased with an increment in precipitation amount and nitrogen addition; the reduction in PF decreased AGB, but increased BGB. The reduced PF treatment induced an enhancement in the variation of soil moisture, which subsequently affected photosynthesis and biomass formation. Overall, there were mismatches in the above- and belowground biomass responses to changes in precipitation regime. Our results suggest the predicted changes in precipitation regime, including precipitation amount and frequency, is likely to alter primary productivity and biomass allocation, especially when interact with nitrogen deposition. Therefore, predicting the influence of global changes on grassland structure and functions requires the consideration of interactions among multiple global change factors.