e14620 Background: Identifying immune-related adverse events (irAEs) or bacterial infections in cancer patients undergoing treatment with PD-(L)1 inhibitors can be challenging. This study aimed to ...assess the effectiveness of the neutrophil-to-lymphocyte ratio (NLR) in distinguishing between irAEs and bacterial infections in cancer patients receiving PD-(L)1 inhibitors. Methods: We conducted a retrospective analysis of cancer patients who received at least one dose of PD-(L)1 inhibitors at Affiliated Cancer Hospital of Zhengzhou University from 2018 to 2023. We compared the changes in peripheral blood cell counts before and after the occurrence of adverse events, as well as the ratio of the NLR at the time of adverse events (post-NLR) to the NLR before adverse events (pre-NLR). Bacterial infections were diagnosed based on clear etiology and/or controlled adverse events through the use of antibiotics without systemic glucocorticoid administration during treatment. irAEs were diagnosed based on clinicolaboratory criteria, or the improvement of immune system disorders after withdrawal of PD-(L)1 inhibitors or systemic glucocorticoid administration, excluding bacterial infection. Data were collected from microbiology, radiography, serology, and physician notes. Results: Among the 4173 patients who were administered PD-(L)1 inhibitors, 217 individuals experienced a total of 249 irAEs, while 256 patients were diagnosed with 257 bacterial infections. When comparing pre-infection levels with those after bacterial infection, it was observed that the NLR increased significantly. Similarly, in the group experiencing irAEs, the NLR also showed a significant increase after the occurrence of the irAEs. Notably, the NLR was significantly higher in patients with bacterial infections compared to those with irAEs 11.08 (6.63, 19.29) vs 2.78 (1.92, 4.31), P < 0.001. Furthermore, the post-NLR/pre-NLR ratio was higher in the bacterial infection group than in the irAEs group 2.86 (1.56, 6.20) vs 1.16 (0.82, 1.76), P < 0.001. Appraising the potential of NLR and the post-NLR/pre-NLR ratio in identifying irAEs and bacterial infections in cancer patients, the receiver operating characteristic (ROC) curve analysis was performed. The area under the curve (AUC) was 0.91 for NLR and 0.81 for the post-NLR/pre-NLR ratio, respectively. Using a cut-off value of 4.56 for NLR and 1.96 for the post-NLR/pre-NLR ratio yielded the highest sensitivity and specificity. Conclusions: The NLR along with the post-NLR/pre-NLR ratio could serve as valuable diagnostic indicators for irAEs and bacterial infections in cancer patients undergoing treatment with PD-(L)1 inhibitors.
In this paper, we have developed epoxidized phenyl silicone rubber (EMVPQ) with good oil and radiation resistance by anionic ring-opening copolymerization and further epoxidation modification. ...Silicone rubbers with both phenyl and epoxy groups were firstly synthesized and main properties of the material were characterized. When the phenyl content in EMVPQ was increased from 5% to 20%, the damping loss peak shifted to the high temperature by 36 °C and the effective damping temperature range was widened by 3 °C. The tensile strength of EMVPQ with 20% phenyl content did not change before and after irradiation. When the epoxy content is only 13%, the EMVPQ retained mechanical properties after immersion at 25 °C or 100 °C for 72 h, but a commercial sample substantially lost its mechanical properties. This work not only promotes the research of epoxidized phenyl silicone rubber, but also opens an effective way for the preparation of high-performance aerospace materials.
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•We firstly designed and synthesized a silicone rubber with both phenyl and epoxy groups.•The epoxidized phenyl silicone rubber exhibit significant advantages over most existing silicone rubber.•Epoxidized phenyl silicone rubber is more conducive to the stability of the material under high temperature conditions.•Epoxidized phenyl silicone rubber has good oil resistance at 100 °C.•The introduction of phenyl and epoxy groups has a greater effect on radiation resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Red paddy soils in southern China originate from various parent materials; however, the respective characteristics of C sequestration efficiency (CSE) are unclear. Here, three cultivated land ...monitoring sites in Jiangxi province were examined, with soils originating from argillaceous rock, quaternary red clay, and granite. We assessed crop yield and soil physicochemical properties over several years and measured soil organic C (SOC) storage, SOC fractions, and chemical structure in 2019 to test differences in CSE characteristics, SOC structure stability, and factors affecting red paddy soils. The change in SOC storage under long‐term fertilization showed the following descending order: red paddy soils derived from argillaceous rock (1.10 t ha−1 yr−1) > granite (0.75 t ha−1 yr−1) > quaternary red clay (0.12 t ha−1 yr−1); the order of CSE was granite (0.24) > argillaceous rock (0.22) > quaternary red clay (0.08). Red paddy soil from argillaceous rock had the highest proportion of recalcitrant organic C (ROC) and SOC stability (aromaticity 0.45). Red paddy soil originating from granite had the lowest ROC proportion (54%) and SOC stability (aromaticity 0.35). Soil properties, organic C input, and amount of N fertilizer explained 53.6% of the total CSE variation. SOC, pH, and organic C input were the main factors affecting CSE, with relative contribution rates of 36.4, 6.2, and 6.3%, respectively. pH (30.4%) was the main factor affecting CSE variation in argillaceous rock paddy soil. Soil organic C (52.2%) was the main factor explain CSE variation in quaternary red clay‐derived red paddy soil. Soil organic C and organic C input explained 39.4 and 21.3% of the variation in CSE in granite‐derived paddy soils. The parent material can directly or indirectly affect CSE through soil texture.
Core ideas
Granite and argillite‐derived soil C sequestration efficiency (CSE) is higher than that of quaternary red clay soil.
Soil organic C (SOC) structural stability was higher in argillite than in granite paddy soil.
SOC, pH, and exogenous organic C input were the main factors affecting CSE.
The parent material can directly or indirectly affect CSE through soil texture.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Soil fungi play critical roles in ecosystem processes and are sensitive to global changes. Elevated atmospheric nitrogen (N) deposition has been well documented to impact on fungal diversity and ...community composition, but how the fungal community assembly responds to the duration effects of experimental N addition remains poorly understood. Here, we aimed to investigate the soil fungal community variations and assembly processes under short- (2 years) versus long-term (13 years) exogenous N addition (∼100 kg N ha
–1
yr
–1
) in a N-rich tropical forest of China. We observed that short-term N addition significantly increased fungal taxonomic and phylogenetic α-diversity and shifted fungal community composition with significant increases in the relative abundance of
Ascomycota
and decreases in that of
Basidiomycota
. Short-term N addition also significantly increased the relative abundance of saprotrophic fungi and decreased that of ectomycorrhizal fungi. However, unremarkable effects on these indices were found under long-term N addition. The variations of fungal α-diversity, community composition, and the relative abundance of major phyla, genera, and functional guilds were mainly correlated with soil pH and NO
3
–
–N concentration, and these correlations were much stronger under short-term than long-term N addition. The results of null, neutral community models and the normalized stochasticity ratio (
NST
) index consistently revealed that stochastic processes played predominant roles in the assembly of soil fungal community in the tropical forest, and the relative contribution of stochastic processes was significantly increased by short-term N addition. These findings highlighted that the responses of fungal community to N addition were duration-dependent, i.e., fungal community structure and assembly would be sensitive to short-term N addition but become adaptive to long-term N enrichment.
Abstract
Endonuclease G (ENDOG), a nuclear-encoded mitochondrial intermembrane space protein, is well known to be translocated into the nucleus during apoptosis. Recent studies have shown that ENDOG ...might enter the mitochondrial matrix to regulate mitochondrial genome cleavage and replication. However, little is known about the role of ENDOG in the cytosol. Our previous work showed that cytoplasmic ENDOG competitively binds with 14-3-3γ, which released TSC2 to repress mTORC1 signaling and induce autophagy. Here, we demonstrate that cytoplasmic ENDOG could also release Rictor from 14-3-3γ to activate the mTORC2-AKT-ACLY axis, resulting in acetyl-CoA production. Importantly, we observe that ENDOG could translocate to the ER, bind with Bip, and release IRE1a/PERK to activate the endoplasmic reticulum stress response, promoting lipid synthesis. Taken together, we demonstrate that loss of ENDOG suppresses acetyl-CoA production and lipid synthesis, along with reducing endoplasmic reticulum stress, which eventually alleviates high-fat diet-induced nonalcoholic fatty liver disease in female mice.
Perovskite LaFeO3 with ABO3 structure is regarded as a potential candidate in electromagnetic wave absorption, considering its unique dielectric-magnetic coupling loss mechanism. However, the limited ...attenuation ability of pristine LaFeO3 restricts its further application. In this work, the dual doping strategy is carried out to improve the dielectric and magnetic loss capacity. Ca and Mn dual doped La0.8Ca0.2Fe1-xMnxO3 are prepared by spray pyrolysis method. The minimum reflection loss (RLmin) of La0.8Ca0.2Fe0.2Mn0.8O3 reaches −52.3 dB with an effective absorption bandwidth (EAB) of 3.92 GHz at the fitting thickness of 2.08 mm. The enhancement of the dielectric loss mainly originates from strengthened dipole polarization induced by the Jahn-Teller distortion which is caused by Ca and Mn double doping. The magnetic loss can be attributed to the improvement of double-exchange between Fe3+ –O2- -Mn3+ and Mn3+ –O2- -Mn4+ owing to the introduction of Mn. This work provides new insights into regulating the electromagnetic wave absorption performance of perovskite.
•Dual doped perovskite oxide La0.8Ca0.2Fe1-xMnxO3 were synthesized via facile spray pyrolysis method.•The Jahn-Teller distortion is achieved by an A/B double-doped perovskite oxide strategy, and the conformational relationship between B–O properties and lattice distortion was investigated, the lattice distortion of LCFMO successfully enhanced the polarization and relaxation process.•Based on Zener's double exchange theory, the Fe3+/Mn4+-O-Mn3+ double exchange channel is constructed to enhance the magnetic loss, and the crystal structure and electron leaps work together to achieve the matching of dielectric and magnetic properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Magnesium isotopes are an emerging tool to study the geological processes recorded in carbonates. Calcite, due to its ubiquitous occurrence and the large Mg isotope fractionation associated with the ...mineral, has attracted great interests in applications of Mg isotope geochemistry. However, the fidelity of Mg isotopes in geological records of carbonate minerals (e.g., calcite and dolomite) against burial metamorphism remains poorly constrained. Here we report our investigation on the Mg isotope systematics of a dolomitized Middle Triassic Geshan carbonate section in eastern China. Magnesium isotope analysis was complemented by analyses of Sr-C-O isotopic compositions, major and trace element concentrations, and petrographic and mineralogical features. Multiple lines of evidence consistently indicated that post-depositional diagenesis of carbonate minerals occurred to the carbonate rocks. Magnesium isotope compositions of the carbonate rocks closely follow a mixing trend between a high δ26Mg dolomite end member and a low δ26Mg calcite end member, irrespective of sample positions in the section and calcite/dolomite ratio in the samples. By fitting the measured Mg isotope data using a two-end member mixing model, an inter-mineral Δ26Mgdolomite-calcite fractionation of 0.72‰ was obtained. Based on the experimentally derived Mg isotope fractionation factors for dolomite and calcite, a temperature of 150–190°C was calculated to correspond to the 0.72‰ Δ26Mgdolomite-calcite fractionation. Such temperature range matches with the burial-thermal history of the local strata, making a successful case of Mg isotope geothermometry. Our results indicate that both calcite and dolomite had been re-equilibrated during burial metamorphism, and based on isotope mass balance of Mg, the system was buffered by dolomite in the section. Therefore, burial metamorphism may reset Mg isotope signature of calcite, and Mg isotope compositions in calcite should be dealt with caution in studies of carbonate rocks with thermal history. By contrast, Mg isotopes of dolomite are less prone to post-depositional resetting due to a number of properties including high Mg abundance and high thermodynamic stability, and Mg isotopes in dolomite may be a more robust recorder for original carbonate precipitates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. ...In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.
Polyacrylamide (PAM) is one of the most important water-soluble polymers that has been extensively applied in water treatment, drug delivery, and flexible electronic devices. The basic properties, ...e.g., microstructure, nanomechanics, and solubility, are deeply involved in the performance of PAM materials. Current research has paid more attention to the development and expansion of the macroscopic properties of PAM materials, and the study of the mechanism involved with the roles of water and ions on the properties of PAM is insufficient, especially for the behaviors of neutral amide side groups. In this study, single molecule force spectroscopy was combined with molecular dynamic (MD) simulations, atomic force microscope imaging, and dynamic light scattering to investigate the effects of monovalent ions on the nanomechanics and molecular conformations of neutral PAM (NPAM). These results show that the single-molecule elasticity and conformation of NPAM exhibit huge variation in different monovalent salt solutions. NPAM adopts an extended conformation in aqueous solutions of strong hydrated ion (acetate), while transforms into a collapse globule in the existence of weakly hydrated ion (SCN-). It is believed that the competition between intramolecular and intermolecular weak interactions plays a key role to adjust the molecular conformation and elasticity of NPAM. The competition can be largely influenced by the type of monovalent ions through hydration or a chaotropic effect. Methods utilized in this study provide a means to better understand the Hofmeister effect of ions on other macromolecules containing amide groups at the single-molecule level.
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IJS, KILJ, NUK, PNG, UL, UM
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