PIM1 alleviated liver oxidative stress and NAFLD by regulating the NRF2/HO-1/NQO1 pathway.

AIMS: Non-alcoholic fatty liver disease (NAFLD) has risen as a significant global public health issue, for which vertical sleeve gastrectomy (VSG) has become an effective treatment method. The study sought to elucidate the processes through which PIM1 mitigates the advancement of NAFLD. The Pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) functions as a serine/threonine kinase. Bioinformatics analysis revealed that reduced PIM1 expression in NAFLD. METHODS: To further prove the role of PIM1 in NAFLD, an in-depth in vivo experiment was performed, in which male C57BL/6 mice were randomly grouped to receive a normal or high-fat diet for 24 weeks. They were operated or delivered the loaded adeno-associated virus which the PIM1 was overexpressed (AAV-PIM1). In an in vitro experiment, AML12 cells were treated with palmitic acid to induce hepatic steatosis. KEY FINDINGS: The results revealed that the VSG surgery and virus delivery of mice alleviated oxidative stress, and apoptosis in vivo. For AML12 cells, the levels of oxidative stress, apoptosis, and lipid metabolism were reduced via PIM1 upregulation. Moreover, ML385 treatment resulted in the downregulation of the NRF2/HO-1/NQO1 signaling cascade, indicating that PIM1 mitigates NAFLD by targeting this pathway. SIGNIFICANCE: PIM1 alleviated mice liver oxidative stress and NAFLD induced by high-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.

Development and external validation of dual online tools for prognostic assessment in elderly patients with high-grade glioma: a comprehensive study using SEER and Chinese cohorts.

Background: Elderly individuals diagnosed with high-grade gliomas frequently experience unfavorable outcomes. We aimed to design two web-based instruments for prognosis to predict overall survival (OS) and cancer-specific survival (CSS), assisting clinical decision-making. Methods: We scrutinized data from the SEER database on 5,245 elderly patients diagnosed with high-grade glioma between 2000-2020, segmenting them into training (3,672) and validation (1,573) subsets. An additional external validation cohort was obtained from our institution. Prognostic determinants were pinpointed using Cox regression analyses, which facilitated the construction of the nomogram. The nomogram's predictive precision for OS and CSS was gauged using calibration and ROC curves, the C-index, and decision curve analysis (DCA). Based on risk scores, patients were stratified into high or low-risk categories, and survival disparities were explored. Results: Using multivariate Cox regression, we identified several prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in elderly patients with high-grade gliomas, including age, tumor location, size, surgical technique, and therapies. Two digital nomograms were formulated anchored on these determinants. For OS, the C-index values in the training, internal, and external validation cohorts were 0.734, 0.729, and 0.701, respectively. We also derived AUC values for 3-, 6-, and 12-month periods. For CSS, the C-index values for the training and validation groups were 0.733 and 0.727, with analogous AUC metrics. The efficacy and clinical relevance of the nomograms were corroborated via ROC curves, calibration plots, and DCA for both cohorts. Conclusion: Our investigation pinpointed pivotal risk factors in elderly glioma patients, leading to the development of an instrumental prognostic nomogram for OS and CSS. This instrument offers invaluable insights to optimize treatment strategies.

Heterointerface engineering of NiFe (oxy)hydroxides/CNTs by in situ anchoring of sub-nano Au for efficient water oxidation.

Heterointerface engineering of NiFe (oxy)hydroxides is a prospective way of improving OER activity by the pre-catalysis of metal hydroxides accompanying the modulation of defects, but enhancement of the kinetics is controversial. Herein, in situ phase transformation of NiFe hydroxides was proposed and heterointerface engineering was optimized by sub-nano Au anchoring in simultaneously formed cation vacancies. Controllable size and concentrations of anchored sub-nano Au in the cation vacancies resulted in the modulation of the electronic structure at the heterointerface, and improved water oxidation activity was ascribed to the enhanced intrinsic activity and charge transfer rate. Here, Au/NiFe (oxy)hydroxide/CNTs with an Fe/Au molar ratio of 24 exhibited an overpotential of ∼236.3 mV at 10 mA cm-2 in 1.0 M KOH under simulated solar light irradiation, which is ∼19.8 mV lower than that without the consumption of solar energy. Spectroscopic studies reveal that the photo-responsive FeOOH in these hybrids and modulation of sub-nano Au anchoring in cation vacancies are favorable in improving solar energy conversion and suppressing photo-induced charge recombination.

Associations of Chinese visceral adiposity index and new-onset stroke in middle-aged and older Chinese adults: an observational study.

BACKGROUND: Stroke represents the second most prevalent contributor to global mortality. The Chinese Visceral Adiposity Index (CVAI) serves as an established metric for assessing visceral adiposity in the Chinese population, exhibiting prognostic capabilities. This investigation aimed to explore the association of CVAI and new-onset stroke among middle-aged and older Chinese populations. METHODS: The study employed data from the 2011 and 2018 China Health and Retirement Longitudinal Study (CHARLS) to assess the association of CVAI and the incidence of new-onset stroke. Utilizing a directed acyclic graph (DAG), 10 potential confounders were identified. Moreover, to explore the association between CVAI and new-onset stroke, three multifactor logistic regression models were constructed, accounting for the identified confounders and mitigating their influence on the findings. RESULTS: The study comprised 7070 participants, among whom 417 (5.9%) experienced new-onset strokes. After controlling for confounding variables, regression analysis suggested that the new-onset stroke's highest risk was linked to the fourth quartile (Q4) of the CVAI, with an odds ratio (OR) of 2.33 and a 95% confidence interval (CI) of 1.67-3.28. The decision tree analysis demonstrated a heightened probability of new-onset stroke among hypertensive individuals with a CVAI equal to or greater than 83, coupled with a C-reactive protein level no less than 1.1 mg/l. Age seemed to have a moderating influence on the CVAI and new-onset stroke association, exhibiting a more prominent interaction effect in participants under 60 years. CONCLUSIONS: In middle-aged and older Chinese populations, a linear relationship was discerned between CVAI and the probability of new-onset stroke. CVAI provides a predictive framework for stroke incidence in this demographic, laying the groundwork for more sophisticated risk prediction models that improve the precision and specificity of stroke risk evaluations.

Application of optical flow algorithm for drift correction in electron microscopy images.

Transmission electron microscopy (TEM) image drift correction has been effectively addressed using diverse approaches, including the cross correlation algorithm (CC) and other strategies. However, most of the strategies fall short of achieving sufficient accuracy or cannot strike a balance between time consumption and accuracy. The present study proposes a TEM image drift correction strategy that enhances accuracy without any additional time consumption. Unlike the CC algorithm that matches pixels one by one, our approach involves the extraction of multiple feature points from the first TEM image and then uses the Lucas-Kanade (LK) optical flow algorithm to calculate the optical field of these feature points in the subsequent TEM images. The LK algorithm is used to calculate the instantaneous velocity of these feature points, which can help track the movement of the TEM image series. In addition, a high-precision sub-pixel level correction strategy by the utilization of linear interpolation during the correction process is developed in this work. Experimental results confirm that this strategy offers superior accuracy in comparison with the CC algorithm and also is insensitive to the size of the image. Furthermore, we offer a semantic segmentation neural network for electron microscope image pre-processing, thereby expanding the applicability of our methodology.

Humidity Sensing Properties of (In+Nb) Doped HfO2 Ceramics.

(In+Nb) co-doped HfO2 ceramics, Hf1-x(In0.5Nb0.5)xO2 (x = 0, 0.005, 0.05, and 0.1), were prepared via a solid-state reaction method. Dielectric measurements reveal that the environmental moisture has an obvious influence on the dielectric properties of the samples. The best humidity response was found in a sample with the doping level of x = 0.005. This sample was therefore selected as a model sample to further investigate its humidity properties. In doing so, nanosized particles of Hf0.995(In0.5Nb0.5)0.005O2 were fabricated via a hydrothermal method and the humidity sensing properties of this material were studied in the relative humidity range of 11-94% based on impedance sensor. Our results show that the material exhibits a large impedance change of nearly four orders of magnitude over the tested humidity range. It was argued that the humidity-sensing properties were related to the defects created by doping, which improves the adsorption capacity for water molecules.

Identification and verification of the temozolomide resistance feature gene DACH1 in gliomas.

Introduction: The most important chemotherapy treatment for glioma patients is temozolomide. However, the development of drug resistance severely restricts the use of temozolomide. Therefore, elucidating the mechanism of temozolomide resistance, enhancing temozolomide sensitivity, and extending patient survival are urgent tasks for researchers. Methods: Temozolomide resistance hub differential genes were identified using differential analysis and protein interaction analysis from the GEO datasets (GSE100736 and GSE113510). These genes were further studied in glioma patients treated with temozolomide in the TCGA and CGGA databases. Patients from the mRNAseq_325 dataset (CGGA) were considered as the training set to construct a risk model for predicting glioma sensitivity to temozolomide, while patients from the mRNAseq_693 dataset (CGGA) and TCGA-GBM dataset were considered as the validation set to evaluate the performance of models. PCR and western blot were performed to determine the difference in expression of the feature gene DACH1 between glioma cells and temozolomide-resistant glioma cells. The alterations in the sensitivity of tumor cells to temozolomide were also observed after DACH1 was silenced. The patients were then divided into two groups based on the expression of DACH1, and the differences in patient survival rates, molecular pathway activation, and level of immune infiltration were compared. Results: Based on four signature genes (AHR, DACH1, MGMT, and YAP1), a risk model for predicting glioma sensitivity to temozolomide was constructed, and the results of timeROC in both the training and validation sets showed that the model had good predictive performance. The expression of the signature gene DACH1 was significantly downregulated in temozolomide-resistant cells, according to the results of the PCR and western blot experiments. The sensitivity of tumor cells to temozolomide was significantly reduced after DACH1 was silenced. DACH1 probably regulates temozolomide resistance in glioblastoma through the transcriptional dysregulation in cancer and ECM. Discussion: This study constructs a risk model that can predict glioma susceptibility to temozolomide and validates the function of the feature gene DACH1, which provides a promising target for the research of temozolomide resistance.

Unveiling the landscape of cytokine research in glioma immunotherapy: a scientometrics analysis.

Background: Cytokines modulate the glioma tumor microenvironment, influencing occurrence, progression, and treatment response. Strategic cytokine application may improve glioma immunotherapy outcomes. Gliomas remain refractory to standard therapeutic modalities, but immunotherapy shows promise given the integral immunomodulatory roles of cytokines. However, systematic evaluation of cytokine glioma immunotherapy research is absent. Bibliometric mapping of the research landscape, recognition of impactful contributions, and elucidation of evolutive trajectories and hot topics has yet to occur, potentially guiding future efforts. Here, we analyzed the structure, evolution, trends, and hotspots of the cytokine glioma immunotherapy research field, subsequently focusing on avenues for future investigation. Methods: This investigation conducted comprehensive bibliometric analyses on a corpus of 1529 English-language publications, from 1 January 2000, to 4 October 2023, extracted from the Web of Science database. The study employed tools including Microsoft Excel, Origin, VOSviewer, CiteSpace, and the Bibliometrix R package, to systematically assess trends in publication, contributions from various countries, institutions, authors, and journals, as well as to examine literature co-citation and keyword distributions within the domain of cytokines for glioma immunotherapy. The application of these methodologies facilitated a detailed exploration of the hotspots, the underlying knowledge structure, and the developments in the field of cytokines for glioma immunotherapy. Results: This bibliometric analysis revealed an exponential growth in annual publications, with the United States, China, and Germany as top contributors. Reviews constituted 17% and research articles 83% of total publications. Analysis of keywords like "interleukin-13," "TGF-beta," and "dendritic cells" indicated progression from foundational cytokine therapies to sophisticated understanding of the tumor microenvironment and immune dynamics. Key research avenues encompassed the tumor microenvironment, epidermal growth factor receptor, clinical trials, and interleukin pathways. This comprehensive quantitative mapping of the glioma immunotherapy cytokine literature provides valuable insights to advance future research and therapeutic development. Conclusion: This study has identified remaining knowledge gaps regarding the role of cytokines in glioma immunotherapy. Future research will likely focus on the tumor microenvironment, cancer vaccines, epidermal growth factor receptor, and interleukin-13 receptor alpha 2. Glioma immunotherapy development will continue through investigations into resistance mechanisms, microglia and macrophage biology, and interactions within the complex tumor microenvironment.

High-Throughput Preparation and Characterization of ZrMoTaW Refractory Multi-Principal Element Alloy Film.

In this work, high-throughput screening technology is applied to four-member refractory multi-principal element alloys (RMPEAs) films with high W content. The exploration of refractory metals such as W is strictly limited by the high melting temperature in this work; a multi-gradient deposition method was introduced to overcome this obstacle. By adjusting the power and distance from the target to the sample, component Zr11Mo11Ta25W53 with the best hardening performance was successfully obtained. The uniformity of the material library was analyzed from the perspectives of phase structure and micromorphology. With the help of Hume-Rothery theory and XRD analysis, it is shown that the film has a stable bcc structure. It is believed that film uniformity, nanoscale size, preferential orientation, surface roughness, and solution mechanism are the pivotal factors to improve hardness performance, especially for high W components. The hardness and modulus of elasticity can reach 20 GPa and 300 GPa, respectively, and the H/Er and H3/Er2 values are 0.067 and 0.065, showing the best wear resistance in many samples.

Synergistic Piezo-Photocatalysis of BiOCl/NaNbO3 Heterojunction Piezoelectric Composite for High-Efficient Organic Pollutant Degradation.

Piezo-photocatalytic technique is a new-emerging strategy to alleviate photoinduced charge recombination and thus enhance catalytic performance. The heterojunction construction engineering is a powerful approach to improve photocatalytic performance. Herein, the BiOCl/NaNbO3 with different molar ratios piezoelectric composites were successfully synthesized by hydrothermal methods. The piezo/photodegradation rate (k value) of Rhodamine B (RhB) for BiOCl/NaNbO3 (BN-3, 0.0192 min-1) is 2.2 and 5.2 times higher than that of BiOCl (0.0089 min-1) and NaNbO3 (0.0037 min-1), respectively. The enhanced performance of BN-3 composite can be attributed to the heterojunction construction between BiOCl and NaNbO3. In addition, the piezo/photodecomposition ratio of RhB for BN-3 (87.4%) is 8.8 and 2.2 times higher than that of piezocatalysis (9.9%) and photocatalysis (40.4%), respectively. We further investigated the mechanism of piezocatalysis, photocatalysis, and their synergy effect of BN-3 composite. This study favors an in-depth understanding of piezo-photocatalysis, providing a new strategy to improve the environmental pollutant remediation efficiency of piezoelectric composites.

IL-18 expression in clinical human pituitary adenoma.

BACKGROUND: IL-18 is known as an interferon-inducing factor that belongs to the IL-1 family, and is synthesized as an inactive precursor protein. OBJECTIVE: The present study aims to investigate the expression of IL-18, IL-18R, R and IL-18 binding protein (BP) mRNA in various types of human pituitary tumors, such as adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)-producing adenomas and non-function adenomas. METHODS: Pituitary adenoma tissues were obtained during the surgery of 41 patients: nine patients had ACTH-producing pituitary adenomas, nine patients had GH-producing pituitary adenomas, five patients had TSH-producing pituitary adenomas, seven patients had PRL-producing pituitary adenomas, and 11 patients had non-functioning adenomas. The mRNA expression levels of IL-18, IL-18BP, IL-18R and IL-18R were quantified using real-time quantitative PCR. RESULTS: The mRNA expression of IL-18 was significantly higher in ACTH-, GH- and PRL-producing adenomas, when compared to non-function tumors. Similarly, a significantly higher mRNA expression of IL-18BP and IL-18R was observed in ACTH-, GH- and PRL-producing adenomas, when compared with non-functional adenomas. In contrast, no upregulation of IL-18R mRNA was observed in any of the pituitary adenomas. CONCLUSIONS: The mRNA levels of IL-18, IL-18BP and IL-18R are significantly elevated in clinical pituitary tumors, such as ACTH-, GH- and PRL-producing adenomas, when compared to non-functional adenomas. These present results suggest the possibility that IL-18 may be involved in the pathogenesis of pituitary adenoma.

In situ synthesis of BiOCl nanosheets on three-dimensional hierarchical structures for efficient photocatalysis under visible light.

Assembling two-dimensional (2D) nanomaterials into three-dimensional (3D) hierarchical structures with novel functions is challenging and has attracted considerable attention. However, it is quite difficult to obtain complex 3D architectures of 2D materials with a uniform and intact structure using traditional methods, such as hydrothermal/solvothermal methods and direct precipitation methods. Here, we use butterfly wing scales as bio-templates to prepare 3D hierarchical BiOCl/Au wing scales for plasmonic photocatalysis. The as-prepared materials exhibit excellent photodegradation of rhodamine B (RhB) under visible light. The degradation rates of BiOCl microspheres and BiOCl and BiOCl/Au butterfly wing scales are 48.8%, 72.6%, and 93.8%, respectively, within 20-min illumination at the same loading capacities. This excellent performance of BiOCl/Au is attributed to the coupling of enhanced carrier separation efficiency and the effect of localized surface plasmon resonance (LSPR) aroused by 3D metallic structures. This study provides a relatively facile method to obtain complex 3D constructure of 2D materials. It also demonstrates a nature-led route to prepare highly efficient plasmonic photocatalysts.

Three-Dimensional High-Entropy Alloy-Polymer Composite Nanolattices That Overcome the Strength-Recoverability Trade-off.

Mechanical metamaterials with three-dimensional micro- and nanoarchitectures exhibit unique mechanical properties, such as high specific modulus, specific strength, and energy absorption. However, a conflict exists between strength and recoverability in nearly all the mechanical metamaterials reported recently, in particular the architected micro/nanolattices, which restricts the applications of these materials in energy storage/absorption and mechanical actuation. Here, we demonstrated the fabrication of three-dimensional architected composite nanolattices that overcome the strength-recoverability trade-off. The nanolattices under study are made up of a high-entropy alloy-coated (14.2-126.1 nm in thickness) polymer strut (approximately 260 nm in the characteristic size) fabricated via two-photon lithography and magnetron sputtering deposition. In situ uniaxial compression inside a scanning electron microscope showed that these composite nanolattices exhibit a high specific strength of 0.027 MPa/kg m3, an ultrahigh energy absorption per unit volume of 4.0 MJ/m3, and nearly complete recovery after compression under strains exceeding 50%, thus overcoming the traditional strength-recoverability trade-off. During multiple compression cycles, the composite nanolattices exhibit a high energy loss coefficient (converged value after multiple cycles) of 0.5-0.6 at a compressive strain beyond 50%, surpassing the coefficients of all the micro/nanolattices fabricated recently. Our experiments also revealed that, for a given unit cell size, the composite nanolattices coated with a high entropy alloy with thickness in the range of 14-50 nm have the optimal specific modulus, specific strength, and energy absorption per unit volume, which is related to a transition of the dominant deformation mechanism from local buckling to brittle fracture of the struts.

F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability.

Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETXF199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca2+ release from intracellular Ca2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETXF199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins.

Shear-induced mixing governs codeformation of crystalline-amorphous nanolaminates.

Deformation of ductile crystalline-amorphous nanolaminates is not well understood due to the complex interplay of interface mechanics, shear banding, and deformation-driven chemical mixing. Here we present indentation experiments on 10 nm nanocrystalline Cu-100 nm amorphous CuZr model multilayers to study these mechanisms down to the atomic scale. By using correlative atom probe tomography and transmission electron microscopy we find that crystallographic slip bands in the Cu layers coincide with noncrystallographic shear bands in the amorphous CuZr layers. Dislocations from the crystalline layers drag Cu atoms across the interface into the CuZr layers. Also, crystalline Cu blocks are sheared into the CuZr layers. In these sheared and thus Cu enriched zones the initially amorphous CuZr layer is rendered into an amorphous plus crystalline nanocomposite.