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Background: Previous structural neuroimaging studies linked cerebellar deficits to temporal lobe epilepsy (TLE). The functions of various cerebellar regions are increasingly being valued, and their changes in TLE patients warrant further in-depth investigation. In this study, we used the Spatially Unbiased Infratentorial (SUIT) toolbox with a new template to evaluate the cerebellar structural abnormalities in patients with TLE, and further explored the relationship between the changes of different cerebellar regions and cognition. Methods: Thirty-two patients with TLE were compared with 39 healthy controls (HC) matched according to age, gender, handedness, and education level. All participants underwent a high-resolution T1-weighted MRI scan on a 3.0 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the SUIT toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with TLE. Results: Compared with HC, TLE patients showed a significant reduction in the volume of gray matter in the Left lobule VI and white matter in the Right Crus II. In the TLE patient group, we conducted partial correlation analysis between the volumes of different cerebellar regions and cognitive rating scale scores, such as MMSE and MoCA. The volume of the Left lobule VI (GM) exhibited a positive correlation with the MMSE score, but no significant correlation was found with the MoCA score. On the other hand, there was no significant correlation observed between the volume of the Right Crus II (WM) and the two cognitive scale scores mentioned above. Furthermore, it was observed that the MMSE was more effective than the MoCA in identifying epilepsy patients with cognitive impairment. Conclusion: This study supported previous research indicating that temporal lobe epilepsy (TLE) is linked to structural changes in the cerebellum, specifically affecting the volume of both gray and white matter. These findings offer valuable insights into the neurobiology of TLE and hold potential to inform the development of enhanced diagnostic methods and more effective treatment approaches.
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Silicon/graphite composites show a high specific capacity and improved cycling stability. However, the intrinsic difference between silicon and graphite, such as unequal volume expansion and lithium-ion diffusion kinetics, causes persistent stress at the silicon/graphite interface and the expansion of the electrical isolation region. Herein, carbon nanotubes (CNTs) were successfully introduced into silicon/carbon composites via ball milling and spray drying, which effectively relieved the stress concentration at the direct contact interface and formed a three-dimensional conductive structure. In addition, CNTs and amorphous carbon acting as "lubricants" further improved the inherent differences between silicon and graphite. As a result, the Si/CNTs/G@C-1 anode increased the cycling performance and rate capability, with a reversible capacity of up to 465 mAh g-1 after 500 cycles at 1 A g-1 and superior rate performance of 523 mAh g-1 at 2 A g-1. It is believed that this strategy may provide a feasible preparation of large-scale high-content silicon-based nanocomposite anodes in lithium-ion batteries.
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This study delves into the formation of ferryl ions (Fe(IV)) within the Fe(II)/peroxydisulfate (PDS) process, a pivotal reaction in advanced oxidation processes (AOPs) aimed at organic pollutant removal. Our findings challenge the conventional view that Fe(IV) predominantly forms through oxygen transfer from PDS to Fe(II), revealing that sulfate radicals (SO4â¢-) play a crucial role in Fe(IV) generation. By employing competitive kinetics, the second-order rate constant for Fe(III) oxidation by SO4â¢- was quantified as 4.58 × 108 M-1 s-1. Factors such as the probe compound concentration, chloride presence, and iron species influence Fe(IV) generation, all of which were systematically evaluated. Additionally, the study explores Fe(IV) formation in various Fe(II)-activated AOPs, demonstrating that precursors like peroxymonosulfate and H2O2 can also directly oxidize Fe(II) to Fe(IV). Through experimental data, kinetic modeling, and oxygen-18 labeling experiments, this research offers a comprehensive understanding of the Fe(II)/PDS system, facilitating the optimization of AOPs for pollutant degradation. Finally, introducing HSO3- was proposed to shift the Fe(II)/PDS process from Fe(IV)-dominated to SO4â¢--dominated mechanisms, thereby enhancing pollutant removal efficiencies.
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Stroke is one of the major causes of disability and death worldwide. The lack of effective medical treatment for stroke heightens the need for new therapeutic targets. In this study, we obtained two microarray data sets from the Gene Expression Omnibus (GEO) database and identified differential genes (DEGs) between MCAO and control groups. Then, enrichment analysis of the DEGs was performed using DAVID and Metascape. The results show 27 DEGs shared between the two datasets. The functional enrichment analysis showed that these genes are mainly enriched in immune response, complement and coagulation cascades, apoptotic processes. The four hub genes (C1qc, Fcgr2b, C1qb, and Cd14) were screened out using the Cytoscape. Next, real-time PCR and Western blot analysis showed that expression of C1q and CD14 increased at 14 days after tMCAO. Furthermore, we took eight small molecule compounds with the lowest score using Cmap and studied their background characteristics. These results are built on a meta-analysis of data, which are generally accessible from the online space. Finally, we evaluated the protective effect of the rolipram through behavior tests after tMCAO, and results showed that the rolipram significantly attenuated neurobehavioral dysfunction at 14 days after brain ischemia. The present results provide novel insights into the biological process and potential therapeutic drugs involved in stroke.
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Computational Biology , Ischemic Stroke , Ischemic Stroke/genetics , Ischemic Stroke/drug therapy , Animals , Male , Mice , Gene Expression Profiling , Lipopolysaccharide Receptors/genetics , Lipopolysaccharide Receptors/metabolism , Neuroprotective Agents/therapeutic use , Complement C1q/genetics , Complement C1q/metabolism , Brain Ischemia/genetics , Brain Ischemia/drug therapyABSTRACT
Purpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response. Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared. Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation. Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.
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Adjuvants, Immunologic , Immunity, Cellular , Mice, Inbred C57BL , Nanoparticles , Vaccines, Subunit , Animals , Vaccines, Subunit/immunology , Vaccines, Subunit/administration & dosage , Nanoparticles/chemistry , Adjuvants, Immunologic/administration & dosage , Female , mRNA Vaccines , Mice , Herpesvirus 3, Human/immunology , Antibodies, Viral/blood , Immunization, Secondary/methods , Viral Envelope Proteins/immunology , Viral Envelope Proteins/administration & dosage , Herpes Zoster Vaccine/immunology , Herpes Zoster Vaccine/administration & dosage , LiposomesABSTRACT
A Ru(II)-catalyzed directed C-H amination of 1,2,3-benzotriazinones with azide compounds has been reported. The reaction has a wide substrate scope of organic azides with good results and represents a useful pathway to the construction of versatile heterocyclic amino products. In addition, the method can be used for the phthalazinones, highlighting the synthetic practicability of the strategy.
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A magnetic FenUiO-66 adsorbent was created to achieve high phosphate adsorption capacity. The incorporation of Fe3O4 facilitated the precipitation and growth of UiO-66 during crystallization, resulting in a shift towards a multilayer heterogeneous distribution of adsorption sites. The increased Fe3O4 content notably enhanced the magnetic properties of FenUiO-66, while negligibly affecting its adsorption performance. The Fe1.5UiO-66 demonstrated exceptional phosphate adsorption capacity (136.54 mg/g), outstanding selectivity, and sustained reusability, with an 80% removal efficiency after nine cycles of treating actual water. The mechanism of phosphate adsorption by FenUiO-66 involved electrostatic attraction, ligand exchange, and linker exchange. Notably, while linker exchange significantly contributed to high adsorption capacity, it resulted in irreversible damage to the FenUiO-66 crystal. These unequivocal findings will serve as a solid foundation for further research and underline the critical role of linkers in the process of phosphate adsorption.
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BACKGROUND: Bufonis Venenum (BV) is a traditional animal-based Chinese medicine with therapeutic effects against cancer. However, its clinical use is significantly restricted due to associated cardiovascular risks. BV's value in China's market is typically assessed based on "content priority," focusing on indicator components. However, these components of BV possess both antitumor activity and toxicity, and the correlation between the antitumor activity and toxicity of BV has not yet been elucidated. PURPOSE: This study employs an integrated multi-omics approach to identify bufadienolide Q-markers and explore the correlation between BV's antitumor activity and toxicity. The aim is to establish a more comprehensive method for BV's quality. METHODS: Normal zebrafish and HepG2 xenograft zebrafish were chosen as activity and toxicity evaluation models. Ultra-high performance liquid chromatography (UHPLC) coupled with a linear ion trap orbitrap (LTQ-Orbitrap) mass spectrometry was used to quantify eight batches of BV and key "toxic and effective" components were screened out. Transcriptomic and metabolomic analyses were performed to elucidate the regulatory mechanisms underlying the antitumor activity and cardiovascular toxicity of the key components in BV. RESULTS: Eight key "toxic and effective" compounds were identified: resibufogenin, cinobufagin, arenobufagin, bufotalin, bufalin, gamabufotalin, desacetylcinobufagin, and telocinobufagin. The findings showed that bufalin and cinobufagin interfered with calcium homeostasis through CaV and CaSR, induced cardiotoxicity, and upregulated CASP9 to activate myocardial cell apoptosis. However, desacetylcinobufagin exhibited greater potential in terms of anti-tumor effects. Combining the results of untargeted and targeted metabolomics revealed that desacetylcinobufagin could have a callback effect on differential lipids and correct abnormal energy and amino acid metabolism caused by cancer, similar to cinobufagin and bufalin. Microscale thermophoresis (MST) ligand binding measurements also showed that the binding of desacetylcinobufagin to GPX4 has a more potent ability to induce ferroptosis in tumor cells compared to cinobufagin. CONCLUSION: An innovative evaluation method based on the zebrafish was developed to investigate the relationship between the toxicity and efficacy of BV. This study identified toxicity and activity Q-markers and explored the mechanism between the two effects of BV. The research data could offer valuable insights into the efficacy of BV. Additionally, desacetylcinobufagin, an active ingredient with low toxicity, was found to enhance the quality of BV.
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The increasing demand for high-performance electrode materials in lithium-ion batteries has driven significant attention towards Nb2O5 due to its high working voltage, large theoretical capacity, environmental friendliness, and cost-effectiveness. However, inherent drawbacks such as poor electrical conductivity and sluggish electrochemical reaction kinetics have hindered its lithium storage performance. In this study, we introduced KCa2Nb3O10 into Nb2O5 to form a heterojunction, creating a built-in electric field to enhance the migration and diffusion of Li+, effectively promoting electrochemical reaction kinetics. Under the regulation of the built-in electric field, the charge transfer resistance of the KCa2Nb3O10/Nb2O5 anode decreased by 3.4 times compared to pure Nb2O5, and the Li+ diffusion coefficient improved by two orders of magnitude. Specifically, the KCa2Nb3O10/Nb2O5 anode exhibited a high capacity of 276 mAh g-1 under 1 C, retaining a capacity of 128 mAh g-1 even at 100 C. After 3000 cycles at 25 C, the capacity degradation was only 0.012% per cycle. Through combined theoretical calculations and experimental validation, it was found that the built-in electric field induced by the heterojunction interface contributed to an asymmetric charge distribution, thereby improving the rates of charge and ion migration within the electrode, ultimately enhancing the electrochemical performance of the electrode material. This study provides an effective approach for the rational design of high-performance electrode materials.
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Accurate assessment of Total Antioxidant Capacity (TAC) in food is crucial for evaluating nutritional quality and potential health benefits. This study aims to enhance the sensitivity and reliability of TAC detection through a dual-signal method, combining colorimetric and photothermal signals. Gold nanorods (AuNRs) were utilized to establish a dual-signal method duo to the colorimetric and photothermal properties. Fenton reaction can etch the AuNRs from the tips, as a result, a blue shift in the longitudinal LSPR absorption peak was obtained, leading to significant changes in color and photothermal effects, facilitating discrimination through both visual observation and thermometer measurements. In the presence of antioxidants, the Fenton reaction was suppressed or inhibited, protecting the AuNRs from etching. The colorimetric and photothermal signals were therefore positively correlated with TAC levels, enabling dual-signal detection of TAC. The linear range of AA was 4-100 µM in both colorimetry and photothermal modes, with detection limits of 1.60 µM and 1.38 µM, respectively. This dual-signal approach achieves low detection limits, enhancing precision and sensitivity. The method thus has the potential to act as a promising candidate for TAC detection in food samples, contributing to improved food quality and safety assessment.
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α-synuclein (α-syn) assembles into structurally distinct fibril polymorphs seen in different synucleinopathies, such as Parkinson's disease and multiple system atrophy. Targeting these unique fibril structures using chemical ligands holds diagnostic significance for different disease subtypes. However, the molecular mechanisms governing small molecules interacting with different fibril polymorphs remain unclear. Here, we investigated the interactions of small molecules belonging to four distinct scaffolds, with different α-syn fibril polymorphs. Using cryo-electron microscopy, we determined the structures of these molecules when bound to the fibrils formed by E46K mutant α-syn and compared them to those bound with wild-type α-syn fibrils. Notably, we observed that these ligands exhibit remarkable binding adaptability, as they engage distinct binding sites across different fibril polymorphs. While the molecular scaffold primarily steered the binding locations and geometries on specific sites, the conjugated functional groups further refined this adaptable binding by fine-tuning the geometries and binding sites. Overall, our finding elucidates the adaptability of small molecules binding to different fibril structures, which sheds light on the diagnostic tracer and drug developments tailored to specific pathological fibril polymorphs.
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Amyloid , Cryoelectron Microscopy , alpha-Synuclein , alpha-Synuclein/metabolism , alpha-Synuclein/chemistry , Amyloid/metabolism , Amyloid/chemistry , Ligands , Humans , Binding Sites , Protein Binding , Parkinson Disease/metabolism , MutationABSTRACT
BACKGROUND: Mitochondrial dysfunction and metabolic reprogramming can lead to the development and progression of hepatocellular carcinoma (HCC). Ferredoxin 1 (FDX1) is a small mitochondrial protein and recent studies have shown that FDX1 plays an important role in tumor cuproptosis, but its role in HCC is still elusive. In this study, we aim to investigate the expression and novel functions of FDX1 in HCC. METHODS: FDX1 expression was first analyzed in publicly available datasets and verified by immunohistochemistry, qRT-PCR and Western blot. In vitro and in vivo experiments were applied to explore the functions of FDX1. Non-targeted metabolomics and RNA-sequencing were used to determine molecular mechanism. mRFP-GFP-LC3 lentivirus transfection, Mito-Tracker Red and Lyso-Tracker Green staining, transmission electron microscopy, flow cytometry, JC-1 staining, etc. were used to analyze mitophagy or ROS levels. Hydrodynamic tail vein injection (HTVi) and patient-derived organoid (PDO) models were used to analyze effect of FDX1 overexpression. RESULTS: FDX1 expression is significantly downregulated in HCC tissues. FDX1 downregulation promotes HCC cell proliferation, invasion in vitro and growth, metastasis in vivo. In addition, FDX1 affects metabolism of HCC cells and is associated with autophagy. We then confirmed that FDX1 deficiency increases ROS levels, activates mitophagy and the PI3K/AKT signaling pathway in HCC cells. Interestingly, scavenging ROS attenuates the tumor-promoting role and mitophagy of FDX1 downregulation. The results of HTVi and PDO models both find that FDX1 elevation significantly inhibits HCC progression. Moreover, low FDX1 expression is associated with shorter survival and is an independent risk factor for prognosis in HCC patients. CONCLUSIONS: Our research had investigated novel functions of FDX1 in HCC. Downregulation of FDX1 contributes to metabolic reprogramming and leads to ROS-mediated activation of mitophagy and the PI3K/AKT signaling pathway. FDX1 is a potential prognostic biomarker and increasing FDX1 expression may be a potential therapeutic approach to inhibit HCC progression.
Subject(s)
Carcinoma, Hepatocellular , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Mitophagy , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Reactive Oxygen Species , Signal Transduction , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Mitophagy/genetics , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Mice , Animals , Cell Line, Tumor , Cell Proliferation , Disease Progression , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Down-Regulation , Mitochondria/metabolism , Mitochondria/genetics , MaleABSTRACT
Introduction: Allium is important vegetables and seasonings in China, Tibet is rich in unique resources of the genus Allium, but lacks development and utilization. Methods: We compared the biological features and comprehensively evaluating the quality of twelve germplasm resources of the genus Allium collected from Tibet. Results: The results revealed that nine germplasm resources were bolting and bloom normally except for SC015, SC019, and SC048, all twelve germplasm resources were able to vegetative growth. The individual differences in moisture, soluble sugar, and protein content among the twelve germplasm resources were relatively small, with pyruvic acid content ranging from 0.11 to 1.12 mg/g and a large variation coefficient. A total of 8 categories and 97 volatile compounds were detected in twelve germplasm resources, the majority possessed the highest proportions of aldehydes and organosulfur compounds, but there were certain differences between the different Allium species. Additionally, 11 to 16 types of free amino acids were present in all germplasm resources, proline exhibited the highest content. The total content of essential and non-essential amino acids in SC009 was the highest. Carbon (C) accounted for the largest proportion of all elements, and the contents of other mineral elements varied greatly among the different plants. Conclusion: In conclusion, combined with biological performance and comprehensive evaluation of quality, SC009 is the excellent germplasm resource suitable for growth and capable of reproduction with good quality. These results improved the exploitation and utilization of the genus Allium in Tibet, as well as provided germplasm resources for high-quality breeding of the genus Allium.
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Objectives: The objective of this study was to investigate the predictive value of erythrocyte distribution width-to-platelet ratio (RPR) combined with procalcitonin (PCT) on 28-day mortality in patients with sepsis. Methods: A total of 193 patients with sepsis admitted to the Affiliated Hospital of Southwest Medical University from January 2013 to January 2018 were selected as the study objects. Univariate and multivariate analyses were used to understand the indicators related to the 28-day prognosis of patients, and the ROC curve was further drawn. The Kaplan-Meier curve was used to evaluate the prognosis of patients. Results: A total of 193 patients were enrolled and divided into the survivor group (=156) and nonsurvivor group (=37) according to the prognosis within 28 days. The median age was 62.5 years, and 64.7% were males. Multivariate analysis showed that PCT and RPR were independent risk factors for 28-day prognosis in sepsis patients. The area under the ROC curve of PCT and RPR were 0.894 and 0.861, respectively, and the cutoff values were 27.04 and 0.12, respectively. Survival curve analysis showed that PCT and RPR were associated with the 28-day prognosis of patients, and the combination of PCT and RPR had a better predictive effect. Conclusions: PCT and RPR are independent predictors of sepsis prognosis. The combined application of PCT and RPR (PCT-RPR) can further improve the predictive performance and provide a reference for the clinical diagnosis, treatment, and prognosis evaluation of sepsis patients.
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Self-propelled nanomotors possess strong propulsion and penetration abilities, which can increase the efficiency of cellular uptake of nanoparticles and enhance their cytotoxicity against tumor cells, opening a new path for treating major diseases. In this study, the concept of driving nanomotors by alternately stretching and contracting a temperature-sensitive polymer (TS-P) chain is proposed. The TS-Ps are successfully linked to one side of Cu2-xSe@Au (CS@Au) nanoparticles to form a Janus structure, which is designated as Cu2-xSe@Au-polymer (CS@Au-P) nanomotors. Under near-infrared (NIR) light irradiation, Cu2-xSe nanoparticles generate photothermal effects that change the system temperature, triggering the alternation of the TS-P structure to generate a mechanical force that propels the motion of CS@Au-P nanomotors. The nanomotor significantly improved the cellular uptake of nanoparticles and enhanced their penetration and accumulation in tumor. Furthermore, the exceptional photothermal conversion efficiency of CS@Au-P nanomotors suggests their potential as nanomaterials for photothermal therapy (PTT). The prepared material exhibited good biocompatibility and anti-tumor effects both in vivo and in vitro, providing new research insights into the design and application of nanomotors in tumor therapy.
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BACKGROUND: Growing evidence suggests that immunotherapy has a positive effect on non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). However, it remains unclear which type of immunotherapy is more efficient. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of different immunotherapy types and determine the optimal option. METHOD: Four databases (PubMed, Cochrane Library databases, Embase, and Web of Science) and ClinicalTrial.gov were searched from inception until January 26, 2023. Randomized controlled trials (RCTs), prospective nonrandomized trials, or observational studies investigating NSCLC patients with BMs treated by immunotherapy were included. The quality of the included studies was evaluated using the Cochrane risk of bias (ROB) tool and the Newcastle-Ottawa Scale (NOS). The efficacy of immunotherapy on NSCLC patients with BMs was evaluated using frequentist random-effects NMA. RESULT: Eleven studies from 1560 citations, encompassing 1437 participants, were included in this NMA. Statistical analysis showed that pembrolizumab (SMD = 4.35, 95% CI [2.21, 6.60]) and nivolumab+ipilimumab (SMD = 3.81, 95% CI [1.21, 6.40]) could improve overall survival (OS). Pembrolizumab (SMD = 3.32, 95% CI [2.75, 3.90]) demonstrated better effects in improving the overall response rate (ORR). No significant difference in adverse event (AE) was observed between immunotherapy and chemotherapy. CONCLUSION: Our findings indicated that pembrolizumab was the most promising immunotherapy for NSCLC patients with BMs. Nivolumab+ipilimumab might be an alternative choice to improve OS. LIMITATION: Inconsistency tests were not performed because of the scarcity of direct comparison. Besides, high heterogeneity was observed in our NMA.
Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Network Meta-Analysis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/secondary , Humans , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/therapy , Brain Neoplasms/secondary , Brain Neoplasms/therapy , Immunotherapy/methods , Immunotherapy/adverse effects , Nivolumab/therapeutic use , Nivolumab/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Ipilimumab/therapeutic use , Ipilimumab/adverse effects , Ipilimumab/administration & dosage , Treatment Outcome , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effectsABSTRACT
The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.
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BACKGROUND CONTEXT: Prior studies have hypothesized that degenerative cervical spondylolisthesis (DCS) may be influenced by loss of stability due to disc, facet joint or cervical alignment. Meanwhile, it is commonly believed that the facet joints and paraspinal muscles participate in maintaining cervical spine stability. However, the impact of paraspinal muscle morphology and detailed facet joint features on DCS requires further investigation. PURPOSE: To compare facet joint characteristics, disc degeneration and muscle morphology between patients with DCS and those without DCS. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Consecutive surgical patients with degenerative cervical spondylosis from June 2016 to August 2023 were recruited. OUTCOME MEASURES: DCS was assessed on X-ray based on the translation distance. Cervical facet joint degeneration (CFD), the facet joint angle on the axial plane (FA-A) and the facet joint angle on the sagittal plane (FA-S), and facet joint tropism (FT) were measured on computerized tomography (CT). Paraspinal muscle degeneration was assessed on magnetic resonance imaging (MRI) including by the adjusted cross-sectional area (aCSA), the functional aCSA, the fat infiltration ratio (FI%). The Pfirrmann grade of the cervical disc was also evaluated. METHODS: Demographic and clinical data were compared in matched and unmatched cohorts. Disc degeneration, muscle degeneration and facet joint characteristics, including FA, FT and CFD, were compared between patients with and without DCS. Furthermore, the degree of CFD was compared with that of adjacent segments in both groups. Additionally, logistic regression was performed to determine independent risk factors for DCS. Finally, the receiver operating characteristic (ROC) curve, area under the curve (AUC) and cutoff value for the risk factors were calculated. RESULTS: A total of 431 surgical patients were propensity score matched for age, sex and BMI, and 146 patients were included in the final analysis, with 73 patients in the DCS group and 73 patients in the non-DCS group. DCS patients exhibited more severe CFD at C4/5 (segment with spondylolisthesis). Additionally, DCS was generally associated with more severe CFD, a more horizontal FA-S, more FT and worse paraspinal muscle health but similar disc degeneration. In addition, anterior spondylolisthesis was related to more severe CFD and decreased functional aCSA of the flexors and extensors. Finally, more severe CFD, a more horizontal FA-S and a higher FI% on deep extensor were revealed to be risk factors for DCS, with cutoff values of 1.5, 44.5Ì, and 37.1%, respectively. CONCLUSIONS: This study demonstrated that CFD, the FA and FT and parasipnal muscle degeneration were associated with DCS. And may provide novel insight into the pathogenesis and nature history of DCS and suggest the evolution of degeneration in the cervical spine.
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The design strategy of designing effective local electronic structures of active sites to improve the oxygen evolution reaction (OER) performance is the key to the success of sustainable alkaline water electrolysis processes. Herein, a series of manganese-doped nickel molybdate porous nanosheets with rich oxygen vacancies on the nickel foam (Mn-NiMoO4/NF PNSs) synthesized by the facile hydrothermal and following annealing routes are used as high-efficiency and robust catalysts towards OER. By virtue of unique nanosheets architectures, more exposed active site, rich oxygen vacancies, tailored electronic structures, and improved electrical conductivity induced by Mn incorporation, as predicted, the optimized Mn0.10-NiMoO4/NF PNSs catalyst exhibits superior the OER performance with a low overpotential of 211 mV at 10 mAâ§cm-2, a small Tafel slope of 41.7 mVâ§dec-1, and an excellent stability for 100 h operated at 100 mAâ§cm-2 in 1.0 M KOH electrolyte. The in-situ Raman measurements reveal the surface dynamic reconstruction. Besides, the results of density functional theory (DFT) calculations unveil the reaction mechanism. This study provides an effective design strategy via Mn incorporation to synergistically engineer electronic structures and oxygen vacancies of metal oxides for efficiently boosting the OER performance.
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The mean emotion from multiple facial expressions can be extracted rapidly and precisely. However, it remains debated whether mean emotion processing is automatic which can occur under no attention. To address this question, we used a passive oddball paradigm and recorded event-related brain potentials when participants discriminated the changes in the central fixation while a set of four faces was presented in the periphery. The face set consisted of one happy and three angry expressions (mean negative) or one angry and three happy expressions (mean positive), and the mean negative and mean positive face sets were shown with a probability of 20% (deviant) and 80% (standard) respectively in the sequence, or the vice versa. The cluster-based permutation analyses showed that the visual mismatch negativity started early at around 92 ms and was also observed in later time windows when the mean emotion was negative, while a mismatch positivity was observed at around 168-266 ms when the mean emotion was positive. The results suggest that there might be different mechanisms underlying the processing of mean negative and mean positive emotions. More importantly, the brain can detect the changes in the mean emotion automatically, and ensemble coding for multiple facial expressions can occur in an automatic fashion without attention.