Dynamic changes of gut microbiota in mouse models of metabolic dysfunction-associated steatohepatitis and its transition to hepatocellular carcinoma.

Dysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction-associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH-associated hepatocellular carcinoma (MASH-HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA-16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH-HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH-fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

The interplay between gut microbiota and the brain-gut axis in Parkinson's disease treatment.

This study delves into the pivotal role of the gut microbiota and the brain-gut axis in Parkinson's Disease (PD), a neurodegenerative disorder with significant motor and non-motor implications. It posits that disruptions in gut microbiota-dysbiosis-and alterations in the brain-gut axis contribute to PD's pathogenesis. Our findings highlight the potential of the gastrointestinal system's early involvement in PD, suggested by the precedence of gastrointestinal symptoms before motor symptoms emerge. This observation implies a possible gut-originated disease pathway. The analysis demonstrates that dysbiosis in PD patients leads to increased intestinal permeability and systemic inflammation, which in turn exacerbates neuroinflammation and neurodegeneration. Such insights into the interaction between gut microbiota and the brain-gut axis not only elucidate PD's underlying mechanisms but also pave the way for novel therapeutic interventions. We propose targeted treatment strategies, including dietary modifications and fecal microbiota transplantation, aimed at modulating the gut microbiota. These approaches hold promise for augmenting current PD treatment modalities by alleviating both motor and non-motor symptoms, thereby potentially improving patient quality of life. This research underscores the significance of the gut microbiota in the progression and treatment of PD, advocating for an integrated, multidisciplinary approach to develop personalized, efficacious management strategies for PD patients, combining insights from neurology, microbiology, and nutritional science.

Maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion for pesticide delivery.

The salt-responsiveness of Pickering emulsions has significantly influenced their applications due to the large amount of salt on the surface of plant leaves. The present study provided a maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion (MACNCs-HIPPEs) that was stable to high-concentration salt and used for pesticide delivery. The stability of MACNCs-HIPPEs was investigated by adjusting the oil-phase volume fraction (φ), the MACNCs concentration, NaCl dosages, and the rheological properties. The high internal phase Pickering emulsion was obtained at φ of 0.8 and MACNCs concentration of 2wt% and showed excellent salt stability (NaCl, 1200 mM) and significant storage stability (60 days). The sustained release of imidacloprid (IMI) from imidacloprid-loaded MACNCs-HIPPEs (IMI@MACNCs-HIPPEs) showed a positive correlation to the temperature (15°C, 25°C, 35°C), indicating clear thermo-responsiveness of the prepared pesticide formulation. The test of spread and retention of IMI@MACNCs-HIPPEs on the leaf surface showed a significant advantage compared with the commercial IMI water dispersible granules (CG). All the advantages mentioned above showed the excellent potential of the MACNCs-HIPPEs in delivering lipophilic pesticides.

Where the cerebral infarction meets child, be vigilant about patent foramen ovale: a case report.

Background: While cerebral infarction in children is rare, its prognosis is poor, and this condition can seriously burden society and families. A correlation between patent foramen ovale (PFO) and ischemic stroke has not been found in pediatric patients. Case presentation: We report a 7-year-old boy who suffered from multiple cerebral infarctions. Subsequently, the patient was diagnosed with an abnormal shunt of PFO. He underwent PFO closure and was followed up for 1 year. The patient did not experience any further cerebral infarction. Conclusions: With this case report, we want to illustrate that although the incidence rate of ischemic cerebral infarction in adolescents is very low, we should not neglect the role of PFO. Therefore, after exclusion other causes of cerebral infarction, PFO should be considered in adolescent and adult stroke patients with adult closure criteria in the same way.

Investigating the Impact of SN-38 on Mouse Brain Metabolism Based on Metabolomics.

Purpose: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism. Methods: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice. Results: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P<0.05). Conclusion: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.

A Stepwise Interventional Strategy for the Removal of Adherent Totally Implanted Central Venous Access Port Catheters.

BACKGROUND: To evaluate the safety and effectiveness of a stepwise interventional strategy for the removal of adherent totally implanted central venous access port catheters, consisting of a guidewire support, antegrade coaxial separation, and retrograde coaxial separation with increasing technical complexity. METHODS: This study has a retrospective design. Thirty-two patients who had failed routine removal of the port catheter and were then transferred to interventional radiology between November 2017 and December 2023 were reviewed. The technical success and complication rates were recorded. RESULTS: All adherent catheters were successfully removed without catheter fragmentation, using guidewire support (n = 21), antegrade coaxial separation (n = 5), and retrograde coaxial separation (n = 6). The technical success rate was 100%, and no complications occurred. CONCLUSIONS: The proposed stepwise interventional strategy successfully removed adherent port catheters, with good safety and high effectiveness. It appeared to reduce the incidence of catheter fracture during the removal of adherent totally implantable central venous access port catheters.

Coupling Antisite Defect and Lattice Tensile Stimulates Facile Isotropic Li-Ion Diffusion.

Despite widely used as a commercial cathode, the anisotropic 1D channel hopping of lithium ions along the [010] direction in LiFePO4 prevents its application in fast charging conditions. Herein, an ultrafast nonequilibrium high-temperature shock technology is employed to controllably introduce the Li-Fe antisite defects and tensile strain into the lattice of LiFePO4. This design makes the study of the effect of the strain field on the performance further extended from the theoretical calculation to the experimental perspective. The existence of Li-Fe antisite defects makes it feasible for Li+ to move from the 4a site of the edge-sharing octahedra across the ab plane to 4c site of corner-sharing octahedra, producing a new diffusion channel different from [010]. Meanwhile, the presence of a tensile strain field reduces the energy barrier of the new 2D diffusion path. In the combination of electrochemical experiments and first-principles calculations, the unique multiscale coupling structure of Li-Fe antisite defects and lattice strain promotes isotropic 2D interchannel Li+ hopping, leading to excellent fast charging performance and cycling stability (high-capacity retention of 84.4% after 2000 cycles at 10 C). The new mechanism of Li+ diffusion kinetics accelerated by multiscale coupling can guide the design of high-rate electrodes.

Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored. METHODS: Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens. RESULTS: Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues. CONCLUSIONS: Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.

Rapid identification of lactic acid bacteria at species/subspecies level via ensemble learning of Ramanomes.

Rapid and accurate identification of lactic acid bacteria (LAB) species would greatly improve the screening rate for functional LAB. Although many conventional and molecular methods have proven efficient and reliable, LAB identification using these methods has generally been slow and tedious. Single-cell Raman spectroscopy (SCRS) provides the phenotypic profile of a single cell and can be performed by Raman spectroscopy (which directly detects vibrations of chemical bonds through inelastic scattering by a laser light) using an individual live cell. Recently, owing to its affordability, non-invasiveness, and label-free features, the Ramanome has emerged as a potential technique for fast bacterial detection. Here, we established a reference Ramanome database consisting of SCRS data from 1,650 cells from nine LAB species/subspecies and conducted further analysis using machine learning approaches, which have high efficiency and accuracy. We chose the ensemble meta-classifier (EMC), which is suitable for solving multi-classification problems, to perform in-depth mining and analysis of the Ramanome data. To optimize the accuracy and efficiency of the machine learning algorithm, we compared nine classifiers: LDA, SVM, RF, XGBoost, KNN, PLS-DA, CNN, LSTM, and EMC. EMC achieved the highest average prediction accuracy of 97.3% for recognizing LAB at the species/subspecies level. In summary, Ramanomes, with the integration of EMC, have promising potential for fast LAB species/subspecies identification in laboratories and may thus be further developed and sharpened for the direct identification and prediction of LAB species from fermented food.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of Shigella flexneri.

Pathogen infections including Shigella flexneri have posed a significant threat to human health for numerous years. Although culturing and qPCR were the gold standards for pathogen detection, time-consuming and instrument-dependent restrict their application in rapid diagnosis and economically less-developed regions. Thus, it is urgently needed to develop rapid, simple, sensitive, accurate, and low-cost detection methods for pathogen detection. In this study, an immunomagnetic beads-recombinase polymerase amplification-CRISPR/Cas12a (IMB-RPA-CRISPR/Cas12a) method was built based on a cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of S. flexneri in the laboratory. Firstly, S. flexneri was specifically captured and enriched by IMB (Shigella antibody-coated magnetic beads), and the genomic DNA was released and used as the template in the RPA reaction. Then, the RPA products were mixed with the pre-loaded CRISPR/Cas12a for fluorescence visualization. The results were observed by naked eyes under LED blue light, with a sensitivity of 5 CFU/mL in a time of 70 min. With no specialized equipment or complicated technical requirements, the IMB-RPA-CRISPR/Cas12a diagnostic method can be used for visual, rapid, and simple detection of S. flexneri and can be easily adapted to monitoring other pathogens.

TGF-ß1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma.

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-ß1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-ß1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-ß/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.

JCAD deficiency delayed liver regenerative repair through the Hippo-YAP signalling pathway.

BACKGROUND AND AIMS: Liver regeneration retardation post partial hepatectomy (PH) is a common clinical problem after liver transplantation. Identification of key regulators in liver regeneration post PH may be beneficial for clinically improving the prognosis of patients after liver transplantation. This study aimed to clarify the function of junctional protein-associated with coronary artery disease (JCAD) in liver regeneration post PH and to reveal the underlying mechanisms. METHODS: JCAD knockout (JCAD-KO), liver-specific JCAD-KO (Jcad△Hep) mice and their control group were subjected to 70% PH. RNA sequencing was conducted to unravel the related signalling pathways. Primary hepatocytes from KO mice were treated with epidermal growth factor (EGF) to evaluate DNA replication. Fluorescent ubiquitination-based cell cycle indicator (FUCCI) live-imaging system was used to visualise the phases of cell cycle. RESULTS: Both global and liver-specific JCAD deficiency postponed liver regeneration after PH as indicated by reduced gene expression of cell cycle transition and DNA replication. Prolonged retention in G1 phase and failure to transition over the cell cycle checkpoint in JCAD-KO cell line was indicated by a FUCCI live-imaging system as well as pharmacologic blockage. JCAD replenishment by adenovirus reversed the impaired DNA synthesis in JCAD-KO primary hepatocyte in exposure to EGF, which was abrogated by a Yes-associated protein (YAP) inhibitor, verteporfin. Mechanistically, JCAD competed with large tumour suppressor 2 (LATS2) for WWC1 interaction, leading to LATS2 inhibition and thereafter YAP activation, and enhanced expression of cell cycle-associated genes. CONCLUSION: JCAD deficiency led to delayed regeneration after PH as a result of blockage in cell cycle progression through the Hippo-YAP signalling pathway. These findings uncovered novel functions of JCAD and suggested a potential strategy for improving graft growth and function post liver transplantation. KEY POINTS: JCAD deficiency leads to an impaired liver growth after PH due to cell division blockage. JCAD competes with LATS2 for WWC1 interaction, resulting in LATS2 inhibition, YAP activation and enhanced expression of cell cycle-associated genes. Delineation of JCADHippoYAP signalling pathway would facilitate to improve prognosis of acute liver failure and graft growth in living-donor liver transplantation.

Analysis of Microbial Diversity and Community Structure of Rhizosphere Soil of Three Astragalus Species Grown in Special High-Cold Environment of Northwestern Yunnan, China.

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

FAM20A-Associated Amelogenesis Imperfecta: Gene Variants with Functional Verification and Histological Features.

OBJECTIVE: To investigate FAM20A gene variants and histological features of amelogenesis imperfecta and to further explore the functional impact of these variants. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to identify pathogenic gene variants in three Chinese families with amelogenesis imperfecta. Bioinformatics analysis, in vitro histological examinations and experiments were conducted to study the functional impact of gene variants, and the histological features of enamel, keratinised oral mucosa and dental follicle. RESULTS: The authors identified two nonsense variants c. 406C > T (p.Arg136*) and c.826C > T (p.Arg176*) in a compound heterozygous state in family 1, two novel frameshift variants c.936dupC (p.Val313Argfs*67) and c.1483dupC (p.Leu495Profs*44) in a compound heterozygous state in family 2, and a novel homozygous frameshift variant c.530_531insGGTC (p.Ser178Valfs*21) in family 3. The enamel structure was abnormal, and psammomatoid calcifications were identified in both the gingival mucosa and dental follicle. The bioinformatics and subcellular localisation analyses indicated these variants to be pathogenic. The secondary and tertiary structure analysis speculated that these five variants would cause structural damage to FAM20A protein. CONCLUSION: The present results broaden the variant spectrum and clinical and histological findings of diseases associated with FAM20A, and provide useful information for future genetic counselling and functional investigation.

Accelerating the Phase Formation Kinetics of Alluaudite Sodium Iron Sulfate Cathodes via Ultrafast Thermal Shock.

Alluaudite sodium iron sulfate (NFS) exhibits great potential for use in sodium-ion battery cathodes due to its elevated operating potential and abundant element reserves. However, conventional solid-state methods demonstrate a low heating/cooling rate and sluggish reaction kinetics, requiring a long thermal treatment to effectively fabricate NFS cathodes. Herein, we propose a thermal shock (TS) strategy to synthesize alluaudite sodium iron sulfate cathodes using either hydrous or anhydrous raw materials. The analysis of the phase formation process reveals that TS treatment can significantly facilitate the removal of crystal water and decomposition of the intermediate phase Na2Fe(SO4)2 in the hydrous precursor. In the case of the anhydrous precursor, the kinetics of the combination reaction between Na2SO4 and FeSO4 can be also accelerated by TS treatment. Consequently, pure NFS phase formation can be completed after a substantially shorter time of post-sintering, thereby saving significant time and energy. The TS-treated NFS cathode derived from hydrous precursor exhibits higher retention after 200 cycles at 1C and better rate capability than the counterpart prepared by conventional long-term tube furnace sintering, demonstrating the great potential of this novel strategy.

Role of C/EBP Homologous Protein in Vascular Stenosis After Carotid Artery Injury.

The study aims to explore the fluctuating expression of C/EBP Homologous Protein (CHOP) following rat carotid artery injury and its central role in vascular stenosis. Using in vivo rat carotid artery injury models and in vitro ischemia and hypoxia cell models employing human aortic endothelial cells (HAECs) and vascular smooth muscle cells (T/G HA-VSMCs), a comprehensive investigative framework was established. Histological analysis confirmed intimal hyperplasia in rat models. CHOP expression in vascular tissues was assessed using Western blot and immunohistochemical staining, and its presence in HAECs and T/G HA-VSMCs was determined through RT-PCR and Western blot. The study evaluated HAEC apoptosis, inflammatory cytokine secretion, cell proliferation, and T/G HA-VSMCs migration through Western blot, ELISA, CCK8, and Transwell migration assays. The rat carotid artery injury model revealed substantial fibrous plaque formation and vascular stenosis, resulting in an increased intimal area and plaque-to-lumen area ratio. Notably, CHOP is markedly elevated in vessels of the carotid artery injury model compared to normal vessels. Atorvastatin effectively mitigated vascular stenosis and suppresses CHOP protein expression. In HAECs, ischemia and hypoxia-induced CHOP upregulation, along with heightened TNFα, IL-6, caspase3, and caspase8 levels, while reducing cell proliferation. Atorvastatin demonstrated a dose-dependent suppression of CHOP expression in HAECs. Downregulation of CHOP or atorvastatin treatment led to reduced IL-6 and TNFα secretion, coupled with augmented cell proliferation. Similarly, ischemia and hypoxia conditions increased CHOP expression in T/G HA-VSMCs, which was concentration-dependently inhibited by atorvastatin. Furthermore, significantly increased MMP-9 and MMP-2 concentrations in the cell culture supernatant correlated with enhanced T/G HA-VSMCs migration. However, interventions targeting CHOP downregulation and atorvastatin usage curtailed MMP-9 and MMP-2 secretion and suppressed cell migration. In conclusion, CHOP plays a crucial role in endothelial injury, proliferation, and VSMCs migration during carotid artery injury, serving as a pivotal regulator in post-injury fibrous plaque formation and vascular remodeling. Statins emerge as protectors of endothelial cells, restraining VSMCs migration by modulating CHOP expression.

A Comprehensive Prognostic and Immune Infiltration Analysis of RBM4 in Pan-Cancer.

BACKGROUND: Aberrant splicing has been closely associated with human cancer, though the precise underlying mechanisms linking the two remain not fully understood. Investigating the role of splicing factors in cancer progression may aid in the development of targeted therapies for dysregulated splicing, thereby opening up new avenues for cancer treatment. RNA-binding motif 4 (RBM4) has been identified as a critical participant in the condensin II complex, which is involved in chromosome condensation and stabilization during mitosis. Its significance in tumors is currently gaining attention. The genetic characteristics of RBM4 suggest its potential to elucidate the malignant progression of tumors in a broader context, encompassing various types of cancer, known as pan-cancer. METHODS: This study aims to comprehensively explore the potential function of RBM4 in pan-cancer by leveraging existing databases such as The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). RESULTS: RBM4 is found to be overexpressed in almost all tumors and exhibits significant prognostic and diagnostic efficacy. The correlation between RBM4 and immune signatures, including immune cell infiltration and immune checkpoint genes, indicates that RBM4 could serve as a guiding factor for immunotherapy. CONCLUSIONS: As a member of the pan-oncogene, RBM4 has the potential to become a biomarker and therapeutic target for various malignant tumors, offering novel possibilities for precision medicine.