Lightweight single-phase Al-based complex concentrated alloy with high specific strength.

Developing light yet strong aluminum (Al)-based alloys has been attracting unremitting efforts due to the soaring demand for energy-efficient structural materials. However, this endeavor is impeded by the limited solubility of other lighter components in Al. Here, we propose to surmount this challenge by converting multiple brittle phases into a ductile solid solution in Al-based complex concentrated alloys (CCA) by applying high pressure and temperature. We successfully develop a face-centered cubic single-phase Al-based CCA, Al55Mg35Li5Zn5, with a low density of 2.40 g/cm3 and a high specific yield strength of 344×103 N·m/kg (typically ~ 200×103 N·m/kg in conventional Al-based alloys). Our analysis reveals that formation of the single-phase CCA can be attributed to the decreased difference in atomic size and electronegativity between the solute elements and Al under high pressure, as well as the synergistic high entropy effect caused by high temperature and high pressure. The increase in strength originates mainly from high solid solution and nanoscale chemical fluctuations. Our findings could offer a viable route to explore lightweight single-phase CCAs in a vast composition-temperature-pressure space with enhanced mechanical properties.

The impact of a lung-protective ventilation mode using transpulmonary driving pressure titrated positive end-expiratory pressure on the prognosis of patients with acute respiratory distress syndrome.

OBJECTIVE: This study aimed to assess the impact of a lung-protective ventilation strategy utilizing transpulmonary driving pressure titrated positive end-expiratory pressure (PEEP) on the prognosis [mechanical ventilation duration, hospital stay, 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP), survival outcome] of patients with Acute Respiratory Distress Syndrome (ARDS). METHODS: A total of 105 ARDS patients were randomly assigned to either the control group (n = 51) or the study group (n = 53). The control group received PEEP titration based on tidal volume [A tidal volume of 6 mL/kg, flow rate of 30-60 L/min, frequency of 16-20 breaths/min, constant flow rate, inspiratory-to-expiratory ratio of 1:1 to 1:1.5, and a plateau pressure ≤ 30-35 cmH2O. PEEP was adjusted to maintain oxygen saturation (SaO2) at or above 90%, taking into account blood pressure], while the study group received PEEP titration based on transpulmonary driving pressure (Esophageal pressure was measured as a surrogate for pleural pressure using an esophageal pressure measurement catheter connected to the ventilator. Tidal volume and PEEP were adjusted based on the observed end-inspiratory and end-expiratory transpulmonary pressures, aiming to maintain a transpulmonary driving pressure below 15 cmH2O during mechanical ventilation. Adjustments were made 2-4 times per day). Statistical analysis and comparison were conducted on lung function indicators [oxygenation index (OI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2)] as well as other measures such as heart rate, mean arterial pressure, and central venous pressure in two groups of patients after 48 h of mechanical ventilation. The 28-day mortality rate, duration of mechanical ventilation, length of hospital stay, and ventilator-associated pneumonia (VAP) incidence were compared between the two groups. A 60-day follow-up was performed to record the survival status of the patients. RESULTS: In the control group, the mean age was (55.55 ± 10.51) years, with 33 females and 18 males. The pre-ICU hospital stay was (32.56 ± 9.89) hours. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was (19.08 ± 4.67), and the mean Murray Acute Lung Injury score was (4.31 ± 0.94). In the study group, the mean age was (57.33 ± 12.21) years, with 29 females and 25 males. The pre-ICU hospital stay was (33.42 ± 10.75) hours. The mean APACHE II score was (20.23 ± 5.00), and the mean Murray Acute Lung Injury score was (4.45 ± 0.88). They presented a homogeneous profile (all P > 0.05). Following intervention, significant improvements were observed in PaO2 and OI compared to pre-intervention values. The study group exhibited significantly higher PaO2 and OI compared to the control group, with statistically significant differences (all P < 0.05). After intervention, the study group exhibited a significant increase in PaCO2 (43.69 ± 6.71 mmHg) compared to pre-intervention levels (34.19 ± 5.39 mmHg). The study group's PaCO2 was higher than the control group (42.15 ± 7.25 mmHg), but the difference was not statistically significant (P > 0.05). There were no significant differences in hemodynamic indicators between the two groups post-intervention (all P > 0.05). The study group demonstrated significantly shorter mechanical ventilation duration and hospital stay, while 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP) showed no significant differences. Kaplan-Meier survival analysis revealed a significantly better survival outcome in the study group at the 60-day follow-up (HR = 0.565, 95% CI: 0.320-0.999). CONCLUSION: Lung-protective mechanical ventilation using transpulmonary driving pressure titrated PEEP effectively improves lung function, reduces mechanical ventilation duration and hospital stay, and enhances survival outcomes in patients with ARDS. However, further study is needed to facilitate the wider adoption of this approach.

Association of immune deficiency with prognosis and corticosteroid treatment benefits among patients with acute respiratory distress syndrome.

Background: The role of corticosteroids in acute respiratory distress syndrome (ARDS) remains contentious. This study aims to investigate the prognostic significance of immune deficiency in patients with ARDS and its response to varying doses of corticosteroids. Methods: This single-center, retrospective cohort study enrolled 657 ARDS patients from January 24, 2008, to September 12, 2022, at Zhongshan Hospital of Fudan University, Shanghai, China. The patients were categorized into a discovery dataset (n=357) and a validation dataset (n=300), based on admission date. Further validation of the results in the validation dataset was used to enhance the credibility of the study conclusions. The study examined the association between immune deficiency and the patients' clinical characteristics, treatment measures, and prognosis. The primary outcome was 28-day mortality post disease onset. Data analysis was conducted from June 15, 2023 to August 15, 2023. Results: The initial risk factor analysis in the discovery dataset was primarily based on the clinical characteristics, and the results suggested that immune deficiency likely impacted overall survival among patients receiving different doses of corticosteroid treatment. Multivariate analysis identified immune deficiency as an independent prognostic factor for overall survival in both the discovery and validation datasets. The final analysis revealed that patients with mild to moderate ARDS [discovery dataset: hazard ratio (HR) =1.719; 95% confidence interval (CI): 1.229-2.406; log-rank test P=0.001; validation dataset: HR =1.874; 95% CI: 1.238-2.837; log-rank test P=0.002] or severe ARDS (discovery dataset: HR =1.874; 95% CI: 1.007-3.488; log-rank test P=0.04; validation dataset: HR =1.698; 95% CI: 1.042-2.768; log-rank test P=0.03) with immune deficiency exhibited lower overall survival rates. Patients with mild to moderate ARDS and immune deficiency showed greater benefits from low-dose corticosteroid treatment (HR =0.409; 95% CI: 0.249-0.671; P<0.001 for interaction), whereas those with severe ARDS and immune deficiency benefitted from both low and high-dose treatments (low corticosteroid: HR =0.299; 95% CI: 0.136-0.654; high corticosteroid: HR =0.458; 95% CI: 0.214-0.981; P=0.005 for interaction). Conclusions: Immune deficiency is an independent risk factor in ARDS. Incorporating it into the disease severity grading system based on the Berlin criteria may enhance personalized treatment approaches for ARDS patients. These findings warrant further validation through prospective, large-scale, multicenter randomized controlled trials (RCTs).

Mesenchymal stem cell-derived extracellular vesicles mitigate neuronal damage from intracerebral hemorrhage by modulating ferroptosis.

BACKGROUND: Hemorrhagic stroke is a devastating cerebrovascular event with a high rate of early mortality and long-term disability. The therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) for neurological conditions, such as intracerebral hemorrhage (ICH), has garnered considerable interest, has garnered considerable interest, though their mechanisms of action remain poorly understood. METHODS: EVs were isolated from human umbilical cord MSCs, and SPECT/CT was used to track the 99mTc-labeled EVs in a mouse model of ICH. A series of comprehensive evaluations, including magnetic resonance imaging (MRI), histological study, RNA sequencing (RNA-Seq), or miRNA microarray, were performed to investigate the therapeutic action and mechanisms of MSC-EVs in both cellular and animal models of ICH. RESULTS: Our findings show that intravenous injection of MSC-EVs exhibits a marked affinity for the ICH-affected brain regions and cortical neurons. EV infusion alleviates the pathological changes observed in MRI due to ICH and reduces damage to ipsilateral cortical neurons. RNA-Seq analysis reveals that EV treatment modulates key pathways involved in the neuronal system and metal ion transport in mice subjected to ICH. These data were supported by the attenuation of neuronal ferroptosis in neurons treated with Hemin and in ICH mice following EV therapy. Additionally, miRNA microarray analysis depicted the EV-miRNAs targeting genes associated with ferroptosis, and miR-214-3p was identified as a regulator of neuronal ferroptosis in the ICH cellular model. CONCLUSIONS: MSC-EVs offer neuroprotective effects against ICH-induced neuronal damage by modulating ferroptosis highlighting their therapeutic potential for combating neuronal ferroptosis in brain disorders.

Insights into the Acidic Site in Manganese Oxide in Terms of the Sulfur and Water Tolerance of Low-Temperature NH3 Selective Catalytic Reduction.

A critical constraint impeding the utilization of Mn-based oxide catalysts in NH3 selective catalytic reduction (NH3-SCR) is their inadequate resistance to water and sulfur. This vulnerability primarily arises from the propensity of SO2 to bind to the acidic site in manganese oxide, resulting in the formation of metal sulfate and leading to the irreversible deactivation of the catalyst. Therefore, gaining a comprehensive understanding of the detrimental impact of SO2 on the acidic sites and elucidating the underlying mechanism of this toxicity are of paramount importance for the effective application of Mn-based catalysts in NH3-SCR. Herein, we strategically modulate the acidity of the manganese oxide catalyst surface through the incorporation of Ce and Nb. Comprehensive analyses, including thermogravimetry, NH3 temperature-programmed desorption, in situ diffused reflectance infrared Fourier transform spectroscopy, and density functional theory calculations, reveal that SO2 exhibits a propensity for adsorption at strongly acidic sites. This mechanistic understanding underscores the pivotal role of surface acidity in governing the sulfur resistance of manganese oxide.

Olverembatinib combined with inotuzumab ozogamicin in relapsed refractory Philadelphia chromosome-positive acute lymphoblastic leukemia: A case report.

RATIONALE: Patients with relapsed and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation are at higher risk of relapse and have shorter overall survival. PATIENT CONCERNS: A 31-year-old man presented to the hematology department with intermittent fever and pancytopenia. He was diagnosed with Ph+ acute lymphoblastic leukemia and experienced 2 relapses during treatment. A drug-resistant T315I mutation was detected in the ABL kinase region during review. DIAGNOSES: Morphological examination of the bone marrow revealed approximately 93.5% lymphoid blast. Flow cytometric analysis confirmed the diagnosis of common B-cell ALL with the following phenotype: CD34, CD45dim, CD19, CD10, cCD79a, CD58dim, CD81dim, cTdT, HLA-DR, CD22dim, CXCR4, CD33dim, CD20, CD25, CD13, CD123. The examination of the ABL kinase region mutation suggested a T315I mutation. INTERVENTIONS: Olverembatinib, a third-generation TKI drug, was administered in combination with inotuzumab ozogamicin to treat the disease. OUTCOMES: The patient achieved morphological remission with a negative flow cytometry MRD test, and the quantification of BCR-ABL transcripts was 0% after 1 cycle of therapy. LESSONS: The third-generation TKI olverembatinib has been proven to be effective in CML patients with the T315I mutation, and it may also be effective in Ph+ acute lymphoblastic leukemia. Some new immune drugs have also shown improvement in the remission rate. Combination therapy with olverembatinib and Ino can achieve a complete molecular response in patients with relapsed and refractory Ph+ ALL with the T315I mutation.

Hepatic immune response of Coilia nasus infected with Anisakidae during ovarian development.

Anisakidae parasitism is a prevalent disease in wild populations of Coilia nasus, and can result in a significant loss of germplasm resources. To elucidate the immune response mechanism of C. nasus livers to Anisakidae infection, we collected and analysed 18 parasitic and 18 non-parasitic livers at gonadal developmental stages II, III, and V using histopathology, molecular biology and transcriptome methods. The hepatic portal area of the parasitic group exhibited an increase in the fibrous stroma and thickened hepatic arteries with positive Ly-6G staining, indicating inflammation and immune responses in the liver. Hepatocyte cytokine levels and the expression of liver function-related genes indicated that fish livers responded similarly to Anisakidae parasitism across different gonadal developmental stages. Oxidative stress indices showed more intense changes in stage II samples, whereas gene expression levels of Nrf2 and C3 were significantly increased in parasitised livers during stage III and V. Liver transcriptome sequencing identified 2575 differentially expressed genes between the parasitic and non-parasitic groups at the three gonadal developmental stages. KEGG pathway analysis showed that natural killer cell-mediated cytotoxicity, the NOD-like receptor signaling pathway, neutrophil extracellular trap formation, and other immune pathways were significantly enriched. Expression patterns varied across developmental stages, suggesting that innate immunity was primarily responsible for the liver immune response to Anisakidae infection during C. nasus migration, possibly related to water temperature changes or shifts in the gonadal developmental stage. In summary, this study investigated the immune response of C. nasus to Anisakidae parasitism under natural conditions, focusing on reproductive aspects and environmental changes, thereby establishing a foundation for elucidating the molecular mechanisms underlying the immune response of Anisakidae in C. nasus.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Vaccination with a Human Papillomavirus L2 Multimer Provides Broad Protection against 17 Human Papillomavirus Types in the Mouse Cervicovaginal Challenge Model.

Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11-88) from five human alphapapillomavirus genotypes in E. coli under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil®9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard in vitro and in vivo toxicology studies suggest a promising safety profile. These findings suggest LBTA's promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).

Ferulic Acid Inhibits Arsenic-Induced Colon Injury by Improving Intestinal Barrier Function.

The prolonged exposure to arsenic results in intestinal barrier dysfunction, which is strongly concerned with detrimental processes such as oxidative stress and the inflammatory response. Ferulic acid (FA), as a phenolic acid, possesses the capability to mitigate arsenic-induced liver damage and cardiotoxic effects dependent on inhibition of oxidative stress and inflammatory responses. FA can mitigate testicular tissue damage and alveolar epithelial dysfunction, the mechanism of which may rely on nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) activation and nuclear factor-kappa B (NF-κB) pathway blocking. Based on the antioxidant and anti-inflammatory properties of FA, we speculated that FA might have the potential to inhibit arsenic-induced intestinal damage. To confirm this scientific hypothesis, mice exposed to sodium arsenite were treated with FA to observe colonic histopathology and TJ protein levels, and oxidative stress and TJ protein levels in Caco-2 cells exposed to sodium arsenite were assessed after FA intervention. In addition, molecular levels of NF-κB and Nrf2/HO-1 pathway in colon and Caco-2 cells were also detected. As shown in our data, FA inhibited arsenic-induced colon injury, which was reflected in the improvement of mucosal integrity, the decrease of down-regulated expression of tight junction (TJ) proteins (Claudin-1, Occludin, and ZO-1) and the inhibition of oxidative stress. Similarly, treatment with FA attenuated the inhibitory effect of arsenic on TJ protein expression in Caco-2 cells. In addition to suppressing the activation of NF-κB pathway, FA retrieved the activation of Nrf2/HO-1 pathway in colon and intestinal epithelial cells induced by arsenic. In summary, our findings propose that FA has the potential to mitigate arsenic-induced intestinal damage by preserving the integrity of intestinal epithelial TJs and suppressing oxidative stress. These results lay the groundwork for the potential use of FA in treating colon injuries caused by arsenic.

Weakly-Supervised Segmentation-Based Quantitative Characterization of Pulmonary Cavity Lesions in CT Scans.

OBJECTIVE: Pulmonary cavity lesion is one of the commonly seen lesions in lung caused by a variety of malignant and non-malignant diseases. Diagnosis of a cavity lesion is commonly based on accurate recognition of the typical morphological characteristics. A deep learning-based model to automatically detect, segment, and quantify the region of cavity lesion on CT scans has potential in clinical diagnosis, monitoring, and treatment efficacy assessment. METHODS: A weakly-supervised deep learning-based method named CSA2-ResNet was proposed to quantitatively characterize cavity lesions in this paper. The lung parenchyma was firstly segmented using a pretrained 2D segmentation model, and then the output with or without cavity lesions was fed into the developed deep neural network containing hybrid attention modules. Next, the visualized lesion was generated from the activation region of the classification network using gradient-weighted class activation mapping, and image processing was applied for post-processing to obtain the expected segmentation results of cavity lesions. Finally, the automatic characteristic measurement of cavity lesions (e.g., area and thickness) was developed and verified. RESULTS: the proposed weakly-supervised segmentation method achieved an accuracy, precision, specificity, recall, and F1-score of 98.48%, 96.80%, 97.20%, 100%, and 98.36%, respectively. There is a significant improvement (P < 0.05) compared to other methods. Quantitative characterization of morphology also obtained good analysis effects. CONCLUSIONS: The proposed easily-trained and high-performance deep learning model provides a fast and effective way for the diagnosis and dynamic monitoring of pulmonary cavity lesions in clinic. Clinical and Translational Impact Statement: This model used artificial intelligence to achieve the detection and quantitative analysis of pulmonary cavity lesions in CT scans. The morphological features revealed in experiments can be utilized as potential indicators for diagnosis and dynamic monitoring of patients with cavity lesions.

Gavage Strategy for Decoction Formula of Traditional Chinese Medicine in Osteosarcoma Model Mice.

Decoction formula is the most commonly used dosage form in traditional Chinese medicine and applied in clinical practice for thousands of years by trans-oral administration, which is characterized by quick effect, easy absorption, and individualized treatment based on the specific syndromes of patients. The quality of the decoction formula is directly responsible for the clinical efficacy of traditional Chinese medicine; therefore, the standardization process of the decoction formula is important to avoid differences in decoction quality caused by subjective factors. Meanwhile, due to the limitations of performing clinical experiments, small animals bearing human diseases, such as mice, are often used in medical research to explore the therapeutic efficacy and comprehensive mechanisms of different interventions, including the decoction formula for traditional Chinese medicine. Consequently, as an important trans-oral administration method, the skilled gavage technique is particularly important to avoid potential esophagus damage and drug spillage, which will ensure an equal amount of medicine being administered to each model animal, leading to accurate experimental results. Furthermore, the standardized method of decoction formula preparation and skilled gavage strategy are necessary to protect animal welfare and minimize the number of animals used. Here, we reported a detailed standardization process of the decoction formula and gavage technique with Yiqi Jiedu decoction in osteosarcoma mouse model as an example. The efficacy was evaluated by the tumor volume. This protocol will maximize animal protection and improve the reliability of research data, therefore providing effective strategies for future investigating therapeutic efficacy and molecular mechanisms of decoction formula for traditional Chinese medicine in vivo.

Nerve growth factor alleviates arsenic-induced testicular injury by enhancing the function of Sertoli cells.

Sertoli cells (SCs) maintain testicular homeostasis and promote spermatogenesis by forming the blood-testis barrier (BTB) and secreting growth factors. The pro-proliferative and anti-apoptotic effects of nerve growth factor (NGF) on SCs have been proved previously. It is still unclear whether the damage effect of arsenic on testis is related to the inhibition of NGF expression, and whether NGF can mitigate arsenic-induced testicular damage by decreasing the damage of SCs induced by arsenic. Here, the lower expression of NGF in testes of arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) was observed through detection of Western blot and Real-time PCR. Subsequently, hematoxylin and eosin (HE) staining, Evans blue staining and transmission electron microscopy were used to evaluate the pathology, BTB permeability and tight junction integrity in testes of control mice, arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) and arsenic + NGF treated mice (freely drinking water containing 15 mg/l of NaAsO2 + intraperitoneal injection with 30 µg/kg of NGF), respectively. Evidently, spermatogenic tubule epithelial cells in testis of arsenic exposed mice were disordered and the number of cell layers was reduced, accompanied by increased permeability and damaged integrity of the tight junction in BTB, but these changes were less obvious in testes of mice treated with arsenic + NGF. In addition, the sperm count, motility and malformation rate of mice treated with arsenic + NGF were also improved. On the basis of the above experiments, the viability and apoptosis of primary cultured SCs treated with arsenic (10 µM NaAsO2) or arsenic + NGF (10 µM NaAsO2 + 100 ng/mL NGF) were detected by Cell counting kit-8 (CCK8) and transferase-mediated DUTP-biotin nick end labeling (TUNEL) staining, respectively. It is found that NGF ameliorated the decline of growth activity and the increase of apoptosis in arsenic-induced SCs. This remarkable biological effect that NGF inhibited the increase of Bax expression and the decrease of Bcl-2 expression in arsenic-induced SCs was also determined by western blot and Real-time PCR. Moreover, the decrease in transmembrane resistance (TEER) and the expression of tight junction proteins ZO-1 and occludin was mitigated in SCs induced by arsenic due to NGF treatment. In conclusion, the above results confirmed that NGF could ameliorate the injury effects of arsenic on testis, which might be related to the function of NGF to inhibit arsenic-induced SCs injury.

Pressure stabilizes ferrous iron in bridgmanite under hydrous deep lower mantle conditions.

Earth's lower mantle is a potential water reservoir. The physical and chemical properties of the region are in part controlled by the Fe3+/ΣFe ratio and total iron content in bridgmanite. However, the water effect on the chemistry of bridgmanite remains unclear. We carry out laser-heated diamond anvil cell experiments under hydrous conditions and observe dominant Fe2+ in bridgmanite (Mg, Fe)SiO3 above 105 GPa under the normal geotherm conditions corresponding to depth > 2300 km, whereas Fe3+-rich bridgmanite is obtained at lower pressures. We further observe FeO in coexistence with hydrous NiAs-type SiO2 under similar conditions, indicating that the stability of ferrous iron is a combined result of H2O effect and high pressure. The stability of ferrous iron in bridgmanite under hydrous conditions would provide an explanation for the nature of the low-shear-velocity anomalies in the deep lower mantle. In addition, entrainment from a hydrous dense layer may influence mantle plume dynamics and contribute to variations in the redox conditions of the mantle.

Study on Pyrolysis Characteristics of Phosphate Tailings under H2O Atmosphere.

The pyrolysis separation of calcium and magnesium from phosphate tailings is an important process due to its high-value resource utilization. In this paper, aiming to address the problems of high energy consumption, a slow decomposition rate and the low activity of decomposition products in the high-temperature pyrolysis of phosphate tailings, the medium-temperature pyrolysis of phosphate tailings under a H2O atmosphere was carried out, and the phase reconstruction and activation of pyrolysis process were discussed. The results showed that compared with N2, air and CO2 atmospheres, the pyrolysis process of phosphate tailings in a H2O atmosphere was changed from two stages to one stage, the starting decomposition temperature was reduced to 500 °C and the decomposition time was shortened to 30 min. The order of the influence of each factor on the pyrolysis of phosphate tailings was temperature > H2O pressure > holding time. Under the optimized pyrolysis conditions, the yield of CaMg(CO3)2 decomposition of phosphate tailings into MgO and CaO was 97.3% and 98.1%, respectively, and the reactivity of MgO was 31.6%. The distribution of Ca and Mg elements in the phosphate tailings after pyrolysis showed a negative correlation, and both of them no longer formed associated compounds; Ca mainly existed in the form of Ca(OH)2, Ca5(PO4)3F, CaSiO3 and CaF2, and Mg mainly existed in the form of MgO, MgF2 and Mg(OH)2.

Novel insight into the formation and improvement mechanism of physical property in fermented tilapia sausage by cooperative fermentation of newly isolated lactic acid bacteria based on microbial contribution.

Single starter can hardly elevate the gel property of fermented freshwater fish sausage. In this work, in order to improve the physical properties of tilapia sausage, two newly isolated strains of lactic acid bacteria (LAB), Latilactobacillus sakei and Pediococcus acidilactici were used for cooperative fermentation of tilapia sausage, followed by the revelation of their formation mechanisms during cooperative fermentation and their improvement mechanisms after comparison with natural fermentation. Both strains, especially L. sakei possessed good growth, acidification ability, and salt tolerance. The gel strength, hardness, springiness, chewiness, whiteness, acidification, and total plate count significantly elevated during cooperative fermentation with starters. Pediococcus, Acinetobacter, and Macrococcus were abundant before fermentation, while Latilactobacillus quickly occupied the dominant position after fermentation for 18-45 h with the relative abundance over 51.5 %. The influence of each genus on the physical properties was calculated through the time-dimension and group-dimension correlation networks. The results suggested that the increase of Latilactobacillus due to the good growth and metabolism of L. sakei contributed the most to the formation and improvement of gel strength, texture properties, color, acidification, and food safety of tilapia sausage after cooperative fermentation. This study provides a novel analysis method to quantitatively evaluate the microbial contribution on the changes of various properties. The cooperative fermentation of LAB can be used for tilapia sausage fermentation to improve its physical properties.

ALKBH5 modulates bone cancer pain in a rat model by suppressing NR2B expression.

Currently, the clinical treatment of bone cancer pain (BCP) is mainly related to its pathogenesis. The aim of the present study was to elucidate the potential role of N6-methyladenosine (m6A) in BCP in the spinal cord dorsal root ganglia (DRG) of BCP rats and its specific regulatory mechanism in N-methyl-d-aspartate receptor subunit 2B (NR2B). A rat model of BCP was constructed by tibial injection of Walker256 cells, and ALKBH5 and NR2B expression in the spinal cord DRG was detected. ALKBH5 was silenced or overexpressed in PC12 cells to verify the regulatory effect of ALKBH5 on NR2B. The specific mechanism underlying the interaction between ALKBH5 and NR2B was investigated using methylated RNA immunoprecipitation and dual-luciferase reporter gene assays. The results showed increased expression of m6A, decreased expression of ALKBH5, and increased expression of NR2B in the DRG of the BCP rat model. Overexpression of ALKBH5 inhibited NR2B expression, whereas interference with ALKBH5 caused an increase in NR2B expression. In NR2B, interference with ALKBH5 caused an increase in m6A modification, which caused an increase in NR2B. Taken together, ALKBH5 affected the expression of NR2B by influencing the stability of the m6A modification site of central NR2B, revealing that ALKBH5 is a therapeutic target for BCP.

Protecting effects of 4-octyl itaconate on neonatal hypoxic-ischemic encephalopathy via Nrf2 pathway in astrocytes.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI). METHODS: We used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes. RESULTS: We found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression. CONCLUSION: Our study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.