Development of an environmentally foamed concrete incorporating red mud.

In this work, an efficient utilization method for red mud (RM) is provided through recycling RM as a mineral admixture for the preparation of foamed concrete (FC). Specifically, FC with different RM contents was prepared and investigated in terms of workability, mechanical properties, and hydration products. Results show that adding RM can significantly shorten the setting time, while it inevitably weakens the mechanical properties and fluidity of FC. However, the compressive strength of FC can still meet the strength predicted by the specification requirements when the RM replaces cement with 60% content (3d > 1.6 MPa). Most importantly, the heavy metals leaching from RM-based FC under the action of rain is still unclear, so a device for simulating stormwater runoff was designed to test the heavy metal leaching risk of RM-based FC. The findings indicate that the solidification of cement and the high basicity of the matrix can effectively reduce the leaching risk of heavy metals from RM in FC. Although the pore structure analysis demonstrates that the porosity and connected pores of FC will be deteriorated as RM concentration increases. The results are of great significance for the recycling of waste and the sustainable development of building materials.

PARP1 inhibition prevents oxidative stress in age-related hearing loss via PAR-Ca2+-AIF axis in cochlear strial marginal cells.

Studies have highlighted oxidative damage in the inner ear as a critical pathological basis for sensorineural hearing loss, especially the presbycusis. Poly(ADP-ribose) polymerase-1 (PARP1) activation responds to oxidative stress-induced DNA damage with pro-repair and pro-death effects resembling two sides of the same coin. PARP1-related cell death, known as parthanatos, whose underlying mechanisms are attractive research hotspots but remain to be clarified. In this study, we observed that aged rats showed stria vascularis degeneration and oxidative damage, and PARP1-dependent cell death was prominent in age-related cochlear disorganization and dysfunction. Based on oxidative stress model of primary cultured stria marginal cells (MCs), we revealed that upregulated PARP1 and PAR (Poly(ADP-ribose)) polymers are responsible for MCs oxidative death with high mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse, while inhibition of PARP1 ameliorated the adverse outcomes. Importantly, the PARylation of apoptosis-inducing factor (AIF) is essential for its conformational change and translocation, which subsequently causes DNA break and cell death. Concretely, the interaction of PAR and truncated AIF (tAIF) is the mainstream in the parthanatos pathway. We also found that the effects of AIF cleavage and release were achieved through calpain activity and mPTP opening, both of which could be regulated by PARP1 via mediation of mitochondria Ca2+ concentration. In conclusion, the PAR-Ca2+-tAIF signaling pathway in parthanatos contributes to the oxidative stress damage observed in MCs. Targeting PAR-Ca2+-tAIF might be a potential therapeutic strategy for the early intervention of presbycusis and other oxidative stress-associated sensorineural deafness.

Treatment of metastatic TFE3 microphthalmia transcription factor translocation renal cell carcinoma: a case report.

Background: Microphthalmia-associated transcription factor/transcription factor E (MiTF/TFE) translocation renal cell carcinoma (RCC) is a rare type of non-clear cell RCC (nccRCC), which is more common in females. Currently, there is no standardized treatment for advanced metastatic microphthalmia translocation RCC (MiT-RCC). The main treatment modalities include surgery, chemotherapy, immunotherapy, anti-vascular endothelial growth factor or vascular endothelial growth factor receptor (VEGFR) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and targeted therapy against the mesenchymal-epithelial transition (MET) factor signaling pathway. Case Description: We present the case of an 8-year-old male patient with hematuria and paroxysmal urinary pain. Based on tumor genetic testing results and targeted drug matching analysis, the patient underwent tumor biopsy, tumor radical surgery with vascular osteotomy, and cervicothoracic lymph node dissection. The patient was then treated with a combination of immunotherapy [sintilimab, a drug directed against programmed cell death receptor-1 (PD-1)] and VEGFR tyrosine kinase inhibitor (TKI) (from pazopanib to sunitinib). Throughout the 10 cycles of conventional chemotherapy (seven courses of sintilimab since the start of the third chemotherapy treatment), the patient's condition remained stable, with no tumor recurrence at the primary site. However, in the later stages, the patient developed a large amount of ascites, and the family requested discontinuation of treatment, ultimately leading to the patient's death. Conclusions: In this case report, we summarize the therapeutic strategy of a young patient with metastatic transcription factor E3 (TFE3) MiT-RCC. For this disease, early immunotherapy and the use of precision-targeted drugs may have a favorable impact on the survival prognosis of the patient but may still be of less benefit in children with advanced multiple metastases. Therefore, further research on tumor driver genes, among other treatment components, is urgently needed to improve precision therapy.

Ultralow-Loading Ruthenium-Iridium Fuel Cell Catalysts Dispersed on Zn-N Species-Doped Carbon.

Developing low-loading platinum-group-metal (PGM) catalysts is one of the key challenges in commercializing anion-exchange-membrane-fuel-cells (AEMFCs), especially for hydrogen oxidation reaction (HOR). Here, ruthenium-iridium nanoparticles being deposited on a Zn-N species-doped carbon carrier (Ru6Ir/Zn-N-C) are synthesized and used as an anodic catalyst for AEMFCs. Ru6Ir/Zn-N-C shows extremely high mass activity (5.87 A mgPGM -1) and exchange current density (0.92 mA cm-2), which is 15.1 and 3.9 times that of commercial Pt/C, respectively. Based on the Ru6Ir/Zn-N-C AEMFCs achieve a peak power density of 1.50 W cm-2, surpassing the state-of-the-art commercial PtRu catalysts and the power ratio of the normalized loading is 14.01 W mgPGM anode -1 or 5.89 W mgPGM -1 after decreasing the anode loading (87.49 µg cm-2) or the total PGM loading (0.111 mg cm-2), satisfying the US Department of Energy's PGM loading target. Moreover, the solvent and solute isotope separation method is used for the first time to reveal the kinetic process of HOR, which shows the reaction is influenced by the adsorption of H2O and OH-. The improvement of the hydrogen bond network connectivity of the electric double layer by adjusting the interfacial H2O structure together with the optimized HBE and OHBE is proposed to be responsible for the high HOR activity of Ru6Ir/Zn-N-C.

Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

P-limitation regulates the accumulation of soil aggregates organic carbon during the restoration of Pinus tabuliformis forest.

Artificial forest restoration is widely recognized as a crucial approach to enhance the potential of soil carbon sequestration. Nevertheless, there is still limited understanding regarding the dynamics of aggregate organic carbon (OC) and the underlying mechanisms driving these dynamics after artificial forest restoration. To address this gap, we studied Pinus tabuliformis forests and adjacent farmland in three recovery periods (13, 24 and 33 years) in the Loess Plateau region. Samples of undisturbed soil from the surface layer were collected and divided into three aggregate sizes: >2 mm (large aggregate), 0.25-2 mm (medium aggregate), and <0.25 mm (small aggregate). The aim was to examine the distribution of OC and changes in enzyme activity within each aggregate size. The findings revealed a significant increase in OC content for all aggregate sizes following the restoration of Pinus tabuliformis forests. After 33 years of recovery, the OC of large aggregates, medium aggregates and micro-aggregates increased by (30.23 ± 9.85)%, (36.71 ± 21.60)% and (37.88 ± 16.07)% respectively compared with that of farmland. Moreover, the restoration of Pinus tabuliformis forests lead to increased activity of hydrolytic enzymes and decreased activity of oxidative enzymes. It is noteworthy that the regulation of carbon in all aggregates is influenced by soil P-limitation. In large aggregates, P-limitation promotes the enhancement of hydrolytic enzyme activity, thereby facilitate OC accumulation. Conversely, in medium and small aggregates, P-limitation inhibits the increase in oxidative enzyme activity, resulting in OC accumulation. The results emphasize the importance of P-limitation in regulating OC accumulation during the restoration of Pinus tabulaeformis forest, in which large aggregates play a leading role.

Supporting equitable and responsible highway safety improvement funding allocation strategies - Why AI prediction biases matter.

The existing methodologies for allocating highway safety improvement funding closely rely on the utilization of crash prediction models. Specifically, these models produce predictions that estimate future crash hazard levels in different geographical areas, which subsequently support the future funding allocation strategies. In recent years, there is a burgeoning interest in applying artificial intelligence (AI)-based models to perform crash prediction tasks. Despite the remarkable accuracy of these AI-based crash prediction models, they have been observed to yield biased prediction outcomes across areas of different socioeconomic statuses. These biases are primarily attributed to the inherent measurement and representation biases of AI-based prediction models. More precisely, measurement bias arises from the selection of target variables to reflect crash hazard levels, while representation bias results from the issue of imbalanced number of samples representing areas with different socioeconomic statuses within the dataset. Consequently, these biased prediction outcomes have the potential to perpetuate an unfair allocation of funding resources, contributing to worsen social inequality over time. Drawing upon a real-world case study in North Carolina, this study designs an AI-based crash prediction model that utilizes previous sociodemographic and crash-related variables to predict future severe crash rate of each area to reflect the crash hazardous level. By incorporating a fair regression framework, this study endeavors to transform the crash prediction model to become both fair and accurate, aiming to support equitable and responsible safety improvement funding allocation strategies.

Autologous cryo-shocked neutrophils enable targeted therapy of sepsis via broad-spectrum neutralization of pro-inflammatory cytokines and endotoxins.

Background: Sepsis is a life-threatening disease characterized by multiple organ failure due to excessive activation of the inflammatory response and cytokine storm. Despite recent advances in the clinical use of anti-cytokine biologics, sepsis treatment efficacy and improvements in mortality remain unsatisfactory, largely due to the mechanistic complexity of immune regulation and cytokine interactions. Methods: In this study, a broad-spectrum anti-inflammatory and endotoxin neutralization strategy was developed based on autologous "cryo-shocked" neutrophils (CS-Neus) for the management of sepsis. Neutrophils were frozen to death using a novel liquid nitrogen "cryo-shock" strategy. The CS-Neus retained the source cell membrane structure and functions related to inflammatory site targeting, broad-spectrum inflammatory cytokines, and endotoxin (LPS) neutralizing properties. This strategy aimed to disable harmful pro-inflammatory functions of neutrophils, such as cytokine secretion. Autologous cell-based therapy strategies were employed to avoid immune rejection and enhance treatment safety. Results: In both LPS-induced sepsis mouse models and clinical patient-derived blood samples, CS-Neus treatment significantly ameliorated cytokine storms by removing inflammatory cytokines and endotoxin. The therapy showed notable anti-inflammatory therapeutic effects and improved the survival rate of mice. Discussion: The results of this study demonstrate the potential of autologous "cryo-shocked" neutrophils as a promising therapeutic approach for managing sepsis. By targeting inflammatory organs and exhibiting anti-inflammatory activity, CS-Neus offer a novel strategy to combat the complexities of sepsis treatment. Further research and clinical trials are needed to validate the efficacy and safety of this approach in broader populations and settings.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

Atomically Dispersed p-Block Aluminum-Based Catalysts for Oxygen Reduction Reaction.

The main group metals are commonly perceived as catalytically inert in the context of oxygen reduction reactions (ORR) due to the delocalized valence orbitals. Regulating the local environment and structure of metal center coordinated by nitrogen ligands (M-Nx) is a promising approach to accelerate catalytic dynamics. Herein, we, for the first time, report the atomically dispersed Al catalysts coordinated with N and C atoms for 4-electron ORR. The axial coordinated pyrrolyl N group (No) is constructed in the Al-N4-No moiety to regulate the p-band structure of Al center, effectively steering the local environment and structure of the square planar Al-N4 sites, which typically exhibit too strong interaction with ORR intermediates. The dynamic covalency competition of axial Al-No and Al-O bonding could endow the Al center with moderate hybridization between Al 3p orbital and O 2p orbital, alleviating the binding energy of ORR intermediates. The as-prepared Al-N4-No electrocatalyst exhibits excellent ORR activity, selectivity, and durability, along with the rapid kinetics as demonstrated by in situ Raman spectroscopy. This work offers a fundamental comprehension of the fine regulation on p-band and guides the rational design of main-group metal-based single atom catalysts.

Influence of waste polyethylene/WCO composite on physical and chemical properties of asphalt.

The use of waste polyethylene (WPE) in modified asphalt is frequently employed to reduce environmental pollution and improve asphalt properties. However, research has shown that using WPE alone as a modifier does not effectively enhance the low-temperature flexibility of asphalt. This study aims to investigate the potential of utilizing WPE and waste cooking oil (WCO) as composite modifiers to enhance the properties of virgin asphalt under both high and low-temperature conditions. The contents of WPE and WCO were used, and the preparation process for the modified asphalt was optimized through an orthogonal experiment. The experimental results indicate that the optimal formulation for the WPE/WCO composite modified asphalt (WPE/WCO-A) is obtained with an additive dosage of 8% and 1% by mass of virgin asphalt for WPE and WCO, respectively, as well as the maintenance process at a temperature of 140 °C and a duration of 2 h. Dynamic shear rheometer (DSR) results reveal that WPE/WCO composite modifier can greatly improve the high-temperature deformation resistance of asphalt. Bending beam rheometer (BBR) tests confirm that WPE adversely affects the low-temperature flexibility of asphalt, while the addition of WCO can improve it. WPE/WCO-A has even better low-temperature properties than virgin asphalt (VA). The Fourier transform infrared spectroscopy (FT-IR) results suggest that the composite modification of asphalt by WPE/WCO modifiers is dominated by physical action. Furthermore, the fluorescence microscopy test results demonstrate that WCO can promote WPE swelling in asphalt. This study offers a novel approach to improve the comprehensive properties of asphalt through composite modification using WPE and WCO.

GDF3 Protects Mice against Sepsis-Induced Acute Lung Injury by Suppression of Macrophage Pyroptosis.

Sepsis-induced ALI is marked by physiological, pathological, and biochemical irregularities caused by infection. Growth differentiation factor 3 (GDF3) is closely associated with the inflammatory response. Accumulating evidence has demonstrated a close relationship between GDF3 expression and the severity and prognosis of sepsis. However, the precise mechanism by which GDF3 protects against ALI induced by sepsis is still unclear. Following the intravenous administration of GDF3 in this research, we noted a rise in the survival rate, a decrease in the severity of histopathological damage as evaluated through HE staining, a decline in the count of inflammatory cells in bronchoalveolar lavage fluid (BALF), a reduction in the ratio of lung wet/dry (W/D) weight, and a noteworthy decrease in the levels of pro-inflammatory cytokines in both serum and BALF when compared to septic mice who underwent cecal ligation and puncture (CLP). These collective findings unequivocally indicate the protective effects of GDF3 against sepsis-induced ALI. In addition, the GDF3 group showed a significant reduction in the mRNA expression of Caspase-1 and NLRP3 when compared to the CLP group. Following this, we performed in vitro tests to confirm these discoveries and obtained comparable outcomes, wherein the administration of GDF3 notably decreased the levels of Caspase-1 and NLRP3 mRNA and protein in macrophages in comparison to the LPS group. Furthermore, GDF3 exhibited the capacity to reduce the secretion of inflammatory molecules from macrophages. By illuminating the mechanism by which GDF 3 regulates macrophages, this offers a theoretical basis for preventing and treating sepsis-induced ALI.

Photothermal therapy of tuberculosis using targeting pre-activated macrophage membrane-coated nanoparticles.

Conventional antibiotics used for treating tuberculosis (TB) suffer from drug resistance and multiple complications. Here we propose a lesion-pathogen dual-targeting strategy for the management of TB by coating Mycobacterium-stimulated macrophage membranes onto polymeric cores encapsulated with an aggregation-induced emission photothermal agent that is excitable with a 1,064 nm laser. The coated nanoparticles carry specific receptors for Mycobacterium tuberculosis, which enables them to target tuberculous granulomas and internal M. tuberculosis simultaneously. In a mouse model of TB, intravenously injected nanoparticles image individual granulomas in situ in the lungs via signal emission in the near-infrared region IIb, with an imaging resolution much higher than that of clinical computed tomography. With 1,064 nm laser irradiation from outside the thoracic cavity, the photothermal effect generated by these nanoparticles eradicates the targeted M. tuberculosis and alleviates pathological damage and excessive inflammation in the lungs, resulting in a better therapeutic efficacy compared with a combination of first-line antibiotics. This precise photothermal modality that uses dual-targeted imaging in the near-infrared region IIb demonstrates a theranostic strategy for TB management.

Four case reports of left anterior descending restenosis treated via the internal mammary artery: A literature review.

Objective: To analyse four cases of intervention via the internal mammary artery-anterior descending branch and provide and summarise the clinical treatment experience. Methods: The clinical data of four patients with distal restenosis of a left anterior descending artery (LAD) anastomosis after left internal mammary artery (LIMA)-LAD bypass surgery, who were admitted to the Gansu Institute of Cardiovascular Diseases between March 2013 and April 2022, were retrospectively analysed and reviewed together with the relevant literature. Results: Among the four patients, one was treated with intracoronary stenting via the internal mammary artery route, two were treated with intracoronary drug-coated balloon dilation (one of whom underwent fractional flow reserve [FFR] testing), and two underwent FFR testing (one of whom had a negative test result until the end of the procedure and continued to take medication during follow-up; the other patient had a positive result and further interventions). There were no deaths or postoperative complications in the group, and the patients were followed up for 4 months to 9 years, with good long-term outcomes. Conclusion: Percutaneous coronary intervention (PCI) via the internal mammary artery route is safe and effective, and patients with anastomotic distal stenosis or anastomotic stenosis of LAD bypass anastomosis may be considered for PCI via the internal mammary artery route.

Measuring the carbon shadow price of agricultural production: a regional-level nonparametric approach.

Climate change poses an urgent threat, necessitating the implementation of measures to actively reduce carbon emissions. The development of effective carbon emission reduction policies requires accurate estimation of the costs involved. In situations where actual prices of commodities are not available in the market, shadow pricing provides a useful method to calculate relative prices between commodities with and without price information. However, most studies focus on the industry, with few contributions on agricultural sector. This paper estimates the shadow price of carbon emissions in the agricultural sector from a provincial perspective, incorporating the impact of livestock into the calculation of carbon emissions and shadow pricing. Our findings indicate that ignoring livestock may overestimate CSP values. On the whole, the level of carbon shadow price is rising, indicating good green development in China's agricultural sector. The two types of convergence results show that there is sigma convergence and beta convergence in the western and central regions, demonstrating a significant improvement in environmental performance.

The chromatin accessibility dynamics during cell fate specifications in zebrafish early embryogenesis.

Chromatin accessibility plays a critical role in the regulation of cell fate decisions. Although gene expression changes have been extensively profiled at the single-cell level during early embryogenesis, the dynamics of chromatin accessibility at cis-regulatory elements remain poorly studied. Here, we used a plate-based single-cell ATAC-seq method to profile the chromatin accessibility dynamics of over 10 000 nuclei from zebrafish embryos. We investigated several important time points immediately after zygotic genome activation (ZGA), covering key developmental stages up to dome. The results revealed key chromatin signatures in the first cell fate specifications when cells start to differentiate into enveloping layer (EVL) and yolk syncytial layer (YSL) cells. Finally, we uncovered many potential cell-type specific enhancers and transcription factor motifs that are important for the cell fate specifications.

Multipath diffusion process and spatial accumulation simulation of Cd in lead-zinc mining areas.

This study combined process simulation and actual measurement to construct a multipath diffusion and spatial accumulation model of Cd in a typical lead-zinc mining area through accuracy and root mean square error(RMSE) analysis. The results indicated that (1) the diffusion of Cd was in a quadratic inverse proportional relationship with the distance from the pollution source within watershed. The average annual atmospheric Cd sedimentation in study area was 0.71 * 10-6 g and the contribution of runoff diffusion to Cd exceeded 80%. (2) With the increase in the concentration range of Cd content (k) carried by unit runoff sediment, the model accuracy and RMSE showed decreasing trends. However, when the lower and upper limits of k were 10% and 90%, the model accuracy reached 75%. (3) Two sub-watersheds with same dominant wind direction but different runoff directions were selected to verify the model accuracy, indicating that the model construction method can precisely simulate the spatial accumulation of Cd in similar mining areas. The results provide a scientific basis for the prevention of heavy metal diffusion in lead-zinc mines. Future research should focus on the migration pathways of heavy metals through vertical infiltration caused by rainfall to further optimise the model structure and accuracy.

Inhibition of mitochondrial function by approved drugs overcomes nasopharyngeal carcinoma chemoresistance.

The development of chemo-resistance in nasopharyngeal carcinoma (NPC) presents a significant therapeutic challenge, and its underlying mechanisms remain poorly understood. In our previous studies, we highlighted the association between isoprenylcysteine carboxylmethyltransferase (ICMT) and chemoresistance in NPC. In this current research, we revealed that both 5-FU and cisplatin-resistant NPC cells exhibited elevated mitochondrial function and increased expression of mitochondrial genes, independent of ICMT. Our investigations further showed that classic mitochondrial inhibitors, such as oligomycin, antimycin, and rotenone, were notably more effective in reducing viability in chemo-resistant NPC cells compared to parental cells. Moreover, we identified two antimicrobial drugs, tigecycline and atovaquone, recognized as mitochondrial inhibitors, as potent agents for decreasing chemo-resistant NPC cells by targeting mitochondrial respiration. Remarkably, tigecycline and atovaquone, administered at tolerable doses, inhibited chemo-resistant NPC growth in mouse models and extended overall survival rates. This work unveils the efficacy of mitochondrial inhibition as a promising strategy to overcome chemo-resistance in NPC. Additionally, our findings highlight the potential repurposing of clinically available drugs like tigecycline and atovaquone for treating NPC patients who develop chemoresistance.