Tuning Two-Dimensional Phthalocyanine Dual Site Metal-Organic Framework Catalysts for the Oxygen Reduction Reaction.

Metal-organic frameworks (MOFs) offer an interesting opportunity for catalysis, particularly for metal-nitrogen-carbon (M-N-C) motifs by providing an organized porous structural pattern and well-defined active sites for the oxygen reduction reaction (ORR), a key need for hydrogen fuel cells and related sustainable energy technologies. In this work, we leverage electrochemical testing with computational models to study the electronic and structural properties in the MOF systems and their relationship to ORR activity and stability based on dual transitional metal centers. The MOFs consist of two M1 metals with amine nodes coordinated to a single M2 metal with a phthalocyanine linker, where M1/M2 = Co, Ni, or Cu. Co-based metal centers, in particular Ni-Co, demonstrate the highest overall activity of all nine tested MOFs. Computationally, we identify the dominance of Co sites, relative higher importance of the M2 site, and the role of layer M1 interactions on the ORR activity. Selectivity measurements indicate that M1 sites of MOFs, particularly Co, exhibit the lowest (<4%), and Ni demonstrates the highest (>46%) two-electron selectivity, in good agreement with computational studies. Direct in situ stability characterization, measuring dissolved metal ions, and calculations, using an alkaline stability metric, confirm that Co is the most stable metal in the MOF, while Cu exhibits notable instability at the M1. Overall, this study reveals how atomistic coupling of electronic and structural properties affects the ORR performance of dual site MOF catalysts and opens new avenues for the tunable design and future development of these systems for practical electrochemical applications.

[Differences of Three Methods in Determining Ozone Sensitivity in Nanjing].

In recent years， ozone （O3） has become an increasingly important air pollutant in China. Identifying the sensitivity of O3 to the precursors volatile organic compounds （VOCs） and nitrogen oxides （NOx） can help make effective abatement strategies. This study compared three methods for determining O3-VOCs-NOx sensitivity： simulated photochemical indicator values and sensitivity coefficients derived from a three-dimensional air quality model and an observation-based model （OBM）， with a case study involving an O3 pollution event that occurred in Nanjing in late July 2017. The results showed that O3 sensitivity based on the photochemical indicator and sensitivity coefficients demonstrated similar spatial variations （over 50% of the grid cells of Nanjing exhibiting identical O3 sensitivity）. However， sensitivity coefficients identified a larger number of areas within a transitional O3 sensitivity regime， as opposed to the VOCs- or NOx-limited regime identified by the photochemical indicator. The determination of the latter was affected by the adopted threshold values. The OBM relied on the quality of the observational data. For example， positive biases in observed NO2 could lead to an underestimation of O3 sensitivity to NOx with the OBM. During the high pollution period， the three methods exhibited significant disparities. The photochemical indicator tended to suggest the VOCs-limited condition， whereas the OBM and sensitivity coefficients indicated the NOx-limited or transitional regimes.

Methylation changes of liver DNA during the formation of gallstones.

Aim: To explore the overall methylation changes in liver tissues during the formation of gallstones, as well as the key pathways and genes involved in the process. Methods: Reduced-representation bisulfite sequencing and RNA sequencing were conducted on the liver tissues of mice with gallstones and control normal mice. Results: A total of 8705 differentially methylated regions in CpG and 1410 differentially expressed genes were identified. The joint analysis indicated that aberrant DNA methylation may be associated with dysregulated gene expression in key pathways such as cholesterol metabolism and bile secretion. Conclusion: We propose for the first time that methylation changes in some key pathway genes in liver tissue may be involved in the formation of gallstones.

Neobractatin induces pyroptosis of esophageal cancer cells by TOM20/BAX signaling pathway.

BACKGROUND: Emerging evidence suggests that pyroptosis, a form of programmed cell death, has been implicated in cancer progression. The involvement of specific proteins in pyroptosis is an area of growing interest. TOM20, an outer mitochondrial membrane protein, has recently garnered attention for its potential role in pyroptosis. Our previous study found that NBT could induce pyroptosis by ROS/JNK pathway in esophageal cancer cells. PURPOSE: This study aims to investigate whether NBT induces pyroptosis and verify whether such effects are involved in up-regulation of TOM20 in esophageal cancer cells. METHODS: The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) was used to analyze the clinical significance of GSDME in esophageal cancer. MTT assay, morphological observation and Western blot were performed to verify the roles of TOM20 and BAX in NBT-induced pyroptosis after CRISPR-Cas9-mediated knockout. Immunofluorescence was used to determine the subcellular locations of BAX and cytochrome c. MitoSOX Red was employed to assess the mitochondrial reactive oxygen species (ROS) level. KYSE450 and TOM20 knockout KYSE450-/- xenograft models were established to elucidate the mechanisms involved in NBT-induced cell death. RESULTS: In this study, NBT effectively upregulated the expression of TOM20 and facilitated the translocation of BAX to mitochondria, which promoted the release of cytochrome c from mitochondria to the cytoplasm, leading to the activation of caspase-9 and caspase-3, and finally induced pyroptosis. Knocking out TOM20 by CRISPR-Cas9 significantly inhibited the expression of BAX and the downstream BAX/caspase-3/GSDME pathway, which attenuated NBT-induced pyroptosis. The elevated mitochondrial ROS level was observed after NBT treatment. Remarkably, the inhibition of ROS by N-acetylcysteine (NAC) effectively suppressed the activation of TOM20/BAX pathway. Moreover, in vivo experiments demonstrated that NBT exhibited potent antitumor effects in both KYSE450 and TOM20 knockout KYSE450-/- xenograft models. Notably, the attenuated antitumor effects and reduced cleavage of GSDME were observed in the TOM20 knockout model. CONCLUSION: These findings reveal that NBT induces pyroptosis through ROS/TOM20/BAX/GSDME pathway, which highlight the therapeutic potential of targeting TOM20 and GSDME, providing promising prospects for the development of innovative and effective treatment approaches for esophageal cancer.

Revealing the Denoising Principle of Zero-Shot N2N-Based Algorithm from 1D Spectrum to 2D Image.

Denoising is a necessary step in image analysis to extract weak signals, especially those hardly identified by the naked eye. Unlike the data-driven deep-learning denoising algorithms relying on a clean image as the reference, Noise2Noise (N2N) was able to denoise the noise image, providing sufficiently noise images with the same subject but randomly distributed noise. Further, by introducing data augmentation to create a big data set and regularization to prevent model overfitting, zero-shot N2N-based denoising was proposed in which only a single noisy image was needed. Although various N2N-based denoising algorithms have been developed with high performance, their complicated black box operation prevented the lightweight. Therefore, to reveal the working function of the zero-shot N2N-based algorithm, we proposed a lightweight Peak2Peak algorithm (P2P) and qualitatively and quantitatively analyzed its denoising behavior on the 1D spectrum and 2D image. We found that the high-performance denoising originates from the trade-off balance between the loss function and regularization in the denoising module, where regularization is the switch of denoising. Meanwhile, the signal extraction is mainly from the self-supervised characteristic learning in the data augmentation module. Further, the lightweight P2P improved the denoising speed by at least ten times but with little performance loss, compared with that of the current N2N-based algorithms. In general, the visualization of P2P provides a reference for revealing the working function of zero-shot N2N-based algorithms, which would pave the way for the application of these algorithms toward real-time (in situ, in vivo, and operando) research improving both temporal and spatial resolutions. The P2P is open-source at https://github.com/3331822w/Peak2Peakand will be accessible online access at https://ramancloud.xmu.edu.cn/tutorial.

hBcl2 overexpression in BMSCs enhances resistance to myelin debris-induced apoptosis and facilitates neuroprotection after spinal cord injury in rats.

After spinal cord injury (SCI), the accumulation of myelin debris at the lesion exacerbates cell death and hinders axonal regeneration. Transplanted bone marrow mesenchymal stem cells (BMSCs) have been proven to be beneficial for SCI repair, but they are susceptible to apoptosis. It remains unclear whether this apoptotic process is influenced by myelin debris. Here, we constructed rat BMSCs overexpressing human B-cell lymphoma 2 (hBcl2) alone (hBcl2 group), BMSCs overexpressing hBcl2 with an endoplasmic reticulum-anchored segment (hBcl2-cb) (cb group), and a negative control group (NC group) for transplantation in this study. Immunocytochemistry staining validated the successful expression of hBcl2 in BMSCs within the hBcl2 group and cb group. All BMSCs from each group exhibited the ability to phagocytize myelin debris. Nevertheless, only BMSCs derived from the hBcl2 group exhibited heightened resistance to apoptosis and maintained prolonged viability for up to 5 days when exposed to myelin debris. Notably, overexpression of hBcl2 protein, rather than its endoplasmic reticulum-anchored counterpart, significantly enhanced the resistance of BMSCs against myelin debris-induced apoptosis. This process appeared to be associated with the efficient degradation of myelin debris through the Lamp1+ lysosomal pathway in the hBcl2 group. In vivo, the hBcl2 group exhibited significantly higher numbers of surviving cells and fewer apoptotic BMSCs compared to the cb and NC groups following transplantation. Furthermore, the hBcl2 group displayed reduced GFAP+ glial scarring and greater preservation of NF200+ axons in the lesions of SCI rats. Our results suggest that myelin debris triggers apoptosis in transplanted BMSCs, potentially elucidating the low survival rate of these cells after SCI. Consequently, the survival rate of transplanted BMSCs is improved by hBcl2 overexpression, leading to enhanced preservation of axons within the injured spinal cord.

COL1A1 regulates the apoptosis of embryonic stem cells by mediating the PITX1/TBX4 signaling.

PURPOSE: The purpose of this study is to explore the regulatory function of COL1A1 against the apoptosis of embryonic stem cells (ESCs) and the potential function in congenital talipes equinovarus (CTEV). METHODS: Muscle tissues were collected from 20 children with CTEV and 20 children without CTEV, followed by detecting the expression of COL1A1 using the RT-PCR method. COL1A1 was knocked down in H1 and H9 human ESCs using the RNA interference technology, followed by determining the level of COL1A1, PITX1, TBX4, HOXD10, Fas, FasL, and Bax using the Western blotting assay. RESULTS: COL1A1 was found markedly upregulated in muscle tissues of CTEV children. In H1 and H9 human ESCs, compared to the empty vector, COL1A1, PITX1, TBX4, HOXD10, Fas, FasL, and Bax were found notably downregulated after transfected with the siRNA targeting COL1A1. CONCLUSION: COL1A1 induced the apoptosis of ESCs by mediating the PITX1/TBX4 signaling and might be a potential target for treating CTEV.

Metabolomics approach to growth-age discrimination in mountain-cultivated ginseng (Panax ginseng C. A. Meyer) using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry.

Mountain-cultivated ginseng is typically harvested after 10 years, while ginseng aged over 15 years is considered wild ginseng. This study aims to differentiate mountain-cultivated ginseng by age, as the fraudulent practice of selling low-aged cultivated ginseng disguised as high-aged one is damaging the market. In this study, LC-MS analyzed 98 ginseng samples, and multivariate statistical analysis identified patterns between samples to select influential components. Machine learning models were developed to identify ginseng samples of different ages. The untargeted metabolomic analysis clearly divided samples aged 4-20 years into three age groups. Twenty-two potential age-dependent biomarkers were discovered to differentiate the three sample groups. Three machine learning models were used to predict new samples, and the optimal model was selected. Some biomarkers could determine age phases according to the differentiation of mountain-cultivated ginseng samples. These biomarkers were thoroughly analyzed for variation trends. The machine learning models established using the screened biomarkers successfully predicted the age group of new samples.

Corrigendum: Efficacy and functionality of sugarcane original vinegar on mice.

[This corrects the article DOI: 10.3389/fmicb.2023.1224666.].

Efficacy and functionality of sugarcane original vinegar on mice.

Introduction: Due to their bioactive compounds and beneficial health effects, functional foods and plant-based natural medicines are widely consumed. Due to its bioactivities, vinegar is one of them that helps humans. Sugarcane original vinegar (SOV) is a special vinegar made from sugarcane as a raw material through biological fermentation processes. Methods: The objective of this study was to assess the effects of sugarcane original vinegar on growth performance, immune response, acute oral toxicity, bacterial reverse mutation, mammalian erythrocyte micronucleus, mouse spermatogonial chromosome aberration, mammalian bone marrow cell chromosome aberration changes, and serum characteristics in mice. Distortion parameters were used to assess its safety, and at the same time, the functionality of SOV was monitored during experimentation. Results: The results show that the SOV has no damage or inhibitory effect on the bone marrow red blood cells of mice and no mutagenic or distortion-inducing effects on the bone marrow cell chromosomes or spermatogonia chromosomes, so it is safe to eat. SOV can improve blood lipids and reduce blood lipid content. Discussion: The study results provide data basis for the intensive processing of sugarcane and the development of high-value SOV products. Sugarcane original vinegar has a beneficial impact on performance, immune response, and chromosomal aberration. The production application influences the vinegar's quality and, consequently, its health benefits.

Application of high-throughput sequencing to analyze the diet of black croaker (Atrobucca nibe) in southern coastal waters of Zhejiang.

This study investigated the feeding habits of black croaker (Atrobucca nibe) to fully understand its role in the food web in southern coastal waters of Zhejiang, China. In total, 225 black croakers were collected in a bottom trawl survey, of which 195 were used for the stomach contents analysis and 30 for high-throughput sequencing (HTS). Both approaches showed that the main prey was shrimp, with Alpheus japonicus being the most predominant. In addition, black croaker also fed on other benthic species, suggesting that it was a demersal predator. Feeding intensity also varied with black croaker body length, as did prey preference, from small-sized species to larger species with increases in fish size; in addition, prey species were more diverse in the large-bodied prey group. Canonical correspondence analysis indicated that the feeding habit of black croaker was most significantly correlated with temperature and dissolved oxygen. HTS was shown to be a feasible high precision semi-quantitative analytical approach, although it must be combined with morphological methods to obtain more complete feeding data; thus, it could provide an effective scientific basis for feeding ecology studies of marine organisms.

Indolo[2,3-b]quinoxaline as a Low Reduction Potential and High Stability Anolyte Scaffold for Nonaqueous Redox Flow Batteries.

Redox flow batteries (RFBs) are a promising stationary energy storage technology for leveling power supply from intermittent renewable energy sources with demand. A central objective for the development of practical, scalable RFBs is to identify affordable and high-performance redox-active molecules as storage materials. Herein, we report the design, synthesis, and evaluation of a new organic scaffold, indolo[2,3-b]quinoxaline, for highly stable, low-reduction potential, and high-solubility anolytes for nonaqueous redox flow batteries (NARFBs). The mixture of 2- and 3-(tert-butyl)-6-(2-methoxyethyl)-6H-indolo[2,3-b]quinoxaline exhibits a low reduction potential (-2.01 V vs Fc/Fc+), high solubility (>2.7 M in acetonitrile), and remarkable stability (99.86% capacity retention over 49.5 h (202 cycles) of H-cell cycling). This anolyte was paired with N-(2-(2-methoxyethoxy)-ethyl)phenothiazine (MEEPT) to achieve a 2.3 V all-organic NARFB exhibiting 95.8% capacity retention over 75.1 h (120 cycles) of cycling.

A novel method for age identification of mountain-cultivated ginseng.

Panax ginseng, a slow-growing perennial herb, is the most praised and popular traditional medicinal herb. Mountain-cultivated ginseng (MCG) and cultivated ginseng (CG) both belong to Panax ginseng C. A. Meyer. The market price and medical effects of this popular health product are closely related to its age. It is widely acknowledged that CG is typically harvested after 4-6 years of growth, but MCG is often collected after 10 years. Until now, the age identification of MCG or mountain wild ginseng (MWG) has remained a major challenge. In this study, we established a novel and rapid method for staining xylem vessels with phloroglucinol and identifying the "annual growth rings" of ginseng by utilizing a stereoscope, which serves as a reliable indicator of the age of MCG. Statistical analysis of the ring radius and the ring density of MCG aged from 1 to 20 years shows that the secondary xylem of MCG increases rapidly in the first 3 years but then gradually slows down from 4 to 10 years, and minor fluctuation is observed in the next 10 years. Meanwhile, the space between the growth rings (ring density) becomes increasingly small with age. This straightforward staining approach can reveal the age of MCG with remarkable clarity and can distinguish MCG from CG. RESEARCH HIGHLIGHTS: A novel rapid staining method for Panax ginseng was established. The age of mountain-cultivated ginseng (MCG) can be identified by microscopic techniques. MCG and cultivated ginseng (CG) can be discriminated by microstructure characteristics.

Effects of Transition Metals on Metal-Octaaminophthalocyanine-Based 2D Metal-Organic Frameworks.

Metal-octaaminophthalocyanine (MOAPc)-based 2D conductive metal-organic frameworks (cMOFs) have shown great potential in several applications, including sensing, energy storage, and electrocatalysis, due to their bimetallic characteristics. Here, we report a detailed metal substitution study on a family of isostructural cMOFs with Co2+, Ni2+, and Cu2+ as both the metal nodes and the metal centers in the MOAPc ligands. We observed that different metal nodes had variations in the reaction kinetics, particle sizes, and crystallinities. Importantly, the electronic structure and conductivity were found to be dependent on both types of metal sites in the 2D cMOFs. Ni-NiOAPc was found to be the most conductive one among the nine possible combinations with a conductivity of 54 ± 4.8 mS/cm. DFT calculations revealed that monolayer Ni-NiOAPc has neither the smallest bandgap nor the highest charge carrier mobility. Hence its highest conductivity stems from its high crystallinity. Collectively, these results provide structure property relationships for MOAPc-based cMOFs with amino coordination units.

UPLC-QTOF-MS with a chemical profiling approach for holistic quality evaluation between a material reference of Wen Dan decoction and its commercial preparations.

BACKGROUND: Wen Dan decoction (WDD) has been a famous classic formula for resolving phlegm since ancient times in China. Currently, there are many types of WDD commercial preparations produced through modern technology. However, it is not known whether the holistic quality of WDD commercial preparations is consistent with the traditional decocting method to exert its proper effects. Therefore, the WDD material reference was studied and prepared, which can represent the traditional Chinese formulation WDD. METHODS: A method based on UPLC-QTOF-MS was developed to evaluate the quality of WDD material reference and commercial prescriptions. At the same time, the multivariate statistical method was used to compare the differences between the material reference and the commercial prescription by principal component analysis (PCA) and heatmap. Finally, the UPLC-QTOF-MS method was established to quantitatively study 11 representative components, including naringin, hesperidin, neohesperidin, liquiritin, glycyrrhizic acid, adenosine, liquiritigenin, tangeretin, eriocitrin, naringenin and synephrine. RESULTS: A total of 107 compounds were identified in the WDD material reference by comparing the retention time and fragment ion characteristics, including 54 flavonoids, 14 triterpenes, 10 organic acids, 7 alkaloids, 7 coumarins and 15 other components. The samples were almost evenly split into two groups, indicating a difference in quality between the WDD material reference and its commercial preparations in multivariate statistical analysis. Eleven major components of linearity, precision, repeatability, stability and recovery rate met the requirements, which were clearly different in commercial preparations and WDD material references. In terms of the content of 11 components in the commercial preparation, only CP8 is close to the material reference, which is in agreement with the statistical analysis of the heatmap. The concentrations of naringin and neohesperidin from the WDD material reference were higher than those from the commercial preparations. CONCLUSIONS: The quality evaluation method established in this study can be used to identify different sources of WDD but also proves that the WDD material reference contains higher naringin. Furthermore, this study confirmed that the preparation technology of WDD commercial prescriptions should be optimized on the basis of WDD material references, producing the closest possible clinical basis for the substance.

Time-resolved single-cell transcriptomics reveals the landscape and dynamics of hepatic cells in sepsis-induced acute liver dysfunction.

Background & Aims: Sepsis-induced acute liver dysfunction often occurs early in sepsis and can exacerbate the pathology by triggering multiple organ dysfunction and increasing lethality. Nevertheless, our understanding of the cellular heterogeneity and dynamic regulation of major nonparenchymal cell lineages remains unclear. Methods: Here, single-cell RNA sequencing was used to profile multiple nonparenchymal cell subsets and dissect their crosstalk during sepsis-induced acute liver dysfunction in a clinically relevant polymicrobial sepsis model. The transcriptomes of major liver nonparenchymal cells from control and sepsis mice were analysed. The alterations in the endothelial cell and neutrophil subsets that were closely associated with acute liver dysfunction were validated using multiplex immunofluorescence staining. In addition, the therapeutic efficacy of inhibiting activating transcription factor 4 (ATF4) in sepsis and sepsis-induced acute liver dysfunction was explored. Results: Our results present the dynamic transcriptomic landscape of major nonparenchymal cells at single-cell resolution. We observed significant alterations and heterogeneity in major hepatic nonparenchymal cell subsets during sepsis. Importantly, we identified endothelial cell (CD31+Sele+Glut1+) and neutrophil (Ly6G+Lta4h+Sort1+) subsets that were closely associated with acute liver dysfunction during sepsis progression. Furthermore, we found that ATF4 inhibition alleviated sepsis-induced acute liver dysfunction, prolonging the survival of septic mice. Conclusions: These results elucidate the potential mechanisms and subsequent therapeutic targets for the prevention and treatment of sepsis-induced acute liver dysfunction and other liver-related diseases. Impact and Implications: Sepsis-induced acute liver dysfunction often occurs early in sepsis and can lead to the death of the patient. Nevertheless, the pathogenesis of sepsis-induced acute liver dysfunction is not yet clear. We identified the major cell types associated with acute liver dysfunction and explored their interactions during sepsis. In addition, we also found that ATF-4 inhibition could be invoked as a potential therapeutic for sepsis-induced acute liver dysfunction.

Characterization of the Pure Black Tea Wine Fermentation Process by Electronic Nose and Tongue-Based Techniques with Nutritional Characteristics.

Wine is an alcoholic beverage, consisting of several compounds in various ranges of concentrations. Wine quality is usually assessed by a sensory panel of trained personnel. Electronic tongues (e-tongues) and electronic noses (e-noses) have been established in recent years to assess the quality of beverages and foods. Response surface and electronic analysis tools were used to examine the quality of black tea wine. The results indicated the optimum initial sugar level (25 °Brix), yeast addition (0.5%), and fermentation temperature (25 °C) for Golden Peony black tea wine. The black tea wine produced under these conditions with 14.0% vol alcohol has as an orange-red color, full wine and tea flavor, and mild and mellow taste. The sourness of the wine was most affected by fermentation factors-yeast addition, fermentation temperature, and initial sugar level. Alcohols, aldehydes, ketones, and alkanes contributed to most of the volatile components under the influence of yeast addition and fermentation temperature. In contrast, nitrogen oxides, aromatics, and organic sulfides contributed under the influence of the initial sugar level. This study provided a facilitated strategy for obtaining the optimum black tea wine fermentation process through electronic nose and tongue-based techniques. The analysis of wines requires new technologies able to detect various different compounds simultaneously, providing worldwide information about the sample instead of information about specific compounds.

Vinegar: A potential source of healthy and functional food with special reference to sugarcane vinegar.

Vinegar is one of the most widely used acidic condiments. Recently, rapid advances have been made in the area of vinegar research. Different types of traditional vinegar are available around the globe and have many applications. Vinegar can be made either naturally, through alcoholic and then acetic acid fermentation, or artificially, in laboratories. Vinegar is the product of acetic acid fermentation of dilute alcoholic solutions, manufactured by a two-step process. The first step is the production of ethanol from a carbohydrate source such as glucose, which is carried out by yeasts. The second step is the oxidation of ethanol to acetic acid, which is carried out by acetic acid bacteria. Acetic acid bacteria are not only producers of certain foods and drinks, such as vinegar, but they can also spoil other products such as wine, beer, soft drinks, and fruits. Various renewable substrates are used for the efficient biological production of acetic acid, including agro and food, dairy, and kitchen wastes. Numerous reports on the health advantages associated with vinegar ingredients have been presented. Fresh sugarcane juice was fermented with wine yeast and LB acetate bacteria to develop a high-quality original sugarcane vinegar beverage. To facilitate the current study, the bibliometric analysis method was adopted to visualize the knowledge map of vinegar research based on literature data. The present review article will help scientists discern the dynamic era of vinegar research and highlight areas for future research.

Protective effect of bioactive iridium nanozymes on high altitude-related hypoxia-induced kidney injury in mice.

Introduction: High altitude-related hypoxia-induced organ damage significantly impacts people who are exposed to acute high-altitude environment. At present, kidney injury still lacks effective treatment strategies. Iridium nanozymes (Ir-NPs) are a nanomaterial with various enzymatic activities and are expected to be used in kidney injury treatment. Methods: In this study, we simulated a high-altitude environment (6000 m) to induce a kidney injury model, and explored the therapeutic effect of Ir-NPs in mice with kidney injury in this environment. Changes in the microbial community and metabolites were analyzed to explore the possible mechanism underlying the improvement of kidney injury during acute altitude hypoxia in mice treated with Ir-NPs. Results: It was discovered that plasma lactate dehydrogenase and urea nitrogen levels were considerably increased in mice exposed to acute altitude hypoxia compared to mice in a normal oxygen environment. Furthermore, there was a substantial increase in IL-6 expression levels in hypoxic mice; contrastingly, Ir-NPs decreased IL-6 expression levels, reduced the levels of succinic acid and indoxyl sulfate in the plasma and kidney pathological changes caused by acute altitude hypoxia. Microbiome analysis showed that bacteria, such as Lachnospiraceae_UCG_006 predominated in mice treated with Ir-NPs. Conclusion: Correlation analysis of the physiological, biochemical, metabolic, and microbiome-related parameters showed that Ir-NPs could reduce the inflammatory response and protect kidney function under acute altitude hypoxia, which may be related to intestinal flora distribution regulation and plasma metabolism in mice. Therefore, this study provides a novel therapeutic strategy for hypoxia-related kidney injury, which could be applied to other hypoxia-related diseases.

PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer.

Doxorubicin (DOX) is an effective chemotherapeutic agent widely used for cancer treatment. However, hypoxia in tumour tissue and obvious adverse effects particularly cardiotoxicity restricts the clinical usage of DOX. Our study is based on the co-administration of haemoglobin-based oxygen carriers (HBOCs) and DOX in a breast cancer model to investigate HBOCs' ability to enhance chemotherapeutic effectiveness and its capabilities to alleviate the side effects induced by DOX. In an in-vitro study, the results suggested the cytotoxicity of DOX was significantly improved when combined with HBOCs in a hypoxic environment, and produced more γ-H2AX indicating higher DNA damage than free DOX did. Compared with administration of free DOX, combined therapy exhibited a stronger tumour suppressive effect in an in-vivo study. Further mechanism studies showed that the expression of various proteins such as hypoxia-inducible factor-1α (HIF-1α), CD31, CD34, and vascular endothelial growth factor (VEGF) in tumour tissues was also significantly reduced in the combined treatment group. In addition, HBOCs can significantly reduce the splenocardiac toxicity induced by DOX, according to the results of the haematoxylin and eosin (H&E) staining and histological investigation. This study suggested that PEG-conjugated bovine haemoglobin may not only reduce the hypoxia in tumours and increase the efficiency of chemotherapeutic agent DOX, but also alleviate the irreversible heart toxicity caused by DOX-inducted splenocardiac dysregulation.