High altitude (HA) has become one of the most challenging environments featuring hypobaric hypoxia, which seriously threatens public health, hence its gradual attraction of public attention over the past decade. The purpose of this study is to investigate the effect of HA hypoxia on iron levels, redox state, inflammation, and ferroptosis in adipose tissue. Here, 40 mice were randomly divided into two groups: the sea-level group and HA hypoxia group (altitude of 5000 m, treatment for 4 weeks). Total iron contents, ferrous iron contents, ROS generation, lipid peroxidation, the oxidative enzyme system, proinflammatory factor secretion, and ferroptosis-related biomarkers were examined, respectively. According to the results, HA exposure increases total iron and ferrous iron levels in both WAT and BAT. Meanwhile, ROS release, MDA, 4-HNE elevation, GSH depletion, as well as the decrease in SOD, CAT, and GSH-Px activities further evidenced a phenotype of redox imbalance in adipose tissue during HA exposure. Additionally, the secretion of inflammatory factors was also significantly enhanced in HA mice. Moreover, the remarkably changed expression of ferroptosis-related markers suggested that HA exposure increased ferroptosis sensitivity in adipose tissue. Overall, this study reveals that HA exposure is capable of inducing adipose tissue redox imbalance, inflammatory response, and ferroptosis, driven in part by changes in iron overload, which is expected to provide novel preventive targets for HA-related illness.

In recent years, chronic liver injury has become a common disease that harms human health. Its clinical manifestations are hepatic steatosis and secondary chronic steatohepatitis, which can quickly transform into liver fibrosis and cirrhosis if not treated in time. Therefore, this study is aimed at searching for new therapeutic targets of chronic liver injury and clarifying the molecular mechanisms of the new targets involved in chronic liver injury. After aquaporin 9 was identified as a target by proteomics, Aqp9^-/- mice were constructed using the CRISPR/Cas9 system. Biochemical and morphological tests were used to verify the effect of Aqp9 knockout on early chronic liver injury. Proteomics, molecular biology, and morphology experiments were used to screen and verify the effects of Aqp9 knockout on its downstream pathway. Through the above experiments, we demonstrated that aquaporin 9 could be used as an intervention target for antagonizing the development of early chronic liver injury and its gene knockout affected downstream inflammation, oxidative stress, apoptosis, and pyroptosis by alleviating hepatic lipotoxicity.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has become increasingly popular during the past few decades, and its indications have extended from patients with normal liver to post-chemotherapy patients and even patients with cirrhosis. However, few studies have assessed the publications in relation to ALPPS. Web of Science was searched to identify studies related to ALPPS published from 2012 to 2021. The analysis was performed using the bibliometric package (Version 3.1.0) in R software. In total, 486 publications were found. These articles were published in 159 journals and authored by 2157 researchers from 694 organizations. The most prolific journal was Annals of Surgery (24 articles and 1170 citations). The most frequently cited article was published in Annals of Surgery (average citations, 72.7; total citations, 727). China was the most productive country for ALPPS publications but had comparatively less interaction with other countries. Both thematic evolution and co-occurrence network analysis showed low numbers of topics such as failure, resection, and safety among the publications but large numbers of highly cited papers on outcomes, prediction, mechanisms, multicenter analysis, and novel procedures such as liver venous deprivation. A total of 196 studies focused the clinical application of ALPPS, and most studies were IDEAL Stages I and II. The specific mechanism of ALPPS liver regeneration remains unclear. This is the first bibliometric analysis offering an overview of the development of ALPPS research publications. Our findings identified prominent studies, countries, institutions, journals, and authors to indicate the future direction of ALPPS research. The role of ALPPS in liver regeneration and the long-term results of ALPPS need further study. Future research directions include comparison of ALPPS with portal vein embolization, liver venous deprivation, and other two-stage hepatectomies as well as patients' quality of life after ALPPS.

As a small-molecule reductant substance, hydrogen gas has an obvious antioxidant function. It can selectively neutralize hydroxyl radicals (^•OH) and peroxynitrite (ONOO^•) in cells, reducing oxidative stress damage. The purpose of this study was to investigate the effect of hydrogen gas (3%) on early chronic liver injury (CLI) induced by CCl₄ and to preliminarily explore the protective mechanism of hydrogen gas on hepatocytes by observing the expression of uncoupling protein 2 (UCP2) in liver tissue. Here, 32 rats were divided into four groups: the control group, CCl₄ group, H₂ (hydrogen gas) group, and CCl₄ + H₂ group. The effect of hydrogen gas on early CLI was observed by serological tests, ELISA, hematoxylin and eosin staining, and oil red O staining. Immunohistochemical staining and Western blotting were used to observe the expression of UCP2 in liver tissues. We found that CCl₄ can induce significant steatosis in hepatocytes. When the hydrogen gas was inhaled, hepatocyte steatosis was reduced, and the UCP2 expression level in liver tissue was increased. These results suggest that hydrogen gas might upregulate UCP2 expression levels, reduce the generation of intracellular oxygen free radicals, affect lipid metabolism in liver cells, and play a protective role in liver cells.

Methylene blue, the FDA‐grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT‐MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT‐MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.

SignificanceWe present an optical technology for a full-process label-free method for brain slice screening. This proposed multiplexed circular polarimetric method has the advantages of simple operation and high accuracy which may provide easily accessible evidence for the future diagnosis of related diseases.AimOne of its missions is to provide a quantifiable, reproducible analysis methodology that can replace or supplement traditional qualitative, subjective pathological analysis.ApproachA label-free, sensitive, and rapid circular polarimetric method based on a multiplexed optical fiber meta-tip is proposed for the digital pathology of ischemic stroke. Polarization information of forward-scattered light is used to identify pathological variations of axon distribution in ischemic stroke tissues. The newly designed optical fiber meta-tip with four channels offers miniature illumination in the multiplexed circular polarimetry method.ResultsOur automated approach achieves more than 90% area under the curve in classifying ischemic stroke brain tissue in around 1 min.ConclusionsThe high-sensitivity and label-free circular polarimetric method based on the multiplexed optical fiber meta-tip renders its potential for rapid digital pathology of various diseases. It will empower the application of digital pathology in future disease diagnosis by quantitatively introducing a new reliable data modality without altering currently established processes.