Multi-interfaced Ni/C@RGO/PTFE composites for electromagnetic protection applications with high environmental stability and durability.

To efficiently address the growing electromagnetic pollution problem, it is urgently required to research high-performance electromagnetic materials that can effectively absorb or shield electromagnetic waves. In addition, the stability and durability of electromagnetic materials in complex practical environments is also an issue that needs to be noticed. Therefore, the starting point for our problem-solving is how to endow magnetic/dielectric multi-interfaced composite materials with excellent electromagnetic protection capability and environmental stability. In this study, magnetic/dielectric multi-interfaced Ni/carbon@reduced graphene oxide/polytetrafluoroethylene (Ni/C@RGO/PTFE) composites were developed to utilize as excellent EWA (electromagnetic wave absorption) and EMI (electromagnetic interference) shielding materials. Due to their diverse heterogeneous interfaces, rich conductive networks, and multiple loss mechanisms, the Ni/C@RGO/PTFE composite exhibits an optimal reflection loss of -61.48 dB and an effective absorption bandwidth of 7.20 GHz, with a filler loading of 5 wt%. Furthermore, Ni/C@RGO/PTFE composite films have an optimal absorption effectiveness value of 9.50 dB and an absorption coefficient of 0.49. Moreover, Ni/C@RGO/PTFE can hold high EWA performance in various corrosive media and maintain more than 90% of EMI shielding effectiveness, which can be attributed to the carbon coating and PTFE matrix acting as dual protective barriers for the susceptible metal Ni, thus obviously improving the stability and durability of composites. Overall, this work presents an effective strategy for the growth of high-performance EWA and EMI shielding materials with outstanding environmental stability and durability, which have wide application prospects in the future.

HIF-1α: A potential therapeutic opportunity in renal fibrosis.

Renal fibrosis is a common outcome of various renal injuries, leading to structural destruction and functional decline of the kidney, and is also a critical prognostic indicator and determinant in renal diseases therapy. Hypoxia is induced in different stress and injuries in kidney, and the hypoxia inducible factors (HIFs) are activated in the context of hypoxia in response and regulation the hypoxia in time. Under stress and hypoxia conditions, HIF-1α increases rapidly and regulates intracellular energy metabolism, cell proliferation, apoptosis, and inflammation. Through reprogramming cellular metabolism, HIF-1α can directly or indirectly induce abnormal accumulation of metabolites, changes in cellular epigenetic modifications, and activation of fibrotic signals. HIF-1α protein expression and activity are regulated by various posttranslational modifications. The drugs targeting HIF-1α can regulate the downstream cascade signals by inhibiting HIF-1α activity or promoting its degradation. As the renal fibrosis is affected by renal diseases, different diseases may trigger different mechanisms which will affect the therapy effect. Therefore, comprehensive analysis of the role and contribution of HIF-1α in occurrence and progression of renal fibrosis, and determination the appropriate intervention time of HIF-1α in the process of renal fibrosis are important ideas to explore effective treatment strategies. This study reviews the regulation of HIF-1α and its mediated complex cascade reactions in renal fibrosis, and lists some drugs targeting HIF-1α that used in preclinical studies, to provide new insight for the study of the renal fibrosis mechanism.

Prediction of COVID-19 Patients' Emergency Room Revisit using Multi-Source Transfer Learning.

The coronavirus disease 2019 (COVID-19) has led to a global pandemic of significant severity. In addition to its high level of contagiousness, COVID-19 can have a heterogeneous clinical course, ranging from asymptomatic carriers to severe and potentially life-threatening health complications. Many patients have to revisit the emergency room (ER) within a short time after discharge, which significantly increases the workload for medical staff. Early identification of such patients is crucial for helping physicians focus on treating life-threatening cases. In this study, we obtained Electronic Health Records (EHRs) of 3,210 encounters from 13 affiliated ERs within the University of Pittsburgh Medical Center between March 2020 and January 2021. We leveraged a Natural Language Processing technique, ScispaCy, to extract clinical concepts and used the 1001 most frequent concepts to develop 7-day revisit models for COVID-19 patients in ERs. The research data we collected were obtained from 13 ERs, which may have distributional differences that could affect the model development. To address this issue, we employed a classic deep transfer learning method called the Domain Adversarial Neural Network (DANN) and evaluated different modeling strategies, including the Multi-DANN algorithm (which considers the source differences), the Single-DANN algorithm (which doesn't consider the source differences), and three baseline methods: using only source data, using only target data, and using a mixture of source and target data. Results showed that the Multi-DANN models outperformed the Single-DANN models and baseline models in predicting revisits of COVID-19 patients to the ER within 7 days after discharge (median AUROC = 0.8 vs. 0.5). Notably, the Multi-DANN strategy effectively addressed the heterogeneity among multiple source domains and improved the adaptation of source data to the target domain. Moreover, the high performance of Multi-DANN models indicates that EHRs are informative for developing a prediction model to identify COVID-19 patients who are very likely to revisit an ER within 7 days after discharge.

HIF-1α mediates renal fibrosis by regulating metabolic remodeling of renal tubule epithelial cells.

Hypoxia-inducible factor 1-α (HIF-1α) mediates the occurrence and development of renal diseases and fibrosis. In the process, dysregulated cellular metabolism was suggested to be involved in several pathological processes. Here, we found that HIF-1α expression was increased in the early stage of renal fibrosis, and significant metabolic remodeling was triggered. Epigenetic events that drive diseases were characterized previously. Our study showed that ten-eleven translocation-2 (TET2) was upregulated in both renal fibrosis models and metabolite-treated samples. Furthermore, we found that the promoter of α-SMA was hypomethylated at CpG sites, which promoted the expression of α-SMA and the occurrence of renal fibrosis. HIF-1α inhibition alleviated renal fibrosis development by improving metabolic remodeling and TET2 activation. Our studies provide novel insight into HIF-1α-mediated metabolic remodeling in the pathogenesis of renal fibrosis and propose a concept that targets this pathway to treat fibrotic disorders.

Exosomes Derived from BMSCs Ameliorate Intestinal Ischemia-Reperfusion Injury by Regulating miR-144-3p-Mediated Oxidative Stress.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a critical pathophysiological process involved in many acute and critical diseases, and it may seriously threaten the lives of patients. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) may be an effective therapeutic approach for I/R injury. AIMS: This study aimed to investigate the role and possible mechanism of BMSC-exos in intestinal I/R injury in vivo and in vitro based on the miR-144-3p and PTEN/Akt/Nrf2 pathways. METHODS: BMSC-exos were isolated from mouse BMSCs by super centrifugation methods. The effects of BMSC-exos on I/R intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway were explored in vivo and in vitro. Furthermore, the relationship between miR-144-3p and PTEN was confirmed by a dual-luciferase reporter assay. The miR-144-3p mimic and inhibitor were used to further clarify the role of miR-144-3p in the mitigation of intestinal I/R by BMSC-exos. RESULTS: BMSC-exos effectively alleviated intestinal pathological injury, reduced intestinal cell apoptosis, relieved oxidative stress and regulated the PTEN/Akt/Nrf2 pathway in vivo and in vitro. In addition, miR-144-3p was significantly reduced in the oxygen and glucose deprivation/reperfusion cell model, and miR-144-3p could directly target PTEN to regulate its expression. Additional studies showed that changing the expression of miR-144-3p in BMSC-exos significantly affected the regulation of intestinal injury, intestinal cell apoptosis, oxidative stress and the PTEN/Akt/Nrf2 pathway in I/R, suggesting that miR-144-3p in BMSC-exos plays an important role in regulating the PTEN/Akt/Nrf2 during intestinal I/R. CONCLUSIONS: BMSC-exos carrying miR-144-3p alleviated intestinal I/R injury by regulating oxidative stress.

Accumulation of polystyrene microplastics induces liver fibrosis by activating cGAS/STING pathway.

The environmental pollution from microplastics has caused concern from the whole society due to its harm to organisms. However, the effect of microplastics on liver damage and fibrosis remains unclear in the case of long-term accumulation. The present study demonstrated that the 0.1 µm microplastic could enter hepatocytes from circulation and result liver damage even at a low concentration. Microplastic exposure could induce DNA damage in both nucleus and mitochondria, by which the dsDNA fragment was translocated into cytoplasm and triggered the DNA sensing adaptor STING. The activation of cGAS/STING pathway initiated the downstream cascade reaction, the NFκB translocated into nucleus and upregulated pro-inflammatory cytokines expression, and thus facilitating liver fibrosis eventually. Furthermore, inhibition of STING could alleviate the liver fibrosis via blocking the NFκB translocation and fibronectin expression. This study provided a valuable insight to elucidate the potential risk and mechanism of hepatic toxicity and fibrosis induced by microplastics.

Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases.

The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).

DNA Damage and Activation of cGAS/STING Pathway Induce Tumor Microenvironment Remodeling.

DNA damage occurs throughout tumorigenesis and development. The immunogenicity of DNA makes it an immune stimulatory molecule that initiates strong inflammatory responses. The cGAS/STING pathway has been investigated as a critical receptor in both exogenous and endogenous DNA sensing to activate the innate immune response. Growing lines of evidence have indicated that activation of the cGAS/STING pathway is critical in antitumor immunity. Recent studies have demonstrated the outstanding advancement of this pathway in tumor-combined immunotherapy; accordingly, increased studies focus on exploration of STING pathway agonists and analogues. However, current studies propose the potential use of the cGAS/STING pathway in tumor initiation and metastasis. Here, we review the molecular mechanisms and activation of the cGAS/STING pathway, and the relationship between DNA damage and this pathway, particularly highlighting the remodeling of immune contexture in tumor environment (TME) triggered by cascade inflammatory signals. A detailed understanding of TME reprogramming initiated by this pathway may pave the way for the development of new therapeutic strategies and rational clinical application.

Determination of cadmium induced acute and chronic reproductive toxicity with Raman spectroscopy.

Cadmium (Cd) is one of the toxic heavy metals which is confirmed to be related to male sterile. Here, confocal Raman spectroscopy was employed to detect biomolecular composition and changes in testis under acute and chronic Cd treatment. Specific Raman shifts associated with mitochondria, nucleic acids, proteins, lipids, and cholesterol were identified which were distinguishing among groups undergoing different Cd treatment times. Supporting evidences were provided by conventional experimental detections. The relevant biochemical parameters, pathological changes, and protein expression related to testosterone synthesis were all changed and consistent with Raman spectrum information. In conclusion, confocal Raman spectroscopy presents a reliable data and provides a novel method which is expected to be a promising strategy in reproduction toxicity research.

Protective effect of Potentilla anserina polysaccharide on cadmium-induced nephrotoxicity in vitro and in vivo.

The aim of this research was to investigate the antioxidant and anti-apoptotic activities of Potentilla anserina polysaccharide (PAP) on kidney damage induced by cadmium (Cd) in vitro and in vivo. PAP has been suggested to have anti-oxidation, anti-apoptosis, immunoregulation, antimicrobial, antitussive, and expectorant abilities. In this study, PAP was extracted and the major components of PAP were analyzed. It was shown that PAP pretreatment remarkably improved redox homeostasis, both in human embryonic kidney 293 (HEK293) cells and in BALB/c mice. Administration of PAP attenuated the mitochondrial dysfunction, degeneration, and fibrosis of kidney induced by Cd. Furthermore, PAP exhibited anti-apoptotic activity, which involved regulating both the mitochondria-mediated intrinsic apoptotic pathway and the death receptor-initiated extrinsic pathway. These results suggest that PAP is a potential therapeutic agent for Cd-induced nephrotoxicity.