Gene Regulation of Neutrophils Mediated Liver and Lung Injury through NETosis in Acute Pancreatitis.

Acute pancreatitis (AP) is one of the most common gastrointestinal emergencies, often resulting in self-digestion, edema, hemorrhage, and even necrosis of pancreatic tissue. When AP progresses to severe acute pancreatitis (SAP), it often causes multi-organ damage, leading to a high mortality rate. However, the molecular mechanisms underlying SAP-mediated organ damage remain unclear. This study aims to systematically mine SAP data from public databases and combine experimental validation to identify key molecules involved in multi-organ damage caused by SAP. Retrieve transcriptomic data of mice pancreatic tissue for AP, lung and liver tissue for SAP, and corresponding normal tissue from the Gene Expression Omnibus (GEO) database. Conduct gene differential analysis using Limma and DEseq2 methods. Perform enrichment analysis using the clusterProfiler package in R software. Score immune cells and immune status in various organs using single-sample gene set enrichment analysis (ssGSEA). Evaluate mRNA expression levels of core genes using reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Validate serum amylase, TNF-α, IL-1ß, and IL-6 levels in peripheral blood using enzyme-linked immunosorbent assay (ELISA), and detect the formation of neutrophil extracellular traps (NETs) in mice pancreatic, liver, and lung tissues using immunofluorescence. Differential analysis reveals that 46 genes exhibit expression dysregulation in mice pancreatic tissue for AP, liver and lung tissue for SAP, as well as peripheral blood in humans. Functional enrichment analysis indicates that these genes are primarily associated with neutrophil-related biological processes. ROC curve analysis indicates that 12 neutrophil-related genes have diagnostic potential for SAP. Immune infiltration analysis reveals high neutrophil infiltration in various organs affected by SAP. Single-cell sequencing analysis shows that these genes are predominantly expressed in neutrophils and macrophages. FPR1, ITGAM, and C5AR1 are identified as key genes involved in the formation of NETs and activation of neutrophils. qPCR and IHC results demonstrate upregulation of FPR1, ITGAM, and C5AR1 expression in pancreatic, liver, and lung tissues of mice with SAP. Immunofluorescence staining shows increased levels of neutrophils and NETs in SAP mice. Inhibition of NETs formation can alleviate the severity of SAP as well as the levels of inflammation in the liver and lung tissues. This study identified key genes involved in the formation of NETs, namely FPR1, ITGAM, and C5AR1, which are upregulated during multi-organ damage in SAP. Inhibition of NETs release effectively reduces the systemic inflammatory response and liver-lung damage in SAP. This research provides new therapeutic targets for the multi-organ damage associated with SAP.

Global Trends in mHealth and Medical Education Research: Bibliometrics and Knowledge Graph Analysis.

Background: Mobile health (mHealth) is an emerging mobile communication and networking technology for health care systems. The integration of mHealth in medical education is growing extremely rapidly, bringing new changes to the field. However, no study has analyzed the publication and research trends occurring in both mHealth and medical education. Objective: The aim of this study was to summarize the current application and development trends of mHealth in medical education by searching and analyzing published articles related to both mHealth and medical education. Methods: The literature related to mHealth and medical education published from 2003 to 2023 was searched in the Web of Science core database, and 790 articles were screened according to the search strategy. The HistCite Pro 2.0 tool was used to analyze bibliometric indicators. VOSviewer, Pajek64, and SCImago Graphica software were used to visualize research trends and identify hot spots in the field. Results: In the past two decades, the number of published papers on mHealth in medical education has gradually increased, from only 3 papers in 2003 to 130 in 2022; this increase became particularly evident in 2007. The global citation score was determined to be 10,600, with an average of 13.42 citations per article. The local citation score was 96. The United States is the country with the most widespread application of mHealth in medical education, and most of the institutions conducting in-depth research in this field are also located in the United States, closely followed by China and the United Kingdom. Based on current trends, global coauthorship and research exchange will likely continue to expand. Among the research journals publishing in this joint field, journals published by JMIR Publications have an absolute advantage. A total of 105 keywords were identified, which were divided into five categories pointing to different research directions. Conclusions: Under the influence of COVID-19, along with the popularization of smartphones and modern communication technology, the field of combining mHealth and medical education has become a more popular research direction. The concept and application of digital health will be promoted in future developments of medical education.

An antiferromagnetic spin phase change memory.

The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.

Emerging Antiferromagnets for Spintronics.

Antiferromagnets constitute promising contender materials for next-generation spintronic devices with superior stability, scalability, and dynamics. Nevertheless, the perception of well-established ferromagnetic spintronics underpinned by spontaneous magnetization seemed to indicate the inadequacy of antiferromagnets for spintronics-their compensated magnetization has been perceived to result in uncontrollable antiferromagnetic order and subtle magnetoelectronic responses. However, remarkable advancements have been achieved in antiferromagnetic spintronics in recent years, with consecutive unanticipated discoveries substantiating the feasibility of antiferromagnet-centered spintronic devices. It is emphasized that, distinct from ferromagnets, the richness in complex antiferromagnetic crystal structures is the unique and essential virtue of antiferromagnets that can open up their endless possibilities of novel phenomena and functionality for spintronics. In this Perspective, the recent progress in antiferromagnetic spintronics is reviewed, with a particular focus on that based on several kinds of antiferromagnets with special antiferromagnetic crystal structures. The latest developments in efficiently manipulating antiferromagnetic order, exploring novel antiferromagnetic physical responses, and demonstrating prototype antiferromagnetic spintronic devices are discussed. An outlook on future research directions is also provided. It is hoped that this Perspective can serve as guidance for readers who are interested in this field and encourage unprecedented studies on antiferromagnetic spintronic materials, phenomena, and devices.

Magnetic-Field Response and Giant Electric-Field Modulation of Cu2S.

Cu2S likely plays an important role in the sharp resistivity transition of LK-99. Nevertheless, this immediately arouses an intriguing question of whether the extraordinary room-temperature colossal magnetoresistance in the initial reports, which has been less focused, originates from Cu2S as well. To resolve this issue, we have systematically investigated the electrical transport and magnetotransport properties of near-stoichiometric Cu2S pellets and thin films. Neither Cu2S nor LK-99 containing Cu2S in this study was found to exhibit the remarkable magnetoresistance effect implied by Lee et al. This implies that Cu2S could not account for all of the intriguing transport properties of the initially reported LK-99, and the initially reported LK-99 samples might contain magnetic impurities. Moreover, based on the crystal-structure-sensitive electrical properties of Cu2S, we have constructed a piezoelectric-strain-controlled device and obtained a giant and reversible resistance modulation of 2 orders of magnitude at room temperature, yielding a huge gauge factor of 160,000.

Fucosyltransferases Regulated by Fusobacterium Nucleatum and Act as Novel Biomarkers in Colon Adenocarcinoma.

Purpose: Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated mortality worldwide. Fucosyltransferases (FUTs) are associated with numerous cancers. We aimed to investigate the functions of FUTs in COAD. Patients and Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the expression and clinical relevance of FUTs in COAD. Real Time Quantitative PCR (RT-qPCR), Western blot, immunohistochemistry and ELISA were used to detect the relative RNA and protein expression levels. Colitis-associated cancer mice treated with Fusobacterium nucleatum were used to illustrate the effects of Fusobacterium nucleatum on FUTs and COAD. Luciferase reporting assay was used to investigate the binding of miRNA to mRNA. Results: TCGA and GEO datasets showed abnormal expression of FUTs in COAD at transcript level. RT-qPCR, Western blot and immunohistochemistry showed increased expression of FUT1, POFUT1 and POFUT2 in COAD. COAD patients with a high expression of FUT1, FUT11, FUT13 (POFUT2) had a worse prognosis, while patients with a high expression of FUT2, FUT3, FUT6 had a better prognosis. FUT1 and POFUT2 could independently predict the prognosis of COAD patients. Functional analysis by CancerSEA database showed that FUT3, FUT6, FUT8, FUT12 (POFUT1) and FUT13 are associated with differentiation, apoptosis, invasion, quiescence, and hypoxia. FUTs are associated with the tumor microenvironment of COAD. FUT1 regulated by miR-939-3p inhibit the expression of MUC2. Fusobacterium nucleatum may affect the expression of FUTs by affecting their transcription factors and miRNA levels. Moreover, Fusobacterium nucleatum promotes COAD progression through the miR-939-3p/FUT1/MUC2 axis. Conclusion: Fucosyltransferases play an important role and may be the mediator of Fusobacterium nucleatum promoting COAD progression.

miR-199a-5p Reduces Chondrocyte Hypertrophy and Attenuates Osteoarthritis Progression via the Indian Hedgehog Signal Pathway.

Osteoarthritis (OA), the most common type of arthritis, is an age-associated disease, characterized by the progressive degradation of articular cartilage, synovial inflammation, and degeneration of subchondral bone. Chondrocyte proliferation is regulated by the Indian hedgehog (IHH in humans, Ihh in animals) signaling molecule, which regulates hypertrophy and endochondral ossification in the development of the skeletal system. microRNAs (miRNAs, miRs) are a family of about 22-nucleotide endogenous non-coding RNAs, which negatively regulate gene expression. In this study, the expression level of IHH was upregulated in the damaged articular cartilage tissues among OA patients and OA cell cultures, while that of miR-199a-5p was the opposite. Further investigations demonstrated that miR-199a-5p could directly regulate IHH expression and reduce chondrocyte hypertrophy and matrix degradation via the IHH signal pathway in the primary human chondrocytes. The intra-articular injection of synthetic miR-199a-5p agomir attenuated OA symptoms in rats, including the alleviation of articular cartilage destruction, subchondral bone degradation, and synovial inflammation. The miR-199a-5p agomir could also inhibit the Ihh signaling pathway in vivo. This study might help in understanding the role of miR-199a-5p in the pathophysiology and molecular mechanisms of OA and indicate a potential novel therapeutic strategy for OA patients.

Topological Hall Effect in Thin Films of an Antiferromagnetic Weyl Semimetal Integrated on Si.

Since the large room-temperature anomalous Hall effect was discovered in noncollinear antiferromagnets, Mn3Sn has received immense research interest as it exhibits abundant exotic physical properties including Weyl points and enormous potential for antiferromagnetic spintronic device applications. In this work, we report the emergence of the topological Hall effect in Mn3Sn films grown on Si that is the workhorse for the modern highly integrated information technology. Importantly, through a series of systematic comparative experiments, the intriguing topological Hall effect phenomenon related to the appearance of the noncoplanar chiral spin structure is found to be induced by the Mn3Sn/SiO2 interface. Furthermore, it was found that the current injection to a Pt/Mn3Sn bilayer Hall bar device can effectively manipulate the chiral spin structure of Mn3Sn, which demonstrates the feasibility of Si-based noncollinear antiferromagnetic spintronics.

Room-temperature magnetoresistance in an all-antiferromagnetic tunnel junction.

Antiferromagnetic spintronics1-16 is a rapidly growing field in condensed-matter physics and information technology with potential applications for high-density and ultrafast information devices. However, the practical application of these devices has been largely limited by small electrical outputs at room temperature. Here we describe a room-temperature exchange-bias effect between a collinear antiferromagnet, MnPt, and a non-collinear antiferromagnet, Mn3Pt, which together are similar to a ferromagnet-antiferromagnet exchange-bias system. We use this exotic effect to build all-antiferromagnetic tunnel junctions with large nonvolatile room-temperature magnetoresistance values that reach a maximum of about 100%. Atomistic spin dynamics simulations reveal that uncompensated localized spins at the interface of MnPt produce the exchange bias. First-principles calculations indicate that the remarkable tunnelling magnetoresistance originates from the spin polarization of Mn3Pt in the momentum space. All-antiferromagnetic tunnel junction devices, with nearly vanishing stray fields and strongly enhanced spin dynamics up to the terahertz level, could be important for next-generation highly integrated and ultrafast memory devices7,9,16.

Chemical Potential Switching of the Anomalous Hall Effect in an Ultrathin Noncollinear Antiferromagnetic Metal.

The discovery of the anomalous Hall effect in noncollinear antiferromagnetic metals represents one of the most important breakthroughs for the emergent antiferromagnetic spintronics. The tuning of chemical potential has been an important theoretical approach to varying the anomalous Hall conductivity, but the direct experimental demonstration has been challenging owing to the large carrier density of metals. In this work, an ultrathin noncollinear antiferromagnetic Mn3 Ge film is fabricated and its carrier density is modulated by ionic liquid gating. Via a small voltage of ≈3 V, its carrier density is altered by ≈90% and, accordingly, the anomalous Hall effect is completely switched off. This work thus creates an attractive new way to steering the anomalous Hall effect in noncollinear antiferromagnets.

Antiferromagnetism in Ni-Based Superconductors.

Due to the lack of any magnetic order down to 1.7 K in the parent bulk compound NdNiO2 , the recently discovered 9-15 K superconductivity in the infinite-layer Nd0.8 Sr0.2 NiO2 thin films has provided an exciting playground for unearthing new superconductivity mechanisms. Herein, the successful synthesis of a series of superconducting Nd0.8 Sr0.2 NiO2 thin films ranging from 8 to 40 nm is reported. The large exchange bias effect is observed between the superconducting Nd0.8 Sr0.2 NiO2 films and a thin ferromagnetic layer, which suggests the existence of the antiferromagnetic order. Furthermore, the existence of the antiferromagnetic order is evidenced by X-ray magnetic linear dichroism measurements. These experimental results are fundamentally critical for the current field.

Intermittent high glucose induces pyroptosis of rat H9C2 cardiomyocytes via sodium-glucose cotransporter 1.

Cardiomyocyte death is an important pathogenic process in cardiac complications of diabetes. Diabetic patients often suffer glycemic variability. Pyroptosis is a form of programmed cell death triggered by inflammasomes and related with caspase-1 and gasdermin D activation. The present study was designed to examine the effects of intermittent high glucose simulating glycemic variability on the pyroptosis of cardiomyocytes in vitro. Rat H9C2 cardiomyocytes were incubated with normal glucose (NG), constant high glucose (CHG) and intermittent high glucose (IHG). Results showed that compared to CHG treatment, IHG further inhibited cell proliferation and promoted cell death of H9C2 cardiomyocytes. In addition, IHG upregulated higher levels of the expressions of inflammasome NLR family pyrin domain containing 3 (NLRP3) and adaptor protein apoptosis-associated speck-like protein containing CARD domain (ASC) and increased higher levels of activated caspase-1 and gasdermin D than CHG treatment. Moreover, the production of reactive oxygen species (ROS) and activation of NF-κB that is induced by IHG were significantly higher than that induced by CHG. Knockdown of sodium-glucose cotransporters 1 (SGLT1) in H9C2 cardiomyocytes was performed and the effects of SGLT1 on IHG-induced pyroptosis was evaluated. The results demonstrated that knockdown of SGLT1 partially reduced IHG-induced pyroptosis, ROS generation and NF-κB activation. Our results indicated that IHG is harmful to cardiomyocytes and it might be partially because of the SGLT1-depedent pyroptosis in cardiomyocytes.

Inhibition of SGLT1 protects against glycemic variability-induced cardiac damage and pyroptosis of cardiomyocytes in diabetic mice.

AIMS: Glycemic variability has been shown to be more harmful in the development of diabetic complication than sustained chronic hyperglycemia. In this present study, we tried to reveal the effects of glycemic variability on cardiac damage in diabetic mice and investigate whether sodium-glucose cotransporter 1 (SGLT1), an important cardiac glucose transporter, functions as an important mediator in the process. MATERIALS AND METHODS: Type 2 diabetes mellitus (DM) mice were induced by a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then glycemic variability in type 2 diabetes mellitus (GVDM) was induced by alternately injecting insulin and glucose to DM mice. In order to determine the roles of SGLT1 in GVDM mice, SGLT1 inhibition was performed using shRNA against SGLT1. The blood glucose level, the cardiac function and myocardial injury were assessed. And the expressions of SGLT1 and the activations of NLRP3/caspase-1 pathway and NF-κB in left ventricular tissues were measured. KEY FINDINGS: The results showed that SGLT1 was highly expressed in heart of GVDM mice compared to control and DM groups, and knockdown of SGLT1 reduced glycemic variability in GVDM mice. Moreover, glycemic variability impaired cardiac function, aggravated cardiac injury and induced NLRP3/caspase-1-mediated inflammatory response and pyroptosis. And knockdown of SGLT1 significantly attenuated the cardiac damages that induced by glycemic variability. SIGNIFICANCE: The results indicated that glycemic variability could cause cardiac damage and induce inflammatory response and pyroptosis of cardiomyocytes in diabetic mice, which could be partially blocked by SGLT1 silence.

Knockdown of SGLT1 prevents the apoptosis of cardiomyocytes induced by glucose fluctuation via relieving oxidative stress and mitochondrial dysfunction.

Fluctuations in the concentration of glucose in the blood is more detrimental than a constantly high level of glucose with respect to the development of cardiovascular complications associated with diabetes mellitus (DM). Sodium glucose cotransporter 2 (SGLT2) inhibitors have been developed as antidiabetic drugs with cardiovascular benefits; however, whether inhibition of SGLT1 protects the diabetic heart remains to be determined. This study investigated the role of SGLT1 in rat H9c2 cardiomyocytes subjected to fluctuating levels of glucose and the underlying mechanisms. The results indicated that knockdown of SGLT1 restored cell proliferation and suppressed the cytotoxicity associated with fluctuating glucose levels. Oxidative stress was induced in H9c2 cells subjected to fluctuating glucose levels, but these changes were effectively reversed by knockdown of SGLT1, as manifested by reductions in the level of intracellular reactive oxygen species and increased antioxidant activity. Further study demonstrated that knockdown of SGLT1 attenuated the mitochondrial dysfunction in H9c2 cells exposed to fluctuating glucose levels, by restoring mitochondrial membrane potential and promoting mitochondrial fusion. In addition, knockdown of SGLT1 downregulated the expression of Bax, upregulated the expression of Bcl-2, and reduced the activation of caspase-3 in H9c2 cells subjected to fluctuating levels of glucose. Collectively, our results show that knockdown of SGLT1 ameliorates the apoptosis of cardiomyocyte caused by fluctuating glucose levels via regulating oxidative stress and combatting mitochondrial dysfunction.