Contrasting effects of music therapy and aromatherapy on perioperative anxiety: A systematic review and meta-analysis.

INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; P =.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; P =.02), while those at 4 hours after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; P <.001). CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicates that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.

Research Progress on Extracellular Matrix Involved in the Development of Preeclampsia.

Preeclampsia (PE) is a serious pregnancy complication, and its primary clinical manifestations are gestational hypertension and proteinuria. Trophoblasts are responsible for the basic functions of the placenta during placental development; recent studies have revealed that placental "shallow implantation" caused by the decreased invasiveness of placental trophoblasts plays a crucial role in PE pathogenesis. The interaction between the cells and the extracellular matrix (ECM) plays a crucial role in trophoblast proliferation, differentiation, and invasion. Abnormal ECM function can result in insufficient migration and invasion of placental trophoblasts, thus participating in PE. This article summarizes the recent studies on the involvement of ECM components, including small leucine-rich proteoglycans, syndecans, glypicans, laminins, fibronectin, collagen, and hyaluronic acid, in the development of PE. ECM plays various roles in PE development, most notably by controlling the activities of trophoblasts. The ECM is structurally stable and can serve as a biological diagnostic marker and therapeutic target for PE.

Light exposure and its applications in human health.

Light exposure has been proven to have a significant impact on human health. As a result, researchers are increasingly exploring its potential benefits and drawbacks. With advancements in understanding light and the manufacturing of light sources, modern health lighting has become widely utilized in daily life and plays a critical role in the prevention and treatment of various illnesses. The use of light in healthcare is a global trend, with many countries actively promoting the development and application of relevant scientific research and medical technology. This field has gained worldwide attention and support from scientists and doctors alike. In this review, we examine the application of lighting in human health and recent breakthroughs in light exposure related to pathology, therapeutic strategies, molecular changes, and more. Finally, we also discuss potential future developments and areas of application.

Impact of pulmonary rehabilitation on patients with different chronic respiratory diseases during hospitalization.

The impact of pulmonary rehabilitation (PR) on patients with different chronic respiratory diseases (CRDs) during hospitalization has not been thoroughly evaluated before. The objectives of the current research were to assess the effect of comprehensive PR management on inpatients' self-management skills, exercise capacity, nutrition assessment and mental health issues and explore whether impacts of PR vary in different CRDs. This retrospective study analyzed the clinical data from 272 inpatients with CRDs receiving PR management during hospitalization between October 2020 and March 2022 in Beijing Chao-Yang Hospital. Significant improvements were found in the patients' ability of daily living (ADL), dyspnea (assessed by modified medical research council dyspnea scale (MMRC)), handgrip strength, maximal inspiratory and expiratory pressure, anxiety (using the 7-item generalized anxiety disorder scale (GAD-7)) and depression (the 9-item patient health questionnaire score (PHQ-9)). There was no significant change in nutrition assessment pre-post PR management during hospitalization. The subgroup analyses were conducted on hospitalized patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, interstitial lung diseases (ILDs) and other CRDs (e.g., lung cancer, diaphragm hemiparesis, obesity, etc.). The results showed that ADL, MMRC score, MIP, MEP, PHQ-9 score improved in all subgroups with CRDs. Handgrip strength of left hand was increased in COPD inpatients and anxiety was improved in all subgroups except for ILDs. Comprehensive PR management was necessary and beneficial for patients with different CRDs during hospitalization.

[Methods for traditional Chinese medicine syndrome-based efficacy evaluation: a review].

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

[Study on mechanism of icariin-induced ferroptosis in HepG2 hepatoma carcinoma cells through PPARG/FABP4/GPX4 pathway].

The aim of this study was to explore the mechanism of icaritin-induced ferroptosis in hepatoma HepG2 cells. By bioinformatics screening, the target of icariin's intervention in liver cancer ferroptosis was selected, the protein-protein interaction(PPI) network was constructed, the related pathways were focused, the binding ability of icariin and target protein was evaluated by molecular docking, and the impact on patients' survival prognosis was predicted and the clinical prediction model was built. CCK-8, EdU, and clonal formation assays were used to detect cell viability and cell proliferation; colorimetric method and BODIPY 581/591 C1 fluorescent probe were used to detect the levels of Fe~(2+), MDA and GSH in cells, and the ability of icariin to induce HCC cell ferroptosis was evaluated; RT-qPCR and Western blot detection were used to verify the mRNA and protein levels of GPX4, xCT, PPARG, and FABP4 to determine the expression changes of these ferroptosis-related genes in response to icariin. Six intervention targets(AR, AURKA, PPARG, AKR1C3, ALB, NQO1) identified through bioinformatic analysis were used to establish a risk scoring system that aids in estimating the survival prognosis of HCC patients. In conjunction with patient age and TNM staging, a comprehensive Nomogram clinical prediction model was developed to forecast the 1-, 3-, and 5-year survival of HCC patients. Experimental results revealed that icariin effectively inhibited the activity and proliferation of HCC cells HepG2, significantly modulating levels of Fe~(2+), MDA, and lipid peroxidation ROS while reducing GSH levels, hence revealing its potential to induce ferroptosis in HCC cells. Icariin was found to diminish the expression of GPX4 and xCT(P<0.01), inducing ferroptosis in HCC cells, potentially in relation to inhibition of PPARG and FABP4(P<0.01). In summary, icariin induces ferroptosis in HCC cells via the PPARG/FABP4/GPX4 pathway, providing an experimental foundation for utilizing the traditional Chinese medicine icariin in the prevention or treatment of HCC.

Palmatine inhibits expression fat mass and obesity associated protein (FTO) and exhibits a curative effect in dextran sulfate sodium (DSS)-induced experimental colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease whose pathogenesis and mechanisms have not been fully described. The m6A methylation modification is a general mRNA modification in mammalian cells and is closely associated with the onset and progression of inflammatory bowel disease (IBD). Palmatine (PAL) is a biologically active alkaloid with anti-inflammatory and protective effects in animal models of colitis. Accordingly, we examined the role of PAL on colitis by regulating N6-methyladenosine (m6A) methylation. METHODS: A rat experimental colitis model was established by 5 % dextran sulfate sodium (DSS) in drinking water for seven days, then PAL treatment was administered for seven days. The colonic tissue pathology was assessed using hematoxylin-eosin (HE) and disease activity index (DAI). In in vitro studies, a human, spontaneously immortalized non-cancerous colon mucosal epithelial cell line (NCM460) was exposed to 2 % DSS and treated with PAL and cell viability was assayed using Cell Counting Kit-8 (CCK-8). The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA) kits. The level of Zonula occludens-1 (ZO-1) was dectected by immunofluorescence. Transepithelial electrical resistance (TEER) of cells was also assessed. The methyltransferase-like 3 (METTL3), METTL14, AlkB homologate 5 (ALKBH5), and fat mass and obesity-associated protein (FTO) expression levels were assessed by western blotting. The localized expression of m6A was measured by immunofluorescence. RESULTS: PAL significantly prevented bodyweight loss and shortening of the colon in experimental colitis rats, as well as decreasing the DAI and histological damage scores. Furthermore, PAL inhibited the levels of inflammatory factors (TNF-α, IL-6, IL-8, and IL-1ß) in both DSS treated rats and NCM460 cells. In addition, PAL enhanced the expression level of ZO-1, and increased the transepithelial electrical resistance to repaire intestinal barrier dysfunction. Colitis occurred due to decreased m6A levels, and the increased FTO expression led to a colitis phenotype. PAL markedly enhanced the METTL3 and METTL14 expression levels while decreasing ALKBH5 and FTO expression levels. CONCLUSIONS: The findings demonstrated that PAL improved DSS-induced experimental colitis. This effect was associated with inhibiting FTO expression and regulating m6A methylation.

A Free Amino Acid Diet Alleviates Colorectal Tumorigenesis through Modulating Gut Microbiota and Metabolites.

Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for cancer therapy effectiveness. This study explored the effects of a casein protein diet (CTL) versus a free amino acid (FAA)-based diet on CRC progression, gut microbiota, and metabolites using carcinogen-induced (AOM/DSS) and spontaneous genetically induced (ApcMin/+ mice) CRC mouse models. Comprehensive approaches including 16s rRNA gene sequencing, transcriptomics, metabolomics, and immunohistochemistry were utilized. We found that the FAA significantly attenuated CRC progression, evidenced by reduced colonic shortening and histopathological alterations compared to the CTL diet. Notably, the FAA enriched beneficial gut bacteria like Akkermansia and Bacteroides and reversed CRC-associated dysbiosis. Metabolomic analysis highlighted an increase in ornithine cycle metabolites and specific fatty acids, such as Docosapentaenoic acid (DPA), in FAA-fed mice. Transcriptomic analysis revealed that FAA up-regulated Egl-9 family hypoxia inducible factor 3 (Egln 3) and downregulated several cancer-associated pathways including Hippo, mTOR, and Wnt signaling. Additionally, DPA was found to significantly induce EGLN 3 expression in CRC cell lines. These results suggest that FAA modulate gut microbial composition, enhance protective metabolites, improve gut barrier functions, and inhibit carcinogenic pathways.

Prediction of cross-border spread of the COVID-19 pandemic: A predictive model for imported cases outside China.

The COVID-19 pandemic has been present globally for more than three years, and cross-border transmission has played an important role in its spread. Currently, most predictions of COVID-19 spread are limited to a country (or a region), and models for cross-border transmission risk assessment remain lacking. Information on imported COVID-19 cases reported from March 2020 to June 2022 was collected from the National Health Commission of China, and COVID-19 epidemic data of the countries of origin of the imported cases were collected on data websites such as WHO and Our World in Data. It is proposed to establish a prediction model suitable for the prevention and control of overseas importation of COVID-19. Firstly, the SIR model was used to fit the epidemic infection status of the countries where the cases were exported, and most of the r2 values of the fitted curves obtained were above 0.75, which indicated that the SIR model could well fit different countries and the infection status of the region. After fitting the epidemic infection status data of overseas exporting countries, on this basis, a SIR-multiple linear regression overseas import risk prediction combination model was established, which can predict the risk of overseas case importation, and the established overseas import risk model overall P <0.05, the adjusted R2 = 0.7, indicating that the SIR-multivariate linear regression overseas import risk prediction combination model can obtain better prediction results. Our model effectively estimates the risk of imported cases of COVID-19 from abroad.

Protective Effects and Mechanisms of Luteolin against Acute Respiratory Distress Syndrome: Network Pharmacology and In vivo and In vitro Studies.

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) is an acute life-threatening disease, and luteolin has the potential to become a therapeutic agent for ARDS. However, its mechanism of action has not yet been clarified. OBJECTIVE: The present study explored the potential effects and mechanisms of luteolin in the treatment of ARDS through network pharmacology analysis and verified them through biological experiments. METHODS: The potential targets of luteolin and ARDS were obtained from online databases. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the underlying molecular mechanisms and to identify hub targets. Molecular docking was used to verify the relationship between luteolin and target proteins. Finally, the effects of luteolin on key signaling pathways and biological processes were verified by in vitro and in vivo experiments. RESULTS: A total of 146 luteolin- and 496 ARDS-related targets were extracted from public databases. The network pharmacological analysis suggested that luteolin could inhibit ARDS through the following potential therapeutic targets: AKT1, RELA, and NFKBIA. Inflammatory and oxidative stress responses were the main biological processes involved, with the AKT/NF-κB signaling pathway being the key signaling pathway targeted by luteolin for the treatment of ARDS. Molecular docking analysis indicated that luteolin had a good binding affinity to AKT1, RELA, and NFKBIA. The in vitro and in vivo experiments revealed that luteolin could regulate the inflammatory response and oxidative stress in the treatment of ARDS by inhibiting the AKT/NF- κB signaling pathway. CONCLUSION: Luteolin could reduce the production of reactive oxygen species and inflammatory factors by inhibiting the AKT/NF-κB signaling pathway, thus reducing apoptosis and attenuating ARDS.

Robotic-Assisted Hip and Knee Arthroplasty: A Bibliometric Analysis Using the Scopus Database.

Robotic-assisted hip and knee arthroplasty represents cutting-edge advancements in orthopedic surgery, harnessing robotic technology to enhance precision, improve clinical outcomes, and facilitate intra-operative procedures. In these robotic-assisted surgeries, the robotic systems assist surgeons in planning and executing joint replacement surgeries, thereby facilitating personalized implant positioning and optimizing the fit and alignment of hip and knee implants. Despite the increasing attention garnered by robotic-assisted hip and knee arthroplasty in recent years, a comprehensive bibliometric analysis using the Scopus database has yet to be conducted. This bibliometric analysis reviews the Scopus database from 1961 until 2022 to investigate the literature on the field of robotic-assisted hip and knee arthroplasty. A total of 577 articles that satisfied the selection criteria were included in this review. The majority of the articles focus more on total knee replacement, compared to total hip replacement and unicompartmental knee arthroplasty. The overwhelming majority of the articles were authored by researchers and clinicians from the United States of America (USA) and the United Kingdom (UK). Similarly, most of the articles with the highest number of citations were authored by researchers and clinicians from these regions. This comprehensive bibliometric analysis using Scopus in the domain of robotic-assisted hip and knee replacement has the potential to act as a roadmap for researchers, clinicians, and policymakers, facilitating informed decision-making, promoting collaborative initiatives, and guiding the development of future studies to further advance the field of robotic-assisted hip and knee arthroplasty.

The double-edged effect of social mobility belief on socioeconomically disadvantaged adolescents' health: The mediating role of intentional self-regulation.

PURPOSE: This study aimed to examine the double-edged effect of social mobility belief on socioeconomically disadvantaged adolescents' mental and physical health and further explore whether intentional self-regulation is the common psychological mechanism of social mobility belief affecting physical and mental health. METHOD: A total of 469 adolescents (Mage = 13.96 years, 49.3% boys) from two rural public schools in China were included in this study. Adolescents completed questionnaires measuring social mobility belief and mental health (life satisfaction, self-esteem, and depression). Physical health (allostatic load) was reflected by six indicators (resting diastolic and systolic blood pressure, body mass index, epinephrine, norepinephrine, and cortisol). RESULTS: Social mobility belief was positively correlated with adolescents' life satisfaction and self-esteem but negatively correlated with depression. Intentional self-regulation mediated the relationships between social mobility belief and mental health. In addition, the results showed that intentional self-regulation mediated the relationship between social mobility belief and adolescents' physical health. CONCLUSIONS: Social mobility belief may be a "skin-deep" resilience resource positively related to mental health but negatively correlated with physical health through intentional self-regulation among socioeconomically disadvantaged adolescents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Tartronic Acid as a Potential Inhibitor of Pathological Calcium Oxalate Crystallization.

Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone-related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.

Targeting foamy macrophages by manipulating ABCA1 expression to facilitate lesion healing in the injured spinal cord.

Spinal cord injury (SCI) triggers a complex cascade of events, including myelin loss, neuronal damage, neuroinflammation, and the accumulation of damaged cells and debris at the injury site. Infiltrating bone marrow derived macrophages (BMDMϕ) migrate to the epicenter of the SCI lesion, where they engulf cell debris including abundant myelin debris to become pro-inflammatory foamy macrophages (foamy Mϕ), participate neuroinflammation, and facilitate the progression of SCI. This study aimed to elucidate the cellular and molecular mechanisms underlying the functional changes in foamy Mϕ and their potential implications for SCI. Contusion at T10 level of the spinal cord was induced using a New York University (NYU) impactor (5 g rod from a height of 6.25 mm) in male mice. ABCA1, an ATP-binding cassette transporter expressed by Mϕ, plays a crucial role in lipid efflux from foamy cells. We observed that foamy Mϕ lacking ABCA1 exhibited increased lipid accumulation and a higher presence of lipid-accumulated foamy Mϕ as well as elevated pro-inflammatory response in vitro and in injured spinal cord. We also found that both genetic and pharmacological enhancement of ABCA1 expression accelerated lipid efflux from foamy Mϕ, reduced lipid accumulation and inhibited the pro-inflammatory response of foamy Mϕ, and accelerated clearance of cell debris and necrotic cells, which resulted in functional recovery. Our study highlights the importance of understanding the pathologic role of foamy Mϕ in SCI progression and the potential of ABCA1 as a therapeutic target for modulating the inflammatory response, promoting lipid metabolism, and facilitating functional recovery in SCI.

High-resolution multi-reflection time-of-flight mass spectrometer with atmospheric pressure interface.

RATIONALE: Atmospheric pressure interface multi-reflection time-of-flight mass spectrometry (API-MRTOF-MS) has the potential to be a rapid and high-resolution analytical tool for versatile applications in chemistry, biology, environmental science, and medicine. METHODS: The ions were reflected in a mass analyzer via electrostatic mirrors and folded flight path. Therefore, flight distances were significantly increased. The ion flight path of the API-MRTOF-MS was extended from meters to over 1 km, and the mass resolution was increased. Furthermore, the mass analysis could be completed at around 10 ms due to the rapid response of TOF-MS. RESULTS: A high-resolution API-MRTOF-MS approach is successfully developed in this study. The mass resolution could achieve 116 050 (full widths at half maximum [FWHM]) for Cs+ ions using an atmospheric pressure electrospray ionization within a total TOF of only 18 ms. An ion transmission efficiency of over 50% was achieved after 600 cycles. CONCLUSIONS: The analytical performance of the newly developed API-MRTOF-MS demonstrated that it is suitable for high resolution and rapid analysis in many fields.

Circular RNA as a source of neoantigens for cancer vaccines.

BACKGROUND: The effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this study investigates the potential of tumor-associated circular RNAs (circRNAs) as an alternative source of neoepitopes in CRC. METHODS: Tumor-associated circRNAs in CRC were identified using the MiOncoCirc database and ribo-depletion RNA sequencing of paired clinical normal and tumor samples. Candidate circRNA expression was validated by quantitative real-time PCR (RT-qPCR) using divergent primers. TransCirc database was used for translation prediction. Human leukocyte antigen binding affinity of open reading frames from potentially translatable circRNA was predicted using pVACtools. Strong binders from messenger RNA-encoded proteins were excluded using BlastP. The immunogenicity of the candidate antigens was functionally validated through stimulation of naïve CD8+ T cells against the predicted neoepitopes and subsequent analysis of the T cells through enzyme-linked immunospot (ELISpot) assay, intracellular cytokine staining (ICS) and granzyme B (GZMB) reporter. The cytotoxicity of T cells trained with antigen peptides was further tested using patient-derived organoids. RESULTS: We identified a neoepitope from circRAPGEF5 that is upregulated in CRC tumor samples from MiOncoCirc database, and two neoepitopes from circMYH9, which is upregulated across various tumor samples from our matched clinical samples. The translation potential of candidate peptides was supported by Clinical Proteomic Tumor Analysis Consortium database using PepQuery. The candidate peptides elicited antigen-specific T cells response and expansion, evidenced by various assays including ELISpot, ICS and GZMB reporter. Furthermore, T cells trained with circMYH9 peptides were able to specifically target and eliminate tumor-derived organoids but not match normal organoids. This observation underscores the potential of circRNAs as a source of immunogenic neoantigens. Lastly, circMYH9 was enriched in the liquid biopsies of patients with CRC, thus enabling a detection-to-vaccination treatment strategy for patients with CRC. CONCLUSIONS: Our findings underscore the feasibility of tumor-associated circRNAs as an alternative source of neoantigens for cancer vaccines targeting tumors with moderate mutation levels.

In Situ Visualization of RNA-Specific Sialylation on Living Cell Membranes to Explore N-Glycosylation Sites.

The small RNAs on living cell membranes were recently found to be N-glycosylated and terminated with sialic acids, although the glycosylation sites and potential functions remain unclear. Herein, we designed a second-generation hierarchical coding strategy (HieCo 2) for in situ visualization of cell surface RNA-specific sialylation. After covalently binding DNA codes to sialic acids and then binding a DNA code to a target RNA via sequence specificity, cascade decoding processes were performed with subsequent signal amplification that enabled sensitive in situ visualization of low-abundance Y5 RNA-specific sialic acids on living cell membranes. The proposed strategy unveils the number of glycosylation sites on a single RNA and reveals the binding preference of glycosylated RNAs to different sialic acid binding-immunoglobulin lectin-type receptors, demonstrating a new route for exploration of the glycosylated RNA-related biological and pathological processes.

NK-cell-elicited gasdermin-D-dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitates HBV-related acute-on-chronic liver failure.

BACKGROUND AIMS: Hepatitis B virus (HBV) infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF. APPROACH RESULTS: We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in pyroptotic liver, and HMGB1 derived from pyroptotic liver constituted an important factor triggering generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of MPO-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF. CONCLUSIONS: Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring liver function of HBV-related ACLF patients.

Identification and Analysis of the MIR399 Gene Family in Grapevine Reveal Their Potential Functions in Abiotic Stress.

MiR399 plays an important role in plant growth and development. The objective of the present study was to elucidate the evolutionary characteristics of the MIR399 gene family in grapevine and investigate its role in stress response. To comprehensively investigate the functions of miR399 in grapevine, nine members of the Vvi-MIR399 family were identified based on the genome, using a miRBase database search, located on four chromosomes (Chr 2, Chr 10, Chr 15, and Chr 16). The lengths of the Vvi-miR399 precursor sequences ranged from 82 to 122 nt and they formed stable stem-loop structures, indicating that they could produce microRNAs (miRNAs). Furthermore, our results suggested that the 2 to 20 nt region of miR399 mature sequences were relatively conserved among family members. Phylogenetic analysis revealed that the Vvi-MIR399 members of dicots (Arabidopsis, tomato, and sweet orange) and monocots (rice and grapevine) could be divided into three clades, and most of the Vvi-MIR399s were closely related to sweet orange in dicots. Promoter analysis of Vvi-MIR399s showed that the majority of the predicted cis-elements were related to stress response. A total of 66.7% (6/9) of the Vvi-MIR399 promoters harbored drought, GA, and SA response elements, and 44.4% (4/9) of the Vvi-MIRR399 promoters also presented elements involved in ABA and MeJA response. The expression trend of Vvi-MIR399s was consistent in different tissues, with the lowest expression level in mature and young fruits and the highest expression level in stems and young leaves. However, nine Vvi-MIR399s and four target genes showed different expression patterns when exposed to low light, high light, heat, cold, drought, and salt stress. Interestingly, a putative target of Vvi-MIR399 targeted multiple genes; for example, seven Vvi-MIR399s simultaneously targeted VIT_213s0067g03280.1. Furthermore, overexpression of Vvi_MIR399e and Vvi_MIR399f in Arabidopsis enhanced tolerance to drought compared with wild-type (WT). In contrast, the survival rate of Vvi_MIR399d-overexpressed plants were zero after drought stress. In conclusion, Vvi-MIR399e and Vvi-MIR399f, which are related to drought tolerance in grapevine, provide candidate genes for future drought resistance breeding.

Alterations of DNA methylation profile in peripheral blood of children with simple obesity.

Purpose: To investigate the association between DNA methylation and childhood simple obesity. Methods: Genome-wide analysis of DNA methylation was conducted on peripheral blood samples from 41 children with simple obesity and 31 normal controls to identify differentially methylated sites (DMS). Subsequently, gene functional analysis of differentially methylated genes (DMGs) was carried out. After screening the characteristic DMGs based on specific conditions, the methylated levels of these DMS were evaluated and verified by pyrosequencing. Receiver operating characteristic (ROC) curve analysis assessed the predictive efficacy of corresponding DMGs. Finally, Pearson correlation analysis revealed the correlation between specific DMS and clinical data. Results: The overall DNA methylation level in the obesity group was significantly lower than in normal. A total of 241 DMS were identified. Functional pathway analysis revealed that DMGs were primarily involved in lipid metabolism, carbohydrate metabolism, amino acid metabolism, human diseases, among other pathways. The characteristic DMS within the genes Transcription factor A mitochondrial (TFAM) and Piezo type mechanosensitive ion channel component 1(PIEZO1) were recognized as CpG-cg05831083 and CpG-cg14926485, respectively. Furthermore, the methylation level of CpG-cg05831083 significantly correlated with body mass index (BMI) and vitamin D. Conclusions: Abnormal DNA methylation is closely related to childhood simple obesity. The altered methylation of CpG-cg05831083 and CpG-cg14926485 could potentially serve as biomarkers for childhood simple obesity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-024-00275-w.