Association of socioeconomic and lifestyle factors with prevalence of diabetes in rural southwest China: a structural equation modelling approach.

OBJECTIVES: This study aimed to investigate the prevalence of diabetes using structural equation modelling (SEM) to examine the pathways and associations of socioeconomic and lifestyle factors on diabetes in rural southwest China. DESIGN: Data were collected from a cross-sectional health interview and examination survey among individuals aged ≥35 years in rural southwest China. Fasting blood glucose, blood pressure, height, weight and waist circumference (WC) were measured for each participant. SEM was employed to assess the relationships between demographic characteristics (sex, age and ethnicity), socioeconomic position (SEP; annual household income, education level and access to medical services), lifestyle factors (obesity status (body mass index and WC) and physical inactivity), hypertension, hyperlipidaemia and family history of diabetes. SETTING: This study was conducted in rural Yunnan Province of China. PARTICIPANTS: 7536 individuals aged ≥35 years consented to participate in the study. RESULTS: The overall prevalence of diabetes in the present study was 8.3%. Prevalence did not differ by gender (prevalence for both men and women was 8.3% (p>0.05)). The results of SEM indicated that SEP, age, ethnicity, obesity status and physical inactivity had both significant direct and indirect effects on diabetes, with total effect size of 0.091, 0.149, -0.094, 0.212 and 0.089, respectively (p<0.01). Family history of diabetes (0.128, p<0.01), hypertension (0.135, p<0.01) and hyperlipidaemia (0.137, p<0.01) were directly associated with diabetes. CONCLUSIONS: Socioeconomic and lifestyle factors have both direct and indirect effects on prevalence of diabetes in rural southwest China. Future efforts to implement comprehensive interventions to promote the prevention and control of diabetes should in particular focus on obese individuals.

Arthroscopic Fixation With Absorbable Suture Anchors for Pipkin Type I Femoral Head Fractures-Letter V Technique.

Femoral head fractures are relatively uncommon high-energy injuries and usually associated with traumatic hip dislocation. Pipkin classified these fractures into 4 types according to the location of the head fragment related to the fovea and associated lesions on the femoral neck or acetabulum. Traditional open reduction and internal fixation for femoral head fracture has been proven to be effective, but it could be associated with significant complications. Arthroscopic fixation with screws is a less-invasive alternative to open reduction and internal fixation that offers several advantages. However, technical challenges could be encountered during the procedure and catastrophic consequences could occur in cases of fixation failure. Therefore, we propose an effective arthroscopic technique for Pipkin type I (small fracture caudal to the fovea capitis) femoral head fractures that uses an absorbable suture anchors. The anchors provide initial stability to the fracture fragments, and then the sutures are tied in a double-pulley fashion to further secure the fracture. Finally, a triangular suture bridge ("letter V") is created, which supplies a convenient and stable fixation for proper femoral head fracture.

Multi-level chiral edge states in Janus M2XS2Se2 (M = V, Ti; X = W, Mo) monolayers with high Curie temperature and sizable nontrivial topological gaps.

Quantum anomalous Hall (QAH) insulators with dissipation-less chiral edge channels provide ideal platforms for the exploration of topological materials and low-power spintronic devices. However, the ultralow operation temperature and small nontrivial gaps are the bottlenecks for QAH insulators towards future applications. Here, a new family of QAH insulators, that is, Janus M2XS2Se2 (M = V, Ti; X = W, Mo) monolayers, are proposed to be ferromagnets with large perpendicular magnetic anisotropy (PMA) and high Curie temperature above room temperature. Moreover, the present M2XS2Se2 monolayers hold sizable nontrivial topological gaps, resulting in the 1st chiral edge state with Chern number C = -1. Unexpectedly, there also exists an occupied 2nd chiral edge state below the Fermi level. Although all M2XS2Se2 monolayers retain their PMA characteristics on application of biaxial strain, various topological phase transitions are present. The V2WS2Se2 monolayer preserves the QAH state regardless of strain, while the V2MoS2Se2 and Ti2WS2Se2 monolayers transform from QAH states to metallic states under tensile strains. The present M2XS2Se2 monolayers show competitive advantages among the reported materials for the development of topological electronic devices.

Additives improve the fermentation quality, anthocyanin content, and biological activity of purple Napier grass silage.

BACKGROUND: Purple Napier grass (PNG), a widely used grass rich in anthocyanin, is commonly employed in the production of silage. However, there is currently limited research on the retention of anthocyanin with or without additives during ensiling. Therefore, this study aimed to investigate the effect of different additives (Lactiplantibacillus plantarum CCZZ1 (LP), glucose, acetic acid, and dried soybean curd residue) on fermentation quality, anthocyanin content, and microbial community structure of PNG silage. RESULTS: Ensiling PNG without additives led to poor fermentation quality and rapid degradation of anthocyanin, resulting in a decline in antioxidant activity and the persistence of harmful microorganisms with high relative abundance. The use of additives, especially LP, effectively increased the relative abundance of L. plantarum, enhancing fermentation quality, the retention of anthocyanin (up to 166% increase rate) and antioxidant activity, while reducing the relative abundance of harmful microorganisms during ensiling for 30 days. Additionally, prolonged ensiling negatively affected the preservation of anthocyanin. Based on both fermentation quality and bioactivity, PNG should be ensiled for 30 days with LP inoculation. CONCLUSION: The employment of additives, especially LP, improved the fermentation quality, anthocyanin retention, and microbial community structure in PNG silage. To optimize both fermentation quality and bioactivity, it is recommended that PNG be ensiled for 30 days with LP inoculation. © 2024 Society of Chemical Industry.

Evaluation of three alternative methods to the plaque reduction neutralizing assay for measuring neutralizing antibodies to dengue virus serotype 2.

BACKGROUND: Dengue is a global public health challenge which requires accurate diagnostic methods for surveillance and control. The gold standard for detecting dengue neutralizing antibodies (nAbs) is the plaque reduction neutralization test (PRNT), which is both labor-intensive and time-consuming. This study aims to evaluate three alternative approaches, namely, the MTT-based (or (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) microneutralization assay, the xCELLigence real-time cell analysis (RTCA), and the immuno-plaque assay-focus reduction neutralization test (iPA-FRNT). METHODS: Twenty-two residual serum samples were tested for DENV-2 nAbs using all four assays at three neutralization endpoints of 50%, 70% and 90% inhibition in virus growth. For each neutralization endpoint, results were compared using linear regression and correlation analyses. Test performance characteristics were further obtained for iPA-FRNT using 38 additional serum samples. RESULTS: Positive correlation of DENV-2 neutralization titers for the MTT-based microneutralization assay and the PRNT assay was only observed at the neutralization endpoint of 50% (r = 0.690). In contrast, at all three neutralization end points, a linear trend and positive correlation of DENV-2 neutralization titers for the xCELLigence RTCA and the PRNT assays were observed, yielding strong or very strong correlation (r = 0.829 to 0.967). This was similarly observed for the iPA-FRNT assay (r = 0.821 to 0.916), which also offered the added advantage of measuring neutralizing titers to non-plaque forming viruses. CONCLUSION: The xCELLigence RTCA and iPA-FRNT assays could serve as suitable alternatives to PRNT for dengue serological testing. The decision to adopt these methods may depend on the laboratory setting, and the utility of additional applications offered by these technologies.

SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2.

Sirtuin 1 (SIRT1) is a histone deacetylase and plays diverse functions in various physiological events, from development to lifespan regulation. Here, in Parkinson's disease (PD) model mice, we demonstrated that SIRT1 ameliorates parkinsonism, while SIRT1 knockdown further aggravates PD phenotypes. Mechanistically, SIRT1 interacts with and deacetylates pyruvate kinase M2 (PKM2) at K135 and K206, thus leading to reduced PKM2 enzyme activity and lactate production, which eventually results in decreased glial activation in the brain. Administration of lactate in the brain recapitulates PD-like phenotypes. Furthermore, increased expression of PKM2 worsens PD symptoms, and, on the contrary, inhibition of PKM2 by shikonin or PKM2-IN-1 alleviates parkinsonism in mice. Collectively, our data indicate that excessive lactate in the brain might be involved in the progression of PD. By improving lactate homeostasis, SIRT1, together with PKM2, are likely drug targets for developing agents for the treatment of neurodegeneration in PD.

Cypher/ZASP drives cardiomyocyte maturation via actin-mediated MRTFA-SRF signalling.

Rationale: Cardiomyocytes (CMs) undergo dramatic structural and functional changes in postnatal maturation; however, the regulatory mechanisms remain greatly unclear. Cypher/Z-band alternatively spliced PDZ-motif protein (ZASP) is an essential sarcomere component maintaining Z-disc stability. Deletion of mouse Cypher and mutation in human ZASP result in dilated cardiomyopathy (DCM). Whether Cypher/ZASP participates in CM maturation and thereby affects cardiac function has not been answered. Methods: Immunofluorescence, transmission electron microscopy, real-time quantitative PCR, and Western blot were utilized to identify the role of Cypher in CM maturation. Subsequently, RNA sequencing and bioinformatics analysis predicted serum response factor (SRF) as the key regulator. Rescue experiments were conducted using adenovirus or adeno-associated viruses encoding SRF, both in vitro and in vivo. The molecular mechanisms were elucidated through G-actin/F-actin fractionation, nuclear-cytoplasmic extraction, actin disassembly assays, and co-sedimentation assays. Results: Cypher deletion led to impaired sarcomere isoform switch and morphological abnormalities in mitochondria, transverse-tubules, and intercalated discs. RNA-sequencing analysis revealed significant dysregulation of crucial genes related to sarcomere assembly, mitochondrial metabolism, and electrophysiology in the absence of Cypher. Furthermore, SRF was predicted as key transcription factor mediating the transcriptional differences. Subsequent rescue experiments showed that SRF re-expression during the critical postnatal period effectively rectified CM maturation defects and notably improved cardiac function in Cypher-depleted mice. Mechanistically, Cypher deficiency resulted in the destabilization of F-actin and a notable increase in G-actin levels, thereby impeding the nuclear localisation of myocardin-related transcription factor A (MRTFA) and subsequently initiating SRF transcription. Conclusion: Cypher/ZASP plays a crucial role in CM maturation through actin-mediated MRTFA-SRF signalling. The linkage between CM maturation abnormalities and the late-onset of DCM is suggested, providing further insights into the pathogenesis of DCM and potential treatment strategies.

Valley-Related Multipiezo Effect and Noncollinear Spin Current in an Altermagnet Fe2Se2O Monolayer.

An altermagnet exhibits many novel physical phenomena because of its intrinsic antiferromagnetic coupling and natural band spin splitting, which are expected to give rise to new types of magnetic electronic components. In this study, an Fe2Se2O monolayer is proven to be an altermagnet with out-of-plane magnetic anisotropy, and its Néel temperature is determined to be 319 K. The spin splitting of the Fe2Se2O monolayer reaches 860 meV. Moreover, an Fe2Se2O monolayer presents a pair of energy valleys, which can be polarized and reversed by applying uniaxial strains along different directions, resulting in a piezovalley effect. Under the strain, the net magnetization can be induced in the Fe2Se2O monolayer by doping with holes, thereby realizing a piezomagnetic property. Interestingly, noncollinear spin current can be generated by applying an in-plane electric field on an unstrained Fe2Se2O monolayer doped with 0.2 hole/formula unit. These excellent physical properties make the Fe2Se2O monolayer a promising candidate for multifunctional spintronic and valleytronic devices.

Modulating the Pronociceptive Effect of Sleep Deprivation: A Possible Role for Cholinergic Neurons in the Medial Habenula.

Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.

Exploring the Relationship Between Sporadic Creutzfeldt-Jakob Disease and Gut Microbiota Through a Mendelian Randomization Study.

Observational studies have shown gut microbiota changes in sporadic Creutzfeldt-Jakob disease patients, but the causal relationship remains unknown. We aimed to determine any causal links between gut microbiota and this prion disease. Using Mendelian randomization analysis, we examined the causal relationship between gut microbiota composition and sporadic Creutzfeldt-Jakob disease. Data on gut microbiota (N = 18,340) and disease cases (5208) were obtained. Various analysis methods were used, including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode. In addition, MR-PRESSO was used to evaluate horizontal pleiotropy and detect outliers. Pleiotropy and heterogeneity were assessed, and reverse analysis was conducted. Negative associations were found between sporadic Creutzfeldt-Jakob disease and family Defluviitaleaceae, family Ruminococcaceae, genus Butyricicoccus, genus Desulfovibrio, and genus Eubacterium nodatum. Genus Lachnospiraceae UCG010 showed a positive correlation. Reverse analysis indicated genetic associations between the disease and decreased levels of family Peptococcaceae, genus Faecalibacterium, and genus Phascolarctobacterium, as well as increased levels of genus Butyrivibrio. No pleiotropy, heterogeneity, outliers, or weak instrument bias were observed. This study revealed bidirectional causal effects between specific gut microbiota components and sporadic Creutzfeldt-Jakob disease. Certain components demonstrated inhibitory effects on disease pathogenesis, while others were positively associated with the disease. Modulating gut microbiota may provide new insights into prion disease therapies. Further research is needed to clarify mechanisms and explore treatments for sporadic Creutzfeldt-Jakob disease.

A novel approach to terminate roof-dependent atrial flutter with epicardial conduction through septopulmonary bundle.

Atrial flutter, a prevalent cardiac arrhythmia, is primarily characterized by reentrant circuits in the right atrium. However, atypical forms of atrial flutter present distinct challenges in terms of diagnosis and treatment. In this study, we examine three noteworthy clinical cases of atypical atrial flutter, which offer compelling evidence indicating the implication of the lesser-known Septopulmonary Bundle (SPB). This inference is based on the identification of distinct electrocardiographic patterns observed in these patients and their favorable response to catheter ablation, which is a standard treatment for atrial flutter. Remarkably, in each case, targeted ablation at the anterior portion of the left atrial roof effectively terminated the arrhythmia, thus providing further support for the hypothesis of SPB involvement. These insightful observations shed light on the potential significance of the SPB in the etiology of atypical atrial flutter and introduce a promising therapeutic target. We anticipate that this paper will stimulate further exploration into the role of the SPB in atrial flutter and pave the way for the development of targeted ablation strategies.

Layer-Dependent Quantum Anomalous Hall and Quantum Spin Hall Effects in Two-Dimensional LiFeTe.

The emergence of an intrinsic quantum anomalous Hall (QAH) insulator with long-range magnetic order triggers unprecedented prosperity for combining topology and magnetism in low dimensions. Here, based on stacked two-dimensional LiFeTe, we confirm that magnetic coupling and topological electronic states can be simultaneously manipulated by just changing the layer numbers. Monolayer LiFeTe shows intralayer ferrimagnetic coupling, behaving as a QAH insulator with Chern number C = 2. Beyond the monolayer, the odd and even layers of LiFeTe correspond to uncompensated and compensated interlayer antiferromagnets, resulting in unexpected QAH and quantum spin Hall (QSH) states, respectively. Moreover, the spin Chern number is proportional to the stacking layer numbers in even-layer LiFeTe, proving that the spin Hall conductivity can be continuously enhanced by increasing layer numbers. Therefore, the odd-even-layer-dependent QAH and QSH effects found in LiFeTe topological insulators offer new insight into regulating quantum states in two-dimensional topological materials.

Enhanced detection of Aspergillus flavus in peanut kernels using a multi-scale attention transformer (MSAT): Advancements in food safety and contamination analysis.

In this study, a multi-scale attention transformer (MSAT) was coupled with hyperspectral imaging for classifying peanut kernels contaminated with diverse Aspergillus flavus fungi. The results underscored that the MSAT significantly outperformed classic deep learning models, due to its sophisticated multi-scale attention mechanism which enhanced its classification capabilities. The multi-scale attention mechanism was utilized by employing several multi-head attention layers to focus on both fine-scale and broad-scale features. It also integrated a series of scale processing layers to capture features at different resolutions and incorporated a self-attention mechanism to integrate information across different levels. The MSAT model achieved outstanding performance in different classification tasks, particularly in distinguishing healthy peanut kernels from those contaminated with aflatoxigenic fungi, with test accuracy achieving 98.42±0.22%. However, it faced challenges in differentiating peanut kernels contaminated with aflatoxigenic fungi from those with non-aflatoxigenic contamination. Visualization of attention weights explicitly revealed that the MSAT model's multi-scale attention mechanism progressively refined its focus from broad spatial-spectral features to more specialized signatures. Overall, the MSAT model's advanced processing capabilities marked a notable advancement in the field of food quality safety, offering a robust and reliable tool for the rapid and accurate detection of Aspergillus flavus contaminations in food.

Nutrient removal and microbial community succession in moving bed biofilm reactor: Effects of influent carbon to nitrogen ratio fluctuation.

This study investigated the nutrient removal and microbial community succession in moving bed biofilm reactor under stable and three levels of influent carbon/nitrogen (C/N) ratio fluctuation (± 10%, ± 20%, and ± 30%). Under the conditions of influent C/N ratio fluctuation, the removal efficiency of COD and PO43--P decreased 4.7-6.4% and 3.7-12.9%, respectively, while the nitrogen removal was almost unaffected. A sharp decrease in the content of culturable functional bacteria related to nitrogen and phosphorus removal including nitrite-oxidizing bacteria (NOB), aerobic denitrifying bacteria (DNB), and polyphosphate-accumulating organisms (PAOs) from the carrier biofilm was observed. Sequencing analysis revealed that the abundance of Candidatus Competibacter increased 10.3-25.9% and became the dominant genus responsible for denitrification, potentially indicating that nitrate was removed via endogenous denitrification under the influent C/N ratio fluctuation. The above results will provide basic data for the nutrient removal in decentralized wastewater treatment under highly variable influent conditions.

Stabilization effect and interaction mechanism of mannoprotein on anthocyanins in mulberry juice.

This study aimed to investigate the problem of color instability in mulberry juice, examine the effect of mannoprotein (MP) dosage on improving the stability of anthocyanins in mulberry juice, and explore the molecular binding mechanism between them. As the mass ratio of anthocyanins to MP of 1.07 × 10-3: 1-1.65 × 10-3: 1, the retention rates of anthocyanins in mulberry juice and simulated system were significantly improved in the photostability experiment, with the highest increase of 128.89 % and 24.11 %, respectively. In the thermal stability experiment, it increased by 7.96 % and 18.49 %, respectively. The synergistic effect of combining MP with anthocyanins has been demonstrated to greatly enhance their antioxidant capacity, as measured by ABTS, FRAP, and potassium ferricyanide reduction method. Furthermore, MP stabilized more anthocyanins to reach the intestine in simulated in vitro digestion. MP and cyanidin-3-glucoside (C3G) interacted with each other through hydrogen bonding and hydrophobic interactions. Specific amino acid residues involved of MP in binding process were identified as threonine (THR), isoleucine (ILE) and arginine (ARG). The identification of the effective mass concentration ratio range and binding sites of MP and anthocyanins provided valuable insights for the application of MP in mulberry juice.

Associations of sedentary behaviors with mental health outcomes in a cohort of patients with minor ischemic stroke.

OBJECTIVE: The relationship between sedentary behaviors and functional outcomes of acute ischemic stroke (AIS) has been previously reported. However, it remains unclear whether sedentary behaviors are associated with mental health outcomes in AIS patients. Therefore, the objective of this study was to investigate the mental health outcomes in patients with minor AIS one year after stroke onset. METHODS: This cross-sectional study recruited 1230 patients with minor AIS (NIHSS ≤ 5) from three hospitals in China. One year after discharge, patients were interviewed using face-to-face questionnaires, including the PHQ-9, GAD-7, and ISI, to assess symptoms of depression, anxiety, and insomnia, respectively. Participants were categorized into the long sedentary time group and the short sedentary time group based on the median sedentary time of all participants. The associations between leisure sedentary time and mental health outcomes were investigated. RESULTS: Participants with a long leisure sedentary time had higher PHQ-9, GAD-7, and ISI scores than those with a short sedentary time. Longer sedentary time was associated with an increased risk of experiencing symptoms of major depression (RR, 95% CI: 1.79, 1.47 to 2.18), anxiety (RR, 95% CI: 3.28, 2.08 to 5.18), and insomnia (RR, 95% CI: 2.58, 2.03 to 3.28) one year after a minor AIS. CONCLUSION: Excessive sedentary time is associated with long-term mental health conditions after stroke. Therefore, reducing the sedentary time might be helpful for preventing poststroke depression, anxiety, and insomnia.

Tobacco exposure and alcohol drinking prevalence and associations with hypertension in rural southwest China: A cross-sectional study.

INTRODUCTION: This study examined the prevalence of tobacco exposure and drinking and ascertained the relationships between tobacco exposure, alcohol drinking, concurrent smoking and drinking, and hypertension in rural southwestern China. METHODS: Data were collected from a cross-sectional health interview and examination survey, which included 7572 adults aged ≥35 years, in rural China. Participant demographic characteristics, smoking habits, exposure to secondhand smoke (SHS), and alcohol drinking habits were obtained using a standard questionnaire. Blood pressure (BP), height, weight, and waist circumference were measured for each participant. RESULTS: The overall prevalence of smoking, SHS exposure, drinking, concurrent smoking and drinking, concurrent exposure to SHS and drinking, and hypertension was 37.7%, 27.4%, 16.2%, 12.6%, 1.6%, and 41.3%, respectively. Males had a significantly higher prevalence of smoking (74.1% vs 2.2%, p<0.01), drinking (31.1% vs 1.7%, p<0.01), and concurrent smoking and drinking than females (25.3% vs 0.3%, p<0.01). However, females had a higher prevalence of SHS exposure than males (30.2% vs 20.6%, p<0.01). Ethnic minorities had a higher prevalence of SHS exposure, drinking, and concurrent smoking and drinking, than Han participants (p<0.01). Participants with a higher education level had a higher prevalence of smoking, drinking, and concurrent smoking and drinking than their counterparts (p<0.01). In contrast, participants with a lower education level had a higher prevalence of SHS exposure than their counterparts (p<0.01). Multivariate logistic regression analysis found that smokers (AOR=1.31; 95% CI: 1.13-1.51), individuals exposed to SHS (AOR=1.24; 95% CI: 1.11-1.43), drinkers (AOR=1.31; 95%: CI: 1.15-1.50), and concurrent smokers and drinkers (AOR=1.45; 95% CI: 1.25-1.67) all had a higher probability of having hypertension (p<0.01). Additionally, concurrent smoking and drinking had the strongest association with the prevalence of hypertension (AOR=1.45; 95% CI: 1.25-1.67; p<0.01). CONCLUSIONS: Socioeconomic factors play an important role in influencing the prevalence of smoking, exposure to SHS, and drinking in rural southwest China. Interventions to prevent and reduce hypertension should, in particular, focus on smokers, individuals exposed to SHS, drinkers, and, in particular, concurrent smokers and drinkers.

Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing cholesterol efflux capacity in macrophage.

Cholesterol efflux capacity (CEC) dysfunction in macrophages is important in atherosclerosis. However, the mechanism underlying CEC dysfunction remains unclear. We described the characteristics of ATF4 and inflammasome activation in macrophages during atherosclerosis through scRNA sequencing analysis. Then model of hyperlipemia was established in ApoE-/- mice; some were treated with tauroursodeoxycholic acid (TUDCA). TUDCA decreased the ATF4, Hspa, and inflammasome activation, reduced plaque area of the artery, and promoted CEC in macrophages. Furthermore, TUDCA abolished oxLDL-induced foam cell formation by inhibiting activation of the PERK/eIF2α/ATF4 and AIM2 inflammasome in macrophages. Further assays revealed ATF4 binding to AIM2 promoter, promoting its transcriptional activity significantly. Then we discovered that ATF4 affected AIM2-mediated foam cell formation by targeting ABCA1, which could be blocked by TUDCA. Our study demonstrated that TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing CEC of macrophage, which provided possibilities for the development of therapies.