Mitigating adverse effects of Cu-containing intrauterine devices using a highly biocompatible Cu5Fe alloy.

Copper-containing intrauterine devices (Cu-IUD) are adopted by worldwide women for contraception with the advantages of long-term effectiveness, reversibility and affordability. However, adverse effects occur in the initial implantation stage of Cu-IUD in uterine because of the burst release of Cu2+. To minimize the burst release, in this study, we designed a series of Cu-Fe alloys with 0.5 wt%, 1 wt% and 5 wt% Fe and also further produced ultrafine grained (UFG) structure for these alloys via equal-channel angular pressing. The microstructures and properties of the coarse grained (CG) Cu, CG Cu-Fe alloys and UFG Cu-Fe alloys were systematically investigated, including grain structure and phase compositions, metallic ions release behavior, electrochemical corrosion performance, and in vitro cytotoxicity. With careful comparison and selection, we chose the CG Cu-5Fe and UFG Cu-5Fe for in vivo tests using rat model, including tissue biocompatibility, in vivo corrosion behavior, and contraceptive effectiveness. Moreover, the corrosion mechanism of the Cu-5Fe alloy and its improved biocompatibility was discussed. Both CG and UFG Cu-5Fe alloys exhibited dramatic suppression of Cu2+ release in simulated uterine fluid for the long-term immersion process. The in vivo tissue compatibility was significantly improved with both CG and UFG Cu-5Fe alloys implanted in the rats' uterine while the high contraceptive efficacy was well maintained. Due to the superior biocompatibility, the CG and UFG Cu-5Fe alloys can be the promising candidate material for Cu-IUD. STATEMENT OF SIGNIFICANCE: A highly biocompatible Cu-Fe alloy was designed and fabricated for Cu-containing intrauterine devices (Cu-IUD). With 5 wt% Fe, the burst release of Cu2+ is inhibited due to the formed galvanic cell of Cu and Fe, resulting in earlier release of Fe3+. As Fe is the most abundant essential trace element of human body, it can mitigate the toxic effects of Cu2+, thus significantly improving both in vitro cell compatibility and in vivo tissue compatibility. More importantly, the Cu-5Fe alloy exhibits 100 % contraceptive efficiency as the CG Cu, but with greatly reduced adverse effects to the uterus tissues. An advanced Cu-IUD can be developed using Cu-Fe alloys.

Emulsifying properties of cellulose nanocrystals with different structures and morphologies from various solanaceous vegetable residues.

The stems of solanaceous vegetables with attractive source of cellulose, have caused severe environmental problems as agricultural residues. For the reutilization of the residues, this study isolated cellulose nanocrystals (CNs) from the stems of tomato, eggplant, and pepper to explore their applications in Pickering emulsions. Detailed analyses of the crystalline structure and morphology revealed differences in their emulsifying properties. Tomato stem CNs had higher crystallinity of 82.1 % and a short, straight rod-like shape with a low aspect ratio of 8.0, while eggplant and pepper CNs were long, curved whisker-like fibers with lower crystallinities of 75.3 % and 75.4 %, respectively. Tomato stem CNs exhibited the best emulsifying properties, attributed to their relatively higher crystallinity and larger crystal brick size enhancing amphiphilicity, along with their lower aspect ratio improving interface coverage, which resulted in stable emulsions across different temperatures, pH levels, and ionic strengths. This study enhances our understanding of how the structure and morphology of CNs influence their emulsifying properties, thereby contributing to the promotion of agricultural waste reutilization.

Knowledge, attitudes, and practices of healthcare professionals toward rehabilitation of peripheral nerve injury.

Peripheral nerve injury (PNI) occurs due to damage of peripheral nerves, with healthcare professionals playing significant roles in PNI rehabilitation. This study aimed to explore the knowledge, attitudes, and practices (KAP) towards PNI rehabilitation among healthcare professionals. This cross-sectional study was conducted on June 2023 in China and healthcare professionals were enrolled. A total of 611 valid questionnaires were collected, with 62.52% female respondents. Mean scores for KAP were 14.26 ± 2.044 (possible range: 0-19), 29.77 ± 3.622 (possible range: 7-35), and 41.55 ± 9.523 (possible range: 11-55), respectively. Multivariate logistic regression revealed positive associations of professional titles (OR = 1.743, 95% CI: 1.083-2.804), occupation (OR = 1.833, 95% CI: 1.151-2.919), and involvement in treatment or care of PNI patients (OR = 1.462, 95% CI: 1.024-2.088) with knowledge. Knowledge (OR = 1.155, 95% CI: 1.042-1.280), gender (OR = 2.140, 95% CI: 1.255-3.646), education (OR = 2.258, 95% CI: 1.131-4.507), and involvement in treatment or care of PNI patients (OR = 2.463, 95% CI: 1.460-4.155) were positively associated with attitude. Attitude (OR = 1.214, 95% CI: 1.148-1.283), bachelor's degree education (OR = 0.548, 95% CI: 0.326-0.919), master's degree or higher (OR = 0.545, 95% CI: 0.308-0.964), having rehabilitation training for PNI (OR = 2.485, 95% CI: 1.633-3.781), and involvement in treatment or care of PNI patients (OR = 2.093, 95% CI: 1.395-3.138) were independently associated with practice. Healthcare professionals exhibited moderate knowledge, positive attitudes, and moderate practices towards the PNI rehabilitation. Those involved in the treatment or care of PNI have significantly higher KAP. Targeted interventions were needed to enhance understanding and promote proactive engagement in clinical practice.

Multi-omics reveals the ecological and biological functions of Enterococcus mundtii in the intestine of lepidopteran insects.

Insect guts offer unique habitats for microbial colonization, with gut bacteria potentially offering numerous benefits to their hosts. Although Enterococcus has emerged as one of the predominant gut commensal bacteria in insects, its establishment in various niches within the gut has not been characterized well. In this study, Enterococcus mundtii was inoculated into the silkworm (Bombyx mori L.) to investigate its biological functions. Genome-based analysis revealed that its successful colonization is related to adherence genes (ebpA, ebpC, efaA, srtC, and scm). This bacterium did not alter the activities of related metabolic enzymes or the intestinal barrier function. However, significant changes in the gene expressions levels of Att2, CecA, and Lys suggest potential adaptive mechanisms of host immunity to symbiotic E. mundtii. Moreover, 16S metagenomics analysis revealed a significant increase in the relative abundance of E. mundtii in the intestines of silkworms following inoculation. The intestinal microbiome displayed marked heterogeneity, an elevated gut microbiome health index, a reduced microbial dysbiosis index, and low potential pathogenicity in the treatment group. Additionally, E. mundtii enhanced the breakdown of carbohydrates in host intestines. Overall, E. mundtii serves as a beneficial microbe for insects, promoting intestinal homeostasis by providing competitive advantage. This characteristic helps E. mundtii dominate complex microbial environments and remain prevalent across Lepidoptera, likely fostering long-term symbiosis between the both parties. The present study contributes to clarifying the niche of E. mundtii in the intestine of lepidopteran insects and further reveals its potential roles in their insect hosts.

Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

Effect of Ephestia kuehniella Eggs on Development and Transcriptome of the Ladybird Beetle Propylea japonica.

The eggs of the Mediterranean flour moth, Ephestia kuehniella, are frequently utilized as alternative diets and have demonstrated promising outcomes when consumed by various insects. Nonetheless, the specific reasons for their effectiveness remain unclear. In our study, we assessed the developmental performance of the ladybird Propylea japonica when fed E. kuehniella eggs, alongside 12 factitious prey or artificial diets. Our findings revealed that ladybirds fed E. kuehniella eggs displayed a performance comparable to those fed the natural prey Megoura crassicauda. Transcriptome profiling of larvae raised on E. kuehniella eggs and M. crassicauda revealed that genes upregulated in the former group were enriched in metabolic pathways associated with carbohydrates, lipids, and other essential nutrients. This suggests that E. kuehniella eggs may have a higher nutrient content compared to natural prey. Furthermore, a notable downregulation in the expression of immune effector genes, such as Attacin and Coleoptericin, was observed, which might be attributed to the lower microbial content in E. kuehniella eggs compared to M. crassicauda. We suggest that the difference between E. kuehniella eggs and M. crassicauda as food sources for P. japonica lies in their nutrient and microbial contents. These findings provide valuable insights for the advancement of innovative artificial breeding systems for natural enemies.

Effect of 18F-DCFPyL PET on changes in management of patients with prostate cancer: a systematic review and meta-analysis.

Purpose: Prostate-specific membrane antigen (PSMA)-targeted imaging has gained increasing interest in its application in prostate cancer lesion detection. Compared with 68Galium (68Ga), 18Fluoride (18F)-labeled imaging agent has easier syntheses, lower price, and a longer half-time. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid positron emission tomography (18F-DCFPyL PET) has been recently approved by the U.S. Food and Drug Administration. Several studies have proven its superiority to conventional imaging techniques in detecting prostate cancer lesions. However, the impact of 18F-DCFPyL PET on the management of patients with prostate cancer is not well established. Thus, we performed a systematic review and meta-analysis of available data to evaluate the impact of 18F-DCFPyL PET on the management of patients with prostate cancer. Methods: The PubMed, Embase, Scopus, and Cochrane databases were searched up to April 2024. Studies that reported the proportion of changes in management after 18F-DCFPyL PET was performed in patients with prostate cancer were included. The Grading of Recommendations Assessment, Development, and Evaluation system was used for the quality evaluation of the included studies. The proportion of changes in management was pooled using a random effects model. Meta-regression analyses were performed to assess the potential correlation between the PET positivity and management changes. Results: Fourteen studies (3,078 patients with prostate cancer) were included in our review and analysis. The pooled percentage of management changes was 43.5% (95% confidence interval [CI]: 33-54%). In patients with biochemical recurrent and for primary staging, the pooled percentage was 50% (95% CI: 39-60%) and 22% (95% CI: 15-29%), respectively. In the meta-regression analyses, PET positivity was detected as a significant predictor of management change (p = 0.0023). Conclusion: 18F-DCFPyL PET significantly affects the management of patients with prostate cancer. Higher PET positivity rate significantly correlated with a higher proportion of management changes in patients with prostate cancer. However, more studies are still needed to confirm the important role of 18F-DCFPyL PET in the management of prostate cancer. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42022339178.

Impact of whole grain highland hull-less barley on the denaturing gradient gel electrophoresis profiles of gut microbial communities in rats fed high-fat diets.

Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) is a traditional non-culture technique that can provide a fingerprint of the microbial community. In the field of gut microbiota analysis, PCR-DGGE still holds potential for development. In the present study, we utilized an improved nested PCR-DGGE approach targeting the V3 region of 16S ribosomal DNA to investigate the impact of whole grain highland hull-less barley (WHLB), a cereal known for its significant hypocholesterolemic effect, on the gut microbiota profiles of high-fat diet rats. Seventy-two male Sprague-Dawley rats were divided into four groups and fed a normal control diet, a high-fat diet, or a high-fat diet supplemented with a low or high dose of WHLB for 4 or 8 weeks. The results revealed that the dominant bands varied among different dose groups and further changed with different treatment times. The compositions of bacterial communities in feces and cecal content were similar, but the dominant bacterial bands differed. After performing double DGGE, extracting the bands, sequencing the DNA, and aligning the sequences, a total of 19 bands were classified under the Firmicutes and Bacteroidetes phyla, while two bands were identified as unclassified uncultured bacteria. The relative abundance of Lactobacillus gasseri, Uncultured Prevotella sp., and Clostridium sp. increased following the administration of WHLB. Illumina-based sequencing was employed to assess the reliability of DGGE, demonstrating its reliability in analyzing the dominant taxonomic composition, although it may have limitations in accurately detecting the alpha diversity of bacterial species. IMPORTANCE: While next-generation sequencing has overshadowed polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), the latter still holds promise for advancing gut microbiota analysis due to its unique advantages. In this study, we used optimized nested PCR-DGGE to investigate the gut microbiota profile of high-fat diet rats after administering whole grain highland hull-less barley. High-throughput sequencing was employed to validate the DGGE results. Our results proved the reliability of PCR-DGGE for analyzing the dominant taxonomic composition while also providing visual evidence of a notable relationship between the composition of cecal and fecal microbial communities, highlighting substantial differences in both richness and abundance.

Mitochondrial ACSS1-K635 acetylation knock-in mice exhibit altered metabolism, cell senescence, and nonalcoholic fatty liver disease.

Acetyl-CoA synthetase short-chain family member 1 (ACSS1) uses acetate to generate mitochondrial acetyl-CoA and is regulated by deacetylation by sirtuin 3. We generated an ACSS1-acetylation (Ac) mimic mouse, where lysine-635 was mutated to glutamine (K635Q). Male Acss1K635Q/K635Q mice were smaller with higher metabolic rate and blood acetate and decreased liver/serum ATP and lactate levels. After a 48-hour fast, Acss1K635Q/K635Q mice presented hypothermia and liver aberrations, including enlargement, discoloration, lipid droplet accumulation, and microsteatosis, consistent with nonalcoholic fatty liver disease (NAFLD). RNA sequencing analysis suggested dysregulation of fatty acid metabolism, cellular senescence, and hepatic steatosis networks, consistent with NAFLD. Fasted Acss1K635Q/K635Q mouse livers showed increased fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1), both associated with NAFLD, and increased carbohydrate response element-binding protein binding to Fasn and Scd1 enhancer regions. Last, liver lipidomics showed elevated ceramide, lysophosphatidylethanolamine, and lysophosphatidylcholine, all associated with NAFLD. Thus, we propose that ACSS1-K635-Ac dysregulation leads to aberrant lipid metabolism, cellular senescence, and NAFLD.

Advances in Aeroengine Cooling Hole Measurement: A Comprehensive Review.

Film cooling technology is of great significance to enhance the performance of aero-engines and extend service life. With the increasing requirements for film cooling efficiency, researchers and engineers have carried out a lot of work on the precision and digital measurement of cooling holes. Based on the above, this paper outlines the importance and principles of film cooling technology and reviews the evolution of cooling holes. Also, this paper details the traditional measurement methods of the cooling hole used in current engineering scenarios with their limitations and categorizes digital measurement methods into five main types, including probing measurement technology, optical measurement technology, infrared imaging technology, computer tomography (CT) scanning technology, and composite measurement technology. The five types of methods and integrated automated measurement platforms are also analyzed. Finally, through a generalize and analysis of cooling hole measurement methods, this paper points out technical challenges and future trends, providing a reference and guidance for forward researches.

Association between the haemoglobin glycation index (HGI) and clinical outcomes in patients with acute decompensated heart failure.

BACKGROUND: A growing number of studies show that people with similar blood glucose levels have different levels of glycosylated haemoglobin (HbA1c), and relying only on HbA1c may lead to clinical decision-making errors. The haemoglobin glycation index (HGI) quantifies the difference in HbA1c among individuals and is strongly linked to the risk of cardiovascular disease. However, the connection between this phenomenon and the poor outcomes of patients with acute decompensated heart failure (ADHF) is currently unknown. PATIENTS AND METHODS: This retrospective, single-centre-based cohort study included 1531 hospitalized patients with ADHF from September 2010 to January 2020. The HGI is calculated from the difference between the observed and predicted HbA1c values [predicted HbA1c = 0.024 × fasting plasma glucose (FPG) (mg/dL)+3.1]. The endpoints examined in the study included all-cause death, cardiovascular (CV) death, and major adverse cardiac events (MACE). We fitted multivariable-adjusted Cox proportional hazard models to investigate the association between the HGI and clinical outcomes. RESULTS: During the five-year follow-up, 427 (27.9%) patients died from all causes, 232 (15.6%) from CV death, and 848 (55.4%) from MACE. The restricted cubic spline analysis also showed that the cumulative risk of all-cause and CV deaths decreased linearly with increasing HGI. According to multivariate Cox proportional hazard models, the highest tertile of the HGI was associated with a lower incidence of all-cause and cardiovascular deaths [all-cause death, adjusted hazard ratio (HR): 0.720, 95% confidence interval (CI): 0.563-0.921, p = 0.009; CV death, adjusted HR: 0.619, 95% CI: 0.445-0.861, p = 0.004]. A 1% increase in the HGI was associated with a 12.5% reduction in the risk of all-cause death and a 20.8% reduction in the risk of CV death. CONCLUSIONS: A high HGI was directly associated with a reduction in all-cause and CV deaths but was not associated with MACE. These findings may be helpful in the management of patients with ADHF.

Recent studies have demonstrated that significant discrepancies between HbA1c and actual blood glucose levels may lead to clinical decision-making errors.The inconsistency of previous research results suggests that the HGI may have different predictive ability in populations with different diseases.

Study on Sensor Fault-Tolerant Control for Central Air-Conditioning Systems Using Bayesian Inference with Data Increments.

A lack of available information on heating, ventilation, and air-conditioning (HVAC) systems can affect the performance of data-driven fault-tolerant control (FTC) models. This study proposed an in situ selective incremental calibration (ISIC) strategy. Faults were introduced into the indoor air (Ttz1) thermostat and supply air temperature (Tsa) and chilled water supply air temperature (Tchws) sensors of a central air-conditioning system. The changes in the system performance after FTC were evaluated. Then, we considered the effects of the data quality, data volume, and variable number on the FTC results. For the Ttz1 thermostat and Tsa sensor, the system energy consumption was reduced by 2.98% and 3.72% with ISIC, respectively, and the predicted percentage dissatisfaction was reduced by 0.67% and 0.63%, respectively. Better FTC results were obtained using ISIC when the Ttz1 thermostat had low noise, a 7-day data volume, or sufficient variables and when the Tsa and Tchws sensors had low noise, a 14-day data volume, or limited variables.

Study on the Impact of Building Energy Predictions Considering Weather Errors of Neighboring Weather Stations.

Weather data errors affect energy management by influencing the accuracy of building energy predictions. This study presents a long short-term memory (LSTM) prediction model based on the "Energy Detective" dataset (Shanghai, China) and neighboring weather station data. The study analyzes the errors of different weather data sources (Detective and A) at the same latitude and longitude. Subsequently, it discusses the effects of weather errors from neighboring weather stations (Detective, A, B, C, and D) on energy forecasts for the next hour and day including the selection process for neighboring weather stations. Furthermore, it compares the forecast results for summer and autumn. The findings indicate a correlation between weather errors from neighboring weather stations and energy consumption. The median R-Square for predicting the next hour reached 0.95. The model's predictions for the next day exhibit a higher Prediction Interval Mean Width (139.0 in summer and 146.1 in autumn), indicating a greater uncertainty.

Leptin Reduction as a Required Component for Weight Loss.

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or liraglutide, synergistically induced greater weight loss and better glucose tolerance in diet-induced obese mice. Furthermore, upon cessation of either liraglutide or FGF21 treatment, the expected immediate weight regain was observed, associated with a rapid increase in circulating leptin levels. Prevention of this leptin surge with leptin neutralizing antibodies slowed down weight gain and preserved better glucose tolerance. Mechanistically, a significant reduction in leptin induced a higher degree of leptin sensitivity in hypothalamic neurons. Our observations support a model that postulates that a reduction of leptin levels is a necessary prerequisite for substantial weight loss, and partial leptin reduction is a viable strategy to treat obesity and its associated insulin resistance.

SOCS3 inhibiting JAK-STAT pathway enhances oncolytic adenovirus efficacy by potentiating viral replication and T-cell activation.

Oncolytic viruses (OVs) are emerging as a potentially useful treatment for malignancies due to the capabilities of direct oncolysis and immune induction. Improving the replication of OVs is an effective approach to enhance the oncolytic effects. Here, we observed that cancer cells with deficiencies in JAK-STAT pathway showed greater sensitivity to oncolytic adenovirus (oAd), and JAK inhibitor could enhance the replication of oAd. Therefore, we constructed a novel oAd expressing SOCS3, a major negative regulator of JAK-STAT pathway, and confirmed that oAd-SOCS3 exhibited a more significant antitumor effect than oAd-Ctrl both in vitro and in vivo. Mechanistically, SOCS3 inhibited the activation of JAK-STAT pathway, resulting in stronger tumor selective replication of oAd and downregulated expression of PD-L1 on cancer cells as well. Both benefits could collectively awaken antitumor immunity. This study highlights the importance of JAK-STAT pathway in viral replication and confirms the treatment of oAd-SOCS3 in potential clinical applications.

Hyperleptinemia contributes to antipsychotic drug-associated obesity and metabolic disorders.

Despite their high degree of effectiveness in the management of psychiatric conditions, exposure to antipsychotic drugs, including olanzapine and risperidone, is frequently associated with substantial weight gain and the development of diabetes. Even before weight gain, a rapid rise in circulating leptin concentrations can be observed in most patients taking antipsychotic drugs. To date, the contribution of this hyperleptinemia to weight gain and metabolic deterioration has not been defined. Here, with an established mouse model that recapitulates antipsychotic drug-induced obesity and insulin resistance, we not only confirm that hyperleptinemia occurs before weight gain but also demonstrate that hyperleptinemia contributes directly to the development of obesity and associated metabolic disorders. By suppressing the rise in leptin through the use of a monoclonal leptin-neutralizing antibody, we effectively prevented weight gain, restored glucose tolerance, and preserved adipose tissue and liver function in antipsychotic drug-treated mice. Mechanistically, suppressing excess leptin resolved local tissue and systemic inflammation typically associated with antipsychotic drug treatment. We conclude that hyperleptinemia is a key contributor to antipsychotic drug-associated weight gain and metabolic deterioration. Leptin suppression may be an effective approach to reducing the undesirable side effects of antipsychotic drugs.

Intranasal Delivery of Endothelial Cell-Derived Extracellular Vesicles with Supramolecular Gel Attenuates Myocardial Ischemia-Reperfusion Injury.

Purpose: Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted extracellular vesicles are closely related to inflammation, thrombosis formation, and other processes after injury. Meanwhile, low-molecular-weight gelators have shown great potential for nasal administration. This study aims to explore the therapeutic effects and significance of endothelial cell-derived extracellular vesicles combined with a hydrogel for nasal administration on myocardial ischemia-reperfusion injury. Methods: We chose a gel system composed of a derivative of glutamine amide and benzaldehyde as the extracellular vesicle delivery vehicle. This hydrogel was combined with extracellular vesicles extracted from mouse aortic endothelial cells and administered multiple times intranasally in a mouse model of ischemia-reperfusion injury to the heart. The delivery efficiency of the extracellular vesicle-hydrogel combination was evaluated by flow cytometry and immunofluorescence. Echocardiography, TTC Evan's Blue and Masson's staining were used to assess mouse cardiac function, infarct area, and cardiac fibrosis level. Flow cytometry, ELISA, and immunofluorescence staining were used to investigate changes in mouse inflammatory cells, cytokines, and vascular neogenesis. Results: The vesicles combined with the hydrogel have good absorption in the nasal cavity. The hydrogel combined with vesicles reduces the levels of pro-inflammatory Ly6C (high) monocytes/macrophages and neutrophils. It can also reduce the formation of microcirculation thrombi in the infarcted area, improve endothelial barrier function, and increase microvascular density in the injured area. As a result, the heart function of mice is improved and the infarct area is reduced. Conclusion: We first demonstrated that the combination of extracellular vesicles and hydrogel has a better absorption efficiency in the nasal cavity, which can improve myocardial ischemia-reperfusion injury by inhibiting inflammatory reactions and protecting endothelial function. Nasal administration of vesicles combined with hydrogel is a potential therapeutic direction.

An alpha-helix variant p.Arg156Pro in LMNA as a cause of hereditary dilated cardiomyopathy: genetics and bioinfomatics exploration.

LMNA gene encodes lamin A/C protein which participates in the construction of nuclear lamina, the mutations of LMNA result in a wide variety of diseases known as laminopathies. LMNA-related dilated cardiomyopathy(LMNA-DCM) is one of the more common laminopathy which characterized by progressive heart failure and arrhythmia. However, the mutation features of LMNA-DCM are yet to be elucidated. Herein we described a dilated cardiomyopathy family carrying novel variant c.467G > C(p.Arg156Pro) of LMNA as heterozygous pathogenic variant identified by whole-exome sequencing. With the help of Alphafold2, we predicted mutant protein structure and found an interrupted α-helix region in lamin A/C. In the analysis of 49 confirmed pathogenic missense of laminopathies, Chi-square test showed the DCM phenotype was related to the α-helix region mutation (p < 0.017). After screening the differentially expressed genes (DEGs) in both mice models and human patients in Gene Expression Omnibus database, we found the variation of α-helix-coding region in LMNA caused abnormal transcriptomic features in cell migration, collagen-containing extracellular matrix, and PI3K-Akt signaling pathway. Subsequently we constructed (TF)-mRNA-microRNA (miRNA) regulatory network and identified 7 key genes (FMOD, CYP1B1, CA3, F2RL1, HAPLIN1, SNAP91, and KANSL1) as potential biomarkers or therapeutic targets in LMNA-DCM patients.

Prognostic value of fibrosis-5 index combined with C-reactive protein in patients with acute decompensated heart failure.

BACKGROUND: Fibrosis-5 (FIB-5) index is a marker of liver fibrosis and has been shown to have a good prognostic value for patients with acute heart failure (AHF), and C-reactive protein (CRP) has inflammatory properties and predicts adverse prognosis in patients with HF. However, the long-term prognostic value of FIB-5 index combined with CRP in patients with acute decompensated HF (ADHF) is yet unclear. METHODS: This retrospective study included 1153 patients with ADHF hospitalized from January 2018 to May 2022.The FIB-5 index was calculated as (albumin [g/L]×0.3 + PLT count [109/L]×0.05)-(ALP [U/L]×0.014 + AST to ALT ratio×6 + 14). Patients were stratified into the following four groups according to the median value of FIB-5 index (=-2.11) and CRP (= 4.5): Group 1 had a high FIB-5 index (FIB-5 index >-2.11) and a low CRP (CRP ≤ 4.5); Group 2 had both low FIB-5 index and low CRP; Group 3 had both high FIB-5 index and high CRP; Group 4 had a low FIB-5 index (FIB-5 index ≤-2.11) and a high CRP (CRP > 4.5). The endpoint was major adverse cardiac and cerebral events (MACCEs). Multivariate Cox analysis was used to evaluate the association of the combination with the development of MACCEs. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analysis were used to compare the accuracy of the combination with a single prognostic factor for predicting the risk of MACCEs. RESULTS: During the mean follow-up period of 584 ± 12 days, 488 (42.3%) patients had MACCEs. Kaplan-Meier analysis revealed that the incidence of MACCEs was different in the four groups (P < 0.001). After adjusting for the confounding factors, the hazard ratio (HR) for MACCEs in Group 4 (low FIB-5 index + high CRP) was the highest (Model 1, HR = 2.04, 95%CI 1.58-2.65, P < 0.001; Model 2, HR = 1.67, 95%CI 1.28-2.18, P < 0.001; Model 3, HR = 1.66, 95%CI: 1.27-2.17, P < 0.001). Additionally, the combination of FIB-5 index and CRP enabled more accurate prediction of MACCEs than FIB-5 index alone (NRI, 0.314,95%CI 0.199-0.429; P < 0.001; IDI, 0.023; 95% CI 0.015-0.032; P < 0.001). CONCLUSIONS: In patients with ADHF, the combination of the FIB-5 index and CRP may be useful in risk stratification in the future.

Intrinsic half-metallicity in two-dimensional Cr2TeX2 (X = I, Br, Cl) monolayers.

Two-dimensional (2D) materials with intrinsic half-metallicity at or above room temperature are important in spin nanodevices. Nevertheless, such 2D materials in experiment are still rarely realized. In this work, a new family of 2D Cr2TeX2 (X = I, Br, Cl) monolayers has been predicted using first-principles calculations. The monolayer is made of five atomic sublayers with ABCAB-type stacking along the perpendicular direction. It is found that the energies for all the ferromagnetic (FM) half-metallic states are the lowest. The phonon spectrum calculations and molecular dynamics simulations both demonstrate that the FM states are stable, indicating the possibility of experimentally obtaining the 2D Cr2TeX2 monolayers with half-metallicity. The Curie temperatures from Monte Carlo simulations are 486, 445, and 451 K for Cr2TeI2, Cr2TeBr2, and Cr2TeCl2 monolayers, respectively, and their half-metallic bandgaps are 1.72, 1.86 and 1.90 eV. The corresponding magnetocrystalline anisotropy energies (MAEs) are about 1185, 502, 899 µeV per Cr atom for Cr2TeX2 monolayers, in which the easy axes are along the plane for the Cr2TeBr2 and Cr2TeCl2 monolayers, but being out of the plane in the Cr2TeI2. Our study implies the potential application of the 2D Cr2TeX2 (X = I, Br, Cl) monolayers in spin nanodevices.