Interaction of general obesity and abdominal obesity with frailty in patients with chronic kidney disease: a nationally representative analysis.

Background: General and abdominal obesity are prevalent, with established associations to frailty in the elderly. However, few studies have investigated these associations in patients with chronic kidney disease (CKD), yielding inconsistent results. Methods: This cross-sectional study analysed data from the National Health and Nutrition Examination Survey (NHANES 2003-2018). Frailty was evaluated by the 36-item frailty index. General obesity was defined as a body mass index (BMI) >30 kg/m2; abdominal obesity was identified if waist circumference (WC) reached 102 cm in men and 88 cm in women. The associations of general and abdominal obesity with frailty were analysed using weighted multivariate logistic regression and restricted cubic splines. The interaction of general and abdominal obesity with frailty was examined. Results: A total of 5604 adult patients (median age 71 years, 42% men) with CKD were included in this analysis, with a median estimated glomerular filtration rate of 57.3 ml/min/1.73 m2. A total of 21% were frail with general obesity and 32% were frail with abdominal obesity. Neither general nor abdominal obesity alone was associated with frailty. There was an interaction between general and abdominal obesity with frailty. Compared with individuals with normal BMI and WC, those with both general and abdominal obesity, rather than either alone, exhibited significantly increased odds of frailty {odds ratio [OR] 1.53 [95% confidence interval (CI) 1.20-1.95]}. General obesity was associated with being frail only when CKD patients had abdominal obesity [OR 1.59 (95% CI 1.08-2.36)]. Conclusions: There may be an interaction between general and abdominal obesity with frailty in patients with CKD. Interventions aimed at preventing frailty should consider both aspects.

Nonlinear and abnormal relationship between turbidity and suspended solids concentration in mountainous rivers: A case study of the Lai Chi Wo river in Hong Kong, China.

Suspended solids concentration (SSC) in a river is closely relevant to river water turbidity. Investigation of their relationship in this study is accompanied by observed turbidity and SSC values, which were obtained from the testing results of water samples and monitored conditions in streamflow. The water samples were collected from two observation stations with a broad range of sediment concentrations in the Lai Chi Wo catchment in Hong Kong, China. We classified the target rainfall events into single-peak event type and dual-peak event type for a distinguished discussion of the relationship between SSC and turbidity in this study. At a finer classification, each event is separated into defined processes for the analysis, where two main processes refer to the periods that SSC rises from a normal state to a peak state first and the followed periods that SSC recesses to ordinary status gradually. It is advised by the analysis results that the estimation of SSC through turbidity values should be based on the same rainfall types for the upstream station. However, the results show that the classification of rainfall types does not need to take downstream areas into consideration. Furthermore, current research implies that the individual established connections between SSC and turbidity value at different stages (particularly referring to the rising period and recessing period) could be applied to estimate SSC at the same station via continuous turbidity values for both this and other ungauged stations with similar topographical features in the future. Meanwhile, this research approach provides new insight exploring various behaviors of sediments at different stages during an integral rainfall event. A comparison of distinguished performances of sediment during corresponding stages in a rainfall event makes contributions to diverse relationship between SSC and turbidity in the mountainous river.

MMP11 as a prognostic biomarker correlated with immune infiltrates in pancreatic adenocarcinoma.

Background: Matrix metalloproteinase 11 (MMP11) plays a vital role in cell proliferation, apoptosis, tumor angiogenesis, migration, and other basic processes. Currently, few studies have examined the value of MMP11 in pancreatic cancer in relation to prognostic risk, diagnostic indicators, and immunotherapy. This study aims to explore the association between MMP11 and the tumor immune microenvironment in pancreatic adenocarcinoma (PAAD). Methods: We selected clinical samples and data downloaded from The Cancer Genome Atlas and Genotype-Tissue Expression, in addition, we use other online data for further analysis. Through a comprehensive bioinformatics investigation, we systematically analyzed the clinical significance and expression level of MMP11 in pancreatic cancer. Results: MMP11 was overexpressed in many cancers, and a higher expression of MMP11 was associated with a poorer prognosis in pancreatic cancer. Conversely, the hypermethylation of MMP11 was associated with better overall survival. The MMP11 expression network had widespread effects on the prognosis and immune activation of PAAD. The expression of MMP11 was significantly associated with a variety of tumor-infiltrating immune cells. An association was also found between MMP11 expression and chemokines in PAAD. High MMP11 expression might be involved in immune cell migration to the tumor microenvironment. Conclusions: MMP11 is a prognostic biomarker for patients in pancreatic cancer and may regulate the tumor immune microenvironment. The potential effects and mechanisms of MMP11 in PAAD require further exploring.

Assessment of prevalence of elevated blood lead levels and risk factors among children and pregnant women in Bihar, India.

BACKGROUND: While modeled estimates and studies in contaminated areas indicate high lead exposure among children in Bihar, India, local data on lead exposure in the child population is limited. OBJECTIVES: To characterize lead exposure, and assess potential sources of lead exposure among a state-representative sample of children and their pregnant mothers residing in Bihar. METHODS: Blood samples were collected from 697 children under five and 55 pregnant women from eight districts in Bihar. Blood lead levels were determined using capillary blood and a portable lead analyzer. Household demographics, home environment, behavior, and nutrition information were collected through computer-assisted personal interviews with primary caregivers. Logistic regression was used to assess associations between potential risk factors and elevated blood lead levels. RESULTS: More than 90% of children and 80% of pregnant women reported blood lead levels ≥5 µg/dL. Living near a lead-related industry and pica behavior of eating soil were significantly associated with increased odds of having elevated blood lead levels. Additional risk factors for having a blood level ≥5 µg/dL included the use of skin lightning cream (aOR = 5.11, 95%CI: 1.62, 16.16) and the use of eyeliners (aOR = 2.81, 95%CI: 1.14, 6.93). Having blood lead levels ≥10 µg/dL was also significantly associated with the household member who had an occupation or hobby involving the use of lead (aOR = 1.75, 95%CI: 1.13, 2.72). DISCUSSION: Elevated blood lead levels were prevalent among children and pregnant women in Bihar, indicating the urgent need for a comprehensive lead poisoning prevention strategy.

Ferritin and Serum Iron in a Causal Relationship with Estrogen Receptor-Negative Breast Cancer: a Two-Sample Mendelian Randomization Study.

BACKGROUND: The aim of this study was to explore the causal relationship between different serum iron statuses (ferritin, transferrin, transferrin saturation, and serum iron) and the occurrence of estrogen receptor (ER)-positive or ER-negative breast cancer. METHODS: The summary data on serum iron status exposure were gathered from the IEU OpenGWAS Project, the UK Biobank, and other databases. Concurrently, the summary data for ER+ and ER- breast cancer are sourced from the Breast Cancer Association Consortium (BCAC). By examining the causal link between iron status and breast cancer, we deployed five distinct Mendelian randomization (MR) algorithms, namely MR-Egger, inverse variance weighted (IVW), weighted median, simple mode, and MR-PRESSO. To assess heterogeneity and horizontal pleiotropy, Cochran's Q and MR-Egger algorithms were applied, respectively. RESULTS: Elevated ferritin levels are associated with an increased risk of ER-negative breast cancer (OR(IVW) = 1.042, 95% CI (1.005, 1.081), p = 0.025; OR (weighted median) = 1.050, 95% CI (1.001, 1.102), p = 0.046; and OR (MR-PRESSO) = 1.042, 95% CI (1.005, 1.081), p = 0.039). Conversely, an increase in the serum iron level is linked to a reduced risk of ER-negative breast cancer (OR (IVW) = 0.791, 95% CI (0.649, 0.962), p = 0.019; and OR (MR-PRESSO) = 0.791, 95% CI (0.649, 0.962), p = 0.028). However, there is no evidence of a causal relationship between transferrin, transferrin saturation, and ER-negative breast cancer. For ER-positive breast cancer, none of the four different iron statuses demonstrated a causal relationship. CONCLUSIONS: Ferritin is positively correlated with ER-negative breast cancer, while serum iron is negatively associated with ER-negative breast cancer. However, there is no causal relationship between the four iron statuses and ER-positive breast cancer.

Saccharopolyspora mangrovi sp. nov., a novel mangrove soil actinobacterium with distinct metabolic potential revealed by comparative genomic analysis.

A novel mangrove soil-derived actinomycete, strain S2-29T, was found to be most closely related to Saccharopolyspora karakumensis 5K548T based on 16 S rRNA sequence (99.24% similarity) and genomic phylogenetic analyses. However, significant divergence in digital DNA-DNA hybridization, average nucleotide identity, and unique biosynthetic gene cluster possession distinguished S2-29T as a distinct Saccharopolyspora species. Pan genome evaluation revealed exceptional genomic flexibility in genus Saccharopolyspora, with > 95% accessory genome content. Strain S2-29T harbored 718 unique genes, largely implicated in energetic metabolisms, indicating different metabolic capacities from its close relatives. Several uncharacterized biosynthetic gene clusters in strain S2-29T highlighted the strain's untapped capacity to produce novel functional compounds with potential biotechnological applications. Designation as novel species Saccharopolyspora mangrovi sp. nov. (type strain S2-29T = JCM 34,548T = CGMCC 4.7716T) was warranted, expanding the known Saccharopolyspora diversity and ecology. The discovery of this mangrove-adapted strain advances understanding of the genus while highlighting an untapped source of chemical diversity.

The suppressive role of NLRP6 in host defense against Streptococcus suis infection.

Streptococcus suis (S. suis) disease is a prevalent zoonotic infectious threat that elicits a systemic inflammatory response in both swine and humans, frequently culminating in high mortality rates. The excessive inflammation triggered by S. suis infection can precipitate tissue damage and sudden death; however, a comprehensive strategy to mitigate this inflammatory response remains elusive. Our study examines the role of NLRP6 in S. suis infection, with a particular focus on its involvement in pathogen regulation. A marked upregulation of NLRP6 was observed in peritoneal macrophages post-infection with S. suis SC19 strain, consequently activating the NLRP6 inflammasome. Furthermore, SC19 infection was found to augment the secretion of pro-inflammatory cytokines IL-1ß via NLRP6 activation, while NLRP6 deficiency mitigates the invasion and adhesion of SC19 to macrophages. In vivo models revealed that NLRP6 deletion enhanced survival rates of SC19-infected mice, alongside a reduction in tissue bacterial load and inflammatory cytokine levels. NLRP6-/- mice were shown to exhibit attenuated inflammatory responses in pulmonary, hepatic, and splenic tissues post-SC19 infection, as evidenced by lower inflammation scores. Flow cytometry analyses further substantiated that NLRP6 is involved in modulating macrophage and neutrophil recruitment during infection. Our findings suggest that NLRP6 negatively regulates host resistance against S. suis infection; its absence results in reduced mortality, bacterial colonization, and a milder inflammatory response. Elucidating the mechanism of NLRP6 in S. suis-induced inflammation provides novel insights and theoretical underpinnings for the prophylaxis and therapeutics of S. suis diseases.

Non-Line-of-Sight Imaging and Vibrometry Using a Comb-Calibrated Coherent Sensor.

Non-line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects, allowing a wide range of applications. Existing NLOS systems rely on pulsed lasers and time-resolved single-photon detectors to capture the information encoded in the time of flight of scattered photons. Despite remarkable advances, the pulsed time-of-flight LIDAR approach has limited temporal resolution and struggles to detect the frequency-associated information directly. Here, we propose and demonstrate the coherent scheme-frequency-modulated continuous wave calibrated by optical frequency comb-for high-resolution NLOS imaging, velocimetry, and vibrometry. Our comb-calibrated coherent sensor presents a system temporal resolution at subpicosecond and its superior signal-to-noise ratio permits NLOS imaging of complex scenes under strong ambient light. We show the capability of NLOS localization and 3D imaging at submillimeter scale and demonstrate NLOS vibrometry sensing at an accuracy of dozen Hertz. Our approach unlocks the coherent LIDAR techniques for widespread use in imaging science and optical sensing.

Causes and consequences of major depressive disorder: An encompassing Mendelian randomization study.

Background: Major depressive disorder (MDD) is a prevalent and debilitating disorder that has been associated with a range of risk factors and outcomes. Causal pathways between MDD and other traits can be studied using genetic variants as instrumental variables. Methods: A literature review was conducted to identify 201 MDD-associated traits. For 115 traits, there were well-powered genome-wide association study (GWAS) results available that could be used to assess the genetic correlation with MDD. Of these, there were 89 meeting criteria for investigating causal associations in both directions using two-sample Mendelian randomization (TSMR). Of the traits that were not captured by GWAS, 43 could be included as outcomes of MDD using one-sample MR (OSMR). A range of methods and sensitivity tests was applied to gauge robustness of results, together with statistical power analyses to aid interpretation. Outcomes: Moderate to strong genetic overlap was found between MDD and most traits. Support for causal effects of MDD liability were found for circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic, and suicide outcomes. Most associations were bidirectional, although there was less evidence for diet, disease, and endocrine traits causing MDD risk. Results were robust across sensitivity analyses. Interpretation: This study provides a systematic overview of traits putatively causally related to MDD, confirming previous findings as well as identifying new associations. Our results highlight the importance of MDD as a risk factor cross-cutting across medical, functional, and psychosocial domains and emphasize the need for concerted efforts at reducing this highly prevalent disorder.

A national survey of pandemic fear and cyberchondria after ending zero-COVID policy: The chain mediating role of alexithymia and psychological distress.

BACKGROUND: More than half the domestic population in China were infected with COVID-19 in two months after ending "zero-infection policy", which severely overwhelmed frontline healthcare providers with stress and fear. However, there is no study to date investigating the associations between nurses' fear of pandemic and cyberchondria. This study aimed to 1) investigate the correlations between fear pandemic and cyberchondria among frontline nurses, and 2) discover its potential mechanism. METHODS: A cross-sectional sample of frontline nurses (N = 8161) was recruited from 98 hospitals across China in February 2023. Participants were invited to complete an online, self-rated standardized questionnaire focused on pandemic fear, alexithymia, psychological distress, and cyberchondria. Environmental, clinical and socioeconomic information were collected for adjustment while conducting chain mediation analysis. RESULTS: When other covariates were controlled, it was found that fear of the pandemic significantly contributed to cyberchondria (b = 0.58, 95%CI [0.56, 0.60], p < .001). The chain mediation model suggested that both alexithymia and psychological distress were mediating factors between pandemic fear and cyberchondria. CONCLUSIONS: The higher the perceived fear, the greater the cyberchondria, which suggests that reducing fear about the pandemic and providing adequate support could reduce the incidence of cyberchondria. As alexithymia and psychological distress may be transdiagnostic mechanisms between fear and cyberchondria, targeted interventions focused on expression dysregulation and emotional identification could be useful.

Efficacy of rituximab-containing regimens used as first-line and rescue therapy for giant cell hepatitis with autoimmune hemolytic anemia a retrospective study.

OBJECTIVE: To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA). METHODS: This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events. RESULTS: Twenty patients (8 females and 12 males; age range 1-26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3-8) versus 14 (5-25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2-101) and 22 (4-41) months, respectively. Two patients in conventional group died of disease progression and infection. CONCLUSIONS: RTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.

Evaluating the Need for Durotomy and Duraplasty in Adults Undergoing Suboccipital Craniectomy for Chiari Decompression: A Case Series Analysis of Radiographic and Clinical Outcomes.

Background Suboccipital craniectomy (SOC) in conjunction with dura opening and duraplasty for posterior fossa decompression is an effective treatment for symptomatic Chiari 1 malformations (CM1), primarily carried out in the pediatric population. However, dural opening and reconstruction are associated with an increased risk of complications, and their necessity in the adult population has not yet been robustly demonstrated. Given differences in clinical presentation and disease severity between the pediatric and adult patients, we aimed to identify if SOC alone with intraoperative ultrasound confirmation of adequate restoration of pulsatile motion of cerebellar tonsil is sufficient to treat symptomatic CM1 while mitigating surgical risks. Methods We identified a retrospective, institutional cohort of adult patients who underwent SOC for Chiari decompression between 2014 and 2023. Demographic, clinical, and radiographic features were extracted for each patient. Clinical outcomes were assessed using the Chicago Chiari Outcome Scale (CCOS) and Motor-Sensory-Sphincter signs score (Clinical Sign Score (CSS)). Radiographic outcomes assessed cerebellar ectopia and associated syrinx characteristics. Results A total of 15 patients were identified, with an average follow-up period of three years. Eight patients underwent SOC with duraplasty, whereas seven patients underwent SOC only without duraplasty. Both groups of patients were of similar age at surgery and had similar nature and duration of symptoms prior to surgery. On pre-operative radiographic evaluation, both groups of patients had similar lengths of cerebellar ectopia (9.9±11.0 mm to 11.1±5.7 mm, p=0.591), and associated syrinxes (75% vs. 42.9%, p=0.205). Intraoperatively, both groups had similar estimated blood losses, though the length of surgery was significantly shorter when durotomy was spared (202±58.3 minutes to 116.3±47.8 minutes, p=0.011). The length of ICU stay was also significantly longer in the durotomy group (1.1±0.6 days to 0.0 days, p<0.001). Neither group reported any post-operative complications. On follow-up, both groups demonstrated similar reductions in cerebellar ectopia and syrinx characteristics. Clinically, the CCOS and CSS scores were similar between the two cohorts at follow-up, with no repeat surgery required in either group. Conclusion Our cohort suggests that for adult CM1 patients, SOC decompression alone without dural reconstruction might lead to comparable clinical and radiographic outcomes to SOC decompression with durotomy/duraplasty, especially if intraoperative ultrasound confirms good cerebrospinal fluid (CSF) flow after SOC. Notably, sparing durotomy and duraplasty is also associated with decreased operative time and decreased ICU stay.

Gastroesophageal reflux disease may causally associate with the increased atrial fibrillation risk: evidence from two-sample Mendelian randomization analyses.

Background: The risk of atrial fibrillation (AF) is increased in individuals with gastroesophageal reflux disease (GERD), according to observational research. The causal significance of this association is still unclear. This study sought to assess GERD's role as a potential contributing factor in AF. Methods: With the use of a two-sample Mendelian randomization (MR) technique, we assessed the causal relationship between GERD and AF. The association of genetic variants with GERD was examined using data from a recent genome-wide association study (GWAS) that included 602,604 people. Data on the association between genetic variations and AF was obtained from a second GWAS with 1,030,836 participants. The effect sizes were examined based on the inverse-variance weighted method. Additional statistical techniques, including MR-Egger, simple mode, weighted mode, MR Pleiotropy Residual Sum, outlier, and weighted median were used in the sensitivity analysis. Results: MR analyses in inverse-variance weighted models, using 76 single nucleotide polymorphisms (SNPs) as markers, revealed a relationship between genetically predicted GERD and a greater AF incidence [odds ratio (OR): 1.165, 95% CI 1.102-1.231; P = 7.637 × 10-8]. According to MR-Egger, there was no evidence of gene pleiotropy that could be found (intercept = 0.003, P = 0.581). The findings of the sensitivity study, which used several MR methods, were found to be reliable. Conclusion: The MR analysis revealed a correlation between GERD and increased AF incidence, supporting the idea that treating patients with GERD as early as possible might reduce their chance of developing AF.

Expression characteristics of lipid metabolism-related genes and correlative immune infiltration landscape in acute myocardial infarction.

Lipid metabolism is an important part of the heart's energy supply. The expression pattern and molecular mechanism of lipid metabolism-related genes (LMRGs) in acute myocardial infarction (AMI) are still unclear, and the link between lipid metabolism and immunity is far from being elucidated. In this study, 23 Common differentially expressed LMRGs were discovered in the AMI-related mRNA microarray datasets GSE61144 and GSE60993. These genes were mainly related to "leukotriene production involved in inflammatory response", "lipoxygenase pathway", "metabolic pathways", and "regulation of lipolysis in adipocytes" pathways. 12 LMRGs (ACSL1, ADCY4, ALOX5, ALOX5AP, CCL5, CEBPB, CEBPD, CREB5, GAB2, PISD, RARRES3, and ZNF467) were significantly differentially expressed in the validation dataset GSE62646 with their AUC > 0.7 except for ALOX5AP (AUC = 0.699). Immune infiltration analysis and Pearson correlation analysis explored the immune characteristics of AMI, as well as the relationship between these identified LMRGs and immune response. Lastly, the up-regulation of ACSL1, ALOX5AP, CEBPB, and GAB2 was confirmed in the mouse AMI model. Taken together, LMRGs ACSL1, ALOX5AP, CEBPB, and GAB2 are significantly upregulated in AMI patients' blood, peripheral blood of AMI mice, myocardial tissue of AMI mice, and therefore might be new potential biomarkers for AMI.

Large-scale greenway exposure reduces sedentary behavior: A natural experiment in China.

As a global public health problem, sedentary behavior has attracted more and more attention. Although numerous studies have demonstrated many benefits of green spaces to health, causal evidence on how green spaces affect people's sedentary behavior is scarce. This study used a natural experiment to evaluate the impact of greenway intervention on sedentary behavior. Two waves of data were collected in 2016 and 2019 (before and after the intervention) at East Lake Greenway (102-km-long) in Wuhan, China, with 1020 participants in 52 neighborhoods. We adopted three major methods to evaluate the impact of greenway intervention on sedentary behavior, including Propensity Score Matching and difference-in-difference (PSM-DID) method (with both individual and neighborhood variables to match samples), continuous treatment DID method (with distance to the greenway as the continuous treatment), and mediation analysis (with moderate to vigorous physical activity or MVPA, and walking time as the mediator). The results revealed that the greenway intervention significantly reduced participants' sedentary time and the intervention has a distance decay effect. The closer to the greenway, the greater decrease in sedentary time after the greenway opening. Furthermore, we found that MVPA and walking time mediate the impact of the greenway intervention on the change in sedentary behavior. The effect of greenway intervention was more beneficial for those under the age of 60, those who were employed, or those who were married. Our findings provided robust evidence that exposure to urban greenways affects sedentary behavior and such green infrastructures help protect public health in high-density urban areas.

Fairer AI in ophthalmology via implicit fairness learning for mitigating sexism and ageism.

The transformative role of artificial intelligence (AI) in various fields highlights the need for it to be both accurate and fair. Biased medical AI systems pose significant potential risks to achieving fair and equitable healthcare. Here, we show an implicit fairness learning approach to build a fairer ophthalmology AI (called FairerOPTH) that mitigates sex (biological attribute) and age biases in AI diagnosis of eye diseases. Specifically, FairerOPTH incorporates the causal relationship between fundus features and eye diseases, which is relatively independent of sensitive attributes such as race, sex, and age. We demonstrate on a large and diverse collected dataset that FairerOPTH significantly outperforms several state-of-the-art approaches in terms of diagnostic accuracy and fairness for 38 eye diseases in ultra-widefield imaging and 16 eye diseases in narrow-angle imaging. This work demonstrates the significant potential of implicit fairness learning in promoting equitable treatment for patients regardless of their sex or age.

MYH7 R453C induced cardiac remodelling via activating TGF-ß/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways.

Hypertrophic cardiomyopathy (HCM) is a monogenic cardiac disorder commonly induced by sarcomere gene mutations. However, the mechanism for HCM is not well defined. Here, we generated transgenic MYH7 R453C and MYH6 R453C piglets and found both developed typical cardiac hypertrophy. Unexpectedly, we found serious fibrosis and cardiomyocyte loss in the ventricular of MYH7 R453C, not MYH6 R453C piglets, similar to HCM patients. Then, RNA-seq analysis and western blotting identified the activation of ERK1/2 and PI3K-Akt pathways in MYH7 R453C. Moreover, we observed an increased expression of fetal genes and an excess of reactive oxygen species (ROS) in MYH7 R453C piglet models, which was produced by Nox4 and subsequently induced inflammatory response. Additionally, the phosphorylation levels of Smad2/3, ERK1/2 and NF-kB p65 proteins were elevated in cardiomyocytes with the MYH7 R453C mutation. Furthermore, epigallocatechin gallate, a natural bioactive compound, could be used as a drug to reduce cell death by adjusting significant downregulation of the protein expression of Bax and upregulated Bcl-2 levels in the H9C2 models with MYH7 R453C mutation. In conclusion, our study illustrated that TGF-ß/Smad2/3, ERK1/2 and Nox4/ROS pathways have synergistic effects on cardiac remodelling and inflammation in MYH7 R453C mutation.

Strategies for the Preparation of Single-Atom Catalysts Using Low-Dimensional Metal-Organic Frameworks.

As single-atom catalysts are important energy materials, their preparation and synthesis methods have become particularly important. The unique structures of low-dimensional metal-organic frameworks and their derivatives provide various strategies for preparing single-atom catalysts. This paper summarizes various strategies for the preparation of single-atom catalysts based on low-dimensional metal-organic frameworks and their derivatives.