A Biodegradable Fiber Calcium Ion Sensor by Covalently Bonding Ionophores on Bioinert Nanoparticles.

Implantable sensors, especially ion sensors, facilitate the progress of scientific research and personalized healthcare. However, the permanent retention of implants induces health risks after sensors fulfill their mission of chronic sensing. Biodegradation is highly anticipated while biodegradable chemical sensors are rare due to concerns about the leakage of harmful active molecules after degradation, such as ionophores. Here, we introduce a novel biodegradable fiber calcium ion sensor, wherein ionophores are covalently bonded with bioinert nanoparticles to replace the classical ion-selective membrane. The fiber sensor demonstrates comparable sensing performance to classical ion sensors and good flexibility. It can monitor the fluctuations of Ca2+ in a four-day lifespan in vivo, and biodegrade in four weeks. Benefiting from the stable bonding between ionophores and nanoparticles, the biodegradable sensor exhibited a good biocompatibility after degradation. Moreover, our approach of bonding active molecules on bioinert nanoparticles can serve as an effective methodology for minimizing health concerns about biodegradable chemical sensors. This article is protected by copyright. All rights reserved.

Elder mistreatment and psychological resilience: the moderating role of social support.

This study examines the possible consequence of elder mistreatment on resilience and whether social support moderates this posited association, using a rural sample of 432 community-dwelling older Chinese adults aged 60 to 79 years. Elder abuse included verbal abuse, physical abuse, or financial exploitation. Social support was measured by The Multidimensional Scale of Perceived Social Support (MSPSS). Resilience was represented by a seven-item scale. Hierarchical regression models indicated that mistreatment is significantly related to low levels of resilience when confounding factors are adjusted. A significant interaction term (abuse × social support) was also detected. Mistreated respondents who reported higher levels of social support were less likely to experience low resilience compared to those with lower levels of social support. Social support buffers against the undesirable effect of mistreatment on resilience, especially for those who were abused.

Discovery of BMP10 as a new gene underpinning congenital heart defects.

OBJECTIVE: Aggregating evidence convincingly establishes the predominant genetic basis underlying congenital heart defects (CHD), though the heritable determinants contributing to CHD in the majority of cases remain elusive. In the current investigation, BMP10 was selected as a prime candidate gene for human CHD mainly due to cardiovascular developmental abnormalities in Bmp10-knockout animals. The objective of this retrospective study was to identify a new BMP10 mutation responsible for CHD and characterize the functional effect of the identified CHD-causing BMP10 mutation. METHODS: Sequencing assay of BMP10 was fulfilled in a cohort of 276 probands with various CHD and a total of 288 non-CHD volunteers. The available family members from the proband harboring an identified BMP10 mutation were also BMP10-genotyped. The effect of the identified CHD-causative BMP10 mutation on the transactivation of TBX20 and NKX2.5 by BMP10 was quantitatively analyzed in maintained HeLa cells utilizing a dual-luciferase reporter assay system. RESULTS: A novel heterozygous BMP10 mutation, NM_014482.3:c.247G>T;p.(Glu83*), was identified in one proband with patent ductus arteriosus (PDA), which was confirmed to co-segregate with the PDA phenotype in the mutation carrier's family. The nonsense mutation was not observed in 288 non-CHD volunteers. Functional analysis unveiled that Glu83*-mutant BMP10 had no transactivation on its two representative target genes TBX20 and NKX2.5, which were both reported to cause CHD. CONCLUSION: These findings provide strong evidence indicating that genetically compromised BMP10 predisposes human beings to CHD, which sheds light on the new molecular mechanism that underlies CHD and allows for antenatal genetic counseling and individualized precise management of CHD.

AMBRA1 promotes intestinal inflammation by antagonizing PP4R1/PP4c mediated IKK dephosphorylation in an autophagy-independent manner.

IκB kinase (IKK) complex is central regulators of the NF-κB pathway, and dysregulation of IKK phosphorylation leads to hyperactivation of proinflammatory response in various chronic inflammatory diseases, including inflammatory bowel disease (IBD). However, the dynamic modulation of IKK phosphorylation and dephosphorylation in intestinal inflammation remains uncharacterized. Here, we found that autophagy/beclin-1 regulator 1 (AMBRA1) was highly expressed in inflamed colons in a colitis mouse model and in clinical IBD samples. Importantly, AMBRA1 deletion significantly decreased proinflammatory cytokine expression and enhanced the therapeutic effect of infliximab on intestinal inflammation. Mechanistically, the N-term F1 domain of AMBRA1 was required for AMBRA1 to competitively interact with protein phosphatase 4 regulatory subunit 1 (PP4R1) and catalytic protein phosphatase 4 (PP4c) to suppress their interactions with IKK, promote the dissociation of the PP4R1/PP4c complex, and antagonize the dephosphorylation activity of this complex towards the IKK complex. In response to TNF-α stimulation, IKKα phosphorylates AMBRA1 at S1043 to stabilize AMBRA1 expression by impairing its binding to Cullin4A (CUL4A) to decrease its CUL4A-mediated K48-linked ubiquitination. Overall, our study identifies an autophagy-independent function of AMBRA1 as a positive modulator of IKK phosphorylation to promote intestinal inflammation, thus providing a new targeted therapeutic strategy for patients with refractory IBD.

Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation.

Type 2 diabetes mellitus (T2DM) patients exhibit greater susceptibility to vascular calcification (VC), which has a higher risk of death and disability. However, there is no specific drug for VC therapy. NLRP3 inflammasome activation as a hallmark event of medial calcification leads to arterial stiffness, causing vasoconstrictive dysfunction in T2DM. Empagliflozin (EMPA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), restrains hyperglycemia with definite cardiovascular benefits. Given the anti-inflammatory activity of EMPA, herein we investigated whether EMPA protected against VC in the aorta of T2DM mice by inhibiting NLRP3 inflammasome activation. Since db/db mice receiving a normal diet developed VC at the age of about 20 weeks, we administered EMPA (5, 10, 20 mg·kg-1·d-1, i.g) to 8 week-old db/db mice for 12 weeks. We showed that EMPA intervention dose-dependently ameliorated the calcium deposition, accompanied by reduced expression of RUNX2 and BMP2 proteins in the aortas. We found that EMPA (10 mg·kg-1·d-1 for 6 weeks) also protected against VC in vitamin D3-overloaded mice, suggesting the protective effects independent of metabolism. We showed that EMPA (10 mg·kg-1·d-1) inhibited the abnormal activation of NLRP3 inflammasome in aortic smooth muscle layer of db/db mice. Knockout (KO) of NLRP3 significantly alleviated VC in STZ-induced diabetic mice. The protective effects of EMPA were verified in high glucose (HG)-treated mouse aortic smooth muscle cells (MOVASs). In HG-treated NLRP3 KO MOVASs, EMPA (1 µM) did not cause further improvement. Bioinformatics and Western blot analysis revealed that EMPA significantly increased the expression levels of basic helix-loop-helix family transcription factor e40 (Bhlhe40) in HG-treated MOVASs, which served as a negative transcription factor directly binding to the promotor of Nlrp3. We conclude that EMPA ameliorates VC by inhibiting Bhlhe40-dpendent NLRP3 inflammasome activation. These results might provide potential significance for EMPA in VC therapy of T2DM patients.

Somatic GATA4 mutation contributes to tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most prevalent cyanotic congenital heart pathology and causes infant morbidity and mortality worldwide. GATA-binding protein 4 (GATA4) serves as a pivotal transcriptional factor for embryonic cardiogenesis and germline GATA4 mutations are causally linked to TOF. However, the effects of somatic GATA4 mutations on the pathogenesis of TOF remain to be ascertained. In the present study, sequencing assay of GATA4 was performed utilizing genomic DNA derived from resected heart tissue specimens as well as matched peripheral blood specimens of 62 patients with non-familial TOF who underwent surgical treatment for TOF. Sequencing of GATA4 was also performed using the heart tissue specimens as well as matched peripheral venous blood samples of 68 sporadic cases who underwent heart valve displacement because of rheumatic heart disorder and the peripheral venous whole blood samples of 216 healthy subjects. The function of the mutant was explored by dual-luciferase activity analysis. Consequently, a new GATA4 mutation, NM_002052.5:c.708T>G;p.(Tyr236*), was found in the heart tissue of one patient with TOF. No mutation was detected in the heart tissue of the 68 cases suffering from rheumatic heart disorder or in the venous blood samples of all 346 individuals. GATA4 mutant failed to transactivate its target gene, myosin heavy chain 6. Additionally, this mutation nullified the synergistic transactivation between GATA4 and T-box transcription factor 5 or NK2 homeobox 5, two genes causative for TOF. Somatic GATA4 mutation predisposes TOF, highlighting the significant contribution of somatic variations to the molecular pathogenesis underpinning TOF.

Integrating Light Diffusion and Conversion Layers for Highly Efficient Multicolored Fiber-Dye-Sensitized Solar Cells.

Fiber solar cells as promising wearable power supplies have attracted increasing attentions recently, while further breakthrough on their power conversion efficiency (PCE) and realization of multicolored appearances remain urgent needs particularly in real-world applications. Here, a fiber-dye-sensitized solar cell (FDSSC) integrated with a light diffusion layer composed of alumina/polyurethane film on the outmost encapsulating tube and a light conversion layer made from phosphors/TiO2/poly(vinylidene fluoride-co-hexafluoropropylene) film on the inner counter electrode is designed. The incident light is diffused to more surfaces of fiber electrodes, then converted on counter electrode and reflected to neighboring photoanode, so the FDSSC efficiently takes advantage of the fiber shape for remarkably enhanced light harvesting, producing a record PCE of 13.11%. These efficient FDSSCs also realize color-tunable appearances, improving their designability and compatibility with textiles. They are further integrated with fiber batteries as power systems, providing a power solution for wearables and emerging smart textiles.

Remote Ischemic Conditioning Mediates Cardio-protection After Myocardial Ischemia/Reperfusion Injury by Reducing 4-HNE Levels and Regulating Autophagy via the ALDH2/SIRT3/HIF1α Signaling Pathway.

Remote ischemic conditioning (RIC) can be effectively applied for cardio-protection. Here, to clarify whether RIC exerts myocardial protection via aldehyde dehydrogenase 2 (ALDH2), we established a myocardial ischemia/reperfusion (I/R) model in C57BL/6 and ALDH2 knockout (ALDH2-KO) mice and treated them with RIC. Echocardiography and single-cell contraction experiments showed that RIC significantly improved myocardial function and alleviated I/R injury in C57BL/6 mice but did not exhibit its cardioprotective effects in ALDH2-KO mice. TUNEL, Evan's blue/triphenyl tetrazolium chloride, and reactive oxygen species (ROS) assays showed that RIC's effect on reducing myocardial cell apoptosis, myocardial infarction area, and ROS levels was insignificant in ALDH2-KO mice. Our results showed that RIC could increase ALDH2 protein levels, activate sirtuin 3 (SIRT3)/hypoxia-inducible factor 1-alpha (HIF1α), inhibit autophagy, and exert myocardial protection. This study revealed that RIC could exert myocardial protection via the ALDH2/SIRT3/HIF1α signaling pathway by reducing 4-HNE secretion.

A Fiber Sensor for Long-Term Monitoring of Extracellular Potassium Ion Fluctuations in Chronic Neuropsychiatric Diseases.

The extracellular potassium ion concentration in the brain exerts a significant influence on cellular excitability and intercellular communication. Perturbations in the extracellular potassium ion level are closely correlated with various chronic neuropsychiatric disorders including depression. However, a critical gap persists in performing real-time and long-term monitoring of extracellular potassium ions, which is necessary for comprehensive profiling of chronic neuropsychiatric diseases. Here, a fiber potassium ion sensor (FKS) that consists of a soft conductive fiber with a rough surface and a hydrophobic-treated transduction layer interfaced with a potassium ion-selective membrane is found to solve this problem. The FKS demonstrates stable interfaces between its distinct functional layers in an aqueous environment, conferring an exceptional stability of 6 months in vivo, in stark contrast to previous reports with working durations from hours to days. Upon implantation into the mouse brain, the FKS enables effective monitoring of extracellular potassium ion dynamics under diverse physiological states including anesthesia, forced swimming, and tail suspension. Using this FKS, tracking of extracellular potassium ion fluctuations that align with behaviors associated with the progression of depression over months is achieved, demonstrating its usability in studying chronic neuropsychiatric disorders from a new biochemical perspective.

Risk factors for peripheral artery disease and diabetic peripheral neuropathy among patients with type 2 diabetes.

AIMS: To investigate the prevalence of peripheral artery disease (PAD) and diabetic peripheral neuropathy (DPN) and the associated risk factors among Chinese patients with type 2 diabetes mellitus. METHODS: A cross-sectional study was conducted using data between November 1, 2018, and December 31, 2022. PAD was defined as ABI ≤ 0.9. DPN diagnosis involved specialized physician assessments using questionnaires and vibration perception threshold tests. Logistic regression analysis was used to identify related factors. We also evaluated the association between the clustering of risk factors and disease incidence. RESULTS: The study population comprised 13,315 patients (mean age: 63.3 years). 4.9 % of the patients had PAD and 43.9 % had DPN. Multivariate regression analysis revealed advanced age, smoking, hypertension, coronary heart disease, dyslipidemia, elevated HbA1c, and uric acid levels as independent risk factors for PAD. For DPN, independent risk factors included advanced age, female gender, hypertension, coronary heart disease, elevated total cholesterol, triglycerides, lipoprotein(a), fasting plasma glucose, HbA1c, alkaline phosphatase, cystatin C, albumin-to-creatinine ratio, and elevated homocysteine levels, whereas apolipoprotein A was a protective factor. The clustering of risk factors was prevalent and associated with higher disease risk. CONCLUSIONS: Our study contributed to identifying high-risk individuals and improving lower limb health among diabetic individuals.

Family characteristics in adolescents with overweight or obesity: a network analysis.

Background: Rates of overweight and obesity continue to grow in adolescents. Overweight and obesity in adolescence are associated with numerous immediate and long-term adverse health conditions. Throughout adolescence, parents and the family have an important and central influence on adolescents' health and lifestyle. The home environment may be a major factor in shaping children's weight. However, our current understanding of the interplay between family-related variables in adolescents with overweight or obesity is limited and fragmented. This study aimed to assess the relationship between family-related variables in adolescents who are overweight or obese using network analysis and inform future health promotion for family-based intervention. Methods: Participants (n = 488) were recruited from middle schools in Nanjing from October 2022 to March 2023. Participants, together with their parents, completed a questionnaire at school about the family food environment, family size, family APGAR index, family physical activity facilities, parental mental health, rearing behavior, parental weight status, drinking history, marital satisfaction, and sociodemographic characteristics. Results: The network split into three distinct communities of items. Network analysis showed that parental mental health and paternal rearing styles-rejection were the most central nodes in the network. In contrast, maternal weight status was the most peripheral and least connected nodes. Conclusion: Family-related variables constituted a connected network in adolescents with overweight or obesity. The pattern of network node connections supports that interventions could prioritize targeting changing parental mental health and paternal rearing styles in adolescents with overweight or obesity.

High-Performance Artificial Ligament Made from Helical Polyester Fibers Wrapped with Aligned Carbon Nanotube Sheets.

Repairing high-load connective tissues, such as ligaments, by surgically implanting artificial grafts after injury is challenging because they lack biointegration with host bones for stable interfaces. Herein, a high-performance helical composite fiber (HCF) ligament by wrapping aligned carbon nanotube (CNT) sheets around polyester fibers is proposed. Anterior cruciate ligament (ACL) reconstruction surgery shows that HCF grafts could induce effective bone regeneration, thus allowing the narrowing of bone tunnel defects. Such repair of the bone tunnel is in strong contrast to the tunnel enlargement of more than 50% for commercial artificial ligaments made from bare polyester fibers. Rats reconstructed with this HCF ligament show normal jumping, walking, and running without limping. This work allows bone regeneration in vivo through a one-step surgery without seeding cells or transforming growth factors, thereby opening an avenue for high-performance artificial tissues.

Discovery of TBX20 as a Novel Gene Underlying Atrial Fibrillation.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients.

Efficacy and safety of perampanel monotherapy in Chinese patients with focal-onset seizures: A single-center, prospective, real-world observational study.

OBJECTIVE: Efficacy and safety of perampanel monotherapy for treating focal-onset seizures (FOS) has been barely studied in China. This observational study aimed to evaluate the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS. METHODS: This single-center, prospective, real-world observational study enrolled patients aged ≥4 years with FOS who visited the Epilepsy Out-Patient Clinic of Nanjing Brain Hospital affiliated to Nanjing Medical University from January 2020 to December 2021. All patients were treated with perampanel monotherapy. Seizure-freedom rates after 6 and 12 months of treatment were calculated. Adverse events (AEs) were recorded. RESULTS: Seventy patients with FOS were enrolled. The mean maintenance perampanel dose was 4.64 ± 1.55 mg/day. The 6- and 12-month retention rates of perampanel monotherapy were 78.6% (55/70) and 70.0% (49/70), respectively. The 6- and 12-month seizure-freedom rates were 69.84% (44/63) and 65.08% (41/63), respectively. Patients with focal to bilateral tonic-clonic seizures had significantly higher 6-month and numerically higher 12-month seizure freedom rates than patients with focal impaired awareness seizures (P = 0.046 and P = 0.204, respectively). Twenty-six (37.1%) patients experienced treatment-emergent AEs, and the most common AE was dizziness. Four (5.7%) patients withdrew from the study due to AEs. No new safety concern was observed. SIGNIFICANCE: This is the first prospective study on the efficacy and safety of perampanel monotherapy in treating Chinese patients with FOS, and perampanel monotherapy was effective and safe in treating Chinese patients aged ≥4 years with FOS up to 12 months. More multicenter, real-world studies with large sample sizes and longer follow-ups are needed to further evaluate the long-term efficacy and safety of perampanel monotherapy.

Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential.

Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

An Implantable Fiber Biosupercapacitor with High Power Density by Multi-Strand Twisting Functionalized Fibers.

Biosupercapacitors (BSCs) that can harvest and store chemical energy show great promise for power delivery of biological applications. However, low power density still limits their applications, especially as miniaturized implants. Here, we report an implantable fiber BSC with maximal power density of 22.6 mW cm-2 , superior to the previous reports. The fiber BSC was fabricated by integrating anode and cathode fibers of biofuel cell with supercapacitor fibers through multi-strand twisting. This twisting structure endowed many channels inside and high electrochemical active area for efficient mass diffusion and charge transfer among different fibers, benefiting high power output. The obtained thin and flexible fiber BSC operated stably under deformations and performed high biocompatibility after implantation. Eventually, the fiber BSC was implanted subcutaneously in rats and successfully realized electrical stimulation of sciatic nerve, showing promise as a power source in vivo.

Spatially resolved metabolomics combined with bioactivity analyses to evaluate the pharmacological properties of two Radix Puerariae species.

ETHNOPHARMACOLOGICAL RELEVANCE: P. lobata and P. thomsonii are medicinal plants with similar pharmacological functions but different therapeutic effects. A novel method is presented herein to investigate metabolites in terms of their distribution and qualification, quantification is necessary to elucidate the different therapeutic effects of the two Puerariae species. AIM OF THE STUDY: The aim of the present study was to perform spatially resolved metabolomics combined with bioactivity analyses to systematically compare the metabolite differences in P. lobata and P. thomsonii by distribution, qualification, quantification, and biological activity to evaluate their pharmacological properties. MATERIALS AND METHODS: Air flow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) was performed to characterize the differences in the metabolite distributions of P. lobata and P. thomsonii. Further qualitative and quantitative analyses of the differential metabolites were performed using liquid chromatography-mass spectrometry (LC-MS). Biological activities correlated with the differences in the metabolites were validated by MTT assays. RESULTS: Some metabolites showed complementary distributions of the phloem and xylem in the two species, saccharide, vitamin, and inosine levels were higher in the phloem of P. thomsonii but higher in the xylem of P. lobata. The 3'-hydroxyl puerarin level was higher in the xylem of P. thomsonii but higher in the phloem of P. lobata. Qualitative and quantitative analyses of the metabolites revealed a total of 52 key differential metabolites. MTT assays showed that daidzein, daidzin, puerarin, ononin, genistin, formononetin, 3'-hydroxy puerarin, 3'-methoxy puerarin, mirificin, and 3'-methoxy daidzin exerted protective effects on H9c2 cells against hypoxia/reoxygenation injury. P. lobata extracts exhibited a significantly better protective efficacy than P. thomsonii extracts. CONCLUSIONS: In this study, AFADESI-MSI combined with LC-MS and biological activities comprehensively elucidated metabolite differences in the distribution, qualification, quantification, and pharmacological properties of P. lobata and P. thomsonii. The results of this study could provide a novel strategy for species identification and quality assessment of similar Chinese herbal medicines.

m6A demethylase ALKBH5 attenuates doxorubicin-induced cardiotoxicity via posttranscriptional stabilization of Rasal3.

The clinical application of anthracyclines such as doxorubicin (DOX) is limited due to their cardiotoxicity. N6-methyladenosine (m6A) plays an essential role in numerous biological processes. However, the roles of m6A and m6A demethylase ALKBH5 in DOX-induced cardiotoxicity (DIC) remain unclear. In this research, DIC models were constructed using Alkbh5-knockout (KO), Alkbh5-knockin (KI), and Alkbh5-myocardial-specific knockout (ALKBH5flox/flox, αMyHC-Cre) mice. Cardiac function and DOX-mediated signal transduction were investigated. As a result, both Alkbh5 whole-body KO and myocardial-specific KO mice had increased mortality, decreased cardiac function, and aggravated DIC injury with severe myocardial mitochondrial damage. Conversely, ALKBH5 overexpression alleviated DOX-mediated mitochondrial injury, increased survival, and improved myocardial function. Mechanistically, ALKBH5 regulated the expression of Rasal3 in an m6A-dependent manner through posttranscriptional mRNA regulation and reduced Rasal3 mRNA stability, thus activating RAS3, inhibiting apoptosis through the RAS/RAF/ERK signaling pathway, and alleviating DIC injury. These findings indicate the potential therapeutic effect of ALKBH5 on DIC.

Association of Systemic Immune Inflammation Index with All-Cause, Cardiovascular Disease, and Cancer-Related Mortality in Patients with Cardiovascular Disease: A Cross-Sectional Study.

Objective: Our research was designed to investigate the relationship between systemic immune inflammation (SII) index and all-cause, cardiovascular disease (CVD), and cancer-related mortality in patients with CVD. Methods: We used the National Health and Nutrition Examination Survey data from 1999 to 2018 to conduct this study. The association between SII index and all-cause, CVD, and cancer-related mortality in patients with CVD was examined using restricted cubic splines (RCS), Cox proportional hazard models, and subgroup analysis, respectively. CVD was defined as a composite of five outcomes of CVD, including coronary heart disease (CHD), congestive heart failure (CHF), angina pectoris, myocardial infarction, and stroke. Additionally, the link between SII index and all-cause, CVD, and cancer-related mortality in patients with a composite of five outcomes of CVD was also explored. Results: In total, 5329 participants were included. The RCS also showed a U-curve correlation between SII index and the all-cause, CVD, and cancer-related mortality in patients with CVD. As compared with the individuals with lowest quartile of SII index, hazard ratios with 95% confidence intervals for all-cause, CVD, and cancer-related mortality across the quartiles were (1.202 (0.981, 1.474), 1.184 (0.967, 1.450), and 1.365 (1.115, 1.672)), (1.116 (0.815, 1.527), 1.017 (0.740, 1.398), and 1.220 (0.891, 1.670)), and (1.202 (0.981, 1.474), 1.184 (0.967, 1.450), and 1.365 (1.115, 1.672)), respectively, in the full-adjusted model. The SII index also had a U-shaped relationship with all-cause, CVD, and cancer-related mortality in patients with CHD, angina, and myocardial infarction. Additionally, the U-shaped relationship between SII index and all-cause, and cancer-related mortality also exists in CHF, and stroke. However, there was a positive linear correlation between SII index and CVD mortality in patients with CHF, and stroke. Conclusion: In the United States general population, the correlation between SII index and all-cause, CVD, and cancer-related mortality showed a U-shaped curve in patients with CVD.

Increased gestational palmitic acid predisposes offspring to congenital heart disease.

Identification of the causes for congenital heart disease (CHD) is a prerequisite for precise prevention and personalized treatment of CHD. Zhao et al.1 show increased that gestational serum palmitic acid (PA) predisposes offspring to CHD by perturbating the MARS/K-Hcy/GATA4 signaling pathway.