SPIN1 facilitates chemoresistance and HR repair by promoting Tip60 binding to H3K9me3.

The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.

Deep enhanced constraint clustering based on contrastive learning for scRNA-seq data.

Single-cell RNA sequencing (scRNA-seq) measures transcriptome-wide gene expression at single-cell resolution. Clustering analysis of scRNA-seq data enables researchers to characterize cell types and states, shedding new light on cell-to-cell heterogeneity in complex tissues. Recently, self-supervised contrastive learning has become a prominent technique for underlying feature representation learning. However, for the noisy, high-dimensional and sparse scRNA-seq data, existing methods still encounter difficulties in capturing the intrinsic patterns and structures of cells, and seldom utilize prior knowledge, resulting in clusters that mismatch with the real situation. To this end, we propose scDECL, a novel deep enhanced constraint clustering algorithm for scRNA-seq data analysis based on contrastive learning and pairwise constraints. Specifically, based on interpolated contrastive learning, a pre-training model is trained to learn the feature embedding, and then perform clustering according to the constructed enhanced pairwise constraint. In the pre-training stage, a mixup data augmentation strategy and interpolation loss is introduced to improve the diversity of the dataset and the robustness of the model. In the clustering stage, the prior information is converted into enhanced pairwise constraints to guide the clustering. To validate the performance of scDECL, we compare it with six state-of-the-art algorithms on six real scRNA-seq datasets. The experimental results demonstrate the proposed algorithm outperforms the six competing methods. In addition, the ablation studies on each module of the algorithm indicate that these modules are complementary to each other and effective in improving the performance of the proposed algorithm. Our method scDECL is implemented in Python using the Pytorch machine-learning library, and it is freely available at https://github.com/DBLABDHU/scDECL.

NEAT1 regulates VSMC differentiation and calcification in as long noncoding RNA NEAT1 enhances phenotypic and osteogenic switching of vascular smooth muscle cells in atherosclerosis via scaffolding EZH2.

Atherosclerosis (AS) is a significant contributor to cardio-cerebrovascular ischemia diseases, resulting in high mortality rates worldwide. During AS, vascular smooth muscle cells (VSMCs) play a crucial role in plaque formation by undergoing phenotypic and osteogenic switching. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has previously been identified as a nuclear regulator that promotes tumorigenesis and metastasis, but its role in regulating VSMCs in AS remains unclear. Our study aimed to investigate the biological functions and specific mechanisms of NEAT1 in regulating VSMCs in AS. We found that NEAT1 was upregulated in the aortas of AS mouse models and dedifferentiated primary VSMCs. Silencing NEAT1 in vitro attenuated the proliferation, migration, and osteogenic differentiation of VSMCs, while NEAT1 overexpression had the opposite effect. Furthermore, NEAT1 promoted VSMC osteogenic differentiation and vascular calcification in both in vivo and in vitro vascular calcification models. We also discovered that NEAT1 directly activates enhancer of zeste homolog 2 (EZH2), an epigenetic enzyme that suppresses the expression of senescence- and antimigration-related genes, by translocating it into the nucleus. CUT&Tag assay revealed that NEAT1 guides EZH2 to the promoters of senescence-related genes (P16, P21, and TIMP3), methylating local histones to reduce their transcription. Our findings suggest that NEAT1 functions in AS by modulating the epigenetic function of EZH2, which enhances the proliferation, migration, and osteogenic differentiation of VSMCs. This study provides new insights into the molecular mechanisms underlying the pathogenesis of AS and highlights the potential of NEAT1 as a therapeutic target of AS.NEW & NOTEWORTHY Our study demonstrates that the upregulation of long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes proliferation and migration during phenotypic switching of vascular smooth muscle cells in atherosclerosis. We also provide in vivo and in vitro evidence that NEAT1 accelerates vascular calcification. Our findings identified the direct interaction between enhancer of zeste homolog 2 (EZH2) and NEAT1 during atherosclerosis. NEAT1 is necessary for EZH2 to translocate from the cytoplasm to the nucleus, where EZH2 epigenetically inhibits the expression of genes related to senescence and antimigration.

Characterization of sciatic nerve myelin sheath during development in C57BL/6 mice.

Myelin sheath plays important roles in information conduction and nerve injury repair in the peripheral nerve system (PNS). Enhancing comprehension of the structure and components of the myelin sheath in the PNS during development would contribute to a more comprehensive understanding of the developmental and regenerative processes. In this research, the structure of sciatic nerve myelin sheath in C57BL/6 mice from embryonic day 14 (E14) to postnatal 12 months (12M) was observed with transmission electron microscopy. Myelin structure appeared in the sciatic nerve as early as E14, and the number and thickness of myelin lamellar gradually increased with the development until 12M. Transcriptome analysis was performed to show the expressions of myelin-associated genes and transcriptional factors involved in myelin formation. The genes encoding myelin proteins (Mag, Pmp22, Mpz, Mbp, Cnp and Prx) showed the same expression pattern, peaking at postnatal day 7 (P7) and P28 after birth, whereas the negative regulators of myelination (c-Jun, Tgfb1, Tnc, Cyr61, Ngf, Egr1, Hgf and Bcl11a) showed an opposite expression pattern. In addition, the expression of myelin-associated proteins and transcriptional factors was measured by Western blot and immunofluorescence staining. The protein expressions of MAG, PMP22, MPZ, CNPase and PRX increased from E20 to P14. The key transcriptional factor c-Jun co-localized with the Schwann cells Marker S100ß and decreased after birth, whereas Krox20/Egr2 increased during development. Our data characterized the structure and components of myelin sheath during the early developmental stages, providing insights for further understanding of PNS development.

3D-Printed Mullite-Reinforced SiC-Based Aerogel Composites.

There is a growing demand for thermal management materials in electronic fields. Aerogels have attracted interest due to their extremely low density and extraordinary thermal insulation properties. However, the application of aerogels is limited by high production costs and the requirement that aerogel structures not be load-bearing. In this study, mullite-reinforced SiC-based aerogel composite (MR-SiC AC) is prepared through 3D printing combined with in situ growth of SiC nanowires in post processing. The fabricated MR-SiC AC not only has ultra-low thermal conductivity (0.021 W K m-1) and high porosity (90.0%), but also a high Young's modulus (24.4 MPa) and high compressive strength (1.65 MPa), both exceeding the measurements of existing resilient aerogels by an order of magnitude. These properties make MR-SiC AC an ideal solution for the precision thermal management of lightweight structures having complex geometry for functional devices.

Identification of BGN positive fibroblasts as a driving factor for colorectal cancer and development of its related prognostic model combined with machine learning.

BACKGROUND: Numerous studies have indicated that cancer-associated fibroblasts (CAFs) play a crucial role in the progression of colorectal cancer (CRC). However, there are still many unknowns regarding the exact role of CAF subtypes in CRC. METHODS: The data for this study were obtained from bulk, single-cell, and spatial transcriptomic sequencing data. Bioinformatics analysis, in vitro experiments, and machine learning methods were employed to investigate the functional characteristics of CAF subtypes and construct prognostic models. RESULTS: Our study demonstrates that Biglycan (BGN) positive cancer-associated fibroblasts (BGN + Fib) serve as a driver in colorectal cancer (CRC). The proportion of BGN + Fib increases gradually with the progression of CRC, and high infiltration of BGN + Fib is associated with poor prognosis in terms of overall survival (OS) and recurrence-free survival (RFS) in CRC. Downregulation of BGN expression in cancer-associated fibroblasts (CAFs) significantly reduces migration and proliferation of CRC cells. Among 101 combinations of 10 machine learning algorithms, the StepCox[both] + plsRcox combination was utilized to develop a BGN + Fib derived risk signature (BGNFRS). BGNFRS was identified as an independent adverse prognostic factor for CRC OS and RFS, outperforming 92 previously published risk signatures. A Nomogram model constructed based on BGNFRS and clinical-pathological features proved to be a valuable tool for predicting CRC prognosis. CONCLUSION: In summary, our study identified BGN + Fib as drivers of CRC, and the derived BGNFRS was effective in predicting the OS and RFS of CRC patients.

Helicobacter pylori induces GBA1 demethylation to inhibit ferroptosis in gastric cancer.

This research investigates potential therapeutic targets for gastric cancer, focusing on ferroptosis-related genes. Gastric cancer is known for its lower survival rates, necessitating new treatment strategies. This study employed Mendelian randomization to identify ferroptosis-related genes and methylation sites in gastric cancer, examining correlations between Helicobacter pylori infection, GBA1 gene expression, and promoter methylation with single-cell datasets and the TCGA-STAD database. We used Helicobacter pylori-infected gastric cancer cell models and used next-generation sequencing to monitor methylation changes pre- and post-infection. GBA1 expression levels were assessed via qRT-PCR and Western blot both before and after infection. The effect of Helicobacter pylori on GC cell proliferation was analyzed using CCK-8 and EdU assays after knocking down the GBA1 gene. The association between Helicobacter pylori infection and ferroptosis, including its reversibility after GBA1 knockdown, was evaluated using FerrOrange, GSH, MDA, and C11-BODIPY assays. Mass spectrometry measured the impact of Helicobacter pylori and GBA1 knockdown on lipid metabolism. An in vivo subcutaneous tumor-bearing model was also established to confirm these findings. Mendelian randomization analysis revealed that high GBA1 expression and reduced methylation levels of its promoter are risk factors for gastric cancer. Single-cell sequencing and TCGA-STAD datasets indicated a positive correlation between Helicobacter pylori infection and GBA1 expression, with a concurrent negative correlation between GBA1 promoter methylation and GBA1 expression. In gastric cancer cell lines, Helicobacter pylori infection was observed to enhance GBA1 expression and decrease methylation levels at its promoter. Additionally, Helicobacter pylori promoted GC cell proliferation, an effect mitigated by knocking down GBA1. Infection also reduced lipid peroxidation, increased glutathione levels, and impeded ferroptosis in GC cells; however, these effects were reversed following GBA1 knockdown. Changes in sphingolipid metabolism induced by I were detected in GC cell lines. In vivo experiments using a subcutaneous tumor-bearing model demonstrated that Helicobacter pylori infection fosters tumorigenesis in GC cells. Our study demonstrates that Helicobacter pylori infection triggers demethylation and upregulation of GBA1, subsequently inhibiting ferroptosis in gastric cancer cells. These findings suggest that targeting the GBA1 pathway may offer a novel therapeutic approach for managing gastric cancer.

Azacitidine combined with venetoclax alleviates AML-MR with TP53 mutation in SDS: a case report and literature review.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive genetic disease, which is prone to transform into myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). TP53 mutation is a driving factor involved in the transformation of SDS into MDS/AML, and in the evolution of MDS to AML. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only curable approach, however, challenge remains regarding the balance between efficacy and the high risk from treatment-related toxicity and mortality to achieve temporary disease control before transplantation to gain time and opportunities for transplantation. At present, pre-transplant bridging therapy has emerged as one of the important options with improved efficacy, reduced tumor burden, and less treatment-related toxicity. Here we reported azacitidine combined with venetoclax was used as pre-transplant bridging regimen in a TP53-mutant AML-MR case developed from SDS. He achieved complete remission with incomplete recovery and proceeded to Allo-HSCT. We hope to provide some evidence and insight for in-depth research and clinical treatment by presenting this case.

A Single Nucleotide Polymorphism in SH2B3/LNK Promotes Hypertension Development and Renal Damage.

BACKGROUND: SH2B3 (SH2B adaptor protein 3) is an adaptor protein that negatively regulates cytokine signaling and cell proliferation. A common missense single nucleotide polymorphism in SH2B3 (rs3184504) results in substitution of tryptophan (Trp) for arginine (Arg) at amino acid 262 and is a top association signal for hypertension in human genome-wide association studies. Whether this variant is causal for hypertension, and if so, the mechanism by which it impacts pathogenesis is unknown. METHODS: We used CRISPR-Cas9 technology to create mice homozygous for the major (Arg/Arg) and minor (Trp/Trp) alleles of this SH2B3 polymorphism. Mice underwent angiotensin II (Ang II) infusion to evaluate differences in blood pressure (BP) elevation and end-organ damage including albuminuria and renal fibrosis. Cytokine production and Stat4 phosphorylation was also assessed in Arg/Arg and Trp/Trp T cells. RESULTS: Trp/Trp mice exhibit 10 mmHg higher systolic BP during chronic Ang II infusion compared to Arg/Arg controls. Renal injury and perivascular fibrosis are exacerbated in Trp/Trp mice compared to Arg/Arg controls following Ang II infusion. Renal and ex vivo stimulated splenic CD8+ T cells from Ang II-infused Trp/Trp mice produce significantly more interferon gamma (IFNg) compared to Arg/Arg controls. Interleukin-12 (IL-12)-induced IFNg production is greater in Trp/Trp compared to Arg/Arg CD8+ T cells. In addition, IL-12 enhances Stat4 phosphorylation to a greater degree in Trp/Trp compared to Arg/Arg CD8+ T cells, suggesting that Trp-encoding SH2B3 exhibits less negative regulation of IL-12 signaling to promote IFNg production. Finally, we demonstrated that a multi-SNP model genetically predicting increased SH2B3 expression in lymphocytes is inversely associated with hypertension and hypertensive chronic kidney disease in humans.. CONCLUSIONS: Taken together, these results suggest that the Trp encoding allele of rs3184504 is causal for BP elevation and renal dysfunction, in part through loss of SH2B3-mediated repression of T cell IL-12 signaling leading to enhanced IFNg production.

Graft-versus-host disease in patients with bone marrow transplants: A retrospective study analyzing outcomes and healthcare burden in US hospitals.

BACKGROUND: Graft-versus-host disease (GVHD) is a recognized complication among individuals undergoing bone marrow transplantation (BMT). There is a requirement for supplementary data regarding the in-patient outcomes of GVHD in individuals who have undergone BMT. Our analysis seeks to assess the healthcare burden and outcomes associated with GVHD in hospitalized patients who have undergone BMT. METHOD: In this retrospective study, we used data from the National Inpatient Sample (NIS) database spanning from 2016 to 2019. Utilizing ICD-10 codes, we distinguished hospitalizations related to BMT and grouped them into two categories: those with GVHD and those without GVHD. Our areas of focus included in-hospital mortality, length of stay, charges, and associations related to GVHD. Unadjusted odds ratios/coefficients were computed through univariable analysis, followed by adjusted odds ratios (aORs)/coefficients from multivariable analysis that considered potential confounding factors. RESULTS: From 2016 to 2019, data were collected from 13,999 hospitalizations with bone marrow transplants. Among them, 836 had GVHD cases. Patient characteristics showed slight differences in mean age and demographics between the two groups, with GVHD patients having a mean age of 51.61 years and higher percentages of males and whites. Analyzing outcomes, patients with GVHD experienced significantly longer hospital stays (41.4 days vs. 21.3 days) and higher total hospital charges ($824,058 vs. $335,765). Adjusting for confounding factors, GVHD posed a substantial risk. The aOR for mortality in GVHD hospitalizations was 7.20 (95% CI: 5.54-9.36, p < .001). The coefficient for the length of stay was 19.36 days (95% CI: 17.29-21.42, p < .001), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889, p < .001) in GVHD cases. Furthermore, GVHD in patients was associated with elevated risks of various medical conditions. The aORs for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in GVHD patients were 2.79 (95% CI: 2.28-3.41, p < .001), 3.30 (95% CI: 2.57-4.24, p < .001), 5.10 (95% CI: 4.01-6.49, p < .001), 4.88 (95% CI: 3.75-6.34, p < .001), 1.45 (95% CI: 1.13-1.86, p = .003), and 3.57 (95% CI: 2.97-4.29, p < .001). CONCLUSION: GVHD in individuals undergoing BMT is linked to elevated mortality rates, prolonged hospitalization, and higher healthcare costs. Moreover, they face a significantly increased risk of developing complications, such as sepsis, pneumonia, acute respiratory failure, C. difficile infection, and AKI. These results underscore the critical need for vigilant monitoring and effective GVHD management to improve patient outcomes and reduce the complications associated with BMT. Nevertheless, further prospective studies are essential to obtain a more profound understanding and a comprehensive assessment of outcomes in these hospitalized patients.

The global burden of disease attributable to high body mass index in 204 countries and territories: Findings from 1990 to 2019 and predictions to 2035.

AIM: Our study aims to provide an updated estimate of age- and sex-specific deaths and disability-adjusted life years (DALYs) associated with high body mass index (BMI) from 1990 to 2019 at the global, regional and national levels, and to forecast the global burden of disease attributed to high BMI from 2020 to 2035. METHODS: We used the data for the number of deaths, DALYs, age-standardized rate (per 100 000 population), percentage change and population attributable fraction from the Global Burden of Disease Study 2019 (GBD 2019) to examine the disease burden attributable to high BMI. We further applied an autoregressive integrated moving average (ARIMA) model to predict the disease burden for the period 2020-2035. RESULTS: From 1990 to 2019, the deaths and DALYs attributable to high BMI increased by 148% and 155.86% for men, and by 111.67% and 121.78% for women, respectively. In 2019, high BMI directly accounted for 8.52% [95% uncertainty intervals (UI) 0.05, 0.12] of all-cause deaths and 5.89% (95% UI 0.04, 0.08) of global DALYs. The highest death rates were observed in men aged 65-69 and women aged 75-79. The highest DALY rates were observed in the age group of 60-64 for both sexes. In 2019, the highest age-standardized deaths and DALY rates were observed in the Central Asia region [163.15 (95% UI 107.72, 223.58) per 100 000 people] and the Oceania region [4643.33 (95% UI 2835.66, 6902.6) per 100 000 people], respectively. Fiji [319.08 (95% UI 213.77, 444.96) per 100 000 people] and Kiribati [10 000.58 (95% UI 6266.55, 14159.2) per 100 000 people] had the highest age-standardized deaths and DALY rates, respectively. In 2019, the highest age-standardized rates of high BMI-related deaths and DALYs were observed in the middle-high socio-demographic index quintile and in the middle socio-demographic index quintile. The age-standardized deaths and DALY rates attributable to high BMI are projected to increase in both sexes from 2020 to 2035. The death rates are projected to rise from 62.79 to 64.31 per 100 000 people, while the DALY rates are projected to rise from 1946 to 2099.54 per 100 000 people. CONCLUSIONS: High BMIs significantly contribute to the global disease burden. The projected rise in deaths and DALY rates attributable to high BMI by 2035 highlights the critical need to address the impact of obesity on public health. Our study provides policymakers with up-to-date and comprehensive information.

Global burden of diseases attributable to intimate partner violence: findings from the Global Burden of Disease Study 2019.

PURPOSE: Our study aims to evaluate the global burden of disease attributable to IPV from 1990 to 2019 at global, regional, national, and socio-demographic index (SDI) levels. Our research question is: What is the global burden of disease attributable to intimate partner violence (IPV) from 1990 to 2019, and how does it vary at global, regional, national, and socio-demographic index (SDI) levels? METHODS: Data parameters for the number of deaths, disability-adjusted life years (DALYs), and age-standardized rate were obtained from the Global Burden of Disease Study 2019. We calculated the percentage change and population attributable fraction with 95% uncertainty intervals. RESULTS: IPV directly accounted for 0.14% [95% UI 0.09%, 0.21%] and 0.32% [95% UI 0.17%, 0.49%] of global all-cause deaths and DALYs in 2019, respectively. The age-standardized deaths and DALYs rates of IPV increased by 12.83% and 4.00% respectively from 1990 to 2019. Women aged 35-39 and 30-34 had the highest deaths and DALYs rate respectively. The highest age-standardized rates of IPV-related deaths and DALYs were observed in Southern Sub-Saharan. Both of deaths and DALYs were high in low-socio-demographic Index (SDI) quintile in 2019. CONCLUSIONS: A higher level of deaths and DALYs attributable to IPV were reported in younger women, in the early 2000s, in Southern Sub-Saharan regions and in low SDI regions. Our study provides policymakers with up-to-date and comprehensive information.

Association of aerobic glycolysis with the structural connectome reveals a benefit-risk balancing mechanism in the human brain.

Aerobic glycolysis (AG), that is, the nonoxidative metabolism of glucose, contributes significantly to anabolic pathways, rapid energy generation, task-induced activity, and neuroprotection; yet high AG is also associated with pathological hallmarks such as amyloid-ß deposition. An important yet unresolved question is whether and how the metabolic benefits and risks of brain AG is structurally shaped by connectome wiring. Using positron emission tomography and magnetic resonance imaging techniques as well as computational models, we investigate the relationship between brain AG and the macroscopic connectome. Specifically, we propose a weighted regional distance-dependent model to estimate the total axonal projection length of a brain node. This model has been validated in a macaque connectome derived from tract-tracing data and shows a high correspondence between experimental and estimated axonal lengths. When applying this model to the human connectome, we find significant associations between the estimated total axonal projection length and AG across brain nodes, with higher levels primarily located in the default-mode and prefrontal regions. Moreover, brain AG significantly mediates the relationship between the structural and functional connectomes. Using a wiring optimization model, we find that the estimated total axonal projection length in these high-AG regions exhibits a high extent of wiring optimization. If these high-AG regions are randomly rewired, their total axonal length and vulnerability risk would substantially increase. Together, our results suggest that high-AG regions have expensive but still optimized wiring cost to fulfill metabolic requirements and simultaneously reduce vulnerability risk, thus revealing a benefit-risk balancing mechanism in the human brain.

Association analysis of the sorting nexin 29 (SNX29) gene copy number variations with growth traits in Diannan small-ear (DSE) pigs.

SNX29 is a potential functional gene associated with meat production traits. Previous studies have shown that SNX29 copy number variation (CNV) could be implicated with phenotype in goats. However, in Diannan small-ear (DSE) pigs, the genetic impact of SNX29 CNV on growth traits remains unclear. Therefore, this study investigated the associations between SNX29 CNVs (CNV10810 and CNV10811) and growth traits in 415 DSE pigs. The results revealed that the CNV10810 mutation was significantly associated with backfat thickness in DSE pigs at 12 and 15 months old (P < 0.05), while the CNV10811 mutation had significant effects on various growth traits at 6 and 12 months old, particularly for body weight, body height, back height and backfat thickness (P < 0.05 or P < 0.001). In conclusion, our results confirm that SNX29 CNV plays a role in regulating growth and development in pigs, thus suggesting its potential application for pig breeding programmes.

Simultaneous removal of tetracycline hydrochloride and hexavalent chromium by heterogeneous Fenton in a photocatalytic fuel cell system.

In this work, a novel double-chamber system (PFC-Fenton), combined photocatalytic fuel cell (PFC) with Fenton, was constructed for tetracycline hydrochloride (TCH) and hexavalent chromium (Cr(VI)) removal and electricity production. Therein, Zn5(OH)6(CO3)2/Fe2O3/BiVO4/fluorine-doped SnO2 (ZIO/BiVO4/FTO) and carboxylated carbon nanotubes/polypyrrole/graphite felt (CCNTs/Ppy/GF) were served as photoanode and cathode, respectively. Under light irradiation, the removal efficiencies of TCH and Cr(VI) with the addition of H2O2 (2 mL) could reach 93.1% and 80.4%, respectively. Moreover, the first-order kinetic constants (7.37 × 10-3 min-1 of TCH and 3.94 × 10-3 min-1 of Cr(VI)) were 5.26 and 5.57 times as much as the absence of H2O2. Simultaneously, the maximum power density could be obtained 0.022 mW/cm2 at a current density of 0.353 mA/cm2. Therein, the main contribution of TCH degradation was ·OH and holes in anode chamber. The synergistic effect of photoelectrons, generated ·O2-, and H2O2 played a crucial role in the reduction of Cr(VI) in cathode chamber. The high-performance liquid chromatography-mass spectrometry indicated that TCH could be partially mineralized into CO2 and H2O. X-ray photoelectron spectroscope and X-ray absorption near-edge structure spectra showed that Cr(VI) could be reduced to Cr(III). After 5 times of cycling, the removal efficiencies of TCH and Cr(VI) were still greater than 70%, indicating the remarkable stability of the PFC-Fenton system. Overall, this system could remove TCH/Cr(VI) and generate power simultaneously without iron sludge formation, demonstrating a promising method to further develop PFC-Fenton technology.

Magnetic Ion-Imprinted Materials for Selective Adsorption of Cr(VI): Adsorption Behavior and Mechanism Study.

With the increase of hexavalent Cr(VI) wastewater discharged from industrial production, it seriously pollutes water bodies and poses a risk to human health. Adsorption is used as an effective means to treat Cr(VI), but its effectiveness is affected by pH, and the adsorption performance decreases when acidity is strong. Furthermore, research on the mechanism of Cr(VI) adsorption using DFT calculations needs to be developed. This study focuses on the development of magnetically responsive core-shell nano-ion imprinted materials (Fe3O4@GO@IIP) through magnetic separation and surface imprinting techniques. Characterization techniques including FT-IR, XRD, and EDS confirmed the core-shell nanostructure of Fe3O4@GO@IIP. Batch adsorption experiments and model simulations demonstrated the exceptional adsorption capacity of Fe3O4@GO@IIP for Cr(VI) in strongly acidic solutions (pH = 1), reaching a maximum of 89.18 mg/g. The adsorption mechanism was elucidated through XPS and DFT calculations, revealing that Fe3O4@GO@IIP operates through electrostatic interactions and chemical adsorption, with charge transfer dynamics quantified during the process. This research provides new insights for addressing Cr(VI) treatment in highly acidic environments.

Novel signaling axis of FHOD1-RNF213-Col1α/Col3α in the pathogenesis of hypertension-induced tunica media thickening.

Hypertension-induced tunica media thickening (TMT) is the most important fundamental for the subsequent complications like stroke and cardiovascular diseases. Pathogenically, TMT originates from both vascular smooth muscle cells (VSMCs) hypertrophy due to synthesizing more amount of intracellular contractile proteins and excess secretion of extracellular matrix. However, what key molecules are involved in the pathogenesis of TMT is unknown. We hypothesize that formin homology 2 domain-containing protein 1 (FHOD1), an amply expressed mediator for assembly of thin actin filament in VSMCs, is a key regulator for the pathogenesis of TMT. In this study, we found that FHOD1 expression and its phosphorylation/activation were both upregulated in the arteries of three kinds of hypertensive rats. Ang-II induced actin filament formation and hypertrophy through activation and upregulation of FHOD1 in VSMCs. Active FHOD1-mediated actin filament assembly and secretions of collagen-1α/collagen-3α played crucial roles in Ang-II-induced VSMCs hypertrophy in vitro and hypertensive TMT in vivo. Proteomics demonstrated that activated FL-FHOD1 or its C-terminal diaphanous-autoregulatory domain significantly upregulated RNF213 (ring finger protein 213), a 591-kDa cytosolic E3 ubiquitin ligase with its loss-of-functional mutations being a susceptibility gene for Moyamoya disease which has prominent tunica media thinning in both intracranial and systemic arteries. Mechanistically, activated FHOD1 upregulated its downstream effector RNF213 independently of its classical pathway of decreasing G-actin/F-actin ratio, transcription, and translation, but dependently on its C-terminus-mediated stabilization of RNF213 protein. FHOD1-RNF213 signaling dramatically promoted collagen-1α/collagen-3α syntheses in VSMCs. Our results discovered a novel signaling axis of FHOD1-RNF213-collagen-1α/collagen-3α and its key role in the pathogenesis of hypertensive TMT.

Maturation of auditory cortex neural responses during infancy and toddlerhood.

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left-right hemisphere P2m maturation is associated with language performance.

Integration of glucose and cardiolipin anabolism confers radiation resistance of HCC.

BACKGROUND AND AIMS: Poor response to ionizing radiation (IR) due to resistance remains a clinical challenge. Altered metabolism represents a defining characteristic of nearly all types of cancers. However, how radioresistance is linked to metabolic reprogramming remains elusive in hepatocellular carcinoma (HCC). APPROACH AND RESULTS: Baseline radiation responsiveness of different HCC cells were identified and cells with acquired radio-resistance were generated. By performing proteomics, metabolomics, metabolic flux, and other functional studies, we depicted a metabolic phenotype that mediates radiation resistance in HCC, whereby increased glucose flux leads to glucose addiction in radioresistant HCC cells and a corresponding increase in glycerophospholipids biosynthesis to enhance the levels of cardiolipin. Accumulation of cardiolipin dampens the effectiveness of IR by inhibiting cytochrome c release to initiate apoptosis. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1) signaling-mediated translational control of hypoxia inducible factor-1α (HIF-1α) and sterol regulatory element-binding protein-1 (SREBP1) remodels such metabolic cascade. Targeting mTORC1 or glucose to cardiolipin synthesis, in combination with IR, strongly diminishes tumor burden. Finally, activation of glucose metabolism predicts poor response to radiotherapy in cancer patients. CONCLUSIONS: We demonstrate a link between radiation resistance and metabolic integration and suggest that metabolically dismantling the radioresistant features of tumors may provide potential combination approaches for radiotherapy in HCC.

Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism.

BACKGROUND: The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation. METHODS: To focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myocardial structure and function were examined using echocardiography, histology, and biochemical assays. We further investigated the underlying effects of mitochondrial AKT1 on mitochondrial structure and function, its interaction with ATP synthase, and explored in vivo metabolism beyond the heart. RESULTS: Upon induction of dominant negative mitochondrial AKT1, CAMDAKT mice developed cardiac fibrosis accompanied by left ventricular hypertrophy and dysfunction. Cardiac mitochondrial oxidative phosphorylation efficiency and ATP content were reduced, mitochondrial cristae structure was lost, and ATP synthase structure was compromised. Conversely, CAMCAKT mice were protected against development of diabetic cardiomyopathy when challenged with a high calorie diet. Activation of mitochondrial AKT1 protected cardiac function and increased fatty acid uptake in myocardium. In addition, total energy expenditure was increased in CAMCAKT mice, accompanied by reduced adiposity and reduced development of fatty liver. CONCLUSION: CAMDAKT mice modeled the effects of impaired mitochondrial signaling which occurs in the diabetic myocardium. Disruption of this pathway is a key step in the development of cardiomyopathy. Activation of mitochondrial AKT1 in CAMCAKT had a protective role against diabetic cardiomyopathy as well as improved metabolism beyond the heart.