Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Core planar cell polarity genes VANGL1 and VANGL2 in predisposition to congenital vertebral malformations.

Congenital scoliosis (CS), affecting approximately 0.5 to 1 in 1,000 live births, is commonly caused by congenital vertebral malformations (CVMs) arising from aberrant somitogenesis or somite differentiation. While Wnt/ß-catenin signaling has been implicated in somite development, the function of Wnt/planar cell polarity (Wnt/PCP) signaling in this process remains unclear. Here, we investigated the role of Vangl1 and Vangl2 in vertebral development and found that their deletion causes vertebral anomalies resembling human CVMs. Analysis of exome sequencing data from multiethnic CS patients revealed a number of rare and deleterious variants in VANGL1 and VANGL2, many of which exhibited loss-of-function and dominant-negative effects. Zebrafish models confirmed the pathogenicity of these variants. Furthermore, we found that Vangl1 knock-in (p.R258H) mice exhibited vertebral malformations in a Vangl gene dose- and environment-dependent manner. Our findings highlight critical roles for PCP signaling in vertebral development and predisposition to CVMs in CS patients, providing insights into the molecular mechanisms underlying this disorder.

TRIM21/USP15 balances ACSL4 stability and the imatinib resistance of gastrointestinal stromal tumors.

BACKGROUND: Imatinib has become an exceptionally effective targeted drug for treating gastrointestinal stromal tumors (GISTs). Despite its efficacy, the resistance to imatinib is common in GIST patients, posing a significant challenge to the effective treatment. METHODS: The expression profiling of TRIM21, USP15, and ACSL4 in GIST patients was evaluated using Western blot and immunohistochemistry. To silence gene expression, shRNA was utilized. Biological function of TRIM21, USP15, and ACSL4 was examined through various methods, including resistance index calculation, colony formation, shRNA interference, and xenograft mouse model. The molecular mechanism of TRIM21 and USP15 in GIST was determined by conducting Western blot, co-immunoprecipitation, and quantitative real-time PCR (qPCR) analyses. RESULTS: Here we demonstrated that downregulation of ACSL4 is associated with imatinib (IM) resistance in GIST. Moreover, clinical data showed that higher levels of ACSL4 expression are positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that the reduced expression of ACSL4 in GIST is attributed to excessive protein degradation mediated by the E3 ligase TRIM21 and the deubiquitinase USP15. CONCLUSION: These findings demonstrate that the TRIM21 and USP15 control ACSL4 stability to maintain the IM sensitive/resistant status of GIST.

iFLAS: positive-unlabeled learning facilitates full-length transcriptome-based identification and functional exploration of alternatively spliced isoforms in maize.

The advent of full-length transcriptome sequencing technologies has accelerated the discovery of novel splicing isoforms. However, existing alternative splicing (AS) tools are either tailored for short-read RNA-Seq data or designed for human and animal studies. The disparities in AS patterns between plants and animals still pose a challenge to the reliable identification and functional exploration of novel isoforms in plants. Here, we developed integrated full-length alternative splicing analysis (iFLAS), a plant-optimized AS toolkit that introduced a semi-supervised machine learning method known as positive-unlabeled (PU) learning to accurately identify novel isoforms. iFLAS also enables the investigation of AS functions from various perspectives, such as differential AS, poly(A) tail length, and allele-specific AS (ASAS) analyses. By applying iFLAS to three full-length transcriptome sequencing datasets, we systematically identified and functionally characterized maize (Zea mays) AS patterns. We found intron retention not only introduces premature termination codons, resulting in lower expression levels of isoforms, but may also regulate the length of 3'UTR and poly(A) tail, thereby affecting the functional differentiation of isoforms. Moreover, we observed distinct ASAS patterns in two genes within heterosis offspring, highlighting their potential value in breeding. These results underscore the broad applicability of iFLAS in plant full-length transcriptome-based AS research.

High-Q metasurface signal isolator for 1.5T surface coil magnetic resonance imaging on the go.

The combination of surface coils and metamaterials remarkably enhance magnetic resonance imaging (MRI) performance for significant local staging flexibility. However, due to the coupling in between, impeded signal-to-noise ratio (SNR) and low-contrast resolution, further hamper the future growth in clinical MRI. In this paper, we propose a high-Q metasurface decoupling isolator fueled by topological LC loops for 1.5T surface coil MRI system, increasing the magnetic field up to fivefold at 63.8 MHz. We have employed a polarization conversion mechanism to effectively eliminate the coupling between the MRI metamaterial and the radio frequency (RF) surface transmitter-receiver coils. Furthermore, a high-Q metasurface isolator was achieved by taking advantage of bound states in the continuum (BIC) for extremely high-resolution MRI and spectroscopy. An equivalent physical model of the miniaturized metasurface design was put forward through LC circuit analysis. This study opens up a promising route for the easy-to-use and portable surface coil MRI scanners.

Mutation breeding of high-stress resistant strains for succinic acid production from corn straw.

The production of succinic acid from corn stover is a promising and sustainable route; however, during the pretreatment stage, byproducts such as organic acids, furan-based compounds, and phenolic compounds generated from corn stover inhibit the microbial fermentation process. Selecting strains that are resistant to stress and utilizing nondetoxified corn stover hydrolysate as a feedstock for succinic acid production could be effective. In this study, A. succinogenes CICC11014 was selected as the original strain, and the stress-resistant strain A. succinogenes M4 was obtained by atmospheric and room temperature plasma (ARTP) mutagenesis and further screening. Compared to the original strain, A. succinogenes M4 exhibited a twofold increase in stress resistance and a 113% increase in succinic acid production when hydrolysate was used as the substrate. By conducting whole-genome resequencing of A. succinogenes M4 and comparing it with the original strain, four nonsynonymous gene mutations and two upstream regions with base losses were identified. KEY POINTS: • A high-stress-resistant strain A. succinogenes M4 was obtained by ARTP mutation •  The production of succinic acid increased by 113% • The mutated genes of A. succinogenes M4 were detected and analyzed.

Association between vascular aging and cognitive function in Chinese adults.

BACKGROUND: Vascular health has been associated with cognition but related evidence is limited in Chinese. The objective of this study was to examine the association of vascular aging assessed by arterial stiffness and blood pressure with cognitive function in an unselected Chinese population. METHODS: In the Tianning Cohort (N = 5158), indicators of arterial stiffness and blood pressure including carotid-femoral pulse wave velocity (cfPWV), ankle-brachial index (ABI), pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Cognitive function was assessed using the Mini Mental State Examination (MMSE) questionnaire. We applied Poisson regression and logistic regression to examine the associations of vascular aging and blood pressure with cognitive function. RESULTS: 76 (1.47%) participants had impaired cognitive function diagnosed by a MMSE score of less than 24 points. Participants with a higher level of PP were more likely to have a decreased score of MMSE (ß=-0.0121, P < 0.001 for log-transformed pulse pressure) and a higher risk of having impaired cognitive function (OR = 5.95, 95%CI: 2.02-17.79, P < 0.001 for log-transformed PP). Per standard deviation increment in SBP was significantly associated with lower MMSE score (ß=-0.0020, P < 0.001) and impaired cognitive function (OR = 1.69, 95%CI: 1.38-2.06, P < 0.001). No significant associations were found regarding other parameters. CONCLUSIONS: Blood pressure and hypertension were associated with cognitive function in Chinese adults. PP may be a potential predictor for impaired cognitive function.

Enhanced Electron Delocalization Induced by Ferromagnetic Sulfur doped C3N4 Triggers Selective H2O2 Production.

For the 2D metal-free carbon catalysts, the atomic coplanar architecture enables a large number of pz orbitals to overlap laterally, thus forming π-electron delocalization, and the delocalization degree of the central atom dominates the catalytic activity. Herein, designing sulfur-doped defect-rich graphitic carbon nitride (S-Nv-C3N4) materials as a model, we propose a strategy to promote localized electron polarization by enhancing the ferromagnetism of ultra-thin 2D carbon nitride nanosheets. The introduction of sulfur (S) further promotes localized ferromagnetic coupling, thereby inducing long-range ferromagnetic ordering and accelerating the electron interface transport. Meanwhile, the hybridization of sulfur atoms breaks the symmetry and integrity of the unit structure, promotes electron enrichment and stimulating electron delocalization at the active site. This optimization enhances the *OOH desorption, providing a favorable kinetic pathway for the production of hydrogen peroxide (H2O2). Consequently, S-Nv-C3N4 exhibits high selectivity (>95 %) and achieves a superb H2O2 production rate, approaching 4374.8 ppm during continuous electrolysis over 300 hour. According to theoretical calculation and in situ spectroscopy, the ortho-S configuration can provide ferromagnetic perturbation in carbon active centers, leading to the electron delocalization, which optimizes the OOH* adsorption during the catalytic process.

Efficacy of epidural steroid injection in the treatment of sciatica secondary to lumbar disc herniation: a systematic review and meta-analysis.

Epidural steroid injection for the treatment of sciatica caused by disc herniation is increasingly used worldwide, but its effectiveness remains controversial. The review aiming to analyze the efficacy of epidural steroid injection on sciatica caused by lumbar disc herniation. Randomized controlled trials (RCTs) investigating the use of epidural steroid injections in the management of sciatica induced by lumbar disc herniation were collected from PubMed and other databases from January, 2008 to December, 2023, with epidural steroid injection in the test group and epidural local anesthetic and/or placebo in the control group. Pain relief rate, assessed by numerical rating scale (NRS) and visual analogue scale (VAS) scores, and function recovery, evaluated by Roland Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI) scores, were recorded and compared. Meta-analysis was performed by Review Manager. In comparison to the control group, epidural steroid injections have been shown to be effective for providing short- (within 3 months) [MD = 0.44, 95%CI (0.20, 0.68), p = 0.0003] and medium-term (within 6 months) [MD = 0.66, 95%CI (0.09,1.22), p = 0.02] pain relief for sciatica caused by lumbar disc herniation, while its long-term pain-relief effect were limited. However, the administration of epidural steroid injections did not lead to a significant improvement on sciatic nerve function in short- [MD = 0.79, 95%CI = (0.39, 1.98), p = 0.19] and long-term [MD = 0.47, 95% CI = (-0.86, 1.80), p = 0.49] assessed by IOD. Furthermore, the analysis revealed that administering epidural steroid injections resulted in a reduction in opioid usage among patients with lumbar disc herniation [MD = -14.45, 95% CI = (-24.61, -4.29), p = 0.005]. The incidence of epidural steroid injection was low. Epidural steroid injection has demonstrated notable efficacy in relieving sciatica caused by lumbar disc herniation in short to medium-term. Therefore, it is recommended as a viable treatment option for individuals suffering from sciatica.

Evolutionary Search and Theoretical Study of Silicene Grain Boundaries' Mechanical Properties.

Defects such as grain boundaries (GBs) are almost inevitable during the synthesis process of 2D materials. To take advantage of the fascinating properties of 2D materials, understanding the nature and impact of various GB structures on pristine 2D sheets is crucial. In this work, using an evolutionary algorithm search, we predict a wide variety of silicene GB structures with very different atomic structures compared with those found in graphene or hexagonal boron-nitride. Twenty-one GBs with the lowest energy were validated by density functional theory (DFT), a majority of which were previously unreported to our best knowledge. Based on the diversity of the GB predictions, we found that the formation energy and mechanical properties can be dramatically altered by adatom positions within a GB and certain types of atomic structures, such as four-atom rings. To study the mechanical behavior of these GBs, we apply strain to the GB structures stepwise and use DFT calculations to investigate the mechanical properties of 9 representative structures. It is observed that GB structures based on pentagon-heptagon pairs are likely to have similar or higher in-plane stiffness and strength compared to the zigzag orientation of pristine silicene. However, an adatom located at the hollow site of a heptagon ring can significantly deteriorate the mechanical strength. For all of the structures, the in-plane stiffness and strength were found to decrease with increasing formation energy. For the failure behavior of GB structures, it was found that GB structures based on pentagon-heptagon pairs have failure behavior similar to that of graphene. We also found that the GB structures with atoms positioned outside of the 2D plane tend to experience phase transitions before failure. Utilizing the evolutionary algorithm, we locate diverse silicene GBs and obtain useful information about their mechanical properties.

Evaluating cognitive performance: Traditional methods vs. ChatGPT.

Background: NLP models like ChatGPT promise to revolutionize text-based content delivery, particularly in medicine. Yet, doubts remain about ChatGPT's ability to reliably support evaluations of cognitive performance, warranting further investigation into its accuracy and comprehensiveness in this area. Method: A cohort of 60 cognitively normal individuals and 30 stroke survivors underwent a comprehensive evaluation, covering memory, numerical processing, verbal fluency, and abstract thinking. Healthcare professionals and NLP models GPT-3.5 and GPT-4 conducted evaluations following established standards. Scores were compared, and efforts were made to refine scoring protocols and interaction methods to enhance ChatGPT's potential in these evaluations. Result: Within the cohort of healthy participants, the utilization of GPT-3.5 revealed significant disparities in memory evaluation compared to both physician-led assessments and those conducted utilizing GPT-4 (P < 0.001). Furthermore, within the domain of memory evaluation, GPT-3.5 exhibited discrepancies in 8 out of 21 specific measures when compared to assessments conducted by physicians (P < 0.05). Additionally, GPT-3.5 demonstrated statistically significant deviations from physician assessments in speech evaluation (P = 0.009). Among participants with a history of stroke, GPT-3.5 exhibited differences solely in verbal assessment compared to physician-led evaluations (P = 0.002). Notably, through the implementation of optimized scoring methodologies and refinement of interaction protocols, partial mitigation of these disparities was achieved. Conclusion: ChatGPT can produce evaluation outcomes comparable to traditional methods. Despite differences from physician evaluations, refinement of scoring algorithms and interaction protocols has improved alignment. ChatGPT performs well even in populations with specific conditions like stroke, suggesting its versatility. GPT-4 yields results closer to physician ratings, indicating potential for further enhancement. These findings highlight ChatGPT's importance as a supplementary tool, offering new avenues for information gathering in medical fields and guiding its ongoing development and application.

METTL3/IGF2BP3-regulated m6A modification of HYOU1 confers doxorubicin resistance in breast cancer.

Chemoresistance is a main reason for therapeutic failure and poor prognosis for breast cancer (BC) patients, especially for triple-negative BC patients. How the molecular mechanisms underlying the chemoresistance to doxorubicin (Dox) in BC is not well understood. Here, we revealed that METTL3/IGF2BP3-regulated m6A modification of HYOU1 increased Dox resistance in BC cells. CCK-8 and Annexin V-FITC/PI staining assays were employed to measure viability and cell death. Western blotting and qRT-PCR assays were applied to assay the expression of genes. Knockdown and rescue experiments were used to assay the role of METTL3, IGF2BP3 and HYOU1 in regulating BC cell responses to Dox. RIP, MeRIP and dual-luciferase activity assays were applied to examine the function of METTL3/IGF2BP3 in the m6A modification of HYOU1 mRNA. It was found that global mRNA m6A methylation levels were upregulated in Dox-resistant BC cell lines. The methyltransferase METTL3 was upregulated in Dox-resistant BC cell lines, and downregulation of METTL3 could overcome this resistance. Furthermore, HYOU1 was identified as a downstream target of METTL3-mediated m6A modification. Downregulation of HYOU1 could overcome Dox resistance, while forced expression of HYOU1 resulted in Dox resistance in BC cells. METTL3 cooperated with IGF2BP3 to modulate the m6A modification of HYOU1 mRNA and increase its stability. Collectively, our findings unveiled the key roles of the METTL3/IGF2BP3/HYOU1 axis in modulating Dox sensitivity in BC cells; thus, targeting this axis might be a potential strategy to increase Dox efficacy in the treatment of BC.

Identification of Putative Quantitative Trait Loci for Improved Seed Oil Quality in Peanuts.

Improving seed oil quality in peanut (Arachis hypogaea) has long been an aim of breeding programs worldwide. The genetic resources to achieve this goal are limited. We used an advanced recombinant inbred line (RIL) population derived from JH5 × KX01-6 to explore quantitative trait loci (QTL) affecting peanut oil quality and their additive effects, epistatic effects, and QTL × environment interactions. Gas chromatography (GC) analysis suggested seven fatty acids components were obviously detected in both parents and analyzed in a follow-up QTL analysis. The major components, palmitic acid (C16:0), oleic acid (C18:1), and linoleic acid (C18:2), exhibited considerable phenotypic variation and fit the two major gene and minor gene mixed-inheritance model. Seventeen QTL explained 2.57-38.72% of the phenotypic variation in these major components, with LOD values of 4.12-37.56 in six environments, and thirty-five QTL explained 0.94-32.21% of the phenotypic variation, with LOD values of 5.99-150.38 in multiple environments. Sixteen of these QTL were detected in both individual and multiple environments. Among these, qFA_08_1 was a novel QTL with stable, valuable and major effect. Two other major-effect QTL, qFA_09_2 and qFA_19_3, share the same physical position as FAD2A and FAD2B, respectively. Eleven stable epistatic QTL involving nine loci explained 1.30-34.97% of the phenotypic variation, with epistatic effects ranging from 0.09 to 6.13. These QTL could be valuable for breeding varieties with improved oil quality.

Degradation mechanism and decomposition of sulfamethoxazole aqueous solution with persulfate activated by dielectric barrier discharge.

The present study focused on the degradation of sulfamethoxazole (SMX) aqueous solution and the toxicity of processing aqueous by the dielectric barrier discharge (DBD) activated persulfate (PS). The effects of input voltage, input frequency, duty cycle, and PS dosage ratio on the SMX degradation efficiency were measured. Based on the results of the Response Surface Methodology (RSM), SMX degradation efficiency reached 83.21% which is 10.54% higher than that without PS, and the kinetic constant was 0.067 min-1 in 30 min when the input voltage at 204 V (input power at 110.6 W), the input frequency at 186 Hz, the duty cycle at 63%, and the PS dosage ratio at 5.1:1. The addition of PS can produce more active particles reached 1.756 mg/L (O3), 0.118 mg/L (H2O2), 0.154 mmol/L (·OH) in 30 min. Furthermore, the DBD plasma system effectively activated an optimal amount of PS, leading to improved removal efficiency of COD, and TOC to 30.21% and 47.21%, respectively. Subsequently, eight primary by-products were pinpointed, alongside the observation of three distinct pathways of transformation. Predictions from the ECOSAR software indicated that most of the degradation intermediates were less toxic than SMX. The biological toxicity experiments elucidated that the treatment with the DBD/PS system effectively reduced the mortality of zebrafish larvae caused by SMX from 100% to 20.13% and improved the hatching rate from 55.69% to 80.86%. In particular, it is important to note that the degradation intermediates exhibit teratogenic effects on zebrafish larvae.

A novel approach for transforming breast cancer stem cells into endothelial cells.

Tumor vascular endothelial cells play a pivotal in the tumor microenvironment, influencing the proliferation, invasion, and metastasis of tumor progression. The present study investigated a novel method for inducing the transformation of breast cancer stem cells into endothelial cells, providing a cellular model investigating anti-angiogenic mechanisms in vitro. The breast cancer cell line MCF-7 was used, and the expression of CD133 was initially detected using flow cytometry. CD133+ breast cancer cells were purified using immunomagnetic bead sorting technology, yielding an MCF-7CD133+ subpopulation. The proliferation ability of these cells was assessed using an MTT assay, while their microsphere formation ability was evaluated using a microsphere formation assay. Post-transformation in an optimized endothelial cell culture medium, expression of endothelial cell markers CD31 and CD105 were detected using flow cytometry. Endothelial cell tube formation assays and DiI-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) assays were employed to analyze the endothelial cell function of the MCF-7CD133+ cells. MDM2/CEN12 gene amplification was detected through fluorescence in situ hybridization (FISH). The MCF-7 breast cancer cell line exhibited 1.7±0.3% trace cells expressing the stem cell surface marker CD133. After anti-CD133 immunomagnetic bead sorting, MCF-7CD133+ and MCF-7CD133- subpopulation cells were obtained, with CD133 expression rates of 85.6±2.8 and 0.18±0.08%, respectively. MTT assay results demonstrated that, after 7 days, the proliferation rate of MCF-7CD133+ cells was significantly higher compared with MCF-7CD133- cells. MCF-7CD133+ subpopulation cells displayed strong stem cell characteristics, growing in suspension in serum-free media and forming tumor cell spheres. In contrast, MCF-7CD133- cells failed to form microspheres. After culturing cells in endothelial cell differentiation and maintenance media, the percentage of MCF-7CD133+ cells before and after endothelial cell culture was 0.3±0.16 and 81.4±8.37% for CD31+ cells and 0.2±0.08 and 83.8±7.24% for CD105+ cells, respectively. Vascular-like structure formation and Ac-LDL phagocytosis with red fluorescence in the tube formation assays confirmed endothelial cell function in the MCF-7CD133+ cells. FISH was used to verify MDM2/CEN12 gene amplification in the induced MCF-7CD133+ cells, indicating tumor cell characteristics. The modified endothelial cell transformation medium effectively induced differentiated tumor stem cells to express vascular endothelial cell markers and exhibit endothelial functions, ideal for in vitro anti-angiogenesis research.

Quantum Spin Exchange Interactions to Accelerate the Redox Kinetics in Li-S Batteries.

Spin-engineering with electrocatalysts have been exploited to suppress the "shuttle effect" in Li-S batteries. Spin selection, spin-dependent electron mobility and spin potentials in activation barriers can be optimized as quantum spin exchange interactions leading to a significant reduction of the electronic repulsions in the orbitals of catalysts. Herein, we anchor the MgPc molecules on fluorinated carbon nanotubes (MgPc@FCNT), which exhibits the single active Mg sites with axial displacement. According to the density functional theory calculations, the electronic spin polarization in MgPc@FCNT not only increases the adsorption energy toward LiPSs intermediates but also facilitates the tunneling process of electron in Li-S batteries. As a result, the MgPc@FCNT provides an initial capacity of 6.1 mAh cm-2 even when the high sulfur loading is 4.5 mg cm-2, and still maintains 5.1 mAh cm-2 after 100 cycles. This work provides a new perspective to extend the main group single-atom catalysts enabling high-performance Li-S batteries.

PeposX-Exhaust: A lightweight and efficient tool for identification of short peptides.

Short peptides have become the focus of recent research due to their variable bioactivities, good digestibility and wide existences in food-derived protein hydrolysates. However, due to the high complexity of the samples, identifying short peptides still remains a challenge. In this work, a tool, named PeposX-Exhaust, was developed for short peptide identification. Through validation with known peptides, PeposX-Exhaust identified all the submitted spectra and the accuracy rate reached 75.36%, and the adjusted accuracy rate further reached 98.55% when with top 5 candidates considered. Compared with other tools, the accuracy rate by PeposX-Exhaust was at least 70% higher than two database-search tools and 15% higher than the other two de novo-sequencing tools, respectively. For further application, the numbers of short peptides identified from soybean, walnut, collagen and bonito protein hydrolysates reached 1145, 628, 746 and 681, respectively. This fully demonstrated the superiority of the tool in short peptide identification.

Dual-site segmentally synergistic catalysis mechanism: boosting CoFeSx nanocluster for sustainable water oxidation.

Efficient oxygen evolution reaction electrocatalysts are essential for sustainable clean energy conversion. However, catalytic materials followed the conventional adsorbate evolution mechanism (AEM) with the inherent scaling relationship between key oxygen intermediates *OOH and *OH, or the lattice-oxygen-mediated mechanism (LOM) with the possible lattice oxygen migration and structural reconstruction, which are not favorable to the balance between high activity and stability. Herein, we propose an unconventional Co-Fe dual-site segmentally synergistic mechanism (DSSM) for single-domain ferromagnetic catalyst CoFeSx nanoclusters on carbon nanotubes (CNT) (CFS-ACs/CNT), which can effectively break the scaling relationship without sacrificing stability. Co3+ (L.S, t2g6eg0) supplies the strongest OH* adsorption energy, while Fe3+ (M.S, t2g4eg1) exposes strong O* adsorption. These dual-sites synergistically produce of Co-O-O-Fe intermediates, thereby accelerating the release of triplet-state oxygen ( ↑ O = O ↑ ). As predicted, the prepared CFS-ACs/CNT catalyst exhibits less overpotential than that of commercial IrO2, as well as approximately 633 h of stability without significant potential loss.

Porcine circovirus type 2 and Glaesserella parasuis serotype 4 co-infection activates Snail1 to disrupt the intercellular junctions and facilitate bacteria translocation across the tracheal epithelium.

Clinically, Porcine circovirus type 2 (PCV2) often causes disease through coinfection with other bacterial pathogens, including Glaesserella parasuis (G. parasuis), which causes high morbidity and mortality. However, the mechanism of PCV2 and G. parasuis serotype 4 (GPS4) co-infection is still not fully understood. In this study, swine tracheal epithelial cells (STEC) were used as a barrier model, and our results showed that PCV2 infection increased the adhesion of GPS4 to STEC, while decreasing the levels of ZO-1, Occludin and increasing tracheal epithelial permeability, and ultimately facilitated GPS4 translocation. Snail1 is a transcriptional repressor, and has been known to induce epithelial-to-mesenchymal transition (EMT) during development or in cancer metastasis. Importantly, we found that Snail1, as a transcriptional repressor, was crucial in destroying the tracheal epithelial barrier induced by PCV2, GPS4, PCV2 and GPS4 coinfection. For the first time, we found that PCV2, GPS4, PCV2 and GPS4 coinfection cross-activates TGF-ß and p38/MAPK signaling pathways to upregulate the expression of Snail1, down-regulate the levels of ZO-1 and Occludin, and thus disrupt the integrity of tracheal epithelial barrier then promoting GPS4 translocation. Finally, PCV2 and GPS4 co-infection also can activate TGF-ß and p38/MAPK signaling pathways in vivo and upregulate Snail1, ultimately down-regulating the expression of ZO-1 and Occludin. Our study elucidates how PCV2 infection promotes GPS4 to breach the tracheal epithelial barrier and aggravate clinical manifestations.

The GDNF-gel/HA-Mg conduit promotes the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway.

Magnesium (Mg)-based conduits have gained more attention in repairing peripheral nerve defects. However, they are limited due to poor corrosion resistance and rapid degradation rate. To tackle this issue, glial cell line-derived neurotrophic factor (GDNF)- Gelatin methacryloyl (Gel)/hydroxylapatite (HA)-Mg nerve conduit was developed and implanted in sciatic nerve defect model in Sprague-Dawley (SD) rats. The sciatic functional index measurement showed that the GDNF-Gel/HA-Mg nerve conduit effectively promoted the recovery of sciatic nerve function. The pathological examination results showed that there were more regenerated nerve tissues in GDNF-Gel/HA-Mg group, with a higher number of regenerating axons, and the thickness of the myelin sheath was significantly larger than that of control group (NC group). Immunofluorescence results revealed that the GDNF-Gel/HA-Mg conduit significantly promoted the expression of genes associated with nerve repair. RNA-seq and molecular test results indicated that GDNF-Gel/HA-Mg might be involved in the repair of peripheral nerve defects by regulating PPAR-γ/RhoA/ROCK signaling pathway. Biological sciences; Neuroscience; Molecular neuroscience; Techniques in neuroscience.