Reverse Reaction Research Articles

Co-free gradient lithium-rich cathode for high-energy batteries with optimized cyclability

Lithium-rich layered oxides (LLOs) hold the promise for high-energy battery cathodes. However, its application has been hindered by voltage decay associated with irreversible reactions at high voltages despite decades of intensive efforts. Here, we first theoretically studied the molecular orbitals of Mn-based Li-rich configurations. We found that the π-bond ring formed within the LiMn6 structure could participate in stable redox reactions as one unit, but Co could disrupt its symmetry. We thus designed and synthesized Co-free concentration-gradient LLOs (CF-CG-LLOs) materials. The combination of concentration gradient and Co removal leads to exceptional capacity retention without any fading over 100 cycles of the pouch cell. More importantly, it exhibits an extraordinarily low voltage decay of 0.15 mV/cycle, accompanied by a high Coulombic efficiency of 99.86%. This concept and demonstration of CF-CG-LLO cathodes reveal a viable avenue toward low-cost, high-energy-density battery cathodes.

Flow field design and visualization for flow-through type aqueous organic redox flow batteries

Aqueous organic redox flow batteries (AORFBs), which exploit the reversible redox reactions of water-soluble organic electrolytes to store electricity, have emerged as a promising electrochemical energy storage technology. Organic electrolytes possess fast electron-transfer rates that are two or three orders of magnitude faster than those of their inorganic or organometallic counterparts; therefore, their performance at the electrode is limited by mass transport. Direct adoption of conventional cell stacks with flow fields designed for inorganic electrolytes may compromise AORFB performance owing to severe cell polarization. Here, we report the design of a flow field for flow-through type AORFBs based on three-dimensional multiphysics simulation, to realize the uniform distribution of electrolyte flow and flow enhancements within a porous electrode. The electrolyte flow is visualized by operando imaging. Our results show that multistep distributive flow channels at the inlet and point-contact blocks at the outlet are crucial geometrical merits of the flow field, significantly reducing local concentration overpotentials. The prototype pH-neutral TEMPTMA/MV cell at 1.5 M assembled with the optimized flow field exhibits a peak power density of 267.3 mW cm-2. The flow field design enables charging of the cell at current densities up to 300 mA cm-2, which is unachievable with the conventional serpentine flow field, where immediate voltage cutoff of the cell occurs. Our results highlight the importance of AORFB cell stack engineering and provide a method to visualize electrolyte flow, which will be appealing to the field of aqueous flow batteries.

High-performance single-atom M/TiO2 catalysts in the reverse water-gas shift reaction: A comprehensive experimental and theoretical investigation

Single-atom catalysts (SACs) offer high efficiency and selectivity in chemical reactions but face challenges in converting CO2 to CO via the reverse water gas shift (RWGS) reactions. This study addresses these challenges by anchoring three noble metals (Ir, Pd, and Ru) onto titania (TiO2) and analyzing their performance. Comprehensive characterization techniques, including electron microscopy, confirmed the uniform dispersion of metal atoms on TiO2. Among the catalysts, Ir/TiO2 exhibited the best results, achieving an 84 % CO2 conversion rate and ∼98 % CO selectivity, surpassing Pd/TiO2 and Ru/TiO2, which gained 56 % and 52 % conversion, respectively. In-situ gas transmission electron microscopy revealed the catalytic behavior of Ir/TiO2, showing Ir atom mobility and the formation of ∼1 nm nanoclusters. Density functional theory (DFT) and in-situ diffuse reflectance infrared spectroscopy (DRIFTs) further explained that the atomically dispersed Ir sites in Ir/TiO2 follow a hydrogen-assisted mechanism, with the COOH* intermediate desorbing and dissociating into CO. These findings suggest SACs' potential to facilitate greener chemical processes and reduce greenhouse gas emissions.

TRPC6 Channel Regulates Airway Remodeling in Chronic Obstructive Pulmonary Disease Causing Right Heart Failure.

The role of the canonical transient receptor potential 6 (TRPC6) channel in chronic obstructive pulmonary disease (COPD) remains poorly understood at the mechanistic level. Objects: This study aims to investigate the involvement of TRPC6 in COPD and its signaling mechanisms in human airway smooth muscle cells (HASMCs). Methods and Results: The study found that mRNA and protein expression of TRPC6 increased in cultured HASMCs that were incubated with nicotine, as measured by reverse transcription quantitative polymerase chain reaction and Western blot analysis. Nicotine treatment significantly enhanced TRPC6 transcriptional activity in HASMCs through nuclear factor (NF)-κB, as demonstrated by co-immunoprecipitation and electrophoretic mobility shift assays. Furthermore, miR-135a/b-5p was shown to downregulate TRPC6 expression in HASMCs at the mRNA and protein levels, as confirmed by luciferase reporter assays. Immunohistochemistry assays in a mouse model of cigarette-induced airway remodeling revealed a significant increase in smooth muscle (SM) cell proliferation and SM layer mass. Conclusion: These findings suggest that nicotine exposure increases HASMC proliferation and migration through NF-κB signaling, and that cigarette smoke inhalation causes airway SM layer remodeling via altered TRPC6-induced Ca2+ influx, which is abolished by miR-135a/b-5p both in vitro and invivo. Antioxid. Redox Signal. 00, 000-000.

Effect of Prednisolone on Clinical and Cytokine mRNA Profiling in Complex Regional Pain Syndrome.

The cardinal clinical features of complex regional pain syndrome type I (CRPS-I) are pain, edema, autonomic changes, and limitation of motoric movement, which may indicate the role of inflammation and cytokines. We report the effect of prednisolone on the clinical severity and mRNA profiling of proinflammatory (tumor necrosis factor (TNF)-α and interleukin (IL)-2) and anti-inflammatory cytokines (IL-10 and transforming growth factor (TGF)-β) in the patient with CRPS-I. Thirty-nine patients with CRPS-I of shoulder joint were enrolled. Their CRPS, Visual Analog Scale (VAS) and Daily Sleep Interference Scale (DSIS) scores were recorded. TNF-α, IL-2, IL-10, and TGF-β gene expressions at mRNA of whole blood were measured by reverse transcriptase polymerase chain reaction. Patients were randomized to prednisolone 20mg or 40mg using 1: 1 randomization. The primary outcome was change in VAS score, and secondary outcomes were change in CRPS and DSIS scores at 1month. Side effects were noted. The patients had increased expressions of TNF-α (p < 0.001) and IL-2 (p < 0.001) and reduced IL-10 (p < 0.01) mRNA compared to the healthy controls. The baseline characteristics were matched between the two treatment arms. At 1month, CRPS, VAS, and DSIS scores improved significantly compared to baseline, which paralleled with improvement in IL-10 (p < 0.032) and reduction in TNF-α (p = 0.046). The improvement in clinical and biomarkers was similar in prednisolone 20mg and 40mg arms. None had to be withdrawn due to severe side effects. Future study in larger cohort may validate these findings.

Irreversible Lattice Expansion Effects in Nanoscale Indium Oxide for CO2 Hydrogenation Catalysis.

Thermal energy has been considered the exclusive driving force in thermochemical catalysis, yet associated lattice expansion effects have been overlooked. To shed new light on this issue, variable temperature in situ high-resolution (scanning) transmission electron microscopy (HR-(S)TEM) and electron energy-loss spectroscopy (EELS) were employed to provide detailed information on the structural changes of an archetype nanoscale indium oxide materials and how these effects are manifest in reverse water gas shift heterogeneous catalytic reactivity. It is found that with increasing temperature and vacuum conditions, an irreversible surface lattice expansion is traced to the formation and migration of oxygen vacancies. Together, these changes are believed to be responsible for the decreased activation energy and improved reaction rate observed for the reverse water gas shift reaction. Studies of this kind provide new insight into how thermal energy affects thermochemical heterogeneous catalysis.

Multi-Electron Transfer Halide Cathode Materials Based on Intercalation-Conversion Reaction Towards All-Solid-State Lithium Batteries.

All-solid-state lithium batteries (ASSLBs) with non-flammable solid-state electrolytes offer high energy density and enhanced safety. However, their energy densities are greatly limited by low-capacity and low-ionic-conductivity oxide cathode materials, typically relying on the intercalation-deintercalation mechanism with a catholyte content of 15~30 wt.%. Here we introduce the LixFeXx+2 (X=Cl, Br) families as high-capacity and high-ionic-conductivity alternatives, operating via a 3 mol e- transfer intercalation-conversion coupling reaction. Notably, the catholyte-free ASSLBs using 95 wt.% LiFeCl3 active material delivers a remarkable capacity of 446 mAh g-1 and a high energy density of 912 Wh kg-1, which surpasses most oxide cathode materials. Of particular interest is the formation of amorphous Fe during the conversion process. The amorphous Fe exhibits high activity, catalyzing the conversion of LiX back to LixFeXx+2, which proves instrumental in realizing reversible intercalation-conversion reactions. These halide cathode materials represent a significant advancement towards high-energy-density ASSLBs.

Evaluation of the Clinical Safety of the Low-Cost Warburg Therapy for the Treatment of Patients With Advanced Cancers.

Rising cancer care costs are becoming cost prohibitive for lower income people worldwide. We developed the Warburg protocol as a low-cost option for the treatment of cancer that was inspired. It was developed to exploit an Achilles heel which is a hallmark of cancer cells; the metabolic requirement for higher levels of glucose than normal cells. The purpose of this report is to assess the clinical safety and affordability of the Warburg therapy as an option for patients with advanced cancers. Between 2021 and 2023, 251 patients with advanced cancers received a total of 8542 treatments with the Warburg therapy. To restrict the supply of blood glucose to cancerous tumors, regular human insulin was administered (IV) sufficient to reduce blood glucose concentrations to hypoglycemic levels for 40-60 min. Subroutine doses of fluorouracil and cyclophosphamide were administered intravenously during this hypoglycemic period. Food or intravenous glucose was given as needed to return blood glucose to euglycemic levels after treatment. Patient symptoms, status, vitals, blood glucose, and hypoglycemic symptoms were monitored throughout treatment. Various blood parameters were measured before and after patients' course of treatment. There were no irreversible adverse reactions in advanced tumor patients of different ages and different cancer types after treatment. There was no significant fluctuation in blood glucose levels in diabetic and non-diabetic patients after treatment, and the weight, vital index and blood biochemical index of patients before and after multiple treatments exhibited little variation. Warburg therapy for the treatment of advanced tumors is clinically feasible, and safe for multiple treatments. It is inexpensive and widely applicable to different patient groups.

Mechanistic insights into retinoic-acid treatment for autism in the improvement of social behavior: evidence from a multi omics study in rats

BackgroundAutism spectrum disorder (ASD) is a lifelong condition. It is characterized by complex etiologies, including disruptions in exogenous retinoic acid (RA) signaling, which may serve as an environmental risk factor. Targeting the RA pathway presents a promising therapeutic avenue, though the precise mechanisms remain to be elucidated. MethodsFemale Sprague–Dawley rats were treated with valproic acid (VPA) during pregnancy to induce an ASD model in their offspring. Some offspring received RA treatment postnatally. Social behavior and brain-functional connectivity were assessed using behavioral tests and functional magnetic resonance imaging (fMRI), respectively. Transcriptomics analysis and proteomics analysis of the hypothalamus identified differentially expressed genes (DEGs) and differentially expressed proteins (DEPs). These were intersected with ASD pathogenic genes (APGs) and ASD pathogenic proteins (APPs) to identify differentially expressed APGs (DE-APGs) and differentially expressed APPs (DE-APPs), which were validated by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Analyses of enrichment of signaling pathways were done using the Kyoto Encyclopedia of Genes and Genomes database. ResultsRA treatment significantly improved social behaviors and revealed distinct patterns of hypo- and hyper-connectivity across various brain regions, with notable changes involving the hypothalamus and facial nerve. Differential analysis revealed 4165 DEGs (DEG 1) and 329 DEPs (DEP 1) between control and VPA groups, and 1610 DEGs (DEG 2) and 197 DEPs (DEP 2) between VPA and RA supplementation (RAS) groups. Twenty-two DE-APGs and five DE-APPs were identified, with key associations found between proteins such as Tbl1xr1 and Myo5a and >13 genes including Nrxn1, Cacna1e, and Gabrb2. Significant alterations in DE-APGs, including Grin2b, Nrxn1, Cacna1e, and Gabrb2, were confirmed via real-time RT-PCR and western blotting. In addition, 22 key signaling pathways were enriched in DEPs and DEGs. ConclusionRA supplementation in ASD rats induced by VPA may ameliorate social deficits and modulated functional connectivity, especially in the hypothalamus and facial nerve regions. This suggests potential therapeutic benefits for neural circuitry dysregulation in ASD. Additionally, RA altered critical gene and protein expressions in hypothalamus, implicating its role in modulating key signaling pathways to mitigate social deficits in ASD. This study provides new insights into the molecular mechanisms of ASD and supports the development of novel therapeutic strategies.

“Three birds with one stone” strategy for building easily reprocessable cellulosic thermosetting resins

Cellulose is the most abundant natural polypolysaccharide and is an ideal raw material to replace petroleum-based plastics. However, natural cellulose is difficult to be thermo-processed like conventional plastics because of the rich and strong hydrogen bonds interactions. In this study, a series of dialdehyde derivatives of cellulose (DACs) were prepared by periodate oxidation of cellulose, and cellulose covalent adaptive networks based on acetal dynamic covalent bonds (ACCs) were prepared using dipentaerythritol as a crosslinker for DAC. This strategy can introduce acetal bonds, weaken hydrogen bonds, and reduce rigidity to kill three birds with one stone. The excellent reprocessing performance of ACCs is attributed to the reconstruction of the cellulose hydrogen bond network by acetal bonds, and the reversible exchange reaction of the acetal bonds at high temperatures endows the cellulose chains with mobility, allowing ACCs to be remodeled by hot pressing at 90°C for 15 min. The excellent stability and reprocessability of ACCs hold the promise of replacing current non-renewable petroleum-based plastics and provide inspiration for the development of other types of biomass plastics.

Cooperation of ICT and intramolecular spirocyclization: Construction of versatile fluorescent probe visualizing triple organelles in three distinct channels

The cooperation and interplay among multiple organelles play essential roles in a variety of crucial biological and pathological procedures. Fluorescent probes enabling discriminative visualization of triple organelles with different emission colors were promising molecular tools to investigate organelles interaction network, which however were rarely reported. Herein, by cooperating the polarity-sensitive intramolecular charge transfer (ICT) mechanism and pH-responsible intramolecular reversible cyclization reaction, we have constructed a fluorescent probe to distinguish lipid droplets (LDs), mitochondria, and lysosomes in three distinct channels without crosstalk emission. The probe (Triorg) presented in ring-open form in lysosomes to emit red fluorescence, while kept in ring-close form in LDs and mitochondria but distinguish the two organelles based on their different polarity. As a result, Triorg discriminated LDs, mitochondria, and lysosomes with blue, green, and red emission channels, respectively. Particularly, Triorg enabled visualizing LDs accumulation and consumption with blue emission, and detecting mitochondrial dysfunction and lysosomal damages with decreased green and red emission, respectively. The lysosomal damage and LDs consumption induced by chlorpromazine (a drug) and phenylarsine oxide (a toxic substance) have been revealed. The amount, morphologies, and three-dimension distribution of the three organelles in live tissues were also successfully visualized with Triorg.

Development and evaluation of an antigen targeting lateral flow test for Crimean-Congo Haemorrhagic Fever

Crimean-Congo Haemorrhagic Fever (CCHF) is a viral haemorrhagic fever with a case fatality rate of 5-25% that has been prioritised for research and development by the World Health Organisation. There are no CCHF rapid diagnostic tests (RDTs) commercially available. We describe the development and evaluation of an antigen-targeting lateral flow immunoassay RDT for CCHF. Prospective clinical samples were collected and tested between July and October 2023 in Türkiye. Retrospective stored samples were obtained from the Central Public Health Laboratory, Baghdad, Iraq. The sensitivity and specificity of the CCHF RDT was compared to reverse transcription quantitative polymerase chain reaction assays. On prospective clinical samples in Türkiye, the sensitivity and specificity of the CCHF RDT was 90.4% [95% CI 81.5-95.3%] (n=73) and 96.2% [95% CI 87.0-99.3%] (n=52), respectively with a sensitivity of 92.9% [95% CI 84.3-96.9%] (n=70) in samples with a cycle threshold (Ct) ≤30. On retrospective stored samples in Iraq, sensitivity and specificity of the RDT was 71.7% [95% CI 59.2-81.5%] (n=60) and 92.5% [95% CI 80.1-97.8%] (n=40), respectively with a sensitivity of 82.2% [95% CI 68.7-90.7%] (n=45) in samples of Ct ≤30. The CCHF RDT was an effective rapid diagnostic test in this preliminary clinical evaluation, showing this RDT has the potential diagnostic capability for use at the point-of-care. Definitive evaluation is now required to ensure the RDT meets the regulatory requirements for commercialisation. The Liverpool School of Tropical Medicine, National Institute for Health Research Health Protection Research Unit in Emerging Zoonotic Infections, The Medical Research Council and The Pandemic Institute.

The effect of carbohydrates with different levels of digestibility on energy metabolism in vivo under hypobaric hypoxic conditions

Current strategies for improving energy supply in hypobaric hypoxic environments are limited. Therefore, this study investigates the effects of four carbohydrates with different levels of digestibility on energy metabolism in vivo in hypobaric hypoxic environments. First, we characterized the four types of carbohydrates. Subsequently, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to characterize the expression of GLUT1, GLUT2, and SGLT1 in the glucose transport pathway in vivo. In addition, the effects of different levels of carbohydrate digestibility on energy expenditure were evaluated in vivo. The results showed that pre-gelatinized corn starch significantly increased GLUT1 gene expression in the hypobaric hypoxic conditions (1.58 times, compared to normobaric normoxic). In addition, pre-gelatinized corn starch increased energy expenditure in the hypobaric hypoxic conditions and performed better in terms of glycogen accumulation and glucose transport. Therefore, pre-gelatinized corn starch administration may be a promising strategy for long-term energy supplementation in hypobaric hypoxic.

Clinical Value of Circ-PNPT1 on Adverse Pregnancy Outcomes of Patients with Gestational Diabetes Mellitus.

Several circular RNAs are associated with important pathophysiological characteristics of gestational diabetes mellitus (GDM). This study intended to measure the expression of circ-PNPT1 in sera of GDM patients and to expound on its values on pregnancy outcomes. Totally 104 GDM patients and 71 healthy controls were recruited. The expression pattern of serum circ-PNPT1 was measured by reverse transcription-quantitative polymerase chain reaction. The diagnostic efficacy of circ-PNPT1 and fasting blood glucose (FBG) on GDM was evaluated by receiver operating characteristic (ROC) analysis. Parameters of glycolipid metabolism were determined using automatic biochemical analyzers. The correlation between circ-PNPT1 and glycolipid metabolism parameters was analyzed using Pearson analysis. GDM patients were divided into a high expression group and a low expression group based on the median value of circ-PNPT1 expression. Curves of adverse neonatal outcomes were drawn by Log Rank analysis. GDM patients exhibited higher circ-PNPT1 expression than healthy controls. The area under the ROC curve of circ-PNPT1 diagnosing GDM was 0.9184 and the cut-off value was 1.435 (90.38% sensitivity, 85.92% specificity). Serum circ-PNPT1 expression was positively correlated with FBG, total cholesterol, and triglyceride in GDM patients. Neonates born to GDM patients with high circ- PNPT1 expression were prone to adverse outcomes. Circ-PNPT1 was highly-expressed in the sera of GDM patients. Circ-PNPT1 affected glycolipid metabolism and its expression had certain reference values on adverse pregnancy outcomes.

Renshen (Radix Ginseng) polysaccharide promotes repair of the mice intestinal mucosa through regulatory mechanisms based on polyamine and human antigen R.

To investigate the mechanism and effect of Renshen (Radix Ginseng) polysaccharide on the migration of intestinal epithelial cell line 6 (IEC-6), as well as the repair mechanism of Renshen (Radix Ginseng) polysaccharide on colonic injury induced by dextran sulfate sodium (DSS) in mice. Mice were fed 3% (w/v) DSS for 6 d to create colonic lesions. A cell-migration model was created using cell scratching. mRNA expression, protein expression, translation efficiency of mRNA, and nucleoplasmic distribution of human antigen R (HuR) were determined by real-time reverse transcription-quantitative polymerase chain reaction, western blotting, a dual luciferase reporter system, and immunofluorescence staining, respectively. Renshen (Radix Ginseng) polysaccharide promoted the migration of IEC-6 cells and affected expression of stromal interaction molecule 1 (STIM1) and cell division cycle 42 (Cdc42) at transcriptional and post-transcriptional levels. Renshen (Radix Ginseng) polysaccharide-induced repair of intestinal mucosal injury may be mediated by increased cell migration via polyamine-based regulatory mechanisms. In vitro and in vivo experiments suggest that Renshen (Radix Ginseng) polysaccharide-induced post-transcriptional regulation of STIM1 and Cdc42 may be related to differences in the regulation of different target genes by HuR. Taken together, these data provide a reference for further exploration of the protective effect of Renshen (Radix Ginseng) on the intestinal mucosa.

A Novel Prognostic Risk Score Model Based on RNA Editing Level in Lower-Grade Glioma

BackgroundLower-grade glioma (LGG) refers to WHO grade 2 and 3 gliomas. Surgery combined with radiotherapy and chemotherapy can significantly improve the prognosis of LGG patients, but tumor progression is still unavoidable. As a form of posttranscriptional regulation, RNA editing (RE) has been reported to be involved in tumorigenesis and progression and has been intensively studied recently. MethodsSurvival data and RE data were subjected to univariate and multivariate Cox regression analysis and lasso regression analysis to establish an RE risk score model. A nomogram combining the risk score and clinicopathological features was built to predict the 1-, 3-, and 5-year survival probability of patients. The relationship among ADAR1, SOD2 and SOAT1 was verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) ResultsA risk model associated with RE was constructed and patients were divided into different risk groups based on risk scores. The model demonstrated strong prognostic capability, with the area under the ROC curve (AUC) values of 0.882, 0.938, and 0.947 for 1-, 3-, and 5-year survival predictions, respectively. Through receiver operating characteristic curve (ROC) curves and calibration curves, it was verified that the constructed nomogram had better performance than age, grade, and risk score in predicting patient survival probability. Apart from this functional analysis, the results of correlation analyses between risk differentially expressed genes (RDEGs) and RE help us to understand the underlying mechanism of RE in LGG. ADAR may regulate the expression of SOD2 and SOAT1 through gene editing. ConclusionIn conclusion, this study establishes a novel and accurate 17-RE model and a nomogram for predicting the survival probability of LGG patients. ADAR may affect the prognosis of glioma patients by influencing gene expression.

N6-methyladenosine (m6A)-circHECA from secondary hair follicle of cashmere goats: identification, regulatory network and expression regulated potentially by methylation of its host gene promoter.

The objective of this study was to identify the N6-methyladenosine (m6A)- circHECA molecule in secondary hair follicles (SHFs) of cashmere goats, and generate its potential regulatory network, as well as explore the potential relationship between transcriptional pattern of m6A-circHECA and promoter methylation of its host gene (HECA). The validation of circHECA m6A sites was performed using methylation immunoprecipitation (Me-RIP) along with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) technique. The nucleus and cytoplasm localizations of m6AcircHECA were performed using SHF stem cells of cashmere goats with RT-qPCR analysis. Based on in-silico analysis, the regulatory networks of m6A-circHECA were generated with related signal pathway enrichment. The methylation level of promoter region of m6A-circHECA host gene (HECA) was assessed by the bisulfite sequencing PCR (BSPPCR) technique. The m6A-circHECA was confirmed to contain four m6A modification sites including m6A-213, m6A-297, m6A-780, and m6A-927, and it was detected mainly in cytoplasm of the SHF stem cells of cashmere goats. The integrated regulatory network analysis showed directly or indirectly complex regulatory relationships between m6A-circHECA of cashmere goats and its potential target molecules: miRNAs, mRNAs, and proteins. The regulatory network and pathway enrichment indicated that m6A-circHECA might play multiple roles in the SHF physiology process of cashmere goats through directly or indirectly interacting or regulating its potential target molecules. A higher methylation level of promoter region of HECA gene in SHFs of cashmere goats might cause the lower expression of m6A-circHECA. The m6A-circHECA might play multiple roles in SHF physiology process of cashmere goats through miRNA mediated pathways along with directly or indirectly interaction with its target proteins. The promoter methylation of m6A-circHECA host gene (HECA) most likely was implicated in its expression inhibition in SHFs of cashmere goats.

METTL14 Regulates the m6A Modification of TRAF6 to Suppress Mitochondrial Dysfunction and Ferroptosis in Dopaminergic Neurons via the cGAS-STING Pathway.

The degeneration of dopaminergic (DA) neurons has emerged as a crucial pathological characteristic in Parkinson's disease (PD). To enrich the related knowledge, we aimed to explore the impact of the METTL14-TRAF6-cGASSTING axis in mitochondrial dysfunction and ferroptosis underlying DA neuron degeneration. 1-methyl-4-phenylpyridinium ion (MPP+) was used to treat DA neuron MN9D to develop the PD cell models. Afterward, a cell counting kit, flow cytometer, DCFH-DA fluorescent probe, and Dipyrromethene Boron Difluoride staining were utilized to measure the cell viability, iron concentration, ROS level, and lipid peroxidation, respectively. Meanwhile, the mitochondrial ultrastructure, the activity of mitochondrial respiratory chain complexes, and levels of malondialdehyde and glutathione were monitored. In addition, reverse transcription-quantitative polymerase chain reaction and western blot assays were adopted to measure the expression of related genes. cGAS ubiquitylation and TRAF6 messenger RNA (mRNA) N6-methyladenosine (m6A) levels, the linkages among METTL14, TRAF6, and the cGAS-STING pathway were also evaluated. METTL14 expression was low, and TRAF6 expression was high after MPP+ treatment. In MPP+-treated MN9D cells, METTL14 overexpression reduced ferroptosis, ROS generation, mitochondrial injury, and oxidative stress (OS) and enhanced mitochondrial membrane potentials. TRAF6 overexpression had promoting impacts on mitochondrial dysfunction and ferroptosis in MPP+-treated MN9D cells, which was reversed by further overexpression of METTL14. Mechanistically, METTL14 facilitated the m6A methylation of TRAF6 mRNA to down-regulate TRAF6 expression, thus inactivating the cGAS-STING pathway. METTL14 down-regulated TRAF6 expression through TRAF6 m6A methylation to inactivate the cGAS-STING pathway, thereby relieving mitochondrial dysfunction and ferroptosis in DA neurons.

Silver functionalized chitosan composite hydrogel with sustained silver release and enhanced antibacterial properties promotes healing of infected wounds

Bacterial infections during wound healing often cause inflammation, which delays the healing process. Therefore, innovative wound dressings are urgently needed to inhibit bacterial infections and promote healing. This study proposes an Ag-functionalized chitosan hydrogel dressing, formed via a Schiff-base reaction between alkynyl Ag substituted chitosan (Ag-CS) and octafunctionalized polyhedral oligomeric silsesquioxane with benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO), to address the issue of bacterial infection in wounds. The hydrogel demonstrated excellent injectability and self-healing properties. AgNPs and alkynyl Ag, produced by the reducing effect of chitosan and the reversible reaction of alkynyl Ag, delay the release of Ag+. Furthermore, the hydrogel exhibits a broad-spectrum antibacterial effect and effectively inhibits bacterial biofilm formation. The release of Ag+ lasts for 7 days, ensuring sustainable antibacterial properties. In a mouse infected wound model, the composite hydrogel significantly accelerated wound healing. By the eighth day, the wound healing rate reached 99 %, whereas the control group achieved only 91 %. Histological and immunofluorescence staining results indicated that hydrogel-treated wounds had faster re-epithelialization, collagen deposition, and angiogenesis, with reduced inflammation. In conclusion, the Ag-functionalized chitosan hydrogel, with sustained Ag release and enhanced antibacterial properties, shows great potential as a wound dressing for promoting the healing of infected wounds.

Effects of carbon dioxide addition on soot dynamics in ethylene/air inverse diffusion flames: An experimental and computational analysis

The effects of carbon dioxide (CO2) addition to ethylene (C2H4)/air inverse diffusion flames (IDFs) to the air stream on soot formation characteristics are investigated with the addition ratio of 0-13.64%. The planar laser-induced fluorescence (PLIF) and planar laser-induced incandescence (PLII) techniques, in conjunction with CoFlame and Chemkin code simulations were utilized to assess the distributions of Polycyclic Aromatic Hydrocarbons (PAHs) and Soot Volume Fraction (SVF). The findings indicate that increasing CO2 addition results in a gradual decrease in the mole fraction of hydroxyl (OH) radicals and flame temperature, accompanied by a reduction of approximately 15% in the reaction zone height in experimental observations and 19% in simulations. The inhibition of soot formation is evident through a consistent decline in the normalized total SVF, a decrease in the peak volume fraction of radial soot distribution, and reduced total SVFs observed across different flame sections at varying heights. In the meanwhile, increasing the CO2 doping ratio significantly reduces the peak signal intensity of PAHs, particularly affecting high molecular weight PAHs (A3-A4, A2-A3) with reductions of up to 75.5%. Furthermore, reductions are noted in the rates of soot inception and subsequent surface growth, accompanied by an upward displacement of the initial inception and growth location. The condensation of PAHs controls the soot surface growth. The thermal and chemical effects of CO2 were differentiated by employing the virtual substance FCO2. The results suggest that the thermal effect of CO2 lowers flame temperature, reduces combustion intensity, and consequently inhibits soot nucleation. The chemical effect of CO2 competes for H radicals through the reverse reaction of CO+OH <=> CO2+H. This process suppresses the formation and growth of PAHs, consequently leading to a reduction in soot production.