Self-protecting CoFeAl-layered double hydroxides enable stable and efficient brine oxidation at 2 A cm-2.

Low-energy consumption seawater electrolysis at high current density is an effective way for hydrogen production, however the continuous feeding of seawater may result in the accumulation of Cl-, leading to severe anode poisoning and corrosion, thereby compromising the activity and stability. Herein, CoFeAl layered double hydroxide anodes with excellent oxygen evolution reaction activity are synthesized and delivered stable catalytic performance for 350 hours at 2 A cm-2 in the presence of 6-fold concentrated seawater. Comprehensive analysis reveals that the Al3+ ions in electrode are etched off by OH- during oxygen evolution reaction process, resulting in M3+ vacancies that boost oxygen evolution reaction activity. Additionally, the self-originated Al(OH)n- is found to adsorb on the anode surface to improve stability. An electrode assembly based on a micropore membrane and CoFeAl layered double hydroxide electrodes operates continuously for 500 hours at 1 A cm-2, demonstrating their feasibility in brine electrolysis.

Disulfidptosis­related lncRNA prognosis model to predict survival therapeutic response prediction in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer, and disulfidptosis is a newly discovered mechanism of programmed cell death. However, the effects of disulfidptosis-related lncRNAs (DR-lncRNAs) in LUAD have yet to be fully elucidated. The aim of the present study was to identify and validate a novel lncRNA-based prognostic marker that was associated with disulfidptosis. RNA-sequencing and associated clinical data were obtained from The Cancer Genome Atlas database. Univariate Cox regression and lasso algorithm analyses were used to identify DR-lncRNAs and to establish a prognostic model. Kaplan-Meier curves, receiver operating characteristic curves, principal component analysis, Cox regression, nomograms and calibration curves were used to assess the reliability of the prognostic model. Functional enrichment analysis, immune infiltration analysis, somatic mutation analysis, tumor microenvironment and drug predictions were applied to the risk model. Reverse transcription-quantitative PCR was subsequently performed to validate the mRNA expression levels of the lncRNAs in normal cells and tumor cells. These analyses enabled a DR-lncRNA prognosis signature to be constructed, consisting of nine lncRNAs; U91328.1, LINC00426, MIR1915HG, TMPO-AS1, TDRKH-AS1, AL157895.1, AL512363.1, AC010615.2 and GCC2-AS1. This risk model could serve as an independent prognostic tool for patients with LUAD. Numerous immune evaluation algorithms indicated that the low-risk group may exhibit a more robust and active immune response against the tumor. Moreover, the tumor immune dysfunction exclusion algorithm suggested that immunotherapy would be more effective in patients in the low-risk group. The drug-sensitivity results showed that patients in the high-risk group were more sensitive to treatment with crizotinib, erlotinib or savolitinib. Finally, the expression levels of AL157895.1 were found to be lower in A549. In summary, a novel DR-lncRNA signature was constructed, which provided a new index to predict the efficacy of therapeutic interventions and the prognosis of patients with LUAD.

Prevalence and genotype distribution of HPV infection from Hangzhou of Zhejiang Province pre- and during COVID-19 pandemic.

Limited data exist on HPV prevalence and genotyping during the COVID-19 pandemic. A total of 130,243 samples from 129, 652 women and 591 men who visited the First People's Hospital of Linping District between 2016 and 2022 were recruited. HPV genotypes were detected by polymerase chain reaction (PCR) amplification and nucleic acid molecular hybridization. Then the prevalence characteristics of HPV genotypes and trends in HPV infection rates from 2016 to 2022 were analyzed. Results showed that among the study population, the overall prevalence of HPV infection was 15.29%, with 11.25% having single HPV infections and 4.04% having multiple HPV infections, consistent with previous findings. HPV genotypes exhibited similar distribution patterns in both male and female groups, with HPV16, HPV52, HPV58, HPV18, and HPV39 being the most prevalent. Age-related analysis unveiled a bimodal pattern in HPV prevalence, with peaks in infection rates observed in individuals below 20 and those aged 61-65 years. Comparing the pre- and during COVID-19 periods revealed significant disparities in HPV infections, with variations in specific HPV genotypes, including 16, 18, 35, 45, 52, 58, 59, and 68. This study provides valuable insights into the prevalence, distribution, and epidemiological characteristics of HPV infections in a large population. It also highlights the potential impact of the COVID-19 pandemic on HPV trends.

Ultrastable Electrolytic Zn-I2 Batteries Based on Nanocarbon Wrapped by Highly Efficient Single-Atom Fe-NC Iodine Catalysts.

Aqueous Zn-iodine (Zn-I2) conversion batteries with iodine redox chemistry suffers the severe polyiodide shuttling and sluggish redox kinetics, which impede the battery lifespan and rate capability. Herein, an ultrastable Zn-I2 battery is introduced based on single-atom Fe-N-C encapsulated high-surface-area carbon (HC@FeNC) as the core-shell cathode materials, which accelerate the I-/I3 -/I° conversion significantly. The robust chemical-physical interaction between polyiodides and Fe-N4 sites tightly binds the polyiodide ions and suppresses the polyiodide shuttling, thereby significantly enhancing the coulombic efficiency. As a result, the core-shell HC@FeNC cathode endows the electrolytic Zn-I2 battery with an excellent capacity, remarkable rate capability, and an ultralong lifespan over 60 000 cycles. More importantly, a practical 253 Wh kg-1 pouch cell shows good capacity retention of 84% after 100 cycles, underscoring its considerable potential for commercial Zn-I2 batteries.

Inhibiting Dissolution of Active Sites in 80 °C Alkaline Water Electrolysis by Oxyanion Engineering.

Commercial alkaline water electrolysers typically operate at 80 °C to minimize energy consumption. However, NiFe-based catalysts, considered as one of the most promising candidates for anode, encounter the bottleneck of high solubility at such temperatures. Herein, we discover that the dissolution of NiFe layered double hydroxides (NiFe-LDH) during operation not only leads to degradation of anode itself, but also deactivates cathode for water splitting, resulting in decay of overall electrocatalytic performance. Aiming to suppress the dissolution, we employed oxyanions as inhibitors in electrolyte. The added phosphates to the electrolyte inhibit the loss of NiFe-LDH active sites at 400 mA cm-2 to 1/3 of the original amount, thus reducing the rate of performance decay by 25-fold. Furthermore, the usage of borates, sulfates, and carbonates yields similar results, demonstrating the reliability and universality of the active site dissolution inhibitor, and its role in elevated water electrolysis.

AS1411 binds to nucleolin via its parallel structure and disrupts the exos-miRNA-27a-mediated reciprocal activation loop between glioma and astrocytes.

The interaction between glioma cells and astrocytes promotes the proliferation of gliomas. Micro-RNAs (miRNAs) carried by astrocyte exosomes (exos) may be involved in this process, but the mechanism remains unclear. The oligonucleotide AS1411, which consists of 26 bases and has a G-quadruplex structure, is an aptamer that targets nucleolin. In this study, we demonstrate exosome-miRNA-27a-mediated cross-activation between astrocytes and glioblastoma and show that AS1411 reduces astrocytes' pro-glioma activity. The enhanced affinity of AS1411 toward nucleolin is attributed to its G-quadruplex structure. After binding to nucleolin, AS1411 inhibits the entry of the NF-κB pathway transcription factor P65 into the nucleus, then downregulates the expression of miRNA-27a in astrocytes surrounding gliomas. Then, AS1411 downregulates astrocyte exosome-miRNA-27a and upregulates the expression of INPP4B, the target gene of miRNA-27a in gliomas, thereby inhibiting the PI3K/AKT pathway and inhibiting glioma proliferation. These results were verified in mouse orthotopic glioma xenografts and human glioma samples. In conclusion, the parallel structure of AS1411 allows it to bind to nucleolin and disrupt the exosome-miRNA-27a-mediated reciprocal activation loop between glioma cells and astrocytes. Our results may help in the development of a novel approach to therapeutic modulation of the glioma microenvironment.

Intelligent near-infrared light-activatable DNA machine with DNA wire nano-scaffold-integrated fast domino-like driving amplification for high-performance imaging in live biological samples.

While there is significant potential for DNA machine-built enzyme-free fluorescence biosensors in the imaging analysis of live biological samples, they persist certain shortcomings. These encompass a deficiency of signal enrichment within a singular interface, uncontrolled premature activation during bio-delivery, and a slow reaction rate due to free nucleic acid collisions. In this contribution, we are committed to resolving the above challenges. Firstly, a single-interface-integrated domino-like driving amplification is constructed. In this conception, a specific target acts as the domino promotor (namely the energy source), initiating a cascading chain reaction that grafts onto a singular interface. Next, an 808 nm near-infrared (NIR) light-excited up-converting luminescence-induced light-activatable biosensing technique is introduced. By locking the target-specific identification segment with a photo-cleavage connector, the up-converted ultraviolet emission can activate target binding in a completely controlled manner. Moreover, a fast reaction rate is achieved by confining nucleic acid collisions within the surface of a DNA wire nano-scaffold, leading to a substantial enhancement in local contact concentration (30.8-fold increase, alongside a 15 times elevation in rate). When a non-coding microRNA (miRNA-221) is positioned as the model low-abundance target for proof-of-concept validation, our intelligent DNA machine demonstrates ultra-high sensitivity (with a limit of detection down to 62.65 fM) and good specificity for this hepatic malignant tumor-associated biomarker in solution detection. Going further, it is worth highlighting that the biosensing system can be employed to carry out high-performance imaging analysis in live bio-samples (ranging from the cellular level to the nude mouse body), thereby propelling the field of DNA machines in disease diagnosis.

Asymmetric Coordination Regulating D-Orbital Spin-Electron Filling in Single-Atom Iron Catalyst for Efficient Oxygen Reduction.

The single-atom Fe-N-C catalyst has shown great promise for the oxygen reduction reaction (ORR), yet the intrinsic activity is not satisfactory. There is a pressing need to gain a deeper understanding of the charge configuration of the Fe-N-C catalyst and to develop rational modulation strategies. Herein, we have prepared a single-atom Fe catalyst with the co-coordination of N and O (denoted as Fe-N/O-C) and adjacent defect, proposing a strategy to optimize the d-orbital spin-electron filling of Fe sites by fine-tuning the first coordination shell. The Fe-N/O-C exhibits significantly better ORR activity compared to its Fe-N-C counterpart and commercial Pt/C, with a much more positive half-wave potential (0.927 V) and higher kinetic current density. Moreover, using the Fe-N/O-C catalyst, the Zn-air battery and proton exchange membrane fuel cell achieve peak power densities of up to 490 and 1179 mW cm-2, respectively. Theoretical studies and in situ electrochemical Raman spectroscopy reveal that Fe-N/O-C undergoes charge redistribution and negative shifting of the d-band center compared to Fe-N-C, thus optimizing the adsorption free energy of ORR intermediates. This work demonstrates the feasibility of introducing an asymmetric first coordination shell for single-atom catalysts and provides a new optimization direction for their practical application.

Innovative Multivariable Model Combining MRI Radiomics and Plasma Indexes Predicts Alzheimer's Disease Conversion: Evidence from a 2-Cohort Longitudinal Study.

To explore the complementary relationship between magnetic resonance imaging (MRI) radiomic and plasma biomarkers in the early diagnosis and conversion prediction of Alzheimer's disease (AD), our study aims to develop an innovative multivariable prediction model that integrates those two for predicting conversion results in AD. This longitudinal multicentric cohort study included 2 independent cohorts: the Sino Longitudinal Study on Cognitive Decline (SILCODE) project and the Alzheimer Disease Neuroimaging Initiative (ADNI). We collected comprehensive assessments, MRI, plasma samples, and amyloid positron emission tomography data. A multivariable logistic regression analysis was applied to combine plasma and MRI radiomics biomarkers and generate a new composite indicator. The optimal model's performance and generalizability were assessed across populations in 2 cross-racial cohorts. A total of 897 subjects were included, including 635 from the SILCODE cohort (mean [SD] age, 64.93 [6.78] years; 343 [63%] female) and 262 from the ADNI cohort (mean [SD] age, 73.96 [7.06] years; 140 [53%] female). The area under the receiver operating characteristic curve of the optimal model was 0.9414 and 0.8979 in the training and validation dataset, respectively. A calibration analysis displayed excellent consistency between the prognosis and actual observation. The findings of the present study provide a valuable diagnostic tool for identifying at-risk individuals for AD and highlight the pivotal role of the radiomic biomarker. Importantly, built upon data-driven analyses commonly seen in previous radiomics studies, our research delves into AD pathology to further elucidate the underlying reasons behind the robust predictive performance of the MRI radiomic predictor.

Lightweight semantic segmentation network for tumor cell nuclei and skin lesion.

In the field of medical image segmentation, achieving fast and accurate semantic segmentation of tumor cell nuclei and skin lesions is of significant importance. However, the considerable variations in skin lesion forms and cell types pose challenges to attaining high network accuracy and robustness. Additionally, as network depth increases, the growing parameter size and computational complexity make practical implementation difficult. To address these issues, this paper proposes MD-UNet, a fast cell nucleus segmentation network that integrates Tokenized Multi-Layer Perceptron modules, attention mechanisms, and Inception structures. Firstly, tokenized MLP modules are employed to label and project convolutional features, reducing computational complexity. Secondly, the paper introduces Depthwise Attention blocks and Multi-layer Feature Extraction modules. The Depthwise Attention blocks eliminate irrelevant and noisy responses from coarse-scale extracted information, serving as alternatives to skip connections in the UNet architecture. The Multi-layer Feature Extraction modules capture a wider range of high-level and low-level semantic features during decoding and facilitate feature fusion. The proposed MD-UNet approach is evaluated on two datasets: the International Skin Imaging Collaboration (ISIC2018) dataset and the PanNuke dataset. The experimental results demonstrate that MD-UNet achieves the best performance on both datasets.

In-situ low-temperature sulfur CVD on metal sulfides with SO2 to realize self-sustained adsorption of mercury.

Capturing gaseous mercury (Hg0) from sulfur dioxide (SO2)-containing flue gases remains a common yet persistently challenge. Here we introduce a low-temperature sulfur chemical vapor deposition (S-CVD) technique that effectively converts SO2, with intermittently introduced H2S, into deposited sulfur (Sd0) on metal sulfides (MS), facilitating self-sustained adsorption of Hg0. ZnS, as a representative MS model, undergoes a decrease in the coordination number of Zn-S from 3.9 to 3.5 after Sd0 deposition, accompanied by the generation of unsaturated-coordinated polysulfide species (Sn2-, named Sd*) with significantly enhanced Hg0 adsorption performance. Surprisingly, the adsorption product, HgS (ZnS@HgS), can serve as a fresh interface for the activation of Sd0 to Sd* through the S-CVD method, thereby achieving a self-sustained Hg0 adsorption capacity exceeding 300 mg g-1 without saturation limitations. Theoretical calculations substantiate the self-sustained adsorption mechanism that S8 ring on both ZnS and ZnS@HgS can be activated to chemical bond S4 chain, exhibiting a stronger Hg0 adsorption energy than pristine ones. Importantly, this S-CVD strategy is applicable to the in-situ activation of synthetic or natural MS containing chalcophile metal elements for Hg0 removal and also holds potential applications for various purposes requiring MS adsorbents.

Near-Infrared Light-Powered and DNA Nanocage-Confined Catalytic Hairpin Assembly Nanobiosensor with a Nucleic Acid Restriction Behavior and Reinforced Enzymatic Resistance for Robust Imaging Assay in Live Biosystems.

While DNA amplifier-built nanobiosensors featuring a DNA polymerase-free catalytic hairpin assembly (CHA) reaction have shown promise in fluorescence imaging assays within live biosystems, challenges persist due to unsatisfactory precision stemming from premature activation, insufficient sensitivity arising from low reaction kinetics, and poor biostability caused by endonuclease degradation. In this research, we aim to tackle these issues. One aspect involves inserting an analyte-binding unit with a photoinduced cleavage bond to enable a light-powered notion. By utilizing 808 nm near-infrared (NIR) light-excited upconversion luminescence as the ultraviolet source, we achieve entirely a controllable sensing event during the biodelivery phase. Another aspect refers to confining the CHA reaction within the finite space of a DNA self-assembled nanocage. Besides the accelerated kinetics (up to 10-fold enhancement) resulting from the nucleic acid restriction behavior, the DNA nanocage further provides a 3D rigid skeleton to reinforce enzymatic resistance. After selecting a short noncoding microRNA (miRNA-21) as the modeled low-abundance sensing analyte, we have verified that the innovative NIR light-powered and DNA nanocage-confined CHA nanobiosensor possesses remarkably high sensitivity and specificity. More importantly, our sensing system demonstrates a robust imaging capability for this cancer-related universal biomarker in live cells and tumor-bearing mouse bodies, showcasing its potential applications in disease analysis.

Investigating the causal role of the gut microbiota in esophageal cancer and its subtypes: a two-sample Mendelian randomization study.

BACKGROUND: Through research on the gut microbiota (GM), increasing evidence has indicated that the GM is associated with esophageal cancer (ESCA). However, the specific cause-and-effect relationship remains unclear. In this study, Mendelian randomization (MR) analysis was applied to investigate the causal relationship between the GM and ESCA, including its subtypes. METHODS: We collected information on 211 GMs and acquired data on ESCA and its subtypes through genome-wide association studies (GWASs). The causal relationship was primarily assessed using the inverse variance weighted (IVW) method. Additionally, we applied the weighted median estimator (WME) method, MR-Egger method, weighted mode, and simple mode to provide further assistance. Subsequent to these analyses, sensitivity analysis was conducted using the MR-Egger intercept test, MR-PRESSO global test, and leave-one-out method. RESULT: Following our assessment using five methods and sensitivity analysis, we identified seven GMs with potential causal relationships with ESCA and its subtypes. At the genus level, Veillonella and Coprobacter were positively correlated with ESCA, whereas Prevotella9, Eubacterium oxidoreducens group, and Turicibacter were negatively correlated with ESCA. In the case of esophageal adenocarcinoma (EAC), Flavonifractor exhibited a positive correlation, while Actinomyces exhibited a negative correlation. CONCLUSION: Our study revealed the potential causal relationship between GM and ESCA and its subtypes, offering novel insights for the advancement of ESCA diagnosis and treatment.

Dynamic chloride ion adsorption on single iridium atom boosts seawater oxidation catalysis.

Seawater electrolysis offers a renewable, scalable, and economic means for green hydrogen production. However, anode corrosion by Cl- pose great challenges for its commercialization. Herein, different from conventional catalysts designed to repel Cl- adsorption, we develop an atomic Ir catalyst on cobalt iron layered double hydroxide (Ir/CoFe-LDH) to tailor Cl- adsorption and modulate the electronic structure of the Ir active center, thereby establishing a unique Ir-OH/Cl coordination for alkaline seawater electrolysis. Operando characterizations and theoretical calculations unveil the pivotal role of this coordination state to lower OER activation energy by a factor of 1.93. The Ir/CoFe-LDH exhibits a remarkable oxygen evolution reaction activity (202 mV overpotential and TOF = 7.46 O2 s-1) in 6 M NaOH+2.8 M NaCl, superior over Cl--free 6 M NaOH electrolyte (236 mV overpotential and TOF = 1.05 O2 s-1), with 100% catalytic selectivity and stability at high current densities (400-800 mA cm-2) for more than 1,000 h.

Biogenerated Oxygen-Related Environmental Stressed Apoptotic Vesicle Targets Endothelial Cells.

The dynamic balance between hypoxia and oxidative stress constitutes the oxygen-related microenvironment in injured tissues. Due to variability, oxygen homeostasis is usually not a therapeutic target for injured tissues. It is found that when administered intravenously, mesenchymal stem cells (MSCs) and in vitro induced apoptotic vesicles (ApoVs) exhibit similar apoptotic markers in the wound microenvironment where hypoxia and oxidative stress co-existed, but MSCs exhibited better effects in promoting angiogenesis and wound healing. The derivation pathway of ApoVs by inducing hypoxia or oxidative stress in MSCs to simulate oxygen homeostasis in injured tissues is improved. Two types of oxygen-related environmental stressed ApoVs are identified that directly target endothelial cells (ECs) for the accurate regulation of vascularization. Compared to normoxic and hypoxic ones, oxidatively stressed ApoVs (Oxi-ApoVs) showed the strongest tube formation capacity. Different oxygen-stressed ApoVs deliver similar miRNAs, which leads to the broad upregulation of EC phosphokinase activity. Finally, local delivery of Oxi-ApoVs-loaded hydrogel microspheres promotes wound healing. Oxi-ApoV-loaded microspheres achieve controlled ApoV release, targeting ECs by reducing the consumption of inflammatory cells and adapting to the proliferative phase of wound healing. Thus, the biogenerated apoptotic vesicles responding to oxygen-related environmental stress can target ECs to promote vascularization.

Effect of Intrinsic Ferroelectric Phase Transition on Hydrogen Evolution Electrocatalysis.

Heterogeneous electrocatalysis closely relies on the electronic structure of the catalytic materials. The ferroelectric-to-paraelectric phase transition of the materials also involves a change in the state of electrons that could impact the electrocatalytic activity, but such correlation remains unexplored. Here, we demonstrate experimentally and theoretically that the intrinsic electrocatalytic activity could be regulated as exampled by hydrogen evolution reaction catalysis over two-dimensional ferroelectric CuInP2S6. The obvious discontinuity in the overpotential and apparent activation energy values for CuInP2S6 electrode are illustrated during the ferroelectric-to-paraelectric phase transition caused by copper displacement around Tc point (318 K), revealing the ferroelectro-catalytic effect on thermodynamics and kinetics of electrocatalysis. When loading Pt single atom on the CuInP2S6, the paraelectric phase one showed an improved hydrogen evolution activity with smaller apparent activation energy over the ferroelectric phase counterpart. This is attributed to the copper hopping between two sulfur planes, which alternate between strong and weak H adsorption at the Pt sites to simultaneously promote H+ reactant adsorption and H2 product desorption.

Current Status and Perspectives of Dual-Atom Catalysts Towards Sustainable Energy Utilization.

The exploration of sustainable energy utilization requires the implementation of advanced electrochemical devices for efficient energy conversion and storage, which are enabled by the usage of cost-effective, high-performance electrocatalysts. Currently, heterogeneous atomically dispersed catalysts are considered as potential candidates for a wide range of applications. Compared to conventional catalysts, atomically dispersed metal atoms in carbon-based catalysts have more unsaturated coordination sites, quantum size effect, and strong metal-support interactions, resulting in exceptional catalytic activity. Of these, dual-atomic catalysts (DACs) have attracted extensive attention due to the additional synergistic effect between two adjacent metal atoms. DACs have the advantages of full active site exposure, high selectivity, theoretical 100% atom utilization, and the ability to break the scaling relationship of adsorption free energy on active sites. In this review, we summarize recent research advancement of DACs, which includes (1) the comprehensive understanding of the synergy between atomic pairs; (2) the synthesis of DACs; (3) characterization methods, especially aberration-corrected scanning transmission electron microscopy and synchrotron spectroscopy; and (4) electrochemical energy-related applications. The last part focuses on great potential for the electrochemical catalysis of energy-related small molecules, such as oxygen reduction reaction, CO2 reduction reaction, hydrogen evolution reaction, and N2 reduction reaction. The future research challenges and opportunities are also raised in prospective section.

Comparative analysis of miRNAs and mRNAs in large yellow croaker head kidney cells (LYCK) provided novel insights into the redox regulation of fish.

Reactive oxygen species (ROS) over-production and oxidative stress resulted from climate change and environmental pollution seriously endangered global fish populations and healthy development of marine aquaculture. Peroxiredoxins (Prxs), a highly conserved family of thiol-specific antioxidants, can mitigate ROS and protect cells from oxidative stress. We previously demonstrated that large yellow croaker PrxIV (LcPrxIV) could not only regulate the pro-inflammatory responses, but also scavenge ROS. However, the underlying mechanism how LcPrxIV regulated immune response and redox homeostasis remains unknown. MicroRNAs (miRNAs) are non-coding RNAs that play important roles in the regulation of various biological processes. In this study, mRNA and miRNA expression profiles from LYCK-pcDNA3.1 and LYCK-PrxIV cells, with or without oxidative stress stimulated by H2O2 were evaluated using high-throughput sequencing. A series of differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs), as well as DEM-DEG pairs were identified from each two-group comparison, respectively. GO and KEGG functional analyses indicated that most significant DEGs were associated with signaling pathways related to oxidative stress and immune response. Subsequent DEM-DEG interaction analysis revealed that miR-731 and miR-1388 may be involved in both redox regulation and immune response via synergistic effect with LcPrxIV. Interestingly, miR-731 could regulate the expression of different down-stream DEGs under different stimulations of LcPrxIV over-expression, H2O2, or both. Moreover, miR-731 could cause the DEG, γ-glutamyl hydrolase (GGH), to be expressed in opposite ways under different stimulations. On the other hand, the expression of miR-1388 could be negatively or positively regulated under the stimulation of LcPrxIV over-expression with or without oxidative stress, thus regulating gene expression of different mRNAs. Based on these results, we speculate that LcPrxIV may participate in immune response or redox regulation by regulating the expression of different down-stream genes through controlling the expression level of a certain miRNA or by regulating the varieties of expressed miRNAs.

Balancing macrophage polarization via stem cell-derived apoptotic bodies for diabetic wound healing.

BACKGROUND: Adipose tissue-derived stem cell-derived apoptotic bodies (ADSC-ABs) have shown great potential for immunomodulation and regeneration, particularly in diabetic wound therapy. However, their local application has been limited by unclear regulatory mechanisms, rapid clearance, and short tissue retention times. METHODS: We analyzed the key role molecules and regulatory pathways of ADSC-ABs in regulating inflammatory macrophages by mRNA sequencing and microRNA (miRNA) sequencing and then verified them by gene knockdown. To prevent rapid clearance, we employed microfluidics technology to prepare methacrylate-anhydride gelatin (GelMA) microspheres (GMS) for controlled release of ABs. Finally, we evaluated the effectiveness of ADSC-AB-laden GMSs (ABs@GMSs) in a diabetic rat wound model. FINDINGS: Our results demonstrated that ADSC-ABs effectively balanced macrophage inflammatory polarization through the janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, mediated by miR-20a-5p. Furthermore, we showed that AB@GMSs had good biocompatibility, significantly delayed local clearance of ABs, and ameliorated diabetic wound inflammation and promoted vascularization, thus facilitating its healing. CONCLUSIONS: Our study reveals the regulatory mechanism of ADSC-ABs in balancing macrophage inflammatory polarization and highlightsthe importance of delaying their local clearance by GMSs. These findings have important implications for the development of novel therapies for diabetic wound healing. FUNDING: This research was supported by the National Key Research and Development Program of China (2020YFA0908200), National Natural Science Foundation of China (82272263, 82002053, 32000937, and 82202467), Shanghai "Rising Stars of Medical Talents" Youth Development Program (22MC1940300), Shanghai Municipal Health Commission (20204Y0354), and Shanghai Science and Technology Development Funds (22YF1421400).