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.

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.

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.

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.

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.

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.

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.

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.

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.

The F-box protein RhSAF destabilizes the gibberellic acid receptor RhGID1 to mediate ethylene-induced petal senescence in rose.

Roses are among the most popular ornamental plants cultivated worldwide for their great economic, symbolic, and cultural importance. Nevertheless, rapid petal senescence markedly reduces rose (Rosa hybrida) flower quality and value. Petal senescence is a developmental process tightly regulated by various phytohormones. Ethylene accelerates petal senescence, while gibberellic acid (GA) delays this process. However, the molecular mechanisms underlying the crosstalk between these phytohormones in the regulation of petal senescence remain largely unclear. Here, we identified SENESCENCE-ASSOCIATED F-BOX (RhSAF), an ethylene-induced F-box protein gene encoding a recognition subunit of the SCF-type E3 ligase. We demonstrated that RhSAF promotes degradation of the GA receptor GIBBERELLIN INSENSITIVE DWARF1 (RhGID1) to accelerate petal senescence. Silencing RhSAF expression delays petal senescence, while suppressing RhGID1 expression accelerates petal senescence. RhSAF physically interacts with RhGID1s and targets them for ubiquitin/26S proteasome-mediated degradation. Accordingly, ethylene-induced RhGID1C degradation and RhDELLA3 accumulation are compromised in RhSAF-RNAi lines. Our results demonstrate that ethylene antagonizes GA activity through RhGID1 degradation mediated by the E3 ligase RhSAF. These findings enhance our understanding of the phytohormone crosstalk regulating petal senescence and provide insights for improving flower longevity.

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.

Boosting cadmium tolerance in Phoebe zhennan: the synergistic effects of exogenous nitrogen and phosphorus treatments promoting antioxidant defense and root development.

Plants possess intricate defense mechanisms to resist cadmium (Cd) stress, including strategies like metal exclusion, chelation, osmoprotection, and the regulation of photosynthesis, with antioxidants playing a pivotal role. The application of nitrogen (N) and phosphorus (P) fertilizers are reported to bolster these defenses against Cd stress. Several studies investigated the effects of N or P on Cd stress in non-woody plants and crops. However, the relationship between N, P application, and Cd stress resistance in valuable timber trees remains largely unexplored. This study delves into the Cd tolerance mechanisms of Phoebe zhennan, a forest tree species, under various treatments: Cd exposure alone, combined Cd stress with either N or P and Cd stress with both N and P application. Our results revealed that the P application enhanced root biomass and facilitated the translocation of essential nutrients like K, Mn, and Zn. Conversely, N application, especially under Cd stress, significantly inhibited plant growth, with marked reductions in leaf and stem biomass. Additionally, while the application of P resulted in reduced antioxidant enzyme levels, the combined application of N and P markedly amplified the activities of peroxidase by 266.36%, superoxide dismutase by 168.44%, and ascorbate peroxidase by 26.58% under Cd stress. This indicates an amplified capacity of the plant to neutralize reactive oxygen species. The combined treatment also led to effective regulation of nutrient and Cd distribution in roots, shoots, and leaves, illustrating a synergistic effect in mitigating toxic impact of N. The study also highlights a significant alteration in photosynthetic activities under different treatments. The N addition generally reduced chlorophyll content by over 50%, while P and NP treatments enhanced transpiration rates by up to 58.02%. Our findings suggest P and NP fertilization can manage Cd toxicity by facilitating antioxidant production, osmoprotectant, and root development, thus enhancing Cd tolerance processes, and providing novel strategies for managing Cd contamination in the environment.

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).

Knowledge, Attitudes, and Practice of General Practitioners Toward Screening of Age-Related Hearing Loss in Community: A Cross-Sectional Study in Shanghai, China.

Background: Age-related hearing loss (ARHL) is experiencing a continuously rising in prevalence among the elderly worldwide. General practitioners (GPs) may have a unique position in its community detection and management. Objective: This study aims to assess the KAP of GPs regarding ARHL through questionnaire, to investigate the role of them in the management and to propose strategies for the hearing screening within the community. Methods: An online survey was administered to 1173 GPs, selected from 56 community health centers (CHCs) in Shanghai during April to June 2022. A scale endorsed by a panel of multidisciplinary experts was used to assess knowledge (7 items), attitudes (12 items), and practice (10 items). A mean score was computed and converted into a scale ranging from 0 to 100. Odds ratios (ORs) were calculated for potential predictors of higher levels of KAP scores (with mean value as a cutoff point) through logistic modelling. Results: A total of 1022 GPs completed the questionnaire with response rate 87.13%. The average scores are 69.90 ± 32.27, 66.09 ± 7.15, and 59.89 ± 21.99 for Knowledge, attitude, and practice, respectively. 24.3% of participants achieve a complete score of knowledge, whereas 5.48% receive zero. 11.6% consider ARHL as not a disease. Above 30.0% are not familiar with the screening tool. 10.8% refuse to undergo hearing screening. Higher levels of compliance in practice are found in the participants with higher levels of knowledge (OR=1.409, p=0.000) and more favorable attitude (OR=1.028, p=0.000). Male (OR=0.708, p=0.036) is associated with lower levels of attitudes. Conclusion: GPs have a low level of ARHL knowledge, a lack of positive attitude towards the detection and management of it, and lower awareness in practice. Further research is required to gain a more comprehensive understanding of the attitudes held by GPs and explore more accessibility strategies.

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.

Development and validation of the screening tool for age-related hearing loss in the community based on the information platform.

INTRODUCTION: Currently, age-related hearing loss has become prevalent, awareness and screening rates remain dismally low. Duing to several barriers, as time, personnel training and equipment costs, available hearing screening tools do not adequately meet the need for large-scale hearing detection in community-dwelling older adults. Therefore, an accurate, convenient, and inexpensive hearing screening tool is needed to detect hearing loss, intervene early and reduce the negative consequences and burden of untreated hearing loss on individuals, families and society. OBJECTIVES: The study harnessed "medical big data" and "intelligent medical management" to develop a multi-dimensional screening tool of age-related hearing loss based on WeChat platform. METHODS: The assessment of risk factors was carried out by cross-sectional survey, logistic regression model and receiver operating characteristic (ROC) curve analysis. Combining risk factor assessment, Hearing handicap inventory for the elderly screening version and analog audiometry, the screening software was been developed by JavaScript language and been evaluated and verified. RESULTS: A total of 401 older adults were included in the cross-sectional study. Logistic regression model (univariate, multivariate) and reference to literature mention rate of risk factors, 18 variables (male, overweight/obesity, living alone, widowed/divorced, history of noise, family history of deafness, non-light diet, no exercising habit, smoking, drinking, headset wearer habit, hypertension, diabetes, hyperlipidemia, cardiovascular and cerebrovascular diseases, hyperuricemia, hypothyroidism, history of ototoxic drug use) were defined as risk factors. The area under the ROC curve (AUC) of the cumulative score of risk factors for early prediction of age-related hearing loss was 0.777 [95% CI (0.721, 0.833)]. The cumulative score threshold of risk factors was defined as 4, to classify the older adults into low-risk (< 4) and high-risk (≥ 4) hearing loss groups. The sensitivity, specificity, positive predictive value, and negative predictive value of the screen tool were 100%, 65.5%, 71.8%, and 100.0%, respectively. The Kappa index was 0.6. CONCLUSIONS: The screening software enabled the closed loop management of real-time data transmission, early warning, management, whole process supervision of the hearing loss and improve self-health belief in it. The software has huge prospects for application as a screening approach for age-related hearing loss.

Photoresponsive CHA-Integrated Self-Propelling 3D DNA Walking Amplifier within the Concentration Localization Effect of DNA Molecular Framework Enables Highly Efficient Fluorescence Bioimaging.

While three-dimensional (3D) DNA walking amplifiers hold considerable promise in the construction of advanced DNA-based fluorescent biosensors for bioimaging, they encounter certain difficulties such as inadequate sensitivity, premature activation, the need for exogenous propelling forces, and low reaction rates. In this contribution, a variety of profitable solutions have been explored. First, a catalytic hairpin assembly (CHA)-achieved nonenzymatic isothermal nucleic acid amplification is integrated to enhance sensitivity. Subsequently, one DNA component is simply functionalized with a photocleavage-bond to conduct a photoresponsive manner, whereby the target recognition occurs only when the biosensor is exposed to an external ultraviolet light source, overcoming premature activation during biodelivery. Furthermore, a special self-propelling walking mechanism is implemented by reducing biothiols to MnO2 nanosheets, thereby propelling forces that are self-supplied to a Mn2+-reliant DNAzyme. By carrying the biosensing system with a DNA molecular framework to induce a unique concentration localization effect, the nucleic acid contact reaction rate is notably elevated by 6 times. Following these, an ultrasensitive in vitro detection performance with a limit of detection down to 2.89 fM is verified for a cancer-correlated microRNA biomarker (miRNA-21). Of particular importance, our multiple concepts combined 3D DNA walking amplifier that enables highly efficient fluorescence bioimaging in live cells and even bodies, exhibiting a favorable application prospect in disease analysis.