Gases and gas-releasing materials for the treatment of chronic diabetic wounds.

Chronic non-healing wounds are a common consequence of skin ulceration in diabetic patients, with severe cases such as diabetic foot even leading to amputations. The interplay between pathological factors like hypoxia-ischemia, chronic inflammation, bacterial infection, impaired angiogenesis, and accumulation of advanced glycosylation end products (AGEs), resulting from the dysregulation of the immune microenvironment caused by hyperglycemia, establishes an unending cycle that hampers wound healing. However, there remains a dearth of sufficient and effective approaches to break this vicious cycle within the complex immune microenvironment. Consequently, numerous scholars have directed their research efforts towards addressing chronic diabetic wound repair. In recent years, gases including Oxygen (O2), Nitric oxide (NO), Hydrogen (H2), Hydrogen sulfide (H2S), Ozone (O3), Carbon monoxide (CO) and Nitrous oxide (N2O), along with gas-releasing materials associated with them have emerged as promising therapeutic solutions due to their ability to regulate angiogenesis, intracellular oxygenation levels, exhibit antibacterial and anti-inflammatory effects while effectively minimizing drug residue-induced damage and circumventing drug resistance issues. In this review, we discuss the latest advances in the mechanisms of action and treatment of these gases and related gas-releasing materials in diabetic wound repair. We hope that this review can provide different ideas for the future design and application of gas therapy for chronic diabetic wounds.

Injectable Dynamic ROS-Responsive COF-Modified Microalgae Gels for In Vivo bFGF Delivery to Treat Diabetic Wounds.

Hypoxia, chronic inflammation, and elevated reactive oxygen species (ROS) production induced by hyperglycemia pose formidable challenges to the healing of diabetic chronic wounds, often resulting in impaired recovery. Currently, sustainable and eco-friendly therapeutic approaches targeting this multifaceted problem remain uncharted. Herein, we develop a unique three-functional covalent organic framework (COF)-modified microalgae gel designed for the preparation and treatment of chronic diabetic wounds. The gel comprises an oxygen-releasing basic fibroblast growth factor (bFGF) microalgae matrix, augmented by an ROS-responsive COF. Although two of these components have been reported to be used in wound healing, the combination of all three functions represents an innovative approach to synergize the treatment of chronic diabetic wounds. Therefore, we propose a new concept of "ligand interlocking" with three functional synergistic effects. Specifically, the COF has a similar effect to the "double Excalibur", which binds bFGF to promote angiogenesis and proliferation and inhibit the inflammatory response of chronic wounds and binds live microalgae to eliminate ROS and release dissolved oxygen to alleviate the hypoxia of wounds. Moreover, in vivo experiments and RNA sequencing analyses similarly demonstrated that the COF-modified microalgae gel reduced the inflammatory cascade cycle in the wound site and promoted vascular and tissue regeneration. We posit that the COF-modified microalgae gel represents a promising strategy for the active in vivo delivery of therapeutics to the wound body in intensive care unit settings.

Multimodal fall detection for solitary individuals based on audio-video decision fusion processing.

Falls often pose significant safety risks to solitary individuals, especially the elderly. Implementing a fast and efficient fall detection system is an effective strategy to address this hidden danger. We propose a multimodal method based on audio and video. On the basis of using non-intrusive equipment, it reduces to a certain extent the false negative situation that the most commonly used video-based methods may face due to insufficient lighting conditions, exceeding the monitoring range, etc. Therefore, in the foreseeable future, methods based on audio and video fusion are expected to become the best solution for fall detection. Specifically, this article outlines the following methodology: the video-based model utilizes YOLOv7-Pose to extract key skeleton joints, which are then fed into a two stream Spatial Temporal Graph Convolutional Network (ST-GCN) for classification. Meanwhile, the audio-based model employs log-scaled mel spectrograms to capture different features, which are processed through the MobileNetV2 architecture for detection. The final decision fusion of the two results is achieved through linear weighting and Dempster-Shafer (D-S) theory. After evaluation, our multimodal fall detection method significantly outperforms the single modality method, especially the evaluation metric sensitivity increased from 81.67% in single video modality to 96.67% (linear weighting) and 97.50% (D-S theory), which emphasizing the effectiveness of integrating video and audio data to achieve more powerful and reliable fall detection in complex and diverse daily life environments.

Network-based analysis identifies potential therapeutic ingredients of Chinese medicines and their mechanisms toward lung cancer.

Lung cancer is one of the most common malignant tumors around the world, which has the highest mortality rate among all cancers. Traditional Chinese medicine (TCM) has attracted increased attention in the field of lung cancer treatment. However, the abundance of ingredients in Chinese medicines presents a challenge in identifying promising ingredient candidates and exploring their mechanisms for lung cancer treatment. In this work, two network-based algorithms were combined to calculate the network relationships between ingredient targets and lung cancer targets in the human interactome. Based on the enrichment analysis of the constructed disease module, key targets of lung cancer were identified. In addition, molecular docking and enrichment analysis of the overlapping targets between lung cancer and ingredients were performed to investigate the potential mechanisms of ingredient candidates against lung cancer. Ten potential ingredients against lung cancer were identified and they may have similar effect on the development of lung cancer. The results obtained from this study offered valuable insights and provided potential avenues for the development of novel drugs aimed at treating lung cancer.

SoftVoting6mA: An improved ensemble-based method for predicting DNA N6-methyladenine sites in cross-species genomes.

The DNA N6-methyladenine (6mA) is an epigenetic modification, which plays a pivotal role in biological processes encompassing gene expression, DNA replication, repair, and recombination. Therefore, the precise identification of 6mA sites is fundamental for better understanding its function, but challenging. We proposed an improved ensemble-based method for predicting DNA N6-methyladenine sites in cross-species genomes called SoftVoting6mA. The SoftVoting6mA selected four (electron-ion-interaction pseudo potential, One-hot encoding, Kmer, and pseudo dinucleotide composition) codes from 15 types of encoding to represent DNA sequences by comparing their performances. Similarly, the SoftVoting6mA combined four learning algorithms using the soft voting strategy. The 5-fold cross-validation and the independent tests showed that SoftVoting6mA reached the state-of-the-art performance. To enhance accessibility, a user-friendly web server is provided at http://www.biolscience.cn/SoftVoting6mA/.

Ultrathin Cu9S5 Nanosheets with Sulfur Vacancy for Multimodal Tumor Therapy.

Multimodal tumor therapy with nanotechnology is an effective and integrative strategy to overcome the limitations of therapeutic efficacy and possible side effects associated with monotherapy. However, the construction of multimodal treatment nanoplatforms often involves various functional components, leading to certain challenges, such as time-consuming synthesis processes, low product yield, and inadequate biocompatibility. To address these issues, we have developed a straightforward method for preparing ultrathin Cu9S5 nanosheets (NSs) with surface defects for photothermal/photodynamic/chemodynamic therapy. The ultrathin morphology of the Cu9S5 NSs (with 2-3 nm) not only confers excellent biocompatibility but also enables broad-spectrum absorption with a remarkable photothermal conversion efficiency (58.96%) under 1064 nm laser irradiation. Moreover, due to the presence of a S vacancy, these Cu9S5 NSs exhibit favorable enzyme-like properties, including reactive oxygen species generation and glutathione consumption, particularly under laser irradiation. The efficacy of related tumor therapy and antibacterial treatment is significantly enhanced by the synergistic activation of photothermal/photodynamic/chemodynamic therapy through 1064 nm laser irradiation, as demonstrated by both in vitro and in vivo experiments. This study presents a novel strategy for multimodal tumor therapy with the prepared ultrathin Cu9S5 NSs, which holds promising pathways for photodynamic therapy in the NIR-II region.

Piceatannol protects against myocardial ischemia/reperfusion injury by inhibiting ferroptosis via Nrf-2 signaling-mediated iron metabolism.

Myocardial tissue ischemia damages myocardial cells. Although reperfusion is an effective technique to rescue myocardial cell damage, it may also exacerbate myocardial cell damage. Ferroptosis, an iron-dependent cell death, occurs following myocardial ischemia-reperfusion (I/R). Piceatannol (PCT) is a natural stilbene compound with excellent antioxidant properties that protect against I/R injury and exerts protective effects against ferroptosis-induced cardiomyocytes following I/R injury; however, the exact mechanism remains to be elucidated. PURPOSE: This study aims to investigate the protective effect and mechanism of PCT on myocardial ischemia-reperfusion injury. METHODS: An ischemia-reperfusion model was established via ligation of the left anterior descending branch of mice's hearts and hypoxia-reoxygenation (H/R) of cardiomyocytes. RESULTS: During ischemia-reperfusion, Nuclear factor E2-related factor 2 (Nrf-2) expression was downregulated, the left ventricular function was impaired, intracellular iron and lipid peroxidation product levels were elevated, and cardiomyocytes underwent ferroptosis. Furthermore, ferroptosis was enhanced following treatment with an Nrf-2 inhibitor. After PCT treatment, Nrf-2 expression significantly increased, intracellular ferrous ions and lipid peroxidation products significantly reduced, Ferroportin1 (FPN1) expression increased, and transferrin receptor-1 (TfR-1) expression was inhibited. CONCLUSIONS: PCT regulates iron metabolism through Nrf-2 to protect against myocardial cell ferroptosis induced by myocardial I/R injury.

MulCNN-HSP: A multi-scale convolutional neural networks-based deep learning method for classification of heat shock proteins.

Heat shock proteins (HSPs) are crucial cellular stress proteins that react to environmental cues, ensuring the preservation of cellular functions. They also play pivotal roles in orchestrating the immune response and participating in processes associated with cancer. Consequently, the classification of HSPs holds immense significance in enhancing our understanding of their biological functions and in various diseases. However, the use of computational methods for identifying and classifying HSPs still faces challenges related to accuracy and interpretability. In this study, we introduced MulCNN-HSP, a novel deep learning model based on multi-scale convolutional neural networks, for identifying and classifying of HSPs. Comparative results showed that MulCNN-HSP outperforms or matches existing models in the identification and classification of HSPs. Furthermore, MulCNN-HSP can extract and analyze essential features for the prediction task, enhancing its interpretability. To facilitate its accessibility, we have made MulCNN-HSP available at http://cbcb.cdutcm.edu.cn/HSP/. We hope that MulCNN-HSP will contribute to advancing the study of HSPs and their roles in various biological processes and diseases.

The impact mechanism of ownership change on university innovation.

The mixed-ownership reform of job invention achievements (MOJIA) is an important exploration of China's sound long-term incentive mechanism for transforming job-related inventions. Based on the data of MOJIA pilot universities and regions from 2012 to 2022, this paper analyzes the relationship and mechanism between MOJIA and university innovation (UI) in China by combining resource dependence theory and institutional theory. The study found that MOJIA has a promotive effect on UI. The findings continue to hold after using parallel trend tests, lagged regressions, alternative UI measures, endogeneity control, and placebo tests. MOJIA can enhance the technology achievement marketability in the regions where universities are located. Moreover, MOJIA can facilitate the technological achievements marketability by improving UI. Heterogeneity analysis found that the lower the administrative level and the university's social reputation, the stronger the promotion effect of MOJIA on UI. The research in this paper provides implications for further improving MOJIA.

Delivery of Small-Molecule Drugs and Protein Drugs by Injectable Acid-Responsive Self-Assembled COF Hydrogels for Combinatorial Lung Cancer Treatment.

Covalent organic frameworks (COFs) have revealed enormous application prospects for cancer therapeutics recently, but their assembly systems face considerable challenges, such as the codelivery of hydrophobic and hydrophilic protein drugs with different physicochemical properties for in vivo delivery and release, as well as endosomal/lysosomal escape of protein drugs. To address these issues, we leveraged the high specific surface area, lipotropism, and structural tunability of boronate ester-linked COFs (COF-1) for the construction of advanced drug delivery systems. We first encapsulated the small-molecule drug doxorubicin (DOX) into a lipophilic COF (COF-1@DOX) and immobilized the functional protein drug ribonuclease A (RNase A) on the surface of the COF (RNase A-COF-1@DOX). We then created a novel composite delivery system (RNase A-COF-1@DOX gel) by cross-linking an albumin-oxygenated hydrogel (gel) network into the pores of COFs, allowing targeted codelivery of protein and small-molecule drugs in vivo. Using in-living body and multichannel fluorescence imaging, we analyzed the in vivo codelivery of protein and small-molecule drugs in a Lewis lung carcinoma (LLC) model. Finally, we applied the RNase A-COF-1@DOX gel to treat lung cancer in mice. This study paves an avenue for constructing COF-based drug delivery systems for lung cancer treatment and holds the potential to be extended to other types of cancer for more effective and targeted therapeutic treatments.

The impact of city financial ecology on firm financing efficiency: Evidence from China's strategic emerging industries.

Based on the concept of bionics and the connotation of city financial ecology, this study constructs a 3-level and 27-indicator evaluation index system, including financial ecology growth, soil, and air. This study uses the entropy-TOPSIS model to weigh indicators objectively and evaluate the financial ecology of 343 China's prefecture-level cities during 2009-2016. This study uses the DEA-Tobit method to assess the financing efficiency of 4013 China's strategic emerging listed firms during 2010-2017 and runs random-effect Tobit panel regressions. Regression results suggest that a city's financial ecology overall has a positive effect on strategic emerging firms' financing efficiency. Therefore, the government should: improve the multi-tiered financial market system and encourage financial innovation; transform the economic growth model and optimize the industrial structure; establish an information-sharing mechanism and construct a social credit system.

Tumor-derived covalent organic framework nanozymes for targeted chemo-photothermal combination therapy.

Covalent organic frameworks (COFs) have garnered enormous attention in anti-cancer therapy recently. However, the intrinsic drawbacks such as poor biocompatibility and low target-specificity greatly restrain the full clinical implementation of COF. Herein, we report a biomimetic multifunctional COF nanozyme, which consists of AIEgen-based COF (TPE-s COF) with encapsulated gold nanoparticles (Au NPs). The nanozyme was co-cultured with HepG2 cells until the cell membrane was fused with lipophilic TPE-s COF-Au@Cisplatin. By using the cryo-shocking method, we fabricated an inactivated form of the TPE-s COF-Au@Cisplatin nanozyme endocytosed in the HepG2 cell membrane (M@TPE-s COF-Au@Cisplatin), which lost their proliferative ability and pathogenicity. Upon laser irradiation, the M@TPE-s COF-Au@Cisplatin nanozymes cleaved, thereby releasing the TPE-s COF-Au nanozyme and Cisplatin to exert their photothermal and drug therapeutic effect. This work opens a new avenue to the synthesis of tumor-derived fluorescent TPE-s COF-Au nanozymes for highly efficient, synergetic, and targeted chemo-photothermal combination therapy of liver cancer.

IPs-GRUAtt: An attention-based bidirectional gated recurrent unit network for predicting phosphorylation sites of SARS-CoV-2 infection.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has generated tremendous concern and poses a serious threat to international public health. Phosphorylation is a common post-translational modification affecting many essential cellular processes and is inextricably linked to SARS-CoV-2 infection. Hence, accurate identification of phosphorylation sites will be helpful to understand the mechanisms of SARS-CoV-2 infection and mitigate the ongoing COVID-19 pandemic. In the present study, an attention-based bidirectional gated recurrent unit network, called IPs-GRUAtt, was proposed to identify phosphorylation sites in SARS-CoV-2-infected host cells. Comparative results demonstrated that IPs-GRUAtt surpassed both state-of-the-art machine-learning methods and existing models for identifying phosphorylation sites. Moreover, the attention mechanism made IPs-GRUAtt able to extract the key features from protein sequences. These results demonstrated that the IPs-GRUAtt is a powerful tool for identifying phosphorylation sites. For facilitating its academic use, a freely available online web server for IPs-GRUAtt is provided at http://cbcb.cdutcm.edu.cn/phosphory/.

MultiScale-CNN-4mCPred: a multi-scale CNN and adaptive embedding-based method for mouse genome DNA N4-methylcytosine prediction.

N4-methylcytosine (4mC) is an important epigenetic mechanism, which regulates many cellular processes such as cell differentiation and gene expression. The knowledge about the 4mC sites is a key foundation to exploring its roles. Due to the limitation of techniques, precise detection of 4mC is still a challenging task. In this paper, we presented a multi-scale convolution neural network (CNN) and adaptive embedding-based computational method for predicting 4mC sites in mouse genome, which was referred to as MultiScale-CNN-4mCPred. The MultiScale-CNN-4mCPred used adaptive embedding to encode nucleotides, and then utilized multi-scale CNNs as well as long short-term memory to extract more in-depth local properties and contextual semantics in the sequences. The MultiScale-CNN-4mCPred is an end-to-end learning method, which requires no sophisticated feature design. The MultiScale-CNN-4mCPred reached an accuracy of 81.66% in the 10-fold cross-validation, and an accuracy of 84.69% in the independent test, outperforming state-of-the-art methods. We implemented the proposed method into a user-friendly web application which is freely available at: http://www.biolscience.cn/MultiScale-CNN-4mCPred/ .

Correlation between mismatch repair statuses and the prognosis of stage I-IV colorectal cancer.

Background: The role of microsatellite instability (MSI) and prognosis for stage II-III colorectal cancer (CRC) has been described, but the role of MSI in stage I and IV CRC is controversial. Methods: A total of 2,540 CRC patients were collected from Huzhou Central Hospital, China, from January 2006 to 2016, and 783 cases were excluded. This retrospective study illustrates the correlation between MMR status and prognosis for 1,757 CRC patients as well as the correlation between MSI and prognosis for CRC patients. Two groups were classified as MSI-H and MSI-L&MSS. If the expression of one or more mismatch repair (MMR) proteins was negative, it was considered as microsatellite instability high expression (MSI-H), whereas positive expression was considered as microsatellite instability low expression and microsatellite stability (MSI-L&MSS), as assessed by correlation analyses. Overall and disease-free survival were analyzed using the Kaplan-Meier method. Univariable and multivariable analyses were conducted using Cox regression. Results: Preoperative serum S-CEA, positive lymph, tumor size, pathologic tumor (Pt) status, node (N) stage, differentiation, chemotherapy, and the 8th Edition of the American Joint Committee on Cancer (AJCC-8) were significantly correlated with MSI (P=0.028, 0.037, 0.019, 0.007, 0.002, <0.001, <0.001, and <0.001, respectively), whereas tumor location was not associated with MSI. Univariable and multivariable analyses showed that MSI was an independent factor for CRC. The 5-year overall survival (OS) and 5-year disease-free survival (DFS, P<0.001) rates differed significantly between the two groups in stages II, III, and IV, whereas stage I did not show a significant difference (P>0.05). Conclusion: MSI-H was associated with a good prognosis for stages II to IV, whereas stage I did not show any significant correlation. Moreover, MSI expression was an independent prognostic factor.

Nanoparticles alleviate non-alcoholic steatohepatitis via ER stress sensor-mediated intestinal barrier damage and gut dysbiosis.

Introduction: The gut microbiota plays an important role in the development of non-alcoholic steatohepatitis (NASH), but the underlying mechanism is unclear. It has been found that the transcription factor XBP1s plays an important role in regulating inflammation and lipid metabolism and maintaining the integrity of intestinal barrier. However, whether XBP1s modulates the development of NASH by regulating the integrity of the intestinal barrier and altering the composition of the gut microbiota remains unknown. Methods: Mice fed with a fat-, fructose-, cholesterol-rich (FFC) diet for 24 weeks successfully established the NASH model, as demonstrated by significant hepatic steatosis, inflammation, hepatocyte injury and fibrosis. The profile of gut microbiota dynamically changed with the different stages of NAFLD via 16S rDNA sequencing the feces from mice fed with FFC diet for 0, 12, or 24 weeks or NASH mice treated with siRNA-loaded folic acid-modified TPGS (hereafter named FT@XBP1). Results: NASH mice had significantly higher abundance of Firmicutes, Blautia and Bacteroides, and lower abundance of Bifidobacterium and GCA-900066575. FT@XBP1 supplementation had a significantly attenuated effect on FFC diet-induced weight gain, hepatic fat accumulation, dyslipidemia, inflammatory cytokines, ER stress and fibrosis. In particularly, FT@XBP1 modulates the composition of the intestinal flora; for example, NASH mice demonstrated higher abundance of Blautia and Bacteroides, and lower abundance of Actinobacteriota, Muribaculaceae and Bifidobacterium, which were partially restored by FT@XBP1 treatment. Mechanistically, FT@XBP1 increased the expression of ZO-1 in the intestine and had the potential to restore intestinal barrier integrity and improve antimicrobial defense to alleviate enterogenic endotoxemia and activation of inflammatory signaling pathways. Discussion: Regulation of the key transcription factor XBP1s can partially restore the intestinal microbiota structure, maintain the integrity of intestinal mucosal barrier, and prevent the progression of NASH, providing new evidence for treating NASH.

Biodegradable Redox-Responsive AIEgen-Based-Covalent Organic Framework Nanocarriers for Long-Term Treatment of Myocardial Ischemia/Reperfusion Injury.

Timely restoration of blood supply after myocardial ischemia is imperative for the treatment of acute myocardial infarction but causes additional myocardial ischemia/reperfusion (MI/R) injury, which has not been hitherto effectively targeted by interventions for MI/R injury. Hence, the development of advanced nanomedicine that can reduce apoptosis of cardiomyocytes while protecting against MI/R in vivo is of utmost importance. Herein, a redox-responsive and emissive TPE-ss covalent organic framework (COF) nanocarrier by integrating aggregation-induced emission luminogens and redox-responsive disulfide motifs into the COF skeleton is developed. TPE-ss COF allows for efficient loading and delivery of matrine, a renowned anti-cryptosporidial drug, which significantly reduces MI/R-induced functional deterioration and cardiomyocyte injury when injected through the tail vein into MI/R models at 5 min after 30 min of ischemia. Moreover, TPE-ss COF@Matrine shows a drastic reduction in cardiomyocyte apoptosis and improvements in cardiac function and survival rate. The effect of the TPE-ss COF carrier is further elucidated by enhanced cardiomyocyte viability and triphenyltetrazolium chloride staining in vitro. This work demonstrates the cardioprotective effect of TPE-ss COFs for MI/R injury, which unleashes the immense potential of using COFs as smart drug carriers for the peri-reperfusion treatment of ischemic heart disease with low cost, high stability, and single postoperative intervention.

Covalent Organic Framework (COF): A Drug and Carrier to Attenuate Retinal Ganglion Cells Death in an Acute Glaucoma Mouse Model.

PURPOSE: We aim to investigate the use of covalent organic framework (COF) nanoparticles in the local treatment of glaucoma, both as a means of protecting retinal ganglion cells (RGCs), and as a carrier for delayed release of the medication rapamycin following a single intravitreal injection. METHODS: a water-dispersible COF, and a COF-based nanoplatform for rapamycin release (COF-Rapa) was constructed. C57BL/6J mice were randomly divided into four groups: intravitreal injection of 1.5 µL normal saline (NS), COF (0.67 ng/µL), rapamycin (300 µM) or COF-Rapa (0.67 ng/µL-300 µM), respectively. The ischemia-reperfusion (I/R) model was established to mimic high intraocular pressure (IOP)-induced retinal injury in glaucoma. Labeling of RGCs by Fluoro-Gold and retinal electroretinogram were used to evaluate retinal function. Immunohistochemistry and Western blotting analyses of retinas were performed. RESULTS: COF nanoparticles were delivered in vitro and in vivo. Six weeks after the COF injection, the number of RGCs was unaffected. In addition, the number of RBPMS-positive RGCs, GFAP-positive astrocytes and Iba1-positive microglia did not differ from the normal control. COF could effectively reduce RGCs death, improve phototransduction function and alleviate the overactivation of microglia compared to NS control after retinal I/R injury. Within six weeks, the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in the retinas could be inhibited by a single intravitreal injection of COF-Rapa. Compared with single COF administration, COF-Rapa significantly reduced the inflammatory reaction after retinal I/R injury. CONCLUSIONS: COF may act as both an RGC protection agent and a carrier for prolonged rapamycin release. This research may lead to the development of novel RGC protection agents and drug delivery techniques, as well as the creation of multifunctional COF-based biomaterials for glaucoma retinopathy.

Enhancer-LSTMAtt: A Bi-LSTM and Attention-Based Deep Learning Method for Enhancer Recognition.

Enhancers are short DNA segments that play a key role in biological processes, such as accelerating transcription of target genes. Since the enhancer resides anywhere in a genome sequence, it is difficult to precisely identify enhancers. We presented a bi-directional long-short term memory (Bi-LSTM) and attention-based deep learning method (Enhancer-LSTMAtt) for enhancer recognition. Enhancer-LSTMAtt is an end-to-end deep learning model that consists mainly of deep residual neural network, Bi-LSTM, and feed-forward attention. We extensively compared the Enhancer-LSTMAtt with 19 state-of-the-art methods by 5-fold cross validation, 10-fold cross validation and independent test. Enhancer-LSTMAtt achieved competitive performances, especially in the independent test. We realized Enhancer-LSTMAtt into a user-friendly web application. Enhancer-LSTMAtt is applicable not only to recognizing enhancers, but also to distinguishing strong enhancer from weak enhancers. Enhancer-LSTMAtt is believed to become a promising tool for identifying enhancers.

Insulin-like growth factor binding protein 7 promotes acute kidney injury by alleviating poly ADP ribose polymerase 1 degradation.

The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.