Refractory COD removal from bio-treated paper wastewater using powdered activated coke adsorption technology with ozonation regeneration: Performance and molecular insights.

The present study employed powdered activated coke (PAC) for the adsorptive removal of refractory COD from the bio-treated paper wastewater (BTPW). The adsorption reached equilibrium after 3 h, resulting in a decrease in the COD concentration from 98.9 mg L-1 in BTPW to 42.6 mg L-1 when utilizing a PAC dosage of 5 g L-1. The dominant fractions of dissolved organic matter in BTPW were hydrophilic acids (HIA), hydrophilic neutrals (HIN), and hydrophobic acids (HOA), accounting for 48.8%, 34.2%, and 17.0% of the total dissolved organic carbon, respectively. Three fractions were all predominantly composed of humic/fulvic acid-like substances, while the HOA fraction exhibited highest susceptibility to adsorption by PAC, followed by the HIA and HIN fractions. FT-ICR MS data revealed PAC preferentially adsorbed the unsaturated and oxygen-rich substances containing more carboxyl groups. Additionally, the spent PAC was regenerated through ozonation and subsequently utilized in the adsorption cycles. The regeneration was successfully conducted under an ozone concentration of 1 mg L-1 for a duration of 10 min, and the regeneration efficiency remained about 87.0% even after undergoing five-cycle of adsorption-regeneration. The findings of this study demonstrate that PAC adsorption is a viable and efficacious treatment technology for efficiently removing refractory COD from BTPW.

Permeable Self-Association of Metal-Organic Framework 808/Ag-Based Fiber Membrane for Broad-Spectrum and Highly Efficient Degradation of Biological and Chemical War Agents.

The threat posed by biological and chemical warfare agents (BCWA) to national security, the environment, and personal health underscores the need for innovative chemical protective clothing. To address the limitations of conventional activated carbon materials, which are prone to falling off and adsorption saturation, an efficient self-association approach was introduced. In this study, we proposed the immobilization of metal-organic framework (MOF) 808 and Ag nanoparticles onto a polypropylene (PP) fiber membrane using a rapid self-association method facilitated by chitosan (CS). The MOF 808/Ag-based (PP-CS/808-Ag) fiber membrane demonstrated exceptional degradation efficiency, achieving a remarkable rate of t1/2 within 2 h for the mustard simulant 2-chloroethyl ethyl sulfide (2-CEES) and a rate of t1/2 = 4.12 min for the G-series simulant dimethyl 4-nitrophenylphosphate (DMNP). A theoretical computational model was developed to determine the overall reaction mechanism, and it was verified that MOF 808 and Ag nanoparticles were mainly involved in the hydrolysis process against 2-CEES and DMNP. The PP-CS/808-Ag composite fiber film was prepared as the core layer, and the fracture strength, bending resistance, and moisture permeability were better than those specified by many countries for biochemical protective clothing, showing that it has a broad application prospect in developing a generation of broad-spectrum bioprotective clothing.

The crosstalk between efflux pump and resistance gene mutation in Helicobacter pylori.

Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in Helicobacter pylori. Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.

Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects.

Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR-insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

A new classification for emergency critically ill patients and analysis of their adverse events during intrahospital transport: A cluster analysis.

BACKGROUND: Critical patients may experience various adverse events during transportation within hospitals. Therefore, quickly evaluating and classifying patients before transporting them from the emergency department and focusing on managing high-risk patients are critical. At present, no unified classification method exists; all the current approaches are subjective. AIMS: To ensure transportation safety, we conducted a cluster analysis of critically ill patients transferred from the emergency department to the intensive care unit. STUDY DESIGN: Single-centre cohort study. This study was conducted at a comprehensive first-class teaching hospital in Beijing. Convenience sampling and continuous enrolment were employed. We collected data from 1 January 2019, to 31 December 2021. All patients were transferred from the emergency department to the intensive care unit, and cluster analysis was conducted using five variables. RESULTS: A total of 584 patients were grouped into three clusters. Cluster 1 (high systolic blood pressure group) included 208 (35.6%) patients. Cluster 2 (high heart rate and low blood oxygen group) included 55 (9.4%) patients. Cluster 3 (normal group) included the remaining 321 (55%) patients. The oxygen saturation levels of all the patients were lower after transport, and the proportion of adverse events (61.8%) was the highest in Cluster 2 (p < .05). CONCLUSIONS: This study utilized data on five important vital signs from a cluster analysis to explore possible patient classifications and provide a reference for ensuring transportation safety. RELEVANCE TO CLINICAL PRACTICE: Before transferring patients, we should classify them and implement targeted care. Changes in blood oxygen levels in all patients should be considered, with a focus on the occurrence of adverse events during transportation among patients with high heart rates and low blood oxygen levels.

IMT030122, A novel engineered EpCAM/CD3/4-1BB tri-specific antibody, enhances T-cell recruitment and demonstrates anti-tumor activity in mouse models of colorectal cancer.

Colorectal cancer is a major global health burden, with limited efficacy of traditional treatment modalities in improving survival rates. However, recently advances in immunotherapy has improved treatment outcomes for patients with this cancer. To address the continuing need for improved treatment efficacy, this study introduced a novel tri-specific antibody, IMT030122, that targets EpCAM, 4-1BB, and CD3. We evaluated the pharmacological efficacy and mechanism of action of IMT030122 in vitro and in vivo. In in vitro studies, IMT030122 exhibited differential binding to antigens and cells expressing EpCAM, 4-1BB, and CD3. Moreover, IMT030122 relied on EpCAM-targeted activation of intracellular CD3 and 4-1BB signaling and mediated T cell cytotoxicity specific to HCT116 colorectal cancer cells. In vivo, IMT030122 demonstrated potent anti-tumor activity, significantly inhibiting the growth of colon cancer HCT116 and MC38-hEpCAM subcutaneous grafts. Further pharmacological analysis revealed that IMT030122 recruited lymphocytes from peripheral blood into colorectal cancer tissue and exerted durable anti-tumor activity, predominantly by promoting the activation, proliferation, and differentiation of CD8T cells. Notably, IMT030122 still exhibited anti-tumor efficacy even in the presence of significantly depleted lymphocytes in colorectal cancer tissue. The potent pharmacological activity and anti-tumor effects of IMT030122 suggest it may enhance treatment efficacy and substantially extend the survival of patients with colorectal cancer in the future.

NETs contribute to psoriasiform skin inflammation: A novel therapeutic approach targeting IL-36 cytokines by a small molecule tetrahydroxystilbene glucoside.

BACKGROUND: Psoriasis, a chronic immune-mediated skin disease with pathological features such as aberrant differentiation of keratinocytes, dermal-epidermal inflammation, and angiogenesis. 2,3,5,4'-Tetrahydroxy stilbene 2-Ο-ß-d-glucoside (2354Glu) is a natural small molecule polyhydrostilbenes isolated from Polygonum multiglorum Thunb. The regulation of IL-36 subfamily has led to new pharmacologic strategies to reverse psoriasiform dermatitis. PURPOSE: Here we investigated the therapeutic potential of 2354Glu and elucidated the underlying mechanism in psoriasis. METHODS: The effects of 2354Glu on IL-36 signaling were assessed by psoriasiform in vivo, in vitro and ex vivo model. The in vivo mice model of psoriasis-like skin inflammation was established by applying imiquimod (IMQ), and the in vitro and ex vitro models were established by stimulating mouse primary keratinocyte, human keratinocytes cells (HaCaT) and ex vivo skin tissue isolated from the mice back with Polyinosine-polycytidylic acid (Poly(I:C)), IMQ, IL-36γ and Lipopolysaccharide (LPS) respectively. Moreover, NETs formation was inhibited by Cl-amidine to evaluate the effect of NETs in psoriatic mouse model. The effects of 2354Glu on skin inflammation were assessed by western blot, H&E, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay and real-time quantitative PCR. RESULTS: In Poly(I:C)-stimulated keratinocytes, the secretion of IL-36 was inhibited after treatment with 2354Glu, similar to the effects of TLR3, P2X7R and caspase-1 inhibitors. In aldara (imiquimod)-induced mice, 2354Glu (100 and 25 mg/kg) improved immune cell infiltration and hyperkeratosis in psoriasis by directly targeting IL-36 in keratinocytes through P2X7R-caspase-1. When treatment with 2354Glu (25 mg/kg) was insufficient to inhibit IL-36γ, NETs reduced pathological features and IL-36 signaling by interacting with keratinocytes to combat psoriasis like inflammation. CONCLUSION: These results indicated that NETs had a beneficial effect on psoriasiform dermatitis. 2354Glu alleviates psoriasis by directly targeting IL-36/P2X7R axis and NET formation, providing a potential candidate for the treatment of psoriasis.

The Role of Immune Cells in DKD: Mechanisms and Targeted Therapies.

Diabetic kidney disease (DKD), is a common microvascular complication and a major cause of death in patients with diabetes. Disorders of immune cells and immune cytokines can accelerate DKD development of in a number of ways. As the kidney is composed of complex and highly differentiated cells, the interactions among different cell types and immune cells play important regulatory roles in disease development. Here, we summarize the latest research into the molecular mechanisms underlying the interactions among various immune and renal cells in DKD. In addition, we discuss the most recent studies related to single cell technology and bioinformatics analysis in the field of DKD. The aims of our review were to explore immune cells as potential therapeutic targets in DKD and provide some guidance for future clinical treatments.

Artificial dermis combined with negative pressure wound therapy and platelet-rich plasma to treat traumatic wounds: a retrospective study.

OBJECTIVE: The reconstruction of complex soft tissue defects with exposure of bones and tendons represents an increasing challenge in wound care, especially in large extremity wounds. The aim of this study was to detect the clinical efficacy of combined use of negative pressure wound therapy (NPWT), artificial dermis (ADM), platelet-rich plasma (PRP) and split-thickness skin grafting (STSG) in the reconstruction of large traumatic extremity skin defects. METHOD: In this study, eight cases were treated with combined therapies for repairing complex extremity wounds and the results were reviewed retrospectively. After surgical debridement, all wounds received ADM, PRP and delayed STSG, which were all aided with NPWT. RESULTS: The patients consisted of five males and three females, with a mean age of 44 years. A total of six lower extremity wounds were located at the foot/ankle, with exposed tendon in five, bone exposure in three and both in two. Of the group, two patients had exposed tendon on arm/hand wounds. The size of wounds and ADM averaged 126cm2 and 42.3cm2, respectively. ADM was used to cover the exposed bone or tendon, the granulation and muscular tissue were covered with vacuum sealing drainage (VSD) directly, for NPWT. The survival rate of ADM averaged 98.9%. The average time for survival of ADM was 12.8 days and the mean uptake of autologous skin graft was 93.5%. Only one patient received repeated skin grafts. All patients achieved successful healing and reported no complications. The mean length of hospital stay was 36.1 days. CONCLUSION: Our study revealed that ADM in conjunction with NPWT, PRP and STSG could be used for repairing large traumatic extremity wounds. Wound closure was achieved without flaps, the aesthetic and functional outcomes were acceptable, and only one patient developed a 35% loss of skin graft. DECLARATION OF INTEREST: This work was supported by grants from the Natural Science Foundation of Hubei Province (grant no. 2020CFB464) and Youth Foundation of Wuhan Municipal Health Commission (grant no. WX20Q15). The authors have no conflicts of interest to declare.

Filamentous prophage Pf4 promotes genetic exchange in Pseudomonas aeruginosa.

Filamentous prophages are widespread among bacteria and play crucial functions in virulence, antibiotic resistance, and biofilm structures. The filamentous Pf4 particles, extruded by an important pathogen Pseudomonas aeruginosa, can protect producing cells from adverse conditions. Contrary to the conventional belief that the Pf4-encoding cells resist reinfection, we herein report that the Pf4 prophage is reciprocally and commonly exchanged within P. aeruginosa colonies, which can repair defective Pf4 within the community. By labeling the Pf4 locus with antibiotic resistance and fluorescence markers, we demonstrate that the Pf4 locus is frequently exchanged within colony biofilms, in artificial sputum media, and in infected mouse lungs. We further show that Pf4 trafficking is a rapid process and capable of rescuing Pf4-defective mutants. The Pf4 phage is highly adaptable and can package additional DNA doubling its genome size. We also report that two clinical P. aeruginosa isolates are susceptible to the Pf4-mediated exchange, and the Pf5 prophage can be exchanged between cells as well. These findings suggest that the genetic exchanging interactions by filamentous prophages may facilitate defect rescue and the sharing of prophage-dependent benefits and costs within the P. aeruginosa community.

A few-shot link prediction framework to drug repurposing using multi-level attention network.

Drug repurposing is a strategy aiming at uncovering novel medical indications of approved drugs. This process of discovery can be effectively represented as a link prediction task within a medical knowledge graph by predicting the missing relation between the disease entity and the drug entity. Typically, the links to be predicted pertain to rare types, thereby necessitating the task of few-shot link prediction. However, the sparsity of neighborhood information and weak triplet interactions result in less effective representations, which brings great challenges to the few-shot link prediction. Therefore, in this paper, we proposed a meta-learning framework based on a multi-level attention network (MLAN) to capture valuable information in the few-shot scenario for drug repurposing. First, the proposed method utilized a gating mechanism and a graph attention network to effectively filter noise information and highlight the valuable neighborhood information, respectively. Second, the proposed commonality relation learner, employing a set transformer, effectively captured triplet-level interactions while remaining insensitive to the size of the support set. Finally, a model-agnostic meta-learning training strategy was employed to optimize the model quickly on each meta task. We conducted validation of the proposed method on two datasets specifically designed for few-shot link prediction in medical field: COVID19-One and BIOKG-One. Experimental results showed that the proposed model had significant advantages over state-of-the-art few-shot link prediction methods. Results also highlighted the valuable insights of the proposed method, which successfully integrated the components within a unified meta-learning framework for drug repurposing.

Biodentine as a pulpotomy medicament for primary molars: a retrospective chart review.

This retrospective chart review study investigates the long-term clinical outcome of Biodentine® (Tricalcium silicate) as a medicament for pulpotomy in primary molars. Data in this retrospective study was collected from the dental records of all patients that had at least one primary molar receive pulpotomy treatment (CDT code: D3221) between 01 July 2012 and 01 July 2015. This data includes child's age, medical history, dental history, dental radiographs, pulpotomy procedure details and follow-up clinical notes. Kaplan-Meier Estimate was used to measure the fraction of successful pulpotomy procedures for up to 24 months. A total of 1758 pulpotomy procedures were performed on 1032 patients in our institute in the three-year period and 21.4% of them (N = 376) had follow-up dental records that qualified for the study. Eleven teeth out of 376 teeth were excluded from the statistical analysis due to loss of/broken stainless steel crowns (3.1%). Seventeen pulpotomy failures were identified out of the remaining 365 procedures. The survival probablity of using Biodentine® as a pulpotomy medicament is 96.3% for 18-month follow-up and 95.4% for 24-month follow-up. Biodentine®, a tricalcium silicate formulation, used as a pulpotomy medicament demonstrates a high clinical success rate (95.4%) over a 24-month peroid in primary molars.

Hyperglycemia-induced STING signaling activation leads to aortic endothelial injury in diabetes.

Hyperglycaemia-induced endothelial dysfunction is a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy. STING, which is a newly discovered regulator of innate immunity, has also been reported to play an important role in various metabolic diseases. However, the role of STING in diabetes-induced endothelial cell dysfunction is unknown. In this study, we established a diabetic macroangiopathy mouse model by streptozotocin (STZ) injection combined with high-fat diet (HFD) feeding and a glucotoxicity cell model in high glucose (HG)-treated rat aortic endothelial cells (RAECs). We found that STING expression was specifically increased in the endothelial cells of diabetic arteries, as well as in HG-treated RAECs. Moreover, genetic deletion of STING significantly ameliorated diabetes-induced endothelial cell dysfunction and apoptosis in vivo. Likewise, STING inhibition by C-176 reversed HG-induced migration dysfunction and apoptosis in RAECs, whereas STING activation by DMXAA resulted in migration dysfunction and apoptosis. Mechanistically, hyperglycaemia-induced oxidative stress promoted endothelial mitochondrial dysfunction and mtDNA release, which subsequently activated the cGAS-STING system and the cGAS-STING-dependent IRF3/NF-kB pathway, ultimately resulting in inflammation and apoptosis. In conclusion, our study identified a novel role of STING in diabetes-induced aortic endothelial cell injury and suggested that STING inhibition was a potential new therapeutic strategy for the treatment of diabetic macroangiopathy. Video Abstract.

[Corrigendum] Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the scratch wound assay experiments shown in Fig. 1 on p. 2413, the panels showing the '0 h' experiments for the respective incubations with VEGF or BC001 were apparently identical. The authors were able to re­examine their original data files, and realized that this figure had been inadverently assembled incorrectly. The revised version of Fig. 1, containing the correct data for the '0 h / BC001' panel, is shown below. Note that the revisions made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 45: 2411­2420, 2014; DOI: 10.3892/ijo.2014.2690].

Nitrogen removal from dewatering liquid of landfill sludge by partial nitrification and denitrification.

Two pilot-scale two-stage anoxic/oxic membrane bioreactors were operated at different dissolved oxygen (DO) levels to evaluate nitrogen removal performances for treating landfill sludge dewatering liquid. Under either high (5.0-6.0 mg/L) or conventional DO (2.0-3.0 mg/L) conditions, partial nitrification (PN)-denitrification was both achieved, and high-concentration free ammonia (FA) ensured stable PN. The high DO system exhibited higher nitrite accumulation (98.5 %) and nitrogen removal (98.0 %), and its nitrogen removal was mainly ascribed to PN-denitrification (53.8 %). Kinetic inhibition tests and microbial sequencing results demonstrated that high DO condition improved the abundance and ability of ammonia-oxidizing bacteria (AOB) rather than nitrite-oxidizing bacteria under the FA inhibition. Pseudomonas, Thauera, and Soehngenia were characteristic genus in the high DO system, and Nitrosomonas was only AOB. Metagenomic analysis confirmed the important role of PN on nitrogen removal in high DO system. This provides valuable references for the efficient and economic treatment of ammonia-rich wastewater.

PARSE: A personalized clinical time-series representation learning framework via abnormal offsets analysis.

BACKGROUND AND OBJECTIVE: Clinical risk prediction of patients is an important research issue in the field of healthcare, which is of great significance for the diagnosis, treatment and prevention of diseases. In recent years, a large number of deep learning-based methods have been proposed for clinical prediction by mining relevant features of patients' health condition from historical Electronic Health Records (EHRs) data. However, most of these existing methods only focus on discovering the time series characteristics of physiological indexes such as laboratory tests and physical examinations, and fail to comprehensively consider the deviation degree of these physiological indexes from the normal range and their stability, thus greatly limiting the prediction performance. METHODS: We propose a personalized clinical time-series representation learning framework via abnormal offsets analysis named PARSE for clinical risk prediction. In PARSE, while extracting relevant temporal features from the original EHR data, we further capture relevant features of abnormal condition as complementary information from the absolute offset of each physiological index's observed values from its normal value and the relative offset between each physiological index's observed values in two adjacent time steps. Finally, an adaptive fusion module is introduced to effectively integrate the above features to obtain the personalized patient's representations for clinical risk prediction. RESULTS: We conduct an in-hospital mortality prediction task on two public real-world datasets. PARSE achieves the highest F1 scores of 48.1% and 40.3%, outperforming the state-of-the-art methods with a boost of 2.4% and 6.2% on two datasets respectively. Furthermore, the results of ablation experiments demonstrate that the two abnormal offsets and the proposed adaptive fusion method are contributing. CONCLUSIONS: PARSE can better extract the risk-related information from the EHRs data and improve the personalization of the patients' representations. Each part of PARSE improves the final prediction performance independently.

The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.

Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.

SPBERE: Boosting span-based pipeline biomedical entity and relation extraction via entity information.

Triplet extraction is one of the fundamental tasks in biomedical text mining. Compared with traditional pipeline approaches, joint methods can alleviate the error propagation problem from entity recognition to relation classification. However, existing methods face challenges in detecting overlapping entities and overlapping relations, which are ubiquitous in biomedical texts. In this work, we propose a novel pipeline method of end-to-end biomedical triplet extraction. In particular, a span-based detection strategy is used to detect the overlapping triplets by enumerating possible candidate spans and entity pairs. The strategy is further used to capture different contextualized representations via an entity model and a relation model, respectively. Furthermore, to enhance interrelation between spans, entity information from the output of the entity model is used to construct the input for the relation model without utilizing any external knowledge. Our approach is evaluated on the drug-drug interaction (DDI) and chemical-protein interaction (CHEMPROT) datasets, exhibiting improvement of the absolute F1-score in relation extraction by 3.5%-3.7% compared prior work. The experimental results highlight the importance of overlapping triplet detection using the span-based approach, acquisition of various contextualized representations via different in-domain pre-trained language models, and early fusion of entity information in the relation model.

NADPH-dependent ROS accumulation contributes to the impaired osteogenic differentiation of periodontal ligament stem cells under high glucose conditions.

Diabetes mellitus is an established risk factor for periodontal disease that can aggravate the severity of periodontal inflammation and accelerate periodontal destruction. The chronic high glucose condition is a hallmark of diabetes-related pathogenesis, and has been demonstrated to impair the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), leading to delayed recovery of periodontal defects in diabetic patients. Reactive oxygen species (ROS) are small molecules that can influence cell fate determination and the direction of cell differentiation. Although excessive accumulation of ROS has been found to be associated with high glucose-induced cell damage, the underlying mechanisms remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) is an important electron donor and functions as a critical ROS scavenger in antioxidant systems. It has been identified as a key mediator of various biological processes, including energy metabolism and cell differentiation. However, whether NADPH is involved in the dysregulation of ROS and further compromise of PDLSC osteogenic differentiation under high glucose conditions is still not known. In the present study, we found that PDLSCs incubated under high glucose conditions showed impaired osteogenic differentiation, excessive ROS accumulation and increased NADPH production. Furthermore, after inhibiting the synthesis of NADPH, the osteogenic differentiation of PDLSCs was significantly enhanced, accompanied by reduced cellular ROS accumulation. Our findings demonstrated the crucial role of NADPH in regulating cellular osteogenic differentiation under high glucose conditions and suggested a new target for rescuing high glucose-induced cell dysfunction and promoting tissue regeneration in the future.

Comparative transcriptomic analysis reveals the underlying molecular mechanism in high-fat diet-induced islet dysfunction.

Obesity, characterized by accumulation of adipose, is usually accompanied by hyperlipidemia and abnormal glucose metabolism, which destroys the function and structure of islet ß cells. However, the exact mechanism of islet deterioration caused by obesity has not yet been fully elucidated. Here, we fed C57BL/6 mice with a high-fat diet (HFD) for 2 (2M group) and 6 months (6M group) to construct obesity mouse models. Then, RNA-based sequencing was used to identify the molecular mechanisms in HFD-induced islet dysfunction. Compared with the control diet, a total of 262 and 428 differentially expressed genes (DEGs) were identified from islets of the 2M and 6M groups, respectively. GO and KEGG enrichment analysis revealed that the DEGs up-regulated in both the 2M and 6M groups are mainly enriched in response to endoplasmic reticulum stress and the pancreatic secretion pathway. DEGs down-regulated in both the 2M and 6M groups are mainly enriched in the neuronal cell body and protein digestion and absorption pathway. Notably, along with the HFD feeding, mRNA expression of islet cell markers was significantly down-regulated, such as Ins1, Pdx1, MafA (ß cell), Gcg, Arx (α cell), Sst (δcell), and Ppy (PP cell). In contrast, mRNA expression of acinar cell markers was remarkably up-regulated, such as Amy1, Prss2, and Pnlip. Besides, a large number of collagen genes were down-regulated, such as Col1a1, Col6a6, and Col9a2. Overall, our study provides a full-scale DEG map regarding HFD-induced islet dysfunction, which was helpful to understand the underlying molecular mechanism of islet deterioration further.