Folate-PEG-PROTAC Micelles for Enhancing Tumor-Specific Targeting Proteolysis In Vivo.

Proteolysis targeting chimeras (PROTACs) technology is rapidly developed as a novel and selective medicinal strategy for the degradation of cellular proteins in cancer therapy. However, the applications of PROTACs as heterobifunctional molecules are largely limited by high molecular weight, low bioavailability, poor permeability, insufficient targeting, and low efficacy in vivo. Herein, self-assembling micelles of FA-PEG-PROTAC are designed for cancer cell selective targeting and reductive-response proteolysis in tumor-bearing mice. FA-PEG-PROTAC is prepared by conjugating folic acid (FA)-PEG with EGFR-targeting PROTAC via a disulfide bond. The FA-PEG-PROTAC micelles, formed by self-assembling, are demonstrated to significantly improve tumor targeting efficacy and exhibit excellent anti-tumor efficacy in the mouse xenograft model compared to the traditional PROTACs. The strategy of applying self-assembled FA-PEG-PROTAC micelles in tumor therapy can not only improve targeted proteolysis efficiency but also broaden applications in the development of PROTAC-based drugs.

The combined application of ear acupuncture in the treatment of allergic rhinitis: A meta-analysis.

Objective: Meta-analysis was used to evaluate the clinical efficacy of auricular acupressure in the treatment of allergic rhinitis. Methods: Randomised controlled trials (RCTS) on the treatment of allergic rhinitis with ear acupuncture were searched by computer in PubMed, Cochrane Library, Embase、Web of Science、China National Knowledge Infrastructure (CNKI), Wanfang Database (Wanfang), VIP database, and China Biomedical Literature Service System (CBM). The search time was from the establishment of the database to September 18, 2022. Meta-analysis was performed using RevMan 5.4 software. Results: A total of 15 papers with 1002 patients were included in the final study. ①Clinical efficiency: The clinical efficiency of ear acupuncture combined with control group was higher than that of control group, and the difference was statistically significant (P < 0.00001); ② Nasal symptom score: the effect of ear acupuncture combined with control group on allergic rhinitis on nasal symptoms was more obvious than that of control group, and the difference was statistically significant (P = 0.004); ③ Nasal itching symptom score: the efficacy of ear acupuncture combined with control group on allergic rhinitis on nasal itching symptom was significantly higher than that of control group, and the difference was statistically significant (P = 0.01). ④Sneeze symptom score: the effect of ear acupuncture combined with control group on allergic rhinitis on nasal itching symptom was more effective than that of control group, and the difference was statistically significant (P < 0.00001); ⑤Score of runny nose symptom: the effect of ear acupuncture combined with control group on allergic rhinitis on runny nose symptom was more obvious than that of control group, the difference was statistically significant (P = 0.004); ⑥Nasal congestion symptom scores: The effect of ear acupuncture combined with control group on allergic rhinitis on nasal congestion symptom was more obvious than that of control group, and the difference was statistically significant (P = 0.003). Conclusion: Ear acupuncture as an adjunctive therapy of allergic rhinitis can achieve better clinical efficacy.

Recent advances in understanding the regulatory mechanism of plasma membrane H+-ATPase through the brassinosteroid signaling pathway.

The polyhydroxylated steroid phytohormone brassinosteroids (BRs) control many aspects of plant growth, development and responses to environmental changes. Plasma membrane (PM) H+-ATPase, the well-known PM proton pump, is a central regulator in plant physiology, which mediates not only plant growth and development, but also adaptation to stresses. Recent studies highlight that PM H+-ATPase is at least partly regulated via the BR signaling. Firstly, the BR cell surface receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and multiple key components of BR signaling directly or indirectly influence PM H+-ATPase activity. Secondly, the SMALL AUXIN UP RNA (SAUR) gene family physically interacts with BRI1 to enhance organ development of Arabidopsis by activating PM H+-ATPase. Thirdly, RNA-sequencing (RNA-seq) assays showed that the expression of some SAUR genes is upregulated under the light or sucrose conditions, which is related to the phosphorylation state of the penultimate residue of PM H+-ATPase in a time-course manner. In this review, we describe the structural and functional features of PM H+-ATPase, and summarize recent progress toward understanding the regulatory mechanism of PM H+-ATPase by BRs, and briefly introduce how PM H+-ATPase activity is modulated by its own biterminal regions and the post-translational modifications.

PHLDA1 is a P53 target gene involved in P53-mediated cell apoptosis.

Pleckstrin homeolike domain, family A, member 1 (PHLDA1) is a multifunctional protein that plays diverse roles in A variety of biological processes, including cell death, and hence its altered expression has been found in different types of cancer. Although studies have shown a regulatory relationship between p53 and PHLDA1, the molecular mechanism is still unclear. Especially, the role of PHLDA1 in the process of apoptosis is still controversial. In this study, we found that the expression of PHLDA1 in human cervical cancer cell lines was correlated with the up-expression of p53 after treatment with apoptosis-inducing factors. Subsequently, the binding site and the binding effect of p53 on the promoter region of PHLDA1 were verified by our bioinformatics data analysis and luciferase reporter assay. Indeed, we used CRISPR-Cas9 to knockout the p53 gene in HeLa cells and further confirmed that p53 can bind to the promoter region of PHLDA1 gene, and then directly regulate the expression of PHLDA1 by recruiting P300 and CBP to change the acetylation and methylation levels in the promoter region. Finally, a series of gain-of-function experiments further confirmed that p53 re-expression in HeLap53-/- cell can up-regulate the reduction of PHLDA1 caused by p53 knockout, and affect cell apoptosis and proliferation. Our study is the first to explore the regulatory mechanism of p53 on PHLDA1 by using the p53 gene knockout cell model, which further proves that PHLDA1 is a target-gene in p53-mediated apoptosis, and reveals the important role of PHLDA1 in cell fate determination.

HIF-1α regulates the cell viability in radioiodine-resistant papillary thyroid carcinoma cells induced by hypoxia through PKM2/NF-κB signaling pathway.

The curative treatment options for papillary thyroid cancer (PTC) encompass surgical intervention, radioactive iodine administration, and chemotherapy. However, the challenges of radioiodine (RAI) resistance, metastasis, and chemotherapy resistance remain inadequately addressed. The objective of this study was to investigate the protective role of hypoxia-inducible factor-1α (HIF-1α) in 131 I-resistant cells and a xenograft model under hypoxic conditions, as well as to explore potential mechanisms. The effects of HIF-1α on 131 I-resistant BCPAP and TPC-1 cells, as well as the xenograft model, were assessed in this study. Cell viability, migration, invasion, and apoptosis rates were measured using Cell Counting Kit-8, wound-healing, Transwell, and flow cytometry assays. Additionally, the expressions of Ki67, matrix metalloproteinase-9 (MMP-9), and pyruvate kinase M2 (PKM2) were examined using immunofluorescence or immunohistochemistry assays. Sodium iodide symporter and PKM2/NF-κBp65 relative protein levels were detected by western blot analysis. The findings of our study indicate that siHIF-1α effectively inhibits cell proliferation, cell migration, and invasion in 131 I-resistant cells under hypoxic conditions. Additionally, the treatment of siHIF-1α leads to alterations in the relative protein levels of Ki67, MMP-9, PKM2, and PKM2/NF-κBp65, both in vivo and in vitro. Notably, the effects of siHIF-1α are modified when DASA-58, an activator of PKM2, is administered. These results collectively demonstrate that siHIF-1α reduces cell viability in PTC cells and rat models, while also mediating the nuclear factor-κB (NF-κB)/PKM2 signaling pathway. Our findings provide a new rationale for further academic and clinical research on RAI-resistant PTC.

Prolonged administration of total glucosides of paeony improves intestinal immune imbalance and epithelial barrier damage in collagen-induced arthritis rats based on metabolomics-network pharmacology integrated analysis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and joint damage with complex pathological mechanisms. In recent years, many studies have shown that the dysregulation of intestinal mucosal immunity and the damage of the epithelial barrier are closely related to the occurrence of RA. Total glucosides of paeony (TGP) have been used clinically for the treatment of RA in China for decades, while the pharmacological mechanism is still uncertain. The purpose of this study was to investigate the regulatory effect and mechanism of TGP on intestinal immunity and epithelial barrier in RA model rats. The results showed that TGP alleviated immune hyperfunction by regulating the ratio of CD3+, CD4+ and CD8+ in different lymphocyte synthesis sites of the small intestine, including Peyer's patches (PPs), intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs). Specially, TGP first exhibited immunomodulatory effects on sites close to the intestinal lumen (IELs and LPLs), and then on PPs far away from the intestinal lumen as the administration time prolonged. Meanwhile, TGP restores the intestinal epithelial barrier by upregulating the ratio of villi height (V)/crypt depth (C) and expression of tight junction proteins (ZO-1, occludin). Finally, the integrated analysis of metabolomics-network pharmacology was also used to explore the possible regulation mechanism of TGP on the intestinal tract. Metabolomics analysis revealed that TGP reversed the intestinal metabolic profile disturbance in CIA rats, and identified 32 biomarkers and 163 corresponding targets; network pharmacology analysis identified 111 potential targets for TGP to treat RA. By intersecting the results of the two, three key targets such as ADA, PNP and TYR were determined. Pharmacological verification experiments showed that the levels of ADA and PNP in the small intestine of CIA rats were significantly increased, while TGP significantly decreased their ADA and PNP levels. In conclusion, purine metabolism may play an important role in the process of TGP improving RA-induced intestinal immune imbalance and impaired epithelial barrier.

Vimentin regulates nuclear segmentation in neutrophils.

Granulocytes are indispensable for various immune responses. Unlike other cell types in the body, the nuclei of granulocytes, particularly neutrophils, are heavily segmented into multiple lobes. Although this distinct morphological feature has long been observed, the underlying mechanism remains incompletely characterized. In this study, we utilize cryo-electron tomography to examine the nuclei of mouse neutrophils, revealing the cytoplasmic enrichment of intermediate filaments on the concave regions of the nuclear envelope. Aided by expression profiling and immuno-electron microscopy, we then elucidate that the intermediate-filament protein vimentin is responsible for such perinuclear structures. Of importance, exogenously expressed vimentin in nonimmune cells is sufficient to form cytoplasmic filaments wrapping on the concave nuclear surface. Moreover, genetic deletion of the protein causes a significant reduction of the number of nuclear lobes in neutrophils and eosinophils, mimicking the hematological condition of the Pelger-Huët anomaly. These results have uncovered a new component establishing the nuclear segmentation of granulocytes.

Heterologous expression of a deacetylase and its application in L-glufosinate preparation.

With potent herbicidal activity, biocatalysis synthesis of L-glufosinate has drawn attention. In present research, NAP-Das2.3, a deacetylase capable of stereoselectively resolving N-acetyl-L-glufosinate to L-glufosinate mined from Arenimonas malthae, was heterologously expressed and characterized. In Escherichia coli, NAP-Das2.3 activity only reached 0.25 U/L due to the formation of inclusive bodies. Efficient soluble expression of NAP-Das2.3 was achieved in Pichia pastoris. In shake flask and 5 L bioreactor fermentation, NAP-Das2.3 activity by recombinant P. pastoris reached 107.39 U/L and 1287.52 U/L, respectively. The optimum temperature and pH for N-acetyl-glufosinate hydrolysis by NAP-Das2.3 were 45 °C and pH 8.0, respectively. The Km and Vmax of NAP-Das2.3 towards N-acetyl-glufosinate were 25.32 mM and 19.23 µmol mg-1 min-1, respectively. Within 90 min, 92.71% of L-enantiomer in 100 mM racemic N-acetyl-glufosinate was converted by NAP-Das2.3. L-glufosinate with high optical purity (e.e.P above 99.9%) was obtained. Therefore, the recombinant NAP-Das2.3 might be an alternative for L-glufosinate biosynthesis.

[Microbial production of S-adenosyl-l-methionine: a review].

S-adenosyl-l-methionine (SAM) is ubiquitous in living organisms and plays important roles in transmethylation, transsulfuration and transamination in organisms. Due to its important physiological functions, production of SAM has attracted increasing attentions. Currently, researches on SAM production mainly focus on microbial fermentation, which is more cost-effective than that of the chemical synthesis and the enzyme catalysis, thus easier to achieve commercial production. With the rapid growth in SAM demand, interests in improving SAM production by developing SAM hyper-producing microorganisms aroused. The main strategies for improving SAM productivity of microorganisms include conventional breeding and metabolic engineering. This review summarizes the recent research progress in improving microbial SAM productivity to facilitate further improving SAM productivity. The bottlenecks in SAM biosynthesis and the solutions were also addressed.

Biomedical named entity recognition based on fusion multi-features embedding.

BACKGROUND: With the exponential increase in the volume of biomedical literature, text mining tasks are becoming increasingly important in the medical domain. Named entities are the primary identification tasks in text mining, prerequisites and critical parts for building medical domain knowledge graphs, medical question and answer systems, medical text classification. OBJECTIVE: The study goal is to recognize biomedical entities effectively by fusing multi-feature embedding. Multiple features provide more comprehensive information so that better predictions can be obtained. METHODS: Firstly, three different kinds of features are generated, including deep contextual word-level features, local char-level features, and part-of-speech features at the word representation layer. The word representation vectors are inputs into BiLSTM as features to obtain the dependency information. Finally, the CRF algorithm is used to learn the features of the state sequences to obtain the global optimal tagging sequences. RESULTS: The experimental results showed that the model outperformed other state-of-the-art methods for all-around performance in six datasets among eight of four biomedical entity types. CONCLUSION: The proposed method has a positive effect on the prediction results. It comprehensively considers the relevant factors of named entity recognition because the semantic information is enhanced by fusing multi-features embedding.

In situ snapshots along a mammalian selective autophagy pathway.

Selective macroautophagy (hereafter referred to as autophagy) describes a process in which cytosolic material is engulfed in a double membrane organelle called an autophagosome. Autophagosomes are carriers responsible for delivering their content to a lytic compartment for destruction. The cargo can be of diverse origin, ranging from macromolecular complexes to protein aggregates, organelles, and even invading pathogens. Each cargo is unique in composition and size, presenting different challenges to autophagosome biogenesis. Among the largest cargoes targeted by the autophagy machinery are intracellular bacteria, which can, in the case of Salmonella, range from 2 to 5 µm in length and 0.5 to 1.5 µm in width. How phagophores form and expand on such a large cargo remains mechanistically unclear. Here, we used HeLa cells infected with an auxotrophic Salmonella to study the process of phagophore biogenesis using in situ correlative cryo-ET. We show that host cells generate multiple phagophores at the site of damaged Salmonella-containing vacuoles (SCVs). The observed double membrane structures range from disk-shaped to expanded cup-shaped phagophores, which have a thin intermembrane lumen with a dilating rim region and expand using the SCV, the outer membrane of Salmonella, or existing phagophores as templates. Phagophore rims establish different forms of contact with the endoplasmic reticulum (ER) via structurally distinct molecular entities for membrane formation and expansion. Early omegasomes correlated with the marker Double-FYVE domain-Containing Protein 1 (DFCP1) are observed in close association with the ER without apparent membrane continuity. Our study provides insights into the formation of phagophores around one of the largest selective cargoes.

The Microbiota-Dependent Treatment of Wuzhuyu Decoction for Chronic Migraine Model Rat Associated with Anxiety-Depression Like Behavior.

We previously found that Wuzhuyu Decoction (WZYD) could affect central and peripheral 5-HT to relieve hyperalgesia in chronic migraine (CM) model rats, possibly related to gut microbiota. However, the exact role of gut microbiota has not been elucidated. Accumulating evidence points to the possibility of treating central nervous system disease via the gut-brain axis. In our study, the inflammatory soup-induced CM model rats presented depression- and anxiety-like behaviors which both related to insufficient 5-HT. It was found that antibiotic administration caused community dysbiosis, and proteobacteria became the main dominant bacteria. The bacteria related to short-chain fatty acids and 5-HT generation were reduced, resulting in reduced levels of 5-HT, tryptophan hydroxylase, and secondary bile acids. Functional prediction-revealed sphingolipid signaling pathway in CM rats was significantly decreased and elevated after WZYD treatment. The effect of WZYD could be weakened by antibiotics. The CM rats exhibited anxiety- and depression-like behavior with 5-HT and number of neurons decreased in the CA1 and CA2 regions of hippocampal. The treatment of WZYD could recover to varying degrees. Antibiotics combined with WZYD attenuate the effect of WZYD on increasing the 5-HT content and related protein expression in the brain stem, plasma and colon, reducing CGRP, c-Fos, and inflammatory factors. And antibiotics also led to colon length increasing and stool retention, so that the antimigraine effect was weakened compared with WZYD. This experiment revealed that gut microbiota mediated WZYD treatment of CM rats with anxiety-depression like behavior.

Effects of chronic heat stress on the immunophenotyping of lymphocytes in immune organs of growing pigs.

This study aimed to investigate the effects of chronic heat stress on the immunophenotyping of lymphocytes in immune organs of growing pigs. A single-factor randomized block design was used, and 15 healthy growing large white barrows (5 litters, 3 pigs/litter) with similar body weight (40.8 kg) were assigned into 3 groups (5 pigs in each group). Groups were: control group (Con, in 23 °C environmental control chamber, fed ad libitum), heat stress group (HS, in 33 °C environmental control chamber, fed ad libitum), and pair-fed group (PF, in 23 °C environmental control chamber, fed diets according to the feed intake of HS group). After a 7-d adaption, the experiment lasted for 21 d. The results showed as follows: (1) activated T cells in the thymus of HS pigs were higher than those in PF pigs (P < 0.05). Monocytes and dendritic cells in the thymus of HS pigs were significantly higher than that in Con and PF pigs (P < 0.05), while the proportions of these 2 lymphocytes in the thymus of Con pigs did not differ from PF pigs (P > 0.05). Compared with Con pigs, the proportion of CD4+ (P < 0.05) and CD8+ T cells (P < 0.10) in the thymus was increased in HS pigs, while the proportion of CD4+ and CD8+ T cells in PF pigs did not differ from Con pigs (P > 0.05). (2) Compared with Con pigs, significantly decreased T cells, increased B cells and monocytes were found in the spleen of pigs exposed to heat stress (P < 0.05); the proportions of these 3 types of lymphocytes were not significantly different between Con and PF pigs (P > 0.05). The proportions of CD4+ T cells and Treg cells in the spleen of pigs exposed to heat stress tended to be lower than those in the Con pigs (P < 0.10). (3) The proportion of lymphocytes in the tonsils of pigs exposed to heat stress did not differ from Con pigs (P > 0.05); compared with PF pigs, the proportion of Treg cells was significantly decreased in HS pigs (P < 0.05). In conclusion, chronic heat stress stimulates the development and maturation of T cells in the pig thymus toward CD4+ and CD8+ T cells and increases the proportion of monocytes and dendritic cells; under the condition of chronic heat stress, the immune response process in the spleen of pigs is enhanced, but chronic heat stress impairs the survival of CD4+ T cells in the spleen.

Chronic heat stress (HS) has become a common hazard to livestock and poultry as global warming intensifies and breeding densities increase, which undoubtedly causes enormous economic losses to animal husbandry annually. Furthermore, it could also negatively impact the immune function of poultry and vaccines, resulting in various animal diseases. Until now, very few studies have focused on how HS affects the immune system of growing pigs, especially the immunophenotyping of lymphocytes in their immune organs (thymus, spleen and tonsils). In this study, the spleen and thymus are more severely affected by chronic HS than tonsils in growing pigs. Chronic HS stimulates the development and maturation of CD4+ and CD8+ T lymphocytes in the thymus. Under chronic HS, the immune response process in the spleen is enhanced, that is, the proportion of monocytes and B lymphocytes supporting immune responses increased, while the proportion of Treg cells decreased; yet long-term HS damaged the survival of CD4+ T lymphocytes in spleen.

An Ensemble Semantic Textual Similarity Measure Based on Multiple Evidences for Biomedical Documents.

With the increasing volume of the published biomedical literature, the fast and effective retrieval of the literature on the sequence, structure, and function of biological entities is an essential task for the rapid development of biology and medicine. To capture the semantic information in biomedical literature more effectively when biomedical documents are clustered, we propose a new multi-evidence-based semantic text similarity calculation method. Two semantic similarities and one content similarity are used, in which two semantic similarities include MeSH-based semantic similarity and word embedding-based semantic similarity. To fuse three different similarities more effectively, after, respectively, calculating two semantic and one content similarities between biomedical documents, feedforward neural network is applied to integrate the two semantic similarities. Finally, weighted linear combination method is used to integrate the semantic and content similarities. To evaluate the effectiveness, the proposed method is compared with the existing basic methods, and the proposed method outperforms the existing related methods. Based on the proven results of this study, this method can be used not only in actual biological or medical experiments such as protein sequence or function analysis but also in biological and medical research fields, which will help to provide, use, and understand thematically consistent documents.

Improvement of S-adenosyl-L-methionine production in Saccharomyces cerevisiae by atmospheric and room temperature plasma-ultraviolet compound mutagenesis and droplet microfluidic adaptive evolution.

To improve S-Adenosyl-L-methionine (a compound with important physiological functions, SAM) production, atmospheric and room temperature plasma and ultraviolet-LiCl mutagenesis were carried out with Saccharomyces cerevisiae strain ZY 1-5. The mutants were screened with ethionine, L-methionine, nystatin and cordycepin as screening agents. Adaptive evolution of a positive mutant UV6-69 was further performed by droplet microfluidics cultivation with ethionine as screening pressure. After adaptation, mutant T11-1 was obtained. Its SAM titer in shake flask fermentation reached 1.31 g/L, which was 191% higher than that of strain ZY 1-5. Under optimal conditions, the SAM titer and biomass of mutant T11-1 in 5 L bioreactor reached 10.72 g/L and 105.9 g dcw/L (142.86% and 34.22% higher than those of strain ZY 1-5), respectively. Comparative transcriptome analysis between strain ZY 1-5 and mutant T11-1 revealed the enhancements in TCA cycle and gluconeogenesis/glycolysis pathways as well as the inhibitions in serine and ergosterol synthesis of mutant T11-1. The elevated SAM synthesis of mutant T11-1 may attribute to the above changes. Taken together, this study is helpful for industrial production of SAM.

In situ structure of intestinal apical surface reveals nanobristles on microvilli.

Microvilli are actin-bundle-supported membrane protrusions essential for absorption, secretion, and sensation. Microvilli defects cause gastrointestinal disorders; however, mechanisms controlling microvilli formation and organization remain unresolved. Here, we study microvilli by vitrifying the Caenorhabditis elegans larvae and mouse intestinal tissues with high-pressure freezing, thinning them with cryo-focused ion-beam milling, followed by cryo-electron tomography and subtomogram averaging. We find that many radial nanometer bristles referred to as nanobristles project from the lateral surface of nematode and mouse microvilli. The C. elegans nanobristles are 37.5 nm long and 4.5 nm wide. Nanobristle formation requires a protocadherin family protein, CDH-8, in C. elegans. The loss of nanobristles in cdh-8 mutants slows down animal growth and ectopically increases the number of Y-shaped microvilli, the putative intermediate structures if microvilli split from tips. Our results reveal a potential role of nanobristles in separating microvilli and suggest that microvilli division may help generate nascent microvilli with uniformity.

Discovering Thematically Coherent Biomedical Documents Using Contextualized Bidirectional Encoder Representations from Transformers-Based Clustering.

The increasing expansion of biomedical documents has increased the number of natural language textual resources related to the current applications. Meanwhile, there has been a great interest in extracting useful information from meaningful coherent groupings of textual content documents in the last decade. However, it is challenging to discover informative representations and define relevant articles from the rapidly growing biomedical literature due to the unsupervised nature of document clustering. Moreover, empirical investigations demonstrated that traditional text clustering methods produce unsatisfactory results in terms of non-contextualized vector space representations because that neglect the semantic relationship between biomedical texts. Recently, pre-trained language models have emerged as successful in a wide range of natural language processing applications. In this paper, we propose the Gaussian Mixture Model-based efficient clustering framework that incorporates substantially pre-trained (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining) BioBERT domain-specific language representations to enhance the clustering accuracy. Our proposed framework consists of main three phases. First, classic text pre-processing techniques are used biomedical document data, which crawled from the PubMed repository. Second, representative vectors are extracted from a pre-trained BioBERT language model for biomedical text mining. Third, we employ the Gaussian Mixture Model as a clustering algorithm, which allows us to assign labels for each biomedical document. In order to prove the efficiency of our proposed model, we conducted a comprehensive experimental analysis utilizing several clustering algorithms while combining diverse embedding techniques. Consequently, the experimental results show that the proposed model outperforms the benchmark models by reaching performance measures of Fowlkes mallows score, silhouette coefficient, adjusted rand index, Davies-Bouldin score of 0.7817, 0.3765, 0.4478, 1.6849, respectively. We expect the outcomes of this study will assist domain specialists in comprehending thematically cohesive documents in the healthcare field.

Drug-Drug Interactions Prediction Using Fingerprint Only.

Combination drug therapy is an efficient way to treat complicated diseases. Drug-drug interaction (DDI) is an important research topic in this therapy as patient safety is a problem when two or more drugs are taken at the same time. Traditionally, in vitro experiments and clinical trials are common ways to determine DDIs. However, these methods cannot meet the requirements of large-scale tests. It is an alternative way to develop computational methods for predicting DDIs. Although several previous methods have been proposed, they always need several types of drug information, limiting their applications. In this study, we proposed a simple computational method to predict DDIs. In this method, drugs were represented by their fingerprint features, which are most widely used in investigating drug-related problems. These features were refined by three models, including addition, subtraction, and Hadamard models, to generate the representation of DDIs. The powerful classification algorithm, random forest, was picked up to build the classifier. The results of two types of tenfold cross-validation on the classifier indicated good performance for discovering novel DDIs among known drugs and acceptable performance for identifying DDIs between known drugs and unknown drugs or among unknown drugs. Although the classifier adopted a sample scheme to represent DDIs, it was still superior to other methods, which adopted features generated by some advanced computer algorithms. Furthermore, a user-friendly web-server, named DDIPF (http://106.14.164.77:5004/DDIPF/), was developed to implement the classifier.

InfersentPPI: Prediction of Protein-Protein Interaction Using Protein Sentence Embedding With Gene Ontology Information.

Protein-protein interaction (PPI) prediction is meaningful work for deciphering cellular behaviors. Although many kinds of data and machine learning algorithms have been used in PPI prediction, the performance still needs to be improved. In this paper, we propose InferSentPPI, a sentence embedding based text mining method with gene ontology (GO) information for PPI prediction. First, we design a novel weighting GO term-based protein sentence representation method to generate protein sentences including multi-semantic information in the preprocessing. Gene ontology annotation (GOA) provides the reliability of relationships between proteins and GO terms for PPI prediction. Thus, GO term-based protein sentence can help to improve the prediction performance. Then we also propose an InferSent_PN algorithm based on the protein sentences and InferSent algorithm to extract relations between proteins. In the experiments, we evaluate the effectiveness of InferSentPPI with several benchmarking datasets. The result shows our proposed method has performed better than the state-of-the-art methods for a large PPI dataset.