Machine learning models can automatically discover biomedical research trends and promote the dissemination of information and knowledge. Text feature representation is a critical and challenging ...task in natural language processing. Most methods of text feature representation are based on word representation. A good representation can capture semantic and structural information. In this paper, two fusion algorithms are proposed, namely, the Tr-W2v and Ti-W2v algorithms. They are based on the classical text feature representation model and consider the importance of words. The results show that the effectiveness of the two fusion text representation models is better than the classical text representation model, and the results based on the Tr-W2v algorithm are the best. Furthermore, based on the Tr-W2v algorithm, trend analyses of cancer research are conducted, including correlation analysis, keyword trend analysis, and improved keyword trend analysis. The discovery of the research trends and the evolution of hotspots for cancers can help doctors and biological researchers collect information and provide guidance for further research.
Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery ...vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXO
EAA-PMO
). EXO
EAA-PMO
elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXO
EAA-PMO
elicited therapeutic levels of dystrophin restoration and functional improvements in
mdx
mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes.
Synopsis
This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer—EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading.
EAA showed high binding affinity to exosomes irrespective of origin.
EAA enabled loading of different nucleic acid drugs on exosomes, with thrombin DNA aptamer inhibitor NU172 loaded on exosomes extended the serum stability.
Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomers (PMOs) were efficiently loaded on exosomes via EAA to form EXO
EAA-PMO
and systemic administration EXO
EAA-PMO
at low doses improved muscle function and pathologies in dystrophic mice.
This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer - EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading.
HCC is the most common fatal malignancy. Although surgical resection is the primary treatment strategy, most patients are not eligible for resection due to tumor heterogeneity, underlying liver ...disease, or comorbidities. Therefore, this study explores the possibility of multi-molecular targeted drug delivery in treating HCC. In this study, we constructed the recombinant adenovirus co-expressing apoptin and melittin (MEL) genes. The inhibitory effect of the recombinant adenovirus on hepatocellular carcinoma cells was detected through experiments on cell apoptosis, migration, invasion, and other factors. The tumor inhibitory effect in vivo was assessed using subcutaneous HCC mice. Results showed that recombinant adenovirus co-expressing anti-tumor genes TAT and apoptin, RGD and MEL can significantly inhibit the proliferation, migration, and invasion of HCC cells by inducing an increase in reactive oxygen species (ROS) levels, upregulation of apoptotic proteins such as Bax, cleaved caspase-3, and cleaved caspase-9, and downregulation of the anti-apoptotic protein Bcl-2. In subcutaneous HCC mice, recombinant adenovirus induced significant apoptosis in tumor, and inhibited tumor growth. In conclusion, recombinant adenovirus co-expressing apoptin and MEL can inhibit the growth and proliferation of tumor cells both in vivo and in vitro.HCC is the most common fatal malignancy. Although surgical resection is the primary treatment strategy, most patients are not eligible for resection due to tumor heterogeneity, underlying liver disease, or comorbidities. Therefore, this study explores the possibility of multi-molecular targeted drug delivery in treating HCC. In this study, we constructed the recombinant adenovirus co-expressing apoptin and melittin (MEL) genes. The inhibitory effect of the recombinant adenovirus on hepatocellular carcinoma cells was detected through experiments on cell apoptosis, migration, invasion, and other factors. The tumor inhibitory effect in vivo was assessed using subcutaneous HCC mice. Results showed that recombinant adenovirus co-expressing anti-tumor genes TAT and apoptin, RGD and MEL can significantly inhibit the proliferation, migration, and invasion of HCC cells by inducing an increase in reactive oxygen species (ROS) levels, upregulation of apoptotic proteins such as Bax, cleaved caspase-3, and cleaved caspase-9, and downregulation of the anti-apoptotic protein Bcl-2. In subcutaneous HCC mice, recombinant adenovirus induced significant apoptosis in tumor, and inhibited tumor growth. In conclusion, recombinant adenovirus co-expressing apoptin and MEL can inhibit the growth and proliferation of tumor cells both in vivo and in vitro.
Polarized Rac1 signaling is a hallmark of many cellular functions, including cell adhesion, motility, and cell division. The two steps of Rac1 activation are its translocation to the plasma membrane ...and the exchange of nucleotide from GDP to GTP. It is, however, unclear whether these two processes are regulated independent of each other and what their respective roles are in polarization of Rac1 signaling. We designed a single-particle tracking (SPT) method to quantitatively analyze the kinetics of Rac1 membrane translocation in living cells. We found that the rate of Rac1 translocation was significantly elevated in protrusions during cell spreading on collagen. Furthermore, combining FRET sensor imaging with SPT measurements in the same cell, the recruitment of Rac1 was found to be polarized to an extent similar to that of the nucleotide exchange process. Statistical analysis of single-molecule trajectories and optogenetic manipulation of membrane lipids revealed that Rac1 membrane translocation precedes nucleotide exchange, and is governed primarily by interactions with phospholipids, particularly PI(3,4,5)P ₃, instead of protein factors. Overall, the study highlights the significance of membrane translocation in spatial Rac1 signaling, which is in addition to the traditional view focusing primarily on GEF distribution and exchange reaction.
Significance Rac1 activation involves two steps: translocation to plasma membrane and nucleotide exchange. Most previous studies focused on the nucleotide exchange cycle. Here we sought to understand membrane translocation dynamics by developing a single-particle tracking-based method. The labeled Rac1 molecules were further adapted for simultaneous FRET sensing of Rac1 nucleotide state, enabling a simultaneous comparison between Rac1 translocation dynamics and its nucleotide exchange dynamics. Elevated membrane recruitment can contribute significantly to polarized Rac1-signaling. This finding draws attention to the importance of spatial regulation of the Rac1 translocation process in the regulation of RhoGTPase signaling. Rac1 recruitment to membrane precedes its interaction with protein factors (e.g., GEFs) and is governed by phospholipid distributions. This finding resolves a long-standing question of the mechanism of Rac1 activation.
Volatile organic compounds (VOCs) are critical precursors of photochemical smog. Quantitatively evaluating the VOC sources and their contributions to ozone formation provides valuable information for ...photochemical pollution abatement. However, due to the fast oxidization of VOCs during transport in the atmosphere, source apportionment via receptor models using measured VOC data inevitably has a systematic deviation. In this study, we conducted a field measurement of VOCs at a suburban site in Beijing and evaluated the influences of photochemical oxidization on VOC source contributions. The initial VOC concentration, defined as the sum of measured VOC concentration and their photochemical losses. The real-time photochemical age-based parameterization method and a sequential reaction model were applied to characterize the photochemical loss of VOCs. Also, the photochemical loss of VOCs was considered in the he positive matrix factorization (PMF) model. Photochemical losses, on average, accounted for 5.6% of total VOCs (TVOCs) and 59.2% of alkenes, indicating that the impact of photochemical reaction cannot be ignored. Alkanes were the most significant contributors to both measured and initial TVOCs, while the alkenes and oxygenated volatile organic compounds (OVOCs), especially ethylene and isoprene, contributed the most to ozone formation potential. By adopting the positive matrix factorization model, seven VOC sources were identified for both measured and initial TVOCs. Vehicular emissions, industrial sources, and biomass burning were the top three contributors to ambient TVOC. Photochemistry significantly influenced the results of source apportionment, e.g., the contribution of biogenic sources (+4.4%), industrial emissions (+2.5%) and solvent usage (+2.5%) based on initial VOCs were larger than that of measured VOCs, while the contribution of gasoline vehicular emissions (−9.9%) was lower than that of measured VOCs. Our results highlight the necessity of adequately considering the photochemical loss of VOCs for accurately apportioning the emission sources.
•Photochemical reaction significantly influenced the VOC concentration.•Photochemical loss accounted for 26.3% initial alkenes and 13.1% initial aromatics.•Vehicle and combustion emissions were the largest contributors to both measured and initial VOC concentration.•Biogenic sources, industrial emissions and solvent usage based on initial VOCs were larger than that of measured VOCs.
This letter presents a feature alignment method for domain adaptive Acoustic Scene Classification (ASC) across recording devices. First, we design a two-stream network, in which each stream processes ...two features, i.e. , Log-Mel spectrogram and delta-deltas, using two sub-networks. Second, we investigate different loss functions for feature alignment between the feature maps obtained by the source and target domains. Last, we present an alternate training strategy to deal with the data imbalance problem between paired and unpaired samples. The experimental results obtained on the DCASE benchmarks demonstrate the effectiveness and superiority of the proposed method. The source code of the proposed method is available at https://github.com/Jingqiao-Zhao/FAASC .
Volatile organic compounds (VOCs) play a crucial role as precursors in the formation of ozone (O3) and secondary PM2.5. It is well-established that some VOC species exhibit high photochemical ...reactivity, leading to deviations between measured and initial concentrations. Therefore, precise source apportionment must consider these photochemical reaction which called photochemical losses. The study was conducted in Langfang, which located in an important site for pollution transferring to Beijing, with August to October as the sampling period. The initial concentrations of the VOC species were estimated using a photochemical age-based parameterization method. The effects of photochemical losses on source apportionment were compared by the positive matrix factorization (PMF) results, based on observed and initial concentration data. The results showed that neglecting photochemical losses would result in an underestimation of VOCs concentration by 6.7% compared to the measured values obtained in this study. Furthermore, olefins and aromatic hydrocarbons were found to be the key components involved in photochemical reactions, with a photochemical loss rate of 28.3% and 23.7%, respectively. VOCs source apportionment revealed that the impact of photochemical loss on source apportionment was significant. Results indicated that biogenic sources (−6.8%) and solvent usage (−5.9%) made a higher contribution based on initial VOCs compared to measured VOCs, while gasoline vehicular emissions showed a lower contribution (+7.9%) than that observed from measured VOCs data. Analysis results also demonstrated that the combustion sources accounted for 14.2% based on measured concentrations and that accounted for 9.5% based on initial concentrations.
•Neglecting photochemical losses resulted in an underestimation of TVOCs by 6.7%.•The OFP increased by approximately 14.0% accounting for photochemical reactions.•Mobile vehicle emissions were identified as the primary source of VOCs in Langfang.
To analyze the change of CT texture features of esophageal squamous cell carcinoma (ESC) during RT delivery and to correlate these changes with the RT responses and survival.
A total of 61 ESC ...patients received radical RT were screened. Weekly CTs (4-6 sets for each patient) were acquired during RT. The tumors, normal esophageal mucosa tissue (NEC) of 5 cm and the spinal cord in the relevant area were delineated. CT texture features were extracted with a home-made tool. The changes of these features were analyzed by t-test. The correlations of the changes of features with RT responses and with patient survival were investigated by Pearson analysis.
The average changes were increased by 0.00072 ±0.00197 for coarseness, by 0.14 ±0.40 for entropy, and by 2.34 ±3.56 for strength. In addition, the average changes were reduced by 8.88 ±15.71cc for volume and by 0.07 ±0.11 for busyness. The changes of the coarseness, strength, STD and entropy in ESC were different for the good and poor response groups. The survival rate of the patients was significantly correlated with the change of coarseness and strength (P = 0.0027 and P = 0.0001).
During RT, changes of CT texture features of ESC, e.g., coarseness, strength, STD, entropy and volume are correlated with radiation response and survival rate. With more clinical data and robust research, CT features, e.g., coarseness and strength, can be selected as outstanding imaging biomarkers for prediction of RT prognosis of ESC.
This study aims to estimate the risk factors of gastrointestinal (GI) bleeding in patients with acute coronary syndrome (ACS) and to evaluate the optimal duration of dual antiplatelet therapy (DAPT).
...We enrolled 1266 patients with ACS in a telephone follow-up program to determine whether any of the patients were hospitalized for GI bleeding. We collected baseline data, laboratory tests, electrocardiograms, and echocardiography covering all ACS patients. Multivariable regression was performed to adjust for confounders and predictors of GI bleeding. At the same time, the optimal duration of DAPT for ACS patients was evaluated.
A total of 1061 ACS patients were included in the study. After 13-68 months, 48 patients (4.5%) were hospitalized for GI bleeding. The risk of GI bleeding was significantly increased in patients treated with DAPT for more than 18 months (hazard ratio 12.792, 5.607-29.185,
< 0.01). Receiver Operating Characteristic curve showed that the duration of DAPT using a cutoff of 14.5 months resulted in a sensitivity of 66.7% and a specificity of 77%.
In patients with ACS, DAPT time are the main risk factors of GI bleeding. The optimal duration of DAPT is 14.5 months.
The profiling of plasma cell-free DNA (cfDNA) is becoming a valuable tool rapidly for tumor diagnosis, monitoring and prognosis. Diverse plasma cfDNA technologies have been in routine or emerging ...use, including analyses of mutations, copy number alterations, gene fusions and DNA methylation. Recently, new technologies in cfDNA analysis have been developed in laboratories, and potentially reflect the status of epigenetic modification, the immune microenvironment and the microbiome in tumor tissues. In this review, the authors discuss the principles, methods and effects of the current cfDNA assays and provide an overview of studies that may inform clinical applications in the near future.
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