ABSTRACT
OBJECTIVE: The aim of this study is to systematically examine and compare the characteristics distinguishing colorectal adenomatous polyps from normal mucosal intestinal microbiota. METHODS: A total of 30 specimens were obtained from patients diagnosed with colorectal adenomatous polyps (adenoma group) who underwent endoscopic removal at Wenzhou People's Hospital between September 2021 and November 2021. Concurrently, 30 normal mucosal specimens were collected from patients without adenomatous polyps (control group). Subsequently, microbiome total DNA extraction was carried out, followed by PCR amplification targeting the V3-V4 region of the 16S rDNA. High-throughput sequencing was conducted using the Illumina MiSeq platform. Subsequent to sequencing, bioinformatics analysis was used to assess the diversity, composition, and functional aspects of the intestinal microbiota in both study groups. RESULTS: A notable dissimilarity in the microbiota structure was identified, specifically within the transverse colon, between these two groups (Pâ <â 0.05). Species composition analysis revealed that Escherichia, Fusobacterium, and Bacteroides were predominant bacteria in both groups, with Escherichia and Enterobacter displaying significant differences at the genera level between the control group and the adenoma group (Pâ <â 0.05). Correlation analysis and functional prediction demonstrated substantial disparities in interactions among dominant intestinal microbial genera within patients from both groups. Additionally, it was discovered that the intestinal microbiomes in patients in the adenoma group exhibited a significantly higher pathogenic potential. CONCLUSION: Upon conducting a comprehensive analysis, it was discerned that the microbiota present in the transverse colon of the control group exhibited distinctive characteristics that may contribute to the maintenance of intestinal health.
ABSTRACT
Steady-state visual evoked potential (SSVEP) is one of the most used brain-computer interface (BCI) paradigms. Conventional methods analyze SSVEPs at a fixed window length. Compared with these methods, dynamic window methods can achieve a higher information transfer rate (ITR) by selecting an appropriate window length. These methods dynamically evaluate the credibility of the result by linear discriminant analysis (LDA) or Bayesian estimation and extend the window length until credible results are obtained. However, the hypotheses introduced by LDA and Bayesian estimation may not align with the collected real-world SSVEPs, which leads to an inappropriate window length. To address the issue, we propose a novel dynamic window method based on reinforcement learning (RL). The proposed method optimizes the decision of whether to extend the window length based on the impact of decisions on the ITR, without additional hypotheses. The decision model can automatically learn a strategy that maximizes the ITR through trial and error. In addition, compared with traditional methods that manually extract features, the proposed method uses neural networks to automatically extract features for the dynamic selection of window length. Therefore, the proposed method can more accurately decide whether to extend the window length and select an appropriate window length. To verify the performance, we compared the novel method with other dynamic window methods on two public SSVEP datasets. The experimental results demonstrate that the novel method achieves the highest performance by using RL.
Subject(s)
Algorithms , Bayes Theorem , Brain-Computer Interfaces , Electroencephalography , Evoked Potentials, Visual , Neural Networks, Computer , Reinforcement, Psychology , Humans , Evoked Potentials, Visual/physiology , Electroencephalography/methods , Discriminant Analysis , Male , Adult , Young Adult , Female , Machine LearningABSTRACT
BACKGROUND: Femoral neck system (FNS) has exhibited some drawbacks, such as non-fit of the plate with the lateral femoral cortex, postoperative pain, and the potential risk of subtrochanteric fractures. We have developed a low-profile FNS system that addresses some compatibility issues in FNS. In this study, we conducted finite element analysis on the 1-hole FNS (1 H-FNS), 2-holes FNS (2 H-FNS), and low-profile FNS (LP-FNS) and compared their biomechanical performance. METHODS: After the mesh convergence analysis, we established three groups of 1 H-FNS, 2 H-FNS, and LP-FNS. The interfragmentary gap, sliding distance, shear stress, and compressive stress and the bone-implant interface compression stress, stiffness, and displacement were determined under the neutral, flexion, or extension conditions of the hip joint, respectively. The stress and displacement of the femur after the implant removal were also investigated. RESULTS: (1) There were no obvious differences among the three FNS groups in terms of the IFM distance. However, the LP-FNS group showed less rotational angle compared with conventional FNS (neutral: 1 H-FNS, -61.64%; 2 H-FNS, -45.40%). Also, the maximum bone-implant interface compression stress was obviously decreased under the neutral, flexion, or extension conditions of the hip joint (1 H-FNS: -6.47%, -20.59%, or -4.49%; 2 H-FNS: -3.11%, 16.70%, or -7.03%; respectively). (2) After the implant removal, there was no notable difference in the maximum displacement between the three groups, but the maximum von Mises stress displayed a notable difference between LP-FNS and 1 H-FNS groups (-15.27%) except for the difference between LP-FNS and 2 H-FNS groups (-4.57%). CONCLUSIONS: The LP-FNS may not only provide the same biomechanical stabilities as the 1 H-FNS and 2 H-FNS, but also have more advantages in rotational resistance especially under the neutral condition of the hip joint, in the bone-implant interface compression stress, and after the implant removal. In addition, the 1 H-FNS and 2 H-FNS have similar biomechanical stabilities except for the maximum von Mises stress after the implant removal. The femur after the LP-FNS removal not only is subjected to relatively little stress but also minimizes stress concentration areas.
Subject(s)
Bone Screws , Femoral Neck Fractures , Finite Element Analysis , Humans , Femoral Neck Fractures/surgery , Biomechanical Phenomena , Fracture Fixation, Internal/instrumentation , Fracture Fixation, Internal/methods , Stress, Mechanical , Femur Neck/diagnostic imaging , Femur Neck/surgeryABSTRACT
PURPOSE: The goal of this study was to evaluate the dose-response relationship between dexmedetomidine and propofol in sedating patients and to determine the optimal dosage of dexmedetomidine during gastrointestinal endoscopy. METHODS: One hundred fifty patients were divided into 5 groups, each receiving a loading dose of dexmedetomidine (0.4, 0.6, 0.8, 1.0 µg/kg) or saline, with propofol for sedation. The median effective concentration (EC50) of propofol was calculated using the modified Dixon up-and-down approach. Adverse effects, vital signs, procedure, and recovery times were recorded. RESULTS: The EC50 of propofol in groups NS, D0.4, D0.6, D0.8, and D1.0 were 3.02, 2.44, 1.97, 1.85, and 1.83 µg/mL, respectively. Heart rate in the dexmedetomidine groups decreased more than the NS group (Pâ <â .001). The mean arterial pressure (MAP) in the NS group experienced a decline compared to groups D0.8 and D1.0 when the plasma concentration and effect-site concentration reached equilibrium. Additionally, the respiratory rate was found to be lower in groups NS, D0.4, D0.6, and D0.8 (Pâ <â .05). Recovery time in groups D0.8 and D1.0 was longer than the NS group (Pâ <â .05). Bruggemann comfort scales score was higher in group D1.0 (Pâ <â .05). No significant difference was found in the incidences of hypotension and bradycardia, and the dose of ephedrine and atropine. Respiratory depression was significantly reduced in groups D0.8 and D1.0 compared to the NS group. CONCLUSION: A single dose of 0.6 to 0.8 µg/kg of dexmedetomidine should be recommended in combination with propofol for gastrointestinal endoscopy. And the EC50 of propofol is 1.97 to 1.85 µg/mL.
Subject(s)
Dexmedetomidine , Dose-Response Relationship, Drug , Endoscopy, Gastrointestinal , Hypnotics and Sedatives , Propofol , Humans , Dexmedetomidine/administration & dosage , Dexmedetomidine/adverse effects , Propofol/administration & dosage , Propofol/adverse effects , Male , Female , Double-Blind Method , Endoscopy, Gastrointestinal/methods , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Adult , Middle Aged , Heart Rate/drug effectsABSTRACT
BACKGROUND: Dysregulated alterations in organelle structure and function have a significant connection with cell death, as well as the occurrence and development of inflammatory diseases. Maintaining cell viability and inhibiting the release of inflammatory cytokines are essential measures to treat inflammatory diseases. Recently, many studies have showed that autophagy selectively targets dysfunctional organelles, thereby sustaining the functional stability of organelles, alleviating the release of multiple cytokines, and maintaining organismal homeostasis. Organellophagy dysfunction is critically engaged in different kinds of cell death and inflammatory diseases. AIM OF REVIEW: We summarized the current knowledge of organellophagy (e.g., mitophagy, reticulophagy, golgiphagy, lysophagy, pexophagy, nucleophagy, and ribophagy) and the underlying mechanisms by which organellophagy regulates cell death. KEY SCIENTIFIC CONCEPTS OF REVIEW: We outlined the potential role of organellophagy in the modulation of cell fate during the inflammatory response to develop an intervention strategy for the organelle quality control in inflammatory diseases.
ABSTRACT
In the past few decades, chemotherapy has been one of the most effective cancer treatment options. Drug resistance is currently one of the greatest obstacles to effective cancer treatment. Even though drug resistance mechanisms have been extensively investigated, they have not been fully elucidated. Recent genome-wide investigations have revealed the existence of a substantial quantity of long non-coding RNAs (lncRNAs) transcribed from the human genome, which actively participate in numerous biological processes, such as transcription, splicing, epigenetics, the cell cycle, cell differentiation, development, pluripotency, immune microenvironment. The abnormal expression of lncRNA is considered a contributing factor to the drug resistance. Furthermore, drug resistance may be influenced by genetic and epigenetic variations, as well as individual differences in patient treatment response, attributable to polymorphisms in metabolic enzyme genes. This review focuses on the mechanism of lncRNAs resistance to target drugs in the study of tumors with high mortality, aiming to establish a theoretical foundation for targeted therapy.
Subject(s)
Antineoplastic Agents , Drug Resistance, Neoplasm , Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Antineoplastic Agents/pharmacology , AnimalsABSTRACT
Desymmetrization of gem-dimethyl groups has been developed as an efficient pathway to achieve asymmetric C(sp3)-H functionalization. Herein, we described a Pd(II)-catalyzed desymmetrizing gem-dimethyl C(sp3)-H alkenylation/aza-Wacker cyclization directed by a bidentate 2-pyridinylisopropyl auxiliary. Chiral α-methyl γ-lactams were obtained in good yields (up to 82%) and high enantioselectivities (up to 91.5% ee).
ABSTRACT
RNA plays an extensive role in a multi-dimensional regulatory system, and its biomedical relationships are scattered across numerous biological studies. However, text mining works dedicated to the extraction of RNA biomedical relations remain limited. In this study, we established a comprehensive and reliable corpus of RNA biomedical relations, recruiting over 30,000 sentences manually curated from more than 15,000 biomedical literature. We also updated RIscoper 2.0, a BERT-based deep learning tool to extract RNA biomedical relation sentences from literature. Benefiting from approximately 100,000 annotated named entities, we integrated the text classification and named entity recognition tasks in this tool. Additionally, RIscoper 2.0 outperformed the original tool in both tasks and can discover new RNA biomedical relations. Additionally, we provided a user-friendly online search tool that enables rapid scanning of RNA biomedical relationships using local and online resources. Both the online tools and data resources of RIscoper 2.0 are available at http://www.rnainter.org/riscoper.
ABSTRACT
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by heterogeneous variants in the PKD1 and PKD2 genes. Genetic analysis of PKD1 has been challenging due to homology with 6 PKD1 pseudogenes and high GC content. METHODS: A single-tube multiplex long-range-PCR and long-read sequencing-based assay termed "comprehensive analysis of ADPKD" (CAPKD) was developed and evaluated in 170 unrelated patients by comparing to control methods including next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification. RESULTS: CAPKD achieved highly specific analysis of PKD1 with a residual noise ratio of 0.05% for the 6 pseudogenes combined. CAPKD identified PKD1 and PKD2 variants (ranging from variants of uncertain significance to pathogenic) in 160 out of the 170 patients, including 151 single-nucleotide variants (SNVs) and insertion-deletion variants (indels), 6 large deletions, and one large duplication. Compared to NGS, CAPKD additionally identified 2 PKD1 variants (c.78_96dup and c.10729_10732dup). Overall, CAPKD increased the rate of variant detection from 92.9% (158/170) to 94.1% (160/170), and the rate of diagnosis with pathogenic or likely pathogenic variants from 82.4% (140/170) to 83.5% (142/170). CAPKD also directly determined the cis-/trans-configurations in 11 samples with 2 or 3 SNVs/indels, and the breakpoints of 6 large deletions and one large duplication, including 2 breakpoints in the intron 21 AG-repeat of PKD1, which could only be correctly characterized by aligning to T2T-CHM13. CONCLUSIONS: CAPKD represents a comprehensive and specific assay toward full characterization of PKD1 and PKD2 variants, and improves the genetic diagnosis for ADPKD.
Subject(s)
High-Throughput Nucleotide Sequencing , Polycystic Kidney, Autosomal Dominant , TRPP Cation Channels , Humans , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/diagnosis , TRPP Cation Channels/genetics , Multiplex Polymerase Chain Reaction/methods , FemaleABSTRACT
BACKGROUND: Interfragmentary motion (IFM) is a complex state that significantly impacts the healing process of fractures following implant placement. It is crucial to fully consider the IFM state after implantation in the design and biomechanical testing of implants. However, current finite element analysis software lacks direct tools for calculating IFM, and existing IFM tools do not offer a comprehensive solution in terms of accuracy, functionality, and visualization. METHODS: In our study, we developed a Python-based algorithm for calculating IFM that addresses limitations. Our algorithm automatically calculated IFM distances, sliding distances, gaps, as well as the angles and rotation of the two fracture surfaces using all nodes on both sides of the fracture ends. Researchers could input data and selected desired parameters in the interface. The algorithm then performed the necessary calculations and presented the results in a clear and concise manner. The algorithm also provided comprehensive data export capabilities, allowing researchers to customize analyses based on specific needs.To provide a more intuitive demonstration of the calculation process and usage of IFM-Cal, we conducted simulations in Ansys using two rectangular blocks to compare the accuracy and function of three different methods (Point based method, contact tool and IFM-Cal). RESULTS: The point-based method and the contact tool could not accurately calculate IFA, while IFM-Cal could provide a comprehensive evaluation of IFA. In simulation 1, the IFM distances calculated using the point sampling method, contact tool, and IFM-Cal were 2.00 mm, 3.15 mm, and 2.00 mm, respectively. In simulation 2, both the point sampling method and contact tool failed to calculate the interfragmentary angle (IFA), while the IFM-Cal algorithm estimated an angle of -7.87°, which had a small error compared to the ground-truth value of 7.9°. CONCLUSION: We have developed an algorithm for computing IFM which can be utilized in finite element analysis and biomechanical experiments. By conducting comparative simulations with other existing algorithms, we have demonstrated the superior accuracy and expanded evaluation capabilities of our algorithm.
Subject(s)
Fractures, Bone , Humans , Finite Element Analysis , Wound Healing , Rotation , Algorithms , Biomechanical PhenomenaABSTRACT
INTRODUCTION: Renal fibrosis (RF), being the most important pathological change in the progression of CKD, is currently assessed by the evaluation of a biopsy. This present study aimed to apply a novel functional MRI (fMRI) protocol named amide proton transfer (APT) weighting to evaluate RF noninvasively. METHODS: Male Sprague-Dawley (SD) rats were initially subjected to bilateral kidney ischemia/reperfusion injury (IRI), unilateral ureteral obstruction, and sham operation, respectively. All rats underwent APT mapping on the 7th and 14th days after operation. Besides, 26 patients underwent renal biopsy at the Nephrology Department of Shanghai Tongji Hospital between July 2022 and May 2023. Patients underwent APT and apparent diffusion coefficient (ADC) mappings within 1 week before biopsy. MRI results of both patients and rats were calculated by comparing with gold standard histology for fibrosis assessment. RESULTS: In animal models, the cortical APT (cAPT) and medullary APT (mAPT) values were positively correlated with the degree of RF. Compared to the sham group, IRI group showed significantly increased cAPT and mAPT values on the 7th and 14th days after surgery, but no group differences were found in ADC values. Similar results were found in human patients. Cortical/medullary APT values were significantly increased in patients with moderate-to-severe fibrosis than in patients with mild fibrosis. ROC curve analysis indicated that APT value displayed a better diagnostic value for RF. Furthermore, combination of cADC and cAPT improved fibrosis detection by imaging variables alone (p < 0.1). CONCLUSION: APT values had better diagnostic capability at early stage of RF compared to ADC values, and the addition of APT imaging to conventional ADC will significantly improve the diagnostic performance for predicting kidney fibrosis.
Subject(s)
Fibrosis , Kidney , Magnetic Resonance Imaging , Rats, Sprague-Dawley , Male , Animals , Fibrosis/diagnostic imaging , Humans , Rats , Middle Aged , Kidney/diagnostic imaging , Kidney/pathology , Magnetic Resonance Imaging/methods , Reperfusion Injury/diagnostic imaging , Female , Adult , Amides , Protons , Kidney Diseases/diagnostic imaging , Kidney Diseases/pathology , Kidney Diseases/diagnosis , Aged , Renal Insufficiency, Chronic/diagnostic imaging , Renal Insufficiency, Chronic/pathology , Ureteral Obstruction/diagnostic imaging , Disease Models, AnimalABSTRACT
Temperature is a key meteorological factor affecting ozone formation. In general, a positive correlation is observed between ozone and temperature, that is, ozone concentration increases with the increase in temperature. However, this relationship may change at extremely high temperatures. When the temperature exceeds a threshold value, the ozone concentration tends to decrease, which is referred to as an ozone suppression event. Ozone suppression events lead to greater uncertainties in the prediction of future air quality under climate change. Based on the national air quality monitoring data, reanalysis data, and meteorological observation data, this study used the Z test to systematically analyze the spatio-temporal characteristics of the critical temperature(Tx) and frequency of ozone suppression events in China during the warm season(April to September) from 2013 to 2020 and further analyzed the possible influencing factors for the occurrence of ozone suppression events. The results showed that approximately 18% of the sites in China experienced ozone suppression events in the warm season from 2013 to 2020. The sites with a high frequency of ozone suppression events were mainly distributed in the central and western regions of China, such as Sichuan, Xinjiang, and Shaanxi, with an average frequency of ten times per year. The critical temperature(Tx) ranged from 19.2 to 39.3â, and the Tx of most sites showed an increasing trend from 2013 to 2020. The high values of Tx were mainly distributed in the central and western regions such as Sichuan, Chongqing, Hunan, and Hubei, whereas the low values of Tx were concentrated in the Qinghai-Tibet Plateau. Contrary to the interannual trend of Tx, the frequency of ozone suppression events decreased significantly in the Beijing-Tianjin-Hebei Region and exhibited a characteristic of "increase-decrease-increase" in the Fenwei Plain, the Yangtze River Delta, and the Chengdu-Chongqing regions. The most significant effect of extreme high temperature on ozone suppresion was found in the Pearl River Delta Region. In addition, ozone precursors(e.g., NO2) and meteorological conditions(wind speed and direction) were possible factors affecting the occurrence of ozone suppression events.
ABSTRACT
Cities are the center of energy consumption. Electrification integrates urban energy structure and achieves the efficient use of clean energy. Exploring the urban impact of accelerated electrification under the low-carbon path is crucial to reducing urban pollution and carbon. Based on the Long-range Energy Alternative Planning System(LEAP-DG), this study set up three scenarios, including the baseline, low-carbon, and accelerated electrification scenarios, to evaluate the emission reduction potential of electrification under different power structures, quantify the contribution of key sectors, and discuss the coordinated emission reduction effect of Dongguan, a typical manufacturing city in Guangdong. The results showed that accelerated electrification under the low-carbon path would reduce the emission intensity of power pollutants, and in 2050, Dongguan will further reduce CO2, NOx, VOC, and CO by 7.35×106, 1.28×104, 1.62×104, and 8.13×104 t; SO2 and PM2.5 emission reductions on the consumption side and increased emissions on the production side had been balanced. Accelerated electrification in the industrial and transportation sectors would reduce CO2 and air pollutant emissions at the same time, and the transportation sector would benefit from the high conversion efficiency of fuel vehicles and electric vehicles, reducing CO2, CO, VOC, and NOx by 5.42×106, 7.76×104, 1.43×104, and 1.06×104 t, respectively, in 2050. In the building sector with high electrification rates, coal power was higher in extra electricity, increasing CO2 and pollutant emissions. Under the optimization of power supply structure, cities can reasonably adjust the electrification of different departments to achieve targeted pollution prevention and control.