Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis ...cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction.
Extracting the flight trajectory of the shuttlecock in a single turn in badminton games is important for automated sports analytics. This study proposes a novel method to extract shots in badminton ...games from a monocular camera. First, TrackNet, a deep neural network designed for tracking small objects, is used to extract the flight trajectory of the shuttlecock. Second, the YOLOv7 model is used to identify whether the player is swinging. As both TrackNet and YOLOv7 may have detection misses and false detections, this study proposes a shot refinement algorithm to obtain the correct hitting moment. By doing so, we can extract shots in rallies and classify the type of shots. Our proposed method achieves an accuracy of 89.7%, a recall rate of 91.3%, and an F1 rate of 90.5% in 69 matches, with 1582 rallies of the Badminton World Federation (BWF) match videos. This is a significant improvement compared to the use of TrackNet alone, which yields 58.8% accuracy, 93.6% recall, and 72.3% F1 score. Furthermore, the accuracy of shot type classification at three different thresholds is 72.1%, 65.4%, and 54.1%. These results are superior to those of TrackNet, demonstrating that our method effectively recognizes different shot types. The experimental results demonstrate the feasibility and validity of the proposed method.
Purpose
3D pulse sequences enable high‐resolution acquisition with a high SNR and ideal slice profiles, which, however, is particularly difficult for diffusion MRI (dMRI) due to the additional phase ...errors from diffusion encoding.
Methods
We proposed a twin navigator‐based 3D diffusion‐weighted gradient spin‐echo (GRASE) sequence to correct the phase errors between shots and between odd and even spin echoes for human whole‐brain acquisition. We then compared the SNR of 3D GRASE and 2D simultaneous multi‐slice EPI within the same acquisition time. We further tested the performance of 2D versus 3D acquisition at equivalent SNR on fiber tracking and microstructural mapping, using the diffusion tensor and high‐order fiber orientation density–based metrics.
Results
The proposed twin navigator approach removed multi‐shot phase errors to some extent in the whole brain dMRI, and the 2D navigator performed better than the 1D navigator. Comparisons of SNR between the 2D simultaneous multi‐slice EPI and 3D GRASE sequences demonstrated that the SNR of the GRASE sequence was 1.4–1.5‐fold higher than the EPI sequence at an equivalent scan time. More importantly, we found a significantly higher fiber cross‐section in the cerebrospinal tract, as well as richer subcortical fibers (U‐fibers) using the 3D GRASE sequence compared to 2D EPI.
Conclusion
The twin navigator‐based 3D diffusion‐weighted‐GRASE sequence minimized the multishot phase error and effectively improved the SNR for whole‐brain dMRI acquisition. We found differences in fiber tracking and microstructural mapping between 2D and 3D acquisitions, possibly due to the different slice profiles.
Purpose
Oscillating gradient (OG) enables the access of short diffusion times for time‐dependent diffusion MRI (dMRI); however, it poses several technical challenges for clinical use. This study ...proposes a 3D oscillating gradient–prepared gradient spin‐echo (OGprep‐GRASE) sequence to improve SNR and shorten acquisition time for OG dMRI on clinical scanners.
Methods
The 3D OGprep‐GRASE sequence consisted of global saturation, diffusion encoding, fat saturation, and GRASE readout modules. Multiplexed sensitivity‐encoding reconstruction was used to correct the phase errors between multiple shots. We compared the scan time and SNR of the proposed sequence and the conventional 2D‐EPI sequence for OG dMRI at 30‐90‐mm slice coverage. We also examined the time‐dependent diffusivity changes with OG dMRI acquired at frequencies of 50 Hz and 25 Hz and pulsed‐gradient dMRI at diffusion times of 30 ms and 60 ms.
Results
The OGprep‐GRASE sequence reduced the scan time by a factor of 1.38, and increased the SNR by 1.74‐2.27 times compared with 2D EPI for relatively thick slice coverage (60‐90 mm). The SNR gain led to improved diffusion‐tensor reconstruction in the multishot protocols. Image distortion in 2D‐EPI images was also reduced in GRASE images. Diffusivity measurements from the pulsed‐gradient dMRI and OG dMRI showed clear diffusion‐time dependency in the white matter and gray matter of the human brain, using both the GRASE and EPI sequences.
Conclusion
The 3D OGprep‐GRASE sequence improved scan time and SNR and reduced image distortion compared with the 2D multislice acquisition for OG dMRI on a 3T clinical system, which may facilitate the clinical translation of time‐dependent dMRI.
The combination of conventional transition‐metal‐catalyzed coupling (2 e− process) and photoredox catalysis (1 e− process) has emerged as a powerful approach to catalyze difficult cross‐coupling ...reactions under mild reaction conditions. Reported is a palladium carbodicarbene (CDC) complex that mediates both a Suzuki–Miyaura coupling and photoredox catalysis for C−N bond formation upon visible‐light irradiation. These two catalytic pathways can be combined to promote both conventional transition‐metal‐catalyzed coupling and photoredox catalysis to mediate C−H arylation under ambient conditions with a single catalyst in an efficient one‐pot process.
A one, two combo: The combination of conventional transition‐metal‐catalyzed coupling (2 e− process) and photoredox catalysis (1 e− process) has emerged as a powerful approach to catalyze difficult cross‐coupling reactions under mild reaction conditions. Reported is the use of a single palladium carbodicarbene (CDC) complex that mediates both a Suzuki–Miyaura coupling and photoredox catalysis for C−N bond formation upon visible‐light irradiation.
•The vascular water exchange MRI (VEXI) is a contrast-agent-free method proposed to assess BBB permeability•Apparent water exchange rate across BBB (AXRBBB) becomes higher specifically in the ...hippocampus, medial orbital frontal cortex, and thalamus in AD•AXRBBB is significantly correlated with cognitive dysfunction
Blood-brain barrier (BBB) impairment is an important pathophysiological process in Alzheimer's disease (AD) and a potential biomarker for early diagnosis of AD. However, most current neuroimaging methods assessing BBB function need the injection of exogenous contrast agents (or tracers), which limits the application of these methods in a large population. In this study, we aim to explore the feasibility of vascular water exchange MRI (VEXI), a diffusion-MRI-based method proposed to assess the BBB permeability to water molecules without using a contrast agent, in the detection of the BBB breakdown in AD. We tested VEXI on a 3T MRI scanner on three groups: AD patients (AD group), mild cognitive impairment (MCI) patients due to AD (MCI group), and the age-matched normal cognition subjects (NC group). Interestingly, we find that the apparent water exchange across the BBB (AXRBBB) measured by VEXI shows higher values in MCI compared with NC, and this higher AXRBBB happens specifically in the hippocampus. This increase in AXRBBB value gets larger and extends to more brain regions (medial orbital frontal cortex and thalamus) from MCI group to the AD group. Furthermore, we find that the AXRBBB values of these three regions is correlated significantly with the impairment of respective cognitive domains independent of age, sex and education. These results suggest VEXI is a promising method to assess the BBB breakdown in AD.
Pharmacological interactions are useful for understanding ligand binding mechanisms of a therapeutic target. These interactions are often inferred from a set of active compounds that were acquired ...experimentally. Moreover, most docking programs loosely coupled the stages (binding-site and ligand preparations, virtual screening, and post-screening analysis) of structure-based virtual screening (VS). An integrated VS environment, which provides the friendly interface to seamlessly combine these VS stages and to identify the pharmacological interactions directly from screening compounds, is valuable for drug discovery.
We developed an easy-to-use graphic environment, iGEMDOCK, integrating VS stages (from preparations to post-screening analysis). For post-screening analysis, iGEMDOCK provides biological insights by deriving the pharmacological interactions from screening compounds without relying on the experimental data of active compounds. The pharmacological interactions represent conserved interacting residues, which often form binding pockets with specific physico-chemical properties, to play the essential functions of a target protein. Our experimental results show that the pharmacological interactions derived by iGEMDOCK are often hot spots involving in the biological functions. In addition, iGEMDOCK provides the visualizations of the protein-compound interaction profiles and the hierarchical clustering dendrogram of the compounds for post-screening analysis.
We have developed iGEMDOCK to facilitate steps from preparations of target proteins and ligand libraries toward post-screening analysis. iGEMDOCK is especially useful for post-screening analysis and inferring pharmacological interactions from screening compounds. We believe that iGEMDOCK is useful for understanding the ligand binding mechanisms and discovering lead compounds. iGEMDOCK is available at http://gemdock.life.nctu.edu.tw/dock/igemdock.php.
Daily urine protein (UP) loss is a cumbersome but important measurement to guide diagnosis and treatment of renal disease. Spot urine protein-creatinine ratio (UPCR) can been applied to estimate ...daily proteinuria. However, the correlations between spot and 24h proteinuria remain controversial. In this cross-sectional study, simultaneous collection of 24h and spot urines were performed from 1,039 (derivation cohort) and 204 CKD patients (validation cohort) of Chang Gung Memorial Hospital, from 2007 to 2017. The correlations between spot UPCR and 24h proteinuria were compared. The mean age of patients of derivation and validation cohort was 63 and 55 years and the mean estimated glomerular filtration rate was 62 ± 35 and 59 ± 36 mL/min/m2, respectively. The correlation coefficient was 0.819 between UPCR and 24hUP. Prediction equation was derived as: Log1024hUP (g) = 0.814 x Log10UPCR (mg/mg) + 0.110 x Gender- 0.004 x Age + 0.004 x Body weight (kg) + 0.002 x CKD stage coefficient- 0.018, where CKD stage coefficient: CKD stage G1 = 1, G2 = 2, G3a = 3.1, G3b = 3.2, G4 = 4, G5 = 5. Correlation coefficient between measured and predicted 24hUP among derivation group and validation group is 0.866 and 0.915, respectively. However, the agreement of spot and daily estimates was less pronounced with proteinuria > 3g than lower values in Bland-Altman analysis. Spot UPCR can accurately predict 24hUP in patients with daily proteinuria below 3g. The development of this equation may facilitate estimation of 24hUP in the clinical practice.
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