Fabrication of Crescent Shaped Microparticles for Particle Templated Droplet Formation.

Crescent-shaped hydrogel microparticles are shown to template uniform volume aqueous droplets upon simple mixing with aqueous and oil media for various bioassays. This emerging "lab on a particle" technique requires hydrogel particles with tunable material properties and dimensions. The crescent shape of the particles is attained by aqueous two-phase separation of polymers followed by photopolymerization of the curable precursor. In this work, the phase separation of poly(ethylene glycol) diacrylate (PEGDA, Mw 700) and dextran (Mw 40 000) for tunable manufacturing of crescent-shaped particles is investigated. The particles' morphology is precisely tuned by following a phase diagram, varying the UV intensity, and adjusting the flow rates of various streams. The fabricated particles with variable dimensions encapsulate uniform aqueous droplets upon mixing with an oil phase. The particles are fluorescently labeled with red and blue emitting dyes at variable concentrations to produce six color-coded particles. The blue fluorescent dye shows a moderate response to the pH change. The fluorescently labeled particles are able to tolerate an extremely acidic solution (pH 1) but disintegrate within an extremely basic solution (pH 14). The particle-templated droplets are able to effectively retain the disintegrating particle and the fluorescent signal at pH 14.

Costunolide mitigates inflammation and promotes extracellualr matrix integrity of thoracic aortic dissection by inhibiting NF-κB signaling.

BACKGROUND: Thoracic aortic dissection (TAD) is one of the most fatal cardiovascular diseases. One of its important pathological characteristics is the local inflammatory response. Many studies have found that Macrophage polarization plays an extremely critical role in the inflammatory progression and tissue remodeling of TAD. Costunolide (CTD) has an improving effect on oxidative stress and inflammation in the body. However, whether it can promote the integrity of extracellular matrix in Aortic dissection and its mechanism are still unclear. METHODS: The male C57BL/6J mice were used to construct an animal model of TAD with ß-aminopropionitrile (BAPN) (100 mg/kg/day, lasting for 28 days), and then CTD (10 mg/kg or 100 mg/kg) was injected intraperitoneally for 28 days to check the survival rate, TAD incidence, aortic morphology and other indicators of the mice. Using hematoxylin-eosin (HE), Masson, Elastin van Gieson (EVG) staining, immunofluorescence (IF), and immunohistochemical staining, the study aimed to determine the therapeutic effects of CTD on an animal model with BAPN-induced TAD. To enhance the examination of the regulatory mechanism of CTD, we conducted transcriptome sequencing on arterial tissues of mice in both the BAPN group and the BAPN + CTD100 group. Next, ANG II were used to construct TAD model in vascular smooth muscle cells (VMSCs). The effects of CTD on the proliferation, migration, invasion, and apoptosis of ANG II-induced cells are to be detected. The expression of MMP2, MMP9, P65, and p-P65 in each group will be examined using Western blot. Finally, the overexpression of IκB kinaseß (IKKß) will be established in VMSCs cells to further explore the protective function of CTD. RESULTS: The result showed that CTD significantly inhibited BAPN induced mortality and TAD incidence in the animal model, improved aortic vascular morphology, promoted the integrity of extracellular matrix in TAD, reduced tissue inflammation, reduced the accumulation of M1 macrophage, promoted M2 macrophage polarization, and reduced the expression of NF-κB pathway related proteins. Mechanistically, CTD significantly weakened the proliferation, migration, invasion, and apoptosis. p-P65 protein expression of TAD cells were induced by ANG II and IKK-ß. CONCLUSION: CTD has the potential to alleviate inflammation, VSMC apoptosis, MMP2/9 levels, and enhance extracellular matrix integrity in TAD by inhibiting the NF-κB signaling pathway.

Clinical analysis of uterine parameters evaluated by preoperative magnetic resonance imaging in patients treated by hysteroscopic approach with previous cesarean scar defect-related abnormal uterine bleeding: a retrospective cohort study.

Background: As the cesarean delivery rate continues to rise globally, the treatment of previous cesarean scar defects (PCSD) remains challenging. This study aimed to analyze the variables that may influence the clinical cure rate of patients with PCSD-related abnormal uterine bleeding (AUB) as determined by preoperative magnetic resonance imaging (MRI) following hysteroscopic therapy. Methods: Women who underwent hysteroscopic surgery for PCSD-related AUB at the Gynecology Department of Third Xiangya Hospital of Central South University from 2018 to 2022 were recruited to this retrospective cohort investigation. A total of 147 patients were enrolled in this study and underwent follow-up over 6 months. The significance of clinical characteristics linked to the clinical cure rate of AUB was examined by logistic regression. Results: There were 64 clinically cured (43.5%) and 83 non-clinically cured (56.5%) patients in the study. There were no significant differences in the age, menstrual duration, gravidity, parity, number of cesarean sections, time since the previous cesarean section, uterus position, width, depth, and thickness of the remaining muscle layer of the defect by MRI T2-weighted images (T2WI) before hysteroscopic surgery between the 2 groups. MRI T2WI of the myometrial thickness adjacent to the defect [P=0.038, odds ratio (OR) =2.095, 95% confidence interval (CI): 1.047-4.261] and the distance from the defect to the external cervical os (P=0.021, OR =2.254, 95% CI: 1.136-4.540) before hysteroscopic surgery are risk factors for the clinical cure rate. Conclusions: The myometrial thickness adjacent to the defect and the distance from the defect to the external cervical os in preoperative MRI are risk factors for clinical cure rate in patients with PCSD-related AUB after hysteroscopic treatment, which is helpful for evaluating the prognosis of disease.

Flex-DLD: Deep Low-Rank Decomposition Model With Flexible Priors for Hyperspectral Image Denoising and Restoration.

Hyperspectral images (HSIs) are composed of hundreds of contiguous waveband images, offering a wealth of spatial and spectral information. However, the practical use of HSIs is often hindered by the presence of complicated noise caused by various factors such as non-uniform sensor response and dark current. Traditional methods for denoising HSIs rely on constrained optimization approaches, where selecting appropriate prior knowledge is critical for achieving satisfactory results. Nevertheless, these traditional algorithms are limited by hand-crafted priors, leaving room for improvement in their denoising performance. Recently, the supervised deep learning technique has emerged as a promising approach for HSI denoising. However, their requirement for paired training data and poor generalization ability on untrained noise distributions pose challenges in practical applications. In this paper, we design a novel algorithm by the synergism of optimization-based methods and deep learning techniques. Specifically, we introduce a plug-and-play Deep Low-rank Decomposition (DLD) model into the optimization framework. Furthermore, we propose an effective mechanism to incorporate traditional prior knowledge into the DLD model. Finally, we provide a detailed analysis of the optimization process and convergence of the proposed method. Empirical evaluations on various tasks, including hyperspectral image denoising and spectral compressive imaging, demonstrate the superiority of our approach over state-of-the-art methods.

Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis.

BACKGROUND: Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms. OBJECTIVES: The aim of this study was to discover novel biomarkers with potentially causal associations with AS. METHODS: We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over 6 years and with AV calcification with the use of cardiac computed tomography, replicated analysis in an independent sample, performed Mendelian randomization, and evaluated gene expression in explanted human AV tissue. RESULTS: Fifty-two proteins cross-sectionally were associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3. Among 3,413 participants in the Cardiovascular Health Study, 6 of those proteins were significantly associated with adjudicated moderate or severe AS, including matrix metalloproteinase 12 (MMP12), complement C1q tumor necrosis factor-related protein 1 (C1QTNF1), and growth differentiation factor-15. MMP12 was also associated with greater increase in AVmax over 6 years, greater degree of AV calcification, and greater expression in calcific compared with normal or fibrotic AV tissue. C1QTNF1 had consistent potential causal effects on both AS and AVmax according to Mendelian randomization analysis. CONCLUSIONS: These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression.

An apicoplast-localized deubiquitinase contributes to the cell growth and apicoplast homeostasis of Toxoplasma gondii.

Toxoplasma gondii is among the most important parasites worldwide. The apicoplast is a unique organelle shared by all Apicomplexan protozoa. Increasing lines of evidence suggest that the apicoplast possesses its own ubiquitination system. Deubiquitination is a crucial step executed by deubiquitinase (DUB) during protein ubiquitination. While multiple components of ubiquitination have been identified in T. gondii, the deubiquitinases involved remain unknown. The aim of the current study was to delineate the localization of TgOTU7 and elucidate its functions. TgOTU7 was specifically localized at the apicoplast, and its expression was largely regulated during the cell cycle. Additionally, TgOTU7 efficiently breaks down ubiquitin chains, exhibits linkage-nonspecific deubiquitinating activity and is critical for the lytic cycle and apicoplast biogenesis, similar to the transcription of the apicoplast genome and the nuclear genes encoding apicoplast-targeted proteins. Taken together, the results indicate that the newly described deubiquitinase TgOTU7 specifically localizes to the apicoplast and affects the cell growth and apicoplast homeostasis of T. gondii.

Garnet Structure-Activated Warm White Light Phosphors Ca3Al2Ge3O12: Dy3+, Eu3+ with Ultrahigh Thermal Stability and Tunable Luminescence.

A series of Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors were successfully prepared by the high-temperature solid-phase method. The phase and morphology of the phosphors were studied by means of Rietveld refinement and scanning electron microscopy. The results show that the phase is pure, and the crystal structure is the Ia3̅d space group. In the Ca3Al2Ge3O12: xDy3+ phosphors, using 380 nm excitation, phosphors showed blue (4F9/2 → 6H15/2) and yellow (4F9/2 → 6H13/2) emission peaks at 481 and 581 nm, respectively. In Ca3Al2Ge3O12: xDy3+, yEu3+ phosphors, the energy transfer was inferred by the spectrum overlap of Dy3+ and Eu3+, and the lifetime attenuation was analyzed from the perspective of dynamics; finally, the band gap structure of the phosphors was analyzed by combining diffuse reflection spectra with the first principle, and the energy transfer mechanism and luminescence mechanism were elaborated by combining theory and practice. The transition from blue white light to red light can be achieved by tuning the range of y in Ca3Al2Ge3O12: 0.015Dy3+, yEu3+. Wherein, when y = 0.07, phosphors, the chromaticity coordinate of warm white CIE is (0.3932, 0.3203), the color temperature is 3093 K, and the warm white light is synthesized. The thermal stability of the synthesized warm white phosphors is 90.1% (423 K), the thermal sensing factors are Samax = 5.51 × 10-4 K-1 (303 K) and Srmax = 0.0359% K-1 (303 K), and the actual quantum efficiency is IQE = 52.48%. These results prove that Ca3Al2Ge3O12: Dy3+, Eu3+ have good application prospects as single-component warm w-LED devices.

A novel single-phase color tunable LiYGeO4:Dy3+, Eu3+ phosphor exhibiting warm white light and excellent thermal stability.

LiYGeO4 phosphors doped with Dy3+ and Eu3+ ions were synthesized using the solid phase method, and their color characteristics were adjustable. The bandgap value of LiYGeO4 calculated by diffuse reflection data is very close to the theoretical value of 3.669 eV, indicating that LiYGeO4 is an ideal candidate for doped rare earth activated ions. The analysis of the emission spectra and fluorescence attenuation curves of Dy3+ and Eu3+ co-doped LiYGeO4 phosphors revealed a clear energy transfer process: energy transfer from Dy3+ to Eu3+. Analysis of emission spectra and fluorescence attenuation curves revealed a transfer of energy from Dy3+ to Eu3+. This transfer mechanism is attributed to the dipole-dipole interactions. In addition, by constantly adjusting the doping levels of Dy3+ and Eu3+, a warm white phosphor with a color temperature of 3881 K was obtained. Finally, the emission intensity of the LiYGeO4:0.015Dy3+,0.02Eu3+ phosphor at 423 K was 86%, indicating that the phosphor has excellent thermal stability and 40% internal quantum efficiency, which proves the potential application of the LiYGeO4 phosphor in white light-emitting diodes (w-LEDs).

microRNA-365 attenuated intervertebral disc degeneration through modulating nucleus pulposus cell apoptosis and extracellular matrix degradation by targeting EFNA3.

This present study is aimed to investigate the role of microRNA-365 (miR-365) in the development of intervertebral disc degeneration (IDD). Nucleus pulposus (NP) cells were transfected by miR-365 mimic and miR-365 inhibitor, respectively. Concomitantly, the transfection efficiency and the expression level of miRNA were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Meanwhile, NP cells apoptosis was measured through propidium iodide (PI)-AnnexinV-fluorescein isothiocyanate (FITC) apoptosis detection kit. Subsequently, immunofluorescence (IF) staining was performed to assess the expression of collagen II, aggrecan and matrix metalloproteinase 13 (MMP-13). In addition, bioinformatic prediction and Luciferase reporter assay were used to reveal the target gene of miR-365. Finally, we isolated the primary NP cells from rats and injected NP-miR-365 in rat IDD models. The results showed that overexpression of miR-365 could effectively inhibit NP cells apoptosis and MMP-13 expression and upregulate the expression of collagen II and aggrecan. Conversely, suppression of miR-365 enhanced NP cell apoptosis and elevated MMP-13 expression, but decreased the expression of collagen II and aggrecan. Moreover, the further data demonstrated that miR-365 mediated NP cell degradation through targeting ephrin-A3 (EFNA3). In addition, the cells apoptosis and catabolic markers were increased in NP cells when EFNA3 upregulated. More importantly, the vivo data supported that miR-365-NP cells injection ameliorated IDD in rats models. miR-365 could alleviate the development of IDD by regulating NP cell apoptosis and ECM degradation, which is likely mediated by targeting EFNA3. Therefore, miR-365 may be a promising therapeutic avenue for treatment IDD through EFNA3.

Feasibility of Two-Screw Anterior Fixation for Odontoid Fractures in a Chinese Population: A Morphometric Study Based on Computed Tomography.

Background: To evaluate the feasibility of treating odontoid fractures in the Chinese population with two cortical screws based on computed tomography (CT) scans and describe a new measurement strategy to guide screw insertion in treating these fractures. Methods: A retrospective review of cervical computed tomographic scans of 128 patients (aged 18-76 years; men, 55 [43.0%]) was performed. The minimum external transverse diameter (METD), minimum external anteroposterior diameter (MEAD), maximum screw length (MSL), and screw projection back angle (SPBA) of the odontoid process were measured on coronal and sagittal CT images. Results: The mean values of METD and MEAD were 10.0 ± 1.1 mm and 12.0 ± 1.0 mm, respectively, in men and 9.2 ± 1.0 mm and 11.0 ± 1.0 mm, respectively, in women. Both measurements were significantly higher in men (p < 0.001). In total, 87 individuals (68%) had METD > 9.0 mm that could accommodate two 3.5-mm cortical screws. The mean MSL value and SPBA range were 34.4 ± 2.9 mm and 13.5°-24.2°, respectively, with no statistically significant difference between men and women. Conclusions: The insertion of two 3.5-mm cortical screws was possible for anterior fixation of odontoid fractures in 87 patients (68%) in our study, and there was a statistically significant difference between men and women.

Dual Responsive Magnetic Drug Delivery Nanomicelles with Tumor Targeting for Enhanced Cancer Chemo/Magnetothermal Synergistic Therapy.

Introduction: Stimulus-responsive nanocarrier systems are promising in cancer treatment. They improve drug stability and facilitate controlled drug release. However, single-responsive nanocarriers still face insufficient tumor targeting and low efficacy. Methods: In this study, we synthesized folate-modified DSPE-PEOz nanomicelles with PEG chains and loaded them with magnetic iron particles and doxorubicin (DOX). Folic acid (FA) was employed as a ligand to target cancer cells actively. The nanomicelles are biocompatible and acid-sensitive drug carriers. Magnetic field-responsive nanoparticles enable moderately controlled magnetothermal therapy of tumors regardless of tumor location. The pH/magnetic field dual-responsive nanomicelles shed their PEG layer in response to tumor tissue acidity and react to magnetic fields through magnetothermal effects. Results: In vitro and in vivo experiments demonstrated that the nanomicelles could efficiently target cancer cells, release drugs in response to pH changes, and enhance drug uptake through magnetothermal effects. Discussion: The dual-responsive magnetic nanomicelles are expected to enhance the anti-cancer efficacy of chemo/magnetothermal synergistic therapy.

Changes in Pulmonary Artery Pressure Late in Life: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Although the prognostic implications of higher pulmonary artery systolic pressure (PASP) are well established, few data exist regarding longitudinal change in pulmonary pressure in late life. OBJECTIVES: The aim of this study was to quantify changes in PASP over 6 years and determine the relative contributions of cardiac and pulmonary dysfunction. METHODS: Among 1,420 participants in the ARIC (Atherosclerosis Risk in Communities) study with echocardiographic measures of PASP at both the fifth (2011-2013) and seventh (2018-2019) visits, longitudinal changes in PASP over about 6.5 years were quantified. Multivariable regression was used to determine the extent to which cardiac and pulmonary dysfunction were associated with changes in PASP and to define the relationship of changes in PASP with dyspnea development. RESULTS: The mean age was 75 ± 5 years at visit 5 and 81 ± 5 years at visit 7, 24% of subjects were Black adults, and 68% were women. Over the 6.5 years, PASP increased by 5 ± 8 mm Hg, from 28 ± 5 to 33 ± 8 mm Hg. PASP increased more in older participants. Predictors of greater increases in PASP included worse left ventricular (LV) systolic and diastolic function, pulmonary function, and renal function. Increases in PASP were associated with concomitant increases in measures of LV filling pressure, including E/e' ratio and left atrial volume index. Each 5 mm Hg increase was associated with 16% higher odds of developing dyspnea (OR: 1.16; 95% CI: 1.07-1.27; P < 0.001). CONCLUSIONS: Pulmonary pressure increased over 6.5 years in late life, was associated with concomitant increases in LV filling pressure, and predicted the development of dyspnea. Interventions targeting LV diastolic function may be effective at mitigating age-related increases in PASP.

An opponent model for agent-based shared decision-making via a genetic algorithm.

Introduction: Shared decision-making (SDM) has received a great deal of attention as an effective way to achieve patient-centered medical care. SDM aims to bring doctors and patients together to develop treatment plans through negotiation. However, time pressure and subjective factors such as medical illiteracy and inadequate communication skills prevent doctors and patients from accurately expressing and obtaining their opponent's preferences. This problem leads to SDM being in an incomplete information environment, which significantly reduces the efficiency of the negotiation and even leads to failure. Methods: In this study, we integrated a negotiation strategy that predicts opponent preference using a genetic algorithm with an SDM auto-negotiation model constructed based on fuzzy constraints, thereby enhancing the effectiveness of SDM by addressing the problems posed by incomplete information environments and rapidly generating treatment plans with high mutual satisfaction. Results: A variety of negotiation scenarios are simulated in experiments and the proposed model is compared with other excellent negotiation models. The results indicated that the proposed model better adapts to multivariate scenarios and maintains higher mutual satisfaction. Discussion: The agent negotiation framework supports SDM participants in accessing treatment plans that fit individual preferences, thereby increasing treatment satisfaction. Adding GA opponent preference prediction to the SDM negotiation framework can effectively improve negotiation performance in incomplete information environments.

Association between albumin-to-globulin ratio and the risk of overall survival in advanced non-small cell lung cancer patients with anlotinib treatment: a retrospective cohort study.

OBJECTIVE: Researches about the association between serum albumin-to-globulin ratio (AGR) and the prognosis of lung cancer are limited. We aimed to investigate the relationship between AGR and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) treated with anlotinib. METHODS: A retrospective cohort study was conducted on 196 advanced NSCLC patients with anlotinib treatment between June 1, 2018 and June 1, 2021. The exposure was AGR, calculated by baseline serum albumin / (serum total protein - serum albumin). The outcome was OS, defined as the period from the date of initial treatment with anlotinib to death or the last follow-up. The univariate and multivariate linear regression models and generalized additive models (GAM) were used to analyze the relationship between AGR and OS. The Kaplan-Meier method was used to analyze the OS. RESULTS: After adjusting for potential confounders, a non-linear relationship was observed between AGR and OS, which had an inflection point of 1.24. The hazard ratio and the confidence intervals on the left and the right sides of the inflection point were 13.05 (0.52 to 327.64) and 0.20 (0.07 to 0.57), respectively. It suggested that AGR was positively associated with OS when AGR was larger than 1.24, for every 1 unit increase in AGR, the risk of death lowered approximately by 80%. CONCLUSIONS: The relationship between AGR and the OS for advanced NSCLC patients with anlotinib is non-linear. AGR level is an independent protective factor for OS in advanced NSCLC patients who received anlotinib therapy.

Non-Contact Monitoring of Fetal Movement Using Abdominal Video Recording.

Fetal movement (FM) is an important indicator of fetal health. However, the current methods of FM detection are unsuitable for ambulatory or long-term observation. This paper proposes a non-contact method for monitoring FM. We recorded abdominal videos from pregnant women and then detected the maternal abdominal region within each frame. FM signals were acquired by optical flow color-coding, ensemble empirical mode decomposition, energy ratio, and correlation analysis. FM spikes, indicating the occurrence of FMs, were recognized using the differential threshold method. FM parameters including number, interval, duration, and percentage were calculated, and good agreement was found with the manual labeling performed by the professionals, achieving true detection rate, positive predictive value, sensitivity, accuracy, and F1_score of 95.75%, 95.26%, 95.75%, 91.40%, and 95.50%, respectively. The changes in FM parameters with gestational week were consistent with pregnancy progress. In general, this study provides a novel contactless FM monitoring technology for use at home.

A review of current effective COVID-19 testing methods and quality control.

COVID-19 is a highly infectious disease caused by the SARS-CoV-2 virus, which primarily affects the respiratory system and can lead to severe illness. The virus is extremely contagious, early and accurate diagnosis of SARS-CoV-2 is crucial to contain its spread, to provide prompt treatment, and to prevent complications. Currently, the reverse transcriptase polymerase chain reaction (RT-PCR) is considered to be the gold standard for detecting COVID-19 in its early stages. In addition, loop-mediated isothermal amplification (LMAP), clustering rule interval short palindromic repeats (CRISPR), colloidal gold immunochromatographic assay (GICA), computed tomography (CT), and electrochemical sensors are also common tests. However, these different methods vary greatly in terms of their detection efficiency, specificity, accuracy, sensitivity, cost, and throughput. Besides, most of the current detection methods are conducted in central hospitals and laboratories, which is a great challenge for remote and underdeveloped areas. Therefore, it is essential to review the advantages and disadvantages of different COVID-19 detection methods, as well as the technology that can enhance detection efficiency and improve detection quality in greater details.

PP2Acα-B'/PR61 Holoenzyme of Toxoplasma gondii Is Required for the Amylopectin Metabolism and Proliferation of Tachyzoites.

Here, we report that the inhibition of the PP2A subfamily by okadaic acid results in an accumulation of polysaccharides in the acute infection stage (tachyzoites) of Toxoplasma gondii, which is a protozoan of global zoonotic importance and a model for the apicomplexan parasites. The loss of the catalytic subunit α of PP2A (ΔPP2Acα) in RHΔku80 leads to the polysaccharide accumulation phenotype in the base of tachyzoites as well as residual bodies and significantly compromises the intracellular growth in vitro and the virulence in vivo. A metabolomic analysis revealed that the accumulated polysaccharides in ΔPP2Acα are derived from interrupted glucose metabolism, which affects the production of ATP and energy homeostasis in the T. gondii knockout. The assembly of the PP2Acα holoenzyme complex involved in the amylopectin metabolism in tachyzoites is possibly not regulated by LCMT1 or PME1, and this finding contributes to the identification of the regulatory B subunit (B'/PR61). The loss of B'/PR61 results in the accumulation of polysaccharide granules in the tachyzoites as well as reduced plaque formation ability, exactly the same as ΔPP2Acα. Taken together, we have identified a PP2Acα-B'/PR61 holoenzyme complex that plays a crucial role in the carbohydrate metabolism and viability in T. gondii, and its deficiency in function remarkably suppresses the growth and virulence of this important zoonotic parasite both in vitro and in vivo. Hence, rendering the PP2Acα-B'/PR61 holoenzyme functionless should be a promising strategy for the intervention of Toxoplasma acute infection and toxoplasmosis. IMPORTANCE Toxoplasma gondii switches back and forth between acute and chronic infections, mainly in response to host immunologic status, which is characterized by flexible but specific energy metabolism. Polysaccharide granules are accumulated in the acute infection stage of T. gondii that have been exposed to a chemical inhibitor of the PP2A subfamily. The genetic depletion of the catalytic subunit α of PP2A leads to this phenotype and significantly affects the cell metabolism, energy production, and viability. Further, a regulatory B subunit PR61 is necessary for the PP2A holoenzyme to function in glucose metabolism and in the intracellular growth of T. gondii tachyzoites. A deficiency of this PP2A holoenzyme complex (PP2Acα-B'/PR61) in T. gondii knockouts results in the abnormal accumulation of polysaccharides and the disruption of energy metabolism, suppressing their growth and virulence. These findings provide novel insights into cell metabolism and identify a potential target for an intervention against a T. gondii acute infection.

Artificial intelligence diagnosis of intrauterine adhesion by 3D ultrasound imaging: a prospective study.

Background: There were a very large number of intrauterine adhesion (IUA) patients. As improving the classification of three-dimensional transvaginal ultrasound (3D-TVUS) of IUA or non-IUA images remains a clinical challenge and is needed to avoid inappropriate surgery. Our study aimed to evaluate deep learning as a method to classify 3D-TVUS of IUA or non-IUA images taken with panoramic technology. Methods: After meeting an inclusion/exclusion criteria, a total of 4,401 patients were selected for this study. This included 2,803 IUA patients and 1,598 non-IUA patients. IUA was confirmed by hysteroscopy, and each patient underwent one 3D-TVUS examination. Four well-known convolutional neural network (CNN) architectures were selected to classify the IUA images: Visual Geometry Group16 (VGG16), InceptionV3, ResNet50, and ResNet101. We used these pretrained CNNs on ImageNet by applying both TensorFlow and PyTorch. All 3D-TVUS images were normalized and mixed together. We split the data set into a training set, validation set, and test set. The performance of our classification model was evaluated according to sensitivity, precision, F1-score, and accuracy, which were determined by equations that used true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) numbers. Results: The overall performances of VGG16, InceptionV3, ResNet50, and ResNet101 were better in PyTorch as opposed to TensorFlow. Through PyTorch, the best CNN model was InceptionV3 with its performance measured as 94.2% sensitivity, 99.4% precision, 96.8% F1-score, and 97.3% accuracy. The area under the curve (AUC) results of VGG16, InceptionV3, ResNet50, and ResNet101 were 0.959, 0.999, 0.997, and 0.999, respectively. PyTorch also successfully transferred information from the source to the target domain where we were able to use another center's data as an external test data set. No overfitting that could have adversely affected the classification accuracy occurred. Finally, we successfully established a webpage to diagnose IUA based on the 3D-TVUS images. Conclusions: Deep learning can assist in the binary classification of 3D-TVUS images to diagnose IUA. This study lays the foundation for future research into the integration of deep learning and blockchain technology.

The efficacy and safety of Gore conformable thoracic stent graft and Valiant Captivia thoracic stent graft for acute type B aortic dissection.

BACKGROUND: To evaluate the safety and efficacy of the conformable thoracic aortic endograft (Conformable TAG Thoracic Endoprosthesis [CTAG]; W. L. Gore & Associates, Flagstaff, Ariz) and Valiant Captivia thoracic stent graft (Medtronic Inc., Santa Rosa, CA) for acute type B aortic dissection (TBAD). METHODS: The early and mid-term outcomes were analyzed for 413 patients undergoing TEVAR using conformable TAG thoracic endoprosthesis and Valiant Captivia thoracic stent graft for acute TBAD. 100 propensity-matched pairs of patients were generated, including 100 patients in the CTAG group and 200 patients in the Valiant Captivia group. RESULTS: Operative mortality were 2.33% (3 of 129) in the CTAG group and 1.76% (5 of 284) in the Valiant Captivia group. The median follow-up was 41.67 (26.00-60.67) months. No significant difference in mortality (9 [7.00%] vs. 36 [12.68%], P = 0.95) or re-intervention rate (3 [2.33%] vs. 20 [7.04%], P = 0.29) was observed between two groups. CTAG group have a lower incidence rate of distal stent graft-induced new entry tear than Valiant Captivia group (2.33% vs. 9.86%, P = 0.045). Lower incidence of type Ia endoleak was identified in the CTAG group (2.22%) than the Valiant Captivia group (14.41%) in patients with type III arch (P = 0.039). CONCLUSIONS: Both Valiant Captivia thoracic stent graft and CTAG thoracic endoprosthesis can be safely performed for acute TBAD with low operative mortality, favorable mid-term survival and freedom from reintervention. CTAG thoracic endoprosthesis had fewer dSINE even with larger oversizing and potentially suitable for type III arch with fewer type Ia endoleaks.

Sex differences in externalizing and internalizing traits and ventral striatal responses to monetary loss.

Ventral striatum (VS) processes rewarding and punishing stimuli. Women and men vary in externalizing and internalizing traits, which may influence neural responses to reward and punishment. To investigate sex differences in how individual traits influence VS responses to reward and punishment, we curated the data of the Human Connectome Project and identified 981 (473 men) subjects evaluated by the Achenbach Adult Self-Report Syndrome Scales. We processed the imaging data with published routines and extracted VS response (ß) to win and to loss vs. baseline in a gambling task for correlation with externalizing and internalizing symptom severity. Men vs. women showed more severe externalizing symptoms and higher VS response to monetary losses (VS-loss ß) but not to wins. Men but not women showed a significant, positive correlation between VS-loss ß and externalizing traits, and the sex difference was confirmed by a slope test. The correlations of VS-loss vs. externalizing and of VS-win vs. externalizing and those of VS-loss vs. externalizing and of VS-loss vs. internalizing traits both differed significantly in slope, confirming its specificity, in men. Further, the sex-specific relationship between VS-loss ß and externalizing trait did not extend to activities during exposure to negative emotion in the face matching task. To conclude, VS responses to loss but not to win and their correlation with externalizing rather than internalizing symptom severity showed sex differences in young adults. The findings highlight the relationship of externalizing traits and VS response to monetary loss and may have implications for psychological models of externalizing behaviors in men.