Computational Pathology for Prediction of Isocitrate Dehydrogenase Gene Mutation from Whole Slide Images in Adult Patients with Diffuse Glioma.

Isocitrate dehydrogenase gene (IDH) mutation is one of the most important molecular markers of glioma. Accurate detection of IDH status is a crucial step for integrated diagnosis of adult-type diffuse gliomas. Herein, a clustering-based hybrid of a convolutional neural network and a vision transformer deep learning model was developed to detect IDH mutation status from annotation-free hematoxylin and eosin-stained whole slide pathologic images of 2275 adult patients with diffuse gliomas. For comparison, a pure convolutional neural network, a pure vision transformer, and a classic multiple-instance learning model were also assessed. The hybrid model achieved an area under the receiver operating characteristic curve of 0.973 in the validation set and 0.953 in the external test set, outperforming the other models. The hybrid model's ability in IDH detection between difficult subgroups with different IDH status but shared histologic features, achieving areas under the receiver operating characteristic curve ranging from 0.850 to 0.985 in validation and test sets. These data suggest that the proposed hybrid model has a potential to be used as a computational pathology tool for preliminary rapid detection of IDH mutation from whole slide images in adult patients with diffuse gliomas.

Human neutrophil peptides 1-3 protect the murine urinary tract from uropathogenic Escherichia coli challenge.

Antimicrobial peptides (AMPs) are critical to the protection of the urinary tract of humans and other animals from pathogenic microbial invasion. AMPs rapidly destroy pathogens by disrupting microbial membranes and/or augmenting or inhibiting the host immune system through a variety of signaling pathways. We have previously demonstrated that alpha-defensins 1-3 (DEFA1A3) are AMPs expressed in the epithelial cells of the human kidney collecting duct in response to uropathogens. We also demonstrated that DNA copy number variations in the DEFA1A3 locus are associated with UTI and pyelonephritis risk. Because DEFA1A3 is not expressed in mice, we utilized human DEFA1A3 gene transgenic mice (DEFA4/4) to further elucidate the biological relevance of this locus in the murine urinary tract. We demonstrate that the kidney transcriptional and translational expression pattern is similar in humans and the human gene transgenic mouse upon uropathogenic Escherichia coli (UPEC) stimulus in vitro and in vivo. We also demonstrate transgenic human DEFA4/4 gene mice are protected from UTI and pyelonephritis under various UPEC challenges. This study serves as the foundation to start the exploration of manipulating the DEFA1A3 locus and alpha-defensins 1-3 expression as a potential therapeutic target for UTIs and other infectious diseases.

Local Mechanical Modulation-Driven Evagination in Invaginated Epithelia.

Local cells can actively create reverse bending (evagination) in invaginated epithelia, which plays a crucial role in the formation of elaborate organisms. However, the precise physical mechanism driving the evagination remains elusive. Here, we present a three-dimensional vertex model, incorporating the intrinsic cell polarity, to explore the complex morphogenesis induced by local mechanical modulations. We find that invaginated tissues can spontaneously generate local reverse bending due to the shift of the apicobasal polarity. Their exact shapes can be analytically determined by the local apicobasal differential tension and the internal stress. Our continuum theory exhibits three regions in a phase diagram controlled by these two parameters, showing curvature transitions from ordered to disordered states. Additionally, we delve into epithelial curvature transition induced by the nucleus repositioning, revealing its active contribution to the apicobasal force generation. The uncovered mechanical principles could potentially guide more studies on epithelial folding in diverse systems.

Emergence, Pattern, and Frequency of Spontaneous Waves in Spreading Epithelial Monolayers.

A striking phenomenon of collective cell motion is that they can exhibit a spontaneously emerging wave during epithelia expansions. However, the fundamental mechanism, governing the emergence and its crucial characteristics (e.g., the eigenfrequency and the pattern), remains an enigma. By introducing a mechanochemical feedback loop, we develop a highly efficient discrete vertex model to investigate the spatiotemporal evolution of spreading epithelia. We find both numerically and analytically that expanding cell monolayers display a power-law dependence of wave frequency on the local heterogeneities (i.e., cell density) with a scaling exponent of -1/2. Moreover, our study demonstrates the quantitative capability of the proposed model in capturing distinct X-, W-, and V-mode wave patterns. We unveil that the phase transition between these modes is governed by the distribution of active self-propulsion forces. Our work provides an avenue for rigorous quantitative investigations into the collective motion and pattern formation of cell groups.

JAK/STAT in leukemia: a clinical update.

Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.

Efficacy and Safety of Vonoprazan-Amoxicillin Dual Regimen With Varying Dose and Duration for Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Study.

BACKGROUND & AIMS: Previous studies confirm vonoprazan-amoxicillin effectiveness for Helicobacter pylori. This study aims to investigate vonoprazan with varying amoxicillin dose and duration. METHODS: This multicenter, prospective, randomized controlled, noninferiority trial enrolled patients with treatment naive H pylori infection from 5 clinical centers. Eligible participants were randomly assigned to H-VA-10 (vonoprazan 20 mg twice a day (b.i.d.) + amoxicillin 750 mg 4 times a day, 10 days), L-VA-10 (vonoprazan 20 mg b.i.d. + amoxicillin 1000 mg b.i.d, 10 days), and H-VA-14 (vonoprazan 20 mg b.i.d + amoxicillin 750 mg 4 times a day, 14 days) in a 1:1:1 ratio. The eradication rate was assessed using the 13C-urea breath test at least 28 days after treatment. RESULTS: Of the 623 eligible patients, 516 patients were randomized. In both the intention-to-treat and per-protocol analyses, eradication rates were comparable between H-VA-10 and H-VA-14 groups (86.6% vs 89.5% and 90.9% vs 94.5%, P = .021 and .013 for noninferiority, respectively). However, eradication rates were significantly lower in the L-VA-10 group than the H-VA-14 group (79.7% vs 89.5% and 82.0% vs 94.5%, P = .488 and .759, respectively). Rates of study withdrawal, loss to follow-up, and adverse events were similar across study groups. CONCLUSIONS: H-VA-10 and H-VA-14 regimens provide satisfactory efficacy for H pylori infection, and the L-VA-10 regimen was inferior. CLINICALTRIALS: gov number: NCT05719831.

Exogenous indole-3-acetic acid promotes the plant growth and accumulation of selenium in grapevine under selenium stress.

To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L- 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L- 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L- 1 IAA.

Excellent Room Temperature Thermoelectric Performance in Mg3 Sb2 -Based Alloys via Multi-Functional Doping of Nb.

Mg3 Sb2 -based alloys are attracting increasing attention due to the excellent room temperature thermoelectric properties. However, due to the presence and easy segregation of charged Mg vacancies, the carrier mobility in Mg3 Sb2 -based alloys is always severely compromised that significantly restricts the room temperature performance. General vacancy compensation strategies cannot synergistically optimize the complicated Mg3 Sb2 structures involving both interior and boundary scattering. Herein, due to the multi-functional doping effect of Nb, the electron scattering inside and across grains is significantly suppressed by inhibiting the accumulation of Mg vacancies, and leading to a smooth transmission channel of electrons. The increased Mg vacancies migration barrier and optimized interface potential are also confirmed theoretically and experimentally, respectively. As a result, a leading room temperature zT of 1.02 is achieved. This work reveals the multi-functional doping effect as an efficient approach in improving room temperature thermoelectric performance in complicated defect/interface associated Mg3 Sb2 -based alloys.

TMEM41B Is an Interferon-Stimulated Gene That Promotes Pseudorabies Virus Replication.

Pseudorabies virus (PRV) is a double-stranded DNA virus that causes Aujeszky's disease and is responsible for economic loss worldwide. Transmembrane protein 41B (TMEM41B) is a novel endoplasmic reticulum (ER)-localized regulator of autophagosome biogenesis and lipid mobilization; however, the role of TMEM41B in regulating PRV replication remains undocumented. In this study, PRV infection was found to upregulate TMEM41B mRNA and protein levels both in vitro and in vivo. For the first time, we found that TMEM41B could be induced by interferon (IFN), suggesting that TMEM41B is an IFN-stimulated gene (ISG). While TMEM41B knockdown suppressed PRV proliferation, TMEM41B overexpression promoted PRV proliferation. We next studied the specific stages of the virus life cycle and found that TMEM41B knockdown affected PRV entry. Mechanistically, we demonstrated that the knockdown of TMEM41B blocked PRV-stimulated expression of the key enzymes involved in lipid synthesis. Additionally, TMEM41B knockdown played a role in the dynamics of lipid-regulated PRV entry-dependent clathrin-coated pits (CCPs). Lipid replenishment restored the CCP dynamic and PRV entry in TMEM41B knockdown cells. Together, our results indicate that TMEM41B plays a role in PRV infection via regulating lipid homeostasis. IMPORTANCE PRV belongs to the alphaherpesvirus subfamily and can establish and maintain a lifelong latent infection in pigs. As such, an intermittent active cycle presents great challenges to the prevention and control of PRV disease and is responsible for serious economic losses to the pig breeding industry. Studies have shown that lipids play a crucial role in PRV proliferation. Thus, the manipulation of lipid metabolism may represent a new perspective for the prevention and treatment of PRV. In this study, we report that the ER transmembrane protein TMEM41B is a novel ISG involved in PRV infection by regulating lipid synthesis. Therefore, our findings indicate that targeting TMEM41B may be a promising approach for the development of PRV vaccines and therapeutics.

A PCR-independent approach for mtDNA enrichment and next-generation sequencing: comprehensive evaluation and clinical application.

BACKGROUND: Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing). RESULTS: By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases. CONCLUSIONS: Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.

Integrating data distribution prior via Langevin dynamics for end-to-end MR reconstruction.

PURPOSE: To develop a novel deep learning-based method inheriting the advantages of data distribution prior and end-to-end training for accelerating MRI. METHODS: Langevin dynamics is used to formulate image reconstruction with data distribution before facilitate image reconstruction. The data distribution prior is learned implicitly through the end-to-end adversarial training to mitigate the hyper-parameter selection and shorten the testing time compared to traditional probabilistic reconstruction. By seamlessly integrating the deep equilibrium model, the iteration of Langevin dynamics culminates in convergence to a fix-point, ensuring the stability of the learned distribution. RESULTS: The feasibility of the proposed method is evaluated on the brain and knee datasets. Retrospective results with uniform and random masks show that the proposed method demonstrates superior performance both quantitatively and qualitatively than the state-of-the-art. CONCLUSION: The proposed method incorporating Langevin dynamics with end-to-end adversarial training facilitates efficient and robust reconstruction for MRI. Empirical evaluations conducted on brain and knee datasets compellingly demonstrate the superior performance of the proposed method in terms of artifact removing and detail preserving.

B1 inhomogeneity corrected CEST MRI based on direct saturation removed omega plot model at 5T.

PURPOSE: CEST can image macromolecules/compounds via detecting chemical exchange between labile protons and bulk water. B1 field inhomogeneity impairs CEST quantification. Conventional B1 inhomogeneity correction methods depend on interpolation algorithms, B1 choices, acquisition number or calibration curves, making reliable correction challenging. This study proposed a novel B1 inhomogeneity correction method based on a direct saturation (DS) removed omega plot model. METHODS: Four healthy volunteers underwent B1 field mapping and CEST imaging under four nominal B1 levels of 0.75, 1.0, 1.5, and 2.0 µT at 5T. DS was resolved using a multi-pool Lorentzian model and removed from respective Z spectrum. Residual spectral signals were used to construct the omega plot as a linear function of 1/ B 1 2 $$ {B}_1^2 $$ , from which corrected signals at nominal B1 levels were calculated. Routine asymmetry analysis was conducted to quantify amide proton transfer (APT) effect. Its distribution across white matter was compared before and after B1 inhomogeneity correction and also with the conventional interpolation approach. RESULTS: B1 inhomogeneity yielded conspicuous artifact on APT images. Such artifact was mitigated by the proposed method. Homogeneous APT maps were shown with SD consistently smaller than that before B1 inhomogeneity correction and the interpolation method. Moreover, B1 inhomogeneity correction from two and four CEST acquisitions yielded similar results, superior over the interpolation method that derived inconsistent APT contrasts among different B1 choices. CONCLUSION: The proposed method enables reliable B1 inhomogeneity correction from at least two CEST acquisitions, providing an effective way to improve quantitative CEST MRI.

Light field image super-resolution based on dual learning and deep Fourier channel attention.

Light field (LF) imaging has gained significant attention in the field of computational imaging due to its unique capability to capture both spatial and angular information of a scene. In recent years, super-resolution (SR) techniques based on deep learning have shown considerable advantages in enhancing LF image resolution. However, the inherent challenges of obtaining rich structural information and reconstructing complex texture details persist, particularly in scenarios where spatial and angular information are intricately interwoven. This Letter introduces a novel, to the best of our knowledge, approach for Disentangling LF Image SR Network (DLISN) by leveraging the synergy of dual learning and Fourier channel attention (FCA) mechanisms. Dual learning strategies are employed to enhance reconstruction results, addressing limitations in model generalization caused by the difficulty in acquiring paired datasets in real-world LF scenarios. The integration of FCA facilitates the extraction of high-frequency information associated with different structures, contributing to improved spatial resolution. Experimental results consistently demonstrate superior performance in enhancing the resolution of LF images.

High-performance multi-junction cascade 1.3†µm quantum dot vertical cavity surface-emitting laser.

A high-performance 5-junction cascade quantum dot (QD) vertical cavity surface-emitting laser (VCSEL) with 1.3 µm wavelength was designed. The characteristics of the QD as active regions and tunnel junctions are combined to effectively increase output power. The photoelectric characteristics of single-junction, 3-junction cascade, and 5-junction cascade QD VCSELs are compared at continuous-wave conditions. Results indicate that the threshold current gradually decreases, and the output power and slope efficiency exponential increase with the increase of the number of active regions. The peak power conversion efficiency of 58.4% is achieved for the 5-junction cascade individual QD VCSEL emitter with 10 µm oxide aperture. The maximum slope efficiency of the device is 6.27 W/A, which is approximately six times than that of the single-junction QD VCSEL. The output power of the 5-junction cascade QD VCSEL reaches 188.13 mW at injection current 30 mA. High-performance multi-junction cascade 1.3-µm QD VCSEL provides data and theoretical support for the preparation of epitaxial materials.

Development and performance of SIAT bPET: a high-resolution and high-sensitivity MR-compatible brain PET scanner using dual-ended readout detectors.

PURPOSE: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a powerful tool for brain imaging, but the spatial resolution of the PET scanners currently used for brain imaging can be further improved to enhance the quantitative accuracy of brain PET imaging. The purpose of this study is to develop an MR-compatible brain PET scanner that can simultaneously achieve a uniform high spatial resolution and high sensitivity by using dual-ended readout depth encoding detectors. METHODS: The MR-compatible brain PET scanner, named SIAT bPET, consists of 224 dual-ended readout detectors. Each detector contains a 26 × 26 lutetium yttrium oxyorthosilicate (LYSO) crystal array of 1.4 × 1.4 × 20 mm3 crystal size read out by two 10 × 10 silicon photomultiplier (SiPM) arrays from both ends. The scanner has a detector ring diameter of 376.8 mm and an axial field of view (FOV) of 329 mm. The performance of the scanner including spatial resolution, sensitivity, count rate, scatter fraction, and image quality was measured. Imaging studies of phantoms and the brain of a volunteer were performed. The mutual interferences of the PET insert and the uMR790 3 T MRI scanner were measured, and simultaneous PET/MRI imaging of the brain of a volunteer was performed. RESULTS: A spatial resolution of better than 1.5 mm with an average of 1.2 mm within the whole FOV was obtained. A sensitivity of 11.0% was achieved at the center FOV for an energy window of 350-750 keV. Except for the dedicated RF coil, which caused a ~ 30% reduction of the sensitivity of the PET scanner, the MRI sequences running had a negligible effect on the performance of the PET scanner. The reduction of the SNR and homogeneity of the MRI images was less than 2% as the PET scanner was inserted to the MRI scanner and powered-on. High quality PET and MRI images of a human brain were obtained from simultaneous PET/MRI scans. CONCLUSION: The SIAT bPET scanner achieved a spatial resolution and sensitivity better than all MR-compatible brain PET scanners developed up to date. It can be used either as a standalone brain PET scanner or a PET insert placed inside a commercial whole-body MRI scanner to perform simultaneous PET/MRI imaging.

Development and application of LC-MS/MS method for the quantification of hydrogen sulfide in the eye.

There are limited studies that report the physiological levels of H2S in the eye. The currently available UV/Vis methods lack the required sensitivity and precision. Hence, the purpose of this study was to develop and validate a sensitive and robust pre-column derivatization LC-MS/MS method to measure changes in H2S levels in tissues from isolated porcine eyes. H2S was derivatized and an LC-MS/MS method was developed to monitor the derivatized product, Sulfide-dibimane (Sdb) using a reverse phase Waters Acquity BEH C18 column (1.7 µm, 2.1 × 100 mm). H2S quantification was performed using multiple-ion reaction monitoring (MRM) in positive mode, with the transitions of m/z 415.0 → m/z 223.0 for Sdb and m/z 353.0 → m/z 285.0 for internal standard (griseofulvin). This method provided a suitable way to quantify H2S and was then successfully adapted to measure H2S levels in isolated porcine iris-ciliary body tissues previously treated in the presence or absence of varying concentrations of lipopolysaccharide (LPS, 5-100 ng/ml), a pro-inflammatory agent. Isolated iris-ciliary bodies (ICB) from porcine eyes were cut into quadrants of approximately 50 mg and homogenized using a 1:3 volume of homogenizing buffer. H2S in the supernatant was then derivatized with monobromobimane and quantified.

Voxel-wise mapping of DCE-MRI time-intensity-curve profiles enables visualizing and quantifying hemodynamic heterogeneity in breast lesions.

OBJECTIVES: To propose a novel model-free data-driven approach based on the voxel-wise mapping of DCE-MRI time-intensity-curve (TIC) profiles for quantifying and visualizing hemodynamic heterogeneity and to validate its potential clinical applications. MATERIALS AND METHODS: From December 2018 to July 2022, 259 patients with 325 pathologically confirmed breast lesions who underwent breast DCE-MRI were retrospectively enrolled. Based on the manually segmented breast lesions, the TIC of each voxel within the 3D whole lesion was classified into 19 subtypes based on wash-in rate (nonenhanced, slow, medium, and fast), wash-out enhancement (persistent, plateau, and decline), and wash-out stability (steady and unsteady), and the composition ratio of these 19 subtypes for each lesion was calculated as a new feature set (type-19). The three-type TIC classification, semiquantitative parameters, and type-19 features were used to build machine learning models for identifying lesion malignancy and classifying histologic grades, proliferation status, and molecular subtypes. RESULTS: The type-19 feature-based model significantly outperformed models based on the three-type TIC method and semiquantitative parameters both in distinguishing lesion malignancy (respectively; AUC = 0.875 vs. 0.831, p = 0.01 and 0.875vs. 0.804, p = 0.03), predicting tumor proliferation status (AUC = 0.890 vs. 0.548, p = 0.006 and 0.890 vs. 0.596, p = 0.020), but not in predicting histologic grades (p = 0.820 and 0.970). CONCLUSION: In addition to conventional methods, the proposed computational approach provides a novel, model-free, data-driven approach to quantify and visualize hemodynamic heterogeneity. CLINICAL RELEVANCE STATEMENT: Voxel-wise intra-lesion mapping of TIC profiles allows for visualization of hemodynamic heterogeneity and its composition ratio for differentiation of malignant and benign breast lesions. KEY POINTS: • Voxel-wise TIC profiles were mapped, and their composition ratio was compared between various breast lesions. • The model based on the composition ratio of voxel-wise TIC profiles significantly outperformed the three-type TIC classification model and the semiquantitative parameters model in lesion malignancy differentiation and tumor proliferation status prediction in breast lesions. • This novel, data-driven approach allows the intuitive visualization and quantification of the hemodynamic heterogeneity of breast lesions.

Learning CT-free attenuation-corrected total-body PET images through deep learning.

OBJECTIVES: Total-body PET/CT scanners with long axial fields of view have enabled unprecedented image quality and quantitative accuracy. However, the ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Therefore, we attempted to generate CT-free attenuation-corrected (CTF-AC) total-body PET images through deep learning. METHODS: Based on total-body PET data from 122 subjects (29 females and 93 males), a well-established cycle-consistent generative adversarial network (Cycle-GAN) was employed to generate CTF-AC total-body PET images directly while introducing site structures as prior information. Statistical analyses, including Pearson correlation coefficient (PCC) and t-tests, were utilized for the correlation measurements. RESULTS: The generated CTF-AC total-body PET images closely resembled real AC PET images, showing reduced noise and good contrast in different tissue structures. The obtained peak signal-to-noise ratio and structural similarity index measure values were 36.92 ± 5.49 dB (p < 0.01) and 0.980 ± 0.041 (p < 0.01), respectively. Furthermore, the standardized uptake value (SUV) distribution was consistent with that of real AC PET images. CONCLUSION: Our approach could directly generate CTF-AC total-body PET images, greatly reducing the radiation risk to patients from redundant anatomical examinations. Moreover, the model was validated based on a multidose-level NAC-AC PET dataset, demonstrating the potential of our method for low-dose PET attenuation correction. In future work, we will attempt to validate the proposed method with total-body PET/CT systems in more clinical practices. CLINICAL RELEVANCE STATEMENT: The ionizing radiation from CT is a major issue in PET imaging, which is more evident with reduced radiopharmaceutical doses in total-body PET/CT. Our CT-free PET attenuation correction method would be beneficial for a wide range of patient populations, especially for pediatric examinations and patients who need multiple scans or who require long-term follow-up. KEY POINTS: • CT is the main source of radiation in PET/CT imaging, especially for total-body PET/CT devices, and reduced radiopharmaceutical doses make the radiation burden from CT more obvious. • The CT-free PET attenuation correction method would be beneficial for patients who need multiple scans or long-term follow-up by reducing additional radiation from redundant anatomical examinations. • The proposed method could directly generate CT-free attenuation-corrected (CTF-AC) total-body PET images, which is beneficial for PET/MRI or PET-only devices lacking CT image poses.

Pseudorabies virus hijacks the Rab6 protein to promote viral assembly and egress.

Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.

Multiple-cycle photochemical cascade reactions.

Cascade reactions represent an efficient and economical synthetic approach, enabling the rapid synthesis of a wide array of structurally complex organic compounds. These compounds, previously inaccessible, can now be synthesized in a remarkably limited number of steps. Concurrently, the photochemical reactions of organic molecules have gained prominence as a potent strategy for accessing a diverse range of radical species and intermediates. This is achieved in a controlled manner under mild conditions. Owing to the relentless endeavors of chemists, significant strides have been made in the realm of photochemical cascade reactions. These advancements have facilitated the synthesis of novel molecular structures with high complexity, structures that are typically challenging to generate under thermal conditions. In this review, we comprehensively summarize and underscore the recent pivotal advancements in visible-light-induced cascade reactions. Our focus is on the elucidation of multiple photochemical catalytic cycles, emphasizing the catalytic activation modes and the types of reactions involved.