Nuclear m6 A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3' processing machinery.

N6-methyladenosine (m6 A) and alternative polyadenylation (APA) are important regulators of gene expression in eukaryotes. Recently, it was found that m6 A is closely related to APA. However, the molecular mechanism of this new APA regulation remains elusive. Here, we show that YTHDC1, a nuclear m6 A reader, can suppress proximal APA sites and produce longer 3' UTR transcripts by binding to their upstream m6 A sites. YTHDC1 can directly interact with the 3' end processing factor FIP1L1 and interfere with its ability to recruit CPSF4. Binding to the m6 A sites can promote liquid-liquid phase separation of YTHDC1 and FIP1L1, which may play an important role in their interaction and APA regulation. Collectively, YTHDC1 as an m6 A "reader" links m6 A modification with pre-mRNA 3' end processing, providing a new mechanism for APA regulation.

Study of Resource Allocation for 5G URLLC/eMBB-Oriented Power Hybrid Service.

With the rapid development of the 5G power Internet of Things (IoT), new power systems have higher requirements for data transmission rates, latency, reliability, and energy efficiency. Specifically, the hybrid service of enhanced mobile broadband (eMBB) and ultra-reliable low-latency communication (URLLC) has brought new challenges to the differentiated service of the 5G power IoT. To solve the above problems, this paper first constructs a power IoT model based on NOMA for the mixed service of URLLC and eMBB. Considering the shortage of resource utilization in eMBB and URLLC hybrid power service scenarios, the problem of maximizing system throughput through joint channel selection and power allocation is proposed. The channel selection algorithm based on matching as well as the power allocation algorithm based on water injection are developed to tackle the problem. Both theoretical analysis and experimental simulation verify that our method has superior performance in system throughput and spectrum efficiency.

Evaluation of pediatric malignancies using total-body PET/CT with half-dose [18F]-FDG.

PURPOSE: To explore the impact of a true half dose of [18F]-FDG on image quality in pediatric oncological patients undergoing total-body PET/CT and investigate short acquisition times with half-dose injected activity. METHODS: One hundred pediatric oncological patients who underwent total-body PET/CT using the uEXPLORER scanner after receiving a true half dose of [18F]-FDG (1.85 MBq/kg) were retrospectively enrolled. The PET images were first reconstructed using complete 600-s data and then split into 300-s, 180-s, 60-s, 40-s, and 20-s duration groups (G600 to G20). The subjective analysis was performed using 5-point Likert scales. Objective quantitative metrics included the maximum standard uptake value (SUVmax), SUVmean, standard deviation (SD), signal-to-noise ratio (SNR), and SNRnorm of the background. The variabilities in lesion SUVmean, SUVmax, and tumor-to-background ratio (TBR) were also calculated. RESULTS: The overall image quality scores in the G600, G300, G180, and G60 groups were 4.9 ± 0.2, 4.9 ± 0.3, 4.4 ± 0.5, and 3.5 ± 0.5 points, respectively. All the lesions identified in the half-dose images were localized in the G60 images, while 56% of the lesions could be clearly identified in the G20 images. With reduced acquisition time, the SUVmax and SD of the backgrounds were gradually increased, while the TBR values showed no statistically significant differences among the groups (all p > 0.1). Using the half-dose images as a reference, the variability in the lesion SUVmax gradually increased from the G180 to G20 images, while the lesion SUVmean remained stable across all age groups. SNRnorm was highly negatively correlated with age. CONCLUSION: Total-body PET/CT with a half dose of [18F]-FDG (1.85 MBq/kg, estimated whole-body effective dose: 1.76-2.57 mSv) achieved good performance in pediatric patients, with sufficient image quality and good lesion conspicuity. Sufficient image quality and lesion conspicuity could be maintained at a fast scanning time of 60 s with half-dose activity.

The image quality, lesion detectability, and acquisition time of 18F-FDG total-body PET/CT in oncological patients.

PURPOSE: The purpose was to investigate the effects of short acquisition time on the image quality and the lesion detectability of oncological 18F-FDG total-body PET/CT. METHODS: Nineteen oncological patients (6/13 women/men, age 65.6 ± 9.4 years) underwent total-body PET/CT on uEXPLORER scanner using 3D list mode. The administration of 18F-FDG was weight-based (4.4 MBq/kg). The acquisition time was 900 s, and PET data were reconstructed into 900-, 180-, 120-, 60-, 30-, and 18-s duration groups. The subjective PET image quality was scored using a 5-point scale (5, excellent; 1, poor) in 3 perspectives: overall quality, noise, and lesion conspicuity. The objective image quality was evaluated by SUVmax and standard deviation (SD) of the liver, SUVmax of the tumor, and tumor-to-background ratio (TBR). The lesion detectability was the percentage of identifiable lesions in the groups of 180 to 18 s using the group 900 s as reference. RESULTS: Our results showed that sufficient and acceptable subjective image quality could be achieved with 60- and 30-s groups, and good image quality scores were given to 180- and 120-s groups without significant difference. For shortened acquisition time, SD was increased, while SUVmax of tumor and TBR remained unchanged. The lesion detectability was decreased with shorter acquisition time, but the detection performance could be maintained until the 60-s group compared with the 900-s group, although the image quality degraded. CONCLUSION: The total-body PET/CT can significantly shorten the acquisition time with maintained lesion detectability and image quality.

Radical SAM-dependent adenosylation catalyzed by l-tyrosine lyases.

The radical S-adenosylmethionine (SAM) superfamily is currently the largest known enzyme family. These enzymes reductively cleave SAM to produce a highly reactive 5'-deoxyadenosyl (dAdo) radical, which abstracts a hydrogen from the substrate and initiates diverse reactions. The canonic dAdo radical-mediated hydrogen abstraction can be changed to radical addition reactions by using olefin-containing substrate analogues, which result in adenosylation reactions. Here we report investigation of the adenosylation reactions catalyzed by four radical SAM l-Tyr lyases (RSTLs), including HydG, FbiC, and two ThiH enzymes from different organisms. We show RSTLs have diverse substrate specificity, and ThiH from E. coli exhibits the highest substrate tolerance toward the tested substrates. We also show ThiH from Clostridium berjerinckii does not act on 4-amino-l-phenylalanine, but catalyzes adenosylation of the corresponding olefin-containing analogue, suggesting adenosylation may occur more easily than the canonic radical SAM reactions. Our study highlights the remarkable catalytic promiscuity of radical SAM enzyme and the potential in using these enzymes for the synthesis of nucleotide-containing compounds.

Low Dose and Low Contrast Medium Coronary CT Angiography Using Dual-Layer Spectral Detector CT.

The aim of the present study was to investigate the performance of low keV mono-energetic reconstructions in spectral coronary computed tomography angiography (CCTA) using spectral detector CT (SDCT) with reduced contrast media and radiation dose.Sixty patients were randomly assigned to Groups A and B (both n = 30) to undergo CCTA on a dual-layer SDCT with tube voltage 120 kVp and 100 kVp (average tube current: 108.5 and 73.8 mAs, respectively), with contrast media volume of 36 mL used in both groups. The mono-energetic 40-80 keV and conventional 120 kVp images in Group A and conventional 100 kVp images in Group B were reconstructed. Quantitative and qualitative image quality (IQ) were evaluated in the aortic root and distal segments of the coronary arteries.The patient characteristics were not significantly different between the two groups (all P≥ 0.47), nor was the effective radiation dose (1.5 ± 0.3 and 1.4 ± 0.3 mSv, P = 0.20). The quantitative IQ in aorta and coronary arteries of mono-energetic 40-60 keV was superior to conventional 120 kVp and 100 kVp images (all P < 0.05). The noise in spectral images was lower compared to conventional images (all P < 0.01). The subjective IQ score of 40-50 keV images was not significantly different from that of 100 kVp images (P > 0.8).The mono-energetic 40-50 keV reconstructions from spectral CCTA using SDCT provide improved IQ compared to conventional techniques while facilitating reduced radiation dose and contrast media.

Diagnostic accuracy of coronary CT angiography: comparison of filtered back projection and iterative reconstruction with different strengths.

PURPOSE: To investigate the diagnostic accuracy of coronary computed tomographic (CT) angiography (CCTA) using filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) of different strength factors with invasive coronary angiography as the reference standard. MATERIALS AND METHODS: Fifty consecutive patients (32 men and 18 women) prospectively underwent electrocardiogram-triggered CCTA on a dual-source CT system. The acquisition window was set depending on the heart rate (HR): HR of less than 60 beats per minute (bpm) at the 70% RR interval, 61 to 80 bpm at 30% to 80% RR interval, and greater than 80 bpm at 30% to 50% RR interval; 100 kV and 359 to 377 mA s for patients with a body mass index of less than 24 kg/m, and 410 to 438 mA s at 120 kV for patients with a body mass index of 24 kg/m or greater. Image data were reconstructed using both FBP and SAFIRE. Sinogram-affirmed iterative reconstruction series were reconstructed using 3 different strength factors. Two blinded observers independently assessed the image quality and image impression of each coronary segment using a 4-point scale (1, non-diagnostic; and 4, excellent). Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured. Filtered back projection and all SAFIRE series were independently evaluated for coronary artery stenosis (>50%), and their diagnostic accuracy was compared with invasive coronary angiography. RESULTS: Statistically significant increases in SNR and CNR were obtained when higher strength factors were used. The highest SNR and CNR were found with the highest SAFIRE strength factor of 5; however, this strength also resulted in a more unfamiliar, "plasticlike" image appearance. Imaging quality scores of FBP and different SAFIRE strengths were 3.37 ± 0.49, 3.41 ± 0.47, 3.52 ± 0.30, and 3.48 ± 0.35, respectively (P < 0.001). The diagnostic accuracies were 92.91%, 93.76%, 95.28%, and 94.94% on per-segment level, respectively (P = 0.993). A tendency toward higher diagnostic performance was observed with SAFIRE strength factor 3 on per-segment analysis, albeit without reaching statistical significance. The effective radiation dose equivalent was 5.7 ± 1.6 mSv. CONCLUSION: Sinogram-affirmed iterative reconstruction provides significant improvements in image noise, SNR, and CNR compared with FBP, which are progressive with increasing SAFIRE strength factors. Sinogram-affirmed iterative reconstruction strength factor 3 or 5 is recommended for use with CCTA.

Aortic dual-energy CT angiography with low contrast medium injection rate.

The contrast medium (CM) induced nephropathy required new CT imaging protocol. This study evaluated the feasibility of low contrast medium (CM) volume and injection flow using aortic dual-energy CT (DECT) angiography with non-linear blending technique. Sixty patients were randomly assigned to two groups: control group (n=30), single-energy CT 70 ml CM at injection rate of 5 ml/s; study group (n=30), DECT mode, 0.5 ml per kg of patient weight CM at injection rate=(weight × 0.5 ml/kg)/(4+scan time). Non-linear blending technique was used for dual-energy images. Mean attention, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of aorta were compared. The level of visible renal artery branches was scored. There was no significant difference between the two groups in the mean aortic attention, SNR and CNR (all P > 0.05). Significant difference was showed in CM injection rate (p < 0.001) and volume (P < 0.001). The renal artery score had no statistically significant difference (P=0.771). Compared conventional scan and CM injection protocol, DECT with non-linear blending technique maintained the image quality of aortic CT angiography with reduced CM volume and flow rate, which could reduce the risks associated with CM injection.

The Role of Total-Body PET in Drug Development and Evaluation: Status and Outlook.

Total-body PET, an emerging technique, enables high-quality simultaneous total-body dynamic PET acquisition and accurate kinetic analysis. It has the potential to facilitate the study of multiple tracers while minimizing radiation dose and improving tracer-specific imaging. This advancement holds promise for enhancing the development and clinical evaluation of drugs, particularly radiopharmaceuticals. Multiple clinical trials are using a total-body PET scanner to explore existing and innovative radiopharmaceuticals. However, challenges persist, along with the opportunities, with regard to the use of total-body PET in drug development and evaluation. Specifically, considerations relate to the role of total-body PET in clinical pharmacologic evaluations and its integration into the theranostic paradigm. In this review, state-of-the-art total-body PET and its potential roles in pharmaceutical research are explored.

All-trans retinoic acid acts as a dual-purpose inhibitor of SARS-CoV-2 infection and inflammation.

Coronavirus disease 2019 (COVID-19) was an epidemic that effected human health caused by SARS-CoV-2 infection. All-trans retinoic acid (ATRA) has anti-inflammatory capability. In this article, we evaluated the effectiveness and revealed the molecular mechanism of ATRA for treating SARS-CoV-2 using deep learning, in vitro studies, multi-scale molecular modeling, and network pharmacology. The DeepDTA model suggested that ATRA would be effective against COVID-19. In vitro studies confirmed the antiviral activity of ATRA. Subsequently, multi-scale molecular modeling indicated that ATRA could binding to angiotensin converting enzyme 2 (ACE2), 3C-like protease (3CLpro), RNA dependent RNA polymerase (RdRp), helicase, and 3'-to-5' exonuclease by non-covalent interactions. Additionally, network pharmacology suggested that ATRA alleviated inflammatory response by regulating the IL-17 signaling pathway and binding with TNF, PTGS2, and MAPK1 directly. In summary, our findings provide the first evidence that ATRA suppresses the entry and replication of SARS-CoV-2, and regulates inflammatory response of host cells.

Low 18F-fluorodeoxyglucose dose positron emission tomography assisted by a deep-learning image-denoising technique in patients with lymphoma.

Background: Patients with lymphoma receive multiple positron emission tomography/computed tomography (PET/CT) exams for monitoring of the therapeutic response. With PET imaging, a reduced level of injected fluorine-18 fluorodeoxyglucose ([18F]FDG) activity can be administered while maintaining the image quality. In this study, we investigated the efficacy of applying a deep learning (DL) denoising-technique on image quality and the quantification of metabolic parameters and Deauville score (DS) of a low [18F]FDG dose PET in patients with lymphoma. Methods: This study retrospectively enrolled 62 patients who underwent [18F]FDG PET scans. The low-dose (LD) data were simulated by taking a 50% duration of routine-dose (RD) PET list-mode data in the reconstruction, and a U-Net-based denoising neural network was applied to improve the images of LD PET. The visual image quality score (1 = undiagnostic, 5 = excellent) and DS were assessed in all patients by nuclear radiologists. The maximum, mean, and standard deviation (SD) of the standardized uptake value (SUV) in the liver and mediastinum were measured. In addition, lesions in some patients were segmented using a fixed threshold of 2.5, and their SUV, metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) were measured. The correlation coefficient and limits of agreement between the RD and LD group were analyzed. Results: The visual image quality of the LD group was improved compared with the RD group. The DS was similar between the RD and LD group, and the negative (DS 1-3) and positive (DS 4-5) results remained unchanged. The correlation coefficients of SUV in the liver, mediastinum, and lesions were all >0.85. The mean differences of SUVmax and SUVmean between the RD and LD groups, respectively, were 0.22 [95% confidence interval (CI): -0.19 to 0.64] and 0.02 (95% CI: -0.17 to 0.20) in the liver, 0.13 (95% CI: -0.17 to 0.42) and 0.02 (95% CI: -0.12 to 0.16) in the mediastinum, and -0.75 (95% CI: -3.42 to 1.91), and -0.13 (95% CI: -0.57 to 0.31) in lesions. The mean differences in MTV and TLG were 0.85 (95% CI: -2.27 to 3.98) and 4.06 (95% CI: -20.53 to 28.64) between the RD and LD groups. Conclusions: The DL denoising technique enables accurate tumor assessment and quantification with LD [18F]FDG PET imaging in patients with lymphoma.

The impact of deep-inspiration breath-hold total-body PET/CT imaging on thoracic 18F-FDG avid lesions compared with free-breathing.

OBJECTIVES: To investigate PET/CT registration and quantification accuracy of thoracic lesions of a single 30-second deep-inspiration breath-hold (DIBH) technique with a total-body PET (TB-PET) scanner, and compared with free-breathing (FB) PET/CT. METHODS: 137 of the 145 prospectively enrolled patients finished a routine FB-300 s PET/CT exam and a 30-second DIBH TB-PET with chest to pelvis low dose CT. The total-body FB-300 s, FB-30 s, and DIBH-30 s PET images were reconstructed. Quantitative assessment (SUVmax and SUVmean of lung and other organs), PET/CT registration assessment and lesion analysis (SUVmax, SUVpeak, SUVmean and tumor-background ratio) were compared with Wilcoxon signed-rank tests. RESULTS: The SUVmax and SUVmean of the lung with DIBH-30 s were significantly lower than those with FB. The distances of the liver dome between PET and CT were significantly smaller with DIBH-30 s than with FB. 195 assessable lesions in 106 patients were included, and the detection sensitivity was 97.9 % and 99.0 % in FB-300 s, and DIBH-30 s, respectively. For both small co-identified lesions (n = 86) and larger co-identified lesions with a diameter ≥ 1 cm (n = 91), the lesion SUVs were significantly greater with DIBH-30 s than with FB-300 s. Regarding lesion location, the differences of the SUVs for the lesions in the lower thorax area (n = 97, p < 0.001) were significant between DIBH-30 s and FB-300 s, while these differences were not statistically significant in the upper thorax (n = 80, p > 0.05). The lesion tumor-to-surrounding-background ratio (TsBR) was significantly increased, both in the upper and lower thorax. CONCLUSION: The TB DIBH PET/CT technique is feasible in clinical practice. It reduces the background lung uptake and achieves better registration and lesion quantification, especially in the lower thorax.

Optimal contrast of computed tomography portal venography using dual-energy computed tomography.

OBJECTIVE: The objective of this study was to evaluate image quality of computed tomography (CT) portal venography using nonlinear blending technique of dual-energy CT (DECT) in portal phase. METHODS: Fifty patients underwent contrast-enhanced abdominal scan with DECT at portal venous phase. The images of 2 energy levels were mixed by a nonlinear blending filter defined by blending center (BC) and blending width (BW) and compared with linear mixing images with a ratio of 0.5. Image quality was evaluated by the images' contrast-to-noise ratios (CNRs) and the grade of visible branches of portal vein (grades 1-6). The BC and BW were optimized for the best CNRs. RESULTS: The portal-to-hepatic contrast was significantly higher when the average of the liver and portal vein CT values was chosen as the BC, and 0 to 20 Hounsfield units were chosen as the BW than when using the default mixing values (80.04 [SD, 28.09] vs 38.55 [SD, 14.49] Hounsfield units, P < 0.001). In the optimized images using the nonlinear mixing technique, the mean CT values for the portal venous system and the CNRs were significantly greater than those of the linear mixing images (P < 0.001). A visible branch grade 5 or greater was assigned to 76% of the patients in the optimized group and 36% of the patients in the default linear mixing group. This difference was significant (P < 0.01). CONCLUSIONS: The nonlinear blending technique of DECT can improve the image quality of portal venography and show more branches of portal vein without changing the conventional scan protocol.

Omni-Frequency Channel-Selection Representations for Unsupervised Anomaly Detection.

Density-based and classification-based methods have ruled unsupervised anomaly detection in recent years, while reconstruction-based methods are rarely mentioned for the poor reconstruction ability and low performance. However, the latter requires no costly extra training samples for the unsupervised training that is more practical, so this paper focuses on improving reconstruction-based method and proposes a novel O mni-frequency C hannel-selection R econstruction (OCR-GAN) network to handle sensory anomaly detection task in a perspective of frequency. Concretely, we propose a Frequency Decoupling (FD) module to decouple the input image into different frequency components and model the reconstruction process as a combination of parallel omni-frequency image restorations, as we observe a significant difference in the frequency distribution of normal and abnormal images. Given the correlation among multiple frequencies, we further propose a Channel Selection (CS) module that performs frequency interaction among different encoders by adaptively selecting different channels. Abundant experiments demonstrate the effectiveness and superiority of our approach over different kinds of methods, e.g., achieving a new state-of-the-art 98.3 detection AUC on the MVTec AD dataset without extra training data that markedly surpasses the reconstruction-based baseline by +38.1 ↑ and the current SOTA method by +0.3 ↑ . The source code is available in the additional materials.

Classification of Motor Imagery Based on Multi-Scale Feature Extraction and the Channel-Temporal Attention Module.

Motor imagery (MI) is a popular paradigm for controlling electroencephalogram (EEG) based Brain-Computer Interface (BCI) systems. Many methods have been developed to attempt to accurately classify MI-related EEG activity. Recently, the development of deep learning has begun to draw increasing attention in the BCI research community because it does not need to use sophisticated signal preprocessing and can automatically extract features. In this paper, we propose a deep learning model for use in MI-based BCI systems. Our model makes use of a convolutional neural network based on a multi-scale and channel-temporal attention module (CTAM), which called MSCTANN. The multi-scale module is able to extract a large number of features, while the attention module includes both a channel attention module and a temporal attention module, which together allow the model to focus attention on the most important features extracted from the data. The multi-scale module and the attention module are connected by a residual module, which avoids the degradation of the network. Our network model is built from these three core modules, which combine to improve the recognition ability of the network for EEG signals. Our experimental results on three datasets (BCI competition IV 2a, III IIIa and IV 1) show that our proposed method has better performance than other state-of-the-art methods, with accuracy rates of 80.6%, 83.56% and 79.84%. Our model has stable performance in decoding EEG signals and achieves efficient classification performance while using fewer network parameters than other comparable state-of-the-art methods.

Exosomes from Inflamed Macrophages Promote the Progression of Parkinson's Disease by Inducing Neuroinflammation.

Inflammation is a common feature both for Parkinson's disease (PD) and obesity-associated metabolic syndromes. Inflammation mediated by inflamed macrophages in white adipose tissue plays a pivotal role for the pathogenesis of metabolic syndromes. Exosomes are important carriers connecting peripheral tissues and the central nervous system (CNS). Therefore, we speculate that exosomes derived from inflamed macrophages may be involved in the pathological progression of PD. Here, we prepared exosomes from lipopolysaccharide (LPS) or interferon gamma (IFNγ) treated macrophages (inflamed macrophages) and examined their potential roles in PD. Our data showed that exosomes from inflamed macrophages stimulate proinflammatory cytokine expression in primary microglia and astrocytes. In vivo, inflamed macrophage exosomes induce behavioral defects in mice as evidenced by shortened duration in the rotarod test and prolonged latency in the pole test. The treatment of exosomes also reduces tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta (SNpc) and striatum. All these PD-like phenotypes are likely due to the activation of microglia and astrocytes induced by exosomes from inflamed macrophages. Exosome sequencing, together with bioinformatics analysis and functional studies, revealed that exosomal miRNAs such as miR-155-5p are likely a key factor for inducing an inflammatory response in glial cells. These results indicate that exosomes derived from inflamed macrophages are likely a causative factor for developing PD. In this regard, inflamed macrophage exosomes might be a linker transducing the peripheral tissue inflammation into the CNS.

Recent advances of long non-coding RNAs in control of hepatic gluconeogenesis.

Gluconeogenesis is the main process for endogenous glucose production during prolonged fasting, or certain pathological conditions, which occurs primarily in the liver. Hepatic gluconeogenesis is a biochemical process that is finely controlled by hormones such as insulin and glucagon, and it is of great importance for maintaining normal physiological blood glucose levels. Dysregulated gluconeogenesis induced by obesity is often associated with hyperglycemia, hyperinsulinemia, and type 2 diabetes (T2D). Long noncoding RNAs (lncRNAs) are involved in various cellular events, from gene transcription to protein translation, stability, and function. In recent years, a growing number of evidences has shown that lncRNAs play a key role in hepatic gluconeogenesis and thereby, affect the pathogenesis of T2D. Here we summarized the recent progress in lncRNAs and hepatic gluconeogenesis.

Evaluation of a respiratory motion-corrected image reconstruction algorithm in 2-[18F]FDG and [68Ga]Ga-DOTA-NOC PET/CT: impacts on image quality and tumor quantification.

Background: Respiratory motions may cause artifacts on positron emission tomography (PET) images that degrade image quality and quantification accuracy. This study aimed to evaluate the effect of a respiratory motion-corrected image reconstruction (MCIR) algorithm on image quality and tumor quantification compared with nongated/nonmotion-corrected reconstruction. Methods: We used a phantom consisting of 5 motion spheres immersed in a chamber driven by a motor. The spheres and the background chamber were filled with 18F solution at a sphere-to-background ratio of 5:1. We enrolled 42 and 16 patients undergoing 2-deoxy-2-[18F]fluoro-D-glucose {2-[18F]FDG} and 68Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide {[68Ga]Ga-DOTA-NOC} PET/computed tomography (CT) from whom 74 and 30 lesions were segmented, respectively. Three reconstructions were performed: data-driven gating-based motion correction (DDGMC), external vital signal module-based motion correction (VSMMC), and noncorrection reconstruction. The standardized uptake values (SUVs) and the volume of the spheres and the lesions were measured and compared among the 3 reconstruction groups. The image noise in the liver was measured, and the visual image quality of motion artifacts was scored by radiologists in the patient study. Results: In the phantom study, the spheres' SUVs increased by 26-36%, and the volumes decreased by 35-38% in DDGMC and VSMMC compared with the noncorrection group. In the 2-[18F]FDG PET patient study, the lesions' SUVs had a median increase of 10.87-12.65% while the volumes had a median decrease of 14.88-15.18% in DDGMC and VSMMC compared with those of noncorrection. In the [68Ga]Ga-DOTA-NOC PET patient study, the lesions' SUVs increased by 14.23-15.45%, and the volumes decreased by 19.11-20.94% in DDGMC and VSMMC. The image noise in the liver was equal between the DDGMC, VSMMC, and noncorrection groups. Radiologists found improved image quality in more than 45% of the cases in DDGMC and VSMMC compared with the noncorrection group. There was no statistically significant difference in SUVs, volumes, or visual image quality scores between DDGMC and VSMMC. Conclusions: MCIR improves tumor quantification accuracy and visual image quality by reducing respiratory motion artifacts without compromised image noise performance or elongated acquisition time in 2-[18F]FDG and [68Ga]Ga-DOTA-NOC PET/CT tumor imaging. The performance of DDG-driven MCIR is as good as that of the external device-driven solution.

11ß-Hydroxysteroid Dehydrogenase Type 1 Facilitates Osteoporosis by Turning on Osteoclastogenesis through Hippo Signaling.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a key enzyme that transform cortisone to cortisol, which activates the endogenous glucocorticoid function. 11ß-HSD1 has been observed to regulate skeletal metabolism, specifically within osteoblasts. However, the function of 11ß-HSD1 in osteoclasts has not been elucidated. In this study, we observed increased 11ß-HSD1 expression in osteoclasts within an osteoporotic mice model (ovariectomized mice). Then, 11ß-HSD1 global knock-out or knock-in mice were employed to demonstrate its function in manipulating bone metabolism, showing significant bone volume decrease in 11ß-HSD1 knock-in mice. Furthermore, specifically knock out 11ß-HSD1 in osteoclasts, by crossing cathepsin-cre mice with 11ß-HSD1flox/flox mice, presented significant protecting effect of skeleton when they underwent ovariectomy surgery. In vitro experiments showed the endogenous high expression of 11ß-HSD1 lead to osteoclast formation and maturation. Meanwhile, we found 11ß-HSD1 facilitated mature osteoclasts formation inhibited bone formation coupled H type vessel (CD31hiEmcnhi) growth through reduction of PDFG-BB secretion. Finally, transcriptome sequencing of 11ß-HSD1 knock in osteoclast progenitor cells indicated the Hippo pathway1 was mostly enriched. Then, by suppression of YAP expression in Hippo signaling, we observed the redundant of osteoclasts formation even in 11ß-HSD1 high expression conditions. In conclusion, our study demonstrated the role of 11ß-HSD1 in facilitating osteoclasts formation and maturation through the Hippo signaling, which is a new therapeutic target to manage osteoporosis.

CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation.

Cancer cells usually exhibit shortened 3' untranslated regions (UTRs) due to alternative polyadenylation (APA) to promote cell proliferation and migration. Upregulated CPSF6 leads to a systematic prolongation of 3' UTRs, but CPSF6 expression in tumors is typically higher than that in healthy tissues. This contradictory observation suggests that it is necessary to investigate the underlying mechanism by which CPSF6 regulates APA switching in cancer. Here, we find that CPSF6 can undergo liquid-liquid phase separation (LLPS), and elevated LLPS is associated with the preferential usage of the distal poly(A) sites. CLK2, a kinase upregulated in cancer cells, destructs CPSF6 LLPS by phosphorylating its arginine/serine-like domain. The reduction of CPSF6 LLPS can lead to a shortened 3' UTR of cell-cycle-related genes and accelerate cell proliferation. These results suggest that CPSF6 LLPS, rather than its expression level, may be responsible for APA regulation in cancer cells.