Value of Semi-Quantitative Parameters of 68Ga-FAPI-04 PET/CT in Primary Malignant and Benign Diseases: A Comparison with 18F-FDG.

Objectives: We aimed to compare the value of the semiquantitative parameters of 68Ga-labeled FAP inhibitor (68Ga-FAPI)-04 positron emission tomography/computed tomography (PET/CT) and 18F-fluorodeoxyglucose (18F-FDG) in diagnosing primary malignant and benign diseases. Materials and Methods: 18F-FDG and 68Ga-FAPI-04 PET/CT images of 80 patients were compared. Semiquantitative parameters, including maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), peak SUV by lean body mass (SULpeak), metabolic tumor volume (or tumor volume of FAPI; FAPI-TV), and TLG (or total lesion activity of FAPI; FAPI-TLA), were automatically obtained using the IntelliSpace Portal image processing workstation with a threshold of 40% SUVmax. The liver blood pool was measured as the background, and the tumor-to-background ratio (TBRliver) was calculated. Results: In all malignant lesions, FAPI-TV and FAPI-TLA were higher in 68Ga-FAPI-04 PET/CT than in 18F-FDG. In the subgroup analysis, 68Ga-FAPI-04 had higher FAPI-TV and FAPI-TLA and lower SUVmax than 18F-FDG had in group A, including gynecological tumor, esophageal, and colorectal cancers. However, six semiquantitative parameters were higher in group B (the other malignant tumors). For the benign diseases, SUVmax, SUVmean, SUVpeak, and SULpeak were lower in 68Ga-FAPI-04 PET/CT than in 18F-FDG. 68Ga-FAPI-04 PET/CT showed a lower liver background and a higher TBRliver than 18F-FDG did. 68Ga-FAPI-04 PET/CT had higher accuracy, sensitivity, and specificity than 18F-FDG had. Conclusion: More accurate semiquantitative parameters and lower abdominal background in 68Ga-FAPI-04 PET/CT make it more competitive in the differential diagnosis of malignant and benign diseases than in 18F-FDG.

Electrochemical Synthesis of Phosphorylated Indoles and Trp-Containing Oligopeptides.

Cp2Fe-mediated electrochemical synthesis of phosphorylated indoles and Trp-containing oligopeptides has been developed, which eliminates the need for external oxidants and yields the desired products in moderate to excellent yields under mild conditions. Importantly, the synthetic applicability was further demonstrated through its easy scalability and the anticancer activity of the product. Remarkably, it presents the first electrochemical protocol to access the phosphorylation of indoles and Trp-containing oligopeptides.

Comparison of 68Ga-FAPI-04 PET/CT with 18F-FDG PET/CT for diagnosis and staging of gastric and colorectal cancer.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of 68Ga-FAPI-04 PET/computed tomography (CT) for the diagnosis of primary and metastatic gastric cancer and colorectal cancer lesions as compared with 18F-FDG PET/CT. MATERIALS AND METHODS: Fifty-nine patients who underwent both 18F-FDG and 68Ga-FAPI-04 for initial staging or restaging were enrolled. Histopathological findings and clinical imaging follow-up were used as the reference standard. The diagnostic performance and TNM staging of the two tracers were calculated and compared. The maximum standardized uptake value (SUVmax), tumour-to-mediastinal blood pool ratio (TBR) (lesions SUVmax/ascending aorta SUVmean), and tumour-to-normal liver parenchyma ratio (TLR) (lesions SUVmax/liver SUVmean) of primary and metastatic lesions between two imaging modalities were measured and compared using the Wilcoxon signed-rank test and paired t-test. RESULTS: The two imaging agents are comparable for the detection of primary tumors. The sensitivity of 68Ga-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT for detecting lymph node metastases, peritoneal metastases, liver metastases, and bone metastases. In the patient-based analysis, the TLR for all lesions was significantly higher with 68Ga-FAPI-04 PET/CT than with 18F-FDG PET/CT (all P < 0.05). The accuracy (92.2 vs. 70.3%, P = 0.002) and sensitivity of 68Ga-FAPI-04 were significantly higher than that of 18F-FDG (78.6 vs. 71.4%, P = 0.011) in determining the lymph node status. 68Ga-FAPI-04 has a higher accuracy in staging (P = 0.041), which is mainly due to the ability of distant metastases detection. CONCLUSION: 68Ga-FAPI-04 PET/CT may be superior in evaluating the diagnostic efficiency and staging accuracy of gastric and colorectal cancer.

The dual role of mesenchymal stem cells in apoptosis regulation.

Mesenchymal stem cells (MSCs) are widely distributed pluripotent stem cells with powerful immunomodulatory capacity. MSCs transplantation therapy (MSCT) is widely used in the fields of tissue regeneration and repair, and treatment of inflammatory diseases. Apoptosis is an important way for tissues to maintain cell renewal, but it also plays an important role in various diseases. And many studies have shown that MSCs improves the diseases by regulating cell apoptosis. The regulation of MSCs on apoptosis is double-sided. On the one hand, MSCs significantly inhibit the apoptosis of diseased cells. On the other hand, MSCs also promote the apoptosis of tumor cells and excessive immune cells. Furthermore, MSCs regulate apoptosis through multiple molecules and pathways, including three classical apoptotic signaling pathways and other pathways. In this review, we summarize the current evidence on the regulation of apoptosis by MSCs.

Water Supply via Pedicel Reduces Postharvest Pericarp Browning of Litchi (Litchi chinensis) Fruit.

Pericarp browning is the key factor for the extension of shelf life and the maintenance of the commercial value of harvested litchi fruit. Water loss is considered a leading factor of pericarp browning in litchi fruit. In this study, based on the distinct structure of litchi fruit, which is a special type of dry fruit with the aril as the edible part, the effects of water supply via pedicel (WSP) treatment on pericarp browning and the fruit quality of litchi were investigated. Compared with the packaging of the control fruit at 25 °C or 4 °C, the WSP treatment was found to significantly reduce pericarp browning and the decay of litchi fruit. The WSP-treated fruit had a higher L* value, total anthocyanin content, and pericarp water content, and the pericarp was thicker. The WSP treatment significantly suppressed the increase in the electrolyte leakage of the pericarp and maintained higher ascorbic acid (AA) contents in the aril. In addition, the WSP treatment was effective in reducing the activity and gene expression of browning-related genes Laccase (ADE/LAC) and Peroxidase (POD) during the storage period. In conclusion, the WSP treatment could be an effective method to delay pericarp browning and maintain the quality of harvested litchi fruit, and this further supports that litchi fruit has dry fruit characteristics.

Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage.

Rationale: Hydrocephalus is a substantial complication after intracerebral hemorrhage (ICH) or intraventricular hemorrhage (IVH) that leads to impaired cerebrospinal fluid (CSF) circulation. Recently, brain meningeal lymphatic vessels (mLVs) were shown to serve as critical drainage pathways for CSF. Our previous studies indicated that the degradation of neutrophil extracellular traps (NETs) after ICH/IVH alleviates hydrocephalus. However, the mechanisms by which NET degradation exerts beneficial effects in hydrocephalus remain unclear. Methods: A mouse model of hydrocephalus following IVH was established by infusing autologous blood into both wildtype and Cx3cr1-/- mice. By studying the features and processes of the model, we investigated the contribution of mLVs and NETs to the development and progression of hydrocephalus following secondary IVH. Results: This study observed the widespread presence of neutrophils, fibrin and NETs in mLVs following IVH, and the degradation of NETs alleviated hydrocephalus and brain injury. Importantly, the degradation of NETs improved CSF drainage by enhancing the recovery of lymphatic endothelial cells (LECs). Furthermore, our study showed that NETs activated the membrane protein CX3CR1 on LECs after IVH. In contrast, the repair of mLVs was promoted and the effects of hydrocephalus were ameliorated after CX3CR1 knockdown and in Cx3cr1-/- mice. Conclusion: Our findings indicated that mLVs participate in the development of brain injury and secondary hydrocephalus after IVH and that NETs contribute to acute LEC injury and lymphatic thrombosis. CX3CR1 is a key molecule in NET-induced LEC damage and meningeal lymphatic thrombosis, which leads to mLV dysfunction and exacerbates hydrocephalus and brain injury. NETs may be a critical target for preventing the obstruction of meningeal lymphatic drainage after IVH.

The mechanism of internal and external efficacy influences residents' pro-environmental behavior through environmental willingness.

The Chinese government's environmental conservation efforts require the active participation of all society. This study investigated how internal and external efficacy influence pro-environmental behavior with environmental willingness as a mediator. This study employed a structural equation model to analyze the data from 1499 survey questionnaires. The analysis revealed that both internal and external efficacy can enhance individuals' pro-environmental behavior in the private and public spheres. External efficacy has a stronger impact on environmental willingness and public sphere environmental behavior, while internal efficacy more significantly influences private sphere environmental behavior. Additionally, environmental willingness only mediates efficacy and public sphere environmental behavior. The innovation of this study is the examination of internal and external efficacy from the perspective of different sources and the comparison of their differential impacts on pro-environmental behavior. Relevant policies should effectively enhance residents' internal and external efficacy to comprehensively improve their level of pro-environmental behavior.

Trappc1 intrinsically prevents ferroptosis of naive T cells to avoid spontaneous autoinflammatory disease in mice.

T lymphocytes are pivotal in adaptive immunity. The role of the trafficking protein particle complex (TRAPPC) in regulating T-cell development and homeostasis is unknown. Using CD4cre -Trappc1flox/flox (Trappc1 cKO) mice, we found that Trappc1 deficiency in T cells significantly decreased cell number of naive T cells in the periphery, whereas thymic T-cell development in Trappc1 cKO mice was identical as WT mice. In the culture assays and mouse models with adoptive transfer of the sorted WT (CD45.1+ CD45.2+ ) and Trappc1 cKO naive T cells (CD45.2+ ) to CD45.1+ syngeneic mice, Trappc1-deficient naive T cells showed significantly reduced survival ability compared with WT cells. RNA-seq and molecular studies showed that Trappc1 deficiency in naive T cells reduced protein transport from the endoplasmic reticulum to the Golgi apparatus, enhanced unfolded protein responses, increased P53 transcription, intracellular Ca2+ , Atf4-CHOP, oxidative phosphorylation, and lipid peroxide accumulation, and subsequently led to ferroptosis. Trappc1 deficiency in naive T cells increased ferroptosis-related damage-associated molecular pattern molecules like high mobility group box 1 or lipid oxidation products like prostaglandin E2, leukotriene B4, leukotriene C4, and leukotriene D4. Functionally, the culture supernatant of Trappc1 cKO naive T cells significantly promoted neutrophils to express inflammatory cytokines like TNFα and IL-6, which was rescued by lipid peroxidation inhibitor Acetylcysteine. Importantly, Trappc1 cKO mice spontaneously developed severe autoinflammatory disease 4 weeks after birth. Thus, intrinsic expression of Trappc1 in naive T cells plays an integral role in maintaining T-cell homeostasis to avoid proinflammatory naive T-cell death-caused autoinflammatory syndrome in mice. This study highlights the importance of the TRAPPC in T-cell biology.

Downregulation of nutrition sensor GCN2 in macrophages contributes to poor wound healing in diabetes.

Poor skin wound healing, which is common in patients with diabetes, is related to imbalanced macrophage polarization. Here, we find that nutrition sensor GCN2 (general control nonderepressible 2) and its downstream are significantly upregulated in human skin wound tissue and mouse skin wound macrophages, but skin wound-related GCN2 expression and activity are significantly downregulated by diabetes and hyperglycemia. Using wound healing models of GCN2-deleted mice, bone marrow chimeric mice, and monocyte-transferred mice, we show that GCN2 deletion in macrophages significantly delays skin wound healing compared with wild-type mice by altering M1 and M2a/M2c polarization. Mechanistically, GCN2 inhibits M1 macrophages via OXPHOS-ROS-NF-κB pathway and promotes tissue-repairing M2a/M2c macrophages through eukaryotic translation initiation factor 2 (eIF2α)-hypoxia-inducible factor 1α (HIF1α)-glycolysis pathway. Importantly, local supplementation of GCN2 activator halofuginone efficiently restores wound healing in diabetic mice with re-balancing M1 and M2a/2c polarization. Thus, the decreased macrophage GCN2 expression and activity contribute to poor wound healing in diabetes and targeting GCN2 improves wound healing in diabetes.

Noninvasive Assessment of HER2 Expression Status in Gastric Cancer Using 18F-FDG Positron Emission Tomography/Computed Tomography-Based Radiomics: A Pilot Study.

Purpose: Immunohistochemistry (IHC) is the main method to detect human epidermal growth factor receptor 2 (HER2) expression levels. However, IHC is invasive and cannot reflect HER2 expression status in real time. The aim of this study was to construct and verify three types of radiomics models based on 18F-fuorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging and to evaluate the predictive ability of these radiomics models for the expression status of HER2 in patients with gastric cancer (GC). Patients and Methods: A total of 118 patients with GC were enrolled in this study. 18F-FDG PET/CT imaging was performed prior to surgery. The LIFEx software package was applied to extract PET and CT radiomics features. The minimum absolute contraction and selection operator (least absolute shrinkage and selection operator [LASSO]) algorithm was used to select the best radiomics features. Three machine learning methods, logistic regression (LR), support vector machine (SVM), and random forest (RF) models, were constructed and verified. The Synthetic Minority Oversampling Technique (SMOTE) was applied to address data imbalance. Results: In the training and test sets, the area under the curve (AUC) values of the LR, SVM, and RF models were 0.809, 0.761, 0.861 and 0.628, 0.993, 0.717, respectively, and the Brier scores were 0.118, 0.214, and 0.143, respectively. Among the three models, the LR and RF models exhibited extremely good prediction performance. The AUC values of the three models significantly improved after SMOTE balanced the data. Conclusions: 18F-FDG PET/CT-based radiomics models, especially LR and RF models, demonstrate good performance in predicting HER2 expression status in patients with GC and can be used to preselect patients who may benefit from HER2-targeted therapy.

Potential diagnostic markers and therapeutic targets for periodontitis and Alzheimer's disease based on bioinformatics analysis.

BACKGROUND AND OBJECTIVE: As a chronic inflammatory disease, periodontitis threatens oral health and is a risk factor for Alzheimer's disease (AD). There is growing evidence that these two diseases are closely related. However, current research is still incomplete in understanding the common genes and common mechanisms between periodontitis and AD. In this study, we aimed to identify common genes in periodontitis and AD and analyze the relationship between crucial genes and immune cells to provide new therapeutic targets for clinical treatment. MATERIALS AND METHODS: We evaluated differentially expressed genes (DEGs) specific to periodontitis and AD. Co-expressed genes were identified by obtaining gene expression profile data from the Gene Expression Omnibus (GEO) database. Using the STRING database, protein-protein interaction (PPI) networks were constructed, and essential genes were identified. We also used four algorithms to identify critical genes and constructed regulatory networks. The association of crucial genes with immune cells and potential therapeutic effects was also assessed. RESULTS: PDGFRB, VCAN, TIMP1, CHL1, EFEMP2, and IGFBP5 were obtained as crucial common genes. Immune infiltration analysis showed that Natural killer cells and Myeloid-derived suppressor cells were significantly differentially expressed in patients with PD and AD compared with the normal group. FOXC1 and GATA2 are important TFs for PD and AD. MiR-23a, miR-23b, miR-23a, and miR-23b were associated with AD and PD. Finally, the hub genes retrieved from the DSigDB database indicate multiple drug molecule and drug-target interactions. CONCLUSION: This study reveals commonalities in common hub genes and immune infiltration between periodontitis and AD, and the analysis of six hub genes and immune cells may provide new insights into potential therapeutic directions for the pathogenesis of periodontitis complicated by AD.

Feasibility of One-Day PET/CT Scanning Protocol with 68Ga-DOTA-FAPI-04 and 18F-FDG for the Detection of Ovarian Cancer Recurrence and Metastasis.

Objective: The objective of this study was to investigate the feasibility of 1-d 68Ga-DOTA-FAPI-04 and 18F-FDG (2-deoxy-2[18F]fluoro-d-glucose) positron emission tomography/computed tomography (PET/CT) for detecting ovarian cancer recurrence and metastasis. Materials and Methods: Fifty-two patients who underwent 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT were divided into 1- and 2-d groups. Image acquisition, injection time, and total waiting time were compared. For the 68Ga-DOTA-FAPI-04 PET/CT scans, low-dose CT scans and low injection dosages were employed, and total radiation dose was assessed for both protocols. The comparative analysis included assessment of patient-based detection rates and lesion-based diagnostic efficacy. Results: The total waiting time was significantly shorter in the 1-d group than in the 2-d group (p = 0.000). The radiation doses stemming from internal radiation and external radiation between the groups showed no differences (p = 0.151 vs. 0.716). In the patient-based analysis, the detection rates for local recurrence, peritoneal, lymph node, and other metastases were not significantly different in both protocols (p ∈ [0.351, 1.000]). For the lesion-based analysis, no differences were noted in terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (p ∈ [0.371, 1.000]). Conclusions: The 1-d PET/CT protocol reduced waiting time and exhibited equivalent detectability compared with the 2-d protocol, suggesting its clinical value.

Single-cell transcriptomic analysis reveals transcriptional and cell subpopulation differences between human and pig immune cells.

BACKGROUND: The pig is a promising donor candidate for xenotransplantation. Understanding the differences between human and swine immune systems is critical for addressing xenotransplant rejection and hematopoietic reconstitution. The gene transcriptional profile differences between human and pig immune cell subpopulations have not been studied. To assess the similarities and differences between pigs and humans at the levels of gene transcriptional profiles or cell subpopulations are important for better understanding the cross-species similarity of humans and pigs, and it would help establish the fundamental principles necessary to genetically engineer donor pigs and improve xenotransplantation. OBJECTIVE: To assess the gene transcriptional similarities and differences between pigs and humans. METHODS: Two pigs and two healthy humans' PBMCs were sorted for 10 × genomics single-cell sequence. We generated integrated human-pig scRNA-seq data from human and pig PBMCs and defined the overall gene expression landscape of pig peripheral blood immune cell subpopulations by updating the set of human-porcine homologous genes. The subsets of immune cells were detected by flow cytometry. RESULTS: There were significantly less T cells, NK cells and monocytes but more B cells in pig peripheral blood than those in human peripheral blood. High oxidative phosphorylation, HIF-1, glycolysis, and lysosome-related gene expressions in pig CD14+ monocytes were observed, whereas pig CD14+ monocytes exhibited lower levels of cytokine receptors and JAK-STAT-related genes. Pig activated CD4+T cells decreased cell adhesion and inflammation, while enriched for migration and activation processes. Porcine GNLY+CD8+T cells reduced cytotoxicity and increased proliferation compared with human GNLY+CD8+T cells. Pig CD2+CD8+γδT cells were functionally homologous to human CD2+CD4+ γδT cells. Pig CD2-CD8-γδT cells expressed genes with quiescent and precursor characteristics, while CD2-CD8+γδT cells expressed migration and memory-related molecules. Pig CD24+ and CD5+B cells are associated with inflammatory responses. CONCLUSION: Our research with integrated scRNA-seq assays identified the different distribution of pig immune cell subpopulations and the different transcriptional profiles of human and pig immune cells. This study enables a deeper understanding of the development and function of porcine immune cells.

The Effects of IL-23/IL-18-Polarized Neutrophils on Renal Ischemia-Reperfusion Injury and Allogeneic-Skin-Graft Rejection in Mice.

Neutrophils display heterogeneity and plasticity with different subgroups and immune-regulatory functions under various surrounding conditions. Neutrophils induced by IL-23/IL-18 (referred to N(IL-23+IL-18) neutrophils) have a unique gene-expression profile, with highly expressing IL-17, MHC-II, and costimulatory molecules. The adoptive transfer of N(IL-23+IL-18) neutrophils significantly increased the pathogenesis in a renal ischemia-reperfusion injury mouse model. N(IL-23+IL-18) neutrophils directly and efficiently induced allogeneic T cell proliferation in vitro. N(IL-23+IL-18) neutrophils enhanced the syngeneic T cell response to allogeneic antigens in mixed-lymphocyte reaction assays. The adoptive transfer of the donor or host N(IL-23+IL-18) neutrophils significantly enhanced the antidonor antibody production in an allogeneic-skin-transplanted mouse model, accompanied by increased Tfh cells in the spleens. Therefore, the neutrophil subset induced by IL-23/IL-18 promotes tissue injury and antidonor humoral response in the allogeneic transplantation mouse model.

Meta-analysis and time trend prediction of the prevalence of hypertension in Chinese college students.

BACKGROUND: To understand the prevalence of hypertension among Chinese college students over the past decade (2010-2020) and predict its future trend, we aim to provide a basis for preventing and controlling hypertension among college students. METHODS: Databases such as Chinese National Knowledge Infrastructure, Wanfang database, PubMed, and Web of Science were searched, and publications on the prevalence of hypertension among Chinese college students from 2010 to 2020 were collected. Search for publications in both Chinese and English databases using keywords "hypertension," "prevalence," "disease status," "cross-sectional survey," "epidemiology," "China," "adolescents," and "college students." Publication screening, data extraction, and quality assessment were independently conducted by 2 researchers. Meta-analysis was performed using Stata 16, and trends in the prevalence of hypertension among college students were analyzed using R 4.2.0. RESULTS: A total of 37 publications were included in this analysis, which involved 233,603 Chinese college students. The Meta-analysis results showed significant heterogeneity among the studies (I2 = 98.9%, P < .05). Using a random-effects model, the overall prevalence of hypertension among college students was estimated to be 3.3% (95% CI = 2.9%-3.6%), with a higher prevalence among male students (6.2%, 95% CI = 5.4%-7.1%) than female students (1.1%, 95% CI = 0.9%-1.3%). The prevalence of hypertension is notably higher in northern regions than in southern regions. The prevalence of hypertension among college students showed an increasing trend from 2010 to 2020. Trend analysis predicted that the prevalence of hypertension among college students will reach 10% and 14.6% by 2030 and 2040, respectively. The risk of hypertension in male students was 4.63 times higher than that of female students (95% CI = 2.97-7.23). Compared normal weight students, overweight and obese students had 3.08 times (95% CI = 2.48-3.82) and 6.69 times (95% CI = 2.25-19.90) higher risk of hypertension, respectively. CONCLUSION: The prevalence of hypertension in Chinese college students was about 3.3%. The prevalence of hypertension in male college students was higher than that in females, and the prevalence in northern regions was generally higher than that in southern regions. The prevalence of hypertension among Chinese college students will reach 10.0% in the next 10 years and 14.6% in the next 20 years. Male and BMI ≥ 24 were risk factors for hypertension among college students.

Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Standard treatment includes chemoimmunotherapy with R-CHOP or similar regimens. Despite treatment advancements, many patients with DLBCL experience refractory disease or relapse. While baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters have shown promise in predicting survival, they may not fully capture lesion heterogeneity. This study aimed to assess the prognostic value of baseline 18F-FDG PET radiomics features in comparison with clinical factors and metabolic parameters for assessing 2-year progression-free survival (PFS) and 5-year overall survival (OS) in patients with DLBCL. RESULTS: A total of 201 patients with DLBCL were enrolled in this study, and 1328 radiomics features were extracted. The radiomics signatures, clinical factors, and metabolic parameters showed significant prognostic value for individualized prognosis prediction in patients with DLBCL. Radiomics signatures showed the lowest Akaike information criterion (AIC) value and highest Harrell's concordance index (C-index) value in comparison with clinical factors and metabolic parameters for both PFS (AIC: 571.688 vs. 596.040 vs. 576.481; C-index: 0.732 vs. 0.658 vs. 0.702, respectively) and OS (AIC: 339.843 vs. 363.671 vs. 358.412; C-index: 0.759 vs. 0.667 vs. 0.659, respectively). Statistically significant differences were observed in the area under the curve (AUC) values between the radiomics signatures and clinical factors for both PFS (AUC: 0.768 vs. 0.681, P = 0.017) and OS (AUC: 0.767 vs. 0.667, P = 0.023). For OS, the AUC of the radiomics signatures were significantly higher than those of metabolic parameters (AUC: 0.767 vs. 0.688, P = 0.007). However, for PFS, no significant difference was observed between the radiomics signatures and metabolic parameters (AUC: 0.768 vs. 0.756, P = 0.654). The combined model and the best-performing individual model (radiomics signatures) alone showed no significant difference for both PFS (AUC: 0.784 vs. 0.768, P = 0.163) or OS (AUC: 0.772 vs. 0.767, P = 0.403). CONCLUSIONS: Radiomics signatures derived from PET images showed the high predictive power for progression in patients with DLBCL. The combination of radiomics signatures, clinical factors, and metabolic parameters may not significantly improve predictive value beyond that of radiomics signatures alone.

Multiple Intrahepatic Inflammatory Myofibroblastic Tumor on 68 Ga-FAPI and 18 F-FDG PET/CT.

ABSTRACT: A 31-year-old man with multiple intrahepatic inflammatory myofibroblastoma tumor was referred to nuclear medicine department to assess its malignant potential. Multiple lesions in the liver exhibited 68 Ga-FAPI uptake at different degrees. Instead, there was no abnormal 18 F-FDG activity in the other hepatic lesions under the normal liver background except for the puncture site. This case reflects tumor heterogeneity of the disease and shows the potential value of 68 Ga-FAPI PET/CT for the evaluation of hepatic inflammatory myofibroblastoma tumor.

mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway.

Myeloid hematopoiesis is a finely controlled consecutive developmental process, which is essential to maintain peripheral innate immune homeostasis. Herein, we found that Rictor deletion caused the remarkable reduction of granulocyte-monocyte progenitors (GMPs), monocytes, and macrophages, while the levels of neutrophils were unaffected. Adoptive transfer of Rictor-deleted GMPs or common myeloid progenitors (CMPs) in syngeneic mice showed poor re-constitution of monocytes compared to wild-type GMPs or CMPs. In addition to decreasing the proliferation of CMPs/GMPs, Rictor deletion preferentially inhibited Ly6C+ monocyte differentiation, while enhancing neutrophil differentiation, as determined by colony formation assays. mTORC2 promotes monocyte development by downregulation of the AKT-Foxo4-activating transcription factor 5 (ATF5)-mitochondrial unfolded protein response (mtUPR) pathway. Genetic overexpression of ATF5 or exposure to ethidium bromide significantly rescued monocyte/macrophage differentiation defects of Rictor-deficient myeloid progenitors. Therefore, Rictor is required for CMP/GMP proliferation and acts as an important switch to balance monocytic and granulocytic lineage commitment in bone marrow.

Proactive and reactive language control in bilingual language production revealed by decoding sustained potentials and electroencephalography oscillations.

Adopting highly sensitive multivariate electroencephalography (EEG) and alpha-band decoding analyses, the present study investigated proactive and reactive language control during bilingual language production. In a language-switching task, Chinese-English bilinguals were asked to name pictures based on visually presented cues. EEG and alpha-band decoding accuracy associated with switch and non-switch trials were used as indicators for inhibition over the non-target language. Multivariate EEG decoding analyses showed that the decoding accuracy in L1 but not in L2, was above chance level shortly after cue onset. In addition, alpha-band decoding results showed that the decoding accuracy in L1 rose above chance level in an early time window and a late time window locked to the stimulus. Together, these asymmetric patterns of decoding accuracy indicate that both proactive and reactive attentional control over the dominant L1 are exerted during bilingual word production, with a possibility of overlap between two control mechanisms. We addressed theoretical implications based on these findings for bilingual language control models.

Wip1 inhibits neutrophil extracellular traps to promote abscess formation in mice by directly dephosphorylating Coronin-1a.

Neutrophil extracellular traps (NETs) participate in the rapid inhibition and clearance of pathogens during infection; however, the molecular regulation of NET formation remains poorly understood. In the current study, we found that inhibition of the wild-type p53-induced phosphatase 1 (Wip1) significantly suppressed the activity of Staphylococcus aureus (S. aureus) and accelerated abscess healing in S. aureus-induced abscess model mice by enhancing NET formation. A Wip1 inhibitor significantly enhanced NET formation in mouse and human neutrophils in vitro. High-resolution mass spectrometry and biochemical assays demonstrated that Coro1a is a substrate of Wip1. Further experiments also revealed that Wip1 preferentially and directly interacts with phosphorylated Coro1a than compared to unphosphorylated inactivated Coro1a. The phosphorylated Ser426 site of Coro1a and the 28-90 aa domain of Wip1 are essential for the direct interaction of Coro1a and Wip1 and for Wip1 dephosphorylation of p-Coro1a Ser426. Wip1 deletion or inhibition in neutrophils significantly upregulated the phosphorylation of Coro1a-Ser426, which activated phospholipase C and subsequently the calcium pathway, the latter of which promoted NET formation after infection or lipopolysaccharide stimulation. This study revealed Coro1a to be a novel substrate of Wip1 and showed that Wip1 is a negative regulator of NET formation during infection. These results support the potential application of Wip1 inhibitors to treat bacterial infections.