Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial 11C-Pittsburgh compound B positron emission tomography (11C-PiB-PET) imaging showed a 24% decrease in global standardized uptake value ratio (SUVR) at 10 months after taxifolin use. During this period, the patient experienced clinical improvement with improved consciousness and reduced recurrent ICH frequency, which may be partly attributable to the potential amyloid-ß (Aß) clearing the effect of taxifolin. However, this effect seemed to have diminished at 15 months, CAA should be considered in young patients presenting with recurrent lobar ICH with a history of childhood neurosurgery, and serial 11C-PiB-PET scans warrant further validation as a strategy for monitoring treatment response in CAA for candidate Aß-clearing therapeutic agents such as taxifolin.

NEDD1 overexpression increases cell proliferation, tumor immune escape, and drug resistance in LUAD.

Background: Neural Precursor Cell Expressed Developmentally Down-Regulated Protein 1 (NEDD1) serves as a crucial factor in promoting cellular mitosis by directly facilitating wheel assembly and daughter centriole biogenesis at the lateral site of parent centrioles, ultimately driving centrosome replication. The amplification of centrosomes and the abnormal expression of centrosome-associated proteins contribute to the invasion and metastasis of non-small cell lung cancer cells. However, the specific mechanism by which NEDD1 contributes to the progression of lung adenocarcinoma (LUAD) remains unexplored. Therefore, the objective of this study is to uncover the role played by NEDD1 in LUAD. Methods: To verify the expression of NEDD1 in pan-carcinoma. The feasibility of NEDD1 as a prognostic marker for LUAD in TCGA and GEO databases was verified. Subsequently, Cox proportional hazard regression analysis was used to screen the prognostic factors of LUAD, so as to analyze the correlation between prognostic factors and NEDD1 expression. For another, NEDD1-related genes were screened for pathway enrichment analysis to verify their possible functions. In addition, the expression of NEDD1 in LUAD was verified by qPCR and IHC, then siRNA was used to construct NEDD1-knocked lung cancer cells for subsequent cytobehavioral experiments. Finally, the distribution of NEDD1 in single-cell samples was revealed, and then the correlation between its overexpression and LUAD immune escape and drug resistance was analyzed. Results: LUAD exhibits upregulation of NEDD1, which in turn promotes the proliferation, migration, invasion, and epithelial-mesenchymal transition of lung cancer cells, thereby contributing to a poor prognosis. Furthermore, the overexpression of NEDD1 is closely associated with immune escape and drug resistance in LUAD. Conclusion: NEDD1 serves as a reliable prognostic marker for LUAD, and its upregulation is associated with increased immune escape and drug resistance. Given these findings, NEDD1 holds potential as a novel therapeutic target for the treatment of LUAD.

Surface hydrophobization of hydrogels via interface dynamics-induced network reconfiguration.

Effective and easy regulation of hydrogel surface properties without changing the overall chemical composition is important for their diverse applications but remains challenging to achieve. We report a generalizable strategy to reconfigure hydrogel surface networks based on hydrogel-substrate interface dynamics for manipulation of hydrogel surface wettability and bioadhesion. We show that the grafting of hydrophobic yet flexible polymeric chains on mold substrates can significantly elevate the content of hydrophobic polymer backbones and reduce the presence of polar groups in hydrogel surface networks, thereby transforming the otherwise hydrophilic hydrogel surface into a hydrophobic surface. Experimental results show that the grafted highly dynamic hydrophobic chains achieved with optimal grafting density, chain length, and chain structure are critical for such substantial hydrogel surface network reconfiguration. Molecular dynamics simulations further reveal the atomistic details of the hydrogel network reconfiguration induced by the dynamic interface interactions. The hydrogels prepared using our strategy show substantially enhanced bioadhesion and transdermal delivery compared with the hydrogels of the same chemical composition but fabricated via the conventional method. Our findings provide important insights into the dynamic hydrogel-substrate interactions and are instrumental to the preparation of hydrogels with custom surface properties.

Identifying potential pathogenesis and immune infiltration in diabetic foot ulcers using bioinformatics and in vitro analyses.

BACKGROUND: Diabetic foot ulcers (DFU) are among the fastest-growing diseases worldwide. Recent evidence has emphasized the critical role of microRNA (miRNA)-mRNA networks in various chronic wounds, including DFU. In this study, we aimed to clarify the miRNA-mRNA axes associated with the occurrence of DFU. METHODS: Expression profiles of miRNAs and mRNAs were extracted from the Gene Expression Omnibus. Differentially expressed genes and differentially expressed miRNAs were identified, and miRNA-mRNA regulatory axes were constructed through integrated bioinformatics analyses. We validated the miRNA-mRNA axes using quantitative real-time PCR (qPCR) and dual-luciferase reporter assays. We conducted an immune infiltration analysis and confirmed the bioinformatics results using immunofluorescence staining. Single-sample gene set enrichment analysis (ssGSEA) was used to analyze the metabolic mechanisms. RESULTS: miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 interactions were identified using in silico analysis. The qPCR results showed apparent dysregulation of these miRNA-mRNA axes in DFU. The dual-luciferase reporter assay confirmed that miR-182-5p targeted CHL1 and MITF, and miR-338-3p targeted NOVA1. We conducted an immune infiltration analysis and observed that key genes correlated with decreased infiltration of M1 macrophages and resting mast cells in DFU. Immunofluorescence staining verified the co-localization of CHL1 and tryptase, while MITF and CD68 showed weak positive correlations. Metabolic pathways related to these three genes were identified using ssGSEA. CONCLUSIONS: In summary, the miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 pathway interactions and decreased infiltration of M1 macrophages and resting mast cells may provide novel clues to the pathogenesis of DFU. TRIAL REGISTRATION: The clinical trial included in this study was registered in the Chinese Clinical Trial Registry ( ChiCTR2200066660 ) on December 13, 2022.

Prediction of coronary heart disease in gout patients using machine learning models.

Growing evidence shows that there is an increased risk of cardiovascular diseases among gout patients, especially coronary heart disease (CHD). Screening for CHD in gout patients based on simple clinical factors is still challenging. Here we aim to build a diagnostic model based on machine learning so as to avoid missed diagnoses or over exaggerated examinations as much as possible. Over 300 patient samples collected from Jiangxi Provincial People's Hospital were divided into two groups (gout and gout+CHD). The prediction of CHD in gout patients has thus been modeled as a binary classification problem. A total of eight clinical indicators were selected as features for machine learning classifiers. A combined sampling technique was used to overcome the imbalanced problem in the training dataset. Eight machine learning models were used including logistic regression, decision tree, ensemble learning models (random forest, XGBoost, LightGBM, GBDT), support vector machine (SVM) and neural networks. Our results showed that stepwise logistic regression and SVM achieved more excellent AUC values, while the random forest and XGBoost models achieved more excellent performances in terms of recall and accuracy. Furthermore, several high-risk factors were found to be effective indices in predicting CHD in gout patients, which provide insights into the clinical diagnosis.

Diagnosis of Seronegative Rheumatoid Arthritis by 68 Ga-FAPI PET/CT.

Early diagnosis of rheumatoid arthritis with the initiation of disease-modifying antirheumatic drugs is important to prevent future disability. Seronegative rheumatoid arthritis lacks the classical immunological markers, thus imposing clinical diagnostic difficulty. In this case, we reported 68 Ga-FAPI PET/CT findings of seronegative rheumatoid arthritis in a 60-year-old lady. This case illustrates how 68 Ga-FAPI PET/CT aids in the diagnosis of seronegative rheumatoid arthritis.

The Complementary Role of PET to Pathology in Differentiating the Primary Origin of a Malignant Skin Nodule from Liver or Lung.

Metastasis from unknown primary is always a challenge because finding the true primary tumor significantly affects subsequent management. We present a case of malignant abdominal wall nodule initially diagnosed as metastasis from hepatocellular carcinoma through excisional biopsy and immunohistochemical (IHC) staining. Dual-tracer positron emission tomography/computed tomography (PET/CT) with 11C-acetate and 18F-FDG, however, showed metabolic findings in favor of metastasis from lung origin, which was finally confirmed by ensuing a lung biopsy with additional IHC stains. This case illustrates the complementary molecular role of PET to pathology, particularly when dual-tracer or multi-tracer PET is used in conjunction with pathology methods for cross referencing and confirmation.

Clinical and neuroimaging markers of neurodegeneration in first-degree relatives of patients with REM sleep behavior disorder with and without isolated rapid eye movement sleep without atonia: A case-control clinical and dopamine PET study.

OBJECTIVES: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD). METHODS: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration. RESULTS: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001). CONCLUSION: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis.

The DnaJ domain-containing heat-shock protein NAL11 determines plant architecture by mediating gibberellin homeostasis in rice (Oryza sativa).

Ideal Plant Architecture 1 (IPA1) is a key regulator of plant architecture. However, knowledge of downstream genes applicable for improving rice plant architecture is very limited. We identified the plant architecture regulatory gene NARROW LEAF 11 (NAL11), which encodes a heat-shock protein (HSP) containing a DnaJ domain. A promising rare allele of NAL11 (NAL11-923del-1552 ) positively selected in Aus cultivars was identified; this allele exhibited increased expression and generated relatively few tillers, thick stems, and large panicles, components of the ideal plant architecture (IPA). NAL11 is involved in regulating the cell cycle and cell proliferation. NAL11 loss-of-function mutants present impaired chloroplast development and gibberellin (GA) defects. Biochemical analyses show that IPA1 directly binds to elements in the missing fragment of the NAL11-923del-1552 promoter and negatively regulates NAL11 expression. Genetic analyses support the hypothesis that NAL11 acts downstream of IPA1 to regulate IPA by modulating GA homeostasis, and NAL11 may be an essential complement for IPA1. Our work revealed that avoidance of the inhibition of NAL11-923del-1552 caused by IPA1 represents a positive strategy for rescuing GA defects accompanied by the upregulation of IPA1 in breeding high-yield rice.

FAAH served a key membrane-anchoring and stabilizing role for NLRP3 protein independently of the endocannabinoid system.

NLRP3, the sensor protein of the NLRP3 inflammasome, plays central roles in innate immunity. Over-activation of NLRP3 inflammasome contributes to the pathogenesis of a variety of inflammatory diseases, while gain-of-function mutations of NLRP3 cause cryopyrin-associated periodic syndromes (CAPS). NLRP3 inhibitors, particularly those that inhibit inflammasome assembly and activation, are being intensively pursued, but alternative approaches for targeting NLRP3 would be highly desirable. During priming NLRP3 protein is synthesized on demand and becomes attached to the membranes of ER and mitochondria. Here, we show that fatty acid amide hydrolase (FAAH), the key integral membrane enzyme in the endocannabinoid system, unexpectedly served the critical membrane-anchoring and stabilizing role for NLRP3. The specific interaction between NLRP3 and FAAH, mediated by the NACHT and LRR domains of NLRP3 and the amidase signature sequence of FAAH, was essential for preventing CHIP- and NBR1-mediated selective autophagy of NLRP3. Heterozygous knockout of FAAH, resulting in ~50% reduction in both FAAH and NLRP3 expression, was sufficient to substantially inhibit the auto-inflammatory phenotypes of the NLRP3-R258W knock-in mice, while homozygous FAAH loss almost completely abrogates these phenotypes. Interestingly, select FAAH inhibitors, in particular URB597 and PF-04457845, disrupted NLRP3-FAAH interaction and induced autophagic NLRP3 degradation, leading to diminished inflammasome activation in mouse macrophage cells as well as in peripheral blood mononuclear cells isolated from CAPS patients. Our results unraveled a novel NLRP3-stabilizing mechanism and pinpointed NLRP3-FAAH interaction as a potential drug target for CAPS and other NLRP3-driven diseases.

Reliability of gradient-based segmentation for measuring metabolic parameters influenced by uptake time on 18F-PSMA-1007 PET/CT for prostate cancer.

Purpose: To determine an optimal setting for functional contouring and quantification of prostate cancer lesions with minimal variation by evaluating metabolic parameters on 18F-PSMA-1007 PET/CT measured by threshold-based and gradient-based methods under the influence of varying uptake time. Methods and materials: Dual time point PET/CT was chosen to mimic varying uptake time in clinical setting. Positive lesions of patients who presented with newly diagnosed disease or biochemical recurrence after total prostatectomy were reviewed retrospectively. Gradient-based and threshold-based tools at 40%, 50% and 60% of lesion SUVmax (MIM 6.9) were used to create contours on PET. Contouring was considered completed if the target lesion, with its hottest voxel, was delineated from background tissues and nearby lesions under criteria specific to their operations. The changes in functional tumour volume (FTV) and metabolic tumour burden (MTB, defined as the product of SUVmean and FTV) were analysed. Lesion uptake patterns (increase/decrease/stable) were determined by the percentage change in tumour SUVmax at ±10% limit. Results: A total of 275 lesions (135 intra-prostatic lesions, 65 lymph nodes, 45 bone lesions and 30 soft tissue lesions in pelvic region) in 68 patients were included. Mean uptake time of early and delayed imaging were 94 and 144 minutes respectively. Threshold-based method using 40% to 60% delineated only 85 (31%), 110 (40%) and 137 (50%) of lesions which all were contoured by gradient-based method. Although the overall percentage change using threshold at 50% was the smallest among other threshold levels in FTV measurement, it was still larger than gradient-based method (median: 50%=-7.6% vs gradient=0%). The overall percentage increase in MTB of gradient-based method (median: 6.3%) was compatible with the increase in tumour SUVmax. Only a small proportion of intra-prostatic lesions (<2%), LN (<4%), bone lesions (0%) and soft tissue lesions (<4%) demonstrated decrease uptake patterns. Conclusions: With a high completion rate, gradient-based method is reliable for prostate cancer lesion contouring on 18F-PSMA-1007 PET/CT. Under the influence of varying uptake time, it has smaller variation than threshold-based method for measuring volumetric parameters. Therefore, gradient-based method is recommended for tumour delineation and quantification on 18F-PSMA-1007 PET/CT.

Lower Posterior Cingulate N-Acetylaspartate to Creatine Level in Early Detection of Biologically Defined Alzheimer's Disease.

Alzheimer's disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.

Striatal dopamine synthesis capacity and its association with negative symptoms upon resolution of positive symptoms in first-episode schizophrenia and delusional disorder.

RATIONALE: How striatal dopamine synthesis capacity (DSC) contributes to the pathogenesis of negative symptoms in first-episode schizophrenia (SZ) and delusional disorder (DD) has seldom been explored. As negative symptoms during active psychotic episodes can be complicated by secondary influences, such as positive symptoms, longitudinal investigations may help to clarify the relationship between striatal DSC and negative symptoms and differentiate between primary and secondary negative symptoms. OBJECTIVE: A longitudinal study was conducted to examine whether baseline striatal DSC would be related to negative symptoms at 3 months in first-episode SZ and DD patients. METHODS: Twenty-three first-episode age- and gender-matched patients (11 DD and 12 SZ) were consecutively recruited through an early intervention service for psychosis in Hong Kong. Among them, 19 (82.6%) patients (9 DD and 10 SZ) were followed up at 3 months. All patients received an 18F-DOPA PET/MR scan at baseline. RESULTS: Baseline striatal DSC (Kocc;30-60) was inversely associated with negative symptoms at 3 months in first-episode SZ patients (rs = - 0.80, p = 0.010). This association remained in SZ patients even when controlling for baseline negative, positive, and depressive symptoms, as well as cumulative antipsychotic dosage (ß = - 0.69, p = 0.012). Such associations were not observed in first-episode DD patients. Meanwhile, the severity of negative symptoms at 3 months was associated with more positive symptoms in DD patients (rs = 0.74, p = 0.010) and not in SZ patients. CONCLUSIONS: These findings highlight the role of striatal DSC in negative symptoms upon resolution of active psychotic episodes among first-episode SZ patients. Baseline striatal dopamine activity may inform future symptom expression with important treatment implications.

Case series: MRD negativity assessment using 11C-Acetate PET with 3-weekly daratumumab-based quadruplet induction in newly diagnosed multiple myeloma.

Complete response (CR) is an important favorable factor for survival in multiple myeloma (MM). However, CR patients continue to relapse, especially in the presence of minimal residual disease (MRD). Bone marrow (BM) MRD is predictive of progression-free survival (PFS) in MM. However, myeloma outside the BM aspiration site may result in subsequent relapse despite MRD-negativity. Therefore, positron emission tomography-computed tomography (PET-CT) based on F-fluorodeoxyglucose (FDG) is a complementary tool to monitor residual disease in MM. However, FDG may miss myeloma lesions that are not FDG-avid. On the other hand, 11C-Acetate (ACT) has been found to be a more sensitive and specific tracer than FDG in MM. Recently, the addition of daratumumab to bortezomib, thalidomide, dexamethasone (VTd) or bortezomib, lenalidomide, dexamethasone (VRd) backbone has been proven to improve outcomes. Herein, we report three newly-diagnosed MM patients achieving deep responses with imaging CR using ACT PET in addition to conventional immunofixation CR and MRD-negative CR after a 3-weekly daratumumab-based quadruplet induction regimen.

Service Quality in Tourism Public Health: Trust, Satisfaction, and Loyalty.

The spread of COVID-19 and large-scale travel restrictions has caused serious damage to the global tourism industry. Tourists pay additional attention to public health services and their health during travel, but studies on tourism public health service quality (TPHSQ) are limited. Therefore, this study aims to define TPHSQ and revise and validate its scale. The result of exploratory factor analysis (EFA) indicates that TPHSQ includes two dimensions "overall environmental image" and "public health facilities and management." And based on 456 valid samples, the relationship among TPHSQ, tourists' trust, satisfaction, and loyalty was validated using the multiple linear regression models. Results revealed the importance of the TPHSQ in improving tourists' satisfaction and recovering their trust and loyalty. These results provided several implications for research, practice, and society that can benefit diverse stakeholders, which could accelerate the recovery of the tourism industry.

MRI-based Alzheimer's disease-resemblance atrophy index in the detection of preclinical and prodromal Alzheimer's disease.

Alzheimer's Disease-resemblance atrophy index (AD-RAI) is an MRI-based machine learning derived biomarker that was developed to reflect the characteristic brain atrophy associated with AD. Recent study showed that AD-RAI (≥0.5) had the best performance in predicting conversion from mild cognitive impairment (MCI) to dementia and from cognitively unimpaired (CU) to MCI. We aimed to validate the performance of AD-RAI in detecting preclinical and prodromal AD. We recruited 128 subjects (MCI=50, CU=78) from two cohorts: CU-SEEDS and ADNI. Amyloid (A+) and tau (T+) status were confirmed by PET (11C-PIB, 18F-T807) or CSF analysis. We investigated the performance of AD-RAI in detecting preclinical and prodromal AD (i.e. A+T+) among MCI and CU subjects and compared its performance with that of hippocampal measures. AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other measures. Among CU subjects, AD-RAI yielded the best specificity (0.95) and accuracy (85.90%) over other measures, while hippocampal volume achieved a higher sensitivity (0.73) than AD-RAI (0.47) in detecting preclinical AD. These results showed the potential of AD-RAI in the detection of early AD, in particular at the prodromal stage.

Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease.

BACKGROUND: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM). HYPOTHESIS: AD is associated with microstructural changes in the fimbria that might be detected by QSM. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy. FIELD STRENGTH / SEQUENCE: 3T; 3D fast-field echo sequence for QSM analysis and 3D T1 -weighted MP-RAGE sequence for anatomical analysis. ASSESSMENT: Segmentation of the left hippocampal fimbria subfield was performed on T1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM. STATISTICAL TESTS: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis. RESULTS: QSMmean and QSMmedian values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSMmean value (area under the curve [AUC] 0.744, P < 0.05) and the QSMmedian value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data. DATA CONCLUSION: The fimbria showed higher magnetic susceptibility in AD compared with controls. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Current status of PSMA PET imaging in prostate cancer.

The past decade has witnessed the rising popularity and acceptance of molecular definitions on disease management. Prostate-specific membrane antigen (PSMA), in light of its molecular nature and cytokinetic properties, has rapidly become the target for development of a variety of functional tracers for PET/CT evaluation of prostate cancer. The most commonly used PSMA-binding analog is 68 Ga-labeled PSMA-11, which is now widely applied in both research and clinical settings. Literature data in the recent years have been enriched by a number of meta-analyses and systemic reviews on the evolving role of PSMA PET in primary diagnosis, staging, detection of biochemical recurrence after primary cancer treatment, identification, and significance of oligometastasis, as well as in restaging and treatment monitoring. Being a highly sensitive and reasonably specific molecular tracer, PSMA-binding analogs have a high potential to possess the majority of imaging characteristics required for a variety of management decisions in prostate malignancy.

The role of dopamine dysregulation and evidence for the transdiagnostic nature of elevated dopamine synthesis in psychosis: a positron emission tomography (PET) study comparing schizophrenia, delusional disorder, and other psychotic disorders.

There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an 18F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (Kocc;30-60 value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean Kocc;30-60 was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions.

Exploration of the Effects of Different Blue LED Light Intensities on Flavonoid and Lipid Metabolism in Tea Plants via Transcriptomics and Metabolomics.

Blue light extensively regulates multiple physiological processes and secondary metabolism of plants. Although blue light quantity (fluence rate) is important for plant life, few studies have focused on the effects of different blue light intensity on plant secondary metabolism regulation, including tea plants. Here, we performed transcriptomic and metabolomic analyses of young tea shoots (one bud and two leaves) under three levels of supplemental blue light, including low-intensity blue light (LBL, 50 µmol m-2 s-1), medium-intensity blue light (MBL, 100 µmol m-2 s-1), and high-intensity blue light (HBL, 200 µmol m-2 s-1). The total number of differentially expressed genes (DEGs) in LBL, MBL and HBL was 1, 7 and 1097, respectively, indicating that high-intensity blue light comprehensively affects the transcription of tea plants. These DEGs were primarily annotated to the pathways of photosynthesis, lipid metabolism and flavonoid synthesis. In addition, the most abundant transcription factor (TF) families in DEGs were bHLH and MYB, which have been shown to be widely involved in the regulation of plant flavonoids. The significantly changed metabolites that we detected contained 15 lipids and 6 flavonoid components. Further weighted gene co-expression network analysis (WGCNA) indicated that CsMYB (TEA001045) may be a hub gene for the regulation of lipid and flavonoid metabolism by blue light. Our results may help to establish a foundation for future research investigating the regulation of woody plants by blue light.