Mechanisms of biodiversity loss under nitrogen enrichment: unveiling a shift from light competition to cation toxicity.

The primary mechanisms contributing to nitrogen (N) addition induced grassland biodiversity loss, namely light competition and soil cation toxicity, are often examined separately in various studies. However, their relative significance in governing biodiversity loss along N addition gradient remains unclear. We conducted a 4-yr field experiment with five N addition rates (0, 2, 10, 20, and 50 g N m-2 yr-1) and performed a meta-analysis using global data from 239 observations in N-fertilized grassland ecosystems. Results from our field experiment and meta-analysis indicate that both light competition and soil cation (e.g. Mn2+ and Al3+) toxicity contribute to plant diversity loss under N enrichment. The relative importance of these mechanisms varied with N enrichment intensity. Light competition played a more significant role in influencing species richness under low N addition (≤ 10 g m-2 yr-1), while cation toxicity became increasingly dominant in reducing biodiversity under high N addition (>10 g m-2 yr-1). Therefore, a transition from light competition to cation toxicity occurs with increasing N availability. These findings imply that the biodiversity loss along the N gradient is regulated by distinct mechanisms, necessitating the adoption of differential management strategies to mitigate diversity loss under varying intensities of N enrichment.

Integration of Hollow Microneedle Arrays with Jellyfish-Shaped Electrochemical Sensor for the Detection of Biomarkers in Interstitial Fluid.

This study integrates hollow microneedle arrays (HMNA) with a novel jellyfish-shaped electrochemical sensor for the detection of key biomarkers, including uric acid (UA), glucose, and pH, in artificial interstitial fluid. The jellyfish-shaped sensor displayed linear responses in detecting UA and glucose via differential pulse voltammetry (DPV) and chronoamperometry, respectively. Notably, the open circuit potential (OCP) of the system showed a linear variation with pH changes, validating its pH-sensing capability. The sensor system demonstrates exceptional electrochemical responsiveness within the physiological concentration ranges of these biomarkers in simulated epidermis sensing applications. The detection linear ranges of UA, glucose, and pH were 0~0.8 mM, 0~7 mM, and 4.0~8.0, respectively. These findings highlight the potential of the HMNA-integrated jellyfish-shaped sensors in real-world epidermal applications for comprehensive disease diagnosis and health monitoring.

Use of serum KL-6 and chest radiographic severity grade to predict 28-day mortality in COVID-19 patients with pneumonia: a retrospective cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a global social and economic impact. An easy assessment procedure to handily identify the mortality risk of inpatients is urgently needed in clinical practice. Therefore, the aim of this study was to develop a simple nomogram model to categorize patients who might have a poor short-term outcome. METHODS: A retrospective cohort study of 189 COVID-19 patients was performed at Shanghai Ren Ji Hospital from December 12, 2022 to February 28, 2023. Chest radiography and biomarkers, including KL-6 were assessed. Risk factors of 28-day mortality were selected by a Cox regression model. A nomogram was developed based on selected variables by SMOTE strategy. The predictive performance of the derived nomogram was evaluated by calibration curve. RESULTS: In total, 173 patients were enrolled in this study. The 28-day mortality event occurred in 41 inpatients (23.7%). Serum KL-6 and radiological severity grade (RSG) were selected as the final risk factors. A nomogram model was developed based on KL-6 and RSG. The calibration curve suggested that the nomogram model might have potential clinical value. The AUCs for serum KL-6, RSG, and the combined score in the development group and validation group were 0.885 (95% CI: 0.804-0.952), 0.818 (95% CI: 0.711-0.899), 0.868 (95% CI: 0.776-0.942) and 0.932 (95% CI: 0.862-0.997), respectively. CONCLUSIONS: Our results suggested that the nomogram based on KL-6 and RSG might be a potential method for evaluating 28-day mortality in COVID-19 patients. A high combined score might indicate a poor outcome in COVID-19 patients with pneumonia.

Activation of Cannabinoid Type 2 Receptor in Microglia Reduces Neuroinflammation through Inhibiting Aerobic Glycolysis to Relieve Hypertension.

BACKGROUND: Studies have shown that the chronic use of cannabis is associated with a decrease in blood pressure. Our previous studies prove that activating the cannabinoid type 2 (CB2) receptor in the brain can effectively reduce blood pressure in spontaneously hypertensive rats; however, the exact mechanism has not been clarified. The objective of this study is to demonstrate that activation of microglial CB2 receptors can effectively reduce the levels of TNF-α, IL-1ß, and IL-6 in the paraventricular nucleus (PVN) through inhibiting aerobic glycolysis, thereby relieving hypertension. METHODS: AngiotensinII (AngII) was administered to BV2 cells and C57 mice to induce hypertension and the release of proinflammatory cytokines. The mRNA and protein expression of the CB2 receptor, TNF-α, IL-1ß, IL-6, and the PFK and LDHa enzymes were detected using RT-qPCR and Western blotting. The Seahorse XF Energy Metabolism Analyzer was used to measure the oxidative phosphorylation and aerobic glycolysis metabolic pathways in BV2 cells. The long-term effects of injecting JWH133, a selective CB2 receptor agonist, intraperitoneally on blood pressure were ascertained. ELISA was used to measure norepinephrine and lactic acid levels while immunofluorescence labeling was used to locate the CB2 receptor and c-Fos. By injecting pAAV-F4/80-GFP-mir30shRNA (AAV2-r-CB2shRNA) into the lateral cerebral ventricle, the CB2 receptor in microglia was specifically knocked down. RESULTS: Activation of CB2 receptors by the agonist JWH133 suppressed TNF-α, IL-1ß, and IL-6 by inhibiting PFK and LDHa enzymes involved in glycolysis, as well as lactic acid accumulation, along with a reduction in glycoPER levels (marks of aerobic glycolysis) in AngII-treated BV2 cells. In AngII-treated mice, the administration of JWH133 specifically activated CB2 receptors on microglia, resulting in decreased expression levels of PFK, LDHa, TNF-α, IL-1ß, and IL-6, subsequently leading to a decrease in c-Fos protein expression within PVN neurons as well as reduced norepinephrine levels in plasma, ultimately contributing to blood pressure reduction. CONCLUSION: The results suggest that activation of the microglia CB2 receptor decreases the neuroinflammation to relieve hypertension; the underlying mechanism is related to inhibiting aerobic glycolysis of microglia.

A novel detection method based on MIRA-CRISPR/Cas13a-LFD targeting the repeated DNA sequence of Trichomonas vaginalis.

BACKGROUND: Trichomonas vaginalis is a protozoan parasite, widely recognized as the most prevalent non-viral sexually transmitted infection (STI) globally. This infection is linked to various complications, including pelvic inflammatory disease, adverse pregnancy outcomes, and an increased risk of acquiring HIV. Current molecular detection methods for T. vaginalis are often costly and technically challenging. METHODS: We developed a novel detection method for T. vaginalis using a multi-enzyme isothermal rapid amplification-clustered regularly interspaced short palindromic repeats (MIRA-CRISPR)/Cas13a-lateral flow device (LFD). This assay targets the repeated DNA sequence (GenBank: L23861.1) of T. vaginalis and is performed at a constant temperature of 37 °C for approximately 1 hour. RESULTS: The detection limit of genomic DNA (gDNA) using our protocol was 1 × 10-4 ng/µl. Specificity was confirmed by the absence of cross-reaction with gDNA from various other microorganisms such as Staphylococcus aureus, Lactobacillus taiwanensis, Escherichia coli, Monilia albicans, Giardia lamblia, or Toxoplasma gondii. Among 30 clinical samples tested, the positive rates of T. vaginalis detection were 33.33% (10/30) by wet mount microscopy, 40% (12/30) by nested polymerase chain reaction (PCR), 40% (12/30) by MIRA-CRISPR/Cas13a-LFD, and 40% (12/30) by the culture method. Compared with the culture method, the gold standard for diagnosing trichomoniasis, wet mount microscopy showed a sensitivity of 83.3% and moderate diagnostic agreement (kappa value = 0.87). Both nested PCR and MIRA-CRISPR/Cas13a-LFD exhibited 100% sensitivity and excellent diagnostic agreement (kappa value = 1). CONCLUSIONS: The MIRA-CRISPR/Cas13a-LFD method is a convenient, rapid, stable, and accurate diagnostic tool for detecting T. vaginalis. This method has the potential to enhance the diagnosis and management of vaginitis, offering a significant improvement over existing diagnostic techniques.

[Photosynthetic characteristics of Leymus chinensis and Medicago sativa in artificial grassland]. / ç¾Šè‰å’Œç´«èŠ±è‹œè“¿äººå·¥è‰åœ°å ‰åˆç‰¹æ€§.

To explore the effect of monoculture and mixture sowing artificial grassland on the photosynthetic characteristics of Leymus chinensis and Medicago sativa, we determined the diurnal variation of photosynthetic properties of L. chinensis and M. sativa under different treatments. The results showed that the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type' in monoculture, the stomatal conductance of M. sativa showed 'unimodal type', and the stomatal conductance and water use efficiency of L. chinensis showed 'bimodal type'. Under the mixed sowing treatment, the diurnal changes of net photosynthetic rate, blade temperature and transpiration rate of L. chinensis and M. sativa showed 'unimodal type', the stomatal conductance and water use efficiency of L. chinensis showed 'unimodal type', and the stomatal conductance of M. sativa showed 'bimodal type'. The peak photosynthetic rate of L. chinensis under mixture was signi-ficantly higher than that under monoculture, being 17.72 and 13.65 µmol CO2·m-2·s-1, respectively. Under monoculture and mixture sowing treatments, the chlorophyll content of L. chinensis was higher than that of M. sativa, nitrogen content of the leaves of L. chinensis was lower than that of M. sativa, and the nitrogen content in the leaves of mixture sowing L. chinensis was significantly higher than that of monoculture sowing L. chinensis, which were 27.60 and 22.55 g·kg-1, respectively. Net photosynthetic rates of L. chinensis and M. sativa were significantly positively correlated with stomatal conductance and transpiration rate, and significantly negatively correlated with intercellular CO2 concentration under different planting methods. Net photosynthetic rate of M. sativa was significantly positively correlated with blade temperature and water use efficiency. In summary, mixed sowing was beneficial to enhance nitrogen content of L. chinensis. Our results provided a theoretical basis for the response of the photosynthetic characteristics of forage to planting mode of artificial grassland.

The Added Value of 18F-FDG PET/CT Compared with 68Ga-PSMA PET/CT in Patients with Castration-Resistant Prostate Cancer.

68Ga-prostate-specific membrane antigen (68Ga-PSMA) PET/CT is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between 68Ga-PSMA and 18F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially 68Ga-PSMA-negative [-], 18F-FDG-positive [+] lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of 18F-FDG PET/CT compared with 68Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional 18F-FDG PET/CT. Methods: The data of 56 patients with CRPC who underwent both 68Ga-PSMA and 18F-FDG PET/CT from May 2018 to February 2021 were retrospectively analyzed. The patients were classified into 2 groups: with or without 68Ga-PSMA-, 18F-FDG+ lesions. The differences in patient characteristics between the 2 groups and predictors of patients who have at least 1 68Ga-PSMA-, 18F-FDG+ lesion were analyzed. Results: Although both the detection rate (75.0% vs. 51.8%, P = 0.004) and the number of positive lesions (135 vs. 95) were higher for 68Ga-PSMA PET/CT than for 18F-FDG PET/CT, there were still 13 of 56 (23.2%) patients with at least 1 68Ga-PSMA-, 18F-FDG+ lesion. Prostate-specific antigen (PSA) and the Gleason score were both higher in patients with 68Ga-PSMA-, 18F-FDG+ lesions than in those without (P = 0.04 and P < 0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and PSA (≥7.9 ng/mL) were associated with the detection rate of patients who had 68Ga-PSMA-, 18F-FDG+ lesions (P = 0.01 and P = 0.04, respectively). The incidences of having 68Ga-PSMA-, 18F-FDG+ lesions in low-probability (Gleason score < 8 and PSA < 7.9 ng/mL), medium-probability (Gleason score ≥ 8 and PSA < 7.9 ng/mL or Gleason score < 8 and PSA ≥ 7.9 ng/mL), and high-probability (Gleason score ≥ 8 and PSA ≥ 7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P < 0.001). Conclusion: Gleason score and PSA are significant predictors of 68Ga-PSMA-, 18F-FDG+ lesions, and CRPC patients with a high Gleason score and PSA may benefit from additional 18F-FDG PET/CT.

Development and validation of a multivariable predictive model for EGFR gene mutation status in patients with lung adenocarcinoma.

Detection of epidermal growth factor receptor (EGFR) is one real dilemma owing to the non-sufficient tissue for testing EGFR mutations in lung adenocarcinoma. A model for predicting EGFR mutations would be helpful for clinical decisions in those patients. A retrospective cohort of 1,196 patients diagnosed with lung adenocarcinoma was investigated between December 1, 2017, and December 31, 2019, in Renji Hospital, Shanghai, China. All patients were tested for EGFR mutations (amplification refractory mutation system, n=1,144; next-generation sequencing, n=52). Of 1,196 patients with lung adenocarcinoma, 944 met the inclusion criteria. A nomogram model was developed based on 567 patients and validated in 377 patients. Variables associated with EGFR mutations were age, sex, smoking history, lepidic predominant subtype, solid predominant subtype, mucinous adenocarcinoma, Ki67 expression, lobulation, solid texture in radiology, and pleural retraction. The nomogram based on the model performed well in the development group (c-index 0.789, 95% CI: 0.751-0.827), and the validation group (c-index 0.809, 95% CI: 0.771-0.847). At the probability cut-point of 0.7, the diagnostic efficiency was 82.7% in patients with NGS liquid biopsy. Decision curve analysis further confirmed the clinical usefulness of the nomogram, which showed that predicting the EGFR mutations probability applying this nomogram would be better than having all patients or none patients use this nomogram. A high probability group (>0.7) by nomogram model may suggest a high possibility of EGFR mutation, if tissue is limited, NGS-based ctDNA with liquid biopsy could be implemented effectively.

Driving mechanism of drift-step-recovery diodes.

Parameters governing forward and reverse pumping of a device mechanism have an important influence on the cutoff and output characteristics of a drift-step-recovery diode (DSRD). Therefore, we analyzed the driving circuit for the DSRD that was used to adjust pumping parameter values. With multiple modules in parallel, a driving method exploiting narrow-pulse pumping is proposed in developing a high-repetition-frequency DSRD pulse generator. In experiments and simulations, one key factor affecting the working stability of this pulse generator operating at repetition frequencies in the megahertz range was found that helped in further optimizing the parameter settings of our 2 kV DSRD driving circuit. From this insight, a 2 kV-5 MHz all-solid-state high-repetition-frequency pulse generator based on the DSRD was developed.

Adipocyte-specific deletion of Depdc5 exacerbates insulin resistance and adipose tissue inflammation in mice.

The mammalian target of rapamycin complex 1 (mTORC1) is a crucial regulator of adipogenesis and systemic energy metabolism. Its dysregulation leads to a diversity of metabolic diseases, including obesity and type 2 diabetes. DEP-domain containing 5 (DEPDC5) is a critical component of GATOR1 complex that functions as a key inhibitor of mTORC1. So far, its function in adipose tissue remains largely unknown. Herein we evaluated how persistent mTORC1 activation in adipocyte via Depdc5 knockout modulates adiposity in vivo. Our data indicated that adipocyte-specific knockout of Depdc5 in aged mice led to reduced visceral fat, aggravated insulin resistance and enhanced adipose tissue inflammation. Moreover, we found that Depdc5 ablation resulted in upregulation of adipose triglyceride lipase (ATGL) in adipocytes and elevated levels of serum free fatty acids (FFAs). Intriguingly, rapamycin treatment did not reverse insulin resistance but alleviated adipose tissue inflammation caused by Depdc5 deletion. Taken together, our findings revealed that mTORC1 activation caused by Depdc5 deletion promotes lipolysis process and further exacerbates insulin resistance and adipose tissue inflammation in mice.

The Heterogeneous Metabolic Patterns of Ganglia in 68Ga-PSMA, 11C-choline, and 18F-FDG PET/CT in Prostate Cancer Patients.

PURPOSE: Studies have indicated that PSMA-positive ganglia represent a diagnostic pitfall for nuclear medicine physicians. No studies have described choline and FDG uptake in ganglia, which may be a source of misdiagnosis. Herein, we described the percentage and uptake pattern of 68Ga-PSMA, 11C-choline and 18F-FDG PET/CT in ganglia and evaluated the heterogeneous metabolic patterns of ganglia to differentiate from lymph node metastases (LNM). METHODS: Thirty-nine patients who underwent 11C-choline PET/CT and 120 patients who underwent 68Ga-PSMA PET/CT and 18F-FDG PET/CT were retrospectively analyzed. The prevalence of PSMA-positive, choline-positive and FDG-positive ganglia was determined, the SUVmax of ganglia in different locations were measured, and the configuration was described. The SUVmax cutoff of PSMA-PET, choline-PET and FDG-PET was determined by ROC curve analysis to differentiate ganglia from LNM. RESULTS: 329 PSMA-positive ganglia were identified in 120 patients, 95 choline-positive ganglia were identified in 39 patients, and 39 FDG-positive ganglia were identified in 34 patients. PSMA-positive uptake was observed in 98.3%, 95.8%, and 80.0% of cervical, coeliac, and sacral ganglia, respectively. Choline-positive uptake was observed in 84.6%, 97.4%, and 61.5% of cervical, coeliac, and sacral ganglia, respectively. FDG-positive uptake was observed in 16.7%, 13.3%, and 2.5% of cervical, coeliac, and sacral ganglia, respectively. Cervical and coeliac ganglia had a higher rate of PSMA-positive uptake than sacral ganglia. Choline uptake was highest in coeliac ganglia followed by cervical and sacral ganglia. PSMA, choline or FDG uptake in LNM was all significantly higher than ganglia. ROC curve analysis revealed that at a 4.1 SUVmax cutoff of PSMA-PET, the sensitivity, specificity and accuracy of LNM identification was 88.4%, 97.9% and 96.2%, respectively. ROC curve analysis revealed that at a 2.35 SUVmax cutoff for choline-PET, the sensitivity, specificity, and accuracy of LNM identification was 95.0%, 92.6% and 93.0%, respectively. ROC curve analysis revealed that at a 2.55 SUVmax cutoff for FDG-PET, the sensitivity, specificity, and accuracy of LNM identification was 77.3%, 87.2%, and 81.9%, respectively. PSMA-, Choline- and FDG-positive ganglia are mainly band-shaped; most LNMs exhibited nodular and teardrop-shaped configuration. CONCLUSION: 68Ga-PSMA and 11C-choline uptake in ganglia was common, and FDG-positive ganglia were observed at lower frequency. Using 68Ga-PSMA, 11C-choline and 18F-FDG uptake and anatomic location and configuration, the differentiation of ganglia from adjacent LNM is feasible.

The added value of 18F-FDG PET/CT compared to 68Ga-PSMA PET/CT in patients with castration-resistant prostate cancer.

Purpose: The 68Ga-PSMA PET/CT is a commonly used imaging modality in prostate cancers. However, few studies have compared the diagnostic efficiency between 68Ga-PSMA and 18F-FDG PET/CT and evaluated whether a heterogeneous metabolic phenotype (especially PSMA-FDG+ lesions) exists in patients with castration-resistant prostate cancer (CRPC). We determined the added value of 18F-FDG PET/CT compared to 68Ga-PSMA PET/CT in CRPC patients and identified CRPC patients who may benefit from additional 18F-FDG PET/CT. Methods: Data of 56 patients with CRPC who underwent both 68Ga-PSMA and 18F-FDG PET/CT from May 2018 to February 2021 were retrospectively analysed. Patients were classified into two groups with or without PSMA-FDG+ lesions. The differences in patient characteristics between the two groups and predictors of patients who having at least one PSMA-FDG+ lesion were analysed. Results: Although both the detection rate (75.0% vs. 51.8%, P = 0.004) and positive lesion number (135 vs. 95) of 68Ga-PSMA PET/CT were higher than 18F-FDG PET/CT, there were still 13/56 (23.2%) patients with at least one PSMA-FDG+ lesion. The prostate-specific antigen (PSA) and Gleason score were both higher in the patients with PSMA-FDG+ lesions than in those without PSMA-FDG+ lesions (P = 0.04 and P<0.001, respectively). Multivariate regression analysis showed that the Gleason score (≥8) and PSA (≥7.9 ng/mL) were associated with the detection rate of patients who had PSMA-FDG+ lesions (P = 0.01 and P = 0.04, respectively). The incidences of having PSMA-FDG+ lesions in low-probability (Gleason score<8 and PSA<7.9 ng/mL), medium-probability (Gleason score≥8 and PSA<7.9 ng/mL or Gleason score<8 and PSA≥7.9 ng/mL), and high-probability (Gleason score≥8 and PSA≥7.9 ng/mL) groups were 0%, 21.7%, and 61.5%, respectively (P<0.001). Conclusion: Gleason score and PSA are significant predictors for PSMA-FDG+ lesions, and CRPC patients with high Gleason score and PSA may benefit from additional 18F-FDG PET/CT.

Use of 68Ga-PSMA-11 and 18F-FDG PET-CT Dual-Tracer to Differentiate Between Lymph Node Metastases and Ganglia.

PURPOSE: Differentiating lymph node metastases (LNM) from peripheral ganglia by physiological prostate-specific membrane antigen (PSMA) uptake is challenging. Two tracers (68Ga-PSMA-11 and 18F-fluorodeoxyglucose [FDG]) metabolic uptake patterns were evaluated by positron emission tomography-computed tomography (PET-CT), searching for differences that could tell ganglia from LNM. METHODS: Dual 68Ga-PSMA-11 and 18F-FDG PET-CT data of 138 prostate cancer patients acquired from June 2018 to December 2019 were retrospectively evaluated. Ganglia and LNM with PSMA-11 uptake above local background were analyzed by the location and PSMA-11-PET and FDG-PET maximum standardized uptake value (SUVmax). RESULTS: PSMA-11-positive ganglia (n = 381) and LNM (n = 83) were identified in 138 and 58 patients, respectively. The LNM SUVmax of PSMA-11-PET (16.4 ± 14.8 vs 2.3 ± 0.7, P < 0.001) and FDG-PET (3.3 ± 3.2 vs 1.5 ± 0.5, P < 0.001) were higher than in ganglia. The probabilities of being an LNM in the low-potential (PSMA-11-PET SUVmax of <4.1 and FDG-PET SUVmax of <2.05), moderate-potential (PSMA-11-PET SUVmax of >4.1 and FDG-PET SUVmax of <2.05, or PSMA-11-PET SUVmax of <4.1 and FDG-PET SUVmax of >2.05), and high-potential (PSMA-11-PET SUVmax of >4.1 and FDG-PET SUVmax of >2.05) groups were 0.9% (3/334), 44.6% (37/83), and 91.5% (43/47), respectively (P < 0.001). The cervical and coeliac ganglia had higher PSMA-11 and FDG uptake than the sacral ganglia (P < 0.001 for all). LNM PSMA-11 and FDG uptake was similar in these three locations. CONCLUSION: The FDG-PET and PSMA-11-PET SUVmax, especially when combined, could well differentiate LNM from ganglia. The tracers uptake differed between cervical/coeliac and sacral ganglia, so the lesion location should be considered during image assessment.

Diagnostic value of 18F-FDG PET/CT in patients with biochemical recurrent prostate cancer and negative 68Ga-PSMA PET/CT.

PURPOSE: 68Ga-PSMA PET/CT has a high detection rate in prostate cancer patients with biochemical recurrence (BCR). However, few studies have reported other imaging methods for BCR with negative 68Ga-PSMA PET/CT findings. We investigated the value of 18F-FDG compared with 68Ga-PSMA and identified BCR patients with 68Ga-PSMA-negative findings who are most likely to benefit from 18F-FDG PET/CT. METHODS: Seventy-two BCR patients with negative 68Ga-PSMA PET/CT findings were retrospectively identified from 510 patients who underwent concomitant 68Ga-PSMA and 18F-FDG PET/CT between June 2018 and August 2020. Patients were categorised into groups with positive or negative 18F-FDG PET/CT findings. Differences in patients' characteristics between these two groups and predictors of positive 18F-FDG findings were analysed. RESULTS: The detection rate of 18F-FDG PET/CT was 16.7% (12/72) in BCR patients with 68Ga-PSMA-negative findings. PSA and Gleason score were significantly higher in the 18F-FDG-positive group than in the 18F-FDG-negative group (P < 0.001 and P < 0.001, respectively). A multivariate analysis indicated that PSA (PSA ≥2.3 ng/mL) and Gleason score (Gleason score ≥ 8) correlated with 18F-FDG-positive findings (P < 0.001 and P = 0.015, respectively). The probabilities of 18F-FDG-positive findings in the low-potential (PSA <2.3 ng/mL and Gleason score <8), moderate-potential (PSA <2.3 ng/mL and Gleason score ≥ 8 or PSA ≥2.3 ng/mL and Gleason score <8), and high-potential (PSA ≥2.3 ng/mL and Gleason score ≥ 8) groups were 0%, 11.5%, and 90.0%, respectively (P < 0.001). CONCLUSION: PSA level and Gleason score are independent predictors of 18F-FDG-positive findings, and BCR patients with 68Ga-PSMA-negative findings with high PSA and Gleason score are most likely to benefit from 18F-FDG PET/CT.

Delayed 18F-FDG PET/CT Appearance of Urachal Adenocarcinomas.

Background: Urachal carcinoma is a rare urological malignancy. Use of 18F-FDG PET/CT in urological oncology has developed slowly because of the urinary elimination of 18F-FDG. We investigated whether delayed postdiuretic 18F-FDG PET/CT could be used for diagnosing urachal carcinoma. Methods: This retrospective study included 6 patients who underwent delayed postdiuretic 18F-FDG PET/CT for the evaluation of urachal carcinoma. The delayed postdiuretic PET/CT parameters and clinical characteristics of urachal carcinoma were investigated. Results: There was no significant difference in the SUVmax between the primary tumors and the urine in the bladder before delayed diuresis (25.4 ± 19.5 vs. 42.9 ± 31.1, P=0.18). However, the SUVmax of the primary tumors was significantly higher than the SUVmax of urine after delayed diuresis (25.4 ± 19.5 vs. 3.5 ± 1.6, P=0.002). Diuretic 18F-FDG PET/CT was positive in all patients when compared with normal liver tissues or urine after delayed diuresis. The SUVmax, TLR, and TUR of the primary tumors were 25.4 (range: 7.2-58.9), 7.0 (range: 1.8-14.7), and 6.8 (range: 3.8-11.3), respectively. Delayed postdiuretic 18F-FDG PET/CT had a negative predictive value of 100% (5/5) for predicting lymph node metastasis. One patient received chemotherapy after radical resection of urachal carcinoma because 18F-FDG PET/CT found lung metastases, and one patient only received chemotherapy because PET/CT found peritoneal and skeletal metastases. Conclusions: Delayed postdiuretic 18F-FDG PET/CT is a useful tool for the preoperative evaluation of urachal carcinoma. 18F-FDG PET/CT may improve clinical decision making and management of urachal carcinomas.

Delayed post-diuretic 18F-FDG PET/CT for preoperative evaluation of renal pelvic cancer.

Background: Application of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in urological oncology was relatively slowly due to the urinary elimination of 18F-FDG. We investigated whether delayed post-diuretic 18F-FDG PET/CT could be used for diagnosing renal pelvic cancer. Methods: 51 patients were included who underwent delayed post-diuretic 18F-FDG PET/CT for detecting renal pelvic space-occupying lesions. The comparations of delayed PET/CT parameters and clinical characteristics between renal pelvic cancer and benign polyp were investigated. Results: Among the 51 patients, 47 were found to have renal pelvic urothelial carcinoma, and 4 had benign polyp. ROC analysis identified the lesion maximum standardized uptake value (SUVmax) of 6.2 as the optimal cut-off value to distinguish from renal pelvic urothelial carcinoma to benign polyp. With the SUVmax cut-off of 6.2, the sensitivity, and specificity for predicting of renal pelvic urothelial carcinoma were 91.5% (43/47), and 100% (4/4). We also found a significant difference in tumor size between the positive (SUVmax > 6.2) and negative (SUVmax ≤ 6.2) PET groups in renal pelvic cancers. In patients with tumor size < 1.1 cm, the probability of being in the negative PET group was 75%. In such patients, a substantial proportion of renal pelvic cancer demonstrated negative SUVmax similar to that in patients with benign polyp. Conclusion: Delayed 18F-FDG PET/CT could be used for differentiating renal pelvic cancer from benign polyp. In patients with small tumor size, renal pelvic cancer may present low 18F-FDG uptake, mimicking the metabolic phenotypes of patients with benign polyp.

Delayed 18F FDG PET/CT Imaging in the Assessment of Residual Tumors after Transurethral Resection of Bladder Cancer.

Background Delayed fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT is used to diagnose bladder cancer. However, it remains difficult to determine whether a lesion with abnormal 18F FDG uptake is tumor residue or recurrence or if it is an inflammatory reaction in patients with bladder cancer after oncologic treatment. Purpose To determine the diagnostic performance of delayed 18F FDG PET/CT in the differentiation of residual tumors from postoperative inflammatory reactions in patients with bladder cancer after initial transurethral resection of bladder tumor (TURBT). Materials and Methods A retrospective clinical study between January 2015 and April 2018 was performed in 79 patients with bladder cancer who had undergone 18F FDG PET/CT within 1 month after initial TURBT. After PET/CT, all patients underwent a second surgery within 2 weeks to confirm the histologic nature of the suspicious lesion and to remove residual tumors. Uni- and multivariable analysis were used to identify predictive factors for residual bladder tumors. Results A total of 79 patients (61 men, 18 women; mean age, 63 years ± 11 [standard deviation]) were enrolled in this study. A total of 98 lesions was studied, 64 (65.3%) of which were residual tumors after initial TURBT. When compared with inflammatory reactions, residual tumors had higher mean standardized uptake value (SUVmean) (mean, 5.8 ± 2.0 vs 9.3 ± 5.4; P < .001), higher maximum standardized uptake value (SUVmax) (mean, 15.5 ± 9.8 vs 22.2 ± 13.6, P = .01), and greater lesion thickness (mean, 9.6 mm ± 4.1 vs 17.9 mm ± 11.1, P < .001) at 18F FDG PET/CT. SUVmean (odds ratio [OR], 1.2; 95% confidence interval [CI]: 1.0, 1.5; P = .049) and lesion thickness (OR, 1.2; 95% CI: 1.0, 1.3; P = .006 or OR, 1.2; 95% CI: 1.1, 1.3; P = .001) were identified as independent predictors for residual tumors with multivariable logistic regression analysis. On the basis of the threshold values of SUVmean and lesion thickness, we revealed a prediction rate of 37.5% (17 of 47), 85.4% (26 of 29), and 98.3% (21 of 22) for residual tumors in low-, moderate-, and high-risk subgroups, respectively. Conclusion Use of fluorine 18 fluorodeoxyglucose PET/CT to differentiate lesions after transurethral resection of bladder tumor indicates that higher mean standardized uptake values and greater lesion thickness are predictive factors for residual tumors in patients with bladder cancer after oncologic treatment. Published under a CC BY 4.0 license.

A new route to N-aromatic heterocycles from the hydrogenation of diesters in the presence of anilines.

The hydrogenation of dicarboxylic acids and their esters in the presence of anilines provides a new synthesis of heterocycles. [Ru(acac)3] and 1,1,1-tris(diphenylphosphinomethyl)ethane (triphos) gave good to excellent yields of the cyclic amines at 220 °C. When aqueous ammonia was used with dimethyl 1,6-hexadienoic acid, ε-caprolactam was obtained in good yield. A side reaction involving alkylation of the amine by methanol was suppressed by using diesters derived from longer chain and branched alcohols. Hydrogenation of optically pure diesters (dimethyl (R)-2-methylbutanedioate and dimethyl (S)-2-methylbutanedioate) with aniline afforded racemic 3-methyl-1-phenylpyrrolidine in 78% yield.

Correlation of pretreatment 18F-FDG uptake with clinicopathological factors and prognosis in patients with newly diagnosed diffuse large B-cell lymphoma.

OBJECTIVES: The aim of this study is to determine the correlation of pretreatment fluorine-18 fluorodeoxyglucose uptake with clinicopathological factors and its prognostic value in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: A cohort of 162 patients with newly diagnosed DLBCL who had undergone pretreatment PET/computed tomography was retrospectively reviewed. The relationship of pretreatment maximum standard uptake value (SUVmax) with clinical factors, molecular markers, and efficacy was evaluated. The value of SUVmax in predicting progression-free survival (PFS) and overall survival was analyzed. RESULTS: In all, 72.9% of the patients received R-CHOP treatment; the rest received CHOP chemotherapy. The median follow-up duration was 30 months (range, 4-124 months). The median SUVmax was 12.2 (range, 1.7-42.7). SUVmax between groups differed significantly with respect to each of International Prognostic Index (IPI) factors, except for age and performance status. High SUVmax was associated with high Ki-67 and Glut-3 protein expression, but not with Glut-1. Complete remission rate differed significantly between the low (SUVmax≤9.0) and the high SUVmax (SUVmax>9.0) groups (91.7 vs. 61.1%, P=0.000). Patients with low SUVmax showed favorable survival (3-year PFS: 92.2 vs. 63.6%, P=0.000; 3-year overall survival: 95.5 vs. 78.3%, P=0.003). On multivariate analyses, SUVmax predicted PFS independent of revised-IPI (SUVmax: P=0.011, hazard ratio 4.784; revised-IPI: P=0.004, hazard ratio 2.551). CONCLUSION: Pretreatment SUVmax was associated with clinicopathological factors, efficacy, and survival outcome. A novel prognostic model on the basis of IPI score/pretreatment SUVmax might be useful for risk stratification of patients with newly diagnosed DLBCL Video abstract: http://links.lww.com/NMC/A55.

Essential role of the N- and C-terminals of laccase from Pleurotus florida on the laccase activity and stability.

POXA1b is the most thermostable laccase isoenzyme from Pleurotus ostreatus. POXA1b is remarkably stable at alkaline pH (the t1/2 at pH 10 was 30 days), and its C-terminal affects its catalytic and stability properties. We cloned POXA1c from P. florida, which showed 99 % identity with POXA1b. POXA1c was functionally expressed in Pichia pastoris. The functions of the N and C termini of POXA1c were investigated using site-directed mutagenesis. Compared with POXA1c, the N-terminal R5V site effectively increased the specific activities for 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and guaiacol by 2- and 3.5-fold, respectively. A C-terminal truncated mutant, POXA1c△13, also increased the specific activities for ABTS and guaiacol by 2.3- and 3.4-fold, respectively. A double mutant, POXA1cΔ13-R5V, combined the R5V and △13 effects. The specific activity of this double mutant for ABTS was 1,321 U/mg, which indicated a 4-fold increase compared with the wild type. The role of residue V5 on laccase catalytic properties was also observed for laccases from Trametes versicolor and Rigidoporus lignosus. The specific activities of the V5R of the laccases from T. versicolor and R. lignosus were half of that of the wild type. The pH and thermal stability analysis of POXA1c and its mutants showed that the enzymes were remarkably stable because they showed 63 % residual activity after incubation for 108 h at 30 °C over a pH range of 4.5 to 9.0. Similar results were observed for POXA1cΔ13-R5V. POXA1cΔ13-R5V can be widely used in industrial biotechnology because of its excellent catalytic properties.