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Accurate air quality forecasting is crucial for public health, environmental monitoring and protection, and urban planning. However, existing methods fail to effectively utilize multi-scale information, both spatially and temporally. There is a lack of integration between individual monitoring stations and city-wide scales. Temporally, the periodic nature of air quality variations is often overlooked or inadequately considered. To overcome these limitations, we conduct a thorough analysis of the data and tasks, integrating spatio-temporal multi-scale domain knowledge. We present a novel Multi-spatial Multi-temporal air quality forecasting method based on Graph Convolutional Networks and Gated Recurrent Units (M2G2), bridging the gap in air quality forecasting across spatial and temporal scales. The proposed framework consists of two modules: Multi-scale Spatial GCN (MS-GCN) for spatial information fusion and Multi-scale Temporal GRU (MT-GRU) for temporal information integration. In the spatial dimension, the MS-GCN module employs a bidirectional learnable structure and a residual structure, enabling comprehensive information exchange between individual monitoring stations and the city-scale graph. Regarding the temporal dimension, the MT-GRU module adaptively combines information from different temporal scales through parallel hidden states. Leveraging meteorological indicators and four air quality indicators, we present comprehensive comparative analyses and ablation experiments, showcasing the higher accuracy of M2G2 in comparison to nine currently available advanced approaches across all aspects. The improvements of M2G2 over the second-best method on RMSE of 72-h future predictions are as follows: PM2.5: 6%∼10%; PM10: 5%∼7%; NO2: 5%∼16%; O3: 6%∼9%. Furthermore, we demonstrate the effectiveness of each module of M2G2 by ablation study. We conduct a sensitivity analysis of air quality and meteorological data, finding that the introduction of O3 adversely impacts the prediction accuracy of PM2.5.

Background: Cancer of unknown primary (CUP) is difficult to diagnose and classify clinically, and the disease develops rapidly. Therefore, the primary tumor detected in patients with CUP plays a profound role in the diagnosis and treatment of patients. The search for the primary tumor of CUP is also one of the indications for 18F-fluoro-2-deoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). Our objective was to evaluate the role of 18 F-FDG PET/CT imaging in primary tumor detection and treatment formulation in patients with CUP. Methods: Sixty-two patients with CUP were selected from a database consisting of 18 802 cases in the Jiangsu Cancer Hospital PET/CT center from May 18, 2016 to November 18, 2022. Clinical data and changes in treatment strategies before and after PET/CT were collected. Results: A total of 42 primary tumors (42/62, 67.7%) were identified by PET/CT examination. The tumor staging of patients before conventional PET/CT imaging (such as CT/magnetic resonance imaging [MRI]/US) and after PET/CT did not change in 28 patients (28/62, 45.2%), whereas for 34 patients (34/62, 54.8%), tumor staging changed. Forty-five patients (45/62, 72.6%) had not developed treatment plans before PET/CT examination, but treatment plans were clarified after PET/CT examination. Thirteen patients (13/62, 21.0%) underwent changes in treatments before and after PET/CT examination. Among the 20 patients (20/62, 32.3%) whose primary tumors were not detected, 16 patients (16/20, 80.0%) had no treatment plans before PET/CT and the treatment plans were defined after PET/CT, 3 patients (3/20, 15.0%) changed the treatment plans before and after PET/CT, and 1 patient (1/20, 5.0%) did not change the treatment plan. Conclusions: The 18 F-FDG PET/CT plays an important role in the detection and staging of primary tumors in patients with CUP. The PET/CT findings can not only help clinicians develop appropriate treatment plans for patients with CUP but also serve as an effective approach to improve real-life treatment strategies for these patients.

Background: Following changes in primary tumor (T) and lymph node (N) staging for nasopharyngeal carcinoma (NPC) in the Eighth Edition AJCC Cancer Staging Manual , simplification of T staging has been proposed. However, a limited range of 2-deoxy-2-[fluorine-18] fluoro- D -glucose positron emission tomography–computed tomography ( 18 F-FDG PET–CT) metabolic parameters has been investigated. Therefore, we aimed to evaluate the primary tumor invasiveness and the lymph node metastasis (LNM) of NPC from a metabolic perspective. Methods: A total of 435 NPC patients underwent 18 F-FDG PET/CT before treatment were retrospectively examined. The primary endpoint was differences in standard uptake value (SUV), lean body mass-normalized SUV (SUL), body surface area-normalized SUV (SUS), glucose-normalized SUV (GN), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and glucose-normalized total lesion glycolysis (GNTLG) of primary tumors and LNM between different T and N stages. The metabolic parameters associated with T and N staging were identified. Results: There were significant differences between all parameters relative to the primary tumor but no significant differences in any parameter relative to the LNM and T stages. Higher mean values of TGN max , TGN mean , TSUV peak , and TSUS max were associated with advanced T stages. Higher mean values of all the LNM parameters were associated with more advanced N stages. Only primary tumor metabolic tumor volume (TMTV), TSUV peak , TSUL max , and TSUS max showed a significant positive association with T staging, while lymph node metabolic tumor volume (LNMTV) and TSUS max were significantly positive in N staging. Conclusions: Our findings suggest that metabolic parameters are useful indicators of tumor invasiveness and LNM based on the Eighth Edition manual. Compared with volume-dependent parameters, TGN max , TGN mean , TSUV peak , and TSUS max may be better indicators of local tumor aggressiveness. SUS max of the primary tumor was associated with LNM. In addition to SUV max , other metabolic parameters (eg, SUL max , SUS max , GN max , and GN mean ) could evaluate tumor aggressiveness and LNM better.

Abstract Background Peroxisome proliferator-activated receptor gamma (PPARγ) is an enhancer of Treg responses, but the mechanisms remain elusive. This study aimed to solve this problem in view of cellular metabolism. Methods Three recognized PPARγ agonists (synthetic agonist: rosiglitazone; endogenous ligand: 15d-PGJ2; natural product: morin) were used as the tools to activate PPARγ. The fatty acid oxidation (FAO) was evaluated through the detection of fatty acid uptake, oxygen consumption rate, mitochondrial mass, mitochondrial membrane potential and acetyl-CoA level. The involvement of UDP-GlcNAc/N-linked glycosylation axis and the exact role of PPARγ in the action of PPARγ agonists were determined by flow cytometry, Q-PCR, western blotting, a commercial kit for enzyme activity and CRISPR/Cas9-mediated knockout. Results Rosiglitazone, 15d-PGJ2 and morin all increased the frequency of CD4+Foxp3+ Treg cells generated from naïve CD4+ T cells, boosted the transcription of Foxp3, IL-10, CTLA4 and TIGIT, and facilitated the function of Treg cells. They significantly promoted FAO in differentiating Treg cells by up-regulating the levels of CD36 and CPT1 but not other enzymes involved in FAO such as ACADL, ACADM, HADHA or HADHB, and siCD36 or siCPT1 dampened PPARγ agonists-promoted Treg responses. Moreover, PPARγ agonists enhanced UDP-GlcNAc biosynthesis and subsequent N-linked glycosylation, but did not affect the expressions of N-glycan branching enzymes Mgat1, 2, 4 and 5. Notably, the enzyme activity of phosphofructokinase (PFK) was inhibited by PPARγ agonists and the effect was limited by siCD36 or siCPT1, implying PFK to be a link between PPARγ agonists-promoted FAO and UDP-GlcNAc biosynthesis aside from acetyl-CoA. Furthermore, PPARγ agonists facilitated the cell surface abundance of TβRII and IL-2Rα via N-linked glycosylation, thereby activating TGF-β/Smads and IL-2/STAT5 signaling, and the connection between N-linked glycosylation and Treg responses was revealed by tunicamycin. However, the increased surface abundance of CD36 was demonstrated to be mainly owing to PPARγ agonists-up-regulated overall expression. Finally, PPARγ antagonist GW9662 or CRISPR/Cas9-mediated knockout of PPARγ constrained the effects of rosiglitazone, 15d-PGJ2 and morin, confirming the exact role of PPARγ. Conclusions The activation of PPARγ enhances Treg responses through up-regulating CD36/CPT1-mediated fatty acid oxidation and subsequent N-glycan branching of TβRII/IL-2Rα, which is beneficial for inflammatory and autoimmune diseases. Graphical abstract Video Abstract

The combined role of inflammatory markers [including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)] and PET/CT metabolic parameters [including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and TLG (total lesion glycolysis)] at baseline in evaluating the binary stage [extensive-stage disease (ED) and limited-stage disease (LD)] of small cell lung cancer (SCLC) is unclear. In this study, we verified that high metabolic parameters and inflammatory markers were related to the binary stage of SCLC patients, respectively (p < 0.05). High inflammatory markers were also associated with high MTV and TLG in patients with SCLC (p < 0.005). Moreover, the incidences of co-high metabolic parameters and inflammatory markers were higher in ED-SCLC (p < 0.05) than those in LD-SCLC. Univariate logistic regression analysis demonstrated that Co-high MTV/NLR, Co-high MTV/MLR, Co-high MTV/SII, Co-high TLG/NLR, Co-high TLG/MLR, and Co-high TLG/SII were significantly related to the binary stage of SCLC patients (p = 0.00). However, only Co-high MTV/MLR was identified as an independent predictor for ED-SCLC (odds ratio: 8.67, 95% confidence interval CI: 3.51–21.42, p = 0.000). Our results suggest that co-high metabolic parameters and inflammatory markers could be of help for predicting ED-SCLC at baseline. Together, these preliminary findings may provide new ideas for more accurate staging of SCLC.

BackgroundA growing number of neuroimaging studies reported that chemotherapy might impair brain functions, leading to persistent cognitive alterations in a subset of cancer patients. The present study aimed to investigate the regional brain glucose metabolism differences between diffuse large B cell lymphoma (DLBCL) patients treated with cyclophosphamide, epirubicin, vincristine, and prednisone and controls using positron emission tomography with 18F-labeled fluoro-2-deoxyglucose integrated with computed tomography (18F-FDG PET/CT) scanning.MethodsWe analyzed 18F-FDG PET data from 205 right-handed subjects (for avoiding the influence of handedness factors on brain function), including 105 post-chemotherapy DLBCL patients and 100 controls. The two groups had similar average age, gender ratio, and years of education. First, we compared the regional brain glucose metabolism using a voxel-based two-sample t-test. Second, we compared the interregional correlation. Finally, we investigated the correlations between the regional brain glucose metabolism and the number of chemotherapy cycles.ResultsCompared with the controls, the post-chemotherapy group showed higher metabolism in the right hippocampus and parahippocampal gyrus (region of interest (ROI) 1) and the left hippocampus (ROI 2), and lower metabolism in the left medial orbitofrontal gyrus (ROI 3), the left medial superior frontal gyrus (ROI 4), and the left superior frontal gyrus (ROI 5). The two groups had different interregional correlations between ROI 3 and ROI 5. In some brain regions—mainly located in the bilateral frontal gyrus—the number of chemotherapy cycles was positively correlated with the regional brain glucose metabolism. Meanwhile, in some bilateral hippocampus regions, these two parameters were negatively correlated.ConclusionThe present study provides solid data on the regional brain glucose metabolism differences between post-chemotherapy DLBCL patients and controls. These results should improve our understanding of human brain functions alterations in post-chemotherapy DLBCL patients and suggest that 18F-FDG PET/CT scanning is a valuable neuroimaging technology for studying chemotherapy-induced brain function changes.

Objectives: Fulminant myocarditis (FM) is a rapidly progressive and frequently fatal form of myocarditis that has been difficult to classify. This study aims to compare the clinical characteristics, treatments and outcomes in patients with fulminant giant cell myocarditis (FGCM) and fulminant lymphocytic myocarditis (FLM).Methods and Results: In our retrospective study, nine patients with FGCM (mean age 47.9 ± 7.5 years, six female) and 7 FLM (mean age 42.1 ± 12.3 years, four female) patients confirmed by histology in the last 11 years were included. Most patients with FGCM and FLM were NYHA functional class IV (56 vs. 100%, p = 0.132). Patients with FGCM had significantly lower levels of high-sensitivity C-reactive protein [hs-CRP, 4.4 (2.0–10.2) mg/L vs. 13.6 (12.6–14.6) mg/L, P = 0.004, data shown as the median with IQR], creatine kinase-myoglobin [CK-MB, 1.4 (1.0–3.2) ng/ml vs. 14.6 (3.0–64.9) ng/ml, P = 0.025, median with IQR], and alanine aminotransferase [ALT, 38.0 (25.0–61.5) IU/L vs. 997.0 (50.0–3,080.0) IU/L, P = 0.030, median with IQR] and greater right ventricular end-diastolic diameter (RVEDD) [2.9 ± 0.3 cm vs. 2.4 ± 0.6 cm, P = 0.034, mean ± SD] than those with FLM. No differences were observed in the use of intra-aortic balloon pump (44 vs. 43%, p = 1.000) and extracorporeal membrane oxygenation (11 vs. 43%, p = 0.262) between the two groups. The long-term survival rate was significantly lower in FGCM group compared with FLM group (0 vs. 71.4%, p = 0.022). A multivariate cox regression analysis showed the level of hs-CRP (hazard ratio = 0.871, 95% confidence interval: 0.761–0.996, P = 0.043) was an independent prognostic factor for FM patients. Furthermore, the level of hs-CRP had a good ability to discriminate between patients with FGCM and FLM (AUC = 0.94, 95% confidence interval: 0.4213–0.9964).Conclusions: The inflammatory response and myocardial damage in the patients with FGCM were milder than those with FLM. Patients with FGCM had distinctly poorer prognoses compared with those with FLM. Our results suggest that hs-CRP could be a promising prognostic biomarker and a hs-CRP level of 11.71 mg/L is an appropriate cutoff point for the differentiating diagnosis between patients with FGCM and FLM.

Objectives: The main aim of this study was to evaluate the differences in metabolic parameters of positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT) measured based on fixed percentage threshold of maximum standard uptake value (SUVmax) and adaptive iterative algorithm (AT-AIA) in patients with cervical cancer. Metabolic parameters in stage III patients subdivided into five groups according to FIGO and T staging (IIIB-T3B, IIIC1-T2B, IIIC1-T3B, IIIC2-T2B, IIIC2-T3B) were compared.Methods: In total, 142 patients with squamous cell cervical cancer subjected to 18F-FDG-PET/CT before treatment were retrospectively reviewed. SUVmax, mean standard uptake value (SUVmean), maximum glucose homogenization (GNmax), mean glucose homogenization (GNmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and glucose homogenization total lesion glycolysis (GNTLG) values measured based on the above two measurement methods of all 142 patients (IIB-IVB) and 102 patients in the above five groups were compared.Results: MTV measured based on fixed percentage threshold of SUVmax was lower than that based on AT-AIA (p < 0.05). MTV40%, MTV0.5, TLG0.5, GNTLG40%, and GNTLG0.5 values were significantly different among the five groups (p < 0.05) while the rest parameters were comparable (p > 0.05). All metabolic parameters of group IIIB-T3B were comparable to those of the other four groups. MTV40%, MTV0.5, GNTLG40%, and GNTLG0.5 in group IIIC1-T2B relative to IIIC1-T3B and those of group IIIC2-T2B relative to group IIIC2-T3B were significantly different. All metabolic parameters of group IIIC1-T2B relative to IIIC2-T2B and those of group IIIC1-T3B relative to group IIIC2-T3B were not significantly different.Conclusion: Metabolic parameters obtained with the two measurement methods showed a number of differences. Selection of appropriate methods for measurement of 18F-FDG-PET/CT metabolic parameters is important to facilitate advances in laboratory research and clinical applications. When stage III patients had the same T stage, their metabolic parameters of local tumor were not significantly different, regardless of the presence or absence of lymph node metastasis, location of metastatic lymph nodes in the pelvic cavity or para-abdominal aorta. These results support the utility of the revised FIGO system for stage III cervical cancer, although our T-staging of stage III disease is incomplete.

Abstract Technologies development for seamless gene editing and marker recycling has allowed frequent genomic engineering in Saccharomyces cerevisiae for desired laboratory strains and cell factory. Alternative new approaches are still required for complicated scenarios. In this study, we report that inducible overexpression of cell wall protein 1 (Cwp1) by galactose addition confers yeast cells a robust growth inhibition. Direct repeats flanking the Gal‐CWP1:selectable marker cassette allow for its homology recombination excision and counter selection upon galactose addition, therefore enable seamless gene editing and marker recycling. We used this strategy and efficiently generated scarless Ade8 deletion mutants. Our results highlight the utility of lethal effect of Cwp1 overexpression a new counter selection strategy and a simple and efficient method for seamless gene editing and marker recycling in S. cerevisiae and potentially other fungi.

In this study, the effect of joint optimization of the principal dimensions and hull form on the hydrodynamic performance of a bulk carrier was studied. In the first part of the joint optimization process, fast principal-dimension optimization of the origin parent ship considering the integrated performance of ship resistance, seakeeping, and maneuverability, as well as their relationships with the principal dimensions were analyzed in detail based on the ship resistance, seakeeping qualities, and maneuverability empirical methods of Holtrop and Mennen, Bales, and K and T indices, respectively. A new parent ship was chosen from 496 sets of hulls after comprehensive consideration. In the remaining part, a further hull form optimization was performed on the new parent ship according to the minimum wave-making resistance. The obtained results demonstrate that: (a) For the case in which the principal dimension of the original parent-type ship is different from that of the owner’s target ship, within the bounds of the relevant constraints from the owner, an excellent parent ship can be obtained by principal-dimension optimization; (b) the joint optimization method considering the principal dimension and hull form optimization can further explore the optimization space and provide a better hull.

BACKGROUND: Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. MATERIALS AND METHODS: FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. RESULTS: Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. CONCLUSION: This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.