Spatiotemporal alterations in the brain oscillations of Arctic explorers.

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

A diagnostic model for Parkinson's disease based on circadian rhythm-related genes.

BACKGROUND: Circadian rhythm (CR) disturbance is intricately associated with Parkinson's disease (PD). However, the involvement of CR-related mechanisms in the pathogenesis and progression of PD remains elusive. METHODS: A total of 141 PD patients and 113 healthy participants completed CR-related clinical examinations in this study. To further investigate the CR-related mechanisms in PD, we obtained datasets (GSE7621, GSE20141, GSE20292) from the Gene Expression Omnibus database to identify differentially expressed genes between PD patients and healthy controls and further selected CR-related genes (CRRGs). Subsequently, the least absolute shrinkage and selection operator (LASSO) followed by logistic algorithms were employed to identify the hub genes and construct a diagnostic model. The predictive performance was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses in the training set and external validation sets. Finally, RT‒qPCR and Western blotting were conducted to verify the expression of these hub genes in blood samples. In addition, Pearson correlation analysis was utilized to validate the association between expression of hub genes and circadian rhythm function. RESULTS: Our clinical observational study revealed that even early-stage PD patients exhibited a higher likelihood of experiencing sleep disturbances, nocturnal hypertension, reverse-dipper blood pressure, and reduced heart rate variability compared to healthy controls. Furthermore, 4 CR-related hub genes (AGTR1, CALR, BRM14, and XPA) were identified and subsequently incorporated as candidate biomarkers to construct a diagnostic model. The model showed satisfactory diagnostic performance in the training set (AUC = 0.941), an external validation set GSE20295 (AUC = 0.842), and our clinical centre set (AUC = 0.805). Additionally, the up-regulation of CALR, BRM14 and the down-regulation of AGTR1, XPA were associated with circadian rhythm disruption. CONCLUSION: CR disturbance seems to occur in the early stage of PD. The diagnostic model based on CR-related genes demonstrated robust diagnostic efficacy, offering novel insights for future clinical diagnosis of PD and providing a foundation for further exploration into the role of CR-related mechanisms in the progression of PD.

Itga5-PTEN signaling regulates striatal synaptic strength and motor coordination in Parkinson's disease.

Background: Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and cognitive dysfunctions. The molecular mechanisms underlying synaptic alterations in PD remain elusive, with a focus on the role of Itga5 in synaptic integrity and motor coordination and TAT-Itga5 was designed to suppress PTEN activity in this investigation. Methods: This study utilized MPTP-induced PD animal models to investigate the expression and role of Itga5 in the striatum. Techniques included quantitative PCR, Western blotting, immunostaining, CRISPR-CasRx-mediated knockdown, electrophysiological assays, behavioral tests, and mass spectrometry. Results: Itga5 expression was significantly reduced in MPTP-induced PD models. In these models, a marked decrease in dendritic spine density and a shift towards thinner spines in striatal GABA neurons were observed, suggesting impaired synaptic integration. Knockdown of Itga5 resulted in reduced dendritic branching, decreased mushroom spines, and increased thin spines, altering synaptic architecture. Electrophysiological analyses revealed changes in action potential and spontaneous excitatory postsynaptic currents, indicating altered synaptic transmission. Motor behavior assessments showed that Itga5 deficiency led to impairments in fine motor control and coordination. Furthermore, Itga5 was found to interact with PTEN, affecting AKT signaling crucial for synaptic development and motor coordination. Conclusion: The study demonstrates that Itga5 plays a critical role in maintaining synaptic integrity and motor coordination in PD. The Itga5-PTEN-AKT pathway represents a potential therapeutic target for addressing synaptic and motor dysfunctions in PD.

Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.

AIM: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap. METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety). RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups. CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

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Precipitation in the plum rain period accounts for 40%-50% of annual precipitation in the monsoon region. To clarify the temporal variability of the isotopic composition of precipitation during the plum rain period from event to interannual time scale and identify the influencing factors, we analyzed the isotopic composition of precipitation and its influencing factors in Nanjing from 2015 to 2022. By using the Hybrid Single-particle Lagran-gian Integrated Trajectory (HYSPLIT) model with specific humidity analysis, we investigated the water vapor source and influencing factors. The results showed that 1) the isotopic abundance of atmospheric precipitation was depleted in the summer and enriched in winter. dx was lower in summer and higher in winter. The isotopic abundance of precipitation from the plum rain was depleted compared to mean value of the whole-year. 2) There was no significant correlation between δ2H and δ18O of the plum rain (precipitation) with local meteorological factors. However, dx was lower in light rain, reflecting the effect of sub-cloud evaporation. The average dx was higher during plum rain period in years with more total plum rain precipitation. 3) The low-latitude South China Sea and the western Pacific Ocean source area provided water vapor for the plum rain. The shift of moisture source region led to abrupt changes in precipitation isotopes. Our results could provide data support for studies on precipitation isotopes in the monsoon region, as well as a reference point for further understanding the precipitation mechanism of the plum rain and stu-dying the seasonal variability of atmospheric circulation in the East Asian monsoon region.

The digestion and dietary carbohydrate pathway contains 100% gene mutations enrichment among 117 patients with major depressive disorder.

Introduction: Major depressive disorder (MDD) is partially inheritable while its mechanism is still uncertain. Methods: This cross-sectional study focused on gene pathways as a whole rather than polymorphisms of single genes. Deep sequencing and gene enrichment analysis based on pathways in Reactome database were obtained to reveal gene mutations. Results: A total of 117 patients with MDD and 78 healthy controls were enrolled. The Digestion and Dietary Carbohydrate pathway (Carbohydrate pathway) was determined to contain 100% mutations in patients with MDD and 0 mutation in matched healthy controls. Discussion: Findings revealed in the current study enable a better understanding of gene pathways mutations status in MDD patients, indicating a possible genetic mechanism of MDD development and a potential diagnostic or therapeutic target.

Maf1 loss regulates spinogenesis and attenuates cognitive impairment in Alzheimer's disease.

Alzheimer's disease is neurodegenerative and characterized by progressive cognitive impairment. Synaptic dysfunction appears in the early stage of Alzheimer's disease and is significantly correlated with cognitive impairment. However, the specific regulatory mechanism remains unclear. Here, we found the transcription factor Maf1 to be upregulated in Alzheimer's disease and determined that conditional knockout of Maf1 in a transgenic mouse model of Alzheimer's disease restored learning and memory function; the downregulation of Maf1 reduced the intraneuronal calcium concentration and restored neuronal synaptic morphology. We also demonstrated that Maf1 regulated the expression of NMDAR1 by binding to the promoter region of Grin1, further regulating calcium homeostasis and synaptic remodelling in neurons. Our results clarify the important role and mechanism of the Maf1-NMDAR1 signalling pathway in stabilizing synaptic structure, neuronal function and behaviour during Alzheimer's disease pathogenesis. This therefore serves as a potential diagnostic and therapeutic target for the early stage of Alzheimer's disease.

Impaired visual-motor functional connectivity in first-episode medication-naïve patients with major depressive disorder.

The perceptual dysfunctions have been fundamental causes of cognitive and emotional problems in patients with major depressive disorder. However, visual system impairment in depression has been underexplored. Here, we explored functional connectivity in a large cohort of first-episode medication-naïve patients with major depressive disorder (n = 190) and compared it with age- and sex-matched healthy controls (n = 190). A recently developed individual-oriented approach was applied to parcellate the cerebral cortex into 92 regions of interest using resting-state functional magnetic resonance imaging data. Significant reductions in functional connectivities were observed between the right lateral occipitotemporal junction within the visual network and 2 regions of interest within the sensorimotor network in patients. The volume of right lateral occipitotemporal junction was also significantly reduced in major depressive disorder patients, indicating that this visual region is anatomically and functionally impaired. Behavioral correlation analysis showed that the reduced functional connectivities were significantly associated with inhibition control in visual-motor processing in patients. Taken together, our data suggest that functional connectivity between visual network and sensorimotor network already shows a significant reduction in the first episode of major depressive disorder, which may interfere with the inhibition control in visual-motor processing. The lateral occipitotemporal junction may be a hub of disconnection and may play a role in the pathophysiology of major depressive disorder.

Genetic variations in the retrograde endocannabinoid signaling pathway in Chinese patients with major depressive disorder.

Background: The retrograde endocannabinoid (eCB) pathway is closely associated with the etiology of major depressive disorder (MDD) at both pathophysiological and genetic levels. This study aimed to investigate the potential role of genetic mutations in the eCB pathway and underlying mechanisms in Han Chinese patients with MDD. Methods: A total of 96 drug-naïve patients with first-episode MDD and 62 healthy controls (HCs) were recruited. Whole-exome sequencing was performed to identify the gene mutation profiles in patients with MDD. Results were filtered to focus on low-frequency variants and rare mutations (minor allele frequencies <0.05) related to depressive phenotypes. Enrichment analyses were performed for 146 selected genes to examine the pathways in which the most significant enrichment occurred. A protein-protein interaction (PPI) network analysis was performed to explore the biological functions of the eCB pathway. Finally, based on current literature, a preliminary analysis was conducted to explore the effect of genetic mutations on the function of this pathway. Results: Our analysis identified 146 (15.02%) depression-related genetic mutations in patients with MDD when compared with HCs, and 37 of the mutations were enriched in the retrograde eCB signaling pathway. Seven hub genes in the eCB pathway were closely related to mitochondrial function, including Complex I genes (NDUFS4, NDUFV2, NDUFA2, NDUFA12, NDUFB11) and genes associated with protein (PARK7) and enzyme (DLD) function in the regulation of mitochondrial oxidative stress. Conclusion: These results indicate that genetic mutations in the retrograde eCB pathway represent potential etiological factors associated with the pathogenesis of MDD.

Individualized Functional Connectome Identified Replicable Biomarkers for Dysphoric Symptoms in First-Episode Medication-Naïve Patients With Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is a heterogeneous syndrome and can be conceptualized as a mixture of dimensional abnormalities across several specific brain circuits. The neural underpinnings of different symptom dimensions in MDD are not well understood. We aimed to identify robust, generalizable, functional connectivity (FC)-based biomarkers for different symptom dimensions in MDD using individualized functional connectomes. METHODS: Patterns of FC associated with symptom severity were identified using a novel, individualized, functional network parcellation analysis in conjunction with hierarchical clustering. Dimension-specific prediction models were trained to estimate symptom severity in first-episode medication-naïve patients (discovery dataset, n = 95) and replicated in an independent validation dataset (n = 94). The correlation between FC changes and symptom changes was further explored in a treatment dataset (n = 55). RESULTS: Two distinct symptom clusters previously identified in patients with MDD, namely dysphoric and anxiosomatic clusters, were robustly replicated in our data. A connectivity biomarker associated with dysphoric symptoms was identified, which mainly involved the default, dorsal attention, and limbic networks. Critically, this brain-symptom association was confirmed in the validation dataset. Moreover, the marker also tracked dysphoric symptom improvement following a 2-week antidepressant treatment. For comparison, we repeated our analyses using a nonindividualized approach and failed to identify replicable brain-symptom biomarkers. Further quantitative analysis indicated that the generalizability of the connectivity-symptom association was hampered when functional regions were not localized in individuals. CONCLUSIONS: This work reveals robust, replicable FC biomarkers for dysphoric symptoms in MDD, demonstrates the advantage of individual-oriented approach, and emphasizes the importance of independent validation in psychiatric neuroimaging analysis.

Discovery of mobocertinib, a potent, oral inhibitor of EGFR exon 20 insertion mutations in non-small cell lung cancer.

In the treatment of non-small cell lung cancer (NSCLC), patients harboring exon 20 insertion mutations in the epidermal growth factor receptor (EGFR) gene (EGFR) have few effective therapies because this subset of mutants is generally resistant to most currently approved EGFR inhibitors. This report describes the structure-guided design of a novel series of potent, irreversible inhibitors of EGFR exon 20 insertion mutations, including the V769_D770insASV and D770_N771insSVD mutants. Extensive structure-activity relationship (SAR) studies led to the discovery of mobocertinib (compound 21c), which inhibited growth of Ba/F3 cells expressing the ASV insertion with a half-maximal inhibitory concentration of 11 nM and with selectivity over wild-type EGFR. Daily oral administration of mobocertinib induced tumor regression in a Ba/F3 ASV xenograft mouse model at well-tolerated doses. Mobocertinib was approved in September 2021 for the treatment of adult patients with advanced NSCLC with EGFR exon 20 insertion mutations with progression on or after platinum-based chemotherapy.

Individualized functional connectome identified generalizable biomarkers for psychiatric symptoms in transdiagnostic patients.

Substantial clinical heterogeneity and comorbidity inherent amongst mental disorders limit the identification of neuroimaging biomarkers that can reliably track clinical symptoms. Strategies that enable generation of meaningful and replicable neurobiological markers at the individual level will push the field of neuropsychiatry forward in developing efficacious personalized treatment. The current study included 142 adult patients with a primary diagnosis of schizophrenia (SCZ), bipolar (BP), or attention deficit/hyperactivity disorder (ADHD), and 67 patient ratings across four behavioral measures. Using functional connectivity derived from a personalized fMRI approach, we identified several candidate imaging markers related to dimensional phenotypes across disorders, assessed the internal and external generalizability of these markers, and compared the probability of replicating findings across datasets using individual and group-averaged defined functional regions. We identified subject-specific connections related to three different clinical domains (attention deficit, appetite-energy, psychosis-positive) in a discovery dataset. Importantly, these connectivity biomarkers were robust and were reproduced in an independent validation dataset. For markers related to neurovegetative symptoms (attention deficit, appetite-energy symptoms), the brain connections involved showed similar connectivity patterns across the different diagnoses. However, psychosis-positive symptoms were associated with connections of varying strength across disorders. Finally, we found that markers for symptom domains were replicable for individually-specified connections, but not for group template-derived connections. Our personalized strategies allowed us to identify meaningful and generalizable imaging markers for symptom domains in patients who exhibit high levels of heterogeneity. These biomarkers may shed new light on the connectivity underpinnings of psychiatric symptoms and lead to personalized interventions.

Memory and processing speed impairments in first-episode drug-naïve patients with major depressive disorder.

BACKGROUND: Cognitive impairment, an intrinsic feature of major depressive disorder (MDD), affects daily and social functioning in depression patients. However, the cognitive impairment profile in MDD remains ambiguous because of the high heterogeneity of previous studies. METHODS: Four cognitive domains, including memory, processing speed, executive function (EF), and attention, were assessed in 184 first-episode drug-naïve (FEDN) MDD patients and matched 71 healthy controls (HCs). The effects of demographic and depressive factors on cognitive performance were analyzed using various statistical methods, including multi-factor analysis of variance, Mann-Whitney U test, and Spearman's rank correlation. In addition, the impact of depression severity on cognitive function was further assessed using subgroup analyses and partial correlation analyses. RESULTS: Age and education significantly impacted most cognitive performances, and depression severity appeared to influence processing speed. Moreover, cognitive scores in memory and processing speed, rather than in EF and attention, were significantly different between FEDN MDD patients and HCs after controlling for sex, age, educational attainment, household income, and body mass index. LIMITATIONS: The number of HCs was relatively small, which may have slightly reduced the study's statistical power. CONCLUSIONS: Age and educational attainment have confirmative confounding effects greater than those of depression in most cognitive functions. More importantly, memory and processing speed were impaired in MDD after strictly controlling for confounders. These findings provide new information for understanding the pattern of cognitive impairment and offer clues for further exploring the pathogenesis of cognitive abnormalities in MDD.

SIAH2 regulates colorectal cancer tumorigenesis via PI3K/ATK signaling pathway.

Colorectal cancer (CRC) is the third most common cancer and the 4th leading cause of cancer-related deaths, although with a dismal prognosis. The SIAH E3 Ubiquitin Protein Ligase 2 (SIAH2) regulates the expression of multiple proteins via ubiquitination and proteasome. However, the biological role of SIAH2 in colorectal cancer tumorigenesis remains controversial. In this work, we found that SIAH2 is an oncogene in colorectal cancer. Moreover, SIAH2 promoted colorectal cancer cell proliferation, migration, invasion, and colony formation. Mechanistically, SIAH2 promoted the PI3K/AKT signaling pathway both in vivo and in vitro. Besides, we discovered that PTEN loss regulates SIAH2-mediated PI3K/AKT signaling pathway activation. In summary, these findings highlight the role of SIAH2 in colorectal cancer progression and provide novel insights for treatment.

Adult-Onset Neuronal Ceroid Lipofuscinosis With a Novel DNAJC5 Mutation Exhibits Aberrant Protein Palmitoylation.

Neuronal ceroid lipofuscinosis (NCL) is composed of a group of inherited neurodegenerative diseases, with the hallmark of lipofuscin deposit (a mixture of lipids and proteins with metal materials) inside the lysosomal lumen, which typically emits auto-fluorescence. Adult-onset NCL (ANCL) has been reported to be associated with a mutation in the DNAJC5 gene, including L115R, L116Δ, and the recently identified C124_C133dup mutation. In this study, we reported a novel C128Y mutation in a young Chinese female with ANCL, and this novel mutation caused abnormal palmitoylation and triggered lipofuscin deposits.

The China Alzheimer Report 2022.

China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) and related dementias (ADRD). AD's incidence rate, morbidity, and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals, families and society. The 'Healthy China Action' plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD. This report describes related epidemiological trends, evaluates the economic burden of the disease, outlines current clinical diagnosis and treatment status and delineates existing available public health resources. More specifically, it examines the public health impact of ADRD, including prevalence, mortality, costs, usage of care, and the overall effect on caregivers and society. In addition, this special report presents technical guidance and supports for the prevention and treatment of AD, provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.

Quantifying the contribution of evaporation from Lake Taihu to precipitation with an isotope-based method.

Moisture recycling plays a crucial role in regional hydrological budgets. The isotopic composition of precipitation has long been considered as a good tracer to investigate moisture recycling. This study quantifies the moisture recycling fractions (fr) in the Lake Taihu region using spatial variations of deuterium excess in precipitation (dP) and surface water vapour flux (dE). Results show that dP at a site downwind of the lake was higher than that at an upwind site, indicating the influence of lake moisture recycling. Spatial variations in dP after sub-cloud evaporation corrections were 2.3, 1.4 and 3.2 ‰, and dE values were 27.4, 32.3 and 31.4 ‰ for the first winter monsoon, the summer monsoon and the second winter monsoon, respectively. Moisture recycling fractions were 0.48 ± 0.13, 0.07 ± 0.03 and 0.38 ± 0.05 for the three monsoon periods, respectively. Both using the lake parameterization kinetic fractionation factors or neglecting sub-cloud evaporation would decrease fr, and the former has a larger influence on the fr calculation. The larger fr in the winter monsoon periods was mainly caused by lower specific humidity of airmasses but comparable moisture uptake along their trajectories compared to the summer monsoon period.

Sex-specific alterations of cortical morphometry in treatment-naïve patients with major depressive disorder.

Major depressive disorder (MDD) shows sex differences in terms of incidence and symptoms, but the neurobiological basis underlying these sex differences remains to be clarified. High resolution T1-weighted Magnetic Resonance Imaging (MRI) scans were obtained from 123 non-comorbid treatment-naïve individuals with MDD and 81 age-, sex-, and handedness-matched healthy controls (HCs). MRI data were preprocessed with FreeSurfer software and four cortical measures were extracted: cortical thickness (CT), surface area (SA), cortical volume (CV), and local gyrification index (LGI). We tested for both sex-specific and sex-nonspecific patterns of cortical anatomic alterations. Regardless of sex, individuals with MDD showed significantly higher LGI in posterior cortex relative to HCs. Significant sex-by-group interactions were observed, and subsequent post-hoc analyses revealed that female individuals with MDD showed significantly lower SA in left ventrolateral prefrontal cortex (vlPFC), lower CV in right rostromedial prefrontal cortex (rmPFC), and higher LGI in left visual cortex compared with sex-matched HCs, whereas the opposite patterns of significant effects were seen in male individuals with MDD relative to their sex-matched HCs. Thus, sex-nonspecific and specific morphometric differences from HCs were found in posterior cortex, while in PFC alterations were highly sex-specific early in the illness course. This may involve sex-specific alterations in brain development or processes related to illness onset. These findings highlight the presence and regional distribution of generalized as well as sex-specific alterations of brain neurobiology in MDD.

Nitrous oxide flux observed with tall-tower eddy covariance over a heterogeneous rice cultivation landscape.

Although croplands are known to be strong sources of anthropogenic N2O, large uncertainties still exist regarding their emission factors, that is, the proportion of N in fertilizer application that escapes to the atmosphere as N2O. In this study, we report the results of an experiment on the N2O flux in a landscape dominated by rice cultivation in the Yangtze River Delta, China. The observation was made with a closed-path eddy covariance system on a 70-m tall tower from October 2018 to December 2020 (27 months). Temperature and precipitation explained 78% of the seasonal and interannual variability in the observed N2O flux. The growing season (May to October) mean flux (1.14 nmol m-2 s-1) was much higher than the median flux found in the literature for rice paddies. The mean N2O flux during the observational period was 0.90 ± 0.71 nmol m-2 s-1, and the annual cumulative N2O emission was 7.6 and 9.1 kg N2O-N ha-1 during 2019 and 2020, respectively. The corresponding landscape emission factor was 3.8% and 4.6%, respectively, which were much higher than the IPCC default direct (0.3%) and indirect emission factors (0.75%) for rice paddies.

Clinical manifestations and imaging and pathological features of giant cell angioblastoma: Report of four cases and literature review.

Giant cell angioblastoma is a relatively rare vasogenic tumour. To date, studies on its clinical manifestations, imaging characteristics, pathological features, and prognosis are extremely limited and unknown, with only a few cases recorded. In this study, four cases of giant cell angioblastoma confirmed by pathological examination were reported to improve our understanding and deep exploration of the tumour spectrum. All cases in our study were male, including two adults and two boys. The lesions were located in the lower segment of the femur, medial condyle of the femur, knee joint, and popliteal fossa. Regarding the imaging characteristics, two patients with lesions in bone showed bone destruction, while the other two had lesions that invaded soft tissues, showing irregular, abnormal signal shadows and obvious enhancement. Histopathological analysis revealed that the nodular tumour tissue was mainly composed of oval and spindle cells, with varying numbers of osteoclast-like multinucleated giant cells, and the interstitial tissues were often filled with blood vessels of different sizes. The immunophenotype demonstrates that endothelial cells of small vessels in nodules expressed CD31, SMA, and ERG, while osteoclast-like multinucleated giant cells and histiocytes expressed CD68 and CD163, and the surrounding cells expressed SMA. All four patients were treated with surgical resection. One of them relapsed 1 month after surgery and received a second surgical resection. No distant metastasis or death occurred during the follow-up period. This study indicates that giant cell angioblastoma is a local invasive vascular tumour that can develop both in children and adults with skin, mucous membrane, soft tissue, and bone involvement. Imaging characteristics show bone destruction and irregular, abnormal signal shadows; in addition, obvious pathological morphological features can be observed. Currently, the treatment is mainly surgical resection, and interferons may be used as adjuvant chemotherapy.