A global meta-analysis of yield-scaled N2 O emissions and its mitigation efforts for maize, wheat, and rice.

Maintaining or even increasing crop yields while reducing nitrous oxide (N2 O) emissions is necessary to reconcile food security and climate change, while the metric of yield-scaled N2 O emission (i.e., N2 O emissions per unit of crop yield) is at present poorly understood. Here we conducted a global meta-analysis with more than 6000 observations to explore the variation patterns and controlling factors of yield-scaled N2 O emissions for maize, wheat and rice and associated potential mitigation options. Our results showed that the average yield-scaled N2 O emissions across all available data followed the order wheat (322 g N Mg-1 , with the 95% confidence interval [CI]: 301-346) > maize (211 g N Mg-1 , CI: 198-225) > rice (153 g N Mg-1 , CI: 144-163). Yield-scaled N2 O emissions for individual crops were generally higher in tropical or subtropical zones than in temperate zones, and also showed a trend towards lower intensities from low to high latitudes. This global variation was better explained by climatic and edaphic factors than by N fertilizer management, while their combined effect predicted more than 70% of the variance. Furthermore, our analysis showed a significant decrease in yield-scaled N2 O emissions with increasing N use efficiency or in N2 O emissions for production systems with cereal yields >10 Mg ha-1 (maize), 6.6 Mg ha-1 (wheat) or 6.8 Mg ha-1 (rice), respectively. This highlights that N use efficiency indicators can be used as valuable proxies for reconciling trade-offs between crop production and N2 O mitigation. For all three major staple crops, reducing N fertilization by up to 30%, optimizing the timing and placement of fertilizer application or using enhanced-efficiency N fertilizers significantly reduced yield-scaled N2 O emissions at similar or even higher cereal yields. Our data-driven assessment provides some key guidance for developing effective and targeted mitigation and adaptation strategies for the sustainable intensification of cereal production.

Identification of epileptic networks with graph convolutional network incorporating oscillatory activities and evoked synaptic responses.

Stereoelectroencephalography (SEEG) offers unique neural data from in-depth brain structures with fine temporal resolutions to better investigate the origin of epileptic brain activities. Although oscillatory patterns from different frequency bands and functional connectivity computed from the SEEG datasets are employed to study the epileptic zones, direct electrical stimulation-evoked electrophysiological recordings of synaptic responses, namely cortical-cortical evoked potentials (CCEPs), from the same SEEG electrodes are not explored for the localization of epileptic zones. Here we proposed a two-stream model with unsupervised learning and graph convolutional network tailored to the SEEG and CCEP datasets in individual patients to perform localization of epileptic zones. We compared our localization results with the clinically marked electrode sites determined for surgical resections. Our model had good classification capability when compared to other state-of-the-art methods. Furthermore, based on our prediction results we performed group-level brain-area mapping analysis for temporal, frontal and parietal epilepsy patients and found that epileptic and non-epileptic brain networks were distinct in patients with different types of focal epilepsy. Our unsupervised data-driven model provides personalized localization analysis for the epileptic zones. The epileptic and non-epileptic brain areas disclosed by the prediction model provide novel insights into the network-level pathological characteristics of epilepsy.

Urbanization can accelerate climate change by increasing soil N2 O emission while reducing CH4 uptake.

Urban land-use change has the potential to affect local to global biogeochemical carbon (C) and nitrogen (N) cycles and associated greenhouse gas (GHG) fluxes. We conducted a meta-analysis to (1) assess the effects of urbanization-induced land-use conversion on soil nitrous oxide (N2 O) and methane (CH4 ) fluxes, (2) quantify direct N2 O emission factors (EFd ) of fertilized urban soils used, for example, as lawns or forests, and (3) identify the key drivers leading to flux changes associated with urbanization. On average, urbanization increases soil N2 O emissions by 153%, to 3.0 kg N ha-1  year-1 , while rates of soil CH4 uptake are reduced by 50%, to 2.0 kg C ha-1  year-1 . The global mean annual N2 O EFd of fertilized lawns and urban forests is 1.4%, suggesting that urban soils can be regional hotspots of N2 O emissions. On a global basis, conversion of land to urban greenspaces has increased soil N2 O emission by 0.46 Tg N2 O-N year-1 and decreased soil CH4 uptake by 0.58 Tg CH4 -C year-1 . Urbanization driven changes in soil N2 O emission and CH4 uptake are associated with changes in soil properties (bulk density, pH, total N content, and C/N ratio), increased temperature, and management practices, especially fertilizer use. Overall, our meta-analysis shows that urbanization increases soil N2 O emissions and reduces the role of soils as a sink for atmospheric CH4 . These effects can be mitigated by avoiding soil compaction, reducing fertilization of lawns, and by restoring native ecosystems in urban landscapes.

Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Risk stratification and molecular heterogeneity of endometrial cancer and expression profile of TIM-3: A retrospective cohort study.

OBJECTIVE: The present study aimed to implement ProMisE classification and risk grouping on a retrospective cohort of 628 patients with endometrial cancer (EC) and determine the molecular heterogeneity across subtypes and subgroups, as well as to investigate the potential beneficiary for TIM-3 checkpoint inhibition in ECs. METHODS: Protein expressions of p53, MMR, TIM-3 and CD8 were measured by immunohistochemistry, and massively parallel sequencing was conducted for 128 cancer-related genes. Patients were categorized into four ProMisE subtypes: MMR-deficient (MMRd), POLE-ultramutated (POLEmut), p53-wild type (p53wt), and p53-abnormal (p53abn), and were subjected to risk classification. RESULTS: 43 (6.9%) patients belonged to POLEmut, 118 (18.8%) to MMRd, 69 (11%) to p53abn, and 398 (63.3%) to p53wt. Compared to the 2016 stratification system, the 2021 ESGO/ESTRO/ESP risk stratification integrated with molecular classification revealed that 11 patients (11/628, 1.8%) were upgraded due to the p53abn signature, whereas 23 patients (23/628, 3.7%) were downgraded due to the POLEmut signature. JAK1 and RAD50 mutations showed higher frequencies in patients with aggressive phenotypes. RAD51B mutation was significantly related to poor RFS of the p53wt subtype but not of the other three molecular subgroups. TIM-3 expression was detected in 30.9% immune cells (ICs) and 29.0% tumor cells (TCs) in ECs, respectively. It was frequently expressed in POLEmut and MMRd ECs as compared to that in the other two molecular subtypes in TCs and ICs. CONCLUSIONS: Our study revealed the molecular heterogeneity across subtypes and subgroups. The new risk stratification system changed the risk grouping of some patients due to the integration of molecular features. RAD51B mutation can further stratify the recurrence risk in the p53wt subtype. Patients with MMRd or POLEmut may benefit most from immunotherapy against TIM-3.

Pretreatment dual-energy CT for predicting early response to induction chemotherapy and survival in nasopharyngeal carcinoma.

OBJECTIVES: To evaluate the predictive performance of pretreatment dual-energy CT (DECT) for early response to induction chemotherapy and survival in nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 56 NPC patients who underwent pretreatment DECT scans with posttreatment follow-up were enrolled. The DECT-derived normalised iodine concentration (nIC), effective atomic number (Zeff), 40-180 keV (20 keV interval), and Mix-0.3 value of the tumour lesions were measured to predict the early response to induction chemotherapy and survival in nasopharyngeal carcinoma. The Mann‒Whitney U test, ROC analysis, Kaplan‒Meier method with log-rank test, and Cox proportional hazards model were performed to evaluate the predictive performance of DECT parameters, respectively. RESULTS: Among all DECT-derived parameters, ROC analysis showed the predictive performances of nIC and Zeff values for early objective response to induction chemotherapy (AUCs of 0.803 and 0.826), locoregional failure-free survival (AUCs of 0.786 and 0.767), progression-free survival (AUCs of 0.856 and 0.731) and overall survival (AUCs of 0.765 and 0.799) in NPC patients, respectively (all p < 0.05). Moreover, multivariate analysis showed that a high nIC value was an independent predictor of poor survival in NPC. In addition, survival analysis indicated that NPC patients with higher nIC values in primary tumours tend to have lower 5-year locoregional failure-free survival, progression-free survival and overall survival rates than those with lower nIC values. CONCLUSIONS: DECT-derived nIC and Zeff values can predict early response to induction chemotherapy and survival in NPC; in particular, a high nIC value is an independent predictive factor of poor survival in NPC. CLINICAL RELEVANCE STATEMENT: Preoperative dual-energy computed tomography may provide predictive value for early response and survival outcomes in patients with nasopharyngeal carcinoma, and facilitate their clinical management. KEY POINTS: • Pretreatment dual-energy computed tomography helps to predict early response to therapy and survival in NPC. • NIC and Zeff values derived from dual-energy computed tomography can predict early objective response to induction chemotherapy and survival in NPC. • A high nIC value is an independent predictive factor of poor survival in NPC.

Novel Causal Relations between Neuronal Networks due to Synchronization.

In the process of information transmission, information is thought to be transmitted from the networks that are activated by the input to the networks that are silent or nonactivated. Here, via numerical simulation of a 3-network motif, we show that the silent neuronal network when interconnected with other 2 networks can exert much stronger causal influences on the other networks. Such an unexpected causal relationship results from high degree of synchronization in this network. The predominant party is consistently the network whose noise is smaller when the noise level in each network is considered. Our results can shed lights on how the internal network dynamics can affect the information flow of interconnected neuronal networks.

The alterations of brain network degree centrality in patients with neovascular glaucoma: a resting-state fMRI study.

PURPOSE: To explore the alterations of whole brain functional network using the degree centrality (DC) analysis in neovascular glaucoma (NVG) and the correlation between DC values and NVG clinical indices. MATERIALS AND METHODS: Twenty NVG patients and twenty normal controls (NC), closely matched in age, sex, and education, were recruited for this study. All subjects underwent comprehensive ophthalmologic examinations and a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The differences in DC values of brain network between NVG and NC groups were analyzed, and correlation analysis was performed to explore the relationships between DC values and clinical ophthalmological indices in NVG group. RESULTS: Compared with NC group, significantly decreased DC values were found in the left superior occipital gyrus and left postcentral gyrus, while significantly increased DC values in the right anterior cingulate gyrus and left medial frontal gyrus in NVG group. (All P < 0.05, FDR corrected). In the NVG group, the DC value in left superior occipital gyrus showed significantly positive correlations with retinal nerve fiber layer (RNFL) thickness (R = 0.484, P = 0.031) and mean deviation of visual field (MDVF) (R = 0.678, P = 0.001). Meanwhile, the DC value in the left medial frontal gyrus demonstrated significantly negative correlations with RNFL (R = - 0.544, P = 0.013) and MDVF (R = - 0.481, P = 0.032). CONCLUSIONS: NVG exhibited decreased network degree centrality in visual and sensorimotor brain regions and increased degree centrality in cognitive-emotional processing brain region. Additionally, the DC alterations might be complementary imaging biomarkers to assess disease severity.

Barriers and facilitators of adherence to awake prone positioning: a qualitative study using the COM-B model.

BACKGROUND: Awake prone positioning (APP) is a recommended therapy for non-intubated ARDS patients, but adherence can be challenging. Understanding the barriers and facilitators of adherence to APP is essential to increase the adherence of therapy and improve patient outcomes. The objective of this study was to explore the barriers and facilitators of adherence to awake prone ventilation using a qualitative approach and the Capability, Opportunity, Motivation-Behavior (COM-B) model. METHODS: Semi-structured, in-depth interviews were conducted with patients involved in awake prone ventilation. Data were analyzed using an adapted inductive thematical approach and mapped onto the COM-B model to identify barriers and facilitators to adherence of APP. RESULTS: Nineteen patients were interviewed (aged 55-92 years). Fifteen themes were identified and mapped directly on to the six COM-B constructs, with "physical challenges" related to physical capability being the primary barrier. These COM-B sub-items reflected five other barriers, including low self-efficacy(M), treatment environment(O), availability of time(O), misconceptions about the treatment(C), and insufficient knowledge(C). Key facilitators in adhering to APP were ability to identify and overcome obstacles(C), availability and affordability of treatment(O), family influences(O), beliefs and trust in treatment(M), fear about the disease(M), and perceived benefits(M). In addition, three factors played the role of both facilitator and barrier, such as media influences(O), healthcare influences(O), and behavioral habits(M). CONCLUSION: The COM-B model was proved to be a useful framework for identifying the barriers and facilitators of adherence to awake prone ventilation. The findings suggest that adherence behavior is a dynamic and balanced process and interventions aimed at improving adherence to APP should address the barriers related to capability, opportunity, and motivation. Healthcare providers should focus on providing proper guidance and training, creating a comfortable environment, and offering social support to improve patients' capability and opportunity. Additionally, promoting patients' positive beliefs and attitudes towards the treatment and addressing misconceptions and fears can further enhance patients' motivation to adhere to the treatment plan.

Distinct histological and clinical features associated with pure uterine serous carcinoma: A single institution experience.

AIM: To ascertain the clinicopathological features, survival, and prognostic factors of pure uterine serous carcinoma (pUSC) and compare its clinicopathological characteristics with those of serous-like grade-3 endometrioid endometrial carcinoma (G3-EEC). METHOD: Consecutive patients with pUSC and p53 abnormal (p53abn) G3-EEC were retrospectively selected between 2014 and 2022. Histological and immunohistochemical features were reviewed, clinical information was collected, and survival analyses were performed. RESULTS: Eighty-five pUSC patients (mean age: 61.6 years) were included. Histologically, pUSC showed a predominantly glandular growth pattern (80.0 %) with high-grade nuclear atypia and obvious nucleoli and 53 cases showed admixtures of architectural patterns. The p53 aberrant expression rate was 98.8 %. 41.5 %, 53.7 %, and 67.5 % of cases were classified as negative for ER, PR, and WT1, respectively. Six (12.3 %) of 49 cases had a HER2 score of 3+ by immunohistochemistry (IHC). The overall survival and progression-free survival rates were 72.9 % and 63.5 %, respectively. Advanced stage, no adjuvant therapy, and lymph node metastasis were independent risk factors for poor survival in pUSC. Twenty-five p53abn G3-EEC patients were assessed. Women with p53abn G3-EEC were on average, younger than those with pUSC (53.4 vs. 61.6 years, P < 0.001). Papillary structures were observed more commonly in pUSC (16 % vs. 36.5 %, P = 0.042). Positive PR expression was significantly associated with p53abn G3-EEC (P = 0.009). Survival did not differ significantly between the subgroups in univariate and multivariate analyses. CONCLUSION: In this contemporary series, we affirm the suboptimal prognosis associated with pUSC, and that the survival associated with pUSC and p53abn G3-EEC are not significantly different. pUSC and p53abn G3-EEC have distinct morphological and immunohistochemical characteristics.

Characteristics of annual NH3 emissions from a conventional vegetable field under various nitrogen management strategies.

High N-fertilizer applications to conventional vegetable production systems are associated with substantial emissions of NH3, a key substance that triggers haze pollution and ecosystem eutrophication and thus, causing considerable damage to human and ecosystem health. While N fertilization effects on NH3 volatilization from cereal crops have been relatively well studied, little is known about the magnitude and yield-scaled emissions of NH3 from vegetable systems. Here we report on a 2-year field study investigating the effect of various types and rates of fertilizer application on NH3 emissions and crop yields for a pepper-lettuce-cabbage rotation system in southwest China. Our results show that both NH3 emissions and direct emission factors of applied N varied largely across seasons over the 2-year period, highlighting the importance of measurements spanning entire cropping years. Across all treatments varying from solely applying urea fertilizers to only using organic manures, annual NH3 emissions ranged from 0.64 to 92.4 kg N ha-1 yr-1 (or 0.07-6.84 g N kg-1 dry matter), equivalent to 0.05-5.99% of the applied N. At annual scale, NH3 emissions correlated positively with soil δ15N values, indicating that soil δ15N may be used as an indicator for NH3 losses. NH3 emissions from treatments fertilized partially or fully with manure were significantly lower compared with the urea fertilized treatment, while vegetable yields remained unaffected. Moreover, full substitution of urea by manure as compared to the partial substitution further reduced the yield-scaled annual NH3 emissions by 79.0-92.4%. Across all vegetable seasons, there is a significant negative relationship between yield-scaled NH3 emissions and crop N use efficiency. Overall, our results suggest that substituting urea by manure and reducing total N inputs by 30-50% allows to reduce NH3 emissions without jeopardizing yields. Such a change in management provides a feasible option to achieve environmental sustainability and food security in conventional vegetable systems.

Metabolic alterations in the visual pathway of retinitis pigmentosa rats: A longitudinal multimodal magnetic resonance imaging study with histopathological validation.

Because retinitis pigmentosa (RP) has been shown to cause degenerative changes in the entire visual pathway, there is an urgent need to perform longitudinal assessments of RP-induced degeneration and identify imaging protocols to detect this degeneration as early as possible. In this study, we assessed a transgenic rat model of RP by using complementary noninvasive magnetic resonance imaging techniques, namely, proton magnetic resonance spectroscopy (1 H-MRS), to investigate the metabolic changes in RP. Our study demonstrated decreased concentrations and ratios to creatine (Cr) of N-acetylaspartate (NAA), glutamate (Glu), γ-aminobutyric acid (GABA), and taurine (Tau), whereas myo-inositol (Ins) and choline (Cho) were increased in the visual cortex of Royal College of Surgeons (RCS) rats compared with control rats (p < 0.05). Furthermore, with the progression of RP, the concentrations of NAA, Glu, GABA, and Tau, and the ratios of GABA/Cr and Tau/Cr significantly decreased over time, whereas the concentrations of Ins and Cho and the ratio of Ins/Cr significantly increased over time (p < 0.05). In addition, in RCS rats, NAA/Cr decreased significantly from 3 to 4 months postnatal (p < 0.001), and Cho/Cr increased significantly from 4 to 5 months postnatal (p = 0.005). Meanwhile, the 1 H-MRS indicators in 5-month postnatal RCS rats could be confirmed by immunohistochemical staining. In conclusion, with the progression of RP, the metabolic alterations in the visual cortex indicated progressive reprogramming with the decrease of neurons and axons, accompanied by the proliferation of gliocytes.

Effect of aggressive versus conservative hydration for early phase of acute pancreatitis in adult patients: A meta-analysis of 3,127 cases.

BACKGROUND: The advantages of aggressive hydration compared to conservative hydration within 24 h for acute pancreatitis (AP) remain controversial in adult patients. A meta-analysis was undertaken to investigate whether aggressive strategies are more beneficial. METHODS: We searched (on February 1, 2021) PubMed, Embase, and the Cochrane Library for eligible trials that assessed the two therapies and performed a meta-analysis. The primary endpoint was in-hospital mortality. Secondary outcomes were adverse events (e.g., renal failure and pancreatic necrosis) within 24 h of treatment. RESULTS: Five randomized controlled trials and 8 observational trials involving 3127 patients were identified. Patients with severe pancreatitis showed significant difference of in-hospital mortality (OR 1.75; 95% CI 1.32-2.33) in aggressive hydration group, which were less susceptible to study type and age. Patients with severe pancreatitis were likely to develop respiratory failure (OR 5.08; 95% CI 2.31-11.15), persistent SIRS (OR 2.83; 95% CI 1.58-5.04), renal failure (OR 2.58; 95% CI 1.90-3.50) with significant difference. A longer hospital stay was observed in patients with severe pancreatitis (WMD 7.61; 95% CI 5.51-9.71; P < 0.05) in the aggressive hydration group. Higher incidence of pancreatic necrosis (OR 2.34; 95% CI 1.60-3.42; P < 0.05) was major susceptible to observational studies, old patients and mild pancreatitis. CONCLUSIONS: Compared to conservative hydration, aggressive hydration increases in-hospital mortality and the incidence of renal failure, pancreatic necrosis with relatively strong evidence. Further investigation should be designed with a definitive follow-up period and therapeutic goals to address reverse causation bias.

Recent Advances on Spinel Zinc Manganate Cathode Materials for Zinc-Ion Batteries.

Zinc metal is abundant in nature, non-toxic, harmless, and cheap. Zinc-ion batteries (ZIBs) have also emerged as the times require, which has attracted scholars' research interest. In the zinc-ion batteries, the cathode material is indispensable. Manganese oxides are widely used in electrode materials because of their various valence states (+2, +3, +4, +7). ZnMn2 O4 (ZMO) is a mixed metal oxide with a spinel structure similar to LiMn2 O4 . Due to the synergistic effect of Zn and Mn, it has the advantages of high theoretical capacity. In recent years, researchers have gradually applied ZnMn2 O4 to zinc ion batteries. In order to obtain high-energy-density zinc ion batteries, it is also very important to match electrolytes with a wide operating voltage window and develop a highly reversible anode. In the first instance, we investigate the research progress of spinel ZnMn2 O4 as a reliable candidate material for zinc ion batteries. Later on, we review the optimization and modification measures of anode and electrolyte to improve the electrochemical properties of spinel ZnMn2 O4 . On this basis, we propose the reasonable research direction and development prospects for this material. It is hoped that there will be a help to researchers in this field.

Dual-energy CT in differentiating benign sinonasal lesions from malignant ones: comparison with simulated single-energy CT, conventional MRI, and DWI.

OBJECTIVES: To explore the value of dual-energy CT (DECT) for differentiating benign sinonasal lesions from malignant ones, and to compare this finding with simulated single-energy CT (SECT), conventional MRI (cMRI), and diffusion-weighted imaging (DWI). METHODS: Patients with sinonasal lesions (38 benign and 34 malignant) who were confirmed by histopathology underwent DECT, cMRI, and DWI. DECT-derived parameters (iodine concentration (IC), effective atomic number (Eff-Z), 40-180 keV (20-keV interval), virtual non-enhancement (VNC), slope (k), and linear-mixed 0.3 (Mix-0.3)), DECT morphological features, cMRI characteristics, and ADC value of benign and malignant tumors were compared using t test or chi-square test. Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance, and the area under the ROC curve (AUC) was compared using the Z test to select the optimal diagnostic approach. RESULTS: Significantly higher DECT-derived single parameters (IC, Eff-Z, 40 keV, 60 keV, 80 keV, slope (k), Mix-0.3) were found in malignant lesions than those of benign sinonasal lesions (all p < 0.004, Bonferroni correction). Combined quantitative parameters (IC, Eff-Z, 40 keV, 60 keV, 80 keV, slope (k)) can improve the diagnostic efficiency for discriminating these two entities. Combination of DECT quantitative parameters and morphological features can further improve the overall diagnostic performance, with AUC, sensitivity, specificity, and accuracy of 0.935, 96.67%, 90.00%, and 93.52%. Moreover, the AUC of DECT was higher than those of Mix-0.3 (simulated SECT), cMRI, DWI, and cMRI+DWI. CONCLUSIONS: Compared with simulated SECT, cMRI, and DWI, DECT appears to be a more accurate imaging technique for differentiating benign from malignant sinonasal lesions. KEY POINTS: • DE can differentiate benign sinonasal lesions from malignant ones based on DECT-derived qualitative parameters. • DECT appears to be more accurate in the diagnosis of sinonasal lesions when compared with simulated SECT, cMRI, and DWI.

A20 attenuates pyroptosis and apoptosis in nucleus pulposus cells via promoting mitophagy and stabilizing mitochondrial dynamics.

BACKGROUND: A20 is an anti-inflammatory molecule in nucleus pulposus (NP) cells. The anti-inflammatory properties of A20 are mainly attributed to its ability to suppress the NF-κB pathway. However, A20 can protect cells from death independently of NF-κB regulation. This study aimed to investigate the effects of A20 on pyroptosis and apoptosis of NP cells induced by lipopolysaccharide (LPS). METHODS: NP cells induced by LPS were used as an in vitro model of the inflammatory environment of the intervertebral disc. Pyroptosis, apoptosis, and mitophagy marker proteins were detected. Then, NP cells were transfected with A20 overexpressed lentivirus or A20-siRNA. Annexin V FITC/PI, Western blotting, and immunofluorescence assays were used to detect the apoptosis, pyroptosis, and mitophagy of NP cells. Furthermore, the expressions of A20, related proteins, and related inflammatory cytokines were detected by western blotting, and ELISA. RESULTS: Apoptosis and pyroptosis of NP cells increased gradually treated with LPS for 12 h, 24 h, and 48 h. Differently, the level of mitophagy increased first and then decreased, and was the highest at LPS treatment for 12 h. Overexpression or knockdown of A20 in NP cells revealed that A20 attenuated the pyroptosis, apoptosis, and production of inflammatory cytokines of NP cells induced by LPS, while A20 sponsored mitophagy, reduced ROS production and collapse of mitochondrial membrane potential (ΔΨm). Moreover, A20 also promoted mitochondrial dynamic homeostasis and attenuated LPS-induced excessive mitochondrial fission. Excitingly, inhibition of mitophagy attenuated the effect of A20 on the negative regulation of pyroptosis of NP cells induced by LPS. Pyroptosis was accompanied by a large release of inflammatory cytokines. Inhibition of pyroptosis also significantly reduced apoptosis of NP cells. Finally, The mitochondria-targeted active peptide SS-31 inhibited LPS-induced pyroptosis and ROS production in NP cells. CONCLUSIONS: To sum up, A20 attenuates pyroptosis and apoptosis of NP cells via promoting mitophagy and stabilizing mitochondrial dynamics. Besides, A20 reduces LPS-induced NP cell apoptosis by inhibiting NLRP3 inflammasome-mediated pyroptosis. It provides theoretical support for the reduction of functional NP cell loss in the intervertebral disc through the gene-targeted intervention of A20.

RING finger protein 128 (RNF128) regulates malignant biological behaviors of colorectal cancer cells via PI3K/AKT signaling pathway.

This study was designed and conducted to clarify the impact of RNF128 expression on malignant biological behaviors of colorectal cancer (CRC) cells and the underlying mechanism. The expression of RNF128 in CRC tissues was analyzed using mRNA sequencing data of TCGA database and was validated by Western blot assay. The experimental studies on biological functions of RNF128 in vitro were conducted to assess its impact on the proliferation, apoptosis, and metastasis of CRC cells. Furthermore, tumor xenograft models in nude mice were established to investigate the relationship between RNF128 expression and tumor growth in vivo. The expression levels of both RNF128 mRNA and protein were significantly increased in CRC tissues (p < .001). The knockdown of RNF128 markedly suppressed the malignant phenotype of HCT116 and SW480 cells in vitro, including cell growth, antiapoptosis, migration, and invasion (p < .001). On the other hand, knockdown of RNF128 exerted a remarkable effect on the growth inhibition of tumor xenografts in vivo (p < .001). Further investigation revealed that RNF128 knockdown lead to a significant decrease in the expression of p-AKT and p-PI3K protein. More importantly, the proliferative, antiapoptotic, metastatic abilities of RNF128-knockdown cells were markedly increased by 740 Y-P treatment (p < .001). These findings further suggested that PI3K/AKT signaling pathway played a key role in RNF128-mediated aggressive phenotype of CRC cells. RNF128 functions as a tumor promoter in the pathogenesis of CRC via regulating PI3K/AKT pathway, and it could be a valuable target for CRC treatment.

Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGß5 signaling.

Metastasis is the leading cause of death in breast cancer patients. Osthole, as an active compound detected in the traditional Chinese medicine Wenshen Zhuanggu Formula, has shown a promising anti-metastatic activity in human breast cancer cells, but the underlying mechanisms remain ambiguous. In this study we elucidated the anti-metastatic mechanisms of osthole in highly metastatic breast cancer cells and a zebrafish xenograft model. We showed that the expression of integrin α3 (ITGα3) and integrin ß5 (ITGß5) was upregulated in highly metastatic MDA-MB-231, MDA-MB-231BO breast cancer cell lines but was downregulated in poorly metastatic MCF-7 breast cancer cell line, which might be the key targets of osthole's anti-metastatic action. Furthermore, we showed that knockdown of ITGα3 and ITGß5 attenuated breast cancer cell migration and invasion possibly via suppression of FAK/Src/Rac1 pathway, whereas overexpression of ITGα3 and ITGß5 caused the opposite effects. Consistently, osthole significantly inhibited breast cancer metastasis by downregulating ITGα3/ITGß5 signaling in vitro and in vivo. These results provide new evidence that osthole may be developed as a candidate therapeutic drug for metastatic breast cancer.

Extramedullary Plasmacytoma of the Sinonasal Cavity: Magnetic Resonance Imaging Characteristics With Readout-Segmented Diffusion-Weighted Imaging and Dual-Energy Computed Tomography Features.

PURPOSE: To determine magnetic resonance imaging (MRI) with readout-segmented diffusion-weighted imaging (RESOLVE-DWI) and dual-energy computed tomography (DECT) features of sinonasal extramedullary plasmacytoma (SN-EMP). METHODS: The MRI and/or DECT of 10 patients with SN-EMP confirmed by pathology were retrospectively reviewed. Apparent diffusion coefficient (ADC) values of RESOLVE-DWI were analyzed in 9 patients. The quantitative parameters derived from DECT, including the iodine concentration (IC), effective atomic number, and the slope (k) of spectral attenuation curve, were measured in 3 patients. RESULTS: On conventional MRI, typical lesions were well defined (7 of 9), and isointense to the brain on both T1WI and T2WI (9 of 9). Most lesions presented with marked enhancement on contrast-enhanced T1WI without significant necrosis (8 of 9). Notably, multiple flow-void signals were observed in all lesions (9 of 9). On RESOLVE-DWI, the average ADC value was 0.55 × 10-3 mm2/s, and the normalized ADC value was 0.66 ± 0.04. On DECT, the average values of IC, effective atomic number, and slope (k) was 2.7 mg/mL, 8.62, and 3.8, respectively. CONCLUSIONS: Some typical MRI features (well-defined mass, isointensity to the brain, marked enhancement without obvious cystic changes, multiple flow voids, and a lower ADC value) strongly suggest the diagnosis of SN-EMP. The quantitative parameters derived from RESOLVE-DWI and DECT may provide more information for the diagnosis of SN-EMP.

Clinicopathological Features of Inflammatory Myofibroblastic Tumor in the Breast.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal spindle cell tumour with low malignant potential which is extremely rare in breasts. Because of the lack of typical imaging and clinical characteristics of IMT, it is easy to misdiagnose before operation. We now report a case of a 37-year-old woman presenting with a mass in her left breast. Ultrasound showed a well-circumscribed lesion in the lower outer quadrant. The patient underwent lumpectomy, and histopathology revealed a tumor which was composed of fusiform cells and inflammatory cells. Immunohistochemistry (IHC) showed tumor cells are positive for vimentin, ALK, BCL2, and SMA. The FISH test demonstrated ALK (2p23) chromosomal translocation (ALK positive). The final diagnosis of breast IMT was rendered with nonclassical morphology. Postoperative 30-month follow-up no evidence showed residual tumor or recurrence. As a very rare tumor, breast IMT could be easily misdiagnosed clinically and pathologically. Complete surgical resection of the tumor is preferred, and it has the risk of recurrence and metastasis.