Targeting non-coding RNAs to overcome osimertinib resistance in EGFR-mutated non-small cell lung cancer.

Osimertinib, a third-generation inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, exhibits remarkable efficacy in prolonging the survival of patients with non-small cell lung cancer (NSCLC) carrying EGFR mutations, surpassing the efficacy of first- and second-generation EGFR tyrosine kinases. Nevertheless, the emergence of osimertinib resistance is inevitable, necessitating an investigation into the underlying mechanisms. Increasing evidence has revealed that non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, play a significant role in the development and progression of lung cancer. These ncRNAs regulate essential signaling pathways, offering a novel avenue for understanding the fundamental mechanisms of osimertinib resistance. Recent studies have reported the significant impact of ncRNAs on osimertinib resistance, achieved through various mechanisms that modulate treatment sensitivity. We provide a concise overview of the functions and underlying mechanisms of extensively researched ncRNAs in the development of osimertinib resistance and emphasize their potential clinical application in EGFR-mutated NSCLC resistant to osimertinib. Finally, we discuss the obstacles that must be addressed to effectively translate ncRNA-based approaches into clinical practice.

Effective extraction and detection of aflatoxins in cereals using nitrogen-rich benzodiimidazole linkage magnetic covalent organic framework based solid phase extraction and HPLC-MS/MS analysis.

Cereals are frequently contaminated by aflatoxins (AFs). The objective of this study was to develop an efficient extraction materials for rapidly extracting and detecting AFs. A novel amino-functionalized benzodiimidazole linkage magnetic covalent organic framework (Fe3O4@BB-COF) was simply fabricated by one-step cyclization and aromatization. The Fe3O4@BB-COF, having multiple N-containing active sites, exhibited excellent extraction capability towards AFs due to synergistic interactions, including the π-π interactions, hydrogen bonding interactions, polar interactions, electrostatic interactions and Lewis acid-base interactions. The Fe3O4@BB-COF based MSPE method for detecting aflatoxins has advantages of simple operation, short extraction time (6 min), and low material consumption (2 mg). This method exhibited satisfactory linearity (0.05-20 µg/kg), and sensitivity (0.01-0.45 µg/L for the detection limits) and accuracy (76.8-97.1 % for recovery) and was successfully applied for extracting and detecting AFs in cereals.

Rational selection of 4,4',4″-(1,3,5-triazine-2,4,6-triyl) trianiline-based covalent organic framework as adsorbent for effective co-extraction of aflatoxins, zearalenone and its metabolites from food and biological samples.

Aflatoxins, zearalenone and its metabolites, as representative hazard mycotoxins cause adverse effects on food safety and human health. Developing a sensitive and reliable extraction and detection method is of great importance for monitoring their residue and exposure levels. In contrast to traditional trial-and-error selection steps, 4,4',4″-(1,3,5-triazine-2,4,6-triyl) trianiline covalent-bonding with 2,5-dihydroxyterephthalaldehyde, namely TAPT-OH-COF was screened as a potential adsorbent utilizing density functional theory calculations prior to the synthesis procedure. After experimental verification, magnetic TAPT-OH-COFs were prepared, characterized and applied for the extraction of aflatoxins, zearalenone and its metabolites from food and biological samples, coupled with high-performance liquid chromatography tandem mass spectrophy detection. Under the optimal conditions, the developed method exhibited low limits of quantification (0.05-0.50 µg/kg), satisfactory recoveries (75.8 %-110.9 %) and good precision with intraday and interday relative standard deviations (RSDs) not exceeding 12.2 %. This study may provide great potential for the selection of candidate adsorbents for multi-mycotoxins extraction from complex samples.

A novel method to select time-varying multivariate time series models for the surveillance of infectious diseases.

BACKGROUND: Describing the transmission dynamics of infectious diseases across different regions is crucial for effective disease surveillance. The multivariate time series (MTS) model has been widely adopted for constructing cross-regional infectious disease transmission networks due to its strengths in interpretability and predictive performance. Nevertheless, the assumption of constant parameters frequently disregards the dynamic shifts in disease transmission rates, thereby compromising the accuracy of early warnings. This study investigated the applicability of time-varying MTS models in multi-regional infectious disease monitoring and explored strategies for model selection. METHODS: This study focused on two prominent time-varying MTS models: the time-varying parameter-stochastic volatility-vector autoregression (TVP-SV-VAR) model and the time-varying VAR model using the generalized additive framework (tvvarGAM), and intended to explore and verify their applicable conditions for the surveillance of infectious diseases. For the first time, this study proposed the time delay coefficient and spatial sparsity indicators for model selection. These indicators quantify the temporal lags and spatial distribution of infectious disease data, respectively. Simulation study adopted from real-world infectious disease surveillance was carried out to compare model performances under various scenarios of spatio-temporal variation as well as random volatility. Meanwhile, we illustrated how the modelling process could help the surveillance of infectious diseases with an application to the influenza-like case in Sichuan Province, China. RESULTS: When the spatio-temporal variation was small (time delay coefficient: 0.1-0.2, spatial sparsity:0.1-0.3), the TVP-SV-VAR model was superior with smaller fitting residuals and standard errors of parameter estimation than those of the tvvarGAM model. In contrast, the tvvarGAM model was preferable when the spatio-temporal variation increased (time delay coefficient: 0.2-0.3, spatial sparsity: 0.6-0.9). CONCLUSION: This study emphasized the importance of considering spatio-temporal variations when selecting appropriate models for infectious disease surveillance. By incorporating our novel indicators-the time delay coefficient and spatial sparsity-into the model selection process, the study could enhance the accuracy and effectiveness of infectious disease monitoring efforts. This approach was not only valuable in the context of this study, but also has broader implications for improving time-varying MTS analyses in various applications.

Deep Learning-Based Simultaneous Temperature- and Curvature-Sensitive Scatterplot Recognition.

Since light propagation in a multimode fiber (MMF) exhibits visually random and complex scattering patterns due to external interference, this study numerically models temperature and curvature through the finite element method in order to understand the complex interactions between the inputs and outputs of an optical fiber under conditions of temperature and curvature interference. The systematic analysis of the fiber's refractive index and bending loss characteristics determined its critical bending radius to be 15 mm. The temperature speckle atlas is plotted to reflect varying bending radii. An optimal end-to-end residual neural network model capable of automatically extracting highly similar scattering features is proposed and validated for the purpose of identifying temperature and curvature scattering maps of MMFs. The viability of the proposed scheme is tested through numerical simulations and experiments, the results of which demonstrate the effectiveness and robustness of the optimized network model.

SIVA-1 interaction with PCBP1 serves as a predictive biomarker for cisplatin sensitivity in gastric cancer and its inhibitory effect on tumor growth in vivo.

Background: SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance in vitro. Nevertheless, the clinical significance of SIVA-1 in GC chemotherapy remains unclear. Methods and results: Immunohistochemistry and histoculture drug response assays were used to determine SIVA-1 expression and the inhibition rate (IR) of agents to GC and to further analyze the relationship between these two phenomena. Additionally, cisplatin (DDP)-resistant GC cells were used to elucidate the role and mechanism of SIVA-1 in vivo. The results demonstrated that SIVA-1 expression was positively correlated with the IR of DDP to GC but not with those of 5-fluorouracil (5-FU) or adriamycin (ADM). Furthermore, SIVA-1 overexpression with DDP treatment synergistically inhibited tumor growth in vivo by increasing PCBP1 and decreasing Bcl-2 and Bcl-xL expression. Conclusions: Our study demonstrated that SIVA-1 may serve as an indicator of the GC sensitivity to DDP, and the mechanism of SIVA-1 in GC resistance to DDP was preliminarily revealed.

Mastering Surface Sulfidation of MnP-MnO2 Heterostructure to Facilitate Efficient Polysulfide Conversion in Li─S Batteries.

The development of lithium-sulfur (Li─S) batteries has been hampered by the shuttling effect of lithium polysulfides (LiPSs). An effective method to address this issue is to use an electrocatalyst to accelerate the catalytic conversion of LiPSs. In this study, heterogeneous MnP-MnO2 nanoparticles are uniformly synthesized and embedded in porous carbon (MnP-MnO2/C) as core catalysts to improve the reaction kinetics of LiPSs. In situ characterization and density functional theory (DFT) calculations confirm that the MnP-MnO2 heterostructure undergo surface sulfidation during the charge/discharge process, forming the MnS2 phase. Surface sulfidation of the MnP-MnO2 heterostructure catalyst significantly accelerated the SRR and Li2S activation, effectively inhibiting the LiPSs shuttling effect. Consequently, the MnP-MnO2/C@S cathode achieves outstanding rate performance (10 C, 500 mAh g-1) and ultrahigh cycling stability (0.017% decay rate per cycle for 2000 cycles at 5 C). A pouch cell with MnP-MnO2/C@S cathode delivers a high energy density of 429 Wh kg-1. This study may provide a new approach to investigating the surface sulfidation of electrocatalysts, which is valuable for advancing high-energy-density Li-S batteries.

Deep learning for the automatic detection and segmentation of parotid gland tumors on MRI.

OBJECTIVES: Parotid gland tumors (PGTs) often occur as incidental findings on magnetic resonance images (MRI) that may be overlooked. This study aimed to construct and validate a deep learning model to automatically identify parotid glands (PGs) with a PGT from normal PGs, and in those with a PGT to segment the tumor. MATERIALS AND METHODS: The nnUNet combined with a PG-specific post-processing procedure was used to develop the deep learning model trained on T1-weighed images (T1WI) in 311 patients (180 PGs with tumors and 442 normal PGs) and fat-suppressed (FS)-T2WI in 257 patients (125 PGs with tumors and 389 normal PGs), for detecting and segmenting PGTs with five-fold cross-validation. Additional validation set separated by time, comprising T1WI in 34 and FS-T2WI in 41 patients, was used to validate the model performance. RESULTS AND CONCLUSION: To identify PGs with tumors from normal PGs, using combined T1WI and FS-T2WI, the deep learning model achieved an accuracy, sensitivity and specificity of 98.2% (497/506), 100% (119/119) and 97.7% (378/387), respectively, in the cross-validation set and 98.5% (67/68), 100% (20/20) and 97.9% (47/48), respectively, in the validation set. For patients with PGTs, automatic segmentation of PGTs on T1WI and FS-T2WI achieved mean dice coefficients of 86.1% and 84.2%, respectively, in the cross-validation set, and of 85.9% and 81.0%, respectively, in the validation set. The proposed deep learning model may assist the detection and segmentation of PGTs and, by acting as a second pair of eyes, ensure that incidentally detected PGTs on MRI are not missed.

SIVA-1 enhances acquired chemotherapeutic drug resistance of gastric cancer in vivo by regulating the ARF/MDM2/p53 pathway.

SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.

Pulmonary Transit Time Derived from First-Pass Perfusion Cardiac MR Imaging: A Potential New Marker for Cardiac Involvement and Prognosis in Light-Chain Amyloidosis.

BACKGROUND: First-pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first-pass perfusion MRI in light-chain (AL) amyloidosis requires further evaluation. PURPOSE: To assess the clinical and prognostic value of PTT in patients with AL amyloidosis. STUDY TYPE: Prospective observational study. POPULATION: 226 biopsy-proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males). FIELD STRENGTH/SEQUENCE: SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first-pass myocardial perfusion imaging with a saturation recovery turbo fast low-angle shot (SR-TurboFLASH) pulse sequence at 3.0T. ASSESSMENT: PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first-pass perfusion MR images. STATISTICAL TESTS: Independent-sample t test, Mann-Whitney U test, Chi-square test, Fisher's exact test, analysis of variance, or Kruskal-Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan-Meier curves, area under receiver operating characteristic curve were used to determine statistical significance. RESULTS: PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow-up of 35 months, 160 patients (70.8%) demonstrated all-cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021-1.102), biochemical (HR 1.055, CI: 1.014-1.097), cardiac MRI-derived (HR 1.077, CI: 1.034-1.123), and therapeutic (HR 1.063, CI: 1.024-1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern. DATA CONCLUSION: PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Mitochondrial fission drives neuronal metabolic burden to promote stress susceptibility in male mice.

Neurons are particularly susceptible to energy fluctuations in response to stress. Mitochondrial fission is highly regulated to generate ATP via oxidative phosphorylation; however, the role of a regulator of mitochondrial fission in neuronal energy metabolism and synaptic efficacy under chronic stress remains elusive. Here, we show that chronic stress promotes mitochondrial fission in the medial prefrontal cortex via activating dynamin-related protein 1 (Drp1), resulting in mitochondrial dysfunction in male mice. Both pharmacological inhibition and genetic reduction of Drp1 ameliorates the deficit of excitatory synaptic transmission and stress-related depressive-like behavior. In addition, enhancing Drp1 fission promotes stress susceptibility, which is alleviated by coenzyme Q10, which potentiates mitochondrial ATP production. Together, our findings unmask the role of Drp1-dependent mitochondrial fission in the deficits of neuronal metabolic burden and depressive-like behavior and provides medication basis for metabolism-related emotional disorders.

Feasibility of Free-Breathing, Non-ECG-Gated, Black-Blood Cine Magnetic Resonance Images With Multitasking in Measuring Left Ventricular Function Indices.

OBJECTIVE: To clinically validate the feasibility and accuracy of cine images acquired through the multitasking method, with no electrocardiogram gating and free-breathing, in measuring left ventricular (LV) function indices by comparing them with those acquired through the balanced steady-state free precession (bSSFP) method, with multiple breath-holds and electrocardiogram gating. MATERIALS AND METHODS: Forty-three healthy volunteers (female:male, 30:13; mean age, 23.1 ± 2.3 years) and 36 patients requiring an assessment of LV function for various clinical indications (female:male, 22:14; 57.8 ± 11.3 years) were enrolled in this prospective study. Each participant underwent cardiac magnetic resonance imaging (MRI) using the multiple breath-hold bSSFP method and free-breathing multitasking method. LV function parameters were measured for both MRI methods. Image quality was assessed through subjective image quality scores (1 to 5) and calculation of the contrast-to-noise ratio (CNR) between the myocardium and blood pool. Differences between the two MRI methods were analyzed using the Bland-Altman plot, paired t-test, or Wilcoxon signed-rank test, as appropriate. RESULTS: LV ejection fraction (LVEF) was not significantly different between the two MRI methods (P = 0.222 in healthy volunteers and P = 0.343 in patients). LV end-diastolic mass was slightly overestimated with multitasking in both healthy volunteers (multitasking vs. bSSFP, 60.5 ± 10.7 g vs. 58.0 ± 10.4 g, respectively; P < 0.001) and patients (69.4 ± 18.1 g vs. 66.8 ± 18.0 g, respectively; P = 0.003). Acceptable and comparable image quality was achieved for both MRI methods (multitasking vs. bSSFP, 4.5 ± 0.7 vs. 4.6 ± 0.6, respectively; P = 0.203). The CNR between the myocardium and blood pool showed no significant differences between the two MRI methods (18.89 ± 6.65 vs. 18.19 ± 5.83, respectively; P = 0.480). CONCLUSION: Multitasking-derived cine images obtained without electrocardiogram gating and breath-holding achieved similar image quality and accurate quantification of LVEF in healthy volunteers and patients.

Prediction of radiation pneumonia after radiotherapy for esophageal cancer using a unified fractional dosiomics combined model.

OBJECTIVE: This study aimed to construct an optimal model to predict radiation pneumonia (RP) after radiotherapy for esophageal cancer using unified fractional dosiomics and to investigate the improvements in the prediction efficiency of each model for RP. METHODS: The clinical data, DVH, pre-treatment CT, and dose distribution of 182 patients were retrospectively analyzed.The independent risk factors were screened using univariate and multivariate logistic regression. The mutual information (MI),least absolute shrinkage and selection operator (LASSO), and recursive feature elimination (RFE) methods were used to screen the omics features. The AUC values of ROC, calibration curves, and clinical decision curves were calculated to evaluate the efficacy and trends of each model. RESULTS: The AUC of dosiomics model were 0.783 and 0.760 in the training and test cohorts, higher than 0.585 and 0.579 in the training and test cohorts of the DVH model. The AUC value of the R + D combination was the highest, reaching 0.833. The combined R + D model had a better calibration degree than the other models (mean absolute error = 0.018) and better net benefit in clinical decision-making. CONCLUSIONS: The radiomics combined dosiomics model was the best combined model to predict RP after radiotherapy for esophageal cancer. The dosiomics model could cover the efficiency of the DVH model and significantly improve the efficiency of the combined model.In the future, we will include other centers for further verification. ADVANCES IN KNOWLEDGE: For the first time, this study used CT images combined dose distribution to predict the occurrence of radiation pneumonitis after radiotherapy for esophageal cancer.

Cell type-specific NRBF2 orchestrates autophagic flux and adult hippocampal neurogenesis in chronic stress-induced depression.

Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2 (NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesis-related protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly, overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice. Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment.

Dopamine D2 receptor on CD4+ T cells is protective against inflammatory responses and signs in a mouse model of rheumatoid arthritis.

BACKGROUND: Dopamine is a neurotransmitter and has been found to regulate lymphocytes by acting on dopamine receptors (DRs). CD4+ T cells express all the five subtypes of DRs, D1R to D5R. Although CD4+ T cells have been involved in pathogenesis of rheumatoid arthritis (RA), roles of DRs expressed on these cells in RA are poorly understood. This study determined whether D2R expressed on CD4+ T cells regulates inflammatory responses and signs in collagen type II (CII)-induced arthritis (CIA), a mouse model of RA. METHODS: DBA/1 mice and C57BL/6 mice with global D1r or D2r deficiency (D1r-/- or D2r-/-) or CD4+ T cell-specific D2r deletion (D2rfl/fl/CD4Cre) were used to prepare CIA model by intradermal injection of CII. D2R agonist sumanirole was intraperitoneally administered in CIA mice. CD4+ T cells obtained from CIA mice were exposed to sumanirole or/and D2R antagonist L-741,626 in vitro. Arthritic symptoms were assessed by clinical arthritis scores. Flow cytometric assay measured frequencies of CD4+ T cell subsets (Th1, Th2, Th17 and Treg cells). Expression of specific transcription factors for the CD4+ T cell subsets was tested by Western blot. Cytokine production was estimated by quantitative PCR and ELISA. RESULTS: CIA mice manifested a bias of CD4+ T cells towards Th1 and Th17 cells. D2r-/- CIA mice showed a stronger bias towards Th1 and Th17 phenotypes than CIA mice, while D1r-/- CIA mice did not show the changes. CD4+ T cell-specific D2r deletion exacerbated both the polarization towards Th1 and Th17 cells and the symptoms of arthritis. Sumanirole administration in CIA mice ameliorated the bias of CD4+ T cells towards Th1 and Th17 phenotypes as well as arthritic symptoms. Sumanirole treatment of in vitro CD4+ T cells obtained from CIA mice promoted the shift to Treg cells, and the effect of sumanirole was blocked by L-741,626. CONCLUSIONS: D2R expressed on CD4+ T cells is protective against imbalance between pro-inflammatory and anti-inflammatory T cells and arthritic symptoms in CIA.

Myeloperoxidase-Sensitive Magnetic Resonance Imaging Assesses Inflammatory Activation State in Experimental Mouse Acute Gout.

BACKGROUND: A novel myeloperoxidase-activatable manganese-based (MPO-Mn) MRI probe may enable the activation state of inflammatory foci to be detected and monitored noninvasively. PURPOSE: To evaluate the inflammatory response in a mouse model of acute gout using MPO as an imaging biomarker and a potential therapeutic target. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 40 male Swiss mice with monosodium urate crystals induced acute gout. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted imaging with 2D fast spoiled gradient recalled echo and T2-weighted imaging with fast recovery fast spin-echo sequences. ASSESSMENT: The difference in contrast-to-noise ratio between left hind limb (lesion) and right hind limb (internal reference) (ΔCNR), and normalized signal-to-noise ratio (nSNR) on the right hind limb were calculated and compared. The expression level and activity of myeloperoxidase (MPO) were analyzed using western blotting and spectrophotometric quantitation activity assay. MPO-positive cell infiltration and lesion volume were evaluated using immunofluorescence staining and T2-weighted images, respectively. STATISTICAL TESTS: Student's t test. A P-value less than 0.05 was considered to be statistically significant. RESULTS: MPO-Mn resulted in a significantly higher ΔCNR than Gd-DTPA (22.54 ± 1.86 vs. 13.90 ± 2.22) but lower nSNR on the reference right hind limb (1.08 ± 0.07 vs. 1.21 ± 0.08). Compared to the nontreatment group, MPO-inhibition resulted in a significantly reduced contrast enhancement at the lesion (17.81 ± 1.58 vs. 22.96 ± 3.12), which was consistent with a remission of the inflammatory response, as evidenced by a substantial reduction of lesion volume (0.55 ± 0.16 mm3 /g vs. 1.14 ± 0.15 mm3 /g), myeloperoxidase expression level (0.98 ± 0.09 vs. 1.48 ± 0.19) and activity (0.75 ± 0.12 vs. 1.12 ± 0.07), and inflammatory cell recruitment. DATA CONCLUSION: MPO-Mn MRI has potential to evaluate the activation state of inflammatory foci in the experimental model of acute gout. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 1.

α-MSH-catabolic enzyme prolylcarboxypeptidase in nucleus accumbens shell ameliorates stress susceptibility in mice through regulating synaptic plasticity.

Emerging evidence demonstrates the vital role of synaptic transmission and structural remodeling in major depressive disorder. Activation of melanocortin receptors facilitates stress-induced emotional behavior. Prolylcarboxypeptidase (PRCP) is a serine protease, which splits the C-terminal amino acid of α-MSH and inactivates it. In this study, we asked whether PRCP, the endogenous enzyme of melanocortin system, might play a role in stress susceptibility via regulating synaptic adaptations. Mice were subjected to chronic social defeat stress (CSDS) or subthreshold social defeat stress (SSDS). Depressive-like behavior was assessed in SIT, SPT, TST and FST. Based on to behavioral assessments, mice were divided into the susceptible (SUS) and resilient (RES) groups. After social defeat stress, drug infusion or viral expression and behavioral tests, morphological and electrophysiological analysis were conducted in PFX-fixed and fresh brain slices containing the nucleus accumbens shell (NAcsh). We showed that PRCP was downregulated in NAcsh of susceptible mice. Administration of fluoxetine (20 mg·kg-1·d-1, i.p., for 2 weeks) ameliorated the depressive-like behavior, and restored the expression levels of PRCP in NAcsh of susceptible mice. Pharmacological or genetic inhibition of PRCP in NAcsh by microinjection of N-benzyloxycarbonyl-L-prolyl-L-prolinal (ZPP) or LV-shPRCP enhanced the excitatory synaptic transmission in NAcsh, facilitating stress susceptibility via central melanocortin receptors. On the contrary, overexpression of PRCP in NAcsh by microinjection of AAV-PRCP alleviated the depressive-like behavior and reversed the enhanced excitatory synaptic transmission, abnormal dendritogenesis and spinogenesis in NAcsh induced by chronic stress. Furthermore, chronic stress increased the level of CaMKIIα, a kinase closely related to synaptic plasticity, in NAcsh. The elevated level of CaMKIIα was reversed by overexpression of PRCP in NAcsh. Pharmacological inhibition of CaMKIIα in NAcsh alleviated stress susceptibility induced by PRCP knockdown. This study has revealed the essential role of PRCP in relieving stress susceptibility through melanocortin signaling-mediated synaptic plasticity in NAcsh.

Li-S Chemistry of Manganese Phosphides Nanoparticles With Optimized Phase.

The targeted synthesis of manganese phosphides with target phase remains a huge challenge because of their various stoichiometries and phase-dependent physicochemical properties. In this study, phosphorus-rich MnP, manganese-rich Mn2 P, and their heterostructure MnP-Mn2 P nanoparticles evenly dispersed on porous carbon are accurately synthesized by a convenient one-pot heat treatment of phosphate resin combined with Mn2+ . Moreover, their electrochemical properties are systematically investigated as sulfur hosts in lithium-sulfur batteries. Density functional theory calculations demonstrate the superior adsorption, catalysis capabilities, and electrical conductivity of MnP-Mn2 P/C, compared with MnP/C and Mn2 P/C. The MnP-Mn2 P/C@S exhibits an excellent capacity of 763.3 mAh g-1 at 5 C with a capacity decay rate of only 0.013% after 2000 cycles. A phase evolution product (MnS) of MnP-Mn2 P/C@S is detected during the catalysis of MnP-Mn2 P/C with polysulfides redox through in situ X-ray diffraction and Raman spectroscopy. At a sulfur loading of up to 8 mg cm-2 , the MnP-Mn2 P/C@S achieves an area capacity of 6.4 mAh cm-2 at 0.2 C. A pouch cell with the MnP-Mn2 P/C@S cathode exhibits an initial energy density of 360 Wh kg-1 .

Comparison between pre- and post-contrast cardiac MRI cine images: the impact on ventricular volume and strain measurement.

To explore whether contrast agent administration will affect ventricular volume and strain parameters measured on cardiac magnetic resonance cine images. This prospective study enrolled 88 patients, including 32 patients with cardiac amyloidosis (CA), 32 patients with hypertrophic cardiomyopathy (HCM), and 24 control participants, to perform steady-state free precession (SSFP)-cine imaging twice, respectively before and after contrast agent injection. Indexed left and right ventricular (LV and RV) volume and LV strain parameters (peak radial strain [PRS], peak circumferential strain [PCS], peak longitudinal strain [PLS]) were analyzed and compared between the pre- and post-contrast cine groups. Compared to the group of pre-contrast cine, the end-diastolic volume index (EDVi) and end-systolic volume index (ESVi) significantly increased in the group using post-contrast cine images (all p < 0.05), especially in the right ventricle. After contrast injection, the right ventricular ejection fraction (RVEF) decreased significantly (p < 0.05), while the left ventricular ejection fraction (LVEF) only reduced for patients with HCM (p < 0.05). The PRS (37.1 ± 15.2 vs. 32.0 ± 15.4, p < 0.001) and PCS (- 14.9 ± 4.3 vs. - 14.0 ± 4.1, p < 0.001) derived from post-contrast cine images reduced significantly in all patients and this tendency remained in subgroup analysis except for PCS in the control group. The administration of a contrast agent may influence the measurements of ventricular volume and strain. Acquiring pre-contrast cine images were suggested for patients who required more accurate right ventricle evaluation or precise strain assessment.

Receptor and Ionic Mechanism of Histamine on Mouse Dorsolateral Striatal Neurons.

The dorsolateral striatum (DLS) is the critical neural substrate that plays a role in motor control and motor learning. Our past study revealed a direct histaminergic projection from the tuberomammillary nucleus (TMN) of the hypothalamus to the rat striatum. However, the afferent of histaminergic fibers in the mouse DLS, the effect of histamine on DLS neurons, and the underlying receptor and ionic mechanisms remain unclear. Here, we demonstrated a direct histaminergic innervation from the TMN in the mouse DLS, and histamine excited both the direct-pathway spiny projection neurons (d-SPNs) and the indirect-pathway spiny projection neurons (i-SPNs) of DLS via activation of postsynaptic H1R and H2R, albeit activation of presynaptic H3R suppressed neuronal activity by inhibiting glutamatergic synaptic transmission on d-SPNs and i-SPNs in DLS. Moreover, sodium-calcium exchanger 3 (NCX3), potassium-leak channels linked to H1R, and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) coupled to H2R co-mediated the excitatory effect induced by histamine on d-SPNs and i-SPNs in DLS. These results demonstrated the pre- and postsynaptic receptors and their downstream multiple ionic mechanisms underlying the inhibitory and excitatory effects of histamine on d-SPNs and i-SPNs in DLS, suggesting a potential modulatory effect of the central histaminergic system on the DLS as well as its related motor control and motor learning.