Identification and potential application of key insecticidal metabolites in Tilia amurensis, a low-preference host of Hyphantria cunea.

Developing effective insecticidal strategies is an important means of reducing the spread and host plant damage by Hyphantria cunea. In this study, key metabolites with insecticidal activity against H. cunea were screened by targeted metabolomics in Tilia amurensis, a low-preference host plant. Subsequently, the potential of key metabolites that could be used as botanical pesticides was evaluated. The results showed that coumarin was the key insecticidal metabolite of T. amurensis and had a significant insecticidal effect and weight inhibition effect on H. cunea larvae. Coumarin treatment significantly decreased the larval nutrient content and the gene expression of rate-limiting enzymes in the glycolytic pathway and tricarboxylic acid cycle. A significantly enhanced detoxification enzyme activity (CarE and GST), antioxidant oxidase activity (SOD and CAT), non-enzymatic antioxidant levels (GSH), and total antioxidant capacity were observed in coumarin-treated larvae. Coumarin treatment resulted in a significant increase in the expression levels of detoxification enzyme genes (CarE1, CarE2, CarE3, GST2, and GST3) and antioxidant oxidase genes (SOD1, CAT1, and CAT2) in H. cunea larvae. Coumarin treatment significantly increased the levels of MDA and H2O2 in larvae but did not cause pathological changes in the ultrastructure of the larval midgut. Coumarin solution sprayed directly or as a microcapsule suspension formulation with coumarin as the active ingredient had significant insecticidal activity against the H. cunea larvae. Overall, coumarin, a key anti-insect metabolite identified from T. amurensis, can significantly inhibit the growth and survival of H. cunea larvae and has the potential to be developed as a botanical pesticide.

Extracellular ATP contributes to the reactive oxygen species burst and exaggerated mitochondrial damage in D-galactosamine and lipopolysaccharide-induced fulminant hepatitis.

Fulminant hepatitis (FH) is a severe clinical syndrome leading to hepatic failure and even mortality. D-galactosamine (D-GalN) plus lipopolysaccharide (LPS) challenge is commonly used to establish an FH mouse model, but the mechanism underlying D-GalN/LPS-induced liver injury is incompletely understood. Previously, it has been reported that extracellular ATP that can be released under cytotoxic and inflammatory stresses serves as a damage signal to induce potassium ion efflux and trigger the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome activation through binding to P2X7 receptor. In this study, we tried to investigate whether it contributed to the fulminant hepatitis (FH) induced by D-GalN plus LPS. In an in vitro cellular model, D-GalN plus extracellular ATP, instead of D-GalN alone, induced pyroptosis and apoptosis, accompanied by mitochondrial reactive oxygen species (ROS) burst, and the oligomerization of Drp1, Bcl-2, and Bak, as well as the loss of mitochondrial membrane potential in LPS-primed macrophages, well reproducing the events induced by D-GalN and LPS in vivo. Moreover, these events in the cellular model were markedly suppressed by both A-804598 (an ATP receptor P2X7R inhibitor) and glibenclamide (an ATP-sensitive potassium ion channel inhibitor); in the FH mouse model, administration of A-804598 significantly mitigated D-GalN/LPS-induced hepatic injury, mitochondrial damage, and the activation of apoptosis and pyroptosis signaling, corroborating the contribution of extracellular ATP to the cell death. Collectively, our data suggest that extracellular ATP acts as an autologous damage-associated molecular pattern to augment mitochondrial damage, hepatic cell death, and liver injury in D-GalN/LPS-induced FH mouse model.

Blocking reverse electron transfer-mediated mitochondrial DNA oxidation rescues cells from PANoptosis.

PANoptosis is a new type of cell death featured with pyroptosis, apoptosis and necroptosis, and is implicated in organ injury and mortality in various inflammatory diseases, such as sepsis and hemophagocytic lymphohistiocytosis (HLH). Reverse electron transport (RET)-mediated mitochondrial reactive oxygen species (mtROS) has been shown to contribute to pyroptosis and necroptosis. In this study we investigated the roles of mtROS and RET in PANoptosis induced by TGF-ß-activated kinase 1 (TAK1) inhibitor 5Z-7-oxozeaenol (Oxo) plus lipopolysaccharide (LPS) as well as the effects of anti-RET reagents on PANoptosis. We showed that pretreatment with anti-RET reagents 1-methoxy PMS (MPMS) or dimethyl fumarate (DMF) dose-dependently inhibited PANoptosis in macrophages BMDMs and J774A.1 cells induced by Oxo/LPS treatment assayed by propidium iodide (PI) staining. The three arms of the PANoptosis signaling pathway, namely pyroptosis, apoptosis and necroptosis signaling, as well as the formation of PANoptosomes were all inhibited by MPMS or DMF. We demonstrated that Oxo/LPS treatment induced RET and mtROS in BMDMs, which were reversed by MPMS or DMF pretreatment. Interestingly, the PANoptosome was co-located with mitochondria, in which the mitochondrial DNA was oxidized. MPMS and DMF fully blocked the mtROS production and the formation of PANoptosome induced by Oxo plus LPS treatment. An HLH mouse model was established by poly(I:C)/LPS challenge. Pretreatment with DMF (50 mg·kg-1·d-1, i.g. for 3 days) or MPMS (10 mg·kg-1·d-1, i.p. for 2 days) (DMF i.g. MPMS i.p.) effectively alleviated HLH lesions accompanied by decreased hallmarks of PANoptosis in the liver and kidney. Collectively, RET and mtDNA play crucial roles in PANoptosis induction and anti-RET reagents represent a novel class of PANoptosis inhibitors by blocking oxidation of mtDNA, highlighting their potential application in treating PANoptosis-related inflammatory diseases. PANoptotic stimulation induces reverse electron transport (RET) and reactive oxygen species (ROS) in mitochondia, while 1-methoxy PMS and dimethyl fumarate can inhibit PANoptosis by suppressing RETmediated oxidation of mitochondrial DNA.

Anti-Necroptotic Effects of Itaconate and its Derivatives.

Itaconate is an unsaturated dicarboxylic acid that is derived from the decarboxylation of the Krebs cycle intermediate cis-aconitate and has been shown to exhibit anti-inflammatory and anti-bacterial/viral properties. But the mechanisms underlying itaconate's anti-inflammatory activities are not fully understood. Necroptosis, a lytic form of regulated cell death (RCD), is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) signaling. It has been involved in the pathogenesis of organ injury in many inflammatory diseases. In this study, we aimed to explore whether itaconate and its derivatives can inhibit necroptosis in murine macrophages, a mouse MPC-5 cell line and a human HT-29 cell line in response to different necroptotic activators. Our results showed that itaconate and its derivatives dose-dependently inhibited necroptosis, among which dimethyl itaconate (DMI) was the most effective one. Mechanistically, itaconate and its derivatives inhibited necroptosis by suppressing the RIPK1/RIPK3/MLKL signaling and the oligomerization of MLKL. Furthermore, DMI promoted the nuclear translocation of Nrf2 that is a critical regulator of intracellular redox homeostasis, and reduced the levels of intracellular reactive oxygen species (ROS) and mitochondrial superoxide (mtROS) that were induced by necroptotic activators. Consistently, DMI prevented the loss of mitochondrial membrane potential induced by the necroptotic activators. In addition, DMI mitigated caerulein-induced acute pancreatitis in mice accompanied by reduced activation of the necroptotic signaling in vivo. Collectively, our study demonstrates that itaconate and its derivatives can inhibit necroptosis by suppressing the RIPK1/RIPK3/MLKL signaling, highlighting their potential applications for treating necroptosis-associated diseases.

Potassium ion efflux induces exaggerated mitochondrial damage and non-pyroptotic necrosis when energy metabolism is blocked.

Damage-associated molecular patterns (DAMPs) such as extracellular ATP and nigericin (a bacterial toxin) not only act as potassium ion (K+) efflux inducers to activate NLRP3 inflammasome, leading to pyroptosis, but also induce cell death independently of NLRP3 expression. However, the roles of energy metabolism in determining NLRP3-dependent pyroptosis and -independent necrosis upon K+ efflux are incompletely understood. Here we established cellular models by pharmacological blockade of energy metabolism, followed by stimulation with a K+ efflux inducer (ATP or nigericin). Two energy metabolic inhibitors, namely CPI-613 that targets α-ketoglutarate dehydrogenase and pyruvate dehydrogenase (a rate-limiting enzyme) and 2-deoxy-d-glucose (2-DG) that targets hexokinase, are recruited in this study, and Nlrp3 gene knockout macrophages were used. Our data showed that CPI-613 and 2-DG dose-dependently inhibited NLRP3 inflammasome activation, but profoundly increased cell death in the presence of ATP or nigericin. The cell death was K+ efflux-induced but NLRP3-independent, which was associated with abrupt reactive oxygen species (ROS) production, reduction of mitochondrial membrane potential, and oligomerization of mitochondrial proteins, all indicating mitochondrial damage. Notably, the cell death induced by K+ efflux and blockade of energy metabolism was distinct from pyroptosis, apoptosis, necroptosis or ferroptosis. Furthermore, fructose 1,6-bisphosphate, a high-energy intermediate of glycolysis, significantly suppressed CPI-613+nigericin-induced mitochondrial damage and cell death. Collectively, our data show that energy deficiency diverts NLRP3 inflammasome activation-dependent pyroptosis to Nlrp3-independent necrosis upon K+ efflux inducers, which can be dampened by high-energy intermediate, highlighting a critical role of energy metabolism in cell survival and death under inflammatory conditions.

Assessment of cytisine as an insecticide candidate for Hyphantria cunea management: Toxicological, biochemical, and control potential insights.

In the present study, the toxicological effects of cytisine on the H. cunea larvae were investigated, and the potential of cytisine as a botanical insecticide through field simulation experiments was evaluated. The results showed that cytisine treatment (0.25-2.5%) exerted significant biotoxic effects on the H. cunea larvae, including diminished weight, disruption of both positive (HcCKS1, HcPLK, HcCCNA) and negative (HcGADD and HcCDKN) regulatory genes associated with larval growth, increased mortality, and heightened oxidative damage (H2O2 and MDA). Cytisine treatment significantly reduced glucose content and inhibited the expression of key rate-limiting enzyme genes (HcPFK, HcPK, HcHK1, HcCS, and HcIDH2) within glycolysis and the tricarboxylic acid cycle pathways. Under cytisine treatment, detoxification enzyme activities (CarE and GST) and expression of detoxification genes (HcCarE1, HcCarE2, HcCarE3, HcGST1, and HcGST3) were inhibited in H. cunea larvae. An increased contents of SOD, CAT, ASA and T-AOC, as well as expression of antioxidant enzyme genes HcSOD1 and HcCAT2, was found in cytisine-treated H. cunea larvae. Simultaneously, this is accompanied by a significant reduction in the expression of four antioxidant enzyme genes (e.g., HcPOD1 and HcPOD2). In the field experiment, a cytisine aqueous solution (25 g/L) with pre-sprayed and directly sprayed ways demonstrated potent insecticidal activity against H. cunea larvae, achieving a mortality rate of 53.75% and 100% at 24 h, respectively. Taken together, cytisine has significantly weight inhibition and lethal toxicity on the H. cunea larvae, and can be developed as a botanical insecticide for H. cunea control.

A Carbazole-1,8-Disulfonamide-Derived Cryptand Receptor for Anion Recognition.

A novel cryptand-like anion receptor 1 was synthesized in reasonable yield by a one-step condensation reaction. The UV-vis spectroscopic titrations indicated that cryptand 1 bound AcO- in preference to other monovalent anions (including its competing F- and H2PO4-) in CH3CN, generating a 1:1 binding complex with Ka = 51,000 M-1. Moreover, the crystal structures revealed that the acetate ion was encapsulated inside the cryptand's cavity in a 1:1 manner, through multiple N-H···O hydrogen bonds (although having two different crystal forms).

Digestive Characteristics of Hyphantria cunea Larvae on Different Host Plants.

Digestive physiology mediates the adaptation of phytophagous insects to host plants. In this study, the digestive characteristics of Hyphantria cunea larvae feeding preferences on different host plants were investigated. The results showed that the body weight, food utilization, and nutrient contents of H. cunea larvae feeding on the high-preference host plants were significantly higher than those feeding on the low-preference host plants. However, the activity of larval digestive enzymes in different host plants presented an opposite trend, as higher α-amylase or trypsin activity was observed in the group feeding on the low-preference host plants than that feeding on the high-preference host plants. Upon treatment of leaves with α-amylase and trypsin inhibitors, the body weight, food intake, food utilization rate, and food conversion rate of H. cunea larvae significantly decreased in all host plant groups. Furthermore, the H. cunea comprised highly adaptable compensatory mechanisms of digestion involving digestive enzymes and nutrient metabolism in response to digestive enzyme inhibitors. Taken together, digestive physiology mediates the adaptation of H. cunea to multiple host plants, and the compensatory effect of digestive physiology is an important counter-defense strategy implemented by H. cunea to resist plant defense factors, especially the insect digestive enzyme inhibitors.

Rational design of a genome-based insulated system in Escherichia coli facilitates heterologous uricase expression for hyperuricemia treatment.

Hyperuricemia is a prevalent disease worldwide that is characterized by elevated urate levels in the blood owing to purine metabolic disorders, which can result in gout and comorbidities. To facilitate the treatment of hyperuricemia through the uricolysis, we engineered a probiotic Escherichia coli Nissle 1917 (EcN) named EcN C6 by inserting an FtsP-uricase cassette into an "insulated site" located between the uspG and ahpF genes. Expression of FtsP-uricase in this insulated region did not influence the probiotic properties or global gene transcription of EcN but strongly increased the enzymatic activity for urate degeneration, suggesting that the genome-based insulated system is an ideal strategy for EcN modification. Oral administration of EcN C6 successfully alleviated hyperuricemia, related symptoms and gut microbiota in a purine-rich food-induced hyperuricemia rat model and a uox-knockout mouse model. Together, our study provides an insulated site for heterologous gene expression in EcN strain and a recombinant EcN C6 strain as a safe and effective therapeutic candidate for hyperuricemia treatment.

Dimethyl fumarate inhibits necroptosis and alleviates systemic inflammatory response syndrome by blocking the RIPK1-RIPK3-MLKL axis.

Necroptosis has been implicated in various inflammatory diseases including tumor-necrosis factor-α (TNF-α)-induced systemic inflammatory response syndrome (SIRS). Dimethyl fumarate (DMF), a first-line drug for treating relapsing-remitting multiple sclerosis (RRMS), has been shown to be effective against various inflammatory diseases. However, it is still unclear whether DMF can inhibit necroptosis and confer protection against SIRS. In this study, we found that DMF significantly inhibited necroptotic cell death in macrophages induced by different necroptotic stimulations. Both the autophosphorylation of receptor-interacting serine/threonine kinase 1 (RIPK1) and RIPK3 and the downstream phosphorylation and oligomerization of MLKL were robustly suppressed by DMF. Accompanying the suppression of necroptotic signaling, DMF blocked the mitochondrial reverse electron transport (RET) induced by necroptotic stimulation, which was associated with its electrophilic property. Several well-known anti-RET reagents also markedly inhibited the activation of the RIPK1-RIPK3-MLKL axis accompanied by decreased necrotic cell death, indicating a critical role of RET in necroptotic signaling. DMF and other anti-RET reagents suppressed the ubiquitination of RIPK1 and RIPK3, and they attenuated the formation of necrosome. Moreover, oral administration of DMF significantly alleviated the severity of TNF-α-induced SIRS in mice. Consistent with this, DMF mitigated TNF-α-induced cecal, uterine, and lung damage accompanied by diminished RIPK3-MLKL signaling. Collectively, DMF represents a new necroptosis inhibitor that suppresses the RIPK1-RIPK3-MLKL axis through blocking mitochondrial RET. Our study highlights DMF's potential therapeutic applications for treating SIRS-associated diseases.

QiHuangYiShen Granules Modulate the Expression of LncRNA MALAT1 and Attenuate Epithelial-Mesenchymal Transition in Kidney of Diabetic Nephropathy Rats.

Background: QiHuangYiShen granules (QHYS), a traditional Chinese herbal medicine formula, have been used in clinical practice for treating diabetic kidney disease for several years by our team. The efficacy of reducing proteinuria and delaying the decline of renal function of QHYS has been proved by our previous studies. However, the exact mechanism by which QHYS exerts its renoprotection remains largely unknown. Emerging evidence suggests that lncRNA MALAT1 is abnormally expressed in diabetic nephropathy (DN) and can attenuate renal fibrosis by modulating podocyte epithelial-mesenchymal transition (EMT). Objective: In the present study, we aimed to explore whether QHYS could modulate lncRNA MALAT1 expression and attenuate the podocyte EMT as well as the potential mechanism related to the Wnt/ß-catenin signal pathway. Methods: SD rats were fed with the high-fat-high-sucrose diet for 8 weeks and thereafter administered with 30 mg/kg streptozotocin intraperitoneally to replicate the DN model. Quality control of QHYS was performed using high-performance liquid chromatography. QHYS were orally administered at 1.25, 2.5, and 5 g/kg doses, respectively, to the DN model rats for 12 weeks. Body weight, glycated haemoglobin, blood urea nitrogen, serum creatinine, 24-h proteinuria, and kidney index were measured. The morphologic pathology of the kidney was evaluated by Hematoxylin-eosin and Masson's trichrome staining. The expression level of lncRNA MALAT1 was determined by quantitative real-time polymerase chain reaction. In addition, the expression levels of podocyte EMT protein markers and Wnt/ß-catenin pathway proteins in renal tissues were evaluated by Western blotting and immunohistochemistry. Results: The results showed that QHYS significantly reduced 24-h proteinuria, blood urea nitrogen, kidney index, and ameliorated glomerular hypertrophy and collagen fiber deposition in the kidney of DN rats. Importantly, QHYS significantly downregulated the expression level of lncRNA MALAT1, upregulated the expression of nephrin, the podocyte marker protein, downregulated the expression of desmin and FSP-1, and mesenchymal cell markers. Furthermore, QHYS significantly downregulated the expression levels of Wnt1, ß-catenin, and active ß-catenin. Conclusion: Conclusively, our study revealed that QHYS significantly reduced proteinuria, alleviated renal fibrosis, and attenuated the podocyte EMT in DN rats, which may be associated with the downregulation of lncRNA MALAT1 expression and inhibition of the Wnt/ß-catenin pathway.

Derivation and Validation of a Prediction Model of End-Stage Renal Disease in Patients With Type 2 Diabetes Based on a Systematic Review and Meta-analysis.

Objectives: To develop and validate a model for predicting the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes. Methods: The derivation cohort was from a meta-analysis. Statistically significant risk factors were extracted and combined to the corresponding risk ratio (RR) to establish a risk assessment model for ESRD in type 2 diabetes. All risk factors were scored according to their weightings to establish the prediction model. Model performance is evaluated using external validation cohorts. The outcome was the occurrence of ESRD defined as eGFR<15 ml min-1 1.73 m-2 or received kidney replacement therapy (dialysis or transplantation). Results: A total of 1,167,317 patients with type 2 diabetes were included in our meta-analysis, with a cumulative incidence of approximately 1.1%. The final risk factors of the prediction model included age, sex, smoking, diabetes mellitus (DM) duration, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and triglyceride (TG). All risk factors were scored according to their weightings, with the highest score being 36.5. External verification showed that the model has good discrimination, AUC=0.807(95%CI 0.753-0.861). The best cutoff value is 16 points, with the sensitivity and specificity given by 85.33% and 60.45%, respectively. Conclusion: The study established a simple risk assessment model including 8 routinely available clinical parameters for predicting the risk of ESRD in type 2 diabetes.

The RIG-I-NRF2 axis regulates the mesenchymal stromal niche for bone marrow transplantation.

Bone marrow-derived mesenchymal stem cells (BMSCs) support bone formation and constitute the stromal niche in regulating hematopoietic stem cells (HSCs). Stromal niche dysfunction affects HSC engraftment during transplantation; however, the underlying mechanisms remain elusive. In the present study, we found that all-trans retinoic acid (ATRA) and inflammation stress upregulated retinoic acid-inducible gene I (RIG-I) in BMSCs. Excess RIG-I expression damaged the clonogenicity, bone-forming ability of BMSCs and particularly their stromal niche function that supports HSC expansion in vitro and engraftment in vivo. Mechanistically, RIG-I elevation promoted the degradation of NRF2, a checkpoint for antioxidant cellular response, by altering the RIG-I-Trim25-Keap1-NRF2 complex, leading to reactive oxygen species (ROS) accumulation and BMSC damage. Genetic inhibition of RIG-I sustained NRF2 protein levels and reduced ROS levels in ATRA-treated BMSCs, thus preserving their clonogenicity, bone-forming ability, and stromal niche function in supporting HSC engraftment in mice. More importantly, RIG-I inhibition recovered the ATRA-treated stromal niche function to enhance HSC engraftment and emergency myelopoiesis for innate immunity against the bacterium Listeria monocytogenes during transplantation. Overall, we identified a noncanonical role of RIG-I in the regulation of the stromal niche for HSC transplantation.

Retinoic Acid Inhibits Tumor-Associated Mesenchymal Stromal Cell Transformation in Melanoma.

Bone marrow mesenchymal stem/stromal cells (BMSCs) can be transformed into tumor-associated MSCs (TA-MSCs) within the tumor microenvironment to facilitate tumor progression. However, the underline mechanism and potential therapeutic strategy remain unclear. Here, we explored that interleukin 17 (IL-17) cooperating with IFNγ transforms BMSCs into TA-MSCs, which promotes tumor progression by recruiting macrophages/monocytes and myeloid-derived suppressor cells (MDSCs) in murine melanoma. IL-17 and IFNγ transformed TA-MSCs have high expression levels of myelocyte-recruiting chemokines (CCL2, CCL5, CCL7, and CCL20) mediated by activated NF-κB signaling pathway. Furthermore, retinoic acid inhibits NF-κB signaling, decreases chemokine expression, and suppresses the tumor-promoting function of transformed TA-MSCs by prohibiting the recruitment of macrophages/monocytes and MDSCs in the tumor microenvironment. Overall, our findings demonstrate that IL-17 collaborating with IFNγ to induce TA-MSC transformation, which can be targeted by RA for melanoma treatment.

Single-Cell Atlas Reveals Fatty Acid Metabolites Regulate the Functional Heterogeneity of Mesenchymal Stem Cells.

Bone marrow mesenchymal stem cells (MSCs) are widely used clinically due to their versatile roles in multipotency, immunomodulation, and hematopoietic stem cell (HSC) niche function. However, cellular heterogeneity limits MSCs in the consistency and efficacy of their clinical applications. Metabolism regulates stem cell function and fate decision; however, how metabolites regulate the functional heterogeneity of MSCs remains elusive. Here, using single-cell RNA sequencing, we discovered that fatty acid pathways are involved in the regulation of lineage commitment and functional heterogeneity of MSCs. Functional assays showed that a fatty acid metabolite, butyrate, suppressed the self-renewal, adipogenesis, and osteogenesis differentiation potential of MSCs with increased apoptosis. Conversely, butyrate supplement significantly promoted HSC niche factor expression in MSCs, which suggests that butyrate supplement may provide a therapeutic approach to enhance their HSC niche function. Overall, our work demonstrates that metabolites are essential to regulate the functional heterogeneity of MSCs.

[Palm vein recognition based on end-to-end convolutional neural network].

OBJECTIVE: We propose a novel palm-vein recognition model based on the end-to-end convolutional neural network. In this model, the convolutional layer and the pooling layer were alternately connected to extract the image features, and the categorical attribute was estimated simultaneously via the neural network classifier. The classification error was minimized via the mini-batch stochastic gradient descent algorithm with momentum to optimize the feature descriptor along with the direction of the gradient descent. Four strategies including data augmentation, batch normalization, dropout, and L2 parameter regularization were applied in the model to reduce the generalization error. The experimental results showed that for classifying 500 subjects form PolyU database and a self-established database, this model achieved identification rates of 99.90% and 98.05%, respectively, with an identification time for a single sample less than 9 ms. The proposed approach, as compared with the traditional method, could improve the accuracy of palm vein recognition in clincal applications and provides a new approach to palm vein recognition.

Squeezed Trajectory Design for Peak RF and Integrated RF Power Reduction in Parallel Transmission MRI.

High peak RF amplitude and excessive specific absorption rate (SAR) are two critical concerns for hardware implementation and patient safety in scientific and clinical research for high field MRI using parallel transmissions (pTX). In this paper, we introduce a squeezing strategy to reduce peak RF amplitude and integrated RF power via direct reshaping of the k-space trajectory. In the existing peak RF / integrated RF power optimization methods gradient amplitude or slew rate is reduced, but the k-space trajectory remains unchanged. Unlike these traditional methods, we worked directly in the excitation k-space to reshape k-space traversal by a squeezing vector in order to achieve peak RF and total RF power optimization, using a particle swarm optimization algorithm. The squeezing strategy was applied to the conventional variable density spiral (CVDS) and the variable rate selective excitation (VERSE) trajectories, dubbed SVDS (squeezed variable density spiral) and SVERSE (squeezing trajectory with VERSE), respectively, for different excitation profiles of small or large tip angles. Pulse acceleration and off-resonance effects were evaluated for an 8-ch pTX via Bloch simulation. CVDS, VERSE, SVDS, and SVERSE pulses were implemented on a 3T scanner with a 2-ch pTX. Phantom and in vivo experiments were performed for reduced FOV (rFOV) imaging. The results show that SVDS pulses simultaneously reduce integrated RF power and peak RF by about 30% on average compared to CVDS pulses for a square pattern ( $80\times80$ mm2) with flip angles of 30°, 90°, and 180°. Compared with the VERSE method under the same peak RF constraints, the SVDS method reduces integrated RF power by an average of 20% for small tip excitations for profiles of slice, rectangular, square, and circle, and has slightly reduced excitation accuracy slightly (about 0.6%, from 6.8% to 7.4%). The SVERSE method shortens the duration of the VERSE pulse by 12.8% at large ti p angle (180°). Feasibility for rFOV imaging was demonstrated with phantom and in vivo experiments with squeezed pulses.

Referenceless one-dimensional Nyquist ghost correction in multicoil single-shot spatiotemporally encoded MRI.

Single-shot spatiotemporally encoded (SPEN) MRI is a novel fast imaging method capable of retaining the time efficiency of single-shot echo planar imaging (EPI) but with distortion artifacts significantly reduced. Akin to EPI, the phase inconsistencies between mismatched even and odd echoes also result in the so-called Nyquist ghosts. However, the characteristic of the SPEN signals provides the possibility of obtaining ghost-free images directly from even and odd echoes respectively, without acquiring additional reference scans. In this paper, a theoretical analysis of the Nyquist ghosts manifested in single-shot SPEN MRI is presented, a one-dimensional correction scheme is put forward capable of maintaining definition of image features without blurring when the phase inconsistency along SPEN encoding direction is negligible, and a technique is introduced for convenient and robust correction of data from multi-channel receiver coils. The effectiveness of the proposed processing pipeline is validated by a series of experiments conducted on simulation data, in vivo rats and healthy human brains. The robustness of the method is further verified by implementing distortion correction on ghost corrected data.

Evaluating the Influence of Spatial Resampling for Motion Correction in Resting-State Functional MRI.

Head motion is one of major concerns in current resting-state functional MRI studies. Image realignment including motion estimation and spatial resampling is often applied to achieve rigid-body motion correction. While the accurate estimation of motion parameters has been addressed in most studies, spatial resampling could also produce spurious variance, and lead to unexpected errors on the amplitude of BOLD signal. In this study, two simulation experiments were designed to characterize these variance related with spatial resampling. The fluctuation amplitude of spurious variance was first investigated using a set of simulated images with estimated motion parameters from a real dataset, and regions more likely to be affected by spatial resampling were found around the peripheral regions of the cortex. The other simulation was designed with three typical types of motion parameters to represent different extents of motion. It was found that areas with significant correlation between spurious variance and head motion scattered all over the brain and varied greatly from one motion type to another. In the last part of this study, four popular motion regression approaches were applied respectively and their performance in reducing spurious variance was compared. Among them, Friston 24 and Voxel-specific 12 model (Friston et al., 1996), were found to have the best outcomes. By separating related effects during fMRI analysis, this study provides a better understanding of the characteristics of spatial resampling and the interpretation of motion-BOLD relationship.