Negative Emotions Recruit the Parabrachial Nucleus Efferent to the VTA to Disengage Instrumental Food Seeking.

The parabrachial nucleus (PBN) interfaces between taste and feeding systems and is also an important hub for relaying distress information and threats. Despite that the PBN sends projections to the ventral tegmental area (VTA), a heterogeneous brain region that regulates motivational behaviors, the function of the PBN-to-VTA connection remains elusive. Here, by using male mice in several behavioral paradigms, we discover that VTA-projecting PBN neurons are significantly engaged in contextual fear, restraint or mild stress but not palatable feeding, visceral malaise, or thermal pain. These results suggest that the PBN-to-VTA input may relay negative emotions under threat. Consistent with this notion, optogenetic activation of PBN-to-VTA glutamatergic input results in aversion, which is sufficient to override palatable feeding. Moreover, in a palatable food-reinforced operant task, we demonstrate that transient optogenetic activation of PBN-to-VTA input during food reward retrieval disengages instrumental food-seeking behaviors but spares learned action-outcome association. By using an activity-dependent targeting approach, we show that VTA DA neurons are disengaged by the PBN afferent activation, implicating that VTA non-DA neurons may mediate PBN afferent regulation. We further show that optogenetic activation of VTA neurons functionally recruited by the PBN input results in aversion, dampens palatable feeding, and disengages palatable food self-administration behavior. Finally, we demonstrate that transient activation of VTA glutamatergic, but not GABAergic, neurons recapitulates the negative regulation of the PBN input on food self-administration behavior. Together, we reveal that the PBN-to-VTA input conveys negative affect, likely through VTA glutamatergic neurons, to disengage instrumental food-seeking behaviors.SIGNIFICANCE STATEMENT The PBN receives multiple inputs and thus is well positioned to route information of various modalities to engage different downstream circuits to attend or respond accordingly. We demonstrate that the PBN-to-VTA input conveys negative affect and then triggers adaptive prioritized responses to address pertinent needs by withholding ongoing behaviors, such as palatable food seeking or intake shown in the present study. It has evolutionary significance because preparing to cope with stressful situations or threats takes priority over food seeking to promote survival. Knowing how appropriate adaptive responses are generated will provide new insights into circuitry mechanisms of various coping behaviors to changing environmental stimuli.

SULT2B1-CS-DOCK2 axis regulates effector T-cell exhaustion in HCC microenvironment.

BACKGROUND AND AIMS: HCC is a malignant disease. Compared with tyrosine kinase inhibitors (the classical therapy), immune checkpoint inhibitors are more effective in the treatment of HCC, despite their limited efficacy. Among these restricted factors, exhaustion of tumor-infiltrated lymphocytes, especially CD8 + T cells, is a core event. We aimed to determine the key factors contributing to CD8 + T-cell infiltration in HCC and investigate the underlying mechanisms. APPROACH AND RESULTS: Using machine learning and multiplex immunohistochemistry analysis, we showed that dedicator of cytokinesis protein 2 (DOCK2) was a potential indicator of infiltrated CD8 + T cells in HCC. Using RNA sequencing, flow cytometry analysis, and mouse HCC models, we demonstrated that DOCK2 inactivation accounted for infiltrated CD8 + T-cell exhaustion in tumors. Using quasi-targeted metabolomics, mass spectrum, and mass cytometry by time of flight analysis, we found that cholesterol sulfate synthesized by sulfotransferase 2B1 in tumor cells suppressed DOCK2 enzymatic activity of T cells. Through virtual screening, molecular docking simulation, and experiments validation, we demonstrated that tolazamide reversed DOCK2 inactivation-mediated CD8 + T-cell exhaustion and enhanced anti-programmed death-ligand 1 antibody+apatinib immunotherapeutic effects on HCC. CONCLUSIONS: This study indicates that DOCK2 controls CD8 + T-cell infiltration in HCC, and cholesterol sulfate synthesized by sulfotransferase 2B1 in tumor cells promotes effector T-cell exhaustion. The findings suggest that the usage of conventional drugs affects immunotherapy efficacy in HCC patients.

GNAQ R183Q somatic mutation contributes to aberrant arteriovenous specification in Sturge-Weber syndrome through Notch signaling.

Episcleral vasculature malformation is a significant feature of Sturge-Weber syndrome (SWS) secondary glaucoma, the density and diameter of which are correlated with increased intraocular pressure. We previously reported that the GNAQ R183Q somatic mutation was located in the SWS episclera. However, the mechanism by which GNAQ R183Q leads to episcleral vascular malformation remains poorly understood. In this study, we investigated the correlation between GNAQ R183Q and episcleral vascular malformation via surgical specimens, human umbilical vein endothelial cells (HUVECs), and the HUVEC cell line EA.hy926. Our findings demonstrated a positive correlation between episcleral vessel diameter and the frequency of the GNAQ R183Q variant. Furthermore, the upregulation of genes from the Notch signaling pathway and abnormal coexpression of the arterial marker EphrinB2 and venous marker EphB4 were demonstrated in the scleral vasculature of SWS. Analysis of HUVECs overexpressing GNAQ R183Q in vitro confirmed the upregulation of Notch signaling and arterial markers. In addition, knocking down of Notch1 diminished the upregulation of arterial markers induced by GNAQ R183Q. Our findings strongly suggest that GNAQ R183Q leads to malformed episcleral vasculatures through Notch-induced aberrant arteriovenous specification. These insights into the molecular basis of episcleral vascular malformation will provide new pathways for the development of effective treatments for SWS secondary glaucoma.

Evaluation the Effect of Anthracyclines on Cardiac Function in Children Lymphoma Survivors by Left Ventricular Myocardial Work.

Anthracycline chemotherapy is associated with the left ventricular (LV) dysfunction, but the conventional echocardiographic parameter is insensitive in detecting subclinical cardiac dysfunction, and the role of echocardiography in children cancer survivors (CCSs) has not been well established. Here, the myocardial work (MW) was employed to evaluate the early effect of the anthracyclines on LV function in children lymphoma survivors, as well as to explore the clinical application value of this modality. 51 children lymphoma survivors treated with anthracyclines were included. During the treatments, the echocardiography was performed at baseline (T0 phase), the 3rd (T1 phase) and 6th (T2 phase) chemotherapeutic cycle, respectively. After that, the conventional echocardiographic parameters, LV global longitudinal strain (GLS), and global myocardial work (GMW) parameters were obtained. Finally, these echocardiographic parameters were compared to distinguish the differences among three groups, and correlation analysis was used to identify relationship between GMW parameters and LV GLS. Compared with the baseline, we found that there are no significant differences for LVEF and other conventional echocardiographic parameters after chemotherapy, but the value of LV lateral E/E' increased at T1 and T2 group. The GLS, global work index, global constructed work, and global work efficiency were decreased, while the global wasted work was increased after chemotherapy (all P < 0.05). The correlation analysis showed that the GLS has significant correlation with GMW parameters (all P < 0.001). The MW, as a new noninvasive echocardiography modality, could be used to quantitatively evaluate the LV MW in children lymphoma survivors treated with anthracyclines, which providing a sensitive method to early detect the children's LV dysfunction after the chemotherapy.

Impact of periodontitis on type 2 diabetes: a bioinformatic analysis.

BACKGROUND: Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. METHODS: A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. RESULTS: Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117-1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001-1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849-13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). CONCLUSIONS: This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets.

Preoperative Subtyping of WHO Grade 1 Meningiomas Using a Single-Shot Ultrafast MR T2 Mapping.

BACKGROUND: Meningioma subtype is crucial in treatment planning and prognosis delineation, for grade 1 meningiomas. T2 relaxometry could provide detailed microscopic information but is often limited by long scanning times. PURPOSE: To investigate the potential of T2 maps derived from multiple overlapping-echo detachment imaging (MOLED) for predicting meningioma subtypes and Ki-67 index, and to compare the diagnostic efficiency of two different region-of-interest (ROI) placements (whole-tumor and contrast-enhanced, respectively). STUDY TYPE: Prospective. PHANTOM/SUBJECTS: A phantom containing 11 tubes of MnCl2 at different concentrations, eight healthy volunteers, and 75 patients with grade 1 meningioma. FIELD STRENGTH/SEQUENCE: 3 T scanner. MOLED, T2-weighted spin-echo sequence, T2-dark-fluid sequence, and postcontrast T1-weighted gradient echo sequence. ASSESSMENT: Two ROIs were delineated: the whole-tumor area (ROI1) and contrast-enhanced area (ROI2). Histogram parameters were extracted from T2 maps. Meningioma subtypes and Ki-67 index were reviewed by a neuropathologist according to the 2021 classification criteria. STATISTICAL TESTS: Linear regression, Bland-Altman analysis, Pearson's correlation analysis, independent t test, Mann-Whitney U test, Kruskal-Wallis test with Bonferroni correction, and multivariate logistic regression analysis with the P-value significance level of 0.05. RESULTS: The MOLED T2 sequence demonstrated excellent accuracy for phantoms and volunteers (Meandiff = -1.29%, SDdiff = 1.25% and Meandiff = 0.36%, SDdiff = 2.70%, respectively), and good repeatability for volunteers (average coefficient of variance = 1.13%; intraclass correlation coefficient = 0.877). For both ROI1 and ROI2, T2 variance had the highest area under the curves (area under the ROC curve = 0.768 and 0.761, respectively) for meningioma subtyping. There was no significant difference between the two ROIs (P = 0.875). Significant correlations were observed between T2 parameters and Ki-67 index (r = 0.237-0.374). DATA CONCLUSION: MOLED T2 maps can effectively differentiate between meningothelial, fibrous, and transitional meningiomas. Moreover, T2 histogram parameters were significantly correlated with the Ki-67 index. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Microbiome-based therapies for periodontitis and peri-implantitis.

OBJECTIVES: Periodontitis and peri-implantitis are oral infectious-inflammatory diseases associated with oral microbial dysbiosis. Microbiome-based therapies, characterized by manipulation of the microbiota, are emerging as promising therapeutic approaches to resolve the microbial dysbiosis and associated dysregulation of immune system. This review aims at summarizing recent progress on microbiome-based therapies in periodontitis and peri-implantitis, promoting a further understanding of the related therapeutic mechanisms. SUBJECTS AND METHODS: Pertinent literatures focused on microbiome-based therapies for periodontitis and peri-implantitis are obtained from PubMed and Web of Science. RESULTS: In this article, we review the roles and therapeutic mechanisms of four microbiome-based therapies, including probiotics, postbiotics, predatory bacteria and phages, and microbiota transplantation, in the management of periodontitis and peri-implantitis. Challenges facing this field are also discussed, highlighting the areas that require more attention and investigation. CONCLUSIONS: Microbiome-based therapies may serve as effective treatment for periodontitis and peri-implantitis. This review presents a new viewpoint to this field.

Evaluation of Schlemm's canal with swept-source optical coherence tomography in primary angle-closure disease.

PURPOSE: To perform an in vivo evaluation of the changes in Schlemm's canal (SC) among patients with primary angle-closure disease (PACD) using swept-source optical coherence tomography (SS-OCT). METHODS: Patients diagnosed with PACD who had not undergone surgery were recruited. The SS-OCT quadrants scanned herein included the nasal and temporal sections at 3 and 9 o'clock, respectively. The diameter and cross-sectional area of the SC were measured. A linear mixed-effects model was performed to analyze the effects of parameters on the SC changes. The hypothesis of interest was related to the angle status (iridotrabecular contact, ITC/open angle, OPN), which was further explored with pairwise comparisons of the estimated marginal means (EMMs) of the SC diameter and SC area. In the ITC regions, the relationship between the trabecular-iris contact length (TICL) percentage and SC parameters was also studied by a mixed model. RESULTS: A total of 49 eyes of 35 patients were included for measurements and analysis. The percentage of observable SCs in the ITC regions was only 58.5% (24/41), whereas it was 86.0% (49/57) in the OPN regions (χ2 = 9.44, p = 0.002). ITC was significantly associated with a decreasing SC size. The EMMs for the diameter and cross-sectional area of SC at the ITC and OPN regions were 203.34 µm versus 261.41 µm (p = 0.006) and 3174.43 µm2 versus 5347.63 µm2 (p = 0.022), respectively. Sex, age, spherical equivalent refraction, intraocular pressure, axial length, extent of angle closure, history of acute attack and treatment with LPI were not significantly associated with SC parameters. In the ITC regions, a larger TICL percentage was significantly associated with a decrease in SC diameter and area (p = 0.003 and 0.019, respectively). CONCLUSIONS: The morphologies of SC could be affected by the angle status (ITC/OPN) in patients with PACD, and ITC was significantly associated with a decreasing SC size. These changes in SC as described by OCT scans might help to elucidate the progression mechanisms of PACD.

Combined Trabeculotomy-Non-Penetrating Deep Sclerectomy for Glaucoma in Sturge-Weber Syndrome.

INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of combined trabeculotomy-non-penetrating deep sclerectomy (CTNS) in the treatment of Sturge-Weber syndrome (SWS) secondary glaucoma. METHODS: This retrospective study reviewed cases that underwent CTNS as initial surgery for SWS secondary glaucoma at our Ophthalmology Department center from April 2019 to August 2020. Surgical success was defined as an intraocular pressure (IOP) ≤ 21 mm Hg with (qualified success) or without (complete success) the use of anti-glaucoma medications. IOP >21 mm Hg or <5 mm Hg despite 3 or more applications of anti-glaucoma medications on 2 consecutive follow-up visits or at the last follow-up, performance of additional glaucoma (IOP-lowering) surgery, or with vision-threatening complications were classified as failure. RESULTS: A total of 22 eyes of 21 patients were included. Twenty-one eyes were of early-onset type and 1 eye was of adulthood onset. For Kaplan-Meier survival analysis, the overall success rates at 1st and 2nd years were 95.2% and 84.9%, while the complete success rates at 1st and 2nd years were 42.9% and 36.7%. At the last follow-up (22.3 ± 4.0 months, range: 11.2∼31.2), overall success was achieved in 19 (85.7%) eyes and complete success in 12 (52.4%) eyes. Postoperative complications included transient hyphema (11/22, 50.0%) and transient Ⅰ degree shallow anterior chamber (1/22, 4.5%), and retinal detachment (1/22, 4.5%). No other severe com plications were detected during the follow-up. CONCLUSION: CTNS significantly reduces IOP in SWS secondary glaucoma patients who have serious episcleral vascular malformation. CTNS in SWS secondary glaucoma patients is safe and effective for short and medium periods. A randomized controlled study comparing the long-term prognosis of SWS early-onset and late-onset glaucoma underwent CTNS is worth conducting.

Hydrophobic Nanoporous Silver with ZIF Encapsulation for Nitrogen Reduction Electrocatalysis.

Electrochemical nitrogen reduction reaction (ENRR) offers a sustainable alternative to the environmentally hazardous Haber-Bosch process for producing ammonia. However, it suffers from an unsatisfactory performance due to its limited active sites and competitive hydrogen evolution reaction. Herein, we design a hydrophobic oleylamine-modified zeolitic imidazolate framework-coated nanoporous silver composite structure (NPS@O-ZIF). The composite achieves a high ammonia yield of (41.3 ± 0.9) µg·h-1·cm-2 and great Faradaic efficiency of (31.7 ± 1.2)%, overcoming the performances of NPS@ZIF and traditional silver nanoparticles@O-ZIF. Our strategy affords more active sites and accessible channels for reactant species due to the porous structure of NPS cores and restrains the evolution of hydrogen by introducing the hydrophobic molecule coated on the ZIF surfaces. Hence, the design of the hydrophobic core-shell composite catalyst provides a valuably practical strategy for ENRR as well as other water-sensitive reactions.

Modulating Orientational Order to Organize Polyhedral Nanoparticles into Plastic Crystals and Uniform Metacrystals.

In nanoparticle self-assembly, the current lack of strategy to modulate orientational order creates challenges in isolating large-area plastic crystals. Here, we achieve two orientationally distinct supercrystals using one nanoparticle shape, including plastic crystals and uniform metacrystals. Our approach integrates multi-faceted Archimedean polyhedra with molecular-level surface polymeric interactions to tune nanoparticle orientational order during self-assembly. Experiments and simulations show that coiled surface polymer chains limit interparticle interactions, creating various geometrical configurations among Archimedean polyhedra to form plastic crystals. In contrast, brush-like polymer chains enable molecular interdigitation between neighboring particles, favoring consistent particle configurations and result in uniform metacrystals. Our strategy enhances supercrystal diversity for polyhedra comprising multiple nondegenerate facets.

Nanoporous Gold Embedded ZIF Composite for Enhanced Electrochemical Nitrogen Fixation.

The electrochemical nitrogen reduction reaction (NRR) offers an energy-saving and environmentally friendly approach to produce ammonia under ambient conditions. However, traditional catalysts have extremely poor NRR performances because of their low activity and the competitive hydrogen evolution reaction. The high catalytic activity of nanoporous gold (NPG) and the hydrophobicity and molecular concentrating effect of the zeolitic imidazolate framework-8 (ZIF-8) were incorporated in the NPG@ZIF-8 nanocomposite so that the ZIF-8 shell could weaken hydrogen evolution and retard reactant diffusion. A highest Faradaic efficiency of 44 % and an excellent rate of ammonia production of (28.7±0.9) µg h-1 cm-2 were achieved, which are superior to traditional gold nanoparticles and NPG. Moreover, the composite catalyst shows high electrochemical stability and selectivity (98 %). The superior NRR performance makes NPG@ZIF-8 one of the most promising water-based NRR electrocatalysts for ammonia production.

A Chemical Approach To Break the Planar Configuration of Ag Nanocubes into Tunable Two-Dimensional Metasurfaces.

Current plasmonic metasurfaces of nanocubes are limited to planar configurations, restricting the ability to create tailored local electromagnetic fields. Here, we report a new chemical strategy to achieve tunable metasurfaces with nonplanar nanocube orientations, creating novel lattice-dependent field localization patterns. We manipulate the interfacial behaviors of Ag nanocubes by controlling the ratio of hydrophilic/hydrophobic molecules added in a binary thiol mixture during the surface functionalization step. The nanocube orientation at an oil/water interface can consequently be continuously tuned from planar to tilted and standing configurations, leading to the organization of Ag nanocubes into three unique large-area metacrystals, including square close-packed, linear, and hexagonal lattices. In particular, the linear and hexagonal metacrystals are unusual open lattices comprising nonplanar nanocubes, creating unique local electromagnetic field distribution patterns. Large-area "hot hexagons" with significant delocalization of hot spots form in the hexagonal metacrystal. With a lowest packing density of 24%, the hexagonal metacrystal generates nearly 350-fold stronger surface-enhanced Raman scattering as compared to the other denser-packing metacrystals, demonstrating the importance of achieving control over the geometrical and spatial orientation of the nanocubes in the metacrystals.

Assembling substrate-less plasmonic metacrystals at the oil/water interface for multiplex ultratrace analyte detection.

Current substrate-less SERS platforms are limited to uncontrolled aggregation of plasmonic nanoparticles or quasi-crystalline arrays of spherical nanoparticles, with no study on how the lattice structures formed by nanoparticle self-assembly affect their detection capabilities. Here, we organize Ag octahedral building blocks into two large-area plasmonic metacrystals at the oil/water interface, and investigate their in situ SERS sensing capabilities. Amphiphilic octahedra assemble into a hexagonal close-packed metacrystal, while hydrophobic octahedra assemble into an open square metacrystal. The lower packing density square metacrystal gives rise to much stronger SERS enhancement than the denser packing hexagonal metacrystal, arising from the larger areas of plasmonic hotspots within the square metacrystal at the excitation wavelength. We further demonstrate the ability of the square metacrystal to achieve quantitative ultratrace detection of analytes from both the aqueous and organic phases. Detection limits are at the nano-molar levels, with analytical enhancement factors reaching 10(8). In addition, multiplex detection across both phases can be achieved in situ without any loss of signal quantitation.

Chirality effects on proline-substituted serine octamers revealed by infrared photodissociation spectroscopy.

Chiral preferences exist in proline-substituted serine octamers. For ions of [L-Ser6 + Pro2]H(+), the stability preference is [L-Ser6 + L-Pro2]H(+) > [L-Ser6 + D-Pro2]H(+) > [L-Ser6 + L-Pro1 + D-Pro1]H(+). Infrared photodissociation (IRPD) experiments were performed for the observed proline-substituted octamer ions in the range from 2700 to 3750 cm(-1). Chiral differentiation was achieved using the IRPD method, and the progressive changes in IRPD spectra due to the substitution were also reflected.

Dioscin Alleviates Periodontitis by Inhibiting NLRP3 Inflammasome Activation via Regulation of K+ Homeostasis and Mitochondrial Function.

Gingival inflammation and alveolar bone loss are characteristic manifestations of periodontitis. Interleukin (IL)-1ß, the maturation of which is mainly regulated by NOD-like receptor protein (NLRP) 3 inflammasome, not only amplifies the inflammatory response but also triggers osteoclastogenesis, thereby accelerating the progression of periodontitis. Dioscin, a natural steroid saponin, has been shown to inhibit NLRP3 inflammasome. Nevertheless, research on the effectiveness of Dioscin for the management of periodontitis remains scarce. In this study, Dioscin was found to dramatically reduce the integral components of NLRP3 inflammasome, ultimately limiting IL-1ß secretion. Notably, the inhibitory impact of Dioscin on NLRP3 inflammasome might be exerted by curbing the generation of mitochondrial (mt) reactive oxygen species (ROS) and oxidized (ox) mtDNA, which were mediated by inhibition of K+ efflux. Furthermore, Dioscin effectively alleviated periodontitis in mice. Overall, the results established that Dioscin could alleviate periodontitis by inhibiting NLRP3 inflammasome via modulation of the K+ efflux-mtROS-ox-mtDNA pathway, holding the potential to treat periodontitis and other NLRP3-driven inflammatory diseases.

Expanding RNA editing toolkit using an IDR-based strategy.

RNA base editors should ideally be free of immunogenicity, compact, efficient, and specific, which has not been achieved for C > U editing. Here we first describe a compact C > U editor entirely of human origin, created by fusing the human C > U editing enzyme RESCUE-S to Cas inspired RNA targeting system (CIRTS), a tiny, human-originated programmable RNA-binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient. Remarkably, a short histidine-rich domain (HRD), which is derived from the internal disordered region (IDR) in the human CYCT1, a protein capable of liquid-liquid phase separation (LLPS), enhanced V1 editing at on-targets as well as off-targets, the latter effect being minor. The V1-HRD fusion protein formed puncta characteristic of LLPS, and various other IDRs (but not an LLPS-impaired mutant) could replace HRD to effectively induce puncta and potentiate V1, suggesting that the diverse domains acted via a common, LLPS-based mechanism. Importantly, the HRD fusion strategy was applicable to various other types of C > U RNA editors. Our study expands the RNA editing toolbox and showcases a general method for stimulating C > U RNA base editors.

Neutrophil and macrophage crosstalk might be a potential target for liver regeneration.

The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single-cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non-parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

Positive Progesterone Receptor Expression in Meningioma May Increase the Transverse Relaxation: First Prospective Clinical Trial Using Single-Shot Ultrafast T2 Mapping.

RATIONALE AND OBJECTIVES: This project aims to investigate the diagnostic performance of multiple overlapping-echo detachment imaging (MOLED) technique-derived transverse relaxation time (T2) maps in predicting progesterone receptor (PR) and S100 expression in meningiomas. MATERIALS AND METHODS: 63 meningioma patients were enrolled from October 2021 to August 2022, who underwent a complete routine magnetic resonance imaging and T2 MOLED, which can characterize the whole brain transverse relaxation time within 32 seconds in a single scan. After the surgical resection of meningiomas, the expression levels of PR and S100 were determined by an experienced pathologist using immunohistochemistry techniques. Histogram analysis was performed in tumor parenchyma based on the parametric maps. Independent t test and Mann-Whitney U test were applied for the comparison of histogram parameters between different groups, with a significance level of P < .05. Logistic regression and receiver operating characteristic (ROC) analysis with 95% confidence interval were conducted for the diagnostic efficiency evaluation. RESULTS: PR-positive group had significantly elevated T2 histogram parameters (P = .001-.049) compared to the PR-negative group. The multivariate logistic regression model with T2 showed the highest area under the ROC curve (AUC) for predicting PR expression (AUC=0.818). Additionally, the multivariate model also had the best diagnostic performance for predicting meningioma S100 expression (AUC=0.768). CONCLUSION: The MOLED technique-derived T2 maps can distinguish PR and S100 status in meningiomas preoperatively.