A promising approach for quantifying focal stroke modeling and assessing stroke progression: optical resolution photoacoustic microscopy photothrombosis.

JOURNAL/nrgr/04.03/01300535-202507000-00025/figure1/v/2024-09-09T124005Z/r/image-tiff To investigate the mechanisms underlying the onset and progression of ischemic stroke, some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex. However, these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied, although ischemic stroke is strongly age-related. In this study, we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser. We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation. Moreover, we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke. Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages, thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

The short-term efficacy of neoadjuvant SOX versus SOX plus immune checkpoint inhibitor following laparoscopic gastrectomy for locally advanced gastric cancer: a multicenter retrospective cohort study in China.

BACKGROUND: This study aims to evaluate the short-term efficacy for locally advanced gastric cancer (LAGC) who accepted laparoscopic gastrectomy (LG) after neoadjuvant SOX versus SOX plus immune checkpoint inhibitors (ICIs). METHODS: LAGC patients who accepted LG after neoadjuvant SOX (SOX-LG, n = 169) and SOX plus ICIs (SOX + ICIs-LG, n = 140) in three medical centers between Jan 2020 and Mar 2024 were analyzed. We compared the tumor regression, treatment-related adverse events (TRAEs), perioperative safety between two groups, and explored the risk factors of postoperative complications (POCs) for LG after neoadjuvant therapy. RESULTS: The baseline characteristics were comparable between two groups (P > 0.05). SOX + ICIs-LG group acquired a higher proportion of objective response (63.6% vs. 46.7%, P = 0.003), major pathological response (43.6% vs. 31.4%, P = 0.001), and pathological complete response (17.9% vs. 9.5%, P = 0.030). There were no significant differences in the TRAEs rates, operation time, R0 resection, retrieved lymph nodes, postoperative first flatus, and hospitalized days, overall and severe POCs between two groups (P > 0.05). Patients in the SOX-ICIs-LG group had lower estimated blood loss (EBL) compared with SOX-LG (P = 0.001). Multivariate analysis showed that more EBL (P = 0.003) and prognostic nutritional index (PNI) < 40 (P = 0.005) were independent risk factors of POCs for LG after neoadjuvant therapy. CONCLUSION: Neoadjuvant SOX plus ICIs brings better tumor regression and similar TRAEs compared with SOX alone for LAGC. SOX + ICIs-LG is safe and feasible to conduct with less EBL. Surgeons should focus on the perioperative management to control POCs for patients with PNI < 40 and more EBL.

Common and unique brain aging patterns between females and males quantified by large-scale deep learning.

There has been extensive evidence that aging affects human brain function. However, there is no complete picture of what brain functional changes are mostly related to normal aging and how aging affects brain function similarly and differently between males and females. Based on resting-state brain functional connectivity (FC) of 25,582 healthy participants (13,373 females) aged 49-76 years from the UK Biobank project, we employ deep learning with explainable AI to discover primary FCs related to progressive aging and reveal similarity and difference between females and males in brain aging. Using a nested cross-validation scheme, we conduct 4200 deep learning models to classify all paired age groups on the main data for females and males separately and then extract gender-common and gender-specific aging-related FCs. Next, we validate those FCs using additional 21,000 classifiers on the independent data. Our results support that aging results in reduced brain functional interactions for both females and males, primarily relating to the positive connectivity within the same functional domain and the negative connectivity between different functional domains. Regions linked to cognitive control show the most significant age-related changes in both genders. Unique aging effects in males and females mainly involve the interaction between cognitive control and the default mode, vision, auditory, and frontoparietal domains. Results also indicate females exhibit faster brain functional changes than males. Overall, our study provides new evidence about common and unique patterns of brain aging in females and males.

Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension.

BACKGROUND: Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy (HE). It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt (TIPS) is related to postoperative HE. AIM: To investigate the relationship between spleen volume and the occurrence of HE. METHODS: This study included 135 patients with liver cirrhosis who underwent TIPS, and liver and spleen volumes were elevated upon computed tomography imaging. The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes. Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE (OHE). Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk. RESULTS: The results showed that 37 (27.2%) of 135 patients experienced OHE during a 1-year follow-up period. Compared with preoperative spleen volume (901.30 ± 471.90 cm3), there was a significant decrease in spleen volume after TIPS (697.60 ± 281.0 cm3) in OHE patients. As the severity of OHE increased, the spleen volume significantly decreased (P < 0.05). Compared with patients with a spleen volume ≥ 782.4 cm3, those with a spleen volume < 782.4 cm3 had a higher incidence of HE (P < 0.05). Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE (hazard ratio = 0.494, P < 0.05). Restricted cubic spline model showed that with an increasing spleen volume, OHE risk showed an initial increase and then decrease (P < 0.05). CONCLUSION: Spleen volume is related to the occurrence of OHE after TIPS. Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

A multi-mode stretching apparatus for in situ synchrotron x-ray scattering of polymer materials.

A compact and versatile tensile apparatus for polymer materials is designed and fabricated. Three distinct stretching modes are developed: constant speed, cyclic, and sinusoidal, with adjustable speeds ranging from 0.001 to 120 mm/s. To capture the true strain of the central region, a high-speed camera has been integrated into the apparatus. The temperature of the sample chamber is controlled by flowing air, enabling a homogeneous temperature in the range of RT ∼200 °C. The apparatus is particularly suitable for a synchrotron beamline. The structural evolution of natural rubber during sinusoidal stretching is investigated by in situ wide-angle x-ray scattering. Scattering patterns, force, clamp position, and sample images are saved simultaneously during stretching. Notably, the results reveal a sinusoidal variation in the crystallinity of crosslinked natural rubber when a sinusoidal strain was applied to the sample. The integration of advanced measurement techniques and controlled experimental conditions ensures the acquisition of reliable and accurate data, providing valuable insights into the structural evolution of materials under dynamic deformation conditions.

Microscopic Study on Superexchange Dynamics of Composite Spin-1 Bosons.

We report on an experimental simulation of the spin-1 Heisenberg model with composite bosons in a one-dimensional chain based on the two-component Bose-Hubbard model. Exploiting our site- and spin-resolved quantum gas microscope, we observed faster superexchange dynamics of the spin-1 system compared to its spin-1/2 counterpart, which is attributed to the enhancement effect of multi-bosons. We further probed the nonequilibrium spin dynamics driven by the superexchange and single-ion anisotropy terms, unveiling the linear expansion of the spin-spin correlations, which is limited by the Lieb-Robinson bound. Based on the superexchange process, we prepared and verified the entangled qutrits pairs with these composite spin-1 bosons, potentially being applied in qutrit-based quantum information processing.

Risk factor analysis and nomogram construction of postoperative complications for patients with locally advanced gastric cancer who received neoadjuvant immunotherapy and chemotherapy.

Introduction: The combination of neoadjuvant immunotherapy and chemotherapy (NICT) has become a common treatment regimen for locally advanced gastric cancer (LAGC). However, the safety and efficacy of radical gastrectomy following NICT (NICT-G) remain controversial. This study aimed to analyze the risk factors influencing postoperative complications (POCs) after NICT-G. Additionally, it aimed to construct a nomogram to provide a clinical reference for predicting POCs. Methods: This study included 177 patients who received NICT-G at the Chinese PLA General Hospital First Medical Center from January 2020 to January 2024. Univariable and multivariable logistic regression models were used to evaluate the risk factors influencing POCs, and a nomogram model was constructed. To evaluate the discrimination and accuracy of the nomogram model, the area under the receiver operating characteristic curve (AUC) and the calibration curve were measured. Results: In 177 patients who received NICT-G, the pathological complete response and major pathological response rates were 15.8% and 45.2%, respectively, whereas the rates of the overall and severe treatment-related adverse events were 71.8% and 15.8%, respectively. In addition, 43 (24.3%) patients developed overall POCs (Clavien-Dindo classification ≥ II). Univariable and multivariable logistic analyses showed that age ≥70 years, greater estimated blood loss, platelet/lymphocyte ratio (PLR) ≤196, neutrophil/lymphocyte ratio (NLR) >1.33, non-R0 resection, and body mass index (BMI) < 18.5 kg/m2 were independent risk factors for overall POCs (p < 0.05). The nomogram model developed using the abovementioned variables showed that the AUC (95% confidence interval [CI]) was 0.808 (95% CI): 0.731-0.885 in predicting the POC risk. The calibration curves showed that the prediction curve of the nomogram was a good fit for the actual POCs (Hosmer-Lemeshow test: χ2 = 5.76, P = 0.451). Conclusion: The independent risk factors for overall POCs in the NICT-G were age ≥ 70 years, greater estimated blood loss, PLR ≤ 196, NLR > 1.33, non-R0 resection, and BMI < 18.5 kg/m2. The nomogram model developed based on the abovementioned indicators showed better accuracy in predicting the POC risk.

Construction and validation of prognostic signatures related to mitochondria and macrophage polarization in gastric cancer.

Background: Increasing evidence reveals the involvement of mitochondria and macrophage polarisation in tumourigenesis and progression. This study aimed to establish mitochondria and macrophage polarisation-associated molecular signatures to predict prognosis in gastric cancer (GC) by single-cell and transcriptional data. Methods: Initially, candidate genes associated with mitochondria and macrophage polarisation were identified by differential expression analysis and weighted gene co-expression network analysis. Subsequently, candidate genes were incorporated in univariateCox analysis and LASSO to acquire prognostic genes in GC, and risk model was created. Furthermore, independent prognostic indicators were screened by combining risk score with clinical characteristics, and a nomogram was created to forecast survival in GC patients. Further, in single-cell data analysis, cell clusters and cell subpopulations were yielded, followed by the completion of pseudo-time analysis. Furthermore, a more comprehensive immunological analysis was executed to uncover the relationship between GC and immunological characteristics. Ultimately, expression level of prognostic genes was validated through public datasets and qRT-PCR. Results: A risk model including six prognostic genes (GPX3, GJA1, VCAN, RGS2, LOX, and CTHRC1) associated with mitochondria and macrophage polarisation was developed, which was efficient in forecasting the survival of GC patients. The GC patients were categorized into high-/low-risk subgroups in accordance with median risk score, with the high-risk subgroup having lower survival rates. Afterwards, a nomogram incorporating risk score and age was generated, and it had significant predictive value for predicting GC survival with higher predictive accuracy than risk model. Immunological analyses revealed showed higher levels of M2 macrophage infiltration in high-risk subgroup and the strongest positive correlation between risk score and M2 macrophages. Besides, further analyses demonstrated a better outcome for immunotherapy in low-risk patients. In single-cell and pseudo-time analyses, stromal cells were identified as key cells, and a relatively complete developmental trajectory existed for stromal C1 in three subclasses. Ultimately, expression analysis revealed that the expression trend of RGS2, GJA1, GPX3, and VCAN was consistent with the results of the TCGA-GC dataset. Conclusion: Our findings demonstrated that a novel prognostic model constructed in accordance with six prognostic genes might facilitate the improvement of personalised prognosis and treatment of GC patients.

Driving Fatigue Detection Based on Hybrid Electroencephalography and Eye Tracking.

EEG-based unimodal method has demonstrated substantial success in the detection of driving fatigue. Nonetheless, the data from a single modality might be not sufficient to optimize fatigue detection due to incomplete information. To address this limitation and enhance the performance of driving fatigue detection, a novel multimodal architecture combining electroencephalography (EEG) and eye tracking data was proposed in this study. Specifically, EEG and eye tracking data were separately input into encoders, generating two one-dimensional (1D) features. Subsequently, these 1D features were fed into a cross-modal predictive alignment module to improve fusion efficiency and two 1D attention modules to enhance feature representation. Furthermore, the fused features were recognized by a linear classifier. To evaluate the effectiveness of the proposed multimodal method, comprehensive validation tasks were conducted, including intra-session, cross-session, and cross-subject evaluations. In the intra-session task, the proposed architecture achieves an exceptional average accuracy of 99.93%. Moreover, in the cross-session task, our method results in an average accuracy of 88.67%, surpassing the performance of EEG-only approach by 8.52%, eye tracking-only method by 5.92%, multimodal deep canonical correlation analysis (DCCA) technique by 0.42%, and multimodal deep generalized canonical correlation analysis (DGCCA) approach by 0.84%. Similarly, in the cross-subject task, the proposed approach achieves an average accuracy of 78.19%, outperforming EEG-only method by 5.87%, eye tracking-only approach by 4.21%, DCCA method by 0.55%, and DGCCA approach by 0.44%. The experimental results conclusively illustrate the superior effectiveness of the proposed method compared to both single modality approaches and canonical correlation analysis-based multimodal methods. Overall, this study provides a new and effective strategy for driving fatigue detection.

[3D printing navigation template assisted pedicle screw placement for the treatment of typeâ ¡old odontoid fractures].

OBJECTIVE: To compare the safety and clinical efficacy of freehand and 3D printing navigation template assisted screw placement in patients with old odontoid fractures of typeⅡ. METHODS: Total of 38 patients with old odontoid fractures of typeⅡwere treated from November 2018 to December 2022, all of which presented as chronic neck pain. According to the different methods of screw insertion into the pedicle, the patients were divided into a navigation template group and a freehand group. In the navigation template group, there were 17 patients including 9 males and 8 females with an average age of (51.30±13.20) years old, disease duration was (22.18±7.59) months. In the freehand group, there 21 patients including 7 males and 14 females with an average age of (49.46±11.92) years old, disease duration was (19.52±9.17) months. The intraoperative blood loss, operation time, and postoperative drainage output were recorded and compared between two groups. The accuracy of screw placement was evaluated by CT scan. Before operation and 1 year after operation, cervical pain was assessed by visual analogue scale(VAS), neurological changes were evaluated by the Japanese Orthopaedic Association (JOA) score, and the degree of spinal cord injury was assessed by the American Spinal Injury Association (ASIA) injury scale. RESULTS: All patients were followed up for (25.31±1.21) months. The operation time of template group (112.00±20.48) min had significantly shorter than that of the freehand group(124.29±15.24) min(P<0.05), while there were no significant differences between two groups in terms of intraoperative blood loss, postoperative drainage, and hospital stay(P>0.05). At 1 year after operation, in template group and freehand group, the VAS [(2.88±0.86), (2.90±0.83)] and JOA [(14.94±1.82), (14.62±2.19)] improved with preoperative [VAS(4.71±0.92), (4.86±0.79) and JOA (12.18±2.30), (11.95±2.31)](P<0.05), with no significant difference between two groups (P>0.05). No significant improvement was observed in ASIA grading in either group at 1 year after operation(P>0.05), and there was no significant difference between two groups(P>0.05). The template group had significantly better accuracy of screw placement in the pedicle of the axis than the freehand group (P<0.05), while no significant difference was observed between two groups in the accuracy of screw placement in the pedicle of the atlas (P>0.05). CONCLUSION: In the treatment of typeⅡold odontoid fractures with posterior pedicle screw fixation, 3D printing navigation template screw placement can significantly shorten the operation time, achieve similar clinical efficacy as free-hand screw placement, and significantly improve the accuracy of screw placement in the pedicle of the axis.

The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitor for patients with locally advanced gastric cancer (LAGC). METHODS: An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. RESULTS: After screening, 6 phase II/III randomized controlled trials (RCTs) and 9 retrospective studies with 2,953 patients were included. In meta-analysis, NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. CONCLUSIONS: The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

GR-pKa: a message-passing neural network with retention mechanism for pKa prediction.

During the drug discovery and design process, the acid-base dissociation constant (pKa) of a molecule is critically emphasized due to its crucial role in influencing the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and biological activity. However, the experimental determination of pKa values is often laborious and complex. Moreover, existing prediction methods exhibit limitations in both the quantity and quality of the training data, as well as in their capacity to handle the complex structural and physicochemical properties of compounds, consequently impeding accuracy and generalization. Therefore, developing a method that can quickly and accurately predict molecular pKa values will to some extent help the structural modification of molecules, and thus assist the development process of new drugs. In this study, we developed a cutting-edge pKa prediction model named GR-pKa (Graph Retention pKa), leveraging a message-passing neural network and employing a multi-fidelity learning strategy to accurately predict molecular pKa values. The GR-pKa model incorporates five quantum mechanical properties related to molecular thermodynamics and dynamics as key features to characterize molecules. Notably, we originally introduced the novel retention mechanism into the message-passing phase, which significantly improves the model's ability to capture and update molecular information. Our GR-pKa model outperforms several state-of-the-art models in predicting macro-pKa values, achieving impressive results with a low mean absolute error of 0.490 and root mean square error of 0.588, and a high R2 of 0.937 on the SAMPL7 dataset.

Functional connectome gradient predicts clinical symptoms of chronic insomnia disorder.

Insomnia is the second most prevalent psychiatric disorder worldwide, but the understanding of the pathophysiology of insomnia remains fragmented. In this study, we calculated the connectome gradient in 50 chronic insomnia disorder (CID) patients and 38 healthy controls (HC) to assess changes due to insomnia and utilized these gradients in a connectome-based predictive modeling (CPM) to predict clinical symptoms associated with insomnia. The results suggested that insomnia led to significant alterations in the functional gradients of some brain areas. Specifically, the gradient scores in the middle frontal gyrus, superior anterior cingulate gyrus, and right nucleus accumbens were significantly higher in the CID patients than in the HC group, whereas the scores in the middle occipital gyrus, right fusiform gyrus, and right postcentral gyrus were significantly lower than in the HC group. Further correlation analysis revealed that the right middle frontal gyrus is positively correlated with the self-rating anxiety scale (r=0.3702). Additionally, the prediction model built with functional gradients could well predict the sleep quality (r=0.5858), anxiety (r=0.6150), and depression (r=0.4022) levels of insomnia patients. This offers an objective depiction of the clinical diagnosis of insomnia, yielding a beneficial impact on the identification of effective biomarkers and the comprehension of insomnia.

Concurrent behavioral modeling and multimodal neuroimaging reveals how feedback affects the performance of decision making in internet gaming disorder.

Internet gaming disorder (IGD) prompts inquiry into how feedback from prior gaming rounds influences subsequent risk-taking behavior and potential neural mechanisms. Forty-two participants, including 15 with IGD and 27 health controls (HCs), underwent a sequential risk-taking task. Hierarchy Bayesian modeling was adopted to measure risky propensity, behavioral consistence, and affection by emotion ratings from last trial. Concurrent electroencephalogram and functional near-infrared spectroscopy (EEG-fNIRS) recordings were performed to demonstrate when, where and how the previous-round feedback affects the decision making to the next round. We discovered that the IGD illustrated heightened risk-taking propensity as compared to the HCs, indicating by the computational modeling (p = 0.028). EEG results also showed significant time window differences in univariate and multivariate pattern analysis between the IGD and HCs after the loss of the game. Further, reduced brain activation in the prefrontal cortex during the task was detected in IGD as compared to that of the control group. The findings underscore the importance of understanding the aberrant decision-making processes in IGD and suggest potential implications for future interventions and treatments aimed at addressing this behavioral addiction.

Safety and efficacy of minimally invasive gastrectomy for older patients with gastric cancer after neoadjuvant chemotherapy and immunotherapy: a propensity score-matched analysis.

BACKGROUND: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). METHODS: The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. RESULTS: The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. CONCLUSION: The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827).

New cembranoid with potent anti-inflammatory effect isolated from Boswellia sacra by inactivating the NF-κB signaling pathway.

Boswellia sacra has the properties of activating blood circulation, fixing pain, subduing swelling and promoting muscle growth. However, the anti-inflammatory active ingredients and molecular mechanisms of Boswellia sacra are still not clearly explored. Boswellia sacra was grounded and extracted using 95% ethanol, the extracts were separated by column chromatography preparation to give compounds. Spectral analysis and quantum calculations confirmed the structures of compounds and identified compound 1 as a new compound. Compounds 1-3 showed potent inhibitory activities and their effects on inflammatory mediator NO and inflammatory cytokines were examined by ELISA assay. Furthermore, their modulatory mechanism on inflammatory signal pathways was explored.

Successful treatment with efgartigimod as an add-on therapy in acute attack of anti-AQP4 antibody-positive NMOSD: a case report.

BACKGROUND: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disease characterized by recurrent myelitis and optic neuritis. It is associated with high rates of relapse and disability. The main treatment strategies for acute attacks include intravenous methylprednisolone pulse (IVMP) treatment and rescue treatment with plasma exchange (PLEX). Recently, the blockade of neonatal Fc receptor (FcRn)-IgG interaction has gained momentum as a therapeutic strategy. Efgartigimod, the first approved FcRn inhibitor for treating generalized myasthenia gravis, has shown impressive safety, efficacy, and tolerability, and is being regarded as "PLEX in a bottle". CASE DESCRIPTION: We report a 65-year-old female patient who was diagnosed with anti-AQP4 antibody positive NMOSD. Add-on treatment with efgartigimod to IVMP and intravenous immunoglobulin (IVIG) at the second acute relapse showed favorable results. CONCLUSION: This case suggests that efgartigimod is a potentially effective add-on therapy in acute attacks of AQP4-IgG-positive NMOSD.

Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.

BACKGROUND: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. METHODS: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. RESULTS: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. CONCLUSIONS: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.

REST Promotes Autophagy in Gastric Cancer by Transcriptionally Activating FABP6 to Inhibit the Akt/mTOR Signaling Pathway.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer-associated death worldwide. Its molecular mechanisms, especially concerning autophagy and various signaling pathways, are not fully understood. Fatty Acid Binding Protein 6 (FABP6) and RE1 Silencing Transcription Factor (REST) emerge as potential key players in this context. This study sought to analyze the functional relationship of FABP6 and REST concerning autophagy and their implications on the Akt/mTOR signaling pathway within GC cells. METHODS: A comprehensive bioinformatics approach was used to identify key prognostic markers in GC. The effects of FABP6 and REST on autophagy along with Akt/mTOR signaling pathways were analyzed by techniques including Western blotting (WB), flow cytometry, Transwell assay, dual luciferase reporter assay, and others. RESULTS: FABP6 was identified as overexpressed in GC, linked with poor prognosis. FABP6 silencing reduces GC cell proliferation, induces S- and G2-phase arrest, and downregulates cyclins CDK2 and CDK4. It also inhibited GC cell invasion/migration and autophagy, effects that were counteracted by MG132. When combined with PI3K inhibitor LY294002c, FABP6 knockdown showed synergistic anti-proliferative effects, modulating the Akt/mTOR pathway. Besides, the transcription factor REST has been shown to directly regulate FABP6 expression, affecting autophagy and the Akt/mTOR signaling pathway in a FABP6-dependent manner. CONCLUSIONS: REST positively regulates autophagy and negatively affects the Akt/mTOR signaling pathway in GC cells in a FABP6-dependent manner, providing valuable insights into regulatory networks involving FABP6 and REST.

Akkermansia muciniphila-derived pentadecanoic acid enhances oxaliplatin sensitivity in gastric cancer by modulating glycolysis.

Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.