Metal chloride cathodes for next-generation rechargeable lithium batteries.

Rechargeable lithium-ion batteries (LIBs) have prospered a rechargeable world, predominantly relying on various metal oxide cathode materials for their abilities to reversibly de-/intercalate lithium-ion, while also serving as lithium sources for batteries. Despite the success of metal oxide, issues including low energy density have raised doubts about their suitability for next-generation lithium batteries. This has sparked interest in metal chlorides, a neglected cathode material family. Metal chlorides show promise with factors like energy density, diffusion coefficient, and compressibility. Unfortunately, challenges like high solubility hamper their utilization. In this review, we highlight the opportunities for metal chlorides in the post-lithium-ion era. Subsequently, we summarize their dissolution challenges. Furthermore, we discuss recent advancements, encompassing liquid-state electrolyte engineering, solid-state electrolytes (SSEs) cooperation, and LiCl-based cathodes. Finally, we provide an outlook on future research directions of metal chlorides, emphasizing electrode fabrication, electrolyte design, the application of SSEs, and the exploration of conversion reactions.

Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome.

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Insulinemic and inflammatory dietary patterns show enhanced predictive potential for gestational diabetes mellitus risk.

CONTEXT: The putative association between proinflammatory and hyperinsulinemic dietary patterns and susceptibility to gestational diabetes mellitus (GDM) remains unclear. OBJECTIVE: We aimed to compare the risk associated with the Mediterranean diet, as well as insulinemic and proinflammatory dietary patterns, in relation to the occurrence of GDM, and evaluate their predictive value. METHODS: We prospectively followed 8, 495 women from the Maternal and Infant Health cohort in Hefei, China (2015-2021). Using a food frequency questionnaire, we calculated the Empirical Dietary Inflammatory Pattern (EDIP), the Empirical Dietary Index for Hyperinsulinemia (EDIH) score, and the Mediterranean diet (MD) score. GDM was diagnosed based on a 2-hour 75-gram oral glucose tolerance test conducted between 24 to 28 weeks of gestation. Logistic regression was used to estimate the risk of GDM, while Receiver Operating Characteristic (ROC) curves were constructed to evaluate the predictive performance of the empirical dietary index for GDM. RESULTS: Participants who followed hyperinsulinemic or proinflammatory dietary patterns to the greatest extent had a higher risk of developing GDM. The OR for the highest quartile compared to the lowest quartile were 1.39 (95% CI: 1.30-1.49) for EDIH and 2.40 (95% CI: 1.88-3.01) for EDIP. The OR for the lowest quartile compared to the highest quartile was 1.33 (95% CI:1.14-1.55)for MD. The ROC curve analysis indicated that the combination of EDIP and EDIH (AUC = 0.81, 95% CI: 0.78-0.82, P = 0.003) can effectively predict the occurrence of GDM. CONCLUSIONS: Utilizing both empirical dietary indexes, EDIP and EDIH, might offer a potentially more effective approach in preventing GDM when compared to solely focusing on adherence to the Mediterranean diet pattern.

Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. METHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort. RESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. CONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.

Changes in Patellar Height and Tibial Posterior Slope after Biplanar High Tibial Osteotomy with Computer-Designed Personalized Surgical Guides: A Retrospective Study.

OBJECTIVE: Medial opening-wedge high tibial osteotomy (MOWHTO) is a surgical procedure to treat medial compartment osteoarthritis in the knee with varus deformity. However, factors such as patellar height (PH) and the sagittal plane's posterior tibial slope angle (PTSA) are potentially overlooked. This study investigated the impact of alignment correction angle guided by computer-designed personalized surgical guide plate (PSGP) in MOWHTO on PH and PTSA, offering insights for enhancing surgical techniques. METHODS: This retrospective study included patients who underwent 3D-printed PSGP-assisted MOWHTO at our institution from March to September 2022. The paired t-tests assessed differences in all preoperative and postoperative measurement parameters. Multivariate linear regression analysis examined correlations between PTSA, CDI (Caton-Deschamps Index), and the alignment correction magnitude. Receiver operating characteristic (ROC) curve analysis determined the threshold of the correction angle, calculating sensitivity, specificity, and area under the curve. RESULTS: A total of 107 patients were included in our study. The CDI changed from a preoperative mean of 0.97 ± 0.13 (range 0.70-1.34) to a postoperative mean of 0.82 ± 0.13 (range 0.55-1.20). PTSA changed from a preoperative mean of 8.54 ± 2.67 (range 2.19-17.55) to a postoperative mean of 10.54 ± 3.05 (range 4.48-18.05). The t-test revealed statistically significant changes in both values (p < 0.05). A significant alteration in patellar height occurred when the correction angle exceeded 9.39°. Moreover, this paper illustrates a negative correlation between CDI change and the correction angle and preoperative PTSA. Holding other factors constant, each 1-degree increase in the correction angle led to a 0.017 decrease in postoperative CDI, and each 1-degree increase in preoperative PTSA resulted in a 0.008 decrease in postoperative CDI. PTSA change was positively correlated only with the correction angle; for each 1-degree increase in the opening angle, postoperative PTS increased by 0.188, with other factors constant. CONCLUSION: This study highlights the effectiveness and precision of PSGP-assisted MOWHTO, focusing on the impact of alignment correction on PH and PTSA. These findings support the optimization of PSGP technology, which offers simpler, faster, and safer surgeries with less radiation and bleeding than traditional methods. However, PSGP's one-time use design and the learning curve required for its application are limitations, suggesting areas for further research.

Unleashing the potential: integrating nano-delivery systems with traditional Chinese medicine.

This review explores the potential of integrating nano-delivery systems with traditional Chinese herbal medicine, acupuncture, and Chinese medical theory. It highlights the intersections and potential of nano-delivery systems in enhancing the effectiveness of traditional herbal medicine and acupuncture treatments. In addition, it discusses how the integration of nano-delivery systems with Chinese medical theory can modernize herbal medicine and make it more readily accessible on a global scale. Finally, it analyzes the challenges and future directions in this field.

A Mesoporous Silica-loaded Multi-functional Hydrogel Enhanced Tendon Healing via Immunomodulatory and pro-regenerative Effects.

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries such as Achilles tendon injury is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, we have pioneered an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, while concurrently delivering mesoporous silica nanoparticles for tendon healing. In our research, we employed CP@SiO2 hydrogel for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. Our results show that CP@SiO2 hydrogel significantly promotes the proliferation and differentiation of tendon-derived stem cells. BrdU assay results indicated a 12% increase in cell growth rate compared to gel treatment. Additionally, PCR results showed an increase in the expression of genes related to tendon differentiation and stemness maintenance. Moreover, the hydrogel effectively mitigated inflammation by promoting M2 polarization and inhibiting M1 polarization, thus alleviating macrophage-induced inflammation. The hydrogel also accelerated the recovery of injured tendon function; biomechanical assessments revealed that at 28 days post-operation, the load-to-failure ratio of tendons in the CP@SiO2 group was 53.28N, surpassing the 32.06N of the model group. Furthermore, we conducted a comprehensive in vivo evaluation using a tendon injury model, which included detailed histological analysis and behavioral observations. Our findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries. This article is protected by copyright. All rights reserved.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Ordered mesoporous nanofibers mimicking vascular bundles for lithium metal batteries.

Hierarchical self-assembly with long-range order above centimeters widely exists in nature. Mimicking similar structures to promote reaction kinetics of electrochemical energy devices is of immense interest, yet remains challenging. Here, we report a bottom-up self-assembly approach to constructing ordered mesoporous nanofibers with a structure resembling vascular bundles via electrospinning. The synthesis involves self-assembling polystyrene (PS) homopolymer, amphiphilic diblock copolymer, and precursors into supramolecular micelles. Elongational dynamics of viscoelastic micelle solution together with fast solvent evaporation during electrospinning cause simultaneous close packing and uniaxial stretching of micelles, consequently producing polymer nanofibers consisting of oriented micelles. The method is versatile for the fabrication of large-scale ordered mesoporous nanofibers with adjustable pore diameter and various compositions such as carbon, SiO2, TiO2 and WO3. The aligned longitudinal mesopores connected side-by-side by tiny pores offer highly exposed active sites and expedite electron/ion transport. The assembled electrodes deliver outstanding performance for lithium metal batteries.

Unraveling varying spatiotemporal patterns of dengue and associated exposure-response relationships with environmental variables in Southeast Asian countries before and during COVID-19.

The enforcement of COVID-19 interventions by diverse governmental bodies, coupled with the indirect impact of COVID-19 on short-term environmental changes (e.g. plant shutdowns lead to lower greenhouse gas emissions), influences the dengue vector. This provides a unique opportunity to investigate the impact of COVID-19 on dengue transmission and generate insights to guide more targeted prevention measures. We aim to compare dengue transmission patterns and the exposure-response relationship of environmental variables and dengue incidence in the pre- and during-COVID-19 to identify variations and assess the impact of COVID-19 on dengue transmission. We initially visualized the overall trend of dengue transmission from 2012-2022, then conducted two quantitative analyses to compare dengue transmission pre-COVID-19 (2017-2019) and during-COVID-19 (2020-2022). These analyses included time series analysis to assess dengue seasonality, and a Distributed Lag Non-linear Model (DLNM) to quantify the exposure-response relationship between environmental variables and dengue incidence. We observed that all subregions in Thailand exhibited remarkable synchrony with a similar annual trend except 2021. Cyclic and seasonal patterns of dengue remained consistent pre- and during-COVID-19. Monthly dengue incidence in three countries varied significantly. Singapore witnessed a notable surge during-COVID-19, particularly from May to August, with cases multiplying several times compared to pre-COVID-19, while seasonality of Malaysia weakened. Exposure-response relationships of dengue and environmental variables show varying degrees of change, notably in Northern Thailand, where the peak relative risk for the maximum temperature-dengue relationship rose from about 3 to 17, and the max RR of overall cumulative association 0-3 months of relative humidity increased from around 5 to 55. Our study is the first to compare dengue transmission patterns and their relationship with environmental variables before and during COVID-19, showing that COVID-19 has affected dengue transmission at both the national and regional level, and has altered the exposure-response relationship between dengue and the environment.

Metabolic difference between patient-derived xenograft model of pancreatic ductal adenocarcinoma and corresponding primary tumor.

BACKGROUND: Patients-derived xenograft (PDX) model have been widely used for tumor biological and pathological studies. However, the metabolic similarity of PDX tumor to the primary cancer (PC) is still unknown. METHODS: In present study, we established PDX model by engrafting primary tumor of pancreatic ductal adenocarcinoma (PDAC), and then compared the tumor metabolomics of PC, the first generation of PDX tumor (PDXG1), and the third generation of PDX tumor (PDXG3) by using 1H NMR spectroscopy. Then, we assessed the differences in response to chemotherapy between PDXG1 and PDXG3 and corresponding metabolomic differences in drug-resistant tumor tissues. To evaluate the metabolomic similarity of PDX to PC, we also compared the metabolomic difference of cell-derived xenograft (CDX) vs. PC and PDX vs. PC. RESULTS: After engraftment, PDXG1 tumor had a low level of lactate, pyruvate, citrate and multiple amino acids (AAs) compared with PC. Metabolite sets enrichment and metabolic pathway analyses implied that glycolysis metabolisms were suppressed in PDXG1 tumor, and tricarboxylic acid cycle (TCA)-associated anaplerosis pathways, such as amino acids metabolisms, were enhanced. Then, after multiple passages of PDX, the altered glycolysis and TCA-associated anaplerosis pathways were partially recovered. Although no significant difference was observed in the response of PDXG1 and PDXG3 to chemotherapy, the difference in glycolysis and amino acids metabolism between PDXG1 and PDXG3 could still be maintained. In addition, the metabolomic difference between PC and CDX models were much larger than that of PDX model and PC, indicating that PDX model still retain more metabolic characteristics of primary tumor which is more suitable for tumor-associated metabolism research. CONCLUSIONS: Compared with primary tumor, PDX models have obvious difference in metabolomic level. These findings can help us design in vivo tumor metabolomics research legitimately and analyze the underlying mechanism of tumor metabolic biology thoughtfully.

Revealing the role of a bridging oxygen in a carbon shell coated Ni interface for enhanced alkaline hydrogen oxidation reaction.

Encapsulating metal nanoparticles inside carbon layers is a promising approach to simultaneously improving the activity and stability of electrocatalysts. The role of carbon layer shells, however, is not fully understood. Herein, we report a study of boron doped carbon layers coated on nickel nanoparticles (Ni@BC), which were used as a model catalyst to understand the role of a bridging oxygen in a carbon shell coated Ni interface for the improvement of the hydrogen oxidation reaction (HOR) activity using an alkaline electrolyte. Combining experimental results and density functional theory (DFT) calculations, we find that the electronic structure of Ni can be precisely tailored by Ni-O-C and Ni-O-B coordinated environments, leading to a volcano type correlation between the binding ability of the OH* adsorbate and HOR activity. The obtained Ni@BC with a optimized d-band center displays a remarkable HOR performance with a mass activity of 34.91 mA mgNi-1, as well as superior stability and CO tolerance. The findings reported in this work not only highlight the role of the OH* binding strength in alkaline HOR but also provide guidelines for the rational design of advanced carbon layers used to coat metal electrocatalysts.

Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

Risk factors and prediction model construction for peripherally inserted central catheter-related infections.

Objective: To establish a predictive modeling for the risk of bloodstream infection associated with peripherally inserted central catheter (PICC). Methods: Patients receiving PICC treatment in Shenzhen People's Hospital from June 2020 to December 2020 were retrospectively enrolled and divided into the infection group and the non-infection group according to the presence and absence of PICC-related infections. Then, relevant clinical information of patients was collected and the predictors of PICC-related infection were screened by the least absolute shrinkage and selection operator regression (LASSO) model. Besides, multivariate logistic regression was used to analyze the influencing factors of PICC-related infection, A nomogram was constructed based on the results of the multivariate analysis. Ultimately, a receiver operating characteristic (ROC) curve was plotted to analyze the application value of influencing factors to predict PICC-related infections. Results: A total of 505 patients were included, including 75 patients with PICC-related infections (14.85%). The main pathogen was gram-positive cocci. The predictors screened by LASSO included age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Multivariate logistic regression analysis showed that independent risk factors of infections related to PICC included age >60 years [odds ratio (OR) = 1.722; 95% confidence interval (CI) = 1.312-3.579; P = 0.006], catheter movement (OR = 1.313; 95% CI = 1.119-3.240; P = 0.014), catheter maintenance cycle >7 days (OR = 2.199; 95% CI = 1.677-4.653; P = 0.000), direct insertion (OR = 1.036; 95% CI = 1.019-2.743; P = 0.000), poor immune function (OR = 2.322; 95% CI = 2.012-4.579; P = 0.000), complications (OR = 1.611; 95% CI = 1.133-3.454; P = 0.019), and body temperature ≥37.2 °C before PICC placement (OR = 1.713; 95% CI = 1.172-3.654; P = 0.012). Besides, the area under the ROC curve was 0.889. Conclusion: PICC-related infections are associated with factors such as age >60 years, catheter movement, catheter maintenance cycle, insertion technique, immune function, complications, and body temperature ≥37.2 °C before PICC placement. Additionally, the LASSO model is moderately predictive for predicting the occurrence of PICC-related infections.

Second-Order Motion-Compensated Echo-Planar Cardiac Diffusion-Weighted MRI: Usefulness of Compressed Sensitivity Encoding.

BACKGROUND: Cardiac diffusion-weighted imaging (DWI) using second-order motion-compensated spin echo (M2C) can provide noninvasive in-vivo microstructural assessment, but limited by relatively low signal-to-noise ratio (SNR). Echo-planar imaging (EPI) with compressed sensitivity encoding (EPICS) could address these issues. PURPOSE: To combine M2C DWI and EPCIS (M2C EPICS DWI), and compare image quality for M2C DWI. STUDY TYPE: Prospective. POPULATION: Ten ex-vivo hearts, 10 healthy volunteers (females, 5 [50%]; mean ± SD of age, 25 ± 4 years), and 12 patients with diseased hearts (female, 1 [8.3%]; mean ± SD of age, 44 ± 16 years; including coronary artery heart disease, congenital heart disease, dilated cardiomyopathy, amyloidosis, and myocarditis). FIELD STRENGTH/SEQUENCE: 3-T, M2C EPICS DWI, and M2C DWI. ASSESSMENT: The apparent SNR (aSNR) and the rating scores were used to evaluate and compared image quality of all three groups. The aSNR was calculated using aSNR = Mean intensity myocardium / Standard deviation myocardium $$ \mathrm{aSNR}={\mathrm{Mean}\ \mathrm{intensity}}_{\mathrm{myocardium}}/{\mathrm{Standard}\ \mathrm{deviation}}_{\mathrm{myocardium}} $$ , and the myocardium was segmented manually. Three observers independently rated subjective image quality using a 5-point Likert scale. STATISTICAL TESTS: Bland-Altman analysis and paired t-tests. The threshold for statistical significance was set at P < 0.05. RESULTS: In healthy volunteers, the aSNR with a b-value of 450 s/mm2 acquired by M2C EPICS DWI was significantly higher than M2C DWI at in-plane resolutions of 3.0 × 3.0, 2.5 × 2.5, and 2.0 × 2.0 mm2. In patients with diseased hearts, the aSNR ofM2C EPICS DWI was also significantly higher than that for M2C DWI (bias of M2C EPICS-M2C = 1.999, 95% limits of agreement, 0.362 to 3.636; mean ± SD, 7.80 ± 1.37 vs. 5.80 ± 0.81). The ADC values of M2C EPICS was significantly higher than M2C DWI in in-vivo hearts. Over 80% of the images with rating scores for M2C EPICS DWI were higher than M2C DWI in in-vivo hearts. DATA CONCLUSION: Cardiac imaging by M2C EPICS DWI may demonstrate better overall image quality and higher aSNR than M2C DWI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Bioinformatics analysis of MMP14+ myeloid cells affecting endothelial-mesenchymal transformation and immune microenvironment in glioma.

Background: Gliomas, known for their complex and aggressive characteristics, are deeply influenced by the tumor microenvironment. Matrix metalloproteinases (MMPs) play a vital role in shaping this environment, presenting an opportunity for novel treatment strategies. Methods: We collected six bulk RNA datasets, one single-cell RNA sequencing (scRNA-seq) dataset, and gene sets related to Matrix Metalloproteinases (MMPs), Endothelial-Mesenchymal Transformation (EndMT), and sprouting angiogenesis. We computed enrichment scores using Gene Set Variation Analysis (GSVA) and Single-sample Gene Set Enrichment Analysis (ssGSEA). To analyze immune infiltration, we employed the CIBERSORT method. Data analysis techniques included the log-rank test, Cox regression, Kruskal-Wallis test, and Pearson correlation. For single-cell data, we utilized tools such as Seurat and CellChat for dimensionality reduction, clustering, and cell communication analysis. Results: 1. MMP14 was identified as an independent prognostic marker, highly expressed in myeloid cells in recurrent glioblastoma, highlighting these cells as functionally significant. 2. C-C Motif Chemokine Ligand (CCL) signaling from MMP14+ myeloid cells was identified as a critical immune regulatory pathway, with high C-C Motif Chemokine Receptor 1 (CCR1) expression correlating with increased M2 macrophage infiltration and PD-L1 expression. 3. Patients with high MMP14 expression showed better responses to bevacizumab combined chemotherapy. 4. Signaling pathways involving Visfatin, VEGF, and TGFb, emanating from myeloid cells, significantly impact endothelial cells. These pathways facilitate EndMT and angiogenesis in gliomas. 5. Nicotinamide Phosphoribosyltransferase (NAMPT) showed a strong link with angiogenesis and EndMT, and its association with chemotherapy resistance and differential sensitivity to bevacizumab was evident. Conclusions: MMP14+ myeloid cells are critical in promoting tumor angiogenesis via EndMT and in mediating immunosuppression through CCL signaling in glioblastoma. MMP14 and NAMPT serve as vital clinical indicators for selecting treatment regimens in recurrent glioma. The study suggests that a combined blockade of CCR1 and CD274 could be a promising therapeutic strategy.

Catalytic polymer self-cleavage for CO2 generation before combustion empowers materials with fire safety.

Polymeric materials, rich in carbon, hydrogen, and oxygen elements, present substantial fire hazards to both human life and property due to their intrinsic flammability. Overcoming this challenge in the absence of any flame-retardant elements is a daunting task. Herein, we introduce an innovative strategy employing catalytic polymer auto-pyrolysis before combustion to proactively release CO2, akin to possessing responsive CO2 fire extinguishing mechanisms. We demonstrate that potassium salts with strong nucleophilicity (such as potassium formate/malate) can transform conventional polyurethane foam into materials with fire safety through rearrangement. This transformation results in the rapid generation of a substantial volume of CO2, occurring before the onset of intense decomposition, effectively extinguishing fires. The inclusion of just 1.05 wt% potassium formate can significantly raise the limiting oxygen index of polyurethane foam to 26.5%, increase the time to ignition by 927%, and tremendously reduce smoke toxicity by 95%. The successful application of various potassium salts, combined with a comprehensive examination of the underlying mechanisms, underscores the viability of this strategy. This pioneering catalytic approach paves the way for the efficient and eco-friendly development of polymeric materials with fire safety.

Potassium-Competitive Acid Blocker Versus Proton Pump Inhibitor: A Pilot Study on Comparable Efficacy in the Treatment of Gastroesophageal Reflux-Related Cough.

Acid inhibitors have been considered in treating gastroesophageal reflux-related cough (GERC). Compared to proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs) have more potent and durable effects on anti-acid secretion. However, whether vonoprazan and esomeprazole have different therapeutic effects on GERC remains unknown. Patients diagnosed with GERC were enrolled in our study and randomly treated with vonoprazan (20 mg, once daily, P-CAB) or esomeprazole (20 mg, twice daily, PPI) for two months. A prokinetic agent was also administered. Patients were followed up once a month. Cough severity visual analogue scale (VAS) was measured as the primary outcome, while cough symptom score (CSS) and scores for cough-related quality-of-life or reflux-related symptoms were the secondary endpoints. A total of 50 patients completed the study, with 25 patients in each group. P-CAB and PPI groups showed similar decreases in cough severity VAS and CSS scores after the 2-month treatment (all P < 0.001). For quality-of-life, the Leicester Cough Questionnaire (LCQ) score increased significantly from baseline in both groups, but the P-CAB group had greater improvement and a higher LCQ score in month 2 (all P ≤ 0.05). For reflux-related symptoms, the Hull Airway Reflux Questionnaire (HARQ) score declined substantially over time in the P-CAB group, while the reflux symptom index (RSI) score decreased in both groups. The P-CAB group tended to have a lower HARQ (P = 0.051) and RSI (P = 0.069) scores in month 2. In conclusion, vonoprazan may be comparable to esomeprazole in cough symptom relief in GERC during the 2-month treatment period, but possibly provides better gains on classic reflux symptoms and quality-of-life. The long-term efficacy of P-CABs on GERC may be worth further exploration. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200067089.

Adherence to Vitamin D Supplementation Recommendations for Breastfed Infants and Young Children: An Analysis of Canadian Community Health Survey Data Cycles From 2015 to 2018.

BACKGROUND: In Canada, nutrition policy, as outlined in the Nutrition for Healthy Term Infants recommendations, includes a daily vitamin D supplement of 10 µg (400 IU) for breastfed infants and young children to support adequate vitamin D status. OBJECTIVES: This study aimed to report on adherence to vitamin D supplementation recommendations for breastfed infants (≤12 months); and for children breastfed >12 mo. METHODS: Canadian Community Health Survey (paired-cycles 2015/2016 and 2017/2018) maternal experiences data for infants born 2012-2018 who received any breastmilk formed the sample (n = 7079). Whether the infant was given a vitamin D supplement (yes/no) and the frequency (daily/almost every day, 1-2/wk, or <1/wk) were surveyed. Weighted data (95% CI) were summarized according to breastfeeding history (exclusive to 6 mo and continuing; partial to 6 mo and continuing; and stopped ≤6 mo). Correlates of supplement adherence were explored using logistic regression. RESULTS: Overall, 87.1% (95% CI: 85.9$, 88.3%) of participants reported giving their infant (≤12 mo) a vitamin D supplement, and of these, 83.3% (95% CI: 81.9%, 84.7%) did so daily/almost every day, 12.4% (95% CI: 11.1%, 13.7%) did so 1-2/wk, and 4.3% (95% CI: 3.6%, 5.0%) did so <1/wk. Lower adjusted odds of adherence were observed among participants reporting: stopped breastfeeding ≤6 mo, lower education or income, recent immigration, and overweight prepregnancy body mass index; higher odds of adherence were observed in the western provinces. Regarding mothers of children >12 mo and breastfed (n = 2312), 58.0% (95% CI: 54.9%, 61.1%) gave a vitamin D supplement daily/almost every day. CONCLUSIONS: Adherence to providing a vitamin D supplement to breastfed infants is high in Canada. Nonetheless, we estimate that ∼27% of mothers are nonadherent to daily/almost every day administration of a vitamin D supplement and that adherence declines in children breastfed >12 mo. Further promotion to support uptake of the current guidance may be necessary, particularly for parents of recent immigration or lower socioeconomic status.

Origin and evolution of pentanucleotide repeat expansions at the familial cortical myoclonic tremor with epilepsy type1 - SAMD12 locus.

Familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1) is caused by (TTTTA)exp(TTTCA)exp repeat expansions in SAMD12, while pure (TTTTA)exp is polymorphic. Our investigation focused on the origin and evolution of pure (TTTTA)exp and (TTTTA)exp(TTTCA)exp at this locus. We observed a founder effect between them. The phylogenetic analysis suggested that the (TTTTA)exp(TTTCA)exp might be generated from pure (TTTTA)exp through infrequent transformation events. Long-read sequencing revealed somatic generation of (TTTTA)exp(TTTCA)exp from pure (TTTTA)exp, likely via long segment (TTTCA) repeats insertion. Our findings indicate close relationships between the non-pathogenic (TTTTA)exp and the pathogenic (TTTTA)exp(TTTCA)exp, with dynamic interconversions. This sheds light on the genesis of pathogenic repeat expansions from ancestral premutation alleles. Our results may guide future studies in detecting novel repeat expansion disorders and elucidating repeat expansion mutational processes, thereby enhancing our understanding of human genomic variation.