Dependence of the formation kinetics of carbon dioxide hydrate on clay aging for solid carbon dioxide storage.

Clay-based marine sediments have great potential for safe and effective carbon dioxide (CO2) encapsulation by storing enormous amounts of CO2 in solid gas hydrate form. However, the aging of clay with time changes the surface properties of clay and complicates the CO2 hydrate formation behaviors in sediments. Due to the long clay aging period, it is difficult to identify the role of clay aging in the formation of CO2 hydrate in marine sediments. Here, we used ultrasonication and plasma treatment to simulate the breakage and oxidation of clay nanoflakes in aging and investigated the influence of clay aging on CO2 hydrate formation kinetics. We found that the breakage and oxidation of clay nanoflakes would disrupt the siloxane rings and graft hydroxyl on the clay nanoflakes. This decreased the negative charge density of clay nanoflakes and weakened the interfacial interaction of clay nanoflakes with the surrounding water. Therefore, the small clay nanoflakes enriched in hydroxyl would disrupt the surrounding tetrahedral water structure analogous to the CO2 hydrate, resulting in the prolongation of CO2 hydrate nucleation. These results revealed the influence of the structure-function relationship of clay nanoflakes with CO2 hydrate formation and are favorable for the development of hydrate-based CO2 storage.

Revealing microbiota characteristics and predicting flavor-producing sub-communities in Nongxiangxing baijiu pit mud through metagenomic analysis and metabolic modeling.

The microorganisms of the pit mud (PM) of Nongxiangxing baijiu (NXXB) have an important role in the synthesis of flavor substances, and they determine attributes and quality of baijiu. Herein, we utilize metagenomics and genome-scale metabolic models (GSMMs) to investigate the microbial composition, metabolic functions in PM microbiota, as well as to identify microorganisms and communities linked to flavor compounds. Metagenomic data revealed that the most prevalent assembly of bacteria and archaea was Proteiniphilum, Caproicibacterium, Petrimonas, Lactobacillus, Clostridium, Aminobacterium, Syntrophomonas, Methanobacterium, Methanoculleus, and Methanosarcina. The important enzymes ofPMwere in bothGH and GT familymetabolism. A total of 38 high-quality metagenome-assembled genomes (MAGs) were obtained, including those at the family level (n = 13), genus level (n = 17), and species level (n = 8). GSMMs of the 38 MAGs were then constructed. From the GSMMs, individual and community capabilities respectively were predicted to be able to produce 111 metabolites and 598 metabolites. Twenty-three predicted metabolites were consistent with the metabonomics detected flavors and served as targets. Twelve sub-community of were screened by cross-feeding of 38 GSMMs. Of them, Methanobacterium, Sphaerochaeta, Muricomes intestini, Methanobacteriaceae, Synergistaceae, and Caloramator were core microorganisms for targets in each sub-community. Overall, this study of metagenomic and target-community screening could help our understanding of the metabolite-microbiome association and further bioregulation of baijiu.

The STOIC2021 COVID-19 AI challenge: Applying reusable training methodologies to private data.

Challenges drive the state-of-the-art of automated medical image analysis. The quantity of public training data that they provide can limit the performance of their solutions. Public access to the training methodology for these solutions remains absent. This study implements the Type Three (T3) challenge format, which allows for training solutions on private data and guarantees reusable training methodologies. With T3, challenge organizers train a codebase provided by the participants on sequestered training data. T3 was implemented in the STOIC2021 challenge, with the goal of predicting from a computed tomography (CT) scan whether subjects had a severe COVID-19 infection, defined as intubation or death within one month. STOIC2021 consisted of a Qualification phase, where participants developed challenge solutions using 2000 publicly available CT scans, and a Final phase, where participants submitted their training methodologies with which solutions were trained on CT scans of 9724 subjects. The organizers successfully trained six of the eight Final phase submissions. The submitted codebases for training and running inference were released publicly. The winning solution obtained an area under the receiver operating characteristic curve for discerning between severe and non-severe COVID-19 of 0.815. The Final phase solutions of all finalists improved upon their Qualification phase solutions.

ENL reads histone ß-hydroxybutyrylation to modulate gene transcription.

Histone modifications are typically recognized by chromatin-binding protein modules (referred to as 'readers') to mediate fundamental processes such as transcription. Lysine ß-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap should be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark, and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation led to the suppressed expression of genes such MYC that drive cell proliferation. Together, our work offered a chemoproteomics approach and identified ENL as a novel histone ß-hydroxybutyrylation effector that regulates gene transcription, providing new insight into the regulation mechanism and function of histone Kbhb.

Elucidating the binding partners of histone post-translational modifications (hPTMs) is key to understanding epigenetic regulatory pathways. Lysine ß-hydroxybutyrylation (Kbhb) is a novel hPTM that couples metabolism to transcription. However, the effectors reading this mark are poorly understood as the Kbhb-mediated protein­protein interactions are weak and transient. Here, we presented a quantitative chemical proteomics approach using multivalent photoaffinity probes to robustly capture interactors of this mark. Thus, we identified ENL as a novel binder of Kbhb of histone H3 lysine 9 (H3K9bhb). Biochemical studies and CUT&Tag analysis further revealed that ENL recognizes H3K9bhb and co-localizes with it on gene promoters to modulate transcription and tumorigenesis. This study highlights ENL as a histone Kbhb reader for the regulation of transcription.

[Spatial distribution patterns and intraspecific and interspecific spatial associations of Quercus myrsinifolia population in Shennongjia, China]. / ç¥žå†œæž¶å°å¶é’å†ˆç§ç¾¤çš„ç©ºé—´åˆ†å¸ƒæ ¼å±€åŠç§å† ç§é—´ç©ºé—´å ³è”.

Quercus myrsinifolia is one of the dominant species in the evergreen broad-leaf forest on the southern slope of Shennongjia. The study of spatial distribution pattern and spatial correlation of Q. myrsinifolia population will help to understand population development and potential ecological processes, as well as the structure and biodiversity maintenance mechanism of evergreen broad-leaf forests at the northern edge of the subtropics. Based on forest dynamic monitoring data from one 1 hm2 permanent plot on the southern slope of Shennongjia, we employed pair correlation functions g(r) and marked correlation functions to analyze the diameter structure of the Q. myrsinifolia population, spatial distribution patterns at different diameter classes, and intraspecific and interspecific spatial associations. The results showed that diameter structure of Q. myrsinifolia population exhibited an inverted 'J'-shaped distribution, suggesting a healthy regeneration status and belonging to a growing population type. The spatial distribution showed a decreasing trend in aggregation with increasing diameter. Positive correlations among individuals strengthened with closer diameter classes, while weakening with larger diameter differences. Interspecific spatial associations showed an increasing correlation of Q. myrsinifolia with understory dominant species with increasing spatial scales, but no correlation was observed with canopy-dominant species. Our results suggested that the spatial pattern of Q. myrsinifolia populations on the southern slope of Shennongjia was mainly influenced by habitat filtering, seed dispersal limitation, and intraspecific and interspecific competition. Furthermore, the adaptive strategies of Q. myrsinifolia varied when they coexisted with different species.

Patient-Reported Outcomes and Complication Profiles of Implant-Based Breast Reconstruction in Patients With Postmastectomy Radiation Therapy.

OBJECTIVE: This study aims to investigate the patient-reported outcomes (PROs) and complications of distinct implant-based breast reconstruction modality for patients with postmastectomy radiation therapy (PMRT). METHODS: A retrospective review was conducted on breast cancer patients with stage II-III disease who performed implant-based breast reconstruction following with PMRT between September 2016 and April 2022. The patients were categorized into two matched groups: (1) patients receiving prepectoral breast reconstruction (PBR) or (2) subpectoral breast reconstruction (SBR) followed by PMRT. Following reconstruction, the patients were further compared for PMRT with the tissue expander (PMRT-TE) versus PMRT with permanent implant (PMRT-PI). PROs were measured with BREAST-Q questionnaire. Early and late complications were recorded and analyzed. RESULTS: A total of 55 eligible patients were recruited. Patients who underwent PBR reported significantly higher satisfaction with breasts scores (P = 0.003) compared with the SBR group. The PMRT-TE group had higher satisfaction with breasts (P = 0.001) but lower physical well-being (P = 0.029) scores compared with PMRT-PI group. Moreover, patients in SBR cohort had a higher risk of capsular contracture (Baker grade III or IV) (20.5% vs 6.3%) and implant dislocation (48.7% vs 12.5%) than patients in PBR cohort. Patients in PMRT-PI group had a slightly higher rate of capsular contracture (Baker grade III or IV) than PMRT-TE group (20.8% vs 12.9%). CONCLUSIONS: PBR was associated with lower rates of late complications, especially for implant dislocation, and higher satisfaction with breasts scores compared to SBR. In addition, compared to PMRT-TE with PMRT-PI, patients in PMRT-TE cohort reported superior PROs of satisfaction with breasts.

Managing Pb-Related Imperfections via Rationally Designed Aniline Derivative with Bilateral Cyano and Acetyl Groups as Lewis Base for High-Efficiency Perovskite Solar Cells Exceeding 24.

Pb-related imperfections (surface or halide vacancy induced uncoordinated Pb2+, Pb-I antisite, and Pb2+ vacancy defects) of the ionic crystal perovskite film seriously restrict the photovoltaic performance of perovskite solar cells (PSCs). Here, an aniline derivative N-(4-cyanophenyl)acetamide (CAL) is rationally designed, incorporating bilateral functional sites of cyano and acetyl groups, acting as Lewis base molecule for managing the Pb-related imperfections in perovskite surface through post-treatment. Theoretical calculation and experimental verification together proved the reduced defect density, improved crystallinity, and inhibited ion migration in the CAL-modified perovskite. Precisely, cyano as a side group and acetyl as another side group can both coordinate with Pb2+ for its low electrostatic potential energy. Further, the aniline core and the π-π conjugate structure in the benzene ring of the ligand tend to form a dimer to improve the mobility for carrier transportation and collection. The strategy demonstrates a champion PCE of 24.35% for the air-processed PSCs with over 1200 hours of maximum power point tracking (MPPT) stability. This study presents a comprehensive approach to overcoming the current Pb-related imperfections induced limitations in PSCs, paving the way for their integration into mainstream solar technologies.

Relationship between the mandibular curve of Spee and the maxillary compensating curve with dentoskeletal morphology : A cross-sectional study in Chinese young adults with normal occlusion.

PURPOSE: The purpose of this cross-sectional study was to use multiple regression analysis to evaluate the relationship between the mandibular curve of Spee (COS) and the maxillary compensating curve with dentoskeletal morphology in young Chinese adults with normal occlusion. METHODS: This study comprised 62 young adults (31 males, mean age: 24.1 ± 2.2 years; 31 females, mean age: 23.3 ± 3.3 years) with Angle class I normal occlusion. For every subject, intraoral scan models of the maxillary and mandibular arches and lateral cephalograms were acquired. The depth of the COS and compensating curve were assessed on the intraoral scan models. Multiple dental arch dimensional and cephalometric variables were screened by univariate analysis. Subsequently, a multiple linear regression model (forward stepwise selection) was constructed to determine which variables were significantly correlated with the two curve depths. RESULTS: In the mandible, the COS depth was deepest at the mesiobuccal cusp of the first molar. Overjet, mandibular arch width and mandibular-occlusal plane angle significantly correlated with the COS depth (P < 0.05), accounting for 33.1% of the variation in the mandibular COS. In the maxilla, the deepest point of the compensating curve was at the distobuccal cusp of the first molar. Mandibular arch perimeter and overbite significantly correlated with the maxillary compensating curve (P < 0.05), explaining 23.3% of the variation. CONCLUSIONS: Overjet, overbite, mandibular-occlusal plane angle, mandibular arch width and perimeter should be considered when reconstructing occlusal curves in clinical orthodontic treatment and in prosthetic restoration.

Cytotoxic and anti-inflammatory polyacetylenes from Tridax procumbens L.

Herein, 17 previously undescribed polyacetylenes and 9 known ones were isolated from Tridax procumbens L. Their structures were identified using spectroscopic techniques (NMR, UV, IR, MS and optical rotation), the modified Mosher method, electronic circular dichroism (ECD) data and ECD calculation. The cytotoxicity of polyacetylenes on six human tumour cell lines (K562, K562/ADR, AGS, MGC-803, SPC-A-1 and MDA-MB-231) was evaluated. (3S,10R)-tridaxin B (2a), (3S,10S)-tridaxin B (2b) and tridaxin F (8) demonstrated substantial cytotoxic effects against the K562 cell line, with half-maximal inhibitory concentration (IC50) values of 2.62, 14.43 and 17.91 µM, respectively. Cell and nucleus morphology assessments and Western blot analysis confirmed that the cytotoxicity of the three polyacetylenes on K562 cells was mediated through a dose-dependent apoptosis pathway. Furthermore, (3S,10R)-tridaxin A (1a) and tridaxin G (9) exhibited considerable inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages, with IC50 values of 15.92 and 20.35 µM, respectively. Further investigations revealed that 9 exerted anti-inflammatory activities by impeding the nuclear translocation of NF-κB and down-regulating the expression of pro-inflammatory factors, including those of iNOS, COX-2, IL-1ß and IL-6, in a concentration-dependent manner. The study provides evidence that polyacetylenes from T. procumbens may serve as a potential source of anti-tumour or anti-inflammatory agents for treating related diseases.

Clinical and radiographic outcomes of implant-supported fixed prostheses with cantilever extension in anterior mandible: A retrospective study.

OBJECTIVES: The objective of this study is to analyze the clinical and radiographic outcomes of implant-supported fixed protheses with cantilever extensions (ISFPCs) in the partially edentulous anterior mandible. MATERIALS AND METHODS: Patients who received anterior mandible implant restoration between January 2016 and December 2021 were included. Patients with two, three, or four continuous missing teeth receiving adjacent implant supported single-unit crowns (ISSCs), ISFPCs, implant-supported fixed protheses without cantilever extensions (ISFPNs) were divided into groups: ISSC+ISSC, ISFPC, ISSC+ISFPC, three-unit ISFPN, ISFPC+ISFPC, or four-unit ISFPN, respectively. We recorded and evaluated survival rates, mechanical and biological complications, peri-implant marginal bone loss (MBL), esthetic outcomes, and patient perceptions. Statistical analysis was performed using linear mixed models (LMM). RESULTS: The study included 87 patients and 152 implants. No implant loss occurred during an average follow-up of 3.48 ± 1.85 years (range: 1-7 years). According to LMM models, prosthetic type had a statistically significant impact on MBL during follow-up periods, in favor of the ISFPC and ISFPC+ISFPC groups (0.16 ± 0.48 mm vs. 0.51 ± 0.49 mm, p = .034; 0.22 ± 0.49 mm vs. 0.60 ± 0.62 mm, p = .043, respectively). Mechanical and biological complications were relatively low and comparable. The four-unit ISFPC group had higher subjective esthetic scores compared with the ISSC+ISSC group (98.6 vs. 83.8, p < .05), and patients in the ISFPC+ISFPC group expressed greater satisfaction with cleanability than the ISFPN group (98.8 vs. 80.6). CONCLUSION: ISFPCs offer a highly predictable treatment option in the anterior mandible, characterized by high survival rates, and comparable complication rates, peri-implant bone stability and esthetics to adjacent ISSCs or ISFPNs.

A Novel tsRNA, m7G-3' tiRNA LysTTT, Promotes Bladder Cancer Malignancy Via Regulating ANXA2 Phosphorylation.

Emerging evidence indicates that transfer RNA (tRNA)-derived small RNAs (tsRNAs), originated from tRNA with high abundance RNA modifications, play an important role in many complex physiological and pathological processes. However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel m7G-modified tsRNA, m7G-3'-tiRNA LysTTT (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an m7G small RNA-modified chip. Moreover, it is found that mtiRL, catalyzed by the tRNA m7G-modifying enzyme mettl1, promotes bladder cancer (BC) malignancy in vitro and in vivo. Mechanistically, mtiRL is found to specifically bind the oncoprotein Annexin A2 (ANXA2) to promote its Tyr24 phosphorylation by enhancing the interactions between ANXA2 and Yes proto-oncogene 1 (Yes1), leading to ANXA2 activation and increased p-ANXA2-Y24 nuclear localization in BC cells. Together, these findings define a critical role for mtiRL and suggest that targeting this novel m7G-modified tsRNA can be an efficient way for to treat BC.

Impacts of microbiota and its metabolites through gut-brain axis on pathophysiology of major depressive disorder.

Major depressive disorder (MDD) is characterized by a high rate of recurrence and disability, which seriously affects the quality of life of patients. That's why a deeper understanding of the mechanisms of MDD pathology is an urgent task, and some studies have found that intestinal symptoms accompany people with MDD. The microbiota-gut-brain axis is the bidirectional communication between the gut microbiota and the central nervous system, which was found to have a strong association with the pathogenesis of MDD. Previous studies have focused more on the communication between the gut and the brain through neuroendocrine, neuroimmune and autonomic pathways, and the role of gut microbes and their metabolites in depression is unclear. Metabolites of intestinal microorganisms (e.g., tryptophan, kynurenic acid, indole, and lipopolysaccharide) can participate in the pathogenesis of MDD through immune and inflammatory pathways or by altering the permeability of the gut and blood-brain barrier. In addition, intestinal microbes can communicate with intestinal neurons and glial cells to affect the integrity and function of intestinal nerves. However, the specific role of gut microbes and their metabolites in the pathogenesis of MDD is not well understood. Hence, the present review summarizes how gut microbes and their metabolites are directly or indirectly involved in the pathogenesis of MDD.

WSSV early protein WSSV004 enhances viral replication by suppressing LDH activity.

White spot syndrome virus (WSSV) is known to upregulate glycolysis to supply biomolecules and energy for the virus's replication. At the viral genome replication stage, lactate dehydrogenase (LDH), a glycolytic enzyme, shows increased activity without any increase in expression. In the present study, yeast 2-hybrid screening was used to identify WSSV proteins that interacted with LvLDH isoform 1 and 2, and these included the WSSV early protein WSSV004. The interaction between WSSV004 and LvLDH1/2 was confirmed by co-immunoprecipitation. Immunofluorescence showed that WSSV004 co-localized with LvLDH1/2 in the cytoplasm. dsRNA silencing experiments showed that WSSV004 was crucial for WSSV replication. However, although WSSV004 silencing led to the suppression of total LvLDH gene expression during the viral late stage, there was nevertheless a significant increase in LvLDH activity at this time. We also used affinity purification-mass spectrometry to identify cellular proteins that interact with WSSV004, and found a total of 108 host proteins and 3 WSSV proteins with which it potentially interacts. Bioinformatics analysis revealed that WSSV004 and its interacting proteins might be responsible for various biological pathways during infection, including vesicular transport machinery and RNA-related functions. Collectively, our study suggests that WSSV004 serves as a multifunctional modulator to facilitate WSSV replication.

Advancing intrauterine adhesion severity prediction: Integrative machine learning approach with hysteroscopic cold knife system, clinical characteristics and hematological parameters.

Intrauterine Adhesion (IUA) constitute a significant determinant impacting female fertility, potentially leading to infertility, miscarriage, menstrual irregularities, and placental complications. The precise assessment of the severity of IUA is pivotal for the customization of personalized treatment plans, aimed at enhancing the success rate of treatments and mitigating reproductive health risks. This study proposes bTLSMA-SVM-FS, a novel feature selection machine learning model that integrates an enhanced slime mould algorithm (SMA), termed TLSMA, with support vector machines (SVM), aiming to develop a predictive model for assessing the severity of IUA. Initially, a series of optimization comparative experiments were conducted on the TLSMA using the CEC 2017 benchmark functions. By comparing it with eleven meta-heuristic algorithms as well as eleven SOTA algorithms, the experimental outcomes corroborated the superior performance of the TLSMA. Subsequently, the developed bTLSMA-SVM-FS model was employed to conduct a thorough analysis of the clinical features of 107 IUA patients from Wenzhou People's Hospital, comprising 61 cases of moderate IUA and 46 cases of severe IUA. The evaluation results of the model demonstrated exceptional performance in predicting the severity of IUA, achieving an accuracy of 86.700 % and a specificity of 87.609 %. Moreover, the model successfully identified critical factors influencing the prediction of IUA severity, including the preoperative Chinese IUA score, production times, thrombin time, preoperative endometrial thickness, and menstruation. The identification of these key factors not only further validated the efficacy of the proposed model but also provided vital scientific evidence for a deeper understanding of the pathogenesis of IUA and the enhancement of targeted treatment strategies.

Panax quinquefolius saponins and panax notoginseng saponins attenuate myocardial hypoxia-reoxygenation injury by reducing excessive mitophagy.

OBJECTIVE: Panax quinquefolius saponins (PQS) and Panax notoginseng saponins (PNS) are key bioactive compounds in Panax quinquefolius L. and Panax notoginseng, commonly used in the treatment of clinical ischemic heart disease. However, their potential in mitigating myocardial ischemia-reperfusion injury remains uncertain. This study aims to evaluate the protective effects of combined PQS and PNS administration in myocardial hypoxia/reoxygenation (H/R) injury and explore the underlying mechanisms. METHODS: To investigate the involvement of HIF-1α/BNIP3 mitophagy pathway in the myocardial protection conferred by PNS and PQS, we employed small interfering BNIP3 (siBNIP3) to silence key proteins of the pathway. H9C2 cells were categorized into four groups: control, H/R, H/R + PQS + PNS, and H/R + PQS + PNS+siBNIP3. Cell viability was assessed by Cell Counting Kit-8, apoptosis rates determined via flow cytometry, mitochondrial membrane potential assessed with the JC-1 fluorescent probes, intracellular reactive oxygen species detected with 2',7'-dichlorodihydrofluorescein diacetate, mitochondrial superoxide production quantified with MitoSOX Red, and autophagic flux monitored with mRFP-GFP-LC3 adenoviral vectors. Autophagosomes and their ultrastructure were visualized through transmission electron microscopy. Moreover, mRNA and protein levels were analyzed via real-time PCR and Western blotting. RESULTS: PQS + PNS administration significantly increased cell viability, reduced apoptosis, lowered reactive oxygen species levels and mitochondrial superoxide production, mitigated mitochondrial dysfunction, and induced autophagic flux. Notably, siBNIP3 intervention did not counteract the cardioprotective effect of PQS + PNS. The PQS + PNS group showed downregulated mRNA expression of HIF-1α and BNIP3, along with reduced HIF-1α protein expression compared to the H/R group. CONCLUSIONS: PQS + PNS protects against myocardial H/R injury, potentially by downregulating mitophagy through the HIF-1α/BNIP3 pathway.

Target organ damage in untreated hypertensive patients with primary aldosteronism.

An increased risk of target organ damage (TOD) has been reported in patients with primary aldosteronism (PA). However, there is relatively little related research on the correlation between the degree of TOD and those with and without PA in newly diagnosed hypertensive patients. The aim of this study was to assess the association between PA and TOD among patients with newly diagnosed hypertension. Newly diagnosed hypertensive patients were consecutively recruited from January 2015 to June 2020 at the University of Hong Kong-Shenzhen Hospital. Patients were stratified into those with and without PA. Data for left ventricular mass index (LVMI), carotid intima-media thickness (CIMT) and plaque, and microalbuminuria were systematically collected. A total of 1044 patients with newly diagnosed hypertension were recruited, 57 (5.5%) of whom were diagnosed with PA. Patients with PA had lower blood pressure, serum lipids, body mass index, and plasma renin activity and a higher incidence of hypokalemia than those without PA. In contrast, the prevalence of left ventricular hypertrophy, increased CIMT, and microalbuminuria was higher in patients with PA than in those without PA. Multivariable regression analysis demonstrated that PA was independently associated with increased LVMI, CIMT and microalbuminuria. Among patients with newly diagnosed hypertension, those with PA had more severe TOD, including a higher LVMI, CIMT and microalbuminuria, than those without PA. These findings emphasize the need for screening TOD in newly diagnosed hypertension due to underlying PA.

Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno-associated virus delivery of vascular endothelial growth factor-C (VEGF-C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF-C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.

Multi-omics analysis of macrophage-associated receptor and ligand reveals a strong prognostic signature and subtypes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a significant contributor to morbidity and mortality worldwide. The interaction between receptors and ligands is the primary mode of intercellular signaling and plays a vital role in the progression of HCC. This study aimed to identify the macrophage-related receptor ligand marker genes associated with HCC and further explored the molecular immune mechanisms attributed to altered biomarkers. Single-cell RNA sequencing data containing primary and recurrent samples were downloaded from the China National GeneBank. Cell types were first identified to explore differences between immune cells from different sample sources. CellChat analysis was used to infer and analyze intercellular communication networks quantitatively. Three molecular subtypes were constructed based on the screened twenty macrophage-associated receptor ligand genes. Bulk RNA-Seq data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. After the screening, the minor absolute shrinkage and selection operator (LASSO) regression model was employed to identify key markers. After collecting peripheral blood and clinical information from patients, an enzyme-linked immunosorbent assay (ELISA) was used to detect the correlation between key markers and IL-10, one of the macrophage markers. After developing a new HCC risk adjustment model and conducting analysis, it was found that there were significant differences in immune status and gene mutations between the high-risk and low-risk groups of patients based on macrophage-associated receptor and ligand genes. This study identified SPP1, ANGPT2, and NCL as key biological targets for HCC. The drug-gene interaction network analysis identified wortmannin, ribavirin, and tarnafloxin as potential therapeutic drugs for the three key markers. In a clinical cohort study, patients with immune checkpoint inhibitor (ICI) resistance had significantly higher expression levels of OPN, ANGPT2, NCL, and IL-10 than patients with ICI-responsiveness. These three key markers were positively correlated with the expression level of IL-10. The signature based on macrophage-associated receptor and ligand genes can accurately predict the prognosis of patients with HCC and the sensitivity to immunotherapy. These results may help guide the development of targeted prevention and personalized treatment of HCC.

Multiplexed representation of others in the hippocampal CA1 subfield of female mice.

Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.

A bibliometric and visual analysis of research trends and hotspots of familial hypertrophic cardiomyopathy: A review.

Familial hypertrophic cardiomyopathy (FHCM) is an inherited cardiac disease caused by mutations of sarcomere proteins and can be the underlining substrate for major cardiovascular events. Early identification and diagnosis of FHCM are essential to reduce sudden cardiac death. So, this paper summarized the current knowledge on FHCM, and displayed the analysis via bibliometrics method. The relevant literature on FHCM were screened searched via the Web of Science Core Collection database from 2012 to 2022. The literatures were was summarized and analyzed via the bibliometrics method analyzed via CiteSpace and VOSviewer according to topic categories, distribution of spatiotemporal omics and authors, as well as references. Since 2012, there are 909 research articles and reviews related to FHCM. The number of publication for the past 10 years have shown that the development of FHCM research has been steady, with the largest amount of literature in 2012. The most published papers were from the United States, followed by the United Kingdom and Italy. The University of London (63 papers) was the institution that published the most research articles, followed by Harvard University (45 papers) and University College London (45 papers). Keywords formed 3 clusters, focused on the pathogenesis of FHCM, the diagnosis of FHCM, FHCM complications, respectively. The bibliometric analysis and visualization techniques employed herein highlight key trends and focal points in the field, predominantly centered around FHCM's pathogenesis, diagnostic approaches, and its complications. These insights are instrumental in steering future research directions in this area.