Macrophage-Derived Exosomes Promoted the Development and Stemness of Inflammatory Bowel Disease-Related Colorectal Cancer via nuclear paraspeckle assembly transcript 1-Mediated miRNA-34a-5p/phosphoprotein enriched in astrocytes 15 Axis.

BACKGROUND: Inflammatory bowel disease (IBD) is closely associated with the development of colorectal cancer (CRC) due to the chronic inflammatory response. Macrophages play critical roles in regulating the microenvironment to facilitate tumor progression. Exosomes are key modulators for the communication between macrophages and tumor cells. The mechanism of macrophage-derived exosomes in IBD-related CRC development remains unclear. METHODS: The macrophages were isolated using fluorescence activating cell sorter (FACS). The RNA and protein expressions in exosomes and CRC cells were examined by quantitative real-time polymerase chain reaction and western blot assays, respectively. CRC cell development was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, BrdU staining, Transwell assay, and spheroid formation assay. The level of stemness was determined by detecting the proportion of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)-positive CRC cells and the expression of LGR5, CD133, and CD44. Molecular interaction experiments were done using luciferase reporter assay and RNA immunoprecipitation assay. Xenograft tumor model in vivo and immunohistochemistry were used to observe the pathological changes. RESULTS: Macrophage-derived exosomes from IBD-related CRC tissues were enriched with nuclear paraspeckle assembly transcript 1 (NEAT1) and able to promote the progression and stemness of CRC both in vitro and in vivo. The exosomal NEAT1 could sponge miR-34a-5p, leading to the restoration of PEA15 expression in CRC cells and promoting the development of CRC. Inhibition of NEAT1 in exosomes could effectivity inhibit the tumor growth in the CRC xenograft model. CONCLUSIONS: These findings provide novel insights into how macrophages affect CRC development and highlight exosomal NEAT1 as a therapeutic target for CRC treatment.

NEAT1 from ulcerative colitis- and colorectal cancer (CRC)-related exosomes promotes the development of CRC by regulating the miR-34a-5p/PEA15 axis in CRC.

The correlation of the liquidus curves and valence electron structures of a ternary lithium halide molten-salt electrolyte for liquid metal batteries.

Liquid metal batteries have received considerable attention owing to their excellent properties. However, an electrolyte with low melting temperature is required to decrease operating temperature for the safety of liquid metal batteries and for saving energy. For revealing the mechanism of low liquefaction temperature, an empirical electron theory of solid molecules was used to study the thermal properties of pure lithium halides and their ternary-phase systems systematically. The theoretical bond lengths, melting points, liquefaction temperatures and mixed energies of pure lithium halides and their ternary phases match the experimental values well. The mechanism of liquefaction temperature for ternary lithium halides depends on their valence electron structures. The liquefaction temperature can be stabilized on a liquidus line or curve through the modulation of the constant number of covalent electrons (nc) and lattice electrons (nl). The liquefaction temperatures on various liquidus lines and curves are positively related to the linear density of valence electron pairs on the strong Li-X bond, bonding factor, and number of valence electrons in the s orbital but are negatively related to the number of valence electrons in the p orbital. With an increase in the linear density of the valence electron pair number and bonding factor, bond strength is enhanced, which increases the resistance of the strong Li-X bond against the break force induced by thermal phonon vibrations, and more thermal phonons with high vibrating energy are required for breaking the strongest Li-X bond at a higher temperature; therefore, the liquefaction temperature increases.

Ten-year survival outcomes of video-assisted thoracic surgery vs. open major lung resection for stage I-III non-small cell lung cancer: a large cohort study in China.

Background: Despite the widespread adoption of video-assisted thoracoscopic surgery (VATS) for major lung resection, the 10-year long-term survival outcomes of non-small cell lung cancer (NSCLC) treated with VATS compared with open major lung resection is lacking. The purpose of this study was to analyze the short- and long-term outcomes of VATS vs. open major lung resection for NSCLC. Methods: The perioperative outcomes and long-term survival of p-stage I-III NSCLC patients who underwent major lung resection via VATS vs. open major lung resection in the Western China Lung Cancer Database (WCLCD) between May 2006 and June 2018 were studied using propensity score matching (PSM). Results: Of the 10,167 patients who underwent surgery for lung malignancies, 6,405 patients with stage I-III NSCLC were included in the study, including 4,224 in the VATS group and 2,181 in the open group. PSM resulted in 1,487 patients in both the VATS and open groups. The patients were matched by patient demographics, Charlson comorbidity index (CCI), tumor histology and TNM stage. Compared with open surgery, major lung resection via VATS resulted in less blood loss (median: 50 vs. 100 mL, P<0.001) and a shorter postoperative hospital stay (7.6±6.0 vs. 8.6±4.9 days, P<0.001) but higher total hospital costs (52.5±21.2 vs. 45.0±16.4 kRMB, P<0.001). The matched cohort showed that patients who underwent major lung resection via VATS had better overall survival (OS) and recurrence-free survival (RFS) than did patients who underwent major lung resection via open surgery (5-year survival: 64.9% vs. 57.7%, P<0.001; 5-year RFS: 50.3% vs. 45.3%, P=0.003). Patients who underwent VATS had a better 10-year OS rate (47.8% vs. 42.6%). According to the subgroup analysis, patients with stage II NSCLC who underwent major lung resection via VATS had better OS and RFS (OS: P<0.001; RFS: P=0.004), while there were no significant differences in OS or RFS between stage I and III NSCLC patients. Conclusions: Major lung resection via the VATS should be the preferred surgical option for stage I-III NSCLC patients due to its superior long-term survival outcome and advantages of less blood loss and shorter postoperative hospital stays.

Study on Vitamin K Levels in Mature Milk of Chinese Lactating Mothers.

OBJECTIVES: This study sought to understand the levels of vitamin K in the mature milk of Chinese lactating mothers, thereby providing a foundation for the development of appropriate intake (AI) of vitamin K for infants aged 0-5 months. METHODS: Five hundred healthy lactating mothers were selected from the mature milk bank established by the Chinese Maternal and Infant Nutrition and Health Cohort by using a simple random sample procedure. Relevant information about lactating mothers and their infants was obtained by a questionnaire survey. Vitamin K1 and vitamin K2 (MK-4 and MK-7) in mature milk were determined by liquid chromatography-tandem mass spectrometry. RESULTS: The total concentration of vitamin K in mature milk was 4.50 (2.85-6.33) ng/mL. The concentrations of vitamin K1, vitamin K2, MK-4, and MK-7 were 2.81 (1.66-4.39) ng/mL, 1.37 (0.75-2.11) ng/mL, 1.20 (0.58-1.97) ng/mL, and 0.13 (0.08-0.19) ng/mL, respectively. The concentration of vitamin K1 was highest and the concentration of MK-7 was lowest. The concentrations of vitamin K2 and MK-4 in mature milk from the south were significantly higher than those in mature milk from the north. The total vitamin K, vitamin K2, and MK-4 concentrations in mature milk of lactating mothers residing in urban areas were higher than those in rural areas. There was a tendency for the concentration of total vitamin K and vitamin K1 to increase with the mother's age. Moreover, the concentration of MK-4 in mature milk was highest in summer, followed by spring and winter. The levels of vitamin K1 and MK-4 in mature milk were found to be affected by lactation stage; they were highest at 91-120 days and lowest at 31-60 days. CONCLUSIONS: Based on the concentration of vitamin K in mature milk found in this study, it is recommended that the appropriate intake of VK for Chinese infants aged 0-5 months is 3.49 µg/d (2.18 µg/d for VK1 and 1.06 µg/d for VK2).

Stiffness Hardening Effect of Wire Rope Isolators under Small Cyclic Loads for Vibration Isolation.

Wire rope isolator (WRI) devices are widely used in vibration reduction industrial equipment, and stiffness is the key parameter that determines isolation effectiveness. WRI devices show slight nonlinearity under small loads, and the manufacturers generally only provide the initial parameters. To investigate the mechanical behavior changes in the WRI devices under repeated loads, five types of WRI specimens were tested under various amplitudes, loading speeds, and preloads. The test results of large symmetrical compression and tension loads showed that the WRI devices demonstrated stable hysteresis curves under repeated loads, while the hysteresis curves were independent of the loading speed. The test results of small cyclic loads with large preloads show that the stiffness of the WRI specimen follows the logarithmic law, with the cycle number under various loading conditions. Particularly, the stiffness of the specimen increases by about 10-30% after 50 cycles. The initial stiffness Ka decreases linearly with the preloads, while the decrease is quadratic in relation to the cyclic load. The hardening coefficient Ca shows a positive correlation with the loading capacity of the WRI devices, while it shows a negative correlation with the preload and cyclic load amplitudes. It is recommended to consider the stiffness increase in the WRI devices during the evaluation of isolation effectiveness.

Clinical Analysis of 32 Cases of Subglottic Benign Airway Stenosis Treated With Montgomery T Silicone Stent.

Objective: To explore the complications of long-term placement of Montgomery T silicone stent (T-tube) in the treatment of subglottic benign airway stenosis (SBAS) and the timing of successful T-tube removal. Methods: We retrospectively collected the clinical data of 32 patients with SBAS who underwent the treatment of T-tube and analyzed their placement and successful removal of the T-tube. Results: There were 22 males and 10 females, aged from 21 to 79 years (60.9 ± 13.7 years). The T-tubes were successfully placed in all 32 patients, and 6 patients (18.8%) with mild stenosis were placed by the intravenous conscious sedation. The longest follow-up period was 60.4 months, and 17 patients (53.1%) had the T-tubes for more than 12 months; 5 patients (15.6%) were changed to the tracheostomy cannula after unplanned removal of the T-tubes for various reasons; the T-tubes were successfully removed in 9 patients (28.1%), and the duration of T-tubes placement was 5.2-22.7 months (12.1 ± 6.3 months), among them anatomical stenosis in 9 patients (100%). Secretion retention was observed in 32 patients (100%), granulation tissue hyperplasia was observed in 9 patients (28.1%), and the normal ventilation was not affected in most patients by bronchoscopic treatment and follow-up; the T-tubes were removed in 3 patients due to severe complications. There was no significant difference in the incidences of secretion retention and granulation tissue hyperplasia between the time point at 1 week, 1 month, 3 months, and 12 months, p > 0.05. In patients with T-tube more than 12 months, the severity of secretion retention at 1 week, 1 month, 3 months, and 12 months was significantly different, p < 0.05, however, there was no significant difference in the severity of granulation tissue hyperplasia, p > 0.05. Conclusions: T-tube is safe and effective in the treatment of SBAS. The severity of secretion retention increased in patients with long-term placement of the T-tube. For patients with mild stenosis and anatomical stenosis, the T-tube removal can be attempted at about 1 year of follow-up.

Study on the complications after implantation of different types of metal stents in rabbit trachea.

OBJECTIVE: To observe the complications and inflammatory responses caused by the different types of metal stents in the trachea of rabbits. METHOD: 79 rabbits were randomly divided into 4 groups and were implanted with the customized nickel-titanium alloy metal stents(fully covered metal stent: group A, bare metal stent: group B, segmented covered metal stent: group C and control group: group D). The complications (tracheal deformation, granulation tissue hyperplasia, scar hyperplasia and secretion retention) of different types of metal stents were compared by observing the anatomical and pathological specimens of dead rabbits; And the expression of inflammatory factors of different types of metal stents were compared by detecting the tissue of tracheas of dead rabbits. RESULTS: (1)There were significant differences in the above four complications among groups A, B and C(p < 0.01). The incidences of tracheal deformation, scar hyperplasia and secretion retention in group A were significantly higher than that in group B(p < 0.0167), however, the incidence of granulation tissue hyperplasia in group A was significantly lower than that in group B(p < 0.0167). The incidence of scar hyperplasia in group A was significantly lower than that in group C(p < 0.0167) and there were no significant differences in other complications between these two groups(p > 0.0167). The incidences of tracheal deformation, scar hyperplasia and secretion retention in group B were significantly lower than that in group C(p < 0.0167), however, the incidence of granulation tissue hyperplasia in group B was significantly higher than that in group C(p < 0.0167). (2)The concentration of IL-1ß in group A was higher than that in group B (p < 0.05 and foldchange>1.2). CONCLUSION: (1)There are significant differences in complications between the fully covered metal stent, bare metal stent and segmented covered metal stent; the incidences of complications between the segmented covered metal stent and fully covered metal stent are similar. (2)Changes in different inflammatory factors can be observed between the fully covered and bare metal stent.

A Comprehensive Proteogenomic and Spatial Analysis of Innate and Acquired Resistance of Metastatic Melanoma to Immune Checkpoint Blockade Therapies.

While a subset of patients with metastatic melanoma achieves durable responses to immune checkpoint blockade (ICB) therapies, the majority ultimately exhibit either innate or acquired resistance to these treatments. However, the molecular mechanisms underlying resistance to ICB therapies remain elusive and are warranted to elucidate. Here, we comprehensively investigated the tumor and tumor immune microenvironment (TIME) of paired pre- and post-treatment tumor specimens from metastatic melanoma patients who were primary or secondary resistance to anti-CTLA-4 and/or anti-PD-1/PD-L1 therapies. Differentially expressed gene (DEG) analysis and single-sample gene set enrichment analysis (ssGSEA) with transcriptomic data identified cell cycle and c-MYC signaling as pathway-based resistance signatures. And weighted gene co-expression network analysis (WGCNA) revealed the activation of a cross-resistance meta-program involving key signaling pathways related to tumor progression in ICB resistant melanoma. Moreover, spatially-resolved, image-based immune monitoring analysis by using NanoString's digital spatial profiling (DSP) and Cyclic Immunofluorescence (CyCIF) showed infiltration of suppressive immune cells in the tumor microenvironment of melanoma with resistance to ICB therapies. Our study reveals the molecular mechanisms underlying resistance to ICB therapies in patients with metastatic melanoma by conducting such integrated analyses of multi-dimensional data, and provides rationale for salvage therapies that will potentially overcome resistance to ICB therapies. Statement of translational relevance: This study paves the way for the creation of innovative therapeutic strategies, aimed at subverting resistance to immune checkpoint blockade (ICB) therapies in metastatic melanoma patients. By unraveling the specific molecular mechanisms underlying resistance, scientists can design effective alternative treatments that target pathways such as pathways associated with cell cycle dysregulation and c-MYC signaling. Furthermore, through the application of advanced immune monitoring techniques such as NanoString Digital Spatial Profiling (DSP) and Cyclic Immunofluorescence (CyCIF), this study has significantly enriched our understanding of the tumor microenvironment. This enhanced characterization facilitates the discovery of potential biomarkers that may forecast a patient's response to ICB treatment. Ultimately, these advancements could potentially refine patient outcomes and foster the development of more personalized cancer treatments in the future.

A Novel Multi-Dimensional Joint Search Method for the Compression of Medical Image Segmentation Models.

Due to the excellent results achieved by transformers in computer vision, more and more scholars have introduced transformers into the field of medical image segmentation. However, the use of transformers will make the model's parameters very large, which occupies a large amount of the computer's resources, making them very time-consuming during training. In order to alleviate this disadvantage, this paper explores a flexible and efficient search strategy that can find the best subnet from a continuous transformer network. The method is based on a learnable and uniform L1 sparsity constraint, which contains factors that reflect the global importance of the continuous search space in different dimensions, while the search process is simple and efficient, containing a single round of training. At the same time, in order to compensate for the loss of accuracy caused by the search, a pixel classification module is introduced into the model to compensate for the loss of accuracy in the model search process. Our experiments show that the model in this paper compresses 30% of the parameters and FLOPs used, while also showing a slight increase in the accuracy of the model on the Automatic Cardiac Diagnosis Challenge (ACDC) dataset.

From molecular subgroups to molecular targeted therapy in rheumatoid arthritis: A bioinformatics approach.

1Background: Rheumatoid Arthritis (RA) is a heterogeneous autoimmune disease with multiple unidentified pathogenic factors. The inconsistency between molecular subgroups poses challenges for early diagnosis and personalized treatment strategies. In this study, we aimed to accurately distinguish RA patients at the transcriptome level using bioinformatics methods. 2Methods: We collected a total of 362 transcriptome datasets from RA patients in three independent samples from the GEO database. Consensus clustering was performed to identify molecular subgroups, and clinical features were assessed. Differential analysis was employed to annotate the biological functions of specifically upregulated genes between subgroups. 3Results: Based on consensus clustering of RA samples, we identified three robust molecular subgroups, with Subgroup III representing the high-risk subgroup and Subgroup II exhibiting a milder phenotype, possibly associated with relatively higher levels of autophagic ability. Subgroup I showed biological functions mainly related to viral infections, cellular metabolism, protein synthesis, and inflammatory responses. Subgroup II involved autophagy of mitochondria and organelles, protein localization, and organelle disassembly pathways, suggesting heterogeneity in the autophagy process of mitochondria that may play a protective role in inflammatory diseases. Subgroup III represented a high-risk subgroup with pathological processes including abnormal amyloid precursor protein activation, promotion of inflammatory response, and cell proliferation. 4Conclusion: The classification of the RA dataset revealed pathological heterogeneity among different subgroups, providing new insights and a basis for understanding the molecular mechanisms of RA, identifying potential therapeutic targets, and developing personalized treatment approaches.

A novel 3D-printed educational model for the training of laparoscopic bile duct Exploration:a pilot study for beginning trainees.

Background: Laparoscopic common bile duct exploration (LCBDE) is a minimally invasive procedure for the removal of bile duct stones that is often performed by experienced hepatobiliary surgeons; beginners do not easily master this approach. Aim: To investigate the effectiveness and practicality of a three-dimensional printed (3DP) anatomical model based on radiographic images in the training of LCBDE techniques and formulate standardized educational workflows. Methods: Colored LCBDE training models were produced using 3DP technology. Twenty standardized training trainees were randomly divided into two groups: a 3DP model training group and a traditional laparoscopic simulation training group. Both groups received the same number of teaching hours. After a 4-weeks training course, the trainees' subjective and objective progress in basic knowledge and manipulations were evaluated and compared. Results: Compared with traditional laparoscopic simulation, 3DP model simulation training is of great significance in improving trainers' understanding of surgical procedures and cooperation during the operation. Trainees with 3DP models training demonstrated a significant improvement in their understanding of the key points of surgery (χ2 = 6.139, p = 0.013) and skills scores, especially in core procedural steps operation. More importantly, the trainees showed higher levels of satisfaction and self-confidence while assisting in the surgery. Conclusion: With the development of 3DP models, improvements in the learning effect for theoretical understanding and practical skills were significant. The present study is the initial educational experience with 3DP models to facilitate the operational capabilities of the trainees for LCBDE.

The association between macrosomia and glucose, lipids and hormones levels in maternal and cord serum: a case-control study.

BACKGROUND: The formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum. METHODS: In the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum. RESULTS: In maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia. CONCLUSION: In conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome.

Association between breastfeeding duration and neurodevelopment in Chinese children aged 2 to 3 years.

OBJECTIVE: The aim of this study was to explore the relationship between breastfeeding duration and neurodevelopment in children aged 2 to 3 years in a Chinese population. METHODS: This study was based on a cross-sectional survey. The data were from the National Nutrition and Health Systematic Survey for children in China which was conducted from 2019 to 2020. Characteristics of parents and children and the breastfeeding duration were obtained using interview-administered questionnaires. Children's neuropsychological development was assessed by a trained child health care physician using the Child Psychological Development Scale. A multivariable linear regression model was used to analyze the association between breastfeeding duration and neuropsychological development. RESULTS: A total 1290 children aged 2-3 years were included in the present analysis. In multivariable linear regression models, after adjustment for potential confounders, children who were breastfed for 7-12 months had a 3.59-point increase in gross motor development (ß = 3.59; 95 % confidence interval [CI]: 1.23 to 6.34), a 3.73-point increase in fine motor development (ß = 3.73; 95 % CI: 1.09 to 6.47), and a 2.87-point in language development (ß = 2.87; 95 % CI: 1.12 to 5.31) compared with those who were never breastfed. Children who were breastfed for > 12 months had a 3.77-point increase in fine motor development (ß = 3.77; 95 % CI: 0.98 to 6.86) compared with those who were never breastfed. CONCLUSIONS: Longer breastfeeding duration was associated with increased gross motor, fine motor, and language scores in our study population. Mothers in China should be encouraged to initiate and continue breastfeeding.

Olanzapine vs. magnesium valproate vs. lamotrigine in anti-N-methyl-D-aspartic acid receptor encephalitis: a retrospective study.

BACKGROUND: This study aimed to compare the impact of olanzapine, magnesium valproate, and lamotrigine as adjunctive treatments for anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. And it is expected to add supporting points related to the rebalance of neurotransmitters in the brain through adjuvant therapy in the clinical management of anti-NMDAR encephalitis. METHODS: This retrospective study included patients diagnosed with anti-NMDAR encephalitis who received standardized immunotherapy at Hunan Brain Hospital between January 2018 and December 2020. RESULTS: Compared to the olanzapine group, both the magnesium valproate and lamotrigine groups showed lower scores on the positive and negative symptom scale (PANSS) total score after 3 weeks of treatment (all P < 0.05). The Montreal Cognitive Assessment Scale (MoCA) scores in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group after 3 weeks and 3 months of treatment (all P < 0.05). After 3 months of treatment, the proportions of patients with a modified Rankin scale score (mRS) of 0-1 in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group (all P < 0.05). The electroencephalogram (EEG) abnormality ranks at 3 months were significantly lower in the magnesium valproate and lamotrigine groups compared with the olanzapine group (all P < 0.05). Furthermore, the Glx/Cr ratio significantly decreased after 3 months of treatment (all P < 0.05) in the magnesium valproate and lamotrigine groups, while the Glx/Cr ratio in the olanzapine group showed no significant change (P > 0.05). CONCLUSION: Compared with olanzapine, the addition of magnesium valproate or lamotrigine to immunotherapy might be associated with a lower PANSS score, higher MoCA score, and lower mRS score. The improvement of neurological functions and cognitive function may be related to the decreased Glx/Cr ratio.

The destruction of cytoplasmic skeleton leads to the change of nuclear structure and the looseness of lamin A submicroscopic network.

The interaction between lamin A and the cytoplasmic skeleton plays a key role in maintaining nuclear mechanical properties. However, the effect of destruction of the cytoplasmic skeleton on the 3D submicroscopic structure of lamin A has not been elucidated. In this study, we developed an image quantization algorithm to quantify changes in the submicroscopic structure of the intact lamin A 3D network within the nucleus. We used blebbistatin or nocodazole to disrupt the fibrillar structure of F-actin or tubulin, respectively, and then quantified changes in the lamin A super-resolution network structure, the morphological and mechanical properties of the nucleus and the spatial distribution of chromosomes. Ultimately, we found for the first time that disruption of the cytoplasmic skeleton changes the lamin A submicroscopic network and nuclear structural characteristics. In summary, this study contributes to understanding the trans-nuclear membrane interaction characteristics of lamin A and the cytoplasmic skeleton.

Identification of Potential Therapeutics for Infantile Hemangioma via in silico Investigation and in vitro Validation.

Introduction: Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5-10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology. Methods: Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD). Results: Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value. Conclusion: Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.

Transcriptomic analysis used to discover potential therapeutics for Infantile Hemangioma (IH). Key IH-related pathways: PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling identified. Identified 44 non-toxic drugs as potential IH therapies via CMap and CTD. Twelve molecular agents show potential as IH therapy candidates. In vitro studies confirmed entinostat, sorafenib, dasatinib, and sirolimus inhibit HemEC cell proliferation and induce apoptosis.

Different care mode alter composition and function of gut microbiota in cerebral palsy children.

Introduction: Specialized care is essential for the recovery of children with cerebral palsy (CP). This study investigates how different care modes impact the gut microbiota. Methods: Fecal samples from 32 children were collected, among whom those cared for by family (n = 21) were selected as the observation group, and those cared for by children's welfare institutions (n = 11) were selected as the control group (registration number of LGFYYXLL-024). The gut microbiota profiles were analyzed. Results: There was no significant difference in the α-diversity of the gut microbiota and the abundance at the phylum level. However, at the genus level, the observation group showed a significant increase in the abundance of butyrate-producing bacteria Bacteroides and Lachnospiracea incertae sedis (P < 0.05), and a significant decrease in the abundance of opportunistic pathogens Prevotella, Clostridium cluster IV, Oscillibacter, and Fusobacterium (P < 0.05). Additionally, lipid metabolism, carbohydrate metabolism, transcription, cellular processes and signaling, and membrane transport were significantly upregulated in the observation group. Lipid metabolism was positively correlated with Bacteroides and Lachnospiracea incertae sedis, indicating a positive impact of the family-centered care mode on bacterial metabolism processes. Discussion: This study highlights that the family-centered care mode had a positive impact on the composition and function of the gut microbiota. The study provides valuable insights into the relationship between care mode and gut microbiota, which can inspire the development of interventions for cerebral palsy.

Flexible Crossbar Molecular Devices with Patterned EGaIn Top Electrodes for Integrated All-Molecule-Circuit Implementation.

Here, a unique crossbar architecture is designed and fabricated, incorporating vertically integrated self-assembled monolayers in electronic devices. This architecture is used to showcase 100 individual vertical molecular junctions on a single chip with a high yield of working junctions and high device uniformity. The study introduces a transfer approach for patterned liquid-metal eutectic alloy of gallium and indium top electrodes, enabling the creation of fully flexible molecular devices with electrical functionalities. The devices exhibit excellent charge transport performance, sustain a high rectification ratio (>103), and stable endurance and retention properties, even when the devices are significantly bent. Furthermore, Boolean logic gates, including OR and AND gates, as well as half-wave and full-wave rectifying circuits, are successfully implemented. The unique design of the flexible molecular device represents a significant step in harnessing the potential of molecular devices for high-density integration and possible molecule-based computing.

Restoration of motion-blurred numeral image using a complex-amplitude diffractive processor.

We propose a complex-amplitude diffractive processor based on diffractive deep neural networks (D2NNs). By precisely controlling the propagation of an optical field, it can effectively remove the motion blur in numeral images and realize the restoration. Comparative analysis of phase-only, amplitude-only, and complex-amplitude diffractive processor reveals that the complex-amplitude network significantly enhances the performance of the processor and improves the peak signal-to-noise ratio (PSNR) of the images. Appropriate use of complex-amplitude networks contributes to reduce the number of network layers and alleviates alignment difficulties. Due to its fast processing speed and low power consumption, complex-amplitude diffractive processors hold potential applications in various fields including road monitoring, sports photography, satellite imaging, and medical diagnostics.