A new machine learning model to predict the prognosis of cardiogenic brain infarction.

Cardiogenic cerebral infarction (CCI) is a disease in which the blood supply to the blood vessels in the brain is insufficient due to atherosclerosis or stenosis of the coronary arteries in the patient's heart, which leads to neurological deficits. To predict the pathogenic factors of cardiogenic cerebral infarction, this paper proposes a machine learning based analytical prediction model. 494 patients with CCI who were hospitalized for the first time were consecutively included in the study between January 2017 and December 2021, and followed up every three months for one year after hospital discharge. Clinical, laboratory and imaging data were collected, and predictors associated with relapse and death in CCI patients at six months and one year after discharge were analyzed using univariate and multivariate logistic regression methods, meanwhile established a new machine learning model based on the enhanced moth-flame optimization (FTSAMFO) and the fuzzy K-nearest neighbor (FKNN), called BITSAMFO-FKNN, which is practiced on the dataset related to patients with CCI. Specifically, this paper proposes the spatial transformation strategy to increase the exploitation capability of moth-flame optimization (MFO) and combines it with the tree seed algorithm (TSA) to increase the search capability of MFO. In the benchmark function experiments FTSAMFO beat 5 classical algorithms and 5 recent variants. In the feature selection experiment, ten times ten-fold cross-validation trials showed that the BITSAMFO-FKNN model proved actual medical importance and efficacy, with an accuracy value of 96.61%, sensitivity value of 0.8947, MCC value of 0.9231, and F-Measure of 0.9444. The results of the trial showed that hemorrhagic conversion and lower LVDD/LVSD were independent risk factors for recurrence and death in patients with CCI. The established BITSAMFO-FKNN method is helpful for CCI prognosis and deserves further clinical validation.

Nanosecond-pulsed plasma protects against bacterial fruit blotch and promotes melon seedling growth.

BACKGROUND: Bacterial fruit blotch (BFB), known as the 'cancer' of cucurbits, is a seed-borne disease of melons caused by Acidovorax citrulli. Traditional chemical treatments for BFB are ineffective and adversely affect the environment. Using dielectric barrier discharge (DBD) nanosecond-pulsed plasma technology, melon seeds were treated to promote germination and growth and to control BFB. RESULTS: Based on the evaluation parameters of seed germination, seedling growth, leaf yellowing and bacterial infection after seed plasma treatments, 9 min at 20 kV was selected as the optimal plasma discharge parameter. In this study, seedling growth was significantly improved after treating melon seeds carrying A. citrulli using this discharge parameter. The number of first true leaves measured on the eighth day was 2.3 times higher and the disease index was reduced by 60.5% compared to the control group. Attenuated total reflectance-Fourier transform infrared measurements show that plasma treatments penetrate the seed coat and denature polysaccharides and proteins in the seed kernel, affecting their growth and sterilization properties. CONCLUSION: Pre-sowing treatment of melon seeds carrying A. citrulli using nanosecond-pulsed plasma technology can effectively control seedling BFB disease and promote melon seedling growth by optimizing DBD parameters. © 2024 Society of Chemical Industry.

Double Droplets Impact an Inclined Superhydrophobic Surface.

The rebound dynamics of double droplets impacting an inclined superhydrophobic surface decorated with macro-ridges are investigated via lattice Boltzmann method (LBM) simulations. Four rebound regions are identified, that is, the no-coalescence-rebound (NCR), the partial-coalescence-rebound of the middle part bounces first (PCR-M), and the side part bounces first (PCR-S), as well as the complete-coalescence-rebound (CCR). The occurrence of the rebound regions strongly depends on the droplet arrangement, the center-to-center distance of the droplets, and the Weber number. Furthermore, the contact time is closely related to the rebound regions. The PCR-M region can significantly reduce the contact time because the energy dissipation in this region may decrease which can promote the rebound dynamic. Intriguingly, the contact time is also affected by the droplet arrangement; i.e., droplets arranged parallel to the ridge dramatically shorten the contact time since this arrangement increases the asymmetry of the liquid film. Therefore, for multidrop impact, the contact time can be effectively manipulated by changing the rebound region and the droplet arrangement. This work focuses on elucidating the wetting behaviors, rebound regions, and contact time of the multiple-droplet impacting an inclined superhydrophobic surface decorated with macro-ridges.

Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.

BACKGROUND: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB). METHODS: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing. RESULTS: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2 and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB. CONCLUSION: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of NB susceptibility gene ALK.

Bouncing Dynamics of Drops' Successive Off-Center Impact.

Bouncing dynamics of a trailing drop off-center impacting a leading drop with varying time intervals and Weber numbers are investigated experimentally. Whether the trailing drop impacts during the spreading or receding process of the leading drop is determined by the time interval. For a short time interval of 0.15 ≤ Δt* ≤ 0.66, the trailing drop impacts during the spreading of the leading drop, and the drops completely coalesce and rebound; for a large time interval of 0.66 < Δt* ≤ 2.21, the trailing drop impacts during the receding process, and the drops partially coalesce and rebound. Whether the trailing drop directly impacts the surface or the liquid film of the leading drop is determined by the Weber number. The trailing drop impacts the surface directly at moderate Weber numbers of 16.22 ≤ We ≤ 45.42, while it impacts the liquid film at large Weber numbers of 45.42 < We ≤ 64.88. Intriguingly, when the trailing drop impacts the surface directly or the receding liquid film, the contact time increases linearly with the time interval but independent of the Weber number; when the trailing drop impacts the spreading liquid film, the contact time suddenly increases, showing that the force of the liquid film of the leading drop inhibits the receding of the trailing drop. Finally, a theoretical model of the contact time for the drops is established, which is suitable for different impact scenarios of the successive off-center impact. This study provides a quantitative relationship to calculate the contact time of drops successively impacting a superhydrophobic surface, facilitating the design of anti-icing surfaces.

Novel quinoxaline analogs as telomeric G-quadruplex ligands exert antitumor effects related to enhanced immunomodulation.

G-quadruplexes (G4s) are commonly formed in the G-rich strand of telomeric DNA. Ligands targeting telomeric G4 induce DNA damage and telomere dysfunction, which makes them potential antitumor drugs. New telomeric G4 ligands with drug-likeness are still needed to be exploited, especially with their antitumor mechanisms thoroughly discussed. In this study, a novel series of quinoxaline analogs were rationally designed and synthesized. Among them, R1 was the most promising ligand for its cytotoxic effects on tumor cells and stabilizing ability with telomeric G4. Cellular assays illustrated that R1 stabilized G4 and induced R-loop accumulation in the telomeric regions, subsequently triggering DNA damage responses, cell cycle arrest in G2/M phase, apoptosis and antiproliferation. Moreover, R1 evoked immunogenic cell death (ICD) in tumor cells, which promoted the maturation of bone marrow derived dendritic cells (BMDCs). In breast cancer mouse model, R1 exhibited a significant decrease in tumor burden through the immunomodulatory effects, including the increase of CD4+ and CD8+ T cells in tumors and cytokine levels in sera. Our research provides a new idea that targeting telomeric G4 induces DNA damage responses, causing antitumor effects both in vitro and in vivo, partially due to the enhancement of immunomodulation.

Expectant management for umbilical artery thrombosis in the third trimester of pregnancy: a case report.

Background: Umbilical artery thrombosis (UAT) is a rare complication of pregnancy and is associated with adverse pregnancy outcomes, including fetal intrauterine distress, intrauterine growth restriction, and still birth. UAT is unpredictable, and prenatal diagnosis is challenging. There is no consensus on the treatment strategy of UAT, especially for patients with prenatal detection of one of the umbilical artery embolisms. In most previous cases, an emergency cesarean section was performed, or intrauterine fetal death occurred at the time of UAT diagnosis. Case presentation: In this report, we describe a case of thrombosis in one of the umbilical arteries detected by routine ultrasonography at 31+3 weeks of gestation in a 34-year-old woman. Following expectant management with intensive monitoring for 4 four days, an emergency cesarean section was performed because of abnormal fetal umbilical cord blood flow and middle cerebral artery blood flow; the newborn was in good condition at birth. The final umbilical cord histopathology revealed thrombosis in one of the umbilical arteries. Both mother and newborn described in this case underwent long-term follow-up for nearly 2 two years and are currently in good health without any complications. Conclusions: Based on our experience, obstetricians should comprehensively consider the current gestational age and fetal intrauterine status when UAT is suspected to determine the best delivery time. The appropriate gestational age should be prolonged as long as the mother and fetus are stable when the fetus is immature, trying our best to complete the corticosteroid treatment to promote fetal lung maturity and magnesium sulfate to protect fetal brain. During expectant management, ultrasound monitoring, electronic fetal heart monitoring, and fetal movement counting should be strengthened. Clinicians should ensure that the patients and their families are informed about all potential risks of expectant management for UAT.

Dopamine D1 receptor in medial prefrontal cortex mediates the effects of TAAR1 activation on chronic stress-induced cognitive and social deficits.

Trace amine-associated receptor 1 (TAAR1) is an intracellular expressed G-protein-coupled receptor that is widely expressed in major dopaminergic areas and plays a crucial role in modulation of central dopaminergic neurotransmission and function. Pharmacological studies have clarified the roles of dopamine D1 receptor (D1R) in the medial prefrontal cortex (mPFC) in cognitive function and social behaviors, and chronic stress can inhibit D1R expression due to its susceptibility. Recently, we identified TAAR1 in the mPFC as a potential target for treating chronic stress-induced cognitive and social dysfunction, but whether D1R is involved in mediating the effects of TAAR1 agonist remains unclear. Combined genomics and transcriptomic studies revealed downregulation of D1R in the mPFC of TAAR1-/- mice. Molecular dynamics simulation showed that hydrogen bond, salt bridge, and Pi-Pi stacking interactions were formed between TAAR1 and D1R indicating a stable TAAR1-D1R complex structure. Using pharmacological interventions, we found that D1R antagonist disrupted therapeutic effect of TAAR1 partial agonist RO5263397 on stress-related cognitive and social dysfunction. Knockout TAAR1 in D1-type dopamine receptor-expressing neurons reproduced adverse effects of chronic stress, and TAAR1 conditional knockout in the mPFC led to similar deficits, along with downregulation of D1R expression, all of these effects were ameliorated by viral overexpression of D1R in the mPFC, suggesting the functional interaction between TAAR1 and D1R. Collectively, our data elucidate the possible molecular mechanism that D1R in the mPFC mediates the effects of TAAR1 activation on chronic stress-induced cognitive and social deficits.

Spatial difference on nitrogen removal in the water based on different resolutions for Sanhuanpao wetland, Northeast China.

The research on the deviations caused by different resolutions is relevant to the study of spatial scale effects. In 2018, spatial interpolations were performed using the removal ratios of the TN, NH4-N, and NO3-N of the layers of different resolutions, respectively. Based on the mean and the standard deviation, the area, shape, and position were obtained for four levels related to the removal ratios of the three nitrogen forms. The linear and 6th function fitting methods were used to reveal the differences in nitrogen removal in wetland water at different spatial resolutions. The results showed that a resolution of 25 times the original was the key scale of the spatial effects. Due to the fact that 52 of the 72 functions did not reach a significant level (P < 0.05), the spatial scale effect of the nitrogen removal was mainly characterized by disorderly fluctuations. The results have a certain extrapolation value for the analysis of spatial scale effects. PRACTITIONER POINTS: The resolution difference was not sufficient to change the spatial pattern of the geographic phenomena. The resolution of 25 times the original was the important scale for determining spatial effects. When studying the spatial scale effects caused by differences in resolution, it was necessary to comprehensively consider various resolutions.

Discovery of a triphenylamine-based ligand that targets mitochondrial DNA G-quadruplexes and activates the cGAS-STING immunomodulatory pathway.

Stabilization of G-quadruplex (G4) structures in mitochondria leads to the damage of mitochondrial DNA (mtDNA), making mtDNA G4s a promising target in the field of cancer therapy in recent years. Damaged mtDNA released into the cytosol can stimulate cytosolic DNA-sensing pathways, and cGAS-STING pathway is a typical one with potent immunostimulatory effects. A few small molecule ligands of mtDNA G4s are identified with antitumor efficacy, but little is known about their results and mechanisms on immunomodulation. In this study, we engineered a series of triphenylamine-based analogues targeting mtDNA G4s, and A6 was determined as the most promising compound. Cellular studies indicated that A6 caused severe mtDNA damage. Then, damaged mtDNA stimulated cGAS-STING pathway, resulting in the following cytokine production of tumor cells and the maturation of DCs. In vivo experiments certified that A6 exerted suppressive influences on tumor growth and metastasis in 4T1 cell-bearing mice by the regulation of TME, including the remodeling of macrophages and the activation of T cells. To our knowledge, it is the first time to report a ligand targeting mtDNA G4s to activate the cGAS-STING immunomodulatory pathway, providing a novel strategy for the future development of mtDNA G4-based antitumor agents.

Construction of molecular subtype model of osteosarcoma based on endoplasmic reticulum stress and tumor metastasis-related genes.

Introduction: Osteosarcoma, the prevailing primary bone malignancy among children and adolescents, is frequently associated with treatment failure primarily due to its pronounced metastatic nature. Methods: This study aimed to establish potential associations between hub genes and subtypes for the treatment of metastatic osteosarcoma. Differentially expressed genes were extracted from patients diagnosed with metastatic osteosarcoma and a control group of non-metastatic patients, using the publicly available gene expression profile (GSE21257). The intersection of these gene sets was determined by focusing on endoplasmic reticulum (ER) stress-related genes sourced from the GeneCards database. We conducted various analytical techniques, including functional and pathway enrichment analysis, WGCNA analysis, protein-protein interaction (PPI) network construction, and assessment of immune cell infiltration, using the intersecting genes. Through this analysis, we identified potential hub genes. Results: Osteosarcoma subtype models were developed using molecular consensus clustering analysis, followed by an examination of the associations between each subtype and hub genes. A total of 138 potential differentially expressed genes related to endoplasmic reticulum (ER) stress were identified. These genes were further investigated using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathways. Additionally, the PPI interaction network revealed 38 interaction relationships among the top ten hub genes. The findings of the analysis revealed a strong correlation between the extent of immune cell infiltration and both osteosarcoma metastasis and the expression of hub genes. Notably, the differential expression of the top ten hub genes was observed in osteosarcoma clusters 1 and 4, signifying their significant association with the disease. Conclusion: The identification of ten key genes linked to osteosarcoma metastasis and endoplasmic reticulum stress bears potential clinical significance. Additionally, exploring the molecular subtype of osteosarcoma has the capacity to guide clinical treatment decisions, necessitating further investigations and subsequent clinical validations.

Coalescence-Induced Jumping of Nanodroplets in a Perpendicular Electric Field: A Molecular Dynamics Study.

Coalescence-induced jumping has promised a substantial reduction in the droplet detachment size and consequently shows great potential for heat-transfer enhancement in dropwise condensation. In this work, using molecular dynamics simulations, the evolution dynamics of the liquid bridge and the jumping velocity during coalescence-induced nanodroplet jumping under a perpendicular electric field are studied for the first time to further promote jumping. It is found that using a constant electric field, the jumping performance at the small intensity is weakened owing to the continuously decreased interfacial tension. There is a critical intensity above which the electric field can considerably enhance the stretching effect with a stronger liquid-bridge impact and, hence, improve the jumping performance. For canceling the inhibition effect of the interfacial tension under the condition of the weak electric field, a square-pulsed electric field with a paused electrical effect at the expansion stage of the liquid bridge is proposed and presents an efficient nanodroplet jumping even using the weak electric field.

Unveiling the Structural Origins of Dynamic Diversity in Pd-Based Metallic Glasses.

The ß-relaxation is one of the major dynamic behaviors in metallic glasses (MGs) and exhibits diverse features. Despite decades of efforts, the understanding of its structural origin and contribution to the overall dynamics of MG systems is still unclear. Here two palladium-based Pd─Cu─P and Pd─Ni─P MGs are reported with distinct different ß-relaxation behaviors and reveal the structural origins for the difference using the advanced X-ray photon correlation spectroscopy and absorption fine structure techniques together with the first-principles calculations. The pronounced ß-relaxation and fast atomic dynamics in the Pd─Cu─P MG mainly come from the strong mobility of Cu atoms and their locally favored structures. In contrast, the motion of Ni atoms is constrained by P atoms in the Pd─Ni─P MG, leading to the weakened ß-relaxation peak and sluggish dynamics. The correlation of atomic dynamics with microscopic structures provides a way to understand the structural origins of different dynamic behaviors as well as the nature of aging in disordered materials.

Effect of magnetic resonance imaging in liver metastases.

This letter to the editor is a commentary on a study titled "Liver metastases: The role of magnetic resonance imaging." Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma (HCC) is the key to achieving precise diagnosis and treatment and improving prognosis. This review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases, describes its main imaging features, and focuses on the added value of the latest imaging tools (such as T1 weighted in phase imaging, T1 weighted out of phase imaging; diffusion-weighted imaging, T2 weighted imaging). In this study, I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.

Combination Therapy with a TLR7 Agonist and a BRD4 Inhibitor Suppresses Tumor Growth via Enhanced Immunomodulation.

JQ-1 is a typical BRD4 inhibitor with the ability to directly fight tumor cells and evoke antitumor immunity via reducing the expression of PD-L1. However, problems arise with the development of JQ-1 in clinical trials, such as marked lymphoid and hematopoietic toxicity, leading to the investigation of combination therapy. SZU-101 is a TLR7 agonist designed and synthesized by our group with potent immunostimulatory activity. Therefore, we hypothesized that combination therapy of SZU-101 and JQ-1 would target innate immunity and adaptive immunity simultaneously, to achieve a better antitumor efficacy than monotherapy. In this study, the repressive effects of the combination administration on tumor growth and metastasis were demonstrated in both murine breast cancer and melanoma models. In 4T1 tumor-bearing mice, i.t. treatment with SZU-101 in combination with i.p. treatment with JQ-1 suppressed the growth of tumors at both injected and uninjected sites. Combination therapy increased M1/M2 ratio in TAMs, decreased PD-L1 expression and promoted the recruitment of activated CD8+ T cells in the TME. In summary, the improved therapeutic efficacy of the novel combination therapy appears to be feasible for the treatment of a diversity of cancers.

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Whole-brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice.

Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.

Bone and joint infection complicated with sepsis in neonates and infants under three months of age.

OBJECTIVE: Studies focusing on bone and joint infections (BJIs) in young infants are rare. Some cases of BJI are accompanied by sepsis. This study aimed to identify the clinical and bacteriological features of sepsis in neonates and young infants with BJIs. METHODS: Neonates and infants younger than 3 months diagnosed with BJI in the present institution from 2014 to 2021 were retrospectively reviewed. Patient characteristics, clinical data, and outcomes were documented and compared between those with and without sepsis. RESULTS: Twenty-five patients with a mean age of 34.8 days were included. Nine BJI cases had concomitant sepsis (group A), and 16 had BJI without sepsis (group B). Within group A, staphylococcus aureus was the major pathogenic germ (5 cases, of which 4 were of the methicillin-resistant staphylococcus aureus (MRSA) type). There was no statistical difference in male-to-female ratio, age, history of hospitalization, anemia, birth asphyxia, peripheral leukocyte counts, C-reactive protein on admission, and sequelae between groups. Univariate analyses indicated a significant difference in the incidence of septic arthritis (SA) combined with osteomyelitis (OM) (88.9% vs 37.5%), congenital deformities (44.4% vs 0%), and mean duration of symptoms (2.83 days vs 9.21 days) in comparisons between groups A and B. CONCLUSION: Staphylococcus aureus is the main pathogenic bacteria in BJI cases complicated with sepsis in neonates and young infants. Among infants younger than 3 months diagnosed with BJI, those with concurrent SA and OM, MRSA infection, or congenital deformities are more likely to develop sepsis.