Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery.

JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Bacterial membrane vesicles from swine farm microbial communities harboring and safeguarding diverse functional genes promoting horizontal gene transfer.

Antibiotic resistance (AMR) poses a significant global health challenge, with swine farms recognized as major reservoirs of antibiotic resistance genes (ARGs). Recently, bacterial membrane vesicles (BMVs) have emerged as novel carriers mediating horizontal gene transfer. However, little is known about the ARGs carried by BMVs in swine farm environments and their transfer potential. This study investigated the distribution, sources, and microbiological origins of BMVs in three key microbial habitats of swine farms (feces, soil, and fecal wastewater), along with the ARGs and mobile genetic elements (MGEs) they harbor. Characterization of BMVs revealed particle sizes ranging from 20 to 500 nm and concentrations from 108 to 1012 particles/g, containing DNA and proteins. Metagenomic sequencing identified BMVs predominantly composed of members of the Proteobacteria phyla, including Pseudomonadaceae, Moraxellaceae, and Enterobacteriaceae, carrying diverse functional genes encompassing resistance to 14 common antibiotics and 74,340 virulence genes. Notably, multidrug resistance, tetracycline, and chloramphenicol resistance genes were particularly abundant. Furthermore, BMVs harbored various MGEs, primarily plasmids, and demonstrated the ability to protect their DNA cargo from degradation and facilitate horizontal gene transfer, including the transmission of resistance genes. In conclusion, this study reveals widespread presence of BMVs carrying ARGs and potential virulence genes in swine farm feces, soil, and fecal wastewater. These findings not only provide new insights into the role of extracellular DNA in the environment but also highlight concerns regarding the gene transfer potential mediated by BMVs and associated health risks.

Photocontrolled ultra-broadband metamaterial absorber around the terahertz regime.

In this paper, we innovatively stack multiple resonant units of photoconductive silicon to design an ultra-broadband metamaterial absorber. By manipulating the conductivity of the silicon with a pump beam, adjustments are made to the amplitude of the wide absorption spectrum spanning 6.6 THz, enabling functional switching from total reflection to near-perfect ultra-broadband absorption. By integrating vanadium dioxide as an intermediary layer, a dual-mode switchable absorber is realized, offering dual control functionalities. Temperature changes enable the absorber to switch between dual-band absorption and ultra-broadband absorption, while variations in pump beam intensity allow for further amplitude adjustments within the absorption spectrum. Impedance matching theory and near-field analysis provide the necessary physical foundation for understanding broadband absorption. Structural parameters, incident angle, and polarization angle of the incident electromagnetic waves are also studied to demonstrate the device's robustness. Our proposed absorbers not only greatly broaden the absorption bandwidth of silicon-based absorbers, but also offer versatility, polarization insensitivity, and robustness over a wide range of incidence angles. Moreover, our design ideas are useful for broadening the bandwidth and enhancing absorption, which enables wider applications in ultra-broadband terahertz absorption and promises extensive prospects.

Life's Essential 8 and its association with osteoarthritis and disability: a cross-sectional study based on the NHANES 2005-2018 database.

PURPOSE: Osteoarthritis (OA) often coexists with risk factors for cardiovascular disease (CVD), worsening symptoms and functional impairment. This cross-sectional study investigated the association between Life's Essential 8 (LE8) and disability in individuals with OA. METHODS: Data from 8334 United States adults (aged ≥ 20) who participated in the 2005-2018 National Health and Nutrition Examination Survey (NHANES) with complete data on LE8 components and disability status were analyzed. LE8 components, including diet, physical activity (PA), nicotine exposure, sleep, body mass index (BMI), blood lipids, glucose, and blood pressure (BP), were scored on a 0-100 scale, categorizing cardiovascular health (CVH) as low, moderate, or high. Disability mainly caused by OA was assessed using a standardized physical functioning questionnaire. Association analyses were performed using multivariable logistic regression, adjusting for demographic, socioeconomic, lifestyle, and health-related covariates. RESULTS: Individuals with CVH scores 10 points higher had a 15% lower prevalence of OA (95% CI 0.81-0.90). Individuals with OA were more than twice as likely to experience disability. High levels of CVH were associated with a lower prevalence of disability in various domains compared to low levels of CVH (all P < 0.05), such as in activities of daily living (OR 0.32, 95% CI 0.18-0.58). Among the LE8 components, BMI, PA, and sleep health were associated with disabilities in all domains, while blood lipid scores were not. CONCLUSION: A higher adherence to LE8 is associated with a lower prevalence of different types of disability in domains of physical functioning and functional limitations in individuals with OA.

A surgical alternative of fusiform penetrating keratoplasty for the management of severe infectious keratitis.

AIM: To describe the surgical procedure of fusiform penetrating keratoplasty (FPK) using multiple trephines of different sizes for treating patients with severe infectious keratitis. METHODS: Fourteen eyes underwent FPK, and 15 eyes received conventional penetrating keratoplasty (PK) were included in the study. The best-corrected visual acuity (BCVA), refractive outcomes, endothelial cell density, and postoperative complications were recorded. RESULTS: The FPK group was followed for an average of 15.3±2.1mo, whereas the PK group was followed for 16.1±1.9mo. The corneal ulcers were elliptical-shaped in all 14 eyes in the FPK group. The mean BCVA (logMAR, 0.26±0.13) showed no statistically significant differences from that in the PK group (logMAR, 0.21±0.12, P>0.05) at 1y after surgery. But the mean curvature, mean astigmatism, and mean spherical equivalent in the FPK group were lower than those in the PK group (P<0.05). Peripheral anterior synechia was observed in one patient in the FPK group, whereas 6 patients in the PK group. Suture loosening and neovascularization were observed in 4 and 5 eyes in the PK group, respectively. No graft immune rejection or elevation of intraocular pressure was observed in the two groups. CONCLUSION: For patients with elliptical-shaped corneas or corneal ulcers, FPK can avoid disrupting of corneal limbus, reduce the risk of postoperative complications, and can result in satisfactory visual quality.

What Radio Waves Tell Us about Sleep!

The ability to assess sleep at home, capture sleep stages, and detect the occurrence of apnea (without on-body sensors) simply by analyzing the radio waves bouncing off people's bodies while they sleep is quite powerful. Such a capability would allow for longitudinal data collection in patients' homes, informing our understanding of sleep and its interaction with various diseases and their therapeutic responses, both in clinical trials and routine care. In this article, we develop an advanced machine learning algorithm for passively monitoring sleep and nocturnal breathing from radio waves reflected off people while asleep. Validation results in comparison with the gold standard (i.e., polysomnography) (n=880) demonstrate that the model captures the sleep hypnogram (with an accuracy of 80.5% for 30-second epochs categorized into Wake, Light Sleep, Deep Sleep, or REM), detects sleep apnea (AUROC = 0.89), and measures the patient's Apnea-Hypopnea Index (ICC=0.90; 95% CI = [0.88, 0.91]). Notably, the model exhibits equitable performance across race, sex, and age. Moreover, the model uncovers informative interactions between sleep stages and a range of diseases including neurological, psychiatric, cardiovascular, and immunological disorders. These findings not only hold promise for clinical practice and interventional trials but also underscore the significance of sleep as a fundamental component in understanding and managing various diseases.

Effect and mechanism of polyphenols containing m-dihydroxyl structure on 2-amino-1-methyl-6-phenylimidazole [4, 5-b] pyridine (PhIP) formation in chemical models and roast pork patties.

2-amino-1-methyl-6-phenylimidazole [4, 5-b] pyridine (PhIP) is a prevalent heterocyclic amine (HAA) found in heated processed meat. This study investigated the inhibitory impact of eight different types of polyphenols containing m-dihydroxyl structure on PhIP formation through a chemical model system. The structure-activity relationship and potential sites of action of polyphenols containing m-dihydroxyl structure were also analyzed. Then, the mechanism of inhibiting PhIP formation by kaempferol, naringenin and quercetin was speculated by UPLC-MS. Results showed that 8 kinds of polyphenols containing m-dihydroxyl structure had significant (P < 0.05) inhibition on the formation of PhIP in the chemical model system in a dose-dependent manner. In addition, PhIP was most significantly inhibited by naringenin at the same concentration, followed by kaempferol and quercetin (83.27%, 80.81% and 79.26%, respectively). UPLC-MS results speculated that kaempferol, naringenin, and quercetin formed a new admixture via an electrophilic aromatic substitution reaction with the intermediate product phenylacetaldehyde, preventing the formation of PhIP.

Social support and sleep quality in people with schizophrenia living in the community: the mediating roles of anxiety and depression symptoms.

Introduction: Research has demonstrated that higher social support is associated with better psychological health, quality of life, cognition, activities of daily living, and social participation, but the relationship between social support and sleep quality remains unknown. This study aims to investigate the mediating effects of anxiety and depression in the relationship between social support and sleep among community-dwelling patients with schizophrenia. Method: Purposive sampling was used to collect face-to-face data from 1,107 community-dwelling patients with schizophrenia in Chengdu, Sichuan Province, China, between April and July 2023. The Athens Insomnia Scale (AIS) was used to assess sleep quality; the Generalized Anxiety Disorder 7-item scale (GAD-7) was utilized to evaluate anxiety symptoms; and the Patient Health Questionnaire-9 (PHQ-9) was employed to assess depressive symptoms. The mediating effect of anxiety and depression symptoms was assessed using the bootstrap method via Model 6 (Serial multiple mediator model) of the SPSS PROCESS macro. Results: Among the 1,107 participants, the proportions of people with schizophrenia experiencing anxiety, depressive symptoms, and poor sleep quality were 22.8, 37.7, and 42.1%, respectively. Mediation analyses indicated that although social support had no direct effect on sleep quality, anxiety and depressive symptoms fully mediated the relationship between social support and sleep quality. Conclusion: Patients with schizophrenia experience low levels of social support and poor sleep quality. To enhance the sleep quality of individuals with schizophrenia, all levels of society (government, medical institutions, and communities) must pay more attention to mental health. Implementing diverse intervention measures to strengthen social support and improve symptoms of anxiety and depression should be considered. This approach may potentially lead to an improvement in sleep quality among individuals with schizophrenia.

Multi-omic Analyses Shed Light on The Genetic Control of High-altitude Adaptation in Sheep.

Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing ∼ 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated ß-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.

Caffeic Acid and Cyclen-Based Hydrogel for Synergistic Antibacterial Therapy.

Caffeic acid is a natural product that contains both phenolic and acrylic functional groups and has been widely employed as an alternative drug to combat chronic infections induced by microbes such as bacteria, fungi, and viruses. Several strategies, including derivatization and nanoformulation, have been applied in order to overcome the issues of water insolubility, poor stability, and the bioavailability of caffeic acid. Here, caffeic acid and cyclen-Zn(II) are incorporated into a G4-assembly by using a phenylborate linker to form the mixed supramolecular prodrug GB-CA/Cy-Zn(II) hydrogel. The delivery system is expected to enhance antibacterial and anti-inflammatory properties during the wound healing process through the synergistic effect of caffeic acid and cyclen-Zn(II). The preparation and physicochemical and mechanical properties of the hydrogel were investigated by NMR, CD, TEM, and rheological assays. The typical inflammatory cytokines and in vitro antibacterial experiments indicated that inflammation and infection can be significant suppressed by the hydrogel treatment. An in vivo infected wound model treated by the hydrogel showed rapid wound healing capacity and biosafety. The current work depicts a simple method to prepare a caffeic acid hydrogel carrier, which facilitates synergistic treatment for inflammation and bacterial infections at the wound site.

Citrus-derived flavanones as neuraminidase inhibitors: In vitro and in silico study.

Neuraminidase (NA) has been well-studied as a therapeutic target for Influenza. However, resistance to the influenza virus has been observed recently. Out of special interest in the utilization of dietary antivirals from citrus, in vitro inhibition activity against NA and in silico studies including molecular docking, molecular dynamic simulation, and a predictive ADMET study, were performed on five citrus-derived flavanones. Encouragingly, citrus-derived flavanones displayed comparable or even more potent in vitro inhibitory activity than oseltamivir carboxylate against NA. Orange peel extract exhibited higher activity than hesperidin. Among the tested compounds, neohesperidin, forming strong hydrogen-bonding interactions with key arginine residues, exhibited the most effective inhibitory activity against NAs from C. perfringens, consistent with the results of molecular dynamics simulations. Although the molecular docking results were inconsistent with the in vitro activity, the binding energy was identical against the wild-type and mutant, suggesting a lower likelihood of developing drug resistance. Moreover, predictive ADMET studies showed favorable pharmacokinetic properties for the tested compounds. Overall, citrus fruit peel emerges as a promising dietary supplement for prevention and treatment of influenza. These findings elucidate the impact of flavanones on NA activity, and the analysis of their binding modes provides valuable insights into the mechanism of NA inhibition.

Intermolecular C-C/C-N σ-bond metathesis enabled by visible light.

Transition-metal-catalyzed double/triple bond metathesis reactions have been well-established due to the ability of transition-metal catalysts to readily interact with π bonds, facilitating the progression of the entire reaction. However, activating σ-bonds to induce σ-bond metathesis is more challenging due to the absence of π bonds and the high bond energy of σ bonds. In this study, we present a novel photo-induced approach that does not rely on transition metals or photosensitizers to drive C-C and C-N σ-bond metathesis reactions. This method enables the cross-coupling of tertiary amines with α-diketones via C-C and C-N single bonds cleavage and recombination. Notably, our protocol exhibits good compatibility with various functional groups in the absence of transition metals and external photosensitizers, resulting in the formation of aryl alkyl ketones and aromatic amides in good to high yields. To gain insights into the mechanism of this pathway, we conducted controlled experiments, intermediate trapping experiments, and DFT (Density Functional Theory) calculations. This comprehensive approach allowed us to elucidate the detailed mechanism underlying this transformative reaction.

Monocyte/macrophage-mediated venous thrombus resolution.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Machine learning identifies key cells and therapeutic targets during ferroptosis after spinal cord injury.

Ferroptosis, a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation, is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury. Thus, in this study, bulk RNA sequencing data (GSE47681 and GSE5296) and single-cell RNA sequencing data (GSE162610) were acquired from gene expression databases. We then conducted differential analysis and immune infiltration analysis. Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms. Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes. Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells, confirming the high expression of Atf3 and Piezo1 in these cells. Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide. In a mouse model of T8 spinal cord injury, low-dose cycloheximide treatment was found to improve neurological function, decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase, and increase levels of the anti-inflammatory cytokine arginase 1. Correspondingly, the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia, while the expression of Acsl4 decreased. Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury, identify the key cell types and genes involved in ferroptosis after spinal cord injury, and validate the efficacy of potential drug therapies, pointing to new directions in the treatment of spinal cord injury.

Usefulness of estimated glucose disposal rate in detecting heart failure: results from national health and nutrition examination survey 1999-2018.

BACKGROUND: Estimated glucose disposal rate (eGDR) is a novel, clinically available, and cost-effective surrogate of insulin resistance. The current study aimed to assess the association between eGDR and prevalent heart failure (HF), and further evaluate the value of eGDR in detecting prevalent HF in a general population. METHODS: 25,450 subjects from the National Health and Nutrition Examination Survey 1999-2018 were included. HF was recorded according to the subjects' reports. Logistic regression was employed to analyze the association between eGDR and HF, the results were summarized as Per standard deviation (SD) change. Then, subgroup analysis tested whether the main result from logistic regression was robust in several conventional subpopulations. Finally, receiver-operating characteristic curve (ROC) and reclassification analysis were utilized to evaluate the potential value of eGDR in improving the detection of prevalent HF. RESULTS: The prevalence of reported HF was 2.96% (753 subjects). After adjusting demographic, laboratory, anthropometric, and medical history data, each SD increment of eGDR could result in a 43.3% (P < 0.001) risk reduction for prevalent HF. In the quartile analysis, the top quartile had a 31.1% (P < 0.001) risk of prevalent HF compared to the bottom quartile in the full model. Smooth curve fitting demonstrated that the association was linear in the whole range of eGDR (P for non-linearity = 0.313). Subgroup analysis revealed that the association was robust in age, sex, race, diabetes, and hypertension subgroups (All P for interaction > 0.05). Additionally, ROC analysis displayed a significant improvement in the detection of prevalent HF (0.869 vs. 0.873, P = 0.008); reclassification analysis also confirmed the improvement from eGDR (All P < 0.001). CONCLUSION: Our study indicates that eGDR, a costless surrogate of insulin resistance, may have a linear and robust association with the prevalent HF. Furthermore, our findings implicate the potential value of eGDR in refining the detection of prevalent HF in the general population.

Risk factors for arrhythmias occurred in cancer patients after chemotherapy: An evidence-based systematic review and meta-analysis.

Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors. Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence. Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows. General patient characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients <60 years of age [OR = 14.33, 95%CI (8.51, 24.13), P＜0.00001]. Patients with a smoking history exhibited a 1.67-fold higher risk of arrhythmia after chemotherapy [OR = 1.67, 95%CI (1.24, 2.25), P = 0.0007]. However, there was no significant correlation between gender and body mass index (BMI) with arrhythmia after chemotherapy in oncology patients (P = 0.52; P = 0.19). Disease-related factors: Patients with a history of hypertension, diabetes, and cardiovascular disease had a 1.93-fold, 1.30-fold, and 1.76-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 1.93, 95%CI (1.66, 2.24), P＜0.00001; OR = 1.30, 95%CI (1.10, 2.52), P = 0.002; OR = 1.76, 95%CI (1.51, 2.05), P＜0.00001]. Additionally, the incidence of arrhythmia increased 1.97 times in patients with electrolyte and acid-base balance disorders following chemotherapy [OR = 1.97, 95%CI (1.41, 2.76), P＜0.00001]. Chemotherapy-related factors: Seven articles examined the association between chemotherapy drugs and post-chemotherapy arrhythmias. The results indicated that oncology patients were 3.03 times more likely to develop arrhythmias with chemotherapy drugs compared to non-chemotherapy drugs [OR = 3.03, 95%CI (2.59, 3.54), P＜0.00001]. Notably, anthracyclines and fluorouracil chemotherapy demonstrated a 2.98-fold and 3.35-fold increased risk of arrhythmia after chemotherapy, respectively [OR = 2.98, 95%CI (2.51, 3.03), P＜0.00001; OR = 3.35, 95%CI (2.20, 5.10), P＜0.00001]. The risk of arrhythmia after chemotherapy was 1.72 times higher in patients with chemotherapy cycles longer than 4 weeks than those with cycles shorter than 4 weeks [OR = 1.72, 95%CI (1.30, 2.28), P = 0.0001]. Conclusion: The occurrence of arrhythmia after chemotherapy in cancer patients was significantly associated with the patient's age, history of smoking, history of hypertension, history of diabetes, history of cardiovascular disease, chemotherapy drug use, and cycle. However, further high-quality evidence is needed to support these results.

Probing charge redistribution at the interface of self-assembled cyclo-P5 pentamers on Ag(111).

Phosphorus pentamers (cyclo-P5) are unstable in nature but can be synthesized at the Ag(111) surface. Unlike monolayer black phosphorous, little is known about their electronic properties when in contact with metal electrodes, although this is crucial for future applications. Here, we characterize the atomic structure of cyclo-P5 assembled on Ag(111) using atomic force microscopy with functionalized tips and density functional theory. Combining force and tunneling spectroscopy, we find that a strong charge transfer induces an inward dipole moment at the cyclo-P5/Ag interface as well as the formation of an interface state. We probe the image potential states by field-effect resonant tunneling and quantify the increase of the local change of work function of 0.46 eV at the cyclo-P5 assembly. Our experimental approach suggest that the cyclo-P5/Ag interface has the characteristic ingredients of a p-type semiconductor-metal Schottky junction with potential applications in field-effect transistors, diodes, or solar cells.

CsMIKC1 regulates inflorescence development and grain production in Cannabis sativa plants.

Female inflorescence is the primary output of medical Cannabis. It contains hundreds of cannabinoids that accumulate in the glandular trichomes. However, little is known about the genetic mechanisms governing Cannabis inflorescence development. In this study, we reported the map-based cloning of a gene determining the number of inflorescences per branch. We named this gene CsMIKC1 since it encodes a transcription factor that belongs to the MIKC-type MADS subfamily. Constitutive overexpression of CsMIKC1 increases inflorescence number per branch, thereby promoting flower production as well as grain yield in transgenic Cannabis plants. We further identified a plant-specific transcription factor, CsBPC2, promoting the expression of CsMIKC1. CsBPC2 mutants and CsMIKC1 mutants were successfully created using the CRISPR-Cas9 system; they exhibited similar inflorescence degeneration and grain reduction. We also validated the interaction of CsMIKC1 with CsVIP3, which suppressed expression of four inflorescence development-related genes in Cannabis. Our findings establish important roles for CsMIKC1 in Cannabis, which could represent a previously unrecognized mechanism of inflorescence development regulated by ethylene.

Pretreatment pulmonary tumor necrosis is a promising prognostic imaging biomarker for first-line anti-PD-1/PD-L1 therapy in advanced lung squamous cell carcinoma: a multi-institutional, propensity score-matching cohort analysis.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better.

A Comprehensive Model Outperformed the Single Radiomics Model in Noninvasively Predicting the HER2 Status in Patients with Breast Cancer.

RATIONALE AND OBJECTIVES: This study aimed to develop predictive models based on conventional magnetic resonance imaging (cMRI) and radiomics features for predicting human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC) and compare their performance. MATERIALS AND METHODS: A total of 287 patients with invasive BC in our hospital were retrospectively analyzed. All patients underwent preoperative breast MRI consisting of fat-suppressed T2-weighted imaging, axial dynamic contrast-enhanced MRI, and diffusion-weighted imaging sequences. From these sequences, radiomics features were derived. Three distinct models were established utilizing cMRI features, radiomics features, and a comprehensive model that amalgamated both. The predictive capabilities of these models were assessed using the receiver operating characteristic curve analysis. The comparative performance was then determined through the DeLong test and net reclassification improvement (NRI). RESULTS: In a randomized split, the 287 patients with BC were allotted to either training (234; 46 HER2-zero, 107 HER2-low, 81 HER2-positive) or test (53; 8 HER2-zero, 27 HER2-low, 18 HER2-positive) at an 8:2 ratio. The mean area under the curve (AUCs) for cMRI, radiomics, and comprehensive models predicting HER2 status were 0.705, 0.819, and 0.859 in training set and 0.639, 0.797, and 0.842 in test set, respectively. DeLong's test indicated that the combined model's AUC surpassed the radiomics model significantly (p < 0.05). NRI analysis verified superiority of the combined model over the radiomics for BC HER2 prediction (NRI 25.0) in the test set. CONCLUSION: The comprehensive model based on the combination of cMRI and radiomics features outperformed the single radiomics model in noninvasively predicting the three-tiered HER2 status in patients with BC.