Clonal evolution from B-cell acute lymphoblastic leukemia with BCR::ABL1 multilineage involvement to acute myeloid leukemia after multiple anti-CD19 chimeric antigen receptor T-cell therapy.

Not available.

ChRIPK1 caused necroptosis signaling pathway deficiency in Crassostrea hongkongensis.

RIPK1/TAK1 are important for programmed cell death, including liver death, necroptosis and apoptosis. However, there have been few published reports on the functions of RIPK1/TAK1 in invertebrates. In this study, full-length ChRIPK1 and ChTAK1 were cloned from C. hongkongensis through the rapid amplification of cDNA ends (RACE) technology. ChRIPK1 has almost no homology with human RIPK1 and lacks a kinase domain at the N-terminus but has a DD and RHIM domain. ChTAK1 is conserved throughout evolution. qRT‒PCR was used to analyze the mRNA expression patterns of ChRIPK1 in different tissues, developmental stages, and V. coralliilyticus-infected individuals, and both were highly expressed in the mantle and gills, while ChRIPK1 was upregulated in hemocytes and gills after V. coralliilyticus or S. aureus infection, which indicates that ChRIPK1 is involved in immune regulation. Fluorescence assays revealed that ChRIPK1 localized to the cytoplasm of HEK293T cells in a punctiform manner, but the colocalization of ChRIPK1 with ChTAK1 abolished the punctiform morphology. In the dual-luciferase reporter assay, both ChRIPK1 and ChRIPK1-RIHM activated the NF-κB signaling pathway in HEK293T cells, and ChTAK1 activated ChRIPK1 in the NF-κB signaling pathway. The apoptosis rate of the hemocytes was not affected by the necroptosis inhibitor Nec-1 but was significantly decreased, and ChRIPK1 expression was knocked down in the hemocytes of C. hongkongensis. These findings indicated that ChRIPK1 induces apoptosis but not necroptosis in oysters. This study provides a theoretical basis for further research on the molecular mechanism by which invertebrates regulate the programmed cell death of hemocytes in oysters.

Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

Comprehensive Classification of the Capitellar Injury Concurrent with Radial Head Fracture.

BACKGROUND: Capitellar injury (CI) includes capitellar cartilage injury (CCI) and capitellar fracture (CF). A comprehensive classification of CI concurrent with radial head fracture (RHF) that can guide surgical strategy is lacking in the literature. Therefore, this study aimed to introduce a comprehensive classification of CI concurrent with RHF and investigate its value. METHODS: A total of 35 patients with CI concurrent with RHF confirmed by surgical exploration were retrospectively analyzed, includingmales in 19 cases and females in 16 cases. RHF was classified according to the Mason classification, and CI was classified into six types, including 3 types of CCI and CF, each based on the site and degrees of injuries (comprehensive classification method proposed in this study). The classification results were analyzed. Two radiologists were selected to independently classify the CI, and the inter- and intra-observer agreements were analyzed with kappa statistics. RESULTS: Mason Type I, II, III, and IV RHF accounted for 14.3%, 48.6%, 37.1%, and 0% of cases, respectively. Type I, II, III, IV, V, and VI CIs accounted for 22.9%, 34.3%, 25.7%, 11.4%, 2.9%, and 2.9% of cases, respectively. Therewas no obvious relationship between the CI and RHF types (p > 0.05). All Type I CIs underwent removal, 9 Type II CIs underwent microfracture repair, and 3 Type II CIs underwent removal. All Type III CIs underwent fixation, one Type IV CI underwent removal, and 3 Type IV CIs underwent fixation, one Type V CI underwent fixation, and one Type VI CI underwent arthroplasty. The inter- and intra-observer kappa coefficients were 0.830 ~ 0.905 and 0.805 ~ 0.892, respectively. At 12 months postoperatively, the elbow function evaluated by MEPS was 91, with an excellent and good rate of 97%. CONCLUSION: Different types of CI differ not only in pathology but also in treatment methods. The CI comprehensive classification put forth in this paper for the first time reflects different types of pathology well, with high consistency and repeatability, and can guide the selection of surgical methods, leading to satisfactory postoperative results.

A Modified Arbuzov-Michalis Reaction for Selective Alkylation of Nucleophiles.

The alkylation of nucleophiles is among the most fundamental and well-developed transformations in chemistry. However, to achieve selective alkylation of complex substrates remains a nontrivial task. We report herein a general and selective alkylation method without using strong acids, bases, or metals. In this method, the readily available phosphinites/phosphites, in combination with ethyl acrylate, function as effective alkylating agents. Various nucleophilic groups, including alcohols, phenols, carboxylic acids, imides, and thiols can be alkylated. This method can be applied in the late-stage alkylation of natural products and pharmaceutical agents, achieving chemo- and site-selective modification of complex substrates. Experimental studies indicate the relative reactivity of a nucleophile depends on its acidity and its steric environment. Mechanistic studies suggest the reaction pathway resembles that of the Arbuzov-Michalis reaction.

The role of liprin-α1 phosphorylation in its liquid-liquid phase separation: regulation by PPP2R5D/PP2A holoenzyme.

Liprin-α1 is a widely expressed scaffolding protein responsible for regulating cellular processes such as focal adhesion, cell motility, and synaptic transmission. Liprin-α1 interacts with many proteins including ELKS, GIT1, liprin-ß, and LAR-family receptor tyrosine protein phosphatase. Through these protein-protein interactions, liprin-α1 assembles large higher-order molecular complexes; however, the regulation of this complex assembly/disassembly is unknown. Liquid-liquid phase separation (LLPS) is a process that concentrates proteins within cellular nano-domains to facilitate efficient spatiotemporal signaling in response to signaling cascades. While there is no report that liprin-α1 spontaneously undergoes LLPS, we found that GFP-liprin-α1 expressed in HEK293 cells occasionally forms droplet-like condensates. MS-based interactomics identified Protein Phosphatase 2A (PP2A)/B56δ (PPP2R5D) trimers as specific interaction partners of liprin-α1 through a canonical Short Linear Interaction Motif (SLiM) in its N-terminal dimerization domain. Mutation of this SLiM nearly abolished PP2A interaction, and resulted in significantly increased LLPS. GFP-liprin-α1 showed significantly increased droplet formation in HEK293 cells devoid of B56δ (PPP2R5D knockout), suggesting that PPP2R5D/PP2A holoenzyme inhibits liprin-α1 LLPS. Guided by reported liprin-α1 Ser/Thr phosphorylation sites, we found liprin-α1 phospho-mimetic mutant at serine 763 (S763E) is sufficient to drive its LLPS. Domain mapping studies of liprin-α1 indicated that the intrinsically disordered region, the N-terminal dimerization domain, and the SAM domains are all necessary for liprin-α1 LLPS. Finally, expression of p.E420K, a human PPP2R5D variant causing Houge-Janssens Syndrome type 1 (also known as Jordan's Syndrome), significantly compromised suppression of liprin-α1 LLPS. Our work identified B56δ-PP2A holoenzyme as an inhibitor of liprin-α1 LLPS via regulation at multiple phosphorylation sites.

Phonon excitations in Eu2Ir2O7 probed by inelastic X-ray scattering.

The study of phonon dynamics and its interplay with magnetic ordering is crucial for understanding the unique quantum phases in the pyrochlore iridates. Here, through inelastic X-ray scattering on a single crystal sample of the pyrochlore iridate Eu2Ir2O7, we map out the phonon excitation spectra in Eu2Ir2O7 and compare them with the theoretical phonon spectra calculated using the density functional theory. Possible phonon renormalization across the magnetic long-range order transition is observed in our experiments, which is consistent with the results of the previous Raman scattering experiments.

Segmentectomy for ground glass-dominant invasive lung cancer with tumour diameter of 2-3 cm: protocol for a single-arm, multicentre, phase III trial (ECTOP1012).

INTRODUCTION: Previous studies demonstrated that wedge resection is sufficient for ground glass-dominant lung adenocarcinoma (LUAD) with tumour diameter ≤2 cm, however, the optimal surgical type for ground glass-dominant LUAD with tumour diameter of 2-3 cm remains unclear. The purpose of this trial is to investigate the safety and efficacy of segmentectomy for ground glass-dominant invasive LUAD with tumour size of 2-3 cm. METHODS AND ANALYSIS: We initiated a phase III trial to investigate whether segmentectomy is suitable for ground glass-dominant invasive LUAD with tumour size of 2-3 cm. This trial plans to enrol 307 patients from multiple institutions including four general hospitals and two specialty cancer hospitals over a period of 5 years. The primary endpoint is 5 year disease-free survival. Secondary endpoints are lung function, 5 year overall survival, the site of tumour recurrence and metastasis, segmentectomy completion rate, radical segmentectomy (R0 resection) completion rate and surgery-related complications. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Centre (reference 2212267-18) and by the institutional review boards of each participating centre. Written informed consent is required from all participants. The study results will be published in a peer-reviewed international journal. TRIAL REGISTRATION NUMBER: NCT05717803.

Effect of occupational stress and resilience on insomnia among nurses during COVID-19 in China: a structural equation modelling analysis.

OBJECTIVES: To explore the effects of occupational stress and resilience on insomnia among Chinese nurses during the COVID-19 pandemic. DESIGN, SETTINGS AND PARTICIPANTS: A quantitative description study. The data were collected via a cross-sectional survey. A total of 725 front-line nurses at three tertiary hospitals in western China were included from December 2022 to January 2023. The Connor-Davidson Resilience Scale, Job Content Questionnaire, and Athens Insomnia Scale were used to collect data from a self-reported online questionnaire. OUTCOME MEASURES: The outcome variable was insomnia, and structural equation modelling was used to assess the associations among resilience, occupational stress and insomnia. RESULTS: The prevalence of insomnia among the participants was 58.76%. The structural equation model showed that resilience had a negative direct effect on insomnia and occupational stress, and occupational stress had a positive direct effect on insomnia. Involvement in COVID-19-related work has a positive effect on insomnia through occupational stress. In contrast, higher education levels improved insomnia through increased resilience. CONCLUSION: A significantly higher prevalence of insomnia has been observed among Chinese nurses during the COVID-19 pandemic. Our study suggests that better resilience may improve insomnia by relieving occupational stress, and implementing measures to promote resilience is essential to reduce occupational stress in nurses and improve their sleep quality.

Segmentectomy versus lobectomy for ground-glass opacity dominant cT1N0 invasive lung adenocarcinoma.

Background: The Japan Clinical Oncology Group (JCOG) 1211 suggested that segmentectomy should be considered as standard treatment for clinical T1N0 (cT1N0) ground glass opacity (GGO). However, over half of patients in JCOG1211 had pre-/minimal invasive adenocarcinoma. This study aims to retrospectively investigate the long-term survival of GGO featured cT1N0 invasive lung adenocarcinoma undergoing segmentectomy or lobectomy. Methods: This study screened patients with primary cT1N0 lung adenocarcinoma who received segmentectomy or lobectomy from 2010-2020. Prior computed tomography (CT) scans before surgery of all patients were reviewed and the inclusion was confirmed according to tumor diameter and consolidation tumor ratio (CTR). GGO nodules between 2-3 cm with CTR ≤0.5 or ≤2 cm with CTR between 0.25-0.5 were finally included. Patients with pathologically diagnosed pre-/minimally invasive lung adenocarcinoma were excluded. Long-term survivals between segmentectomy group and lobectomy group were compared after propensity score matching (PSM). Recurrence and postoperative complication events were also analyzed. Results: In total, 617 patients were enrolled, 159 received segmentectomy and 458 received lobectomy. Clinicopathological characteristics were well distributed between two groups. With a median follow-up time of 61.1 months (IQR: 42.3-71.7 months), after PSM, the 5-year overall survival rate was 98.8% (97.9-99.6%) for lobectomy and 99.3% (98.2-99.8%) for segmentectomy (P=0.42), the 5-year relapse-free survival rate was 95.3% (92.2-97.6%) for lobectomy and 95.2% for segmentectomy (92.3-98.7%) (P=0.81). The proportion of recurrence was 4.1% for lobectomy and 4.4% for segmentectomy (P=0.89). The proportion of grade 2 and above early postoperative complications was 9.6% for lobectomy and 8.8% for segmentectomy (P=0.86). Conclusions: For cT1N0 GGO featured invasive lung adenocarcinoma (2 cm < tumor diameter ≤3 cm, CTR ≤0.5 or tumor diameter ≤2 cm, 0.25< CTR ≤0.5), postoperative outcomes between segmentectomy group and lobectomy group were comparable. Concerning minimally invasive surgical strategy, segmentectomy should be confirmed as the standard surgical approach.

Non-Invasive Monitoring of the Impact of Low-Level Viremia on Liver Fibrosis in Treated Chronic Hepatitis B Patients.

Background: Chronic hepatitis B (CHB) presents a global health challenge due to its potential to cause severe liver conditions such as hepatocellular carcinoma (HCC) and cirrhosis. Prior research has established a correlation between CHB infection with low-level viremia (LLV) and liver disease progression, such as increased HCC incidence. This study aims to investigate whether LLV during treatment with nucleos(t)ide analogs (NAs) contributes to the accelerated progression of liver fibrosis (LF). Methods: This retrospective cohort study at Jinhua Central Hospital focused on CHB patients undergone NA monotherapy for over 96 weeks. Patients were categorized into maintained virological response (MVR) and LLV groups based on hepatitis B virus (HBV) DNA levels. The study assessed LF using various markers and methods, including chitinase 3-like 1 protein (CHI3L1), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and transient elastography. Results: Analysis was conducted on 92 CHB patients, categorized into LLV (n=42) and MVR (n=50) groups, following the exclusion of 101 patients for various reasons. Significant findings included lower baseline HBV DNA in MVR (<20 IU/mL) compared to LLV (67.8 IU/mL, P<0.001) and different AST/ALT ratios (LLV: 1.1, MVR: 1.36, P=0.011). LF was assessed using CHI3L1, FIB-4, and APRI, with LLV showing a higher baseline CHI3L1 (LLV:83.3 ng/mL vs MVR: 54.5 ng/mL, P=0.016) and scores compared to MVR, indicative of fibrosis. CHI3L1 levels in LLV were higher at baseline and weeks 48, 72, and 96 than MVR, with significance at baseline (P=0.038) and week 48 (P=0.034). Liver stiffness measurement (LSM) showed a time-dependent decline in both groups but no significant intergroup differences. Conclusion: Non-invasive monitoring of CHB patients who have received treatment indicates that LLV contributes to the progression of LF, necessitating proactive adjustment of antiviral treatment strategies.

Impacts of Major Changes in China's COVID-19 Prevention and Control Policies on Emergency Department Visits: A Quasi-Experiment.

Objective: This study aims to evaluate the impact of COVID-19 prevention and control policies on the frequency of emergency department (ED) visits in a large tertiary hospital in central China, from January 2018 to September 2023. Methods: We conducted a multi-stage interrupted time series analysis to investigate the impact of various epidemic control policies on weekly ED visits at a tertiary hospital in Hunan Province, China. The study period ranged from January 1, 2018, to September 30, 2023, and was divided into four distinct periods: pre-epidemic, pandemic, normalized control, and end of control. Using a quasi-Poisson regression model, we examined the specific effects of these policies on emergency visits, with a particular focus on stratifying patients based on respiratory versus non-respiratory diseases. Results: Compared to the pre-pandemic period, the number of ED visits in a tertiary hospital decreased by 38.5% (95% CI: 25.1% to 49.8%) during the COVID-19 pandemic, of which the number of ED visits for respiratory diseases increased by 79.4% (95% CI: 13.2% to 177.2%) and the number of ED visits for non-respiratory diseases decreased by 45.9% (95% CI: -55.7% to -34.2%). After the end of the epidemic control, the total number of ED visits increased by 31.5% (95% CI: 19.1% to 45.0%), with the number of ED visits for respiratory diseases rising by 379.2% (95% CI: 275.9% to 511.8%), but with no significant change in the number of ED visits for non-respiratory emergencies. Conclusion: Control policies were associated with people avoiding emergency care for non-respiratory related reasons during the pandemic, while the end of control policies was associated with a sharp rise in emergency care for respiratory diseases. This study provides a scientific basis for the different changes in ED visits under the implementation of varying epidemic prevention and control policies.

Clinical and hematological characteristics of children infected with the omicron variant of SARS-CoV-2: role of the combination of the neutrophil: lymphocyte ratio and eosinophil count in distinguishing severe COVID-19.

Purpose: Investigate the clinical/hematological characteristics of children infected with the Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and identify an effective indicator to distinguish coronavirus disease 2019 (COVID-19) severity in children. Methods: A retrospective study was conducted through electronic medical records from pediatric patients. The demographic, clinical, and routine blood test (RBT) features of children diagnosed by real-time PCR for SARS-CoV-2 were collected. Results: Data of 261 patients were analyzed. The most common abnormality shown by RBTs was increased monocyte count (68%). Children had "mild-moderate" or "severe" forms of COVID-19. Prevalence of abnormal neutrophil count (p = 0.048), eosinophil count (p = 0.006), mean corpuscular volume (p = 0.033), mean platelet volume (p = 0.006), platelet-large cell ratio (p = 0.043), and red blood cell distribution width-standard deviation (p = 0.031) were significantly different in the two types. A combination of the neutrophil: lymphocyte ratio (NLR) and eosinophil count for diagnosing severe COVID-19 presented the largest AUC (0.688, 95% CI = 0.599-0.777; p < 0.001), and the AUC increased with a decrease in age. Conclusions: Combination of the NLR and eosinophil count might be a promising indicator for identifying severe COVID-19 in children at infection onset.

Characterization of winter PM2.5 source contributions and impacts of meteorological conditions and anthropogenic emission changes in the Sichuan Basin, 2002-2020.

In this study, the Weather Research and Forecasting (WRF) model and Community Multiscale Air Quality-Integrated Source Apportionment Method (CMAQ-ISAM) were utilized, which were integrated with the Multiresolution Emission Inventory for China (MEIC) emission inventory, to simulate winter PM2.5 concentrations, regional transport, and changes in emission source contributions in the Sichuan basin (SCB) from 2002 to 2020, considering variations in meteorological conditions and anthropogenic emissions. The results indicated a gradual decrease in the basin's winter average PM2.5 concentration from 300 µg/m3 to 120 µg/m3, with the most significant decrease occurring after 2014, reflecting the actual impact of China's air pollution control measures. Spatially, the main pollution area shifted from Chongqing to Chengdu and the western basin. The sources of PM2.5 at the eastern and western margins of the basin have remained stable and have been dominated by local emissions for many years, while the sources of PM2.5 in the central part of the basin have evolved from a multiregional co-influenced source during the early period to a high proportion of local emissions; except for boundary condition sources, residential sources were the main PM2.5 sources in the basin (approximately 29.70 %), followed by industrial sources (approximately 14.11 %). Industrial sources exhibited higher contributions in Chengdu and Chongqing and gradually stabilized with residential sources over the years, while residential sources dominated in the eastern and western parts of the basin and exhibited a declining trend. Meteorological conditions exacerbated pollution in the whole basin from 2008 to 2014, especially in the west (21-40 µg/m3). The eastern basin and Chongqing exhibited more years with alleviated meteorological pollution, including a 40+ µg/m3 decrease in Chongqing from 2002 to 2005. Reduced anthropogenic emissions alleviated annual pollution levels, with a greater reduction (> -20 µg/m3) after 2011 due to pollution control measures.

Integrating Vision-Language Models for Accelerated High-Throughput Nutrition Screening.

Addressing the critical need for swift and precise nutritional profiling in healthcare and in food industry, this study pioneers the integration of vision-language models (VLMs) with chemical analysis techniques. A cutting-edge VLM is unveiled, utilizing the expansive UMDFood-90k database, to significantly improve the speed and accuracy of nutrient estimation processes. Demonstrating a macro-AUCROC of 0.921 for lipid quantification, the model exhibits less than 10% variance compared to traditional chemical analyses for over 82% of the analyzed food items. This innovative approach not only accelerates nutritional screening by 36.9% when tested amongst students but also sets a new benchmark in the precision of nutritional data compilation. This research marks a substantial leap forward in food science, employing a blend of advanced computational models and chemical validation to offer a rapid, high-throughput solution for nutritional analysis.

Breast lesions on MRI in mass and non-mass enhancement: Kaiser score and modified Kaiser score + for readers of variable experience.

OBJECTIVES: To compare the diagnostic performance of three readers using BI-RADS and Kaiser score (KS) based on mass and non-mass enhancement (NME) lesions. METHODS: A total of 630 lesions, 393 malignant and 237 benign, 458 mass and 172 NME, were analyzed. Three radiologists with 3 years, 6 years, and 13 years of experience made diagnoses. 596 cases had diffusion-weighted imaging, and the apparent diffusion coefficient (ADC) was measured. For lesions with ADC > 1.4 × 10-3 mm2/s, the KS was reduced by 4 as the modified KS +, and the benefit was assessed. RESULTS: When using BI-RADS, AUC was 0.878, 0.915, and 0.941 for mass, and 0.771, 0.838, 0.902 for NME for Reader-1, 2, and 3, respectively, better for mass than for NME. The diagnostic accuracy of KS was improved compared to BI-RADS for less experienced readers. For Reader-1, AUC was increased from 0.878 to 0.916 for mass (p = 0.005) and from 0.771 to 0.822 for NME (p = 0.124). Based on the cut-off value of BI-RADS ≥ 4B and KS ≥ 5 as malignant, the sensitivity of KS by Readers-1 and -2 was significantly higher for both Mass and NME. When ADC was considered to change to modified KS +, the AUC and the accuracy for all three readers were improved, showing higher specificity with slightly degraded sensitivity. CONCLUSION: The benefit of KS compared to BI-RADS was most noticeable for the less experienced readers in improving sensitivity. Compared to KS, KS + can improve specificity for all three readers. For NME, the KS and KS + criteria need to be further improved. CLINICAL RELEVANCE STATEMENT: KS provides an intuitive method for diagnosing lesions on breast MRI. BI-RADS and KS face greater difficulties in evaluating NME compared to mass lesions. Adding ADC to the KS can improve specificity with slightly degraded sensitivity. KEY POINTS: KS provides an intuitive method for interpreting breast lesions on MRI, most helpful for novice readers. KS, compared to BI-RADS, improved sensitivity in both mass and NME groups for less experienced readers. NME lesions were considered during the development of the KS flowchart, but may need to be better defined.

A large-aperture, high-power ultrawideband radiation system with beam broadening capacity.

Due to the limited maximum output power of the pulsers based on avalanche transistors, high-power ultrawideband (UWB) radiation systems usually synthesize plenty of modules simultaneously to achieve a high peak effective potential (rEp). However, this would lead to an increased aperture size as well as a narrower beam, which would limit their applications in intentional electromagnetic interference fields. In this paper, a high-power UWB radiation system with beam broadening capacity is developed. To achieve beam broadening in the time domain, a power-law time delay distribution method is proposed and studied by simulation, and then the relative excitation time delays of the modules are optimized to achieve higher rEp and avoid beam splitting in the beam broadening mode. In order to avoid false triggering of the pulser elements when implementing the beam broadening, the mutual coupling effect in the system is analyzed and suppressed by employing onboard high-pass filters, since the mutual coupling effect is much more severe in the low-frequency range. Finally, a radiation system with 36 modules is developed. Measuring results indicate that in the high-rEp mode, the developed system could achieve a maximum effective potential rEp of 313.6 kV and a maximum pulse-repetition-rate of 20 kHz. In the beam broadening mode, its half-peak-power beam width in the H-plane is broadened from the original value of 3.9° to 7.9°, with a maximum rEp of 272.9 kV. The polarization direction of the system could be flexibly adjusted by a built-in motor.

Epimedium-Curculigo herb pair enhances bone repair with infected bone defects and regulates osteoblasts through LncRNA MALAT1/miR-34a-5p/SMAD2 axis.

Infected bone defects (IBDs) are the common condition in the clinical practice of orthopaedics. Although surgery and anti-infective medicine are the firstly chosen treatments, in many cases, patients experience a prolonged bone union process after anti-infective treatment. Epimedium-Curculigo herb pair (ECP) has been proved to be effective for bone repair. However, the mechanisms of ECP in IBDs are insufficiency. In this study, Effect of ECP in IBDs was verified by micro-CT and histological examination. Qualitative and quantitative analysis of the main components in ECP containing medicated serum (ECP-CS) were performed. The network pharmacological approaches were then applied to predict potential pathways for ECP associated with bone repair. In addition, the mechanism of ECP regulating LncRNA MALAT1/miRNA-34a-5p/SMAD2 signalling axis was evaluated by molecular biology experiments. In vivo experiments indicated that ECP could significantly promote bone repair. The results of the chemical components analysis and the pathway identification revealed that TGF-ß signalling pathway was related to ECP. The results of in vitro experiments indicated that ECP-CS could reverse the damage caused by LPS through inhibiting the expressions of LncRNA MALAT1 and SMAD2, and improving the expressions of miR-34a-5p, ALP, RUNX2 and Collagen type І in osteoblasts significantly. This research showed that ECP could regulate the TGF-ß/SMADs signalling pathway to promote bone repair. Meanwhile, ECP could alleviate LPS-induced bone loss by modulating the signalling axis of LncRNA MALAT1/miRNA-34a-5p/ SMAD2 in IBDs.

The Molecular Mechanism of Radix Paeoniae Rubra.-Cortex Moutan. Herb Pair in the Treatment of Atherosclerosis: A Work Based on Network Pharmacology and In Vitro Experiments.

Radix Paeoniae Rubra. (Chishao, RPR) and Cortex Moutan. (Mudanpi, CM) are a pair of traditional Chinese medicines that play an important role in the treatment of atherosclerosis (AS). The main objective of this study was to identify potential synergetic function and underlying mechanisms of RPR-CM in the treatment of AS. The main active ingredients, targets of RPR-CM and AS-related genes were obtained from public databases. A Venn diagram was utilized to screen the common targets of RPR-CM in treating AS. The protein-protein interaction network was established based on STRING database. Biological functions and pathways of potential targets were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Cytoscape was used to construct the drug-compound-target-signal pathway network. Molecular docking was performed to verify the binding ability of the bioactive ingredients and the target proteins. The endothelial inflammation model was constructed with human umbilical vein endothelial cells stimulated with ox-LDL, and the function of RPR-CM in treating AS was verified by CCK-8 assay, enzyme-linked immunosorbent assay, and qPCR. In this study, 12 active components and 401 potential target genes of RPR-CM were identified, among which quercetin, kaempferol and baicalein were considered to be the main active components. A total of 1903 AS-related genes were identified through public databases and four GEO datasets (GSE57691, GSE72633, GSE6088 and GSE199819). There are 113 common target genes of RPR-CM in treating AS. PPI network analysis identified 17 genes in cluster 1 as the core targets. Bioinformatics analysis showed that RPR-CM in AS treatment was associated with multiple downstream biological processes and signal pathways. PTGS2, JUN, CASP3, TNF, IL1B, IL6, FOS, STAT1 were identified as the core targets of RPR-CM, and molecular docking showed that the main bioactive components of RPR-CM had good binding ability with the core targets. RPR-CM extract significantly inhibited the levels of inflammatory factors TNF-α, IL-6, IL-1ß, MCP-1, VCAM-1 and ICAM-1 in HUVECs, and inhibited endothelial inflammation. This study revealed the active ingredients of RPR-CM, and identified the key downstream targets and signaling pathways in the treatment of AS, providing theoretical basis for the application of RPR-CM in prevention and treatment of AS.