MXRA7 is involved in monocyte-to-macrophage differentiation.

Macrophages are critical in mediating immune and inflammatory responses, while monocyte-to-macrophage differentiation is one of the main macrophage resources that involves various matrix proteins. Matrix remodeling associated 7 (MXRA7) was recently discovered to affect a variety of physiological and pathological processes related to matrix biology. In the present study, we investigated the role of MXRA7 in monocyte-to-macrophage differentiation in vitro. We found that knockdown of MXRA7 inhibited the proliferation of THP-1 human monocytic cells. Knockdown of MXRA7 increased the adhesion ability of THP-1 cells through upregulation the expression of adhesion molecules VCAM-1 and ICAM1. Knockdown of MXRA7 alone could promoted the differentiation of THP-1 cells to macrophages. Furthermore, the MXRA7-knockdown THP-1 cells produced a more significant upregulation pattern with M1-type cytokines (TNF-α, IL-1ß and IL-6) than with those M2-type molecules (TGF-ß1 and IL-1RA) upon PMA stimulation, indicating that knockdown of MXRA7 facilitated THP-1 cells differentiation toward M1 macrophages. RNA sequencing analysis revealed the potential biological roles of MXRA7 in cell adhesion, macrophage and monocyte differentiation. Moreover, MXRA7 knockdown promoted the expression of NF-κB p52/p100, while PMA stimulation could increase the expression of NF-κB p52/p100 and activating MAPK signaling pathways in MXRA7 knockdown cells. In conclusion, MXRA7 affected the differentiation of THP-1 cells toward macrophages possibly through NF-κB signaling pathways.

Quantitative analysis of the dominant external factors influencing elite speed Skaters' performance using BP neural network.

Introduction: Speed skating, being a popular winter sport, imposes significant demands on elite skaters, necessitating their effective assessment and adaptation to diverse environmental factors to achieve optimal race performance. Objective: The aim of this study was to conduct a thorough analysis of the predominant external factors influencing the performance of elite speed skaters. Methods: A total of 403 races, encompassing various race distances and spanning from the 2013 to the 2022 seasons, were examined for eight high-caliber speed skaters from the Chinese national team. We developed a comprehensive analytical framework utilizing an advanced back-propagation (BP) neural neural network model to assess three key factors on race performance: ice rink altitude, ice surface temperature, and race frequency. Results: Our research indicated that the performance of all skaters improves with higher rink altitudes, particularly in races of 1,000 m and beyond. The ice surface temperature can either enhance or impaire performance and varies in its influences based on skaters' technical characteristics, which had a perceptible or even important influence on races of 1,500 m and beyond, and a negligible influence in the 500 m and 1,000 m races. An increase in race frequency generally contributed to better performance. The influence was relatively minor in the 500 m race, important in the 3,000 m race, and varied among individuals in the 1,000 m and 1,500 m races. Conclusion: The study results offer crucial guidelines for speed skaters and coaches, aiding in the optimization of their training and competition strategies, ultimately leading to improved competitive performance levels.

Progress in the study of reproductive toxicity of platinum-based antitumor drugs and their means of prevention.

Platinum-based antitumor drugs are broad-spectrum agents with unique mechanisms of action. Combination chemotherapy regimens based on platinum drugs are commonly used in cancer treatment. However, these drugs can cause various adverse reactions in the human body through different routes of administration, including reproductive toxicity, genetic toxicity, and embryonic developmental toxicity. Preventing adverse effects is crucial to enhance patients' quality of life and reduce healthcare costs. This article discusses the types and developmental history of antitumor active platinum compounds, their mechanisms of action, routes of administration, and their potential reproductive, genetic, and embryonic developmental toxicity. This text explores preventive measures based on animal experimental results. Its aim is to provide references for personalized treatment and occupational protection when using platinum drugs. The continuous progress of science and technology, along with the deepening of medical research, suggests that the application of platinum drugs will broaden. Therefore, the development of new platinum drugs will be an important direction for future research.

A ground reaction force model of speed skating based on non-contact measurement system.

Accurate collection and analysis of ground reaction force (GRF) data are crucial for optimizing the technical movements of speed skaters; however, it has been a challenge for the limitations of experimental equipment and application scenarios. Therefore, we proposed a novel approach for estimating GRF based on kinematics obtained from markerless video tracking systems and achieved low errors compared with the experimental data. Our method allows for further biomechanical analysis, including muscle force and power, during speed skating competitions.

Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

Analysis of the correlation between immune cell characteristics and insomnia: a Mendelian randomization study.

Insomnia, recognized as a prevalent sleep disorder, has garnered extensive attention within the realm of public health. Recent studies indicate a close interaction between the immune system and sleep; however, the specific mechanism remains not yet fully understood. Based on the publicly available Genome-Wide Association Study (GWAS) data, we used two-sample Mendelian randomization (MR) analyses to investigate the associations between 731 immune cell traits and insomnia risk. Five MR analysis methods and a comprehensive sensitivity analysis were used to evaluate the reliability of the results. In this study, we identified that 14 immune characteristics among four immune profiles [median fluorescence intensity (MFI), relative cell count (RC), absolute cell count (AC), and morphological parameters (MP)] demonstrated a significant causal association with insomnia. Specifically, eight immune cell characteristics were associated with an increased risk of insomnia, including CD11c+ monocyte% (P < 0.001), CD11c+ HLA DR++ monocyte% (P = 0.004), CD86+ plasmoid dendritic cell (DC) AC (P < 0.001), CD33br HLA DR+ CD14dim AC (P < 0.001), CD8dim AC (P = 0.002), CCR2 on CD14+ CD16- monocyte (P < 0.001), CD39 on monocyte (P < 0.001), and SSC-A on myeloid DC (P < 0.001). Six immune cell characteristics demonstrated protective effects against insomnia, including PB/PC %B cell (P < 0.001), CM CD4+% CD4+ (P < 0.001), T-cell AC (P < 0.001), BAFF-R on IgD- CD38br (P < 0.001), CD16-CD56 on HLA DR+ NK cells (P < 0.001), and CD14 on CD33br HLA DR+ CD14dim (P < 0.001). Our study established the correlation between immune cell characteristics and insomnia, offering a novel theoretical foundation for the concept of sleep-immune cross talk.NEW & NOTEWORTHY This study investigated the association between 731 immune cell characteristics and insomnia using Mendelian randomization, revealing that 14 immune cell characteristics across four groups of immune traits (MFI, RC, AC, and MP) have a significant and causal association with insomnia risk. Our results contribute to the understanding of the sleep-immune cross talk doctrine and offer a new theoretical basis for immune modulation in treating insomnia.

Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia.

Background: Satisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence. Methods: Here, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes. Results: According to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model's risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines. Conclusions: The 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis.

Double layer spherical nanoparticles with hyaluronic acid coating to enhance oral delivery of exenatide in T2DM rats.

Soybean phospholipid was used as an amphiphilic material to form reverse micelles (RMs) in medium glycerol monolinoleate (Maisine) with Exenatide (EXT.) encapsulated in the polar core formed by the hydrophilic part of phospholipid. Cremopher RH40 and caprylocaproyl macrogol-8 glycerides EP/caprylocaproyl polyoxyl-8 glycerides NF (Labrasol) were added as surfactants to prepare reverse micelles-self emulsifying drug delivery system (RMs-SEDDS). On this basis, oil in water (O/W) emulsion was further prepared. By adding DOTAP, the surface of the emulsion was positively charged. Finally, hyaluronic acid wrapping in the outermost layer by electrostatic adsorption and reverse micelles-O/W-sodium hyaluronate (RMs-O/W-HA) nanoparticles containing Exenatide were prepared. RMs-SEDDS was spherical with an average particle size of 213.6 nm and RMs-O/W-HA was double-layered spherical nanoparticle with an average particle size of 309.2 nm. HA coating enhanced the adhesion of nanoparticles (NPs), and RMs-O/W-HA increased cellular uptake through CD44-mediated endocytosis. Pharmacodynamics results showed that RMs-SEDDS and RMs-O/W-HA could reduce blood glucose in type 2 diabetic rats, protect pancreatic ß cells to a certain extent, and relieve insulin resistance and hyperlipemia complications with good safety.

Microlens array device for laser light shaping in laser scanning smart headlights.

We present, what we believe to be, a novel microlens array (MLA) scheme for laser light shaping in laser scanning smart headlight. The laser spot has a Gaussian distribution that may reach a high peak power density in the central part, which is called hot spot. When the laser beam is applied to a phosphor plate for luminous conversion, the hot spot of Gaussian beam causes thermal quench and decreases luminous efficacy. To avoid this effect, an MLA is used, so as to achieve a uniform energy distribution. In this study, we propose a laser scanning smart headlight fabricated by a new MLA structure, with an arrangement providing both light uniformity and shaping. The novel MLA is designed by two-dimensional micro-concave lens array yielding a flat-top beam. The flexible fabrication process employs laser drilling to shape the micro-hole array on the glass substrate surface and then etch it to form MLA without requiring any mask lithography process. The full-width half maximum (FWHM) of light output distribution can be adjusted by the glass etching parameters, and the light distribution could be controlled by the arranged layout of the array. Thus, beams with FWHM divergence ranging from 5° to 34° has been fabricated and characterized. The typical pixel shape is a rectangle with two different FWHMs in two orthogonal directions, and the fabrication method achieves this goal as well. This novel design and unique maskless process of the MLAs is a promising tool for development the next generation laser scanning smart headlight.

Identification and validation of a 7-genes prognostic signature for adult acute myeloid leukemia based on aging-related genes.

To explore effects of aging-related genes (ARGs) on the prognosis of Acute Myeloid Leukemia (AML), a seven-ARGs signature was developed and validated in AML patients. The numbers of seven-ARG sequences were selected to construct the survival prognostic signature in TCGA-LAML cohort, and two GEO datasets were used independently to verify the prognostic values of signature. According to seven-ARGs signature, patients were categorized into two subgroups. Patients with high-risk prognostic score were defined as HRPS-group/high-risk group, while others were set as LRPS-group/low-risk group. HRPS-group presented adverse overall survival (OS) than LRPS-group in TCGA-AML cohort (HR=3.39, P<0.001). In validation, the results emphasized a satisfactory discrimination in different time points, and confirmed the poor OS of HRPS-group both in GSE37642 (HR=1.96, P=0.001) and GSE106291 (HR=1.88, P<0.001). Many signal pathways, including immune- and tumor-related processes, especially NF-κB signaling, were highly enriched in HRPS-group. Coupled with high immune-inflamed infiltration, the HRPS-group was highly associated with the driver gene and oncogenic signaling pathway of TP53. Prediction of blockade therapy targeting immune checkpoint indicated varied benefits base on the different ARGs signature score, and the results of predicted drug response suggested that Pevonedistat, an inhibitor of NEDD8-activating enzyme, targeting NF-κB signaling, may have potential therapeutic value for HRPS-group. Compared with clinical factors alone, the signature had an independent value and more predictive power of AML prognosis. The 7-ARGs signature may help to guide clinical-decision making to predict drug response, and survival in AML patients.

Is red cell distribution width a prognostic factor in patients with breast cancer? A meta-analysis.

Purpose: The current study aimed to investigate whether red blood cell distribution width (RDW) can predict the prognosis of patients with breast cancer (BC). Methods: We searched four databases, including PubMed, Embase, Cochrane Library databases, and CNKI, from inception to Jun 13, 2022. The primary outcome was overall survival (OS), and the secondary outcome was disease-free survival (DFS). A subgroup analysis was conducted based on different treatments. This meta-analysis was performed with RevMan 5.3 (The Cochrane Collaboration, London, United Kingdom). Results: A total of seven studies including 4,884 BC patients were identified. The high RDW group had a larger tumor size (OR = 2.12, 95% CI = 1.67 to 2.68, P < 0.01), higher proportions of advanced stage tumors (OR = 1.77, 95% CI = 1.38 to 2.27, P < 0.01), more lymph node metastases (OR = 2.00, 95% CI = 1.58 to 2.51, P < 0.01) and lower HER-2 expression (OR = 0.76, 95% CI = 0.61 to 0.95, P = 0.02). For prognosis, after pooling all the data, we found that the high RDW group was associated with worse OS (HR = 2.12, 95% CI = 1.47 to 3.08, P < 0.01) and DFS (HR = 1.77, 95% CI = 1.32 to 2.37, P < 0.01). The subgroup analysis found that RDW had prognostic significance but only for surgery-only patients (HR = 2.41, 95% CI = 1.67 to 3.49, P < 0.01). Conclusion: High RDW was associated with worse OS and DFS. Therefore, RDW was a simple predictive factor for the prognosis of BC patients.

Two triplet emitting states in one emitter: Near-infrared dual-phosphorescent Au20 nanocluster.

Intrinsic dual-emission (DE) of gold nanoclusters in the near-infrared (NIR) are fascinating for fundamental importance and practical applications, but their synthesis remains a formidable challenge and sophisticated excited-state processes make elucidating DE mechanisms much more arduous. Here, we report an all-alkynyl-protected gold nanocluster, Au20, showing a prolate Au12 tri-octahedral kernel surrounded by two Au2(CZ-PrA)3 dimers, four Au(CZ-PrA)2 monomers, and two CZ-PrA- bridges. Au20 exhibits distinguished photophysical properties including NIR DE at 820 and 940 nm, microsecond radiative relaxation, and 6.26% photoluminescent quantum yield at ambient environment in nondegassed solution. Combining systematic studies on steady/transient spectroscopy and theoretical calculation, we identified two triplet charge transfer (CT) states, ligand-to-kernel and kernel-based CT states as DE origins. Furthermore, this NIR DE exhibits highly independent and sensitive response to surrounding environments, which well coincide with its mechanism. This work not only provides a substantial structure model to understand a distinctive DE mechanism but also motivates the further development of NIR DE materials.

Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation.

OBJECTIVE: Kidney renal clear cell carcinoma (KIRC) is a common renal malignancy that has a poor prognosis. As a member of the F box family, cyclin F (CCNF) plays an important regulatory role in normal tissues and tumors. However, the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear. METHODS: Bioinformatics methods were used to analyze The Cancer Genome Atlas (TCGA) database to obtain gene expression and clinical prognosis data. The CCK8 assay, EdU assay, and xenograft assay were used to detect cell proliferation. The cell senescence and potential mechanism were assessed by SA-ß-gal staining, Western blotting, as well as ELISA. RESULTS: Our data showed that CCNF was highly expressed in KIRC patients. Meanwhile, downregulation of CCNF inhibited cell proliferation in vivo and in vitro. Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1 (CDK1), increasing the proinflammatory factors interleukin (IL)-6 and IL-8, and then enhancing the expression of p21 and p53. CONCLUSION: We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence. Therefore, CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.

Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China.@*METHODS@#A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses.@*RESULTS@#The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001).@*CONCLUSION@#Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.

Application of metabonomics strategy in sepsis / 中国小儿急救医学

Sepsis is a heterogeneous disease with a complex pathogenesis and diverse clinical manifestations.Sepsis leads to disruption of biochemical homeostasis, which strongly promotes changes in metabolites in the body.Initial differences in metabolites may predict the severity of the disease, and changes in metabolites over time may useful in assessing treatment response, predicting progression of disease progression or clinical outcomes.This review focused on the studies related to the application of metabolomics strategy in sepsis, which could help to understand the potential value of sepsis metabolomics in the pathogenesis, diagnosis, prognosis and treatment of sepsis.

Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City / 中华预防医学杂志

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

Numerical optimization of pacing strategy in cross-country skiing based on Gauss pseudo-spectral method.

In cross-country skiing competitions, the choice of pacing strategy is of decisive significance to athletes' performance. A reasonable pacing strategy is essential for athletes to improve their performance. In this paper, the mathematical models of cross-country skiing simulation and pacing optimization are established, including motion model, athlete power output model, and optimization model. The actual competition data of a Chinese athlete in Guyangshu 1.5 km track was compared with the model simulation results. The whole process time error is less than 3%, which verifies the accuracy of the motion and power output model. Gauss pseudo-spectral method is applied to the optimization model. By changing the distribution of athletes' power output, the racing time is minimized under the condition that the total energy output remains unchanged. Compared with the pacing strategy before optimization, the optimized racing time was shortened by 12.6 s, which verifies the effectiveness of the optimization model. Optimized results show that in the first significant uphill section, a recommendation is to use a more conservative strategy, while in the latter half of uphill sections the power output should be increased.