Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.

Sepsis is a leading cause of in-hospital mortality resulting from a dysregulated response to infection. Novel immunomodulatory therapies targeting macrophage metabolism have emerged as an important focus for current sepsis research. However, understanding the mechanisms underlying macrophage metabolic reprogramming and how they impact immune response requires further investigation. Here, we identify macrophage-expressed Spinster homolog 2 (Spns2), a major transporter of sphingosine-1-phosphate (S1P), as a crucial metabolic mediator that regulates inflammation through the lactate-reactive oxygen species (ROS) axis. Spns2 deficiency in macrophages significantly enhances glycolysis, thereby increasing intracellular lactate production. As a key effector, intracellular lactate promotes pro-inflammatory response by increasing ROS generation. The overactivity of the lactate-ROS axis drives lethal hyperinflammation during the early phase of sepsis. Furthermore, diminished Spns2/S1P signaling impairs the ability of macrophages to sustain an antibacterial response, leading to significant innate immunosuppression in the late stage of infection. Notably, reinforcing Spns2/S1P signaling contributes to balancing the immune response during sepsis, preventing both early hyperinflammation and later immunosuppression, making it a promising therapeutic target for sepsis.

A new mechanism in negative pressure wound therapy: interleukin-17 alters chromatin accessibility profiling.

Negative pressure wound therapy (NPWT) is extensively used in clinical settings to enhance the healing of wounds. Despite its widespread use, the molecular mechanisms driving the efficacy of NPWT have not been fully elucidated. In this study, skin wound-healing models were established, with administration of NPWT. Vimentin, collagen I, and MMP9 of skin tissues were detected by immunofluorescence (IF). Gene expression analysis of skin wound tissues was performed by RNA-sequencing (RNA-seq). Protein expression was assayed by a Western blotting or IF assay, and mRNA levels were quantified by quantitative PCR. Chromatin accessibility profiles of fibroblasts following NPWT or IL-17 exposure were analyzed by ATAC-seq. In rat wound-healing models, NPWT promoted wound repair by promoting reepithelialization, extracellular matrix (ECM) synthesis, and proliferation, which mainly occurred in the early stage of wound healing. These differentially expressed genes (DEGs) in NPWT wounds versus control wounds were enriched in the IL-17 signaling pathway. IL-17 was identified as an upregulated factor following NPWT in skin wounds. Moreover, the IL-17 inhibitor secukinumab (SEC) could abolish the promoting effect of NPWT on wound healing. Importantly, chromatin accessibility profiles were altered following NPWT and IL-17 stimulation in skin fibroblasts. Our findings suggest that NPWT upregulates IL-17 to promote wound healing by altering chromatin accessibility, which is a novel mechanism for NPWT's efficacy in wound healing.NEW & NOTEWORTHY To our knowledge, this is the first report of the efficacy of negative pressure wound therapy (NPWT) in promoting wound healing via IL-17. Moreover, NPWT and IL-17 can alter chromatin accessibility. Our study identifies a novel mechanism for NPWT's efficacy in wound healing.

Perceived control, self-management efficacy, and quality of life in patients treated with radiation therapy for breast cancer: a longitudinal study.

OBJECTIVE: This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. METHODS: Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. RESULTS: Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (ß = 0.30, P < 0.001), presence of chemotherapy (ß = 18.33, P = 0.024), and duration of illness (ß = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (ß = - 2.95, P < 0.001), cancer experience (ß = - 0.46, P < 0.001), and type of medical insurance (ß = - 2.77, P = 0.021) had the negative effect on the change in QoL. CONCLUSION: The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.

Basic Helix-Loop-Helix (bHLH) Transcription Factors Regulate a Wide Range of Functions in Arabidopsis.

The basic helix-loop-helix (bHLH) transcription factor family is one of the largest transcription factor gene families in Arabidopsis thaliana, and contains a bHLH motif that is highly conserved throughout eukaryotic organisms. Members of this family have two conserved motifs, a basic DNA binding region and a helix-loop-helix (HLH) region. These proteins containing bHLH domain usually act as homo- or heterodimers to regulate the expression of their target genes, which are involved in many physiological processes and have a broad range of functions in biosynthesis, metabolism and transduction of plant hormones. Although there are a number of articles on different aspects to provide detailed information on this family in plants, an overall summary is not available. In this review, we summarize various aspects of related studies that provide an overview of insights into the pleiotropic regulatory roles of these transcription factors in plant growth and development, stress response, biochemical functions and the web of signaling networks. We then provide an overview of the functional profile of the bHLH family and the regulatory mechanisms of other proteins.

[Prevalence of pediatric asthma in the rural areas of China: a Meta analysis].

OBJECTIVE: To systematically review the prevalence of pediatric asthma in the rural areas of China, and to provide data for the prevention and treatment of pediatric asthma. METHODS: PubMed, Cochrane, China National Knowledge Infrastructure, Wanfang Database, and Embase were searched for cross-sectional studies on the prevalence of pediatric asthma in the rural areas of China published up to August 31, 2019. Two researchers independently conducted preliminary screening and data extraction. Stata 14.0 and R software were used to perform a Meta analysis of prevalence rate. Subgroup analysis was also performed. RESULTS: A total of 24 articles were reviewed, with a sample size of 212 814 children, among whom there were 3 254 children with asthma, with an overall prevalence rate of 2.02% (95%CI: 1.67%-2.36%). Boys had a significantly higher prevalence rate than girls (3.64% vs 2.03%, P<0.001). The annual prevalence rate increased from 1.21% in 1990-1999 to 3.36% in 2011-2015. The prevalence rate of pediatric asthma was 3.15% in South China, which was higher than that in East China (2.31%), Southwest China (2.15%), North China (1.19%), and Central China (1.12%). Preschool children had the highest prevalence rate of 2.63%, followed by infants and young children (2.48%) and school-age children (1.41%). CONCLUSIONS: The prevalence rate of pediatric asthma is relatively low but tends to increase in the rural areas of China. Boys have a higher prevalence rate of asthma than girls, and the prevalence rate is higher in South China. Preschool children have the highest prevalence rate.

S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Danhong Injection Attenuates High-Fat-Induced Atherosclerosis and Macrophage Lipid Accumulation by Regulating the PI3K/AKT Insulin Pathway.

BACKGROUND AND AIMS: High-fat diet (HFD) is reported to induce atherosclerosis and insulin resistance. Macrophage lipid accumulation has been implicated as key mediators during the development of HFD-induced atherosclerosis. Traditional Chinese formula, which has long been used to improve disorder of glucose and lipid metabolism of patients, is now gradually being used as complementary therapy. This study aimed to investigate the effect of Danhong injection (DHI), a Chinese medicine used for the treatment of coronary artery disease, on atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: We observed the effects of DHI on HFD-induced atherosclerosis in a mice model, macrophage lipid accumulation in an ox-LDL-stimulated macrophage model, and the role of PI3K/AKT insulin pathway in the process of DHI ameliorating atherosclerosis. The data demonstrated that DHI attenuated atherosclerosis by ameliorating blood lipids, reducing the atherosclerotic index and atherosclerotic plaque area in HFD-induced atherosclerotic mice, and inhibiting TC levels in an ox-LDL-induced macrophage model. By estimating the levels of serum insulin resistance-related indexes and protein expression of GLUT-4, DHI treatment dramatically inhibited the levels of fasting serum NEFA and fasting serum insulin and promoted the protein expression of GLUT-4 in aortas of the HFD-induced atherosclerotic mice. Moreover, according to the hints provided by microarray-based transcriptional profiling, the results demonstrated that DHI treatment also promoted the activation of PI3K/AKT insulin signaling pathway induced by IRS-1 in aortas of HFD-induced atherosclerotic mice. Furthermore, in an ox-LDL-induced macrophage model, the activation of PI3k/AKT signaling pathway also effectively functioned in the process of DHI inhibiting macrophage lipid accumulation. CONCLUSIONS: These results highlight that DHI treatment attenuates atherosclerosis and macrophage lipid accumulation by promoting the activation of PI3K/AKT insulin signaling pathway. It provides new insights into the molecular mechanism of DHI and its therapeutic potential in the treatment of atherosclerosis.

[Reproductive characteristics and habitat factors of Acanthopanax giraldii].

The growth parameters,clonal propagation parameters and sexual reproduction parameters of Acanthopanax giraldii population were systematically investigated and analyzed by means of population ecology in this study. The correlation among the above mentioned parameters and the correlation among canopy density,topography and soil fertility factors were analyzed. It is clear that there was a significant correlation among the clonal ramets,the fruit production capacity of the cluster and the new shoot production capacity of the A. giraldii. Sexual reproduction and clonal reproduction played an important role in the continuation of the population. Illumination was the key ecological factor that determined growth type. The increase in canopy density changed the population from " group clonal growth" to " guerrilla clonal growth",and the higher stand closure degree and low-strength herb layer competition was a necessary condition for seed germination and colonization. Under the background of natural forest protection and sustainable development of resources,the reproductive characteristics of wild A. giraldii resulted in the decrease of its recoverable quantity.

Stereoselective Synthesis of the ABC Ring System of Aspterpenacids.

Aspterpenacids A and B are sesterterpenoids that possess a unique and highly congested 5/3/7/6/5 fused ring system. These compounds also contain a sterically encumbered isopropyl trans-hydrindane motif and a cyclopropane motif bearing two quaternary centers, which make them remarkably challenging synthetic targets. Herein, we report the successful construction of the key highly substituted ABC ring system in a stereoselective manner.

Total Synthesis of Astellatol.

A nearly-30-year-old unanswered synthetic puzzle, astellatol, has been solved in an enantiospecific manner. The highly congested pentacyclic skeleton of this rare sesterterpenoid, which possesses a unique bicyclo[4.1.1]octane motif, ten stereocenters, a cyclobutane that contains two quaternary centers, an exo-methylene group, and a sterically encumbered isopropyl trans-hydrindane motif, makes astellatol arguably one of the most challenging targets for sesterterpenoid synthesis. An intramolecular Pauson-Khand reaction was exploited to construct the right-hand side scaffold of this sesterterpenoid. An unprecedented reductive radical 1,6-addition, mediated by SmI2 , forged the cyclobutane motif. Last, a strategic oxidation/reduction step provided not only the decisive solution for the remarkably challenging late-stage transformations, but also a highly valuable unravelling of the notorious issue of trans-hydrindane synthesis. Importantly, the synthesis of astellatol showcases a rapid, scalable strategy to access diverse complex isopropyl trans-hydrindane sesterterpenoids.

Swallowing rehabilitation of patients undergoing T-tube implantation for the treatment of laryngotracheal stenosis.

OBJECTIVE: Patients with laryngotracheal stenosis (LTS) often have dysphagia after laryngotracheal reconstruction with T-tube insertion, which affects the quality of life. The purpose of this study is to observe the effect of swallowing rehabilitation therapy on the improvement of quality of life in patients of otolaryngology-head and neck surgery with dysphagia undergoing T-tube implantation treatment through longitudinal study. METHODS: Thirty-eight patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation were recruited. All patients received swallowing rehabilitation therapy. The assessment of swallowing function was performed using the 10-item Eating Assessment Tool (EAT-10), the 30 mL water swallow test (WST), and flexible endoscopic evaluation of swallow (FEES). RESULTS: After swallowing rehabilitation therapy, timing of swallowing, grade of dysphagia, performance on FEES and 30 mL WST, and EAT-10 score all improved. Thirty-eight patients successfully transitioned to oral feeding and were able to remove their nasogastric tubes without experiencing any complications, including aspiration pneumonia. CONCLUSION: For patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation, swallowing rehabilitation therapy could improve swallowing function of the patients, so as to reduce the potential harm caused by the pain and complications of surgery experienced by patients.

Effects of folic acid supplementation on cognitive impairment: A meta-analysis of randomized controlled trials.

OBJECTIVE: With the increasing number of patients with cognitive impairment, nonpharmacological ways to delay cognitive impairment have attracted people's attention, such as lifestyle changes and nutritional supplementation. Folic acid supplementation appears to be a promising treatment option. However, it remains controversial whether folic acid supplementation is effective in delaying adult's cognitive impairment. Therefore, we conducted a meta-analysis to analyze the effects of folic acid supplementation on different cognitive impairments. METHODS: We systematically searched PubMed, Web of Science, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), WanFang and VIP databases for randomized controlled trials on January 22, 2024. The included population comprised those diagnosed with cognitive impairment. We included trials that compared folic acid treatment with placebo, other dosing regimens, or other intervention controls. Conducting quality evaluation of included studies according to the Cochrane Risk of Bias tool. Statistical analyses were performed using Review Manager software. RESULTS: Twenty-two trials, including 3604 participants, met inclusion criteria. Compared with controls, the cognitive function of Alzheimer's disease (AD) patients showed improvement with folic acid supplementation: supplementation with < 3 mg (standardized mean differences (SMD) = 0.15, 95% confidence interval (CI) -0.10 to 0.41), and supplementing with ≥ 3 mg folic acid could improve cognitive function in AD patients (SMD = 1.03, 95% CI 0.18 to 1.88). Additionally, it reduced homocysteine (HCY) levels (mean differences (MD) = -4.74, 95% CI -8.08 to -1.39). In mild cognitive impairment (MCI) patients, cognitive function improved with folic acid supplementation: supplementation with > 400 µg (SMD = 0.38, 95% CI 0.13 to 0.63), and supplementation with ≤ 400 µg (SMD = 1.10, 95% CI 0.88 to 1.31). It also reduced HCY levels at intervention ≤ 6 months (MD = -3.93, 95% CI -5.05 to -2.82) and intervention > 6 months (MD = -4.38, 95% CI -5.15 to -3.61). However, supplementing with folic acid did not improve cognitive function in vascular cognitive impairment (VCI) patients, with folic acid supplements < 3 mg (SMD = -0.07, 95% CI -0.23 to -0.08), folic acid supplements ≥ 3 mg (SMD = 0.46, 95% CI -0.57 to 1.49), however, it reduced HCY levels at intervention > 6 months (MD = -5.91, 95% CI -7.13 to -4.69) and intervention ≤ 6 months (MD = -11.15, 95% CI -12.35 to -9.95). CONCLUSIONS: Supplement folic acid is beneficial to the cognitive profile of patients with MCI, supplementation with ≥ 3 mg folic acid can improve cognitive function in AD patients.

Split-level folding, step-type tension-relieving suture technique, and the evaluation on scar minimization.

BACKGROUND: Prevailing tension-reducing suture methods have a spectrum of issues. This study presents a straightforward yet highly efficacious suture technique known as the Split-level Folding, Step-type Tension-relieving Suture technique, which could play a pivotal role in preempting incisional scarring. AIMS: To introduce Split-level Folding, Step-type Tension-relieving Suture technique and assess its effect on scar minimization. METHODS: A retrospective analysis of 64 patients who underwent treatment utilizing the proposed suturing methodology. Assessment parameters included the Patient and Observer Scar Assessment Scale (POSAS), the Vancouver Scar Scale (VSS), scar width, complications, and all evaluated at 6- and 12-month postoperatively. RESULTS: At 12-month follow-up, the POSAS and VSS scores in the normal suture group (32.58 ± 5.43, 3.58 ± 1.39) were considerably higher than the step-type suture group (29.75 ± 3.56, p = 0.0007; 2.78 ± 1.17, p = 0.0006). Moreover, the step-type suture group showcased a significantly narrower average incision scar width (1.62 ± 0.36) than the normal suture group (1.87 ± 0.42, p = 0.0004). This novel tension-relieving suture technique that effectively circumvents the occurrence of persistent localized eversion and other complications often associated with traditional tension-relieving sutures. CONCLUSIONS: The Split-level Folding, Step-type Tension-relieving Suture technique emerges as a highly promising option for averting incisional scarring. This suture method works well for incisions on the chest, back, and extremities, resulting in significantly better long-term outcomes.

Surface-plasmon-induced modification on the spontaneous emission spectrum via subwavelength-confined anisotropic Purcell factor.

The mechanism of using the anisotropic Purcell factor to control the spontaneous emission linewidths in a four-level atom is theoretically demonstrated; if the polarization angle bisector of the two dipole moments lies along the axis of large/small Purcell factor, destructive/constructive interference narrows/widens the fluorescence center spectral lines. Large anisotropy of the Purcell factor, confined in the subwavelength optical mode volume, leads to rapid spectral line narrowing of atom approaching a metallic nanowire, nanoscale line width pulsing following periodically varying decay rates near a periodic metallic nanostructure, and dramatic modification on the spontaneous emission spectrum near a custom-designed resonant plasmon nanostructure. The combined system opens a good perspective for applications in ultracompact active quantum devices.

Spirituality as a Mediator Between Social Support and Benefit Finding Among Advanced Cancer Patients.

BACKGROUND: Social support and benefit finding (BF) are important for cancer patients. The relationship between social support and BF has not been studied sufficiently in patients with advanced cancer, and the mechanism through which social support might influence BF is unclear. OBJECTIVE: This study aimed to investigate the relationship between social support and BF in Chinese patients with advanced cancer as mediated by their perceptions of spirituality. METHODS: This was a correlation study with a cross-sectional design. We recruited advanced-cancer patients (n = 208) from China. Patients' sociodemographic and clinical characteristics were collected, and they were asked to complete the Benefit Finding Scale, the Multidimensional Scale of Perceived Social Support, and the Spiritual Attitude and Involvement List. RESULTS: Social support was associated with greater spirituality and greater BF ( P < .01). Spirituality was positively correlated with BF ( P < .01). Results from mediation analysis identified that both the indirect effect of social support on BF via spirituality (indirect effect, 0.268; 95% confidence interval, 0.147-0.419) and its direct effect on BF (direct effect, 0.233; 95% confidence interval, 0.031-0.429) were statistically significant, suggesting a partial mediatory effect of spirituality between social support and BF. CONCLUSIONS: Our findings supported a positive association between social support and BF among Chinese advanced-cancer patients. The mediatory role of spirituality should provide a new perspective for augmentation of BF in these patients. IMPLICATIONS FOR PRACTICE: Interventions that help enhance social support and spirituality in patients with advanced cancer could facilitate their BF.

Fear of progression, loneliness, and hope in patients with gastrointestinal cancer: a cross-sectional relational study.

Introduction: In recent years, fear of disease progression (FoP) has become one of the most common psychological problems in cancer patients. However, there are fewer studies on the FoP in patients with gastrointestinal tumors. We aimed to assess the level of FoP in patients with gastrointestinal tumors and analyze the factors related to FoP. We also aimed to examine the relationship among loneliness, hope and FoP in patients with gastrointestinal cancer. Methods: A cross-sectional survey was conducted on three Grade A hospitals in southwestern China from November 2021 to July 2022. The demographic and clinical characteristics questionnaire, Fear of Disease Progression Scale (FoP-Q-SF), Cancer Loneliness Scale (CLS), and Herth Hope Index (HHI) were included in this study. Data analysis included descriptive statistics, independent samples t-tests, one-way analysis of variance, and multiple linear regression analysis. Results: In total, 245 gastrointestinal cancer patients participated in this study. The average (standard deviation) FoP score in patients was 32.94 ± 10.64. In total, 245 gastrointestinal cancer patients participated in this study. The average (standard deviation) FoP score in patients was 32.94 ± 10.64. The average score of CLS was 17.65 ± 6.71, and that for the HHI was 31.27 ± 7.73. Pearson correlation analysis showed that FoP was negatively significant correlated with hope level (r = -0.522) and FoP was positively significant correlated with loneliness (r = 0.545). Linear regression analysis showed that educational level, age, living condition, hope, and loneliness were the significant predictors of FoP and explained 53.10% of the variability in FoP (F = 16.372). Conclusion: Findings highlight the need to strengthen attention to FoP in gastrointestinal cancer patients. Our study showed that gastrointestinal cancer patients who have a high school education, are age 45 to 59, live alone, high level of loneliness, and low level of hope have higher FoP. Medical staff should enhance clinical screening of FoP and consider the formulation of relevant interventions for high-risk groups to reduce loneliness among patients, raise their hope level, and reduce their FoP.

An experimental model of peripheral nerve electrical injury in rats.

INTRODUCTION: Although several studies have investigated models of nerve electrical injury, only a few have focused on electrical injury to peripheral nerves, which is a common and intractable problem in clinical practice. Here, we describe an experimental rat model of peripheral nerve electrical injury and its assessment. METHODS: A total of 120 animals were subjected to short-term corrective electrostimulation (50 Hz, 1-s duration) applied at varying voltages (control, 65, 75, 100, 125, and 150 V) to the exposed left sciatic nerve. Behavioural testing, electrophysiological measurements, and histopathological observation of the sciatic nerve were conducted at 1-, 2-, 4-, and 8-w follow-ups. RESULTS: No functional defects were noted in the groups that received 65-V stimulation at any time point. Sciatic nerve functional defects were found after 2 w in animals that received 75-V stimulation, but function returned to normal after 4 w. In animals that received 100-V and 125-V stimulation, functional defects were observed at 4 w, but had partially recovered by 8 w. Conversely, animals that received 150-V stimulation did not show recovery after 8 w. CONCLUSION: We presented a model of peripheral nerve electrical injury that avoided the interference of various external factors, such as current instability, compression of the surrounding tissues, and altered blood supply. The model allowed quantitation and ranking of the nerve injury into four degrees. It facilitated effective evaluation of nerve function impairment and repair after injury. It can be used post-surgically to evaluate peripheral nerve impairment and reconstruction and enables translational interpretation of results, which may improve understanding of the mechanisms underlying the progression of peripheral nerve electrical injury.

Polydatin radiosensitizes lung cancer while preventing radiation injuries by modulating tumor-infiltrating B cells.

BACKGROUND: Acquired radio-resistance and the undesired normal tissue radiation injuries seriously discount the therapeutic effect of lung cancer radiotherapy. In this study, we aimed to explore the role and potential mechanism of polydatin in simultaneously decreasing radioresistance and radiation injuries. METHODS: The tumor-bearing model of nude mice was used to investigate the tumor inhibition of polydatin on lung cancer and its effect on radiosensitivity, and the effect of polydatin on B cell infiltration in cancerous tissue was investigated. In addition, we performed systemic radiotherapy on BABL/C mice and evaluated the protective effect of polydatin on radiation injury by the Kaplan-Meier survival curve. Moreover, the regulation of polydatin on proliferation and apoptosis of A549 cells was also investigated in vitro. RESULTS: In this study, it is first found that polydatin inhibits the growth and promotes the radiosensitivity of lung cancer while reducing the radiation damage of the healthy tissue. Further, it is evidenced that the major mechanism relies on its regulation on body's immune function, and in particular, the inhibition of radiation-induced B cell infiltration in tumor tissue. CONCLUSION: These findings show that in addition to tumor inhibition, polydatin also promotes the sensitivity and reduces the adverse reactions of radiotherapy, making itself a promising candidate for boosting lung cancer radiotherapy efficacy.

3D biomechanical properties of the layered esophagus: Fung-type SEF and new constitutive model.

BACKGROUND AND PURPOSE: Most current studies on the passive biomechanical properties of esophageal tissues directly use the exponential strain energy function (SEF) to fit and calculate the constants of the constitutive equation. In the context of the extensive application of exponential SEF, in-depth research on the exponential SEF is still lacking. The purpose of this study is to combine the exponential function with the polynomial SEF to obtain the most suitable constitutive equation to describe the three-dimensional passive behavior of the esophagus. METHODS: fresh pig esophagus with a length of 13 cm in the middle position was selected as esophageal samples. The esophageal sample was separated into muscular layer and mucosal layer with surgical scissors. Stretch-inflation mechanical tests of the intact esophagus, esophageal muscular, and esophageal mucosa were carried out on a triaxial test machine. The external radius, axial force, and internal pressure were recorded simultaneously. The seven-parameter Fung-type SEF and several new SEFs combining polynomials and exponents were used to fit the experimental data curves. RESULTS: The stretch-inflation test data and the morphometric parameters at the zero-stress state of the layered esophagus were obtained. The new SEF with polynomial and exponential combination is more suitable to describe describing the three-dimensional passive biomechanical properties of esophageal tissue. Among them, New-Fung13 SEF is more suitable for describing the passive biomechanical properties of intact esophageal tissue, Sokolis-Fung13 SEF is more suitable for the esophageal muscle layer, and New-Fung10 SEF is more suitable for the esophageal mucosa. The constitutive parameters of the optimal constitutive model for each layer of the esophagus were obtained.

Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation.

BACKGROUND: Atherosclerosis is a progressive chronic disease characterised by aberrant lipid metabolism and a maladaptive inflammatory response. As atherosclerosis-driven cardiovascular disease remains the major cause of morbidity and mortality worldwide, more effective clinical therapies are urgently needed. Traditional Chinese Medicine (TCM) has demonstrated efficacy against atherosclerosis, with Qing-Xue-Xiao-Zhi formula (QXXZF) having been approved for clinical treatment of patients with atherosclerosis. However, the mechanisms underlying the anti-atherosclerotic activity of QXXZF remain unknown. PURPOSE: To investigate the anti-atherosclerotic effect of QXXZF and reveal its mechanisms using preclinical models. METHODS: In vivo, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-choline diet (HHD) to induce atherosclerosis. Serum metabolomic profiling was used to identify the concentration of trimethylamine N-oxide (TMAO) in mice. In vitro, RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) from WT and TLR4-/- C57BL/6 mice were used to explore the effects of QXXZF on macrophages. After confirming the therapeutic effects of QXXZF, mass spectrometry and network pharmacology analyses were used to predict and investigate the main components and the anti-atherogenic mechanisms of QXXZF in the context of atherosclerosis. RESULTS: Our results showed QXXZF significantly suppressed the development of atherosclerosis, as evidenced by the decreased atherosclerotic plaques in the aorta and aortic root, reduced plasma lipid levels and decreased serum TMAO content in HHD-fed ApoE-/- mice. Meanwhile, QXXZF effectively reduced foam cell formation in oxidized low-density lipoprotein (ox-LDL) and TMAO-stimulated RAW264.7 macrophages and BMDMs. Moreover, QXXZF facilitated reverse cholesterol transport (RCT) in macrophages by upregulating the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1. Mechanistic studies revealed that QXXZF influenced cholesterol metabolism by inhibiting the TLR4-mediated nuclear factor kappa B (NF-κB) axis. Importantly, TLR4 knockout abolished the influence of QXXZF on macrophages. CONCLUSION: QXXZF promotes lipid efflux and inhibits macrophage-mediated inflammation, producing a therapeutic effect against atherosclerosis. Our study provides new insight into the mechanism of QXXZF against atherosclerosis.