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Introduction: Understanding the genuine experiences and requirements of caregivers and implementing targeted interventions can have a positive impact on the physical and mental well-being of caregivers with children diagnosed with rheumatic diseases, ultimately reducing their burden and enhancing their quality of life. While there has been a gradual increase in research in this area in recent years, there remains a gap in the evidence that comprehensively and systematically reflects the actual experiences and needs of caregivers. We will employ a mixed-methods approach to evaluate the real-life experiences and requirements of caregivers for children diagnosed with rheumatic diseases to provide insights for both research and clinical interventions. METHODS AND ANALYSIS: All types of studies (quantitative, qualitative, and mixed-methods) involving caregivers of children aged 0 to 18 with rheumatic diseases will be included. We will conduct a comprehensive search across multiple databases, including MEDLINE (PubMed), Embase (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, WanFang, and VIP, as well as the grey literature, to identify primary studies published in either English or Chinese since 2000. Two independent reviewers will conduct the selection process and cross-check the data extraction. The focus of interest will be on understanding the experiences and needs of caregivers for pediatric rheumatic disease patients. In our systematic review, we will employ the 2018 version of the Mixed Methods Assessment Tool (MMAT) to evaluate study quality, and we will apply a convergent integration approach to synthesize the data., Ethics and Dissemination: Ethical approval is not needed, as no primary data will be collected. The results will be made available through a peer-reviewed publication., Systematic Review Registration: PROSPERO 42023465302., Competing Interests: Ethics approval and consent to participate: Secondary data analysis does not require ethical approval. The results of the study will be published in a peer-reviewed journal. Competing interests: The authors declare that they have no conflicts of interest., (© 2025. The Author(s).)

Background: The ability to thrive at work has been demonstrated to be closely linked to the development of nurses.Effective utilization of strengths and maintaining hope are essential elements for clinical nurses' ability to flourish in their roles. Nevertheless, the relationship between strengths use, hope, and thriving at work remains underexplored. This study aimed to identify distinct subgroups of clinical nurses based on their strengths use and to examine the mediating effect of hope between strengths use and thriving at work. The findings are intended to inform clinical managers on strategies to enhance nurses' work performance and care quality., Methods: A convenience sample of 568 clinical nurses from two tertiary hospitals in Guangzhou City, Guangdong Province, China, was recruited between January and March 2024. The survey collected sociodemographic data and included the Adult Dispositional Hope Scale, Strengths Use Scale, and Thriving at Work Scale. Potential categories of nurse strengths use characteristics were identified using potential profile analysis, and potential relationships between variables were determined using Pearson correlation analysis, Bayesian factor robustness analyses, and Mediation analysis., Results: LPA identified three distinct groups based on strengths use: low (30.8%), moderate (64.9%), and high (13.2%).The significant mediating effect of hope in the relationship between strengths use based on latent profile analysis and thriving at work was observed (SE = 0.61,95%CI = -10.01, -7.62; SE = 0.76,95%CI = -18.91, -15.91, respectively)., Conclusions: There exists heterogeneity in nurses' strengths use. Hope plays a significant role in mediating the relationship between strengths use and thriving at work. It is recommended that nursing administrators or leaders pay attention to differences in individual levels of strengths use, encourage strengths-based practices and design interventions that foster hope, thereby promoting greater thriving in their professional roles., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Guangdong Hospital of Traditional Chinese Medicine (No. YE2022-355-01). Informed consent was obtained from all participants after a verbal explanation of the process and purpose of the study, which was in accordance with the Declaration of Helsinki. Data privacy and anonymity were assured to the participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma., Methods: Wild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17's pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses., Results: Animal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17., Conclusion: In the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development., Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05332834., Competing Interests: GX, XQ, RD, CWH, LHL, WL, WCW, and SOL are employed by SinoMab BioSciences Limited. SP, KW, AvH, CE, SR, and AH are employed by Celerion Inc., (Copyright © 2024 Xu, Paglialunga, Qian, Ding, Webster, van Haarst, Engel, Hui, Lam, Li, Wu, Rasmussen, Hunt and Leung.)

Niemann-Pick disease Type C (NPC) is a neurodegenerative disease mainly caused by the mutation in NPC1 gene, leading to massive accumulation of unesterified cholesterol in the late endosome/lysosome of cells. Impaired phenotype of microglia is a hallmark in Npc1 mutant mice (Npc1 -/- mice). However, the mechanism of Npc1 in regulating microglial function is still unclear. Here, we showed that the reactive microglia in the neonatal Npc1 -/- mice indicated by the increased lysosome protein CD68 and phagocytic activity were associated with disrupted TREM2-mTOR signaling in microglia. Furthermore, in Npc1-deficient BV2 cells, genetic deletion of Trem2 partially restored microglial function, probably via restored mTOR signaling. Taken together, our findings indicated that loss of Npc1 in microglia caused changes of their morphologies and the impairment of lysosomal function, which were linked to the TREM2-mTOR signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC)., Methods: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups., Results: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01)., Conclusions: YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

The CC chemokine receptor 6 (CCR6) is a potential target for chronic inflammatory diseases. Previously, we reported an active CCR6 structure in complex with its cognate chemokine CCL20, revealing the molecular basis of CCR6 activation. Here, we present two inactive CCR6 structures in ternary complexes with different allosteric antagonists, CCR6/SQA1/OXM1 and CCR6/SQA1/OXM2. The oxomorpholine analogues, OXM1 and OXM2 are highly selective CCR6 antagonists which bind to an extracellular pocket and disrupt the receptor activation network. An energetically favoured U-shaped conformation in solution that resembles the bound form is observed for the active analogues. SQA1 is a squaramide derivative with close-in analogues reported as antagonists of chemokine receptors including CCR6. SQA1 binds to an intracellular pocket which overlaps with the G protein site, stabilizing a closed pocket that is a hallmark of inactive GPCRs. Minimal communication between the two allosteric pockets is observed, in contrast to the prevalent allosteric cooperativity model of GPCRs. This work highlights the versatility of GPCR antagonism by small molecules, complementing previous knowledge of CCR6 activation, and sheds light on drug discovery targeting CCR6., (© 2024. The Author(s).)

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most prevalent gynecologic malignancies globally. The prognosis is abysmal once cervical cancer progresses to lymphatic metastasis. Anoikis, a specialized form of apoptosis induced by loss of cell adhesion to the extracellular matrix, plays a critical role. The prediction model based on anoikis-related genes (ARGs) expression and clinical data could greatly aid clinical decision-making. However, the relationship between ARGs and CESC remains unclear., Methods: ARGs curated from the GeneCards and Harmonizome portals were instrumental in delineating CESC subtypes and in developing a prognostic framework for patients afflicted with this condition. We further delved into the intricacies of the immune microenvironment and pathway enrichment across the identified subtypes. Finally, our efforts culminated in the creation of an innovative nomogram that integrates ARGs. The utility of this prognostic tool was underscored by Decision Curve Analysis (DCA), which illuminate its prospective benefits in guiding clinical interventions., Results: In our study, We discerned a set of 17 survival-pertinent, anoikis-related differentially expressed genes (DEGs) in CESC, from which nine were meticulously selected for the construction of prognostic models. The derived prognostic risk score was subsequently validated as an autonomous prognostic determinant. Through comprehensive functional analyses, we observed distinct immune profiles and drug response patterns among divergent prognostic stratifications. Further, we integrated the risk scores with the clinicopathological characteristics of CESC to develop a robust nomogram. DCA corroborated the utility of our model, demonstrating its potential to enhance patient outcomes through tailored clinical treatment strategies., Conclusion: The predictive signature, encompassing nine pivotal genes, alongside the meticulously constructed nomogram developed in this research, furnishes clinicians with a sophisticated tool for tailoring treatment strategies to individual patients diagnosed with CESC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Ying, Ding, Xing, Wang, Pan, Pan, Xiang and Liu.)

A dual NIR fluorescent probe Cy-ND is developed for viscosity sensing with λ ex/em = 766/806 nm, making it apt for biological analysis, whose response is validated through DFT and TDDFT computations. Cy-ND successfully detected viscosity changes amidst acute alcohol-induced liver injury and liver ischemia-reperfusion injury.

Postbiotics, as emerging products, were added to infant formula, but their safety and efficacy are unclear. To clarify this issue, we wrote this meta-analysis. We searched PubMed, Embase, Web of Science and ProQuest from its establishment to February 2023. The review was registered on PROSPERO database (CRD42022352405). The effects of infant formula with and without postbiotics were compared, and the incidence of serious adverse events (SAEs), digestive symptoms, concentration of stool secretory immunoglobulin A (SIgA), and growth and development indexes were analyzed. Nine randomized controlled trials with 2065 participants were included. The addition of postbiotics to infant formula was found to increase the concentration of stool SIgA (P < 0.05) with very low certainty of evidence, without significantly impacting the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain and gastrointestinal disorders, the daily weight gain, the total gain in body length and the daily head circumference gain (all P > 0.05). Adding postbiotics to the formula is safe for infants, which would not increase the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain, and gastrointestinal disorders, and could increase the concentration of stool SIgA. IMPACT: Our study provides evidence that the addition of postbiotics to infant formula is safe but not effective. This is the first systematic review and meta-analysis of postbiotics. This study provides strong evidence for the safety of postbiotics and lays a foundation for related clinical trials., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

A mitochondria-targeted far-red fluorescent probe LY-1 with AIE character was formulated to track cell viscosity alterations with excellent sensitivity and selectivity, which was used to discriminate between mitophagy and ferroptosis in cancer cells. Probe LY-1 is expected to be an effective vehicle for the diagnosis of mitochondrial viscosity relevant diseases.

Electric vehicles have received extensive attention due to their unique energy efficiency and good emission reduction effects. While a large-scale of electric vehicles are gradually replacing traditional fuel vehicles, it is necessary to ensure the energy efficiency of electric vehicles and the effectiveness of their emission reduction effects. This study conducted a bibliometric analysis of scientific publications on energy efficiency and emission reduction effects of electric vehicles from 2003 to 2022, using a variety of bibliometric tools such as R Studio, biblioshiny and VOSviewer. The results showed the gradual elimination of traditional energy vehicles, where electric vehicles play an important role in connecting energy efficiency and emission control. The results also showed the top publication outlets, citations trackers, authors with thematic evaluation of energy efficiency and emission reduction effects of electric vehicles. The contribution of the study is manifold. The academic contribution of the present study is the bibliometric analysis which will help academicians to get a quick overview of the most popular journals, top collaborators, documents, authors, and scientific knowledge structure. Secondly, policy makers, environmentalists, researchers, and academician will definitely get a pathway how they should go for future research. Finally, this study suggests more researches trend to focus on the sales of electric vehicles, automobile exhaust emissions, sensitivity analysis of electric vehicles, energy storage analysis to improve the energy efficiency of electric vehicles, and V2G related to the energy efficiency of electric vehicle clusters., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Plenty of publications had been written in the last several decades on acute myocardial infarction (AMI) in women. However, there are few bibliometric analyses in such field. In order to solve this problem, we attempted to examine the knowledge structure and development of research about AMI in women based on analysis of related publications., Method: The Web of Science Core Collection was used to extract all publications regarding AMI in women, ranging from January 2000 to August 2022. Bibliometric analysis was performed using VOSviewer, Cite Space, and an online bibliometric analysis platform., Results: A total of 14,853 publications related to AMI in women were identified from 2000 to 2022. Over the past 20 years, the United States had published the most articles in international research and participated in international cooperation the most frequently. The primary research institutions were Harvard University and University of Toronto. Circulation was the most cited journal and had an incontrovertible academic impact. 67,848 authors were identified, among which Harlan M Krumholz had the most significant number of articles and Thygesen K was co-cited most often. And the most common keywords included risk factors, disease, prognosis, mortality, criteria and algorithm., Conclusion: The research hotspots and trends of AMI in women were identified and explored using bibliometric and visual methods. Researches about AMI in women are flourishing. Criteria and algorithms might be the focus of research in the near future, which deserved great attentions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Xu, Yang, Shen, Wang, Niu, Chen, Li, Chen, Wang, HE and Ding.)

Atherosclerosis is a chronic inflammatory disease and the main pathology behind most cardiovascular diseases and the overactivation of macrophages initiates the development of atherosclerosis. However, the specific functions of oxidized low-density lipoprotein (ox-LDL) in macrophages remain elusive. Macrophages derived from monocyte (THP-1) were treated with ox-LDL and were used to generate atherosclerosis in an in vitro model. NLRP3 inflammasome markers were examined using quantitative RT-PCR and Western blotting. Cytokines were measured using ELISA. Chromatin immunoprecipitation (ChIP) was utilized to detect nuclear factor kappa B (NF-κB) and TRIM64 interactions. A fat-rich diet was applied to ApoE-/- mice for in vivo studies. ox-LDL promoted TRIM64 expression in a time-dependent manner. According to loss- and gain-of-function analyses, TRIM64 enhanced the activation of NLRP3 inflammasomes and the expression of downstream molecules. TRIM64 directly interacted with IκBα and promoted IκBα ubiquitination at K67 to activate NF-κB signaling. We detected direct binding between NF-κB and the TRIM64 promoter, as well as enhanced TRIM64 expression. Our study revealed an interaction between TRIM64 and NF-κB in the development of atherosclerosis. TRIM64 and NF-κB formed a positive feedback to activate NF-κB pathway. ox-LDL induces foam cell formation and TRIM64 expression TRIM64 regulates ox-LDL-induced foam cell formation, pyroptosis and inflammation via the NF-κB signaling TRIM64 activates NF-κB signaling by ubiquitination of IκBα NF-κB inhibition attenuates atherosclerosis in HFD-induced ApoE (-/-) mice., (© 2022. The Author(s).)

Increased levels of serum free fatty acids (FFAs) are closely associated with microvascular dysfunction. In our previous study, a coronary microvascular dysfunction (CMD) model was successfully established via lipid infusion to increase the levels of serum FFAs in mice. However, the underlying mechanisms remained poorly understood. Therefore, the aim of the present study was to explore the mechanism underlying FFA‑induced CMD. A CMD mouse model was established via lipid combined with heparin infusion for 6 h to increase the concentration of serum FFAs. Following the establishment of the model, the coronary flow reserve (CFR), extent of leukocyte activation and cardiac microvascular structures were assessed in the mice. Cardiac microvascular endothelial cells (CMECs) were treated with different concentrations of palmitic acid and cell viability was evaluated. Changes in the expression levels of AMP‑activated protein kinase (AMPK), Krüppel‑like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS) were identified by immunohistochemical and western blot analyses. Experiments using AMPK activator, KLF2 overexpression plasmid, small interfering RNAs and nicorandil were subsequently designed to investigate the potential involvement of the AMPK/KLF2/eNOS signaling pathway. These experiments revealed that FFAs could induce CMD in mice, which was characterized by reduced CFR (1.89±0.37 vs. 2.74±0.30) and increased leukocyte adhesion (4,350±1,057.5 vs. 11.8±5.4 cells/mm 2 ) compared with the control mice. CD11b expression and intracellular reactive oxygen species (ROS) levels were increased in CMD model mice compared with control mice. Serum TNF‑α and IL‑6 levels were higher in the model group than in the control group. Transmission electron microscopy revealed that CMECs in heart tissues of model mice were severely swollen. In addition, palmitic acid decreased CMEC viability and increased ROS production in a dose‑dependent manner. Notably, the AMPK/KLF2/eNOS signaling pathway was demonstrated to be suppressed by FFAs both in vivo and in vitro . Activation of this axis with AMPK activator, KLF2 overexpression plasmid or nicorandil restored the CFR in CMD model mice, inhibited oxidative stress and increased CMEC viability. Taken together, the results of the present study demonstrated that FFAs could induce CMD via inhibition of the AMPK/KLF2/eNOS signaling pathway, whereas activation of this pathway led to the alleviation of FFA‑induced CMD, which may be a therapeutic option for CMD.

A sensitive and reliable method was developed to determine befotertinib (D-0316) and its metabolite D-0865 from human plasma by LC-MS/MS. The samples were prepared by simple protein precipitation and 2 µL of the supernatant were chromatographed on a C18 analytical column (ACE Excel 2 Super C 18 , 50 × 2.1 mm). Elution was performed with mobile phase A (10 mM ammonium acetate in water containing 1 % formic acid) and mobile phase B (acetonitrile containing 1 % formic acid) under a gradient program in a total run time of 4 min. Triple Quadruple 5500 equipped with Turbo Ion Spray source and multiple reaction monitoring (MRM) were used for the analysis detection. The transitions were m/z 568.3 → 72.1 m/z (befotertinib), m/z 554.2 → 497.2 (D-0865), and m/z 455.2 → 164.9 (verapamil, internal standard). According to the Chinese Pharmacopeia Commission and ICH Harmonised Guideline for Bioanalytical Method Validation, this method was validated within the spectrum of its accuracy, precision, selectivity, linearity, recovery, matrix effect, and stability. This LC-MS/MS method was successfully applied for the quantitation of befotertinib and its metabolite D-0865 in human plasma during the pharmacokinetics study of befotertinib in non-small cell lung cancer (NSCLC) patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lieming Ding reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment and equity or stocks. Hua Li reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Yang Wang reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Ru Ding reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Chen Chen reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Zhixuan Tian reports a relationship with Suzhou Sanclinty Co., ltd that includes: employment. Hongnan Yin reports a relationship with Suzhou Sanclinty Co., ltd that includes: employment.]., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sigmoid colon adenocarcinoma has a high incidence among gastrointestinal tumors, and it very rarely metastasizes to the penis. The literature reports that the prognosis after penile metastasis is generally poor, with a median survival of about 9 mo. Metachronous isolated metastasis to the penis originating from sigmoid colon adenocarcinoma has not been reported so far. Here, we report a case of sigmoid colon adenocarcinoma with isolated penile metastasis occurring 2 years after surgery. The mass was pathologically confirmed as metastatic adenocarcinoma, and oral chemotherapy with capecitabine was given after surgery. The tumor did not recur during the 2-year follow-up period., Case Summary: A 79-year-old man presented to the urology department with "a mass located at the root of the penis since 1 mo". Enhanced computed tomography (CT) examination suggested a 12 mm × 10 mm × 9 mm nodule at the root of the right penile corpus cavernosum. Cranial, pulmonary, and abdominal CT; and bone scan did not show any tumorigenic lesions. The carcinoembryonic antigen (CEA) level was slightly elevated (6.01 ng/mL, reference value 0-5 ng/mL). The patient had undergone laparoscopic radical sigmoidectomy for sigmoid colon cancer 2 years ago. The postoperative pathology showed moderately differentiated adenocarcinoma of the sigmoid colon, and the stage was PT2N0M0. The penile mass was removed under general anesthesia. The postoperative pathology showed adenocarcinoma, and immunohistochemistry showed CDX2(+), CK20(+), and Villin(+). Based on the medical history, he was diagnosed with penile metastasis from sigmoid colon adenocarcinoma. The CEA level returned to normal (3.34 ng/mL) 4 d after surgery. Oral chemotherapy with capecitabine was given subsequently, and tumor recurrence was not found during the 2-year follow-up period., Conclusion: To our knowledge, this is a rare case of metachronous isolated penile metastasis from sigmoid colon adenocarcinoma. The penis is a potential site of metastasis of colon adenocarcinoma, and the possibility of metastasis should be considered in patients with a history of colon cancer who present with a penile mass. Solitary penile metastasis can be removed surgically, in combination with chemotherapy, and it may have good long-term outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

This study was aimed at evaluating the adoption value of ultrasound imaging features on fetal cerebral hemodynamics in preeclampsia patients based on the partial difference algorithm and the hybrid segmentation network (HSegNet) algorithm. Forty pregnant women with preeclampsia diagnosed by ultrasound examination were selected as the research objects, and another forty normal pregnant women were selected as the control. Then, by using the partial differential algorithm, the imaging of fetal cerebral hemodynamics in preeclampsia patients was enhanced and optimized, and the general clinical data and experimental results were collected. The results showed that the automatic labeling of fetal cerebral artery in fetal middle cerebral artery (MCA) hemodynamic images was realized by HSegNet algorithm model, and the final accuracy was 97.3%, which had a good consistency with the manual annotation of doctors. Education level was a protective factor for preeclampsia (odds ratio (OR) = 0.535). Body mass index (BMI) and family history of hypertension during pregnancy were independent risk factors for preeclampsia (OR = 1.286, and 2.774, respectively). MCA end-diastolic volume (EDV) of preeclampsia fetuses was higher than that of normal fetuses. The MCA systolic-diastolic ratio (S/D), the pulsatility index (PI), and the resistive index (RI) in the preeclampsia group were significantly lower than those in the normal pregnancy group. The results showed that MCA PI, MCA RI, and MCA S / D had certain predictive values for the occurrence of adverse pregnancy outcomes ( P < 0.05). In summary, the intelligent algorithm-based fetal MCA hemodynamic ultrasound image in the study could effectively predict pregnancy outcomes of patients and provide certain theoretical support for the subsequent reduction of adverse pregnancy outcomes in patients with preeclampsia., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Di Zhu et al.)

Salvianolic acid B (Sal B) is an effective treatment agent for ischemic disease in China. However, Sal B's effects on peripheral arterial disease (PAD) and its mechanism remains poorly understood. Macrophage polarization plays a crucial role in PAD. Nevertheless, treatment modalities that increase the population of anti-inflammatory (M2) macrophages are limited. This study aimed to explore the protective effects of Sal B on limb perfusion and investigate the mechanism of Sal B-induced macrophage polarization. C57BL/6 male mice (6 weeks) were randomized into control, Model + NS, and Model + Sal B groups ( n  = 5). Then, we established a hind limb ischemia mouse model to assess the Sal B's role (15 mg/kg/d) in PAD. We quantified the blood perfusion via laser speckle contrast imaging (LSCI) and measured the capillary density and muscle edema with CD31 and H&E staining. The Sal B-induced macrophage polarization was confirmed by qPCR and ELISA. The results showed that the Sal B group exhibited a significant improvement in the blood perfusion, capillary density, muscle edema, and M2 markers gene expressions. Cell migration and tube formation were promoted in the endothelial cells stimulated with a culture supernatant from Sal B-treated macrophages. In contrast, endothelial functions improved by Sal B-treated macrophages were impaired in groups treated with SIRT1 and PI3K inhibitors. These findings provide evidence for Sal B's protective role in PAD and demonstrate the enhancement of macrophage polarization via the SIRT1/PI3K/AKT pathway., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wenhao Niu et al.)

Background: The compound Danshen Dripping Pill (CDDP), which is a mixture of extracts from Radix Salviae and Panax notoginseng, is a patented traditional Chinese medicine that is widely used in multiple countries for relieving coronary heart disease (CHD), but its pharmacological mechanism has not been fully elucidated. In this study, we screened the key pharmacological pathways and targets of CDDP that act on CHD using a network pharmacology-based strategy, and the angiogenic activity of CDDP was directly visually investigated in zebrafish embryos in vivo., Methods: The potential therapeutic targets and pathways were predicted through a bioinformatics analysis. The proangiogenic effects of CDDP were examined using vascular sprouting assays on subintestinal vessels (SIVs) and optic arteries (OAs) as well as injury assays on intersegmental vessels (ISVs). Pharmacological experiments were applied to confirm the pathway involved., Results: Sixty-five potential therapeutic targets of CDDP on CHD were identified and enriched in the PI3K/AKT and VEGF/VEGFR pathways. An in vivo study revealed that CDDP promoted angiogenesis in SIVs and OAs in a dose-dependent manner and relieved the impairments in ISVs induced by lenvatinib, a VEGF receptor kinase inhibitor (VRI). In addition, Vegfaa and Kdrl expression were significantly upregulated after CDDP treatment. Furthermore, the proangiogenic effect of CDDP could be abolished by PI3K/AKT pathway inhibitors., Conclusions: CDDP has a proangiogenic effect, the mechanism of which involves the VEGF/VEGFR and PI3K/AKT signaling pathways. These results suggest a new insight into the cardiovascular protective effect of CDDP., (© 2022. The Author(s).)

Three new aglain derivatives (1-3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7-10), and three steroids (11-13) were isolated from Aglaia odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4-7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC 50 values in the range of 0.03-8.40 μM. In particular, the cytotoxicity of compound 5 was six times stronger than that of the positive control (adriamycin) in HEL cell lines., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension., Methods: In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg., Results: Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P =0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P =0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups., Conclusions: SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine., Registration: URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a major impact on global human health. During the spread of SARS-CoV-2, weakened host immunity and the use of vaccines with low efficacy may result in the development of more-virulent strains or strains with resistance to existing vaccines and antibodies. The prevalence of SARS-CoV-2 mutant strains differs between regions, and this variation may have an impact on the effectiveness of vaccines. In this study, an epidemiological investigation of SARS-CoV-2 in Portugal was performed, and the VSV-ΔG-G* pseudovirus system was used to construct 12 spike protein epidemic mutants, D614G, A222V+D614G, B.1.1.7, S477N+D614G, P1162R+D614G+A222V, D839Y+D614G, L176F+D614G, B.1.1.7+L216F, B.1.1.7+M740V, B.1.258, B.1.258+L1063F, and B.1.258+N751Y. The mutant pseudoviruses were used to infect four susceptible cell lines (Huh7, hACE2-293T-293T, Vero, and LLC-MK2) and 14 cell lines overexpressing ACE2 from different species. Mutant strains did not show increased infectivity or cross-species transmission. Neutralization activity against these pseudoviruses was evaluated using mouse serum and 11 monoclonal antibodies. The neutralizing activity of immunized mouse serum was not significantly reduced with the mutant strains, but the mutant strains from Portugal could evade nine of the 11 monoclonal antibodies tested. Neutralization resistance was mainly caused by the mutations S477N, N439K, and N501Y in the spike-receptor binding domain. These findings emphasize the importance of SARS-CoV-2 mutation tracking in different regions for epidemic prevention and control., (© 2021. The Author(s).)

Aims: The aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E 2 -2,3-Q) and 17β-estradiol-3,4-quinone (E 2 -3,4-Q), in human albumin (Alb) and hemoglobin (Hb) derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts., Settings and Design: Cohort Methods and Material: Blood samples derived from breast cancer 5-year survivors without recurrence were collected. Albumin and hemoglobin adducts of E 2 -3,4-Q and E 2 -2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment., Statistical Analysis: All data are expressed as mean ± standard deviation of three determinations. We used Student's t -test to examine subgroups. Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses. Linear correlations were investigated between individual adduct levels by simple regression. Statistical analysis was performed using the SPSS Statistics 20.0., Results: Result confirmed that logged levels of E 2 -2,3-Q-derived adducts correlated significantly with those of E 2 -3,4-Q-derived adducts (correlation coefficient r =.336-.624). Mean levels of E 2 -2,3-Q-4-S-Alb and E 2 -3,4-Q-2-S-Alb in 5-year survivors were reduced by 60-70% when compared to those in the breast cancer patients with less than one year of diagnosis/preoperative treatment (P<.001)., Conclusions: Our findings add support to the theme that hormonal therapy including aromatase inhibitors and Tamoxifen may dramatically reduce burden of estrogen quinones. We hypothesize that combination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients.

Inflammasomes are intracellular multiprotein complexes that help trigger and maintain the inflammatory response as part of the innate immune system. Recently, it has been increasingly recognized that aberrant inflammasome activation is critically involved in endothelial dysfunction in a variety of human diseases, such as atherosclerosis, acute lung injury (ALI), and type 2 diabetes. The molecular mechanisms underlying endothelial inflammasome activation, however, have not been completely elucidated. In the present study, we identified orphan nuclear receptor Nur77 as a novel regulator in controlling inflammasome activation in vascular endothelial cells (ECs). We demonstrated that LPS-induced inflammasome activation was significantly inhibited by ectopic overexpression of Nur77, predominantly through transcriptional suppression of caspase-1 expression in vascular ECs. Consistent with this observation, we found that LPS-induced inflammasome activation was significantly augmented in lung ECs isolated from Nur77-knockout mice. Mechanistically, we showed that Nur77-induced inhibition of caspase-1 expression was due to an inhibition of IRF1 (IFN regulatory factor 1) expression and its subsequent binding to the caspase-1 promoter. Importantly, in a mouse model of LPS-induced ALI, Nur77 knockout led to a marked activation of caspase-1 in the lung, increased alveolar and circulating IL-1β levels, and exacerbated ALI, all of which were substantially inhibited by administration of caspase-1 inhibitor. Together, our results support the presence of an important role for Nur77 in controlling inflammasome activation in vascular ECs and suggest that Nur77 could be a novel therapeutic target for the treatment of human diseases associated with aberrant inflammasome activation, such as ALI and atherosclerosis.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to decrease the adverse cardiac events and risks of cardiovascular mortality among patients with or without diabetes, which has made these drugs promising treatment options for patients with chronic heart failure. Cardiac dysfunction is a common and severe side effect induced by cancer chemotherapies, which seriously affects the prognosis and life quality of tumor patients. However, it is not clear whether SGLT2 inhibitors have cardiovascular benefits in patients with cancer chemotherapy-related cardiac dysfunction. We aimed to determine whether empagliflozin (EMPA), an SGLT2 inhibitor, has a protective role against sunitinib (SNT)-induced cardiac dysfunction in a mouse model. Methods: Male C57BL/6J mice were randomized into control (control, n = 8), empagliflozin (EMPA, n = 8), sunitinib (SNT, n = 12), or sunitinib and empagliflozin coadministration (SNT + EMPA, n = 12) groups. EMPA, SNT, or SNT-combined EMPA was given via oral gavage for consecutive 28 days. Cardiovascular functions and pathological changes were examined, and the underlying mechanisms of EMPA's effects were investigated in H9c2 cardiomyocytes. Results: Mice in the SNT group exhibited dramatically elevated blood pressure (systolic blood pressure [SBP] 134.30 ± 6.455 mmHg vs. 114.85 ± 6.30 mmHg) and impaired left ventricular function (left ventricular ejection fraction [LVEF] 50.24 ± 3.06% vs. 84.92 ± 2.02%), as compared with those of the control group. However, EMPA could ameliorate SNT-induced cardiotoxicity, both in terms of SBP (117.51 ± 5.28 mmHg vs. 134.30 ± 6.455 mmHg) and LVEF (76.18 ± 5.16% vs. 50.24 ± 3.06 %). In H9c2 cardiomyocytes, SNT-induced cardiomyocyte death and cell viability loss as well as dysfunction of adenosine 5'-monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling-mediated autophagy were restored by EMPA. However, these favorable effects mediated by EMPA were blocked by the inhibition of AMPK or autophagy. Conclusion: EMPA could ameliorate SNT-induced cardiac dysfunction via regulating cardiomyocyte autophagy, which was mediated by the AMPK-mTOR signaling pathway. These findings supported that SGLT2 inhibitor therapy could be a potential cardioprotective approach for cardiovascular complications among patients receiving SNT. However, these favorable effects still need to be validated in clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ren, Sun, Zhang, Hu, Hu, Zhao, He, Ding, Wang and Liang.)

Eicosanoids play important roles in the cardiovascular system. The metabolic disorders involving some eicosanoids in the pathophysiologic process include myocardial infarction and myocardial ischaemia-reperfusion injury. Percutaneous coronary intervention (PCI) is often the first-choice strategy for acute ST-segment elevation myocardial infarction (STEMI) according to current guidelines. This study aimed to investigate the dynamic eicosanoid metabolic profile in STEMI patients after PCI. The eicosanoid profiles in plasma of 20 patients at seven times (30 minutes before surgery; 6, 12, 24, and 72 hours after surgery; 1 day before discharge; and 28 days after surgery) were studied by using metabolomics. Levels of PGE2, PGD2, and TXA2 were decreased significantly and EETs contents were increased significantly at 6 hours after PCI. EETs were hydrolysed to DHETs within a short time after surgery (12-72 hours). 20-HETE content was significantly increased. In samples taken at the time of discharge and at follow-up after discharge, LTB4 level continued to increase. This work suggests that change in content of some functional eicosanoids may be involved in cardiac injury and repair after PCI in a synergistic manner., (© 2020 John Wiley & Sons Australia, Ltd.)

Lead halide perovskite have attracted world-wide attention regarding their serious hazards on ecological environment and human health. To improve both the emission intensity and stability of Cs 2 AgInCl 6 , this study explores using SiO 2 to structurally adjust Cs 2 AgInCl 6 . Note that including SiO 2 changed the growth style and crystal morphology of Cs 2 AgInCl 6 from an octahedron to a truncated octahedron. After structural adjustment, the unit cells scattered, and the absorption limit broke. Moreover, SiO 2 was demonstrated to passivate the material's surface to form an anti-oxidation protective layer. Consequently, the photoluminescence emission intensity increased by 181.5% and the stability of Cs 2 AgInCl 6 improved by 83.11%. This work provides a methodology and reference for future improvements to the luminescence of Cs 2 AgInCl 6 . Furthermore, a novel double-emission phenomenon (λ ex = 365 nm: λ em ≈ 580 nm; λ ex = 325 nm: λ em ≈ 505 nm) of Cs 2 AgInCl 6 at cryogenic temperatures (20 K) was discovered; this phenomenon explains the shoulder emission problem of 400-450 nm at room temperature and clarifies the luminescence mechanism of Cs 2 AgInCl 6 ., (Copyright © 2020 Elsevier B.V. All rights reserved.)

More and more exosome-based therapeutics are being developed with advances in nanotechnology and precision medicine. Exosome is a kind of tiny vesicles with a bilayer of phospholipids, which can transfer biological macromolecules to recipients to influence the biological process. M2 macrophages are closely related to the occurrence and development of serious diseases such as tumor. In addition to the traditional concept of macrophage functions such as opsonization, secretion of cytokines and other soluble factors, some studies have found that the exosome derived from M2 macrophages can influence the development of disease by carrying microRNA, long noncodingRNA and functional proteins to regulate target gene expression as well as related proteins synthesis recently. Here, we outlined the biogenesis of the exosome and its biological functions in disease. Then we focused on elucidating the effects of the exosome derived from M2 macrophages on several diseases and its mechanisms. Finally, we discussed the appropriateness and inappropriateness in existing potential applications based on exosomes and macrophages.

Context: Recent studies have shown compound Danshen dripping pills (CDDP) could improve microcirculation in ischemic/reperfusion injury and other microvascular disorders. The mechanism for CDDP's role in microcirculation is not clear., Objective: To explore the protective effects of CDDP on microvascular dysfunction., Materials and Methods: C57BL/6 male mice (6-8 weeks) were randomized into control, model and CDDP groups ( n  = 10), which were treated with normal saline or CDDP (105.30 mg/kg), respectively. Then, lipid emulsion and heparin were infused via mice jugular vein to establish systemic microvascular dysfunction model. Coronary flow reserve (CFR) and leukocytes adhesion on microvascular wall were measured. Relative CD11b and CD62L expression levels on neutrophils were measured by flow cytometric analysis. Expression level of forkhead box transcription factor O1 (FOXO1) mRNA was identified by real-time PCR., Results: Lipid infusion significantly attenuated the CFR (1.84 ± 0.14 vs. 2.65 ± 0.02) and increased the number of leukocytes adherent to microvascular wall in cremaster (4067.00 ± 581.20 cells/mm 2 vs. 10.67 ± 4.81 cells/mm 2 ). The expression level of CD11b and FOXO1 in neutrophils was also up-regulated by lipid infusion. Pre-treatment with CDDP significantly improved CFR (2.57 ± 0.29 vs. 1.84 ± 0.14), decreased the number of leukocytes adherent to microvascular wall (2500.00 ± 288.70 cells/mm 2 vs. 4067.00 ± 581.20 cells/mm 2 ) and down-regulated CD11b and FOXO1 expression. Discussion and conclusions: Pre-treatment with CDDP could prevent lipid infusion-induced systemic microvascular disorder including coronary and peripheral microvascular dysfunction. Down-regulated FOXO1 and decreased leukocyte adhesion might play an important role in the mechanisms of CDDP's efficacy.

A 34-year-old Chinese woman found a lump in her left leg for more than 3 weeks without any discomfort. Grossly, the tumor was relatively well delineated with focal infiltration. Histopathologic evaluation showed a compact fascicular spindle cell proliferation with variable myxoid and collagenous stroma and scattered inflammatory infiltrate. Immunohistochemically, the tumor cells showed positive expression of ALKD5F3 and SMA and negative expression of CD34, desmin, and cytokeretin. Fluorescence in situ hybridization analysis of the ALK locus showed break-apart signals in 20% of tumor cells, and DNA sequencing discovered a novel CLIP2-ALK fusion gene. The lesion was diagnosed as an inflammatory myofibroblastic tumor (IMT). To the best of our knowledge, this is the first case with CLIP2-ALK gene fusion in the somatic soft tissue IMTs., (© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Objectives: Rapid risk stratification and timely treatment are critical to favorable outcomes for patients with acute coronary syndrome (ACS). Our objective was to identify patient and system factors that influence time-dependent quality indicators (QIs) for patients with unstable angina/non-ST elevation myocardial infarction (NSTEMI) in the emergency department (ED)., Methods: A retrospective, cohort study was conducted during a 42-month period of all patients 24 years or older suspected of having ACS as defined by receiving an electrocardiogram and at least 1 cardiac biomarker test. Cox regression was used to model the effects of patient characteristics, ancillary service use, staffing provisions, equipment availability, and ED and hospital crowding on ACS QIs., Results: Emergency department adherence rates to national standards for electrocardiogram readout time and biomarker turnaround time were 42% and 37%, respectively. Cox regression models revealed that chief complaints without chest pain and the timing of stress testing and medication administration were associated with the most significant delays., Conclusions: Patient and system factors both significantly influenced QI times in this cohort with unstable angina/NSTEMI. These results illustrate both the complexity of diagnosing patients with NSTEMI and the competing effects of clinical and system factors on patient flow through the ED.

Memory is no longer a privilege of adaptive immunity. Innate immune cells can exhibit a long-term immune activation after infection or vaccination, which is called "trained immunity." In addition to defense against mycobacterial infection, BCG-induced trained immunity can also exert nonspecific protection, which is regulated by metabolic rewiring and epigenetic reprograming. Enhanced glycolysis and glutamine-driven tricarboxylic acid cycle have been proven to be important metabolic pathways for trained immunity induced by BCG, which is dependent on Akt/mTOR pathway.

Four new sesquiterpenoids, phellinignins A-D (1-4), together with four known ones (5-8), were isolated from cultures of the fungus Phellinus igniarius. The structures were established by extensive spectroscopic methods including MS, NMR, and the single crystal X-ray diffraction. Compounds 1-3 and 5-8 are tremulane sesquiterpenoids, while compound 4 possesses a new carbon skeleton that might derive from an illudane framework. Compounds 1, 2, 4, and 5 showed certain cytotoxicities to three human cancer cell lines., (Copyright © 2019. Published by Elsevier B.V.)

Background: Radioresistance leads to treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, enhancing the radiosensitivity of NPC cells would likely increase the effectiveness of radiotherapy. Annexin VII (Annexin A7, ANXA7) might be a tumor promoter in NPC but its functions in radiosensitivity remain unclear., Methods: NPC cell lines CNE2-shANXA7 and CNE2-pLKO.1 were generated and CNE2-shANXA7 nude mice xenograft tumor models were established. The main effects and molecular mechanisms of ANXA7 knockdown in NPC radiosensitivity were studied in vitro and in vivo by analyzing cell viability, clonogenicity, apoptosis, cell cycle distribution, tumor radioresponse and immunohistochemistry assay., Results: ANXA7 knockdown revealed potentially enhanced NPC cell radiosensitivity via apoptosis and increased the cell number at the G2/M phase. In the xenograft model, NPC cells with ANXA7 knockdown were dramatically sensitive to irradiation and tumor growth was significantly suppressed. Compared to CNE2-pLKO.1 xenografts, CNE2-shANXA7 showed more γ-H2AX foci and less phospho-DNA PKcs., Conclusions: ANXA7 knockdown increased the radiosensitivity of NPC by enhancing apoptosis, modulating the cell cycle distribution into more radiosensitive phases, promoting DNA damage, and inhibiting repair. We showed that decreased ANXA7 levels enhanced radiosensitivity and provided insights into the therapeutic targets for NPC radiotherapy.

Objective: This study aimed to compare cutaneous microvascular function in coronary artery disease (CAD) patients including obstructive CAD (ObCAD) (n = 133) and non-obstructive CAD (NObCAD) (n = 129) with that of age and gender matched healthy controls (n = 83) using laser speckle contrast imaging (LSCI) coupled with post-occlusive reactive hyperemia (PORH)., Methods: LSCI system was used to assess subjects' cutaneous blood flow at rest and during PORH. CAD patients were divided into ObCAD and NObCAD group based on coronary angiography results., Results: Microvascular reactivity induced by PORH was significantly reduced in NObCAD group in comparison with control or ObCAD group (p < 0.05). Although, the PORH responses of ObCAD patients were also attenuated compared to controls, they did not reach statistical significance (p > 0.05)., Conclusion: NObCAD patients are more likely to develop cutaneous microvascular dysfunction than ObCAD patients, which may reflect the difference in the underlying mechanisms of myocardial ischemia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

For understanding the environmental behavior and toxicity of Ag nanoparticles (Ag-NPs), a quantitative method for characterizing the AgNPs in soils and sediments is urgently needed. In this study, we validated a previously developed extraction method by optimizing the extraction of silver nanoparticles from soil and sediment samples to which engineered AgNPs had been added. The samples were analyzed by single particle inductively coupled plasma mass spectrometry (SP-ICP-MS). Initially, different extraction conditions were evaluated to validate the optimal extraction procedure. Then the optimal extraction procedure was applied to environmental soil and sediment samples spiked with AgNPs. The extraction data for Ag-NPs with sizes below 30 nm was not shown due to the particle size detection limit of the SP-ICP-MS method (∼20 nm). The number concentrations of Ag particles extracted from different environmental soils and sediments matrices were in the range of (12 ± 1-23 ± 1) × 10 7 particles/g soil. Similarly, 53.4-100.0% of the particulate Ag mass was recovered. For the relatively low Ag mass recovery of Guiyu agricultural soil, the Ag mass recovery shows great improvement (from 53.4 to 105.8%) by the soil dilution using SiO 2 . The optimal method was validated to be feasible for extracting Ag-NPs from environmental soils and sediments, except for the soil with high soil organic matter (SOM) content. The SiO 2 dilution of soil provides a promising way to promote the extraction of Ag-NPs in soil (or sediment) with high SOM content, which could further promote the study on the environmental behavior and toxicity of Ag-NPs in soil and sediment environment.

Using a probabilistic material flow analysis model, we investigate the mass balance and occurrence of nano-silver in the environment of Hunan, renowned as "the home to non-ferrous metals" in China. The model builds on China-specific production and environmental information and incorporates sulfidation of nano-silver in urban wastewater treatment systems. We predict that the bulk of nano-silver (>90%), primarily originating from production and consumption of nano-silver products, ends up in sewage treatment plants (STPs, 5.3t/a), followed by the landfill (4.7t/a). More than 99% of nano-silver in STPs reacts with sulfide and thus does not appear in effluents. Direct release of nano-silver from production and consumption is identified as the dominant source of nano-silver in the environment, most of which enters surface water (0.71t/a). As such, regulation of direct emissions from production and consumption of nano-silver products can be of priority for local environmental management. The modeled regional concentrations (modes) of nano-silver are 0.9ng/L in surface water, 20ng/kg in soil, 6.9μg/kg in sediment, and negligible in the air, which agree well with measurements in the modeled region. Based on the modeled concentrations, we calculate that the risk characterization ratio is <1 in the air, surface water and soil, which means that nano-silver currently poses no risk to organisms living in these environmental compartments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

N ε -carboxymethyl-lysine (CML), a major isoform of advanced glycation end products (AGEs), plays a crucial role in the functional damage of diabetes mellitus. However, it is not clear whether ALT-711 (alagebrium), an inhibitor of AGEs, is capable to rescue CML-induced poor angiogenesis, as well as the underlying mechanism. MicroRNA-27b (miR-27b) promotes angiogenesis through down-regulation of anti-angiogenic protein thrombospondin-1 (TSP-1). Here, we used diabetic mice with hindlimb ischemia to investigate whether miR-27b/TSP-1 signaling is involved in the pathology of critical limb ischemia (CLI) in diabetes mellitus. We additionally examined the effect of ALT-711 on the tube formation of endothelial cells treated with CML-BSA. Compared with control group, the lower blood flow recovery was observed in the ischemic lower limbs of diabetic mice, with decreased expression of vascular endothelial growth factor (VEGF) and miR-27b and increased TSP-1 expression. CML-BSA reduced the tube formation ability of endothelial cells, decreased VEGF and miR-27b expression, and increased TSP-1 expression, whereas this trend was reversed by ALT-711. The miR-27b mimic promoted tube formation, increased VEGF expression, and decreased TSP-1 expression, whereas these effects were abolished by TSP-1 overexpression. Moreover, miR-27b silencing suppressed ALT-711-induced promotion of tube formation under CML-BSA treatment, with reduced VEGF and augmented TSP-1 expression. Taken together, the present study demonstrated that ALT-711 can rescue CML-induced functional angiogenesis damage via miR-27b/TSP-1 signaling cascades. These results indicate new therapeutic strategies for diabetes patients with CLI., Competing Interests: None.

We tested six kinds of commercially available baby products containing nano-silver and divided them into two categories: baby food containers and baby oral care products, according to usage. We measured the total mass of silver, particle size, particle number concentration and the mobility under different simulated conditions. The total mass of silver in baby products and migration solutions was quantified by ICP-MS analysis, and the size of the migrated particles was investigated by single particle ICP-MS and transmission electron microscopy-energy dispersive spectrometer. Nano-silver has different migration behaviour in different materials, and the total mass of silver released in 3% acetic acid was generally highest for plastic material, while highest in 10% ethanol for silicone material. For baby food containers and baby oral care products, the total amount of silver in the migration solutions varied from 2.98 to 126.46 ng/dm 2 and from 2.01 to 2.83 ng/g, respectively. The research shows that the use of baby products containing silver may expose babies to silver nanoparticles.

Warfarin exerts its anticoagulation activity by blocking the vitamin K-epoxide cycle. A quantitative understanding of how warfarin and related genes interact with the vitamin K-epoxide cycle and the associated change of coagulation activity in the human body may help study the pharmacodynamics of warfarin. The plasma concentration of vitamin K 1 (VK 1 ) and vitamin K 1 2,3-epoxide (VK 1 O) could reflect the status of vitamin K-epoxide cycle. However, their determination is a challenging task due to their extremely low concentrations in human plasma and the severe interferences caused by co-extracted lipids. In this study, we developed an LC-APCI-MS/MS method for the simultaneous determination of VK 1 and VK 1 O in human plasma using stable deuterium-labeled vitamin K 1 (vitamin K 1 -d7) as the internal standard (IS). Plasma samples were prepared through protein denaturation followed by one-step liquid extraction with cyclohexane. Chromatographic separation of analytes from isobaric interferences and endogenous ion suppressor was performed on a Synergi Hydro-RP column (150 mm × 4.6 mm, 4 μm) under the reversed-phase condition with isocratic elution. The selective reaction monitoring (SRM) transitions were chosen as m/z = 451.5→187.3 for VK 1 , m/z = 467.5→161.2 for VK 1 O, and m/z = 458.6→194.3 for IS in APCI positive mode. The assay was linear in the range of 100-10,000 pg/mL for the two analytes and achieved considerable extraction recoveries (87.8-93.3%, 91.0-96.9%, and 92.0% for VK 1 , VK 1 O, and IS, respectively), negligible matrix effects (93.6-96.0%, 96.3-100.1%, and 95.5%), and high selectivity with a small sample volume requirement (0.2 mL) and short run time (15 min). The validated method was successfully applied in a clinical pharmacodynamic study of warfarin, and the clotting activity was found to be negatively correlated with the plasma concentration ratio of VK 1 O to VK 1 ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To explore the association between clock circadian regulator circadian locomotor output cycles kaput gene (CLOCK) and the forming of atherosclerotic plaques and its underlying mechanisms, mouse aortic endothelial cells (MAECs) and atherosclerosis (AS) mouse model were recruited for our study. The apoE gene knockout mouse was used as the model of AS and we accelerated the formation of unstable plaques through the combination of carotid artery ligation and high-fat (HF) diet administration (0.2% cholesterol, 20% fat). The mRNA and protein expressions of CLOCK in peripheral blood monouclear cells of acute coronary syndrome (ACS) patients or mouse AS model were detected by qPCR, western blot analysis and immunohistochemical staining. The number of adherent cells and atherosclerotic plaques was counted to assess the effects of CLOCK on the progression of ACS, and adherence-associated genes, such as vascular cell adhesion molecule (VCAM)-1, C-C motif chemokine ligand 2 (CCL-2), and CCL-5. The results showed that CLOCK expression was significantly increased in both ACS patients and AS mouse model. The levels of CLOCK, leukemia inhibitory factor (LIF), intercellular adhesion molecule 1 (ICAM-1), perilipin 2 (ADFP), nuclear factor kappa B (NF-κB), and plasminogen activator inhibitor-1 (PAI-1), as well as the number of atherosclerotic plaques were elevated in the AS mouse model, as compared with the control group. Chromatin immunoprecipitation assay showed that CLOCK bound directly to the promoter of PAI-1 gene and CLOCK could positively regulate the expressions of LIF, ICAM-1, ADFP, NF-κB, and PAI-1. Reduction of CLOCK expression would decrease the expressions of VCAM-1, CCL-2, and CCL-5, and the number of adherent cells and atherosclerotic plaques, but these effects were neutralized when PAI-1 was simultaneously overexpressed in either mouse model or MAECs. Our results demonstrate that CLOCK overexpression triggers the formation of atherosclerotic plaques by directly upregulating PAI-1 expression.