Search

Background: Dyslipidemia is increasingly recognized as an essential risk factor for cardiovascular diseases. However, few studies illustrated the effects of ambient temperature exposure (TE) on lipid levels in children. The study aimed to examine the association between ambient TE and lipid levels in children., Methods: Based on a prospective cohort, a total of 2423 children (with 4466 lipids measure person-time) were collected from 2014 to 2019. The meteorological observation data and adjusted variables were collected. Mixed-effect models and generalized additive mixed model (GAMM) were applied to investigate the association between ambient TE and lipid levels., Results: A significant negative association was observed between TE and low-density lipoprotein cholesterol (LDL-C) or total cholesterol (TC) levels both in all children [LDL-C, β(95%CI) = -0.350(-0.434,-0.265), P < 0.001; TC, β(95%CI) = -0.274(-0.389,-0.160), P < 0.001] and by different sex group. However, no significant association was found in low-density lipoprotein cholesterol (HDL-C) or triglycerides (TG) levels. The estimated optimal ambient TEs for LDL-C were 18.273 °C and 18.024 °C for girls and boys, respectively. For TC, the optimal ambient TEs were 17.949 °C and 18.024 °C, respectively. With ambient TE decreased, the risk of dyslipidemia increased for both boys [OR = 0.032(0.006,0.179), P < 0.001] and girls [OR = 0.582(0.576,0.587), P < 0.001]., Conclusion: This study provided a comprehensive illustration about the associations between ambient TE and lipid levels in different sex and ages from a prospective cohort study. The findings will provide evidence for the government to prevent dyslipidemia in vulnerable children through regulating TE., 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 Elsevier Inc. All rights reserved.)

Background: Predicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes., Objective: The aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes., Methods: We assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose<54 mg/dL) levels. The validation data set of 427 patients of European-American ancestry in the United States was used to validate the models and examine their generalizations. The predictive performance of the models was evaluated according to the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC)., Results: For the difficult-to-predict mild hypoglycemia events, the LSTM model consistently achieved AUC values greater than 97% in the primary data set, with a less than 3% AUC reduction in the validation data set, indicating that the model was robust and generalizable across populations. AUC values above 93% were also achieved when the LSTM model was applied to both type 1 and type 2 diabetes in the validation data set, further strengthening the generalizability of the model. Under different satisfactory levels of sensitivity for mild and severe hypoglycemia prediction, the LSTM model achieved higher specificity than the SVM and RF models, thereby reducing false alarms., Conclusions: Our results demonstrate that the LSTM model is robust for hypoglycemia prediction and is generalizable across populations or diabetes subtypes. Given its additional advantage of false-alarm reduction, the LSTM model is a strong candidate to be widely implemented in future CGM devices for hypoglycemia prediction., (© Jian Shao, Ying Pan, Wei-Bin Kou, Huyi Feng, Yu Zhao, Kaixin Zhou, Shao Zhong. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

This study aims to investigate the effects of obstructive sleep apnea on paediatric psychological and behavioural abnormalities. A total of 1086 paediatric patients with obstructive sleep apnea and 728 sample snoring controls were enrolled in the study. Patients with obstructive sleep apnea underwent bilateral tonsillectomy plus adenoidectomy or adenoidectomy alone. Repeated Autism Behaviour Checklist, Spence Children's Anxiety Scale, and Children's Depression Inventory were performed to assess the autism symptoms, anxiety level and depressive symptoms before and after surgery. The score of Autism Behaviour Checklist in preschool children with obstructive sleep apnea was higher than that in control. In school children with obstructive sleep apnea, the score of Spence Children's Anxiety Scale was also higher. School children with obstructive sleep apnea with depressive symptoms were significantly higher than that in control. The scores of Autism Behaviour Checklist, Spence Children's Anxiety Scale, and Children's Depression Inventory in the obstructive sleep apnea group after surgery were significantly lower than that before surgery. Our study showed that the score of Spence Children's Anxiety Scale and Children's Depression Inventory had a close correlation with the illness course and hypoxia duration. The Spence Children's Anxiety Scale and Children's Depression Inventory scores are also closely associated with the Autism Behaviour Checklist score. These results suggest that obstructive sleep apnea may have a significant impact on autism symptoms, anxiety levels and depressive symptoms in children. We found that the longer the duration of the obstructive sleep apnea course and hypoxia, the greater the impact on anxiety level and depressive symptoms. The suspected autism symptoms, anxiety level and depressive symptoms in children with obstructive sleep apnea were also significantly correlated. Thus, early detection and timely treatment may often reverse the psychological and behavioural abnormalities caused by obstructive sleep apnea., (© 2023 European Sleep Research Society.)

Background: With the global increase in the use of injectable fillers, more cases with serious adverse events such vision loss are being reported. This article aims to review the cases of hyaluronic acid (HA) filler-related vision loss and to discuss the potential efficacy of hyaluronidase (HYASE) treatment via different given methods., Methods: A total of 29 articles presenting 144 cases of HA filler-related vision loss were included in this study., Results: Most cases of HA filler-related vision impairment were reported from China, followed by Korea. The majority of cases were seen in women. The nose, forehead and glabella were the most commonly injection sites. All cases had vision impairment and nearly all cases were unilateral with immediate onset of visual signs and symptoms. Ophthalmic artery occlusion (OAO) and central retinal artery occlusion (CRAO) were the two most commonly involved arterial obstruction patterns featured with a very poor prognosis followed by branch retinal artery occlusion (BRAO), the most favorable involved arterial pattern for a better prognosis. HYASE given subcutaneously and intra-arterially helped with visual recovery to different degrees, while retrobulbar HYASE seemed to be less helpful., Conclusion: Complications after HA-based filler injection are extremely rare but can cause disastrous visual impairment. HYASE given subcutaneously and intra-arterially helped with visual recovery to different extents, and the efficacy might be reinforced when performed together, while retrobulbar HYASE seemed to be less helpful. However, to accurately access the efficacy of HYASE via different administration methods, further randomized controlled trials are needed., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Hypoxia-inducible factor 1 alpha (HIF1α), under hypoxic conditions, is known to play an oxygen sensor stabilizing role by exerting context- and cell-dependent stimulatory and inhibitory functions in immune cells. Nevertheless, how HIF1α regulates T cell differentiation and functions in tumor settings has not been elucidated. Herein, we demonstrated that T-cell-specific deletion of HIF1α improves the inflammatory potential and memory phenotype of CD8 + T cells. We validated that T cell-specific HIF1α ablation reduced the B16 melanomas development with the indication of ameliorated antitumor immune response with enhanced IFN-γ + CD8 + T cells despite the increase in the Foxp3 + regulatory T-cell population. This was further verified by treating tumor-bearing mice with a HIF1α inhibitor. Results indicated that HIF1α inhibitor also recapitulates HIF1α ablation effects by declining tumor growth and enhancing the memory and inflammatory potential of CD8 + T cells. Furthermore, a combination of Treg inhibitor with HIF1α inhibitor can substantially reduce tumor size. Collectively, these findings highlight the notable roles of HIF1α in distinct CD8 + T-cell subsets. This study suggests the significant implications for enhancing the potential of T cell-based antitumor immunity by combining HIF1α and Tregs inhibitors., (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Background: Robot-assisted fracture reduction systems can potentially reduce the risk of infection and improve outcomes, leading to significant health and economic benefits. However, these systems are still in the laboratory stage and not yet ready for commercialization due to unresolved difficulties. While previous reviews have focused on individual technologies, system composition, and surgical stages, a comprehensive review is necessary to assist future scholars in selecting appropriate research directions for clinical use. Methods: A literature review using Google Scholar identified articles on robot-assisted fracture reduction systems. A comprehensive search yielded 17,800, 18,100, and 16,700 results for "fracture reduction," "computer-assisted orthopedic surgery," and "robot-assisted fracture reduction," respectively. Approximately 340 articles were selected, and 90 highly relevant articles were chosen for further reading after reviewing the abstracts. Results and Conclusion: Robot-assisted fracture reduction systems offer several benefits, including improved reduction accuracy, reduced physical work and radiation exposure, enhanced preoperative planning and intraoperative visualization, and shortened learning curve for skill acquisition. In the future, these systems will become integrated and practical, with automatic preoperative planning and high intraoperative safety., 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 © 2023 Kou, Zhou, Lin, Kuang and Sun.)

Purpose: This study aimed to investigate the association between preoperative inflammation-associated blood cell markers and the prognosis of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) who underwent nephrectomy., Patients and Methods: We retrospectively analyzed data from our single-center cohort of patients who underwent radical or partial nephrectomy for non-metastatic ccRCC. The optimal cutoff values for red blood cell distribution width (RDW), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR) were determined using X-tile software. We evaluated recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) using the Kaplann-Meier method. Cox proportional-hazards regression models were utilized to assess predictors of RFS, CSS, and OS. The predictive accuracy was evaluated using Harrell's Concordance Index (C-index)., Results: A total of 444 patients who underwent nephrectomy were included in the study. The optimal cutoff values for RDW, PLR, NLR, and LMR were determined as 13.1, 157.3, 3.4, and 2.7, respectively. On univariate Cox regression analysis, NLR, PLR, and LMR were significant predictors for RFS, CSS, and OS. After adjusting for important prognostic factors, only NLR remained a significant prognostic marker for both CSS and OS. When NLR was added to the stage, size, grade, and necrosis (SSIGN) model, the C-index increased from 0.777 to 0.826 for CSS and from 0.703 to 0.734 for OS. Similarly, when NLR was added to the University of California, Los Angeles, Integrated Staging System (UISS), the C-index increased from 0.796 to 0.811 for CSS and from 0.735 to 0.745 for OS., Conclusion: NLR is a reliable prognostic biomarker for patients with non-metastatic ccRCC. The prognostic capabilities of UISS and SSIGN models could be improved by adding NLR to UISS and SSIGN models., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Cheng et al.)

The helper CD4 +  T cell-type 17 (Th17) cells and regulatory CD4 +  T cells (Tregs) are balanced through numerous molecular regulators, particularly metabolic factors, and their alteration causes immune dysregulation. Herein, we report that peroxisome proliferator of activated receptor-alpha (Pparα), a lipid metabolism regulator, suppresses Th17 differentiation. We demonstrated that Pparα ablation improves Th17 and pro-Th17 factor HIF-1α by enhancing the expression and nuclear localization of NFκB-activator IκB kinase-alpha (IKKα). Unexpectedly, we found that IKKα directly interacts with RORγt and enhances the expression of Il17a gene. Meanwhile, IKKα also interacts with Foxp3, leading to the post-translational regulation of Foxp3 by elevating its proteasomal degradation, and influencing Th17 development. Pparα deficiency leads to enhanced Th17 development in vivo and is associated with enhanced pathology in a murine experimental autoimmune encephalomyelitis (EAE) model. Overall, our data indicate that Pparα may serve as a potential therapeutic target for autoimmune and inflammatory diseases., (© 2023. The Author(s).)

The pelvis and its surrounding soft tissues create a complicated mechanical environment that greatly affects the success of fixing broken pelvic bones with surgical navigation systems and/or surgical robots. However, the modeling of the pelvic structure with the more complex surrounding soft tissues has not been considered in the current literature. The study developed an integrated finite element model of the pelvis, which includes bone and surrounding soft tissues, and verified it through experiments. Results from the experiments showed that including soft tissue in the model reduced stress and strain on the pelvis compared to when it was not included. The stress and strain distribution during pelvic loading was similar to what is typically seen in research studies and more accurate in modeling the pelvis. Additionally, the correlation with the experimental results from the predecessor's study was strong (R 2 = 0.9627). The results suggest that the integrated model established in this study, which includes surrounding soft tissues, can enhance the comprehension of the complex biomechanics of the pelvis and potentially advance clinical interventions and treatments for pelvic injuries.

Slurry reflux is a low-cost slurry reduction technology, which can solve the problem that a large amount of slurry cannot be completely consumed in a biogas plant. Anaerobic digestion (AD) of corn stalks with slurry reflux and non-reflux was compared and evaluated in continuous anaerobic digestion to clarify the effects of slurry reflux on AD with organic loading rate (OLR) variation. It was found that slurry reflux increased cumulative methane production and improved system stability. The average methane yield of the slurry reflux group was 224.19 mL/gVS, which was 41.35% higher than that of the non-reflux group. High-throughput sequencing results showed that slurry reflux increased the microbial community richness. The dominant microorganisms in the reflux group were in phylum Bacteroidetes, which have the capacity to degrade polymers, and Methanothrix , which is an aceticlastic methanogen. The relative abundances of Bacteroidetes and Methanothrix were 32.41% and 41.75%, respectively. Clostridium III and Saccharofermentans , which are related to syntrophic acetate oxidation and hydrolysis, were increased in relative abundance in the slurry reflux system. The increase of the OLR altered the main methane-producing pathway from the acetoclastic methanogenic pathway to the hydrogenotrophic methanogenic pathway in the AD system, and the slurry reflux can delay this trend. This study provided an effective way for the reduction and utilization of slurry in a biogas plant.

Introduction: Allergic rhinitis (AR) in children is associated with various comorbidities, posing challenges for treatment and management. There have been few investigations of these multimorbidities in Chinese children with AR. Here, we investigated the prevalence of multimorbidities in children with moderate to severe AR and analyzed the influencing factors using real-world data., Methods: In total, 600 children who visited the outpatient clinic of our hospital and were diagnosed with moderate-severe AR were prospectively enrolled. All children underwent allergen detection and electronic nasopharyngoscopy. Parents or guardians completed a questionnaire that included age, sex, mode of delivery, feeding pattern, and familial history of allergy. The multimorbidities investigated included atopic dermatitis (AD), asthma, allergic conjunctivitis (AC), chronic rhinosinusitis (CRS), adenoid hypertrophy (AH), tonsil hypertrophy (TH), recurrent epistaxis, and recurrent respiratory tract infections (RRTIs)., Results: The AR multimorbidities reported in children were as follows: recurrent epistaxis (46.5%), AC (46.3%), AD (40.7%), asthma (22.5%), RRIs (21.3%), CRS (20.5%), AH (19.7%), and TH (12.5%). In univariate logistic regression analysis, age (&lt;6 years), birth mode, familial history of allergy, and single dust mite allergy were associated with AR multimorbidity (p &lt; 0.05). Multivariate logistic regression revealed that a familial history of allergy was an independent risk factor for AC (odds ratio [OR] = 1.539, 95% confidence interval [CI]: 1.104-2.145) and AH (OR = 1.506, 95% CI: 1.000-2.267) (p &lt; 0.05). Age (&lt;6 years) was independently associated with the risk of AD (OR = 1.405, 95% CI: 1.003-1.969) and RRTIs (OR = 1.869, 95% CI: 1.250-2.793) (p &lt; 0.05), cesarean section with AR and CRS risk (OR = 1.678, 95% CI: 1.100-2.561), and single dust mite allergy with asthma (OR = 1.590, 95% CI: 1.040-2.432) and CRS (OR = 1.600, 95% CI: 1.018-2.515) risk (p &lt; 0.05). Further, non-dust mite allergy was independently associated with AR and CRS (OR = 2.056, 95% CI: 1.084-3.899)., Conclusion: AR was found to be accompanied by different comorbidities, including both allergic and non-allergic comorbidities, complicating disease treatment. These findings demonstrated that age (&lt;6 years), familial history of allergy, types of allergens, and cesarean section were risk factors for different multimorbidities associated with AR., (© 2023 S. Karger AG, Basel.)

The clinical application of gentamicin may lead to acute kidney injury (AKI), and the nephrotoxicity of gentamicin is related to the pathological mechanism of several oxidative and inflammatory cytokines. Plant-derived essential oils have good anti-inflammatory and antioxidant properties. This study aimed to clarify the protective effect of Amomum tsao-ko essential oils (AOs) on gentamicin-induced AKI in rats and its possible mechanism. The rat AKI model was induced by intraperitoneal injection of gentamicin. After 14 days of oral AO treatment, the renal function and pathological changes of the kidney tissues were evaluated, and the level of kidney tissue oxidative stress was detected. The content of inflammatory cytokines was measured by ELISA. The expression of ERK1/2, JNK1/2, p38, NF-κB, caspase-3, and Bax/Bcl-2 proteins were estimated by Western blot analysis. The results showed that taking AO reduced the contents of serum urea and creatinine in AKI rats and improve the pathological changes and oxidative stress of the kidney tissue in rats. At the same time, AO reduced inflammation and apoptosis during AKI by regulating the MAPK pathway. The data show that AO has a protective effect on the kidneys and may be a potential drug for treating kidney injury.

Adenoid hypertrophy is a common disease in pediatric otorhinolaryngology. Surgical resection is the main treatment at present, but many children still face the risk of postoperative recurrence or even secondary surgery. In order to reduce the postoperative recurrence rate and provide reference information for clinical medical staff and parents of the children, this review was carried out to analyze the domestic and foreign pertinent literature in recent years and put forward overall prevention strategies base on the related factors of recurrence., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Multiple myeloma (MM) is a malignant plasma cancer which remains difficult to be cured. Recently, numerous research studies have appeared, exploring MM from molecular level. However, there is no study about the impact of metabotropic glutamate receptors (mGluRs), especially mGluR5, on MM progression. Thus, the present research was dedicated to the exploration of the influence of mGluR5 on MM., Objectives: In this research, we used quantitative real-time polymerase chain reaction (qRT-PCR) to check the gene expression in MM, western blot assay to check the protein expression of the gene, MTT assay to quantify the cell viability, and flow cytometry (FCM) apoptosis method to evaluate cell apoptosis in order to acquire the results. The purpose was to assess the role of mGluR5 in MM cells., Material and Methods: The qRT-PCR was used and it was found that mGluR5 was overexpressed in MM cell lines and MM tissues compared to normal ones. To better observe the function of mGluR5 in MM, cell viability and apoptosis were checked using MTT and FCM apoptosis assays after the treatment with agonists and antagonists., Results: Agonist-induced mGluR5 upregulation could promote MM cell viability and inhibit apoptosis. The same results were obtained through MTT and FCM apoptosis assays after upregulation and downregulation of mGluR5 by transfection. To further investigate the inner mechanism, the effect of mGluR5 on Ras-MAPK pathway was checked using western blot. It was found that the upregulation of mGluR5 could activate the Ras-MAPK pathway., Conclusions: The mGluR5 might be involved in promoting cell proliferation and inhibiting cell apoptosis in MM. It can be an essential biomarker in the screening for MM and a potential part of future MM therapies.

Aim: We aim to develop a signature that could accurately predict prognosis and evaluate the response to immune checkpoint blockade (ICB) in bladder urothelial carcinoma (BLCA)., Methods: Based on comprehensive analysis of public database, we identified prognosis-related hub genes and investigated their predictive values for the ICB response in BLCA., Results: Among 69 common DEGs, three genes (AURKA, BIRC5, and CKS1B) were associated with poor prognosis, and which were related to histological subtypes, TP53 mutation status, and the C2 (IFN-gamma dominant) subtype. Three genes and their related risk model can effectively predict the response of immunotherapy. Their related drugs were identified through analysis of drug bank database., Conclusions: Three genes could predict prognosis and evaluate the response to ICB in BLCA., Competing Interests: The authors declare that there are no competing interests associated with this manuscript., (Copyright © 2022 Ya Guo et al.)

Adrenocortical carcinoma (ACC) is a rare type of tumor with a poor prognosis. Ferroptosis is a relatively novel form of programmed cell death driven by iron‑dependent lipid peroxidation accumulation. Recent evidence suggests that IFNγ facilitates erastin‑induced ferroptosis, which contributed to anticancer therapy in various types of cancer. However, it has remained elusive whether the regulation of IFNγ on ferroptosis has a positive role in the treatment of ACC. Thus, the aim of the present study was to explore the effects of IFNγ on erastin‑induced ferroptosis in the ACC cell line NCI‑H295R and investigate the underlying mechanisms. Cell viability was assessed using a Cell Counting Kit‑8 assay, an ethynyldioxyuridine proliferation assay and Live/Dead staining. The levels of iron, reactive oxygen species, lipid peroxidation and mitochondrial damage were also assessed. Western blot and reverse transcription‑quantitative PCR analyses were used to determine the underlying molecular mechanisms involved in the erastin‑induced ferroptosis of NCI‑H295R cells. The results suggested that IFNγ promoted erastin‑induced ferroptotic cell death. Furthermore, IFNγ enhanced erastin‑induced ferroptosis, as evidenced by the accumulation of iron, as well as the increase in lipid peroxidation and promotion of mitochondrial damage. Further analysis suggested that IFNγ enhanced ferroptosis by suppressing the expression of solute carrier family 7 member 11, an important negative regulator of ferroptosis, and this was achieved via activation of the JAK/STAT pathway in NCI‑H295R cells. The present study provided experimental evidence on the activity and mechanism of ferroptosis enhanced by IFNγ in ACC and may give critical insight into the immunotherapeutic management of ACC.

Background: Increasing evidence have depicted that DNA repair-related genes (DRGs) are associated with the prognosis of colorectal cancer (CRC) patients. Thus, the aim of this study was to evaluate the impact of DNA repair-related gene signature (DRGS) in predicting the prognosis of CRC patients. Method: In this study, we retrospectively analyzed the gene expression profiles from six CRC cohorts. A total of 1,768 CRC patients with complete prognostic information were divided into the training cohort ( n = 566) and two validation cohorts ( n = 624 and 578, respectively). The LASSO Cox model was applied to construct a prediction model. To further validate the clinical significance of the model, we also validated the model with Genomics of Drug Sensitivity in Cancer (GDSC) and an advanced clear cell renal cell carcinoma (ccRCC) immunotherapy data set. Results: We constructed a prognostic DRGS consisting of 11 different genes to stratify patients into high- and low-risk groups. Patients in the high-risk groups had significantly worse disease-free survival (DFS) than those in the low-risk groups in all cohorts [training cohort: hazard ratio (HR) = 2.40, p < 0.001, 95% confidence interval (CI) = 1.67-3.44; validation-1: HR = 2.20, p < 0.001, 95% CI = 1.38-3.49 and validation-2 cohort: HR = 2.12, p < 0.001, 95% CI = 1.40-3.21). By validating the model with GDSC, we could see that among the chemotherapeutic drugs such as oxaliplatin, 5-fluorouracil, and irinotecan, the IC50 of the cell line in the low-risk group was lower. By validating the model with the ccRCC immunotherapy data set, we can clearly see that the overall survival (OS) of the objective response rate (ORR) with complete response (CR) and partial response (PR) in the low-risk group was the best. Conclusions: DRGS is a favorable prediction model for patients with CRC, and our model can predict the response of cell lines to chemotherapeutic agents and potentially predict the response of patients to immunotherapy., 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 © 2022 Lv, Wang, Zhong, Cai, Fan, Li, Kou, Huang, Duan, Hu, Zhu, He and Gao.)

Objective: To analyze the clinical characteristics and factors affecting surgical efficiency in children with severe laryngomalacia. Methods: Retrospectively collect medical records of children with severe laryngomalacia who underwent supraglottoplasty in Children's Hospital of Chongqing Medical University between January 1, 2015 and May 1, 2019. And analyze the clinical characteristics, the improvement of main symptoms at different time points, and the influence factors on the surgical efficiency. Results: According to the anatomical classification of severe laryngomalacia, type Ⅳ accounted for the highest proportion（66.1%）, and type Ⅰ was the lowest（3.6%）. All children had stridor and dyspnea, 82.1% cases presented feeding difficulties, and 67.9% cases presented failure to thrive. The proportion of children with medical comorbidities was 62.5%, of which congenital heart disease had the highest incidence（39.3%） The surgical efficiency of severe laryngomalacia without comorbidities was 100.0%, with one type of comorbidity was 96.0%, with multiple comorbidities was 30.0%（ P <0.01）. Stridor, dyspnea, feeding difficulties were significantly improved at one month after surgery in most cases. In the group of surgical age less than 3 months, the surgical efficiency were 61.5%, 61.5% and 69.2% at 1, 3, 6 months after surgery, respectively; the surgical efficiency of children without comorbidities were 100.0%（ P >0.05） at 1, 3 ,6 months after surgery. In the group of surgical age older than 3 months, the surgical efficiency of children were 100.0% at 1, 3, 6 months after surgery regardless with or without comorbidities. The surgical failure rate and reoperation rate in children without comorbidities was 0, but in the children with comorbidities were 22.9%（ P <0.05） and 20.0%（ P <0.05）, respectively. The surgical failure rate and reoperation rate in children with multiple comorbidities was significantly higher than children with only one comorbidity（70.0% vs. 4.0%; 60.0% vs. 4.0%, P <0.01）. The overall operation success rate was 85.7% in severe laryngomalacia children in our hospital. Conclusion: Most children with severe laryngomalacia are associated with multiple medical comorbidities, and with more complex anatomical types. Supraglottoplasty can effectively improve the symptoms in most children with severe laryngomalacia. The existence of multiple comorbidities is the main cause of surgical failure., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with frequent metastatic spread and poor prognosis. The disease can occur at any age with unexpected biological behavior. Recent genome-wide studies of ACC have contributed to our understanding of the disease, but diagnosis of ACC remains a challenge, even for multidisciplinary expert teams. Patients with ACC are frequently diagnosed in advanced stages and have limited therapeutic options. Therefore, for earlier diagnosis and better clinical management of adrenocortical carcinoma, specific, sensitive, and minimal invasive markers are urgently needed. Over several decades, great efforts have been made in discovering novel and reliable diagnostic and prognostic biomarkers including microRNAs, steroid profilings, circulating tumor cells, circulating tumor DNAs and radiomics. In this review, we will summarize these novel noninvasive biomarkers and analyze their values for diagnosis, predicting prognosis, and disease monitoring. Current problems and possible future application of these non-invasive biomarkers will also be discussed., 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 © 2022 Cheng, Kou, Zhu, Yu and Zhu.)

The present study tested the hypothesis that 30 low-intensity (10%) eccentric contractions (10%EC) or two maximal voluntary isometric contractions at a long muscle length (2MVIC) that were performed at two days before maximal eccentric exercise of the elbow flexors consisting of five sets of six maximal eccentric contractions (MaxEC) would reduce increases in biceps brachii distal myotendinous junction displacement (MTJd) over the eccentric contractions during MaxEC. Sedentary young men were randomly placed (n = 12/group) to a control group that performed two bouts of MaxEC (CONT-1st, CONT-2nd) separated by two weeks, or one of two preconditioning groups that performed 10%EC or 2MVIC at 20° elbow flexion at two days prior to MaxEC. All exercises were performed by the non-dominant arm. MTJd of each contraction was assessed by B-mode ultrasound, and its changes over sets were compared among the groups. The average MTJd from the start to the end of six eccentric contractions in the first set was similar among the groups (6.4 ± 0.7 mm). The MTJd increased from the first to fifth set, but the increase was smaller (P < .05) for the 10%EC (13 ± 6%) and 2MVIC (16 ± 9%) groups, and CONT-2nd (3 ± 6%) when compared with CONT-1st (60 ± 12%). Both 10%EC and 2MVIC groups showed smaller (P < .05) changes in all muscle damage markers after MaxEC similarly when compared with CONT-1st, but the changes were greater than those after CONT-2nd. These results supported the hypothesis that protective effect was associated with less MTJd changes, suggesting that this is associated with the mechanisms underpinning the preconditioning effect on muscle damage., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected via calculating Pearson's correlation coefficient. Three prognosis-related autophagy lncRNAs were identified via univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed via analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients., 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 Guo, Yang, Wang, Xu, Kou and Luo.)

Background: Radiomics refers to the extraction of a large amount of image information from medical images, which can provide decision support for clinicians. In this study, we developed and validated a radiomics-based nomogram to predict the prognosis of colorectal cancer (CRC). Methods: A total of 381 patients with colorectal cancer (primary cohort: n = 242; validation cohort: n = 139) were enrolled and radiomic features were extracted from the vein phase of preoperative computed tomography (CT). The radiomics score was generated by using the least absolute shrinkage and selection operator algorithm (LASSO). A nomogram was constructed by combining the radiomics score with clinicopathological risk factors for predicting the prognosis of CRC patients. The performance of the nomogram was evaluated by the calibration curve, receiver operating characteristic (ROC) curve and C-index statistics. Functional analysis and correlation analysis were used to explore the underlying association between radiomic feature and the gene-expression patterns. Results: Five radiomic features were selected to calculate the radiomics score by using the LASSO regression model. The Kaplan-Meier analysis showed that radiomics score was significantly associated with disease-free survival (DFS) [primary cohort: hazard ratio (HR): 5.65, 95% CI: 2.26-14.13, P < 0.001; validation cohort: HR: 8.49, 95% CI: 2.05-35.17, P < 0.001]. Multivariable analysis confirmed the independent prognostic value of radiomics score (primary cohort: HR: 5.35, 95% CI: 2.14-13.39, P < 0.001; validation cohort: HR: 5.19, 95% CI: 1.22-22.00, P = 0.026). We incorporated radiomics signature with the TNM stage to build a nomogram, which performed better than TNM stage alone. The C-index of the nomogram achieved 0.74 (0.69-0.80) in the primary cohort and 0.82 (0.77-0.87) in the validation cohort. Functional analysis and correlation analysis found that the radiomic signatures were mainly associated with metabolism related pathways. Conclusions: The radiomics score derived from the preoperative CT image was an independent prognostic factor and could be a complement to the current staging strategies of colorectal cancer., 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 Cai, Duan, Wang, Huang, Zhu, Zhong, Lv, Li, Kou, Wu and Gao.)

The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications. Notably, TGF-β induces USP44 expression during iTreg differentiation. USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Quantitative detection of phospholipids at the single cell level remains in challenge. Herein, the TiO 2 -coated Fe 3 O 4 nanoparticles were synthesized to selectively enrich trace phospholipids from single cell, which were then eluted using 1.5% ammonia/methanol (w/w) for sensitive detection by electrospray ionization mass spectrometry. Under the optimal experimental conditions, eighteen phospholipids in single cell samples were detected and identified by MS/MS experiments. The limit-of-detections (LODs) were 0.012 μg/L for phosphatidylcholine (PC, 34:1) and 0.014 μg/L for phosphatidylcholine (PC, 36:2) in PBS matrix, with the linear range of 0.05-50 μg/L (R 2  ≥ 0.999). The recovery rates of 94.90-104.00% were obtained, with the relative standard deviations (RSDs ≤ 6.90%). Quantitative determination of PC in real unicellular samples was also achieved, with the concentration of 1.82-2.11 μg/L for PC(34:1) and 1.25-1.65 μg/L for PC(36:2) in six types of single cell, opening up possibilities for quantitative analysis of trace compounds in complex bio-samples. A set of 6 types of tumor cells were analyzed and further differentiated by the partial least squares-discriminant analysis (PLS-DA). Conclusively, a facile method for the direct quantification of phospholipids in single cell samples has been developed, showing potential applications for advanced investigation of phosphorylated substance at the single cell level., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recently, the negative absorption in graphene-based metamaterials became a very attractive direction of THz electronic devices. Here we propose a graphene-dielectric hybrid meta-structure to realize photo-induced enhanced negative absorption in the THz regime, which results from strong graphene-light interaction. The negative absorption is derived from the degradation of the conductivity of graphene under optical pump. Meanwhile, the graphene-dielectric hybrid meta-structure introduces dispersion relation and resonance mode, which can couple with the incident wave to construct a strong resonance. In this case, both the dispersion of the propagating waves and resonance are contributed to the graphene-light interaction and enhance the negative absorption, in which the resonance coupling determines the distribution of negative absorption, and the maximum is dominated by dispersion. More importantly, compared with the previous work, the negative absorption is increased by nearly 100 times by adopting this meta-structure.

A total of 15 representative organophosphorus pesticides (OPPs), a class of water pollutants causing serious global concerns, have been sensitively quantified by internal extractive electrospray ionization mass spectrometry (iEESI-MS) after enrichment with Fe 3 O 4 -ZrO 2 innovatively synthesized in our lab by a one step coprecipitation method. For the premium enrichment, the amounts of Fe 3 O 4 -ZrO 2 , pH value, adsorption time, type and volume of desorption solvent, and shaking time of desorption were systematically optimized. Under optimized conditions, the proposed method provided low limits of detection (LODs) of 0.14-16.39 ng L -1 with relative standard deviations (RSDs) of less than 8.7%. A wide linear response range of about 4 orders of magnitude was achieved with linear coefficients ( R 2 ) of 0.9921-0.9999 for all the analytes tested. The present method also provided good recoveries (85.4-105.9%) with acceptable precision (RSDs < 7.2%) in spiked environmental water samples. Furthermore, multiple analytes including dimethoate, omethoate, etc. were simultaneously detected in a single sample run, which was accomplished within 1 min, resulting in significantly improved analytical throughput for quantitative analysis of bulk amounts of samples. The experimental results demonstrated that Fe 3 O 4 -ZrO 2 -iEESI-MS provided advantages, including high sensitivity, high speed, and reasonable selectivity for the detection of OPPs, showing potential applications in environmental water sample analysis and environmental science.

In this study, we aimed to evaluate the toxic effects, changes in life span, and expression of various metabolism-related genes in Caenorhabditis elegans, using RNA interference (RNAi) and mutant strains, after 3-bromopyruvate (3-BrPA) treatment. C. elegans was treated with various concentrations of 3-BrPA on nematode growth medium (NGM) plates, and their survival was monitored every 24 h. The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction (qPCR). Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase (HK) genes. The average life span of C. elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group. hxk-1, hxk-2, and hxk-3 were overexpressed after the treatment with 3-BrPA. After successfully interfering hxk-1, hxk-2, and hxk-3, the 50% lethal concentration (LC 50 ) of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control. All the cyp35 genes tested were overexpressed, except cyp-35B3. The induction of cyp-35A1 expression was most obvious. The LC 50 values of the mutant strains cyp-35A1, cyp-35A2, cyp-35A4, cyp-35B3, and cyp-35C1 were lower than that of the control. Thus, the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes, and the cyp-35 family plays a key role in the metabolism of 3-BrPA.

In this work, we have successfully designed and formulated a doxorubicin-loaded polypeptide-based multilayer assembled gold nanorod (DH-GNR). We have hypothesized that near-infrared (NIR) laser irradiation of DH-GNR will combine the benefits of chemotherapy and photothermal therapy. The GNR was surface functionalized with poly-glutamic acid (PGA) and poly-l-Lysine (PLL) with a final layer of hyaluronic acid (HA) that could also serve as a targeting ligand toward the overexpressed CD44 receptors in ovarian cancer cells. The zigzag ζ potential of nanoparticle is a proof of successful assembly of alternative polymers on the GNR surface. NIR irradiation exhibited a burst release of drug in pH 7.4 and pH 5.0 buffer conditions. The combination of doxorubicin (DOX)-based chemotherapy and GNR-based photothermal therapy exhibited a synergistic effect in killing the SKOV3 cancer cells. DH-GNR(+NIR) induced a 82.5% apoptosis (combined early and late apoptosis) compared with only 35.2 and 38.5% for DOX or DH-GNR(-NIR) treated cell group. Results clearly suggest that the excessive reactive oxygen species (ROS) generation in DH-GNR (+NIR) might be responsible for the cell apoptosis and cell death. The promising anticancer effect of DH-GNR will be of great potential in the treatment of ovarian cancers and worth further development for treating other malignant tumors., (© 2019 The Author(s).)

The aim of the present study was to investigate the expression and role of the co‑stimulatory molecule T‑lymphocyte activation antigen CD86 (CD86) in dendritic cells (DCs) from the peripheral blood of patients with allergic rhinitis (AR) compared with those from healthy individuals. It was observed that mature DCs from the peripheral blood of patients with AR expressed high levels of the co‑stimulatory molecule CD86, but not CD80, compared with healthy control subjects. CD86 expression levels in DCs decreased significantly following transfection with siRNA in a lentiviral vector. Furthermore, the level of transforming growth factor‑β1 produced by T cells co‑cultured with DCs was significantly increased in the siRNA group, while interleukin (IL)‑4 and IL‑5 production was significantly decreased. The findings of the present study indicated that CD86 may play a pivotal role in the regulatory T cell/type 2 helper T cell imbalance in allergic inflammation.

Background: Although cryopreservation has been widely used in clinical practice, it remains limited to small or thin bloodless tissues with a simple structure and function. In August of 2002, the authors performed the first successful transplantation of a cryopreserved vascularized rat hind limb. Subsequently, the authors extended this cryopreservation technique to the preservation of human fingers., Methods: In December of 2002 and December of 2003, the authors performed two in situ implantations of cryopreserved amputated fingers for two patients by means of the "two-step" and programmed cryopreservation methods. In case 1, computed tomographic angiography was performed on the affected hand 6 months after surgery. In case 2, pieces of skin were obtained from the thawed amputated finger for pathologic examination before replantation., Results: One finger was cryopreserved for 81 days and the other for 5 days. Both fingers were replanted successfully. Computed tomographic angiography revealed a patent radial proper digital artery in case 1. The pathologic results of case 2 showed satisfactory skin cell morphology. After 15- and 14-year follow-up assessments of the two patients, the replanted fingers achieved satisfactory appearance and function., Conclusions: The authors confirmed the effectiveness of deep cryopreservation for the long-term preservation of human fingers. The current application scope of these cryopreservation techniques includes small limbs with minimal amounts of muscle tissue., Clinical Question/level of Evidence: Therapeutic, V.

With the rapid growth of material innovations, multishelled hollow nanostructures are of tremendous interest due to their unique structural features and attractive physicochemical properties. Continued effort has been made in the geometric manipulation, composition complexity, and construction diversity of this material, expanding its applications. Energy storage technology has benefited from the large surface area, short transport path, and excellent buffering ability of the nanostructures. In this work, the general synthesis of multishelled hollow structures, especially with architecture versatility, is summarized. A wealth of attractive properties is also discussed for a wide area of potential applications based on energy storage systems, including Li-ion/Na-ion batteries, supercapacitors, and Li-S batteries. Finally, the emerging challenges and outlook for multishelled hollow structures are mentioned., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Reducing the deposit of discharge products and suppressing the polysulfide shuttle are critical to enhancing reaction kinetics in Li-S batteries. Herein, a Pt@Ni core-shell bimetallic catalyst with a patch-like or complete Ni shell based on a confined catalysis reaction in porous carbon spheres is reported. The Pt nanodots can effectively direct and catalyze in situ reduction of Ni 2+ ions to form core-shell catalysts with a seamless interface that facilitates the charge transfer between the two metals. Thus, the bimetallic catalysts offer a synergic effect on catalyzing reactions, which shows dual functions for catalytic oxidation of insoluble polysulfides to soluble polysulfides by effectively reducing the energy barrier with simultaneous strong adsorption, ensuring a high reversible capacity and cycling stability. A novel process based on the Pt@Ni core-shell bimetallic catalyst with a patch-like Ni shell is proposed: electronic migration from Ni to Pt forces Ni to activate Li 2 S 2 /Li 2 S molecules by promoting the transformation of Li-S-Li to Ni-S-Li, consequently releasing Li + and free electrons, simultaneously enhancing protonic/electronic conductivity. The presence of the intermediate state Ni-S-Li is more active to oxidize Li 2 S to polysulfides. The Li 2 S bound to adjacent Pt sites reacts with abundant -S-Li species and then releases the Pt sites for the next round of reactions., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Terahertz (THz) radiation has received much attention during the past few decades for its potential applications in various fields, such as spectroscopy, imaging, and wireless communications. To use terahertz waves for data transmission in different application systems, the efficient and rapid modulation of terahertz waves is required and has become an in-depth research topic. Since the turn of the century, research on metasurfaces has rapidly developed, and the scope of novel functions and operating frequency ranges has been substantially expanded, especially in the terahertz range. The combination of metasurfaces and semiconductors has facilitated both new opportunities for the development of dynamic THz functional devices and significant achievements in THz modulators. This paper provides an overview of THz modulators based on different kinds of dynamic tunable metasurfaces combined with semiconductors, two-dimensional electron gas heterostructures, superconductors, phase-transition materials, graphene, and other 2D material. Based on the overview, a brief discussion with perspectives will be presented. We hope that this review will help more researchers learn about the recent developments and challenges of THz modulators and contribute to this field.

Quantification of ultra-trace analytes in complex biological samples using micro-solid-phase extraction followed by direct detection with internal extractive electrospray ionization mass spectrometry (μSPE-iEESI-MS) was demonstrated. 1-Hydroxypyrene (1-OHP) and papaverine at attomole levels in human raw urine samples were analyzed under negative and positive ion detection mode, respectively. The μSPE was simply prepared by packing a disposable syringe filter with octadecyl carbon chain (C18)-bonded micro silica particles, which were then treated as the "bulk sample" after the analytes were efficiently enriched by the C18 particles. Under the optimized experimental conditions, the analytes were readily eluted by isopropanol/water (80/20, V/V) at a high voltage of ± 4.0 kV, producing analyte ions under ambient conditions. The limit of detection (LOD) was 0.02 pg/L (9.2 amol) for 1-hydroxypyrene and 0.02 pg/L (5.9 amol) for papaverine. The acceptable linearity (R 2  > 0.99), signal stability (RSD ≤ 10.7%), spike recoveries (91-95%), and comparable results for real urine samples were also achieved, opening up possibilities for quantitative analysis of trace compounds (at attomole levels) in complex bio-samples. Graphical abstract.

Here we report a highly scalable yet flexible triple-layer structured porous C/SiO 2 membrane via a facile phase inversion method for advancing Li-sulfur battery technology. As a multifunctional current-collector-free cathode, the conductive dense layer of the C/SiO 2 membrane offers hierarchical macropores as an ideal sulfur host to alleviate the volume expansion of sulfur species and facilitate ion/electrolyte transport for fast kinetics, as well as spongelike pores to enable high sulfur loading. The triple-layer structured membrane cathode enables the filling of most sulfur species in the macropores and additional loading of a thin sulfur slurry on the membrane surface, which facilitates ion/electrolyte transport with faster kinetics than the conventional S/C slurry-based cathode. Furthermore, density functional theory simulations and visual adsorption measurements confirm the critical role of the doped SiO 2 nanoparticles (∼10 nm) in the asymmetric C membrane in suppressing the shuttle effect of polysulfides via chemisorption and electrocatalysis. The rationally designed C/SiO 2 membrane cathodes demonstrate long-term cycling stability of 300 cycles at a high sulfur loading of 2.8 mg cm -2 with a sulfur content of ∼75%. This scalable yet flexible self-supporting cathode design presents a useful strategy for realizing practical applications of high-performance Li-S batteries.

Regulatory T cells (Tregs) are crucial mediators of immune control. The characteristic gene expression and suppressive functions of Tregs depend considerably on the stable expression and activity of the transcription factor FOXP3. Transcriptional regulation of the Foxp3 gene has been studied in depth, but both the expression and function of this factor are also modulated at the protein level. However, the molecular players involved in posttranslational FOXP3 regulation are just beginning to be elucidated. Here, we found that TRAF6-deficient Tregs were dysfunctional in vivo ; mice with Treg-restricted deletion of TRAF6 were resistant to implanted tumors and displayed enhanced anti-tumor immunity. We further determined that FOXP3 undergoes K63-linked ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. In the absence of TRAF6 activity or upon mutation of the ubiquitination site, FOXP3 displayed aberrant, perinuclear accumulation and disrupted regulatory function. Thus, K63-linked ubiquitination by TRAF6 ensures proper localization of FOXP3 and facilitates the transcription factor's gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing regulator that may be targeted in novel tolerance-breaking therapies., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Supercharged protein ions produced by electrospray ionization are extremely efficient proton donors for secondary ionization. Here, by electrospraying the protein solutions containing 5% 1,2-butylene carbonate, the supercharged protein ions with unusually high proton density were produced as the primary ions for the ionization of exhaled breath samples in the extractive electrospray ionization mass spectrometry (EESI-MS), which resulted in the enhanced ionization efficiency for the breath analytes even with relatively low gas phase basicity. Moreover, the total number of metabolites detected in breath increased by about 260% in the mass range of 200-500 Da, owing to the substantial signal enhancement for breath metabolites, providing complementary and additional information to conventional SESI.

Background: Hypoxic conditions area key feature of allergic rhinitis (AR), however, the role of hypoxia in AR remains to be fully understood. The aim of this study was to survey the effect of hypoxia on the Th17 response in AR patients by investigating the action of hypoxia-influenced signaling pathways on Th17 differentiation., Methods: 23 AR patients and 15 healthy controls were recruited for this study. Under normoxia and hypoxic conditions, the expression of HIF-1α, AhR, CYP1A1 and CYP1B1 and the presence of Th17 cells in CD4 + T cells were measured. Furthermore, the amount of ARNT combined with either HIF-1α or AhR was determined after the exposure of 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl easter (ITE) with normoxia and hypoxia., Results: HIF-1α and AhR expression were higher in CD4 + T cells from AR patients than in those from healthy controls. In a hypoxic environment, the expression of HIF-1α was elevated in CD4 + T cells of both AR patients and healthy controls. Meanwhile, the suppressive effects of a non-toxic AhR ligand (ITE) on the Th17 response and its positive effects on IL-10 production were suppressed in the cells of AR patients and healthy controls under hypoxia. These effects were arisen from HIF-1α out-competing AhR for ARNT binding which limited the activity of the AhR pathway., Conclusions: The present results suggest that hypoxia is capable of promoting the Th17 response by reducing AhR activity via HIF-1α activity. Thus hypoxia may be intimately involved in the pathogenesis of AR., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study, a facile method based on molecularly imprinted polymers (MIPs) combined with internal extractive electrospray ionization tandem mass spectrometry (iEESI-MS/MS) was developed for the quantitative analysis of fluoroquinolones (FQs) in environmental water samples. FQ molecules in water samples were captured by the MIPs, which was retained on a 0.22 μm syringe filter. Then, an electrospray solution selected as the elution solution was employed to extract the FQs from the MIPs, getting an eluate of FQs for mass spectrometric interrogation. Under the optimized experimental conditions, low limits of detection (LODs, 0.015-0.026 μg L -1 ), with relative standard deviations (RSDs) less than 8.81% ( n = 6) were obtained. The present method also provides good recoveries (91.14-103.60%) with acceptable precision (RSDs < 6.18%) and have no serious matrix effects for environmental water samples. The experimental results demonstrated that MIPs-iEESI-MS/MS has advantages including easy use, high speed (less than 3 min per sample) and high sensitivity for the analysis of FQs in environmental water samples, showing potential application in environmental science and water safety control., 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., (This journal is © The Royal Society of Chemistry.)

The anaerobic fermentation of crop straw and animal wastes is increasingly used for the biogas and green energy generation, as well as reduction of the environmental pollution. The anaerobic cofermentation of corn stalks inoculated by cow dung was found to achieve higher biogas production and cellulose biodegradation. In this study, the effect of mixing corn stalks with cow dung at five different fermentation stages (0, 7, 15, 23, and 31 days of the total fermentation cycle of 60 days) on the further cofermentation process was explored, in order to optimize the corn straw utilization rate and biogas production capacity. In addition, the straw microstructure evolution was investigated by the SEM and XRD methods to identify the optimal conditions for the straw biodegradation process enhancement. The five test groups exhibited nearly identical total biogas productivity values but strongly differed by daily biogas yields (the maximal biogas generation rate being 524.3 ml/d). Based on the degradation characteristics of total solids (TS), volatile solids (VS), and lignocellulose, groups #1 and #3 (0 and 15 days) had the most significant degradation rates of VS (43.73%) and TS (42.07%), respectively, while the largest degradation rates of cellulose (62.70%) and hemicellulose (50.49%) were observed in group #4 (23 days) and group #1 (0 days), respectively. The SEM analysis revealed strong microstructural changes in corn stalks after fermentation manifested by multiple cracks and striations, while the XRD results proved the decrease in peak intensity of cellulose 〈002〉 crystal surface and the reduced crystallinity after cofermentation. The results of this study are assumed to be quite instrumental to the further optimization of the corn stalk anaerobic digestion by inoculation with digested manure for lignocellulose degradation enhancement and biogas productivity improvement.

Objectives: Allergic rhinitis (AR) and asthma often occur concomitantly and are the two most common inflammatory conditions of the airways in children. Large-scale studies investigating the comorbidity of asthma and AR in children are rare. So, we performed a meta-analysis to describe the comorbidity rate of asthma and AR in Chinese children., Methods: We retrieved related studies from Pubmed, Science, Springer, Elsevier, Embase, BMJ, and four Chinese biomedical databases, including Wanfang Data, VIP, CBM, and CNKI. From these individual studies, the comorbidity rate of asthma and AR in Chinese children was extracted and pooled to generate summary effect estimates in R version 3.2.3., Results: The meta-analysis included 25 cross-sectional studies. The results indicated that in China, the incidence of asthma in children with AR is 35.01% (95% CI: 32.32%-37.70%) and the incidence of AR in children with asthma is 54.93% (95% CI: 53.05%-56.80%)., Conclusions: The comorbidity of AR and asthma is high in Chinese children. Statistically, the prevalence of AR was higher in children with asthma, as opposed to the prevalence of asthma in children with AR. The comorbidity rate of AR and asthma signifies the importance of improving the recognition and treatment under both conditions by respiratory physicians and otolaryngologists., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: Ovarian cancer is one of the deadly causes of gynecological cancer related mortality worldwide. Despite initial responses to chemotherapy, the disease consistently relapses. Therefore there is an urgent need for identification of anticancer lead molecules for treatment and management of ovarian cancer. The present study evaluated the anticancer activity of cucurbitacin-A on ovarian SKVO3 cancer cells., Methods: The cell viability of SKVO3 cells was evaluated by MTT assay, while clonogenic assay was used to evaluate the effects on cancer cell colony formation. DAPI staining using fluorescence microscopy was used to evaluate the effects of the compound on apoptosis. Flow cytometry was used to study the effects on cell cycle phase distribution, reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) loss., Results: Cucurbitacin-A exhibited an IC50 of 40 μM against ovarian SKVO3 cancer cell line. It also caused DNA damage in SKVO3 cells and also prompted ROS mediated alterations in MMP. On the other hand, it triggered cell cycle arrest of SKVO3 at G2/M checkpoint. The activation of the PI3K/AKT/mTOR pathway plays a vital role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. The results showed that cucurbitacin-A considerably inhibited the expression levels of key proteins of PI3K/Akt/ mTOR signaling pathway., Conclusion: The study showed that cucurbitacin-A is a potent agent against ovarian cancer cells, can be considered for further in vivo research and can also be developed as a possible lead molecule.

Antibiotics contamination in food products is of increasing concern due to their potential threat on human health. Herein solid-phase extraction based on magnetic molecularly imprinted polymers coupled with internal extractive electrospray ionization mass spectrometry (MMIPs-SPE-iEESI-MS) was designed for the quantitative analysis of trace fluoroquinolones (FQs) in raw milk samples. FQs in the raw milk sample (2 mL) were selectively captured by the easily-lab-made magnetic molecularly imprinted polymers (MMIPs), and then directly eluted by 100 µL electrospraying solvent biased with +3.0 kV to produce protonated FQs ions for mass spectrometric characterization. Satisfactory analytical performance was obtained in the quantitative analysis of three kinds of FQs (i.e., norfloxacin, enoxacin, and fleroxacin). For all the samples tested, the established method showed a low limit of detection (LOD ≤ 0.03 µg L -1 ) and a high analysis speed (≤4 min per sample). The analytical performance for real sample analysis was validated by a nationally standardized protocol using LC-MS, resulting in acceptable relative error values from -5.8% to +6.9% for 6 tested samples. Our results demonstrate that MMIPs-SPE-iEESI-MS is a new strategy for the quantitative analysis of FQs in complex biological mixtures such as raw milk, showing promising applications in food safety control and biofluid sample analysis.

Objective: To determine the effect of Radix Angelicae Sinensis and Radix Hedysari (RAS-RH) on radiosensitivity of human liver cancer H22 cells to heavy ion ¹²C⁶⁺and its possible mechanism., Methods: The experiment involved a comparison of proliferation of H22 cells (detected by CCK-8 assay) between four groups: control,drug (RAS-RH),radiation,and combination (RAS-RH+radiation). H22 cells were treated with different doses of radiation alone or radiation followed by RAS-RH. The radiation enhancement effect of RAS-RH on H22 was detected by Colony forming assay. The effect of RAS-RH on the apoptosis of H22 cells was detected by flow cytometry. The influence of RAS-RH on the expression levels of related protein Survivin and Caspase-9 was investigated by Western blot., Results: RAS-RH inhibited the proliferation of H22 cells,with a time and dose dependency [inhibitory concentration 20% (IC 20 )=(117.60±2.15) mg/L]. The survival rate of H22 cells decreased significantly with the increase of heavy ion ¹²C⁶⁺. The two survival curves produced by the Graph Pad Prism 5.0 software were clearly separated. The combination group demonstrated smaller shoulder area at low dosage and lower survival rate of cells compared with radiation group,with a sensitization enhancement ratio ( SER ) of 1.39±0.07. The combination group (100 mg/L RAS-RH+2 Gy) had higher apoptosis rate and Caspase-9 protein expression level,and lower Survivin protein expression level,compared with other 3 groups ( P <0.01)., Conclusion: RAS-RH has radiation sensitization effect on human hepatocellular carcinoma H22 cells. The mechanism may be related to down-regulation of Survivin protein expression and up regulation of Caspase-9 protein expression.

Background/aims: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC., Methods: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting. The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation assay., Results: Cell growth was inhibited by bufalin in a time and dose-dependent manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA expression in H1975 cells, but strongly promoted Mcl-1 protein degradation. Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect NOXA protein levels, but downregulated the expression of p-GSK-3β. GSK-3 inhibitor and GSK-3β siRNA resulted in increased levels of Mcl-1 and reversed the bufalin-induced Mcl-1 degradation., Conclusion: Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3β activation was involved in bufalin-induced apoptosis., (© 2017 The Author(s)Published by S. Karger AG, Basel.)

This article proposes a methane production approach through sequenced anaerobic digestion of kitchen waste, determines the hydrolysis constants and reaction orders at both low total solid (TS) concentrations and high TS concentrations using the initial rate method, and examines the population growth model and first-order hydrolysis model. The findings indicate that the first-order hydrolysis model better reflects the kinetic process of gas production. During the experiment, all the influential factors of anaerobic fermentation retained their optimal values. The hydrolysis constants and reaction orders at low TS concentrations are then employed to demonstrate that the first-order gas production model can describe the kinetics of the gas production process. At low TS concentrations, the hydrolysis constants and reaction orders demonstrated opposite trends, with both stabilizing after 24 days at 0.99 and 1.1252, respectively. At high TS concentrations, the hydrolysis constants and the reaction orders stabilized at 0.98 (after 18 days) and 0.3507 (after 14 days), respectively. Given sufficient reaction time, the hydrolysis involved in anaerobic fermentation of kitchen waste can be regarded as a first-order reaction in terms of reaction kinetics. This study serves as a good reference for future studies regarding the kinetics of anaerobic digestion of kitchen waste.

Objective To observe the effect of Astragalus membranaceus (AM) on expression levels of helper T cell 17 (Th17) and its related factors in patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were sampled from 31 AR patients (recruited in the AR group) and 22 healthy subjects (recruited in the control group). PBMCs were isolated and in-vitro inter- vened by high and low dose AM injection (2 000 and 500 μg/mL) respectively for 24 h. mRNA expression levels of related orphan receptor C (RORC) were detected by real time quantitative PCR (RT-qPCR). Ex- pression levels of IL-17A and IL-22 in the supernatant were measured by ELISA. Expression levels of Th17 cells were measured by flow cytometry. Results Expression levels of Th17, RORC mRNA, IL- 17A, and IL-22 were higher in the AR group than in the control group (P <0. 01). mRNA expression levels of RORC, Th17 and its cytokines were not changed statistically in the AR group and the control group after PBMCs were intervened by low dose AM (P>0. 05). After intervened by high dose AM,mRNA expres- sion levels of RORC decreased statistically in the AR group and the control group (P <0. 05 for the AR group, P <0. 01 for the control group). Meanwhile,the expression levels of Th-17 and its cytokines de- creased in the AR group and the control group with statistical difference (P <0. 01). Conclusions Ex- cessive activation of Th17 is one of key factors-for AR. AM could further inhibit inflammation of AR and control the inflammation state of AR possibly through inhibiting the differentiation of Th17 cells and promo- ting the release of its cytokines.

Interleukin (IL)-12B is a key regulator in the protection against allergic reaction induced by various allergens in patients with allergic rhinitis (AR). This study was performed to investigate the associations between single nucleotide polymorphisms in the IL-12B gene and AR in a Chinese Han population. A total of 543 patients with AR and 600 healthy controls were genotyped for IL-12B/rs6887695, rs10045431, rs3212227, rs3212217, and rs2082412 using polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR direct sequencing. The expression of IL-12B mRNA in peripheral blood mononuclear cells (PBMCs) obtained from normal controls was detected by quantitative real-time PCR. Levels of interferon (IFN)-γ and IL-4 in culture supernatants were measured by enzyme-linked immunosorbent assay. The frequencies of the rs3212227 genotype with the CC and C alleles were higher in patients with AR (p c = 8.55 × 10(-4); p c = 4.20 × 10(-4), respectively) than in normal controls. After peptidoglycan stimulation in PBMCs, IL-12 mRNA expression was reduced in healthy carriers of the CC genotype of rs3212227. Additionally, decreased production of IFN-γ was observed in patients having the CC genotype as compared with that in patients having the AC and AA genotypes. In contrast, IL-4 expression was higher in patients with the CC genotype than in patients with the other two genotypes. The IL-12B gene was involved in mediating susceptibility to AR.

Allergic rhinitis (AR) is a global health problem. The effectiveness of currently available medications is limited and therefore investigation for more effective drugs is essential. The aim of the present study was to establish a model of AR in guinea pigs that can be utilized for the further investigation of new drugs. Guinea pigs were intranasally sensitized with 1 µg Staphylococcal enterotoxin B (SEB) dissolved in 40 µl saline once daily for 14 days. One week after the last sensitization, the same treatment was applied intranasally once every four days for a total of 30 times. In the treatment group, terfenadine was administered orally 70 min before the 4th, 14th and 24th challenge. Sneezing and nasal scratching were evaluated following each of the 30 challenges. The quantity of antigen-specific antibodies in the serum was measured. Between the 19th and 30th challenges, the guinea pigs in the model group produced significant biphasic elevations in sneezing number, with peaks 10 min-2 h and 4-8 h after the SEB challenges. In addition, the guinea pigs produced significantly more sneezing in the first peak during the 19th to 30th challenges than during the first to 18th challenges (P<0.01). Terfenadine significantly inhibited the early- and late-phase sneezing at all challenge times. The serum levels of SEB-specific immunoglobulin (Ig) E and IgG 1 were higher in the model group in comparison with those in the control group (P<0.01). This experiment demonstrated that SEB can induce typical AR with biphasic sneezing in guinea pigs. Histamine may play an important role in the early- and the late-phase sneezing in the model of AR. This model can be potentially used for the investigation of new drugs.