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Integrating Fenton chemistry and nanomedicine into cancer therapy has significantly promoted the development of chemodynamic therapy (CDT). Nanoscale polyoxometalates (POMs), with their reversible redox properties, exhibit promising potential in developing outstanding CDT drugs by exploring their Fenton-like catalytic reactivity in tumor environments. However, such research is still in its infancy due to the challenges of acquiring POMs that are both easily prepared and possess ideal therapeutic effects, physiological solubility, biocompatibility and safety. In this work, we report the synthesis of a new crystalline antimonotungstate {Dy 2 Sb 2 W 7 O 23 (OH)(DMF) 2 (SbW 9 O 33 ) 2 } (1, DMF=N, N-dimethylformamide) with gram-scale high yield via a facile "one-pot" solvothermal reaction. 1 exhibits not only a soluble and water-stable POM nanocluster, but also excellent catalytic activity for hydroxyl radical-generating Fenton-like reactions. Further biomedical studies reveal that 1 can trigger cell apoptosis and promote lipid peroxidation, exhibiting high cytotoxicity and selectivity towards B16-F10 mouse melanoma cancer cells with an IC 50 value of 4.75 μM. Especially, 1 can inhibit melanoma growth in vivo with favorable biosafety, achieving a 5.2-fold reduction in tumor volume and a weight loss of 76.0 % at the dose of 70 μg/kg. This research not only demonstrates the immense potential of antimonotungstates in CDT drug development for the first time but also provides new insights and directions for the development of novel anticancer drugs., (© 2024 Wiley-VCH GmbH.)

Background: Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer., Aim: To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis., Methods: One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis., Results: The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I ( P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference ( P < 0.05)., Conclusion: HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions., Competing Interests: Conflict-of-interest statement: The authors declared no conflict of interest existing in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Three-amino-loop-extension (TALE) family belongs to the homeobox gene superfamily and occurs widely in plants, playing a crucial role in regulating their growth and development. Currently, genome-wide analysis of the TALE family has been completed in many plants. However, the systematic identification and hormone response analysis of the TALE gene family in barley are still lacking. In this study, 21 TALE candidate genes were identified in barley, which can be divided into KNOX and BELL subfamilies. Barley TALE members in the same subfamily of the phylogenetic tree have analogically conserved motifs and gene structures, and segmental duplications are largely responsible for the expansion of the HvTALE family. Analysis of TALE orthologous and homologous gene pairs indicated that the HvTALE family has mainly undergone purifying selective pressure. Through spatial structure simulation, HvKNOX5-HvKNOX6 and HvKNOX5-HvBELL11 complexes are all formed through hydrogen bonding sites on both the KNOX2 and homeodomain (HD) domains of HvKNOX5, which may be essential for protein interactions among the HvTALE family members. Expression pattern analyses reveal the potential involvement of most HvTALE genes in responses to exogenous hormones. These results will lay the foundation for regulation and function analyses of the barley TALE gene family in plant growth and development by hormone regulation., 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 Liao, Huang, Xiong, Duo, Ma, Du and Duan.)

Background: Early and appropriate antibiotic treatment improves the clinical outcome of patients with sepsis. There is an urgent need for rapid identification (ID) and antimicrobial susceptibility testing (AST) of bacteria that cause bloodstream infection (BSI). Rapid ID and AST can be achieved by short-term incubation on solid medium of positive blood cultures using MALDI-TOF mass spectrometry (MS) and the BD M50 system. The purpose of this study is to evaluate the performance of rapid method compared to traditional method., Methods: A total of 124 mono-microbial samples were collected. Positive blood culture samples were short-term incubated on blood agar plates and chocolate agar plates for 5 ∼ 7 h, and the rapid ID and AST were achieved through Zybio EXS2000 MS and BD M50 System, respectively., Results: Compared with the traditional 24 h culture for ID, this rapid method can shorten the cultivation time to 5 ∼ 7 h. Accurate organism ID was achieved in 90.6% of Gram-positive bacteria (GP), 98.5% of Gram-negative bacteria (GN), and 100% of fungi. The AST resulted in the 98.5% essential agreement (EA) and 97.1% category agreements (CA) in NMIC-413, 99.4% EA and 98.9% CA in PMIC-92, 100% both EA and CA in SMIC-2. Besides, this method can be used for 67.2% (264/393) of culture bottles during routine work. The mean turn-around time (TAT) for obtaining final results by conventional method is approximately 72.6 ± 10.5 h, which is nearly 24 h longer than the rapid method., Conclusions: The newly described method is expected to provide faster and reliable ID and AST results, making it an important tool for rapid management of blood cultures (BCs). In addition, this rapid method can be used to process most positive blood cultures, enabling patients to receive rapid and effective treatment., (© 2024. The Author(s).)

Introduction: Vascular neointimal hyperplasia, a pathological process observed in cardiovascular diseases such as atherosclerosis and pulmonary hypertension, involves the abundant presence of vascular smooth muscle cells (VSMCs). The proliferation, migration, and autophagy of VSMCs are associated with the development of neointimal lesions. Circular RNAs (circRNAs) play critical roles in regulating VSMC proliferation and migration, thereby participating in neointimal hyperplasia. However, the regulatory roles of circRNAs in VSMC autophagy remain unclear., Objectives: We aimed to identify circRNAs that are involved in VSMC autophagy-mediated neointimal hyperplasia, as well as elucidate the underlying mechanisms., Methods: Dual-luciferase reporter gene assay was performed to validate two competing endogenous RNA axes, hsa&#95;circ&#95;0001402/miR-183-5p/FKBP prolyl isomerase like (FKBPL) and hsa&#95;circ&#95;0001402/miR-183-5p/beclin 1 (BECN1). Cell proliferation and migration analyses were employed to investigate the effects of hsa&#95;circ&#95;0001402, miR-183-5p, or FKBPL on VSMC proliferation and migration. Cell autophagy analysis was conducted to reveal the role of hsa&#95;circ&#95;0001402 or miR-183-5p on VSMC autophagy. The role of hsa&#95;circ&#95;0001402 or miR-183-5p on neointimal hyperplasia was evaluated using a mouse model of common carotid artery ligation., Results: Hsa&#95;circ&#95;0001402 acted as a sponge for miR-183-5p, leading to the suppression of miR-183-5p expression. Through direct interaction with the coding sequence (CDS) of FKBPL, miR-183-5p promoted VSMC proliferation and migration by decreasing FKBPL levels. Besides, miR-183-5p reduced BECN1 levels by targeting the 3'-untranslated region (UTR) of BECN1, thus inhibiting VSMC autophagy. By acting as a miR-183-5p sponge, overexpression of hsa&#95;circ&#95;0001402 increased FKBPL levels to inhibit VSMC proliferation and migration, while simultaneously elevating BECN1 levels to activate VSMC autophagy, thereby alleviating neointimal hyperplasia., Conclusion: Hsa&#95;circ&#95;0001402, acting as a miR-183-5p sponge, increases FKBPL levels to inhibit VSMC proliferation and migration, while enhancing BECN1 levels to activate VSMC autophagy, thus alleviating neointimal hyperplasia. The hsa&#95;circ&#95;0001402/miR-183-5p/FKBPL axis and hsa&#95;circ&#95;0001402/miR-183-5p/BECN1 axis may offer potential therapeutic targets for neointimal hyperplasia., 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. Production and hosting by Elsevier B.V.)

Background: Porcine circovirus type 2 (PCV2) infection is ubiquitous around the world. Diagnosis of the porcine circovirus-associated disease requires clinic-pathological elements together with the quantification of viral loads. Furthermore, given pig farms in regions lacking access to sufficient laboratory equipment, developing diagnostic devices with high accuracy, accessibility, and affordability is a necessity., Objectives: This study aims to investigate two newly developed diagnostic tools that may satisfy these criteria., Methods: We collected 250 specimens, including 170 PCV2-positive and 80 PCV2-negative samples. The standard diagnosis and cycle threshold (Ct) values were determined by quantitative polymerase chain reaction (qPCR). Then, two point-of-care (POC) diagnostic platforms, convective polymerase chain reaction (cPCR, qualitative assay: positive or negative results are shown) and EZtargex (quantitative assay: Ct values are shown), were examined and analyzed., Results: The sensitivity and specificity of cPCR were 88.23% and 100%, respectively; the sensitivity and specificity of EZtargex were 87.65% and 100%, respectively. These assays also showed excellent concordance compared with the qPCR assay (κ = 0.828 for cPCR and κ = 0.820 for EZtargex). The statistical analysis showed a great diagnostic power of the EZtargex assay to discriminate between samples with different levels of positivity., Conclusions: The two point-of-care diagnostic platforms are accurate, rapid, convenient and require little training for PCV2 diagnosis. These POC platforms can discriminate viral loads to predict the clinical status of the animals. The current study provided evidence that these diagnostics were applicable with high sensitivity and specificity in the diagnosis of PCV2 infection in the field., Competing Interests: Schweitzer Biotech Company (SBC) Ltd. is the sponsor of the project. Hsieh WJ, Lin CC, and Ting JM. are employees of the SBC. However, the authors declare that the research was conducted with integrity, following all ethical guidelines. All other authors declare no competing interests., (© 2024 The Korean Society of Veterinary Science.)

Background: Intestinal obstruction is a common occurrence in clinical practice. However, the occurrence of herpes zoster complicated by intestinal obstruction after abdominal surgery is exceedingly rare. In the diagnostic and treatment process, clinicians consider it crucial to identify the primary causes of its occurrence to ensure effective treatment and avoiding misdiagnosis., Case Summary: Herein, we present the case of a 40-year-old female patient with intestinal obstruction who underwent laparoscopic appendectomy and developed herpes zoster after surgery. Combining the patient's clinical manifestations and relevant laboratory tests, it was suggested that the varicella zoster virus reactivated during the latent period after abdominal surgery, causing herpes zoster. Subsequently, the herpes virus invaded the visceral nerve fibers, causing gastrointestinal dysfunction and loss of intestinal peristalsis, which eventually led to intestinal obstruction. The patient was successfully treated through conservative treatment and antiviral therapy and subsequently discharged from the hospital., Conclusion: Pseudo-intestinal obstruction secondary to herpes zoster infection is difficult to distinguish from mechanical intestinal obstruction owing to various causes. In cases of inexplicable intestinal obstructions, considering the possibility of a viral infection is essential to minimize misdiagnosis and missed diagnoses., Competing Interests: Conflict-of-interest statement: The authors have no conflicting interests to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

To elucidate the agronomic and environmental effects of single basal application of controlled-release blended fertilizer in summer maize, and optimize management measures of nitrogen fertilizer for grain production in North China Plain, we conducted a field experiment in Dezhou Modern Agricultural Science and Technology Park in Shandong Province. There were four treatments: CK (no N fertilizer), FFP (farmer's fertilizing practice, 240 kg N·hm -2 ), OPT (optimized nitrogen application, 210 kg N·hm -2 ), and CRBF (controlled-release blended fertilizer with single basal application, 210 kg N·hm -2 ). We compared maize yield and reactive nitrogen loss, and quantitatively evaluated the carbon and nitrogen footprints by using life cycle assessment method. The results showed that nitrogen application significantly increased summer maize yield. Compared with FFP, OPT and CRBF increased summer corn yield by 0.7% and 2.9%, respectively, decreased the total amount of ammonia volatilization, N 2 O emission, and nitrate leaching by 13.0% and 72.7%, 13.3% and 37.5%, 20.5% and 23.5% respectively. Compared with CK, nitrogen application significantly increased the global warming potential (GWP) of summer maize production. Compared with FFP, GWP and greenhouse gas emission intensity of OPT decreased by 3.8% and 4.2%, while the reduction of CRBF were 8.7% and 12.0%, respectively. Compared with CK, nitrogen application significantly increased the carbon and nitrogen footprint of summer maize production. The production and transportation of nitrogen fertilizer and soil greenhouse gas emission were the main contributing factors of the carbon footprint, with contribution rates of 54%-60% and 24%-31%, respectively. Nitrate leaching was the main contributing factor of nitrogen footprint, with contribution rate of 57%-94%. Compared with FFP, the carbon and nitrogen footprints of OPT and CRBF were reduced by 11.0% and 16.5%, 19.6% and 28.4%, respectively. Considering the yield, reactive nitrogen loss and carbon and nitrogen footprint, we recommended the single basal application of controlled-release blended fertilizer as an effective nitrogen fertilizer management measure to promote grain clean production in the North China Plain.

Objective: Murine CD19 chimeric antigen receptor T-cell (CAR-T) products have been approved for the treatment of refractory/relapsed (R/R) B-cell acute lymphocytic leukemia (B-ALL) ; moreover, humanized products are also undergoing clinical trials. This study aimed to explore the differences in safety and short- and long-term follow-up efficacy between humanized and murine CD19 CAR-T-cells for treating relapsed and refractory B-ALL. Methods: Clinical data of 80 patients with R/R B-ALL treated with CD19-targeted CAR-T-cells at the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between May 2016 and March 2023 were analyzed, which included 31 patients with murine CAR-T and 49 with humanized products. Results: The proportion of patients with cytokine-release syndrome (CRS) in the murine and humanized groups was 63.1% and 65.3%, respectively. Moreover, a higher proportion of patients suffered from severe CRS in the murine group than in the humanized CAR-T group (19.4% vs 8.2%, P =0.174). Furthermore, one patient per group died of grade 5 CRS. The incidence of grade 1-2 immune effector cell-associated neurotoxicity syndrome (ICANS) was 12.9% and 6.1%, respectively; severe ICANS were not observed. Among patients receiving murine CAR-T-cells, an overall response (OR) was observed in 74.2%. Conversely, the OR rate of patients receiving humanized CAR-T-cells was 87.8%. During the median follow-up time of 10.5 months, the median recurrence-free survival (RFS) of patients with murine CAR-T-cells was 12 months, which was as long as that of patients with humanized CAR-T-cells. The median overall survival (OS) were not reached in both groups. Of the 45 patients with a bone marrow burden over 20% at baseline, humanized CAR-T therapy was associated with a significantly improved RFS (43.25% vs 33.33%, P =0.027). Bridging transplantation was an independent factor in prolonging OS ( χ (2)=8.017, P =0.005) and PFS ( χ (2)=6.584, P =0.010). Common risk factors, such as age, high proportion of bone marrow blasts, and BCR-ABL fusion gene expression, had no significant effect on patients' long-term follow-up outcomes. Three patients reached complete remission after reinfusion of humanized CAR-T-cells. However, one patient relapsed one month after his second infusion of murine CAR-T-cells. Conclusions: The results indicate that humanized CAR-T therapy showed durable efficacy in patients with a higher tumor burden in the bone marrow without any influence on safety. Moreover, it could overcome immunogenicity-induced CAR-T resistance, providing treatment options for patients who were not treated successfully with CAR-T therapies.

Purpose: This study aimed to investigate whether RNA m6A participated in the differentiation and proliferation of dental pulp stem cells and improved peripheral nerve regeneration using a rat model of crushed mental nerve injury., Materials and Methods: The components of RNA m6A were analyzed through qRT-PCR, while cell proliferation of different groups, including over-expression METTL3 (OE-METTL3) hDPSCs group, knock-down METTL3 (KD-METTL3) hDPSCs group and hDPSCs group in vitro, was clarified by MTT assay. Five groups were designed, namely, Control group, Sham group, hDPSCs group, OE-METTL3 group and KD-METTL3 group. After crushed right mental nerve injury, cells of different groups were transplanted into the lesion area (6 ul in volume). At one, two and three weeks later, histomorphometric analysis and sensory test were conducted in vivo., Results: qRT-PCR results showed that "METTL3" was participated in the differentiation of dental pulp stem cells. There were differences (P < 0.05) between OE-METTL3 group and control group in MTT results in the third, fourth and sixth days. Moreover, the sensory test revealed significant differences (P < 0.05) in difference score and gap score between OE-METTL3 group and KD-METTL3 group in the first and third weeks. The axon counts and retrograde labeled neurons significantly increased in OE-METTL3 group compared with KD-METTL3 group., Conclusions: These results demonstrated that RNA m6A participated in the differentiation and proliferation of dental pulp stem cells, and that OE-METTL3 group exhibited the greater ability to improve peripheral nerve regeneration than KD-METTL3 group and hDPSCs group., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the vaginal microecological status of vaginitis population and non-vaginitis population of gynecological female outpatients. Methods: A total of 30 265 women who visited the gynecological outpatient clinic of Beijing Obstetrics and Gynecology Hospital from December 2018 to December 2020 completed vaginal microecological examination. After removing the follow-up patients, 23 181 women were divided into group with symptoms and signs of vaginitis (6 697 cases) and group without symptoms and signs of vaginitis (16 484 cases), according to whether the women with symptoms and signs of vaginitis or not. And the vaginal microecological status of the two groups was compared and analyzed. Results: (1) The total detection rate of vaginitis in the initial women was 34.87% (8 083/23 181), of which 46.10% (3 087/6 697) in group with symptoms and signs of vaginitis and 30.31% (4 996/16 484) in group without symptoms and signs of vaginitis, nearly 1/3 of the gynecological outpatients without signs and symptoms of vaginitis had vaginitis. (2) Among the types of simple vaginitis, vulvovaginal candidiasis (VVC) was the most frequent in group with symptoms and signs of vaginitis (16.01%, 1 072/6 697), followed by aerobic vaginitis (AV; 12.83%, 859/6 697), with significant differences compared with group without symptoms and signs of vaginitis (all P <0.001). There were no statistical differences between the two groups of bacterial vaginosis (BV) and trichomonal vaginitis (TV), indicating that BV and TV were more likely to be neglected (all P >0.05). (3) The proportion of various combinations of vaginitis among 2 632 cases of mixed vaginitis were, in descending order: BV+AV, VVC+AV, BV+AV+VVC, AV+TV, AV+TV+BV, BV+VVC. (4) Microecological analysis of 15 098 cases diagnosed with non-vaginitis had normal flora (including those with normal flora and those with normal flora but decreased function) in 14 013 cases (92.81%, 14 013/15 098), abnormal flora in 429 cases (2.84%, 429/15 098) and the BV intermediate in 656 cases (4.34%, 656/15 098); this indicated that the vast majority of the microecological tests were normal in the vaginal microbiota of those without vaginitis. Conclusions: Microecological examination could diagnose multiple pathogenic infections at once, and is especially important as a guide for the definitive diagnosis of mixed vaginitis and vaginitis with atypical clinical symptoms. Vaginal infections such as BV and TV that are easily overlooked should be concerned.

Many human activities require high cognitive performance over long periods, while impairments induced by sleep deprivation influence various aspects of cognitive abilities, including working memory (WM), attention, and processing speed. Based on previous research, vagal nerve stimulation can modulate cognitive abilities, attention, and arousal. Two experiments were conducted to assess the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) to relieve the deleterious effects of sleep deprivation. In the first experiment, 35 participants completed N-back tasks at 8:00 a.m. for two consecutive days in a within-subject study. Then, the participants received either taVNS or earlobe stimulation (active control) intervention in two sessions at random orders after 24 h of sustained wakefulness. Then, they completed the N-back tasks again. In the second experiment, 30 participants completed the psychomotor vigilance task (PVT), and 32 completed the N-back tasks at 8:00 a.m. on the first and second days. Then, they received either taVNS or earlobe stimulation at random orders and finished the N-back and PVT tasks immediately after one hour. In Experiment 1, taVNS could significantly improve the accuracy rate of participants in spatial 3-back tasks compared to active control, which was consistent with experiment 2. However, taVNS did not specifically enhance PVT performance. Therefore, taVNS could be a powerful intervention for acute sleep deprivation as it can improve performance on high cognitive load tasks and is easy to administer., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest: None.

Background: Visceral adiposity plays a key role in the development of insulin resistance (IR), so surrogate index that can indicate visceral obesity may have higher predictive value for IR. This study aimed to establish and validate a new predictive model including indicator of visceral obesity for IR., Methods: The study population consisted of two cohorts. The derivation cohort was a group of 667 patients with newly diagnosed type 2 diabetes and the population undergoing a routine health checkup was the validation cohort. The predictive model was established by the logistic regression analysis. Its value for predicting IR was compared with other surrogate indices by the receiver operating characteristic curve., Results: The odds ratio (OR) of age, visceral fat area (VFA), triglyceride (TG), fasting plasma glucose (FPG), and alanine aminotransferase (ALT) for IR was 1.028 (95% CI, 1.008-1.048) ( P < 0.01), 1.016 (95% CI, 1.009-1.023) ( P < 0.001), 1.184 (95% CI, 1.005-1.396) ( P < 0.05), 1.334 (95% CI, 1.225-1.451) ( P < 0.001), and 1.021 (95% CI, 1.001-1.040) ( P < 0.05). The formula of the predictive model was (0.0293 × age + 1.4892 × Ln VFA + 0.4966 × Ln TG + 2.784 × Ln FPG + 0.6906 × Ln ALT)/2. The area under the curve was the largest among all the previously reported predictors., Conclusions: This study established and validated a predicting model for IR and confirmed its predictive value in comparison with other surrogate indicators, which will offer a simple and effective tool to measure IR in future large population studies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Shi Zhang et al.)

This study aimed to assess how several sweeteners (white sugar, Siraitia grosvenorii fruit, mogrosides, and stevia glycoside) affected the flavor, fatty acid composition, and quality of braised pork. The findings indicated that braised meat prepared with sweeteners differed from typical braised pork. When simmered for 60 min, the typical braised pork with white granulated sugar exhibited a significant cooking loss (CL) and little water content. Significantly more than in the group containing Siraitia grosvenorii , mogroside, and stevia glycoside, the Thiobarbituric acid (TBARS) value increased by 14.39% (P < 0.05). The sample in the group that included mogroside had a low CL rate. After 40 min of stewing, the lean pork has the highest L* value, but the 60-min stew sample is nicely colored and stretchy. Mogroside can prevent protein, and lipid oxidation, is thermally stable and reduces CL during stewing. Additionally, Siraitia grosvenorii and stevia glycosides help prevent oxidation from intensifying during stewing. When Siraitia grosvenorii is added, lipid oxidation is significantly inhibited, and stevia glycosides are more beneficial for enhancing meat color. With an increase in heating time, the fatty acids in braised pork reduced; the unsaturated fatty acid (UFA) of the Siraitia grosvenorii fruit (SF) and mg group also fell somewhat, and the UFA: SFA ratio was higher than that of the white sugar (WS) group. The SFA content of the braised meat in the stevia glycoside group was higher than that of the WS group. In all, 75 volatile flavor elements in braised pork were discovered by Gas chromatography-ion mobility spectrometry (GC-IMS). The sweetener increased alcohols, esters, and acids in the braised pork. As stewing time increased, ketones decreased, but aldehydes and esters increased. The pork formed antioxidant peptides with great nutritional value after cooking. Braised pork with mogroside and stevia glycoside additions primarily have some protein color protection and antioxidant effects. This study may offer fresh perspectives on applying natural sweeteners and enhancing braised pork's flavor., 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 He, Zhang, Yang, Zhang, Cui, Du, Zhao and Sun.)

Cystic renal masses are often encountered during abdominal imaging. Although most of them are benign simple cysts, some cystic masses have malignant characteristics. The Bosniak classification system provides a useful way to classify cystic masses. The Bosniak classification is based on the results of a well-established computed tomography protocol. Over the past 30 years, the classification system has been refined and improved. This paper reviews the literature on this topic and compares the advantages and disadvantages of different screening and classification methods. Patients will benefit from multimodal diagnosis for lesions that are difficult to classify after a single examination., (© 2021 American Institute of Ultrasound in Medicine.)

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cardiac autonomic function. However, the response rate of the traditional tonic paradigm is low, and the results remain inconsistent. A recent pilot study presented a novel burst paradigm to activate the cardiac parasympathetic system, which might offer a new approach to treat cardiac autonomic function. The present study reassessed the effect of burst taVNS on modulating heart rate variability and explored the difference between burst and traditional tonic paradigms., Materials and Methods: Forty-two young adults were recruited for this study. Each participant underwent three types of taVNS with sham (30 sec of stimulation), tonic (25 Hz, 500 μsec), and burst (five pulses at 500 Hz every 200 msec) paradigms, respectively, with simultaneous electrocardiogram recording. One-way analysis of variance, multivariate analysis of variance, and linear regression were used for analysis. Multiple testing was performed using Bonferroni correction., Results: Both burst and tonic paradigms induced a significant decrease in heart rate, which continued until poststimulation, and increased cardiac parasympathetic activity. Moreover, two parasympathetic system indicators showed significant increase only in burst taVNS. The response rates during burst (35.7%) and tonic (38.1%) stimulations were both higher than that during sham stimulation (11.9%). The response to taVNS showed parameter specificity with few nonresponders to the tonic paradigm responding to the burst paradigm. The overall response rate increased from 38.1% in tonic taVNS to 54.8% in taVNS using both burst and tonic paradigms. For both burst and tonic responders, baseline cardiac parasympathetic activity was found to be significantly negatively correlated with changes during stimulation., Conclusion: The burst parameter could be used as an alternative strategy for regulating cardiac parasympathetic function by taVNS, which has the potential to be used as a complementary paradigm to traditional tonic taVNS for promoting clinical treatment efficacy., (Copyright © 2022. Published by Elsevier Inc.)

In the summer of 2019, field measurements of ozone (O 3 ) and its precursors[volatile organic compounds (VOCs) and nitrogen oxides (NO x )] were carried out at an urban site in Ji'nan. We found that the daily maximum 8-hour averages φ (O 3 ) were (103.0±14.5)×10 -9 . The average φ (NO x ) and φ (VOCs), which are ozone precursors, were (16.7±11.3)×10 -9 and (22.4±9.4)×10 -9 , respectively. The ·OH reactivity of VOCs was determined (9.6±3.8) s -1 . Ji'nan suffered from serious O 3 pollution. An observation-constrained chemical box model was deployed to evaluate in situ photochemical O 3 production, which indicated that chemical reactions made positive contributions to O 3 production rates between 07:00 and 19:00 LT, with the average hourly O 3 production rate of 35.6×10 -9 h -1 . To evaluate the effectiveness of various ozone precursor control strategies in reducing ozone pollution, we combined the observation-based model (OBM) with the relative incremental reactivity (RIR) method. The key indicators that affect the local ozone production rate were identified. Ji'nan was under VOC-limited conditions and the key VOC precursors were alkenes. The O 3 formation mechanism changed from the VOC-limited regime in the morning to the transitional regime in the afternoon. Correspondingly, the simulated local O 3 production rate was increased from 18.3×10 -9 h -1 to 29.6×10 -9 h -1 . To further explore the role of anthropogenic emissions in ozone pollution, we used the positive matrix factorization (PMF) model to identify the major sources contributing to VOCs. The major sources in Ji'nan were vehicular exhaust and gasoline evaporation, accounting for more than 50% of the observed VOCs. Therefore, constraints on vehicular emissions is the most effective strategy to control O 3 pollution in Ji'nan.

Objective: The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy, which is a strong predictor of mortality in patients with severe sepsis. Simvastatin plays an important role in reducing inflammation. In addition, the gut has long been hypothesized to be the "motor" of critical illness, driving or aggravating sepsis by the increased intestinal permeability and bacterial translocation. Whether simvastatin plays a role in severe endotoxin-induced coagulopathy through the gut is unclear., Methods: In this study, mice were administered 20 mg/kg simvastatin by gavage for 2 weeks and then intraperitoneally injected with 50 mg/kg endotoxin. Twelve h later, cytokine release, coagulation dysfunction, organ damage, and survival were assessed. Besides, the intestinal barrier, permeability, bacteria abundance, and translocation were evaluated., Results: We found that the severity of endotoxin-induced coagulopathy was significantly improved in simvastatin-pretreated mice, who showed attenuated depletion of coagulation factors and platelets, decreased plasminogen activator inhibitor-1 (PAI-1) expression, reduced organ fibrin deposition, and improved survival time. Also, simvastatin reduced epithelial apoptosis and improved intestinal barrier function by upregulating antimicrobial peptides, lysozyme, and mucins. Simvastatin increased Lactobacillales counts, while the lipopolysaccharide group showed increased Desulfovibrio and Mucispirillum, which can produce harmful toxins. Finally, the decreased intestinal permeability in the simvastatin group caused reduced bacterial translocation in the organs and blood, both in terms of quantity and species., Conclusion: Simvastatin improves the prognosis of severe endotoxemia, and the intestinal microenvironment participates in this process., (© 2022. The Author(s).)

Objective: To explore the incidence, clinical and microbiological characteristics and risk factors of infection in patients with acute lymphoblastic (ALL) , non-Hodgkin lymphoma (NHL) , and multiple myeloma (MM) within 28 days after CAR-T cell infusion. It provides data support for early identification of infection and the rational use of antibacterial drugs in these patients. Methods: We retrospectively analyzed the baseline data of 170 patients with ALL, NHL and MM who received chimeric antigen receptor-modified T (CAR-T) -cell treatment in the Department of Hematology of Wuhan Union Hospital from January 2016 to December 2020, and the clinical characteristics of infection within 28 days after infusion, including 72 patients with ALL, 56 patients with NHL, and 42 patients with MM; we used Poisson regression and Cox proportional hazard regression models to assess high-risk factors for infection before and after infusion, respectively. Results: Among 170 patients, 119 infections occurred in 99 patients within 28 days, with a cumulative infection rate of 58.2%. Seventy-eight patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%. The infection density was 2.01, and the median time for the first infection was about 12 days after infusion. The adjusted baseline characteristic model showed that ALL patients, previous 30 days of infection history, refractory disease, absolute neutrophil count (ANC) <0.5×10(9)/L before infusion and ≥4 prior antitumor treatment regimens had a higher infection density within 28 days; grade 3 or 4 CRS was the only high-risk factor related to infection after infusion in the multivariate analysis. Conclusion: Infection is a common complication of CAR-T cell therapy in patients with hematologic malignancy. Bacterial infections occur in most patients regardless of the type of disease. ALL patients, previous 30 days of infection history, refractory disease, ANC<0.5×10(9)/L before infusion and grade 3 or 4 CRS are risk factors for infection. Chinese Clinical Trial Register:: ChiCTR-OIC-17011180, ChiCTR1800018143.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of many vascular remodeling diseases. Because long non-coding RNAs (lncRNAs) play a critical role in cardiovascular diseases, we analyzed the key lncRNAs that regulate VSMC proliferation. Microarray analysis identified 2,643 differentially expressed lncRNAs (DELs) and 3,720 differentially expressed coding genes (DEGs) between fetal bovine serum (FBS) starvation-induced quiescent human aortic smooth muscle cells (HASMCs) and platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferative HASMCs. Gene Ontology and pathway analyses of the identified DEGs and DELs demonstrated that many lncRNAs were enriched in pathways related to cell proliferation. One of the upregulated lncRNAs in proliferative HASMC was HIF1A anti-sense RNA 2 (HIF1A-AS2). HIF1A-AS2 suppression decreased HASMC proliferation via the miR-30e-5p/CCND2 mRNA axis. We have thus identified key DELs and DEGs involved in the regulation of PDGF-BB induced HASMC proliferation. Moreover, HIF1A-AS2 promotes HASMC proliferation, suggesting its potential involvement in VSMC proliferative vascular diseases., 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 Lin, Chen, Gong, Xu, Du, Wang, Yang, Wang, Liu, Kong, Li, Liu, Li, Dong and Sun.)

White light interferometry is a well-established surface recovery technique. In this paper, a white light signal processing algorithm based on phase error compensation using spectrum selection is proposed. The derived nonlinear phase distribution from the correlogram is modeled as the combination of random errors and systemic deviations. By developing a new, to the best of our knowledge, recovery algorithm, the phase noise can be separated from the linear map and significantly attenuated. Based on the proposed algorithm, the spectrum features of white light LEDs and halogen lamps are investigated in detail. The inner products defined by three selected points are employed to generate a coefficient to evaluate the linearity of an unwrapped phase map within a certain spectrum region. The optimal spectrum range corresponding to the best measurement performance can then be located where the coefficient approximates 1 and the spectrum energy stays relatively high. The simulations are carried out under different levels of SNR and scan step noises, which show that the new method can effectively reduce additional disturbance from the recovered topography. In experiments, the system with the proposed method is first calibrated by a step height standard (VLSI, 182.7±2.0 n m ) with the repeatability of 0.44 nm. A silicon wafer and three roughness standards are also tested to further verify the robustness of the new method.

Kinesin family member 18A (KIF18A) is significantly overexpressed and is related to the poor prognosis of human cancers. However, the function of KIF18A in esophageal cancer (EC) is still unclear. Human EC cell lines were used in this study. KIF18A expression in human tissues was assessed using Gene Expression Profiling Interactive Analysis 2.0 (GEPIA2). The expressions of KIF18A or IGF2BP3 in EC cells were detected using qRT-PCR or WB. Cells were transfected using si-KIF18A, si-IGF2BP3, and plasmid IGF2BP3. The abilities of proliferation, migration, and invasion were detected by EdU, wound-healing, and transwell assay. The interaction between KIF18A and IGF2BP3 was predicted by starBase v3.0 and studied by RIP and RNA stability assay. Colony formation assay was used to reflect the changes of radiosensitivity in EC cells. KIF18A was upregulated in EC, and KIF18A knockdown inhibited EC cell proliferation, migration, invasion, and radioresistance. The prediction in starBase and RIP assay results showed that KIF18A mRNA could bind to IGF2BP3 protein in EC cells. RNA stability assay was performed to confirm that IGF2BP3 affects mRNA stability of KIF18A. Further studies also showed that IGF2BP3 could positively regulate KIF18A on proliferation, migration, invasion, and radioresistance. Our findings first revealed an oncogenic effect of KIF18A in human EC progression. KIF18A expression was associated with radioresistance of EC cells. The binding relationship between KIF18A and IGF2BP3 might influence the mRNA stability of KIF18A in EC cell lines., 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 © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective Asymptomatic carotid stenosis (ACS) is closely associated to the incidence of severe cerebrovascular diseases. Early identifying the individuals with ACS and its associated risk factors could be beneficial for primary prevention of stroke. This study aimed to investigate a machine-learning algorithm for the detection of ACS among high-risk population of stroke based on the associated risk factors.Methods A novel model of machine learning was utilized to screen the associated predictors of ACS based on 30 potential risk factors. The algorithm of this model adopted a random forest pattern based on the training data and then was verified using the testing data. All of the original data were retrieved from the China National Stroke Screening and Prevention Project (CNSSPP), including demographic, clinical and laboratory characteristics. The individuals with high risk of stroke were enrolled and randomly divided into a training group and a testing group at a ratio of 4:1. The identification of carotid stenosis by carotid artery duplex scans was set as the golden standard. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was used to evaluate the efficacy of the model in detecting ACS.Results Of 2841 high risk individual of stroke enrolled, 326 (11.6%) were diagnosed as ACS by ultrasonography. The top five risk factors contributing to ACS in this model were identified as family history of dyslipidemia, high level of low-density lipoprotein cholesterol (LDL-c), low level of high-density lipoprotein cholesterol (HDL-c), aging, and low body mass index (BMI). Their weights were 11.8%, 7.6%, 7.1%, 6.1%, and 6.1%, respectively. The total weight of the top 15 risk factors was 85.5%. The AUC values of the model for detecting ACS with training dataset and testing dataset were 0.927 and 0.888, respectively.Conclusions This study demonstrated that the machine-learning algorithm could be used to identify the risk factors for ACS among high risk population of stroke. Family history of dyslipidemia may be the most important risk factor for ACS. This model could be a suitable tool to optimize the clinical approach for the primary prevention of stroke.

Objective: The aim of the present study was to use pharmacokinetic quantitative parameters with histogram and texture features on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between the luminal A and luminal B molecular subtypes of breast cancer., Methods: We retrospectively reviewed the data of 94 patients with histopathologically proven breast cancer. The pharmacokinetic quantitative parameters (K trans , K ep , and V e ) with their corresponding histogram and texture features based on preoperative DCE-MRI were obtained. The parameters were compared using the Mann-Whitney U-test between the luminal A and luminal B groups, the human epidermal growth factor receptor-2 (HER2)-positive luminal B and HER2-negative luminal B groups, and the lymph node metastasis (LNM)-positive and LNM-negative groups. Receiver operating characteristic curves were generated for parameters that presented significant between-group differences., Results: The maximum values of K trans , K ep , and V e , and the mean and 90th percentile values of V e were significantly higher in the luminal B group than in the luminal A group. Among the texture features, only skewness of K trans significantly differed between the luminal A and B groups. All histogram features of K trans were higher in the HER2-positive luminal B group than in the HER2-negative luminal B group. However, no parameter differed between the LNM-positive and LNM-negative groups., Conclusion: Pharmacokinetic quantitative parameters with histogram and texture features obtained from DCE-MRI are associated with the molecular subtypes of breast cancer, and may serve as potential imaging biomarkers to differentiate between the luminal A and luminal B molecular subtypes., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Epigenetic modifications play critical roles in modulating gene expression, yet their roles in regulatory networks in human cell lines remain poorly characterized. We integrated multiomics data to construct directed regulatory networks with nodes and edges labeled with chromatin states in human cell lines. We observed extensive association of diverse chromatin states and network motifs. The gene expression analysis showed that diverse chromatin states of coherent type-1 feedforward loop (C1-FFL) and incoherent type-1 feedforward loops (I1-FFL) contributed to the dynamic expression patterns of targets. Notably, diverse chromatin state compositions could help C1- or I1-FFL to control a large number of distinct biological functions in human cell lines, such as four different types of chromatin state compositions cooperating with K562-associated C1-FFLs controlling "regulation of cytokinesis," "G1/S transition of mitotic cell cycle," "DNA recombination," and "telomere maintenance," respectively. Remarkably, we identified six chromatin state-marked C1-FFL instances (HCFC1-NFYA-ABL1, THAP1-USF1-BRCA2, ZNF263-USF1-UBA52, MYC-ATF1-UBA52, ELK1-EGR1-CCT4, and YY1-EGR1-INO80C) could act as prognostic biomarkers of acute myelogenous leukemia though influencing cancer-related biological functions, such as cell proliferation, telomere maintenance, and DNA recombination. Our results will provide novel insight for better understanding of chromatin state-mediated gene regulation and facilitate the identification of novel diagnostic and therapeutic biomarkers of human cancers.

MDS is a heterogeneous disease with diverse clinical manifestations, and an effective prognostic evaluation tool for MDS patients is needed. To achieve more accurate prognosis assessment for Chinese MDS patients, here we examined several scoring systems and explored the implications of gene mutations. The prognostic conditions were stratified against three different score systems (International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and Revised International Prognostic Scoring System (IPSS-R)) were retrospectively applied to 110 de novo MDS patients in study cohort in our hospital and the prognostic conditions were stratified respectively. IPSS-R out-performed the others, since it had less overlaps in survival curve, especially in the relatively low-risk group. Furthermore, genetic mutations were identified in 84 out of 110 patients and their association with overall survival (OS) were determined. Among them, sixty-three percent patients had at least one-point mutation, including thirty-five patients with normal karyotypes. The presence of TP53 mutations, but not TET2, DNMT3A or ASXL1 mutations was significantly correlated with shorter OS. A new model incorporating IPSS-R and TP53 mutations into survival analysis was proposed, and the prognostic value of this model was validated to be predominant in a 190-primary MDS patient independent cohort. Our data suggested that IPSS-R was more suitable for Chinese population. Attentions should be paid to the unfavourable mutations that might exert impact on the survival, especially in patients with relatively low risk., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7 th to 21 st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM-induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM-induced expression of α-smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor-β1, interleukin-1β, and tumor necrosis factor-α in the lungs of BLM-stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM-induced murine model., (© 2019 International Federation for Cell Biology.)

An emerging body of evidence has promoted the understanding of the role of microRNAs (miRNAs) in tumorigenesis and progression, but the mediating function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. In this study, miR-449b-3p was downregulated in NPC specimens (P < .001) and cells (P < .05). Cytological and animal experiments provided evidence that miR-449b-3p inhibited NPC metastasis in vitro and in vivo. Disintegrin and metalloproteinase 17 (ADAM17) was revealed as a direct target of miR-449b-3p. Rescue experiments suggested that the downregulation of ADAM17 in the miR-449b-3p knockdown cells partially reversed the inhibition of cell invasion and migration. Luciferase reporter assay, chromatin immunoprecipitation assay, and Western blot analysis showed that ADAM17 could suppress the promoter activity and expression of miR-449b-3p by inducing NF-κB transcriptional activity. In conclusion, our study provided new insights into the underlying mechanism of the invasion and metastasis of NPC. The novel miR-449b-3p/ADAM17/NF-κB feedback loop could be a target for the clinical treatment of NPC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Nasopharyngeal Carcinoma is limited by the various severe side-effects and surgery is rarely performed. Iosliquiritigenin has a series of biological activities, such as antiviral, anti-free radical and antitumor. However, the role and underlying mechanism of isoliquiritigenin in nasopharyngeal carcinoma have not been understood yet. Herein, the results revealed that isoliquiritigenin could inhibit cell proliferation in nasopharyngeal carcinoma cell lines, including C666-1 and CNE2, in both Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay. In addition, isoliquiritigenin promoted nasopharyngeal carcinoma cell apoptosis, with the up-regulations of Bax, Caspase-3 and Caspase-9 and the down-regulation of Bcl-2. Meanwhile, isoliquiritigenin suppressed nasopharyngeal carcinoma cells migration and invasion with the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9. Furthermore, the expression of miR-32 was up-regulated in the nasopharyngeal carcinoma tissues, while isoliquiritigenin could significantly down-regulate the expression of miR-32. And over-expression of miR-32 promoted the nasopharyngeal carcinoma cells growth, migration and invasion, and suppressed apoptosis. However, isoliquiritigenin treatment dramatically inhibited the effect of miR-32. Besides, luciferase reporter assay confirmed that large tumor suppressor 2 (LATS2) was a direct target of miR-32. And isoliquiritigenin increased the expression of LATS2, while silencing of LATS2 promoted the nasopharyngeal carcinoma cells growth. Moreover, western blotting discovered that isoliquiritigenin inhibited nasopharyngeal carcinoma cells growth via Wnt signaling pathway. Finally, CNE2 cells transplanted xenografts tumor model in nude mice were performed and it suggested that isoliquiritigenin could inhibit the development of xenografts nude mice, along with the decrease of tumor volume and the expression of miR-32 and LATS2. Overall, isoliquiritigenin was confirmed to be a potent anti-nasopharyngeal carcinoma compound both in vitro and in vivo, and accomplished by regulation of miR-32/LATS2/Wnt., (Copyright © 2019. Published by Elsevier B.V.)

Cerebral blood flow (CBF) reduction underlies unfavorable outcomes after subarachnoid hemorrhage (SAH). Transient receptor potential melastatin-4 (TRPM4) has a pivotal role in cerebral artery myogenic tone maintenance and CBF regulation under physiological conditions. However, the role of TRPM4 in CBF reduction after SAH is unclear. In this study, we aimed at testing whether TRPM4 would contribute to CBF reduction after SAH in vivo and determining underlying mechanisms. Rat SAH model was established by stereotaxic injection of autologous nonheparinized arterial blood at the suprasellar cistern. A TRPM4 blocker, 9-phenanthrol (9-Phe), was infused through an intraventricular catheter connected to a programmed subcutaneous pump to evaluate the contribution of TRPM4 to SAH outcomes. TRPM4 expression and translocation in cerebral artery myocytes were detected by immunoblotting. Macroscopic currents in cerebral artery myocytes were determined by whole-cell patch clamp. Myogenic tone of cerebral arteries was studied by pressurized myography. Cortical and global CBFs were measured via laser Doppler flowmetry and fluorescent microspheres, respectively. After SAH, TRPM4 translocation and macroscopic current density increased significantly. Furthermore, TRPM4 accounted for a greater proportion of myogenic tone after SAH, suggesting an upregulation of TRPM4 activity in response to SAH. Cortical and global CBFs were reduced after SAH, but were restored significantly by 9-Phe, implying that TRPM4 contributed to CBF reduction after SAH. Collectively, these discoveries show that increased TRPM4 activity has a pivotal role in CBF reduction after SAH, and provide a novel target for the management of cerebral perfusion dysfunction following SAH.

Epithelial-mesenchymal transition (EMT) is considered a prerequisite for tumor invasion and metastasis in many cancers. However, the mechanisms underlying EMT in nasopharyngeal carcinoma (NPC) is largely unknown. In this study, we found that transforming growth factor-β (TGF-β), which reportedly promotes EMT in multiple cancers, can trigger EMT and increase the invasive and migratory capacities of NPC cells. Conversely, the downregulation of SMAD4, a vital member of the canonical TGF-β pathway, reversed the TGF-β-induced EMT, invasion, and migration. Further experiments revealed that SMAD4 was the target of miRNA-34a, which was downregulated in NPC tissues and suppressed NPC cell metastasis in vivo. miRNA-34a overexpression also antagonized the TGF-β-induced EMT progression, invasion, and migration through SMAD4 inhibition. However, the restoration of SMAD4 expression rescued the inhibitory effects of miRNA-34a on tumorigenesis. All these results confirmed that miRNA-34a suppressed the TGF-β-induced EMT, invasion, and migration of NPC cells by directly targeting SMAD4, which indicated the potential of miR-34a as a therapeutic target against NPC., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Qinghai-Tibetan Plateau, one of the regions on the earth that receives the most solar radiation, is the world's highest alpine meadow ecosystem, with significance to regional and global carbon cycles. To examine the effects of solar radiation on ecosystem carbon dynamics in an alpine meadow, the net ecosystem CO 2 exchange (NEE), solar radiation, diffuse radiation, and related environmental variables were measured using eddy-covariance technique and micro-meteorological system. Sky conditions were divided into three categories of clear days (CI≥0.7), cloudy days (0.32 ·m -2 ·s -1 ) appeared in photosynthetic photon flux density (PPFD) of approximately 1400 μmol·m -2 ·s -1 , corresponding the CI of 0.6-0.7 in cloudy days, which was higher than the maximum NEE in clear days (-0.57 mg CO 2 ·m -2 ·s -1 ) (negative and positive NEE represented carbon uptake and emission, respectively, here absolute value was used to describe NEE). With the increases of diffuse radiation, NEE increased logarithmically when CI<0.6, reached the highest value when CI ranged from 0.6 to 0.7, and then decreased when CI≥0.7, indicating that photo-inhibition might occur under high solar radiation conditions and increasing diffuse radiation would improve carbon sequestration of alpine meadow. Ecosystem respiration (R e ) increased exponentially with the increases of air temperature (T a ). The maximum NEE was found at the air temperature of about 15 ℃ from the relationship of NEE and air temperature, but NEE tended to decrease with increasing air temperature when T a >15 ℃. Under clear sky day conditions, R e increased with increasing CI due to the increases of air temperature, with negative effects on NEE. NEE increased with the increases of VPD up to 0.6 kPa, then slowly decreased when VPD>0.6 kPa, illustrating that NEE was reduced due to the relatively high VPD. Our results suggested that strong solar radiation on clear days would not increase carbon uptake capacity of alpine meadow, while cloudy days with clearness index of 0.6-0.7 would help increase carbon sequestration on the Qinghai-Tibetan Plateau.

The present study aims to investigate the radiosensitization effect of the migration and invasion inhibitory protein (MIIP) gene on nasopharyngeal carcinoma (NPC) cells. The MIIP gene was transfected into NPC 5-8F and CNE2 cells. The level of MIIP was analyzed by quantitative reverse transcription-polymerase chain reaction analysis and western blot. The changes in radiosensitivity of the cells were analyzed by colony formation assay. The changes in cell apoptosis and cycle distribution following irradiation were detected by flow cytometry. The expression of BCL2 associated X, apoptosis regulator/B-cell lymphoma 2 was evaluated using western blot. DNA damage was analyzed by counting γ-H2AX foci. The expression levels of γ-H2AX were evaluated by immunofluorescence and western blot. In a previous study by the authors, the results indicated that the expression of MIIP gene evidently increased in MIIP-transfected 5-8F (5-8F OE) and MIIP-transfected CNE2 (CNE2 OE) cells compared with the parental or negative control cells. In the present study, the survival rate of 5-8F OE and CNE2 OE cells markedly decreased following irradiation (0, 2, 4, 6 and 8 Gy) compared with the negative control (5-8F NC and CNE2 NC) and the untreated (5-8F and CNE2) groups. The expression of MIIP was able to increase apoptosis, which resulted in G2/M cell cycle arrest and DNA damage repair was attenuated in 5-8F and CNE2 cells following irradiation as measured by the accumulation of γ-H2AX. It was indicated that MIIP expression is associated with the radiosensitivity of NPC cells and has a significant role in regulating cell radiosensitivity.

Vasoactive intestinal peptide (VIP) is one of the most abundant neuropeptides in the lungs with various biological characters. We have reported that VIP inhibited the expressions of TREM-1 and IL-17A, which are involved in the initiation and amplification of inflammation in acute lung injury (ALI). However, the overall effect of VIP on ALI remains unknown. The aim of this study is to investigate the therapeutic effect of VIP mediated by lentivirus (Lenti-VIP) on lipopolysaccharide (LPS)-induced murine ALI. We found that the expression of intrapulmonary VIP peaked at day7 after the intratracheal injection of Lenti-VIP. Lenti-VIP increased the respiratory rate, lung compliance, and tidal volume, while decreased airway resistance in ALI mice, detected by Buxco system. Lenti-VIP significantly reduced inflammatory cell infiltration and maintained the integrity of the alveolar septa. Lenti-VIP also remarkably decreased the total protein level, the number of neutrophil and lactate dehydrogenase activity in the bronchoalveolar lavage fluid of LPS-induced ALI mice. In addition, Lenti-VIP down-regulated pro-inflammatory tumor necrosis factor (TNF)-α mRNA and protein expression, while up-regulated anti-inflammatory interleukin-10 mRNA and protein expression in lungs of ALI mice. Furthermore, we observed that VIP reduced the TNF-α expression in murine macrophages under LPS stimulation through protein kinase C and protein kinase A pathways. Together, our findings show that in vivo administration of lentivirus expressing VIP exerts a potent therapeutic effect on LPS-induced ALI in mice via inhibiting inflammation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In recent years, miR-152 has been dysregulated in a variety of tumors and used as a tumor suppressor. Nevertheless, its role in nasopharyngeal carcinoma (NPC) remains unidentified., Materials and Methods: Real-time quantitative PCR (polymerase chain reaction) was performed to analyze the expression of miR-152 in NPC cell lines. MiR-152 expression profiles in NPC tissues were obtained from Gene Expression Omnibus (GEO GSE36682). The effect of miR-152 on the invasion and proliferation of NPC cells was determined through cell invasion, wound healing, and cell viability assays. Apoptosis was examined by flow cytometry, and Western blot was performed to measure expression of the target gene. Pyrosequencing was used to detect the methylation level of NPC cells., Results: In this study, miR-152 was downregulated in the NPC tissues and cell lines. When miR-152 was enhanced, the invasion and migration of NPC cells were inhibited. However, miR-152 had no effect on the proliferation of NPC cells. Luciferase reporter gene analysis was performed, and the results showed that DNMT1 (DNA (cytosine-5)-methyltransferase 1) is a direct target of miR-152 in NPC cells. DNMT1 downregulation and miR-152 overexpression both reversed the effects of miR-152 inhibition on the NPC cells. In addition, miR-152 expression increased as a result of the inhibition of the methylation level of miR-152 when DNMT1 expression was downregulated., Conclusion: The overexpression of miR-152 inhibited the migration and invasion of NPC cells by targeting DNMT1. Furthermore, DNMT1 regulated miR-152 expression through DNA methylation. Overall, the novel miR-152-DNMT1 regulatory circuit may provide better understanding of the pathogenesis of NPC and new epigenetic therapeutic target in NPC., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background/aims: Parkinson's disease (PD) is a frequently occurring condition that resulted from the loss of midbrain neurons, which synthesize the neurotransmitter dopamine. In this study, we established mouse models of PD to investigate the expression of microRNA-128 (miR-128) and mechanism through which it affects apoptosis of dopamine (DA) neurons and the expression of excitatory amino acid transporter 4 (EAAT4) via binding to axis inhibition protein 1 (AXIN1)., Methods: Gene expression microarray analysis was performed to screen differentially expressed miRNAs that are associated with PD. The targeting relationship between miR-128 and AXIN1 was verified via a bioinformatics prediction and dual-luciferase reporter gene assay. After separation, DA neurons were subjected to a series of inhibitors, activators and shRNAs to validate the mechanisms of miR-128 in controlling of AXIN1 in PD. Positive protein expression of AXIN1 and EAAT4 in DA neurons was determined using immunocytochemistry. miR-128 expression and the mRNA and protein levels of AXIN1 and EAAT4 were evaluated via RT-qPCR and Western blot analysis, respectively. DA neuron apoptosis was evaluated using TUNEL staining., Results: We identified AXIN1 as an upregulated gene in PD based on the microarray data of GSE7621. AXIN1 was targeted and negatively mediated by miR-128. In the DA neurons, upregulated miR-128 expression or sh-AXIN1 increased the positive expression rate of EAAT4 together with mRNA and protein levels, but decreased the mRNA and protein levels of AXIN1, apoptosis rate along with the positive expression rate of AXIN1; however, the opposite trend was found in response to transfection with miR-128 inhibitors., Conclusion: Evidence from experimental models revealed that miR-128 might reduce apoptosis of DA neurons while increasing the expression of EAAT4 which might be related to the downregulation of AXIN1. Thus, miR-128 may serve as a potential target for the treatment of PD., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: A recent study found that dysregulated microRNA-184 (miR-184) is involved in the proliferation and survival of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the detailed mechanisms of invasion, migration and metastasis of NPC cells., Methods: Quantitative reverse-transcription PCR (qRT-PCR) and Western blot were used to confirm the expression levels of miR-184 and Notch2. NPC cell invasion and migration were subsequently examined using in vitro cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target gene prediction databases and dual-luciferase reporter assay were adopted to validate the target genes of miR-184., Results: MiR-184 was downregulated in the NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells, whereas miR-184 mimics inhibited the invasive ability of such cells. The protein level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell invasion and metastasis by regulating EMT progression. MiRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-184. Such a notion was then validated by results of dual-luciferase reporter assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the inhibitory effects of miR-184 on EMT progression in NPC cells., Conclusion: MiR-184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the invasion, migration and metastasis of NPC., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objective: To explore the perinatal outcome of vaginal birth after cesarean (VBAC) in women with advanced age. Methods: Totally 2 587 women delivered after one or two prior cesarean sections (gestational age≥28 weeks) in the First Affiliated Hospital of Kunming Medical University from July 2013 to February 2017. 909 trial of labor after cesarean(TOLAC) cases of singleton pregnancy with one prior cesarean section were studied retrospectively. According to the age, of the 909 TOLAC cases, 237 were the advanced age group, and 672 cases were the low age group. The maternal and neonatal outcomes between the two groups were compared. Results: The percentage of TOLAC in women with advanced age was 32.4% (237/731), and VBAC rate was 88.2% (209/237). The percentage of TOLAC in younger women was 36.2% (672/1 856), and VBAC rate was 82.4% (554/672). The difference of the TOLAC rate between the two groups was not significant ( P >0.05), and the VBAC rate of the advanced age group was higher than the low age group ( P <0.05). In the comparison of the two groups, the proportion of bachelor degree or above(55.7%,132/237), the prepregnancy BMI (22.4±3.0) kg/m(2), pregnant interval time (68.5±38.3) months, the proportion of gestational hypertension (8.4%,20/237), the proportion of gestational diabetes(34.6%,82/237) and the rate of the neonatal ICU admission (18.1%,43/237) in the advanced age group were higher than those of the low age group ( P <0.05), respectively. And there were no significant differences in the rate of postpartum hemorrhage, the rate of postpartum hemorrhage≥1 500 ml, the rate of postpartum transfusion, puerperal morbidity, neonatal birth weight, neonatal 5 min Apgar score<7 score, umbilical artery blood pH<7.0, neonatal tracheal intubation and respiratory distress syndrome (all P >0.05). In all TOLAC cases, the rate of uterine rupture was 0.11%(1/909) and there was no maternal and neonatal death. Conclusion: VBAC is a safe and feasible way of delivery for singleton pregnancy after one prior cesarean section in women with advanced age.

Background: Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects., Methods: We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size-signed differential mapping (AES-SDM). We used DTI query software for fibre tracking., Results: Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle., Limitations: The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data., Conclusion: By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.

Our ability to predict how temperature modifies phenology at the community scale is limited by our lack of understanding of responses by functional groups of flowering plants. These responses differ among species with different life histories. We performed a reciprocal transplant experiment along four elevation gradients (e.g., 3,200, 3,400, 3,600 and 3,800 m) to investigate the effects of warming (transferred downward) and cooling (transferred upward) on plant flowering functional groups (FFGs) and community phenological sequences (i.e., seven phenological events). Warming significantly decreased early-spring-flowering (ESF) plant coverage and increased mid-summer-flowering plant (MSF) coverage, while cooling had the opposite effect. All community phenological events were advanced by warming and delayed by cooling except for the date of complete leaf-coloring, which showed the opposite response. Warming and cooling could cause greater advance or delay in early-season phenological events of the community through increased coverage of MSF species, and warming could delay late-season phenological events of the community by increased coverage of ESF species. These results suggested that coverage change of FFGs in the community induced by temperature change could mediate the responses of the community phenological events to temperature change in the future. The response of phenological events to temperature change at the species level may not be sufficient to predict phenological responses at the community-level due to phenological compensation between species in the community., (© 2016 by the Ecological Society of America.)