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Deep, large-diameter caisson shafts are a popular means of constructing underground storage and attenuation tanks and pumping stations for the water and wastewater industry. One of the key design concerns for these structures is resistance to flotation during periods when the tanks are only partially filled or empty. In this paper, two-dimensional numerical analysis is used to explore the undrained uplift resistance provided by under-reaming the walls of the caisson shaft to create an enlarged base. The primary aim of the study is to assess the influence of the taper angle of the anchor (i.e. the protruded base) on the resulting uplift resistance. The effects of the anchor–soil interface roughness factor, soil weight, surcharge pressure and caisson radius are also investigated. The results indicate that the effect of the taper angle on both the uplift bearing capacity and the developed horizontal reaction can be very significant. The numerical output informs the development of a closed-form approach for application in routine design. The new design method is shown to provide an excellent agreement with both finite-element and additional finite-element limit analysis calculations. By way of example, the proposed design method is applied to a hypothetical design scenario.

Yuling Xing,1,2 Jinhu Chen,1,2 Jing Liu,1,2 Guangyao Song,1,3 Huijuan Ma1,3 1Department of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China; 2Graduate School of Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 3Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of ChinaCorrespondence: Huijuan MaDepartment of Endocrinology, Hebei General Hospital, Shijiazhuang, 050017, People’s Republic of China, Tel +86 18032838686, Email huijuanma76@163.comPurpose: To investigate the association between serum uric acid-to-creatinine ratio (SUA/Cr) and the risk of developing metabolic-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: Overall, 1434 patients with T2DM who were admitted to Hebei General Hospital from January 2019 to December 2019 were selected as the study subjects. According to abdominal ultrasound findings, patients were divided into two groups: MAFLD group and non-MAFLD group. A total of 734 patients were diagnosed with MAFLD. Participants were divided into three study groups according to the SUA/Cr ratio. Chi-square test and one-way analysis of variance were used to perform a comparison between groups. The relationship between SUA/Cr ratio and MAFLD risk was analyzed using correlation analysis and regression analysis. Furthermore, subgroup analyses were performed to verify the robustness of the results.Results: The detection rate of MAFLD in patients with T2DM was 51.2%, and the detection rate of progressive liver fibrosis in T2DM patients with MAFLD was 36.6%. A significantly higher SUA/Cr ratio was seen in the MAFLD group than in the non-MAFLD group. After adjusting for confounding factors, multivariate logistic regression analysis revealed that the SUA/Cr ratio was an independent risk factor for MAFLD development. Stronger correlations were found in participants with a body mass index ranging between 23 and 28 kg/m2, HbA1C > 7%, or female sex.Conclusion: An elevated SUA/Cr index is independently correlated with an increased risk of MAFLD in Chinese adults with T2DM.Keywords: metabolic-associated fatty liver disease, type 2 diabetes, SUA/Cr

Hot forging forming of railway wagon bogie adapter is a new railway wagon bogie adapter processing technology. In this paper, a hot forging die for railway wagon bogie adapter was designed, and the forming quality were analyzed by using DEFORM-3D software. Then, the feasibility of the process was verified by experiments. It was found that using this mold can eliminate the defects such as loose as-cast in metal smelting process, optimize the microstructure, forging products with good density, product quality and other characteristics of stability.

Background Mutations and/or duplications in the chromosome 2q24.3 region are known to be responsible for various epilepsy phenotypes. However, microdeletion in childhood epilepsy is rarely reported. Case presentation A two-and-a-half-year-old girl with no history of hypocalcemia or seizures developed new symptoms of generalized tonic-clonic epilepsy. The clinical manifestations were growth retardation, prominent forehead, closed anterior fontanelle, and poor muscle tension. Peripheral blood, echocardiography, abdominal ultrasound, and electroencephalogram (EEG) examinations were all normal. No karyotype abnormality was found in the patient, but a single nucleotide polymorphism (SNP) array test detected that a 3.5 Mb single-copy microdeletion had occurred in the q24.2-q24.3 region on chromosome 2. Fluorescence in situ hybridization (FISH) tests revealed that the 2q24 fragment was inserted into the q11.2 region of the patient's chromosome 15, as well as that of her sister. In both cases, the patient's mother is the source carrier of the chromosome 15 insertion. Conclusions The deletion of the sodium channel gene cluster (SCN1A, SCN2A, and SCN3A), but not SCN1A haploinsufficiency ​alone, may contribute to complex infant epilepsy syndromes. However, the pathogenic mechanism still needs to be studied further.

Most video-and-language representation learning approaches employ contrastive learning, e.g., CLIP, to project the video and text features into a common latent space according to the semantic similarities of text-video pairs. However, such learned shared latent spaces are not often optimal, and the modality gap between visual and textual representation can not be fully eliminated. In this paper, we propose Expectation-Maximization Contrastive Learning (EMCL) to learn compact video-and-language representations. Specifically, we use the Expectation-Maximization algorithm to find a compact set of bases for the latent space, where the features could be concisely represented as the linear combinations of these bases. Such feature decomposition of video-and-language representations reduces the rank of the latent space, resulting in increased representing power for the semantics. Extensive experiments on three benchmark text-video retrieval datasets prove that our EMCL can learn more discriminative video-and-language representations than previous methods, and significantly outperform previous state-of-the-art methods across all metrics. More encouragingly, the proposed method can be applied to boost the performance of existing approaches either as a jointly training layer or an out-of-the-box inference module with no extra training, making it easy to be incorporated into any existing methods., Accepted to NeurIPS 2022

Jian Wang,1 Ge Zhao,2 Guang Song,3 Jing Liu2 1Department of Anesthesiology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Jing LiuDepartment of Obstetrics, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, Liaoning Province, 110001, People’s Republic of ChinaTel +86 24 8328 2599Email liujing9936@163.comObjective: Cesarean section (CS) is one of the most frequently performed major surgical interventions. Local anesthetic techniques, a universal component of perioperative multimodal analgesia, are reportedly effective in reducing pain scores and opioid requirements. However, the optimal local anesthetic technique for postoperative CS pain remains unclear.Methods: Six databases were searched, and a Bayesian network meta-analysis was performed. The outcomes included cumulative morphine consumption and pain scores at four time points, time to first analgesic request, postoperative nausea and vomiting, pruritus, and sedation.Results: Sixty-eight studies with 5039 pregnant women were included. Six local anesthetic techniques were involved, including transversus abdominis plane block (TAPB), ilioinguinal and iliohypogastric nerve block, quadratus lumborum blocks, transversalis fascia plane block, erector spinae block, and wound infiltration. Compared to inactive controls, TAPB reduced cumulative morphine consumption at 6, 12, 24, and 48 h, pain scores at 6, 12, and 24 h (with the exception of 24 h at rest), the risk of postoperative nausea and vomiting, and sedation. Compared with inactive controls, ilioinguinal and iliohypogastric nerve block reduced cumulative morphine consumption at 6 and 24 h and pain scores at 6, 12, and 24 h during movement. Compared with inactive controls, quadratus lumborum blocks reduced cumulative morphine consumption at 24 and 48 h and pain scores at 6 and 12 h and lengthened the time to first analgesic request. Compared with inactive controls, wound infiltration reduced cumulative morphine consumption at 12 and 24 h, pain scores at 12 and 24 h during movement, and risk of sedation. Compared with inactive controls, erector spinae block reduced pain scores at 6 and 12 h. Transversalis fascia plane block was found to have similar outcomes to inactive controls.Conclusion: TAPB is the most comprehensive local anesthetic technique for postoperative CS analgesia in the absence of intrathecal morphine.Keywords: Cesarean section, postoperative pain, network meta-analysis, local anesthesia

Xiao Tang,1 Hongya Zhang,1 Yanxiang Zhao,2 Fang Lei,1 Qigui Liu,1 Dongmei Hu,1 Guorong Li,1 Guirong Song1 1Department of Health Statistics, School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, 116044, People’s Republic of China; 2Department of Mathematics, George Washington University, Washington, DC, USACorrespondence: Guirong SongDepartment of Health Statistics, School of Public Health, Dalian Medical University, No. 9 South Road, Lvshun District, Dalian City, Liaoning Province, 116044, People’s Republic of ChinaTel +86-411-86110328Email songsara110@163.comBackground: Obesity is well recognized as a risk factor for cardiometabolic diseases. The development of obesity is a dynamic process that can be described as a multistate process with an emphasis on transitions between weight states. However, it is still unclear what convenient biomarkers predict transitions between weight states. The aim of this study was to show the dynamic nature of weight status in adults stratified by age and sex and to explore blood markers of metabolic syndrome (MetS) that predict transitions between weight states.Methods: This study involved 9795 individuals aged 18 to 56 at study entry who underwent at least two health check-ups in the eight-year period of study in the health check-up centre of our institution. Weight, height and biochemical indices were measured at each check-up. The participants were divided into four groups based on age and sex (young male, middle-aged male, young female and middle-aged female groups). A multistate Markov model containing 3 states (healthy weight, overweight and obesity) was adopted to study the longitudinal weight data.Results: Young people were more likely to transit between weight states than middle-aged people, and middle-aged people were more resistant to recover from worse states. The mean sojourn time in obesity was greatest in the middle-aged male group (6.23 years), and the predicted rate of obesity beginning with healthy weight was greatest in the young male group (13.7%). In multivariate models, age group and triglyceride (TG) and high-density lipoprotein cholesterol (HDL) levels were significant for specific transitions in females, whereas age group and HDL levels were significant in males. In females, if HDL levels increased 1 mmol/L, the probability of progression from healthy weight to overweight decreased by 37.0% (HR= 0.63), and the probabilities of recovery (overweight to healthy weight and obesity to overweight) increased by 62.0% (HR= 1.62) and 1.23-fold (HR= 2.23), respectively. In males, if TG levels increased 1 mmol/L, the risk of progression from healthy weight to overweight increased by 24.0% (HR= 1.24). Each unit increase in HDL levels was associated with a 0.99-fold (HR= 1.99) increase in the chance of recovery from overweight to healthy weight and with a 0.37-fold (HR= 0.63) decrease in the risk of progression from healthy weight to overweight.Conclusion: The weight status of young people was less stable than that of middle-aged people. Males were more likely to become overweight and more resistant to recover from worse states than females. Young males with healthy weight were more likely to develop obesity than other healthy weight groups. Blood lipid levels, especially HDL, were predictors of weight transitions in adults. Prevention and intervention measures should be applied early.Keywords: obesity, multistate Markov model, triglyceride, high-density lipoprotein cholesterol, low density lipoprotein cholesterol

Gang Wang,1,* Guobin Song,1,2,* Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanhong XuDepartment of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui Province, 230022, People’s Republic of ChinaEmail xyhong1964@163.comBackground: Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is a novel method that can be used to identify pathogens and has potential applications in the detection of drug-resistant bacteria.Purpose: To evaluate the ability of a MALDI-TOF MS-based broth micro-dilution method in detecting the minimum inhibitory concentration (MIC) values of Klebsiella pneumoniae to ceftriaxone and imipenem.Materials and Methods: Sixty strains of K. pneumoniae with different levels of resistance to carbapenems and cephalosporins were randomly collected. The 0.5 McFarland (Mc) concentration of the bacterial suspension was inoculated in cation-adjusted Mueller-Hinton broth (CAMHB) with a final cell turbidity of 5× 105 CFU/mL. The broth was incubated with serial concentrations of antibiotics. After centrifuging the bacterial suspensions, the lysed cells were analyzed by MALDI-TOF MS to identify the growth-promoting or inhibitory effects on K. pneumoniae. The molecular mechanisms of resistance were investigated by PCR and DNA sequencing analysis.Results: The expression of known resistance genes (blaKPC, blaFOX, blaDHA, blaCTX-M and blaTEM) was detected in the 30 carbapenems-resistant strains. The agreement between the MIC values derived from the MALDI-TOF MS analysis and from the broth micro-dilution method was 61.7% for ceftriaxone and 71.7% for imipenem. According to the Clinical and Laboratory Standards Institute (CLSI) breakpoint of resistance to ceftriaxone and imipenem, the 60 isolates were accurately classified as resistant or susceptible isolates with 100% sensitivity and 100% specificity.Conclusion: The transmission and infection of multidrug-resistant bacteria could be better managed and treated with the rapid identification of strains and antimicrobial susceptibility. A MALDI-TOF MS-based susceptibility test could be used to identify resistance of K. pneumoniae within a short time-frame. This approach could potentially be used as a supplementary antimicrobial susceptibility test that could be investigated on more bacterial species combined with different antibiotics.Keywords: Klebsiella pneumoniae, matrix-assisted laser desorption ionization–time of flight mass spectrometry, carbapenemases, extended-spectrum β-lactamases, antimicrobial susceptibility test

Hang Zhao,1 Yong Tang,1 Chong Zheng,2 Luping Ren,1,* Guangyao Song1,* 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Pediatric Orthopaedics, Shijiazhuang the Third Hospital, Shijiazhuang, Hebei, 050011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Luping Ren; Guangyao Song 348, Heping West Road, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaTel +8631185988975; +8631185988556Email renluping1122@163.com; sguangyao2@163.comPurpose: This study aimed to examine whether 25-hydroxyvitamin D (25OHD) levels (an indicator of vitamin D status) are independently associated with insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: This was a cross-sectional study. Participants with T2DM were recruited from the Department of Endocrinology in Hebei General Hospital according to inclusion and exclusion criteria. Data on basic characteristics and blood parameters were collected. We used the IR index (20/[fasting C-peptide × fasting plasma glucose]) to evaluate IR. Potential confounding factors were selected from comparisons among different IR index groups of quartiles and were adjusted in different models.Results: We included 172 subjects (121 men and 51 women) whose mean age was 53.2± 10.6 years. Body mass index (BMI), DM course, insulin use, glycated hemoglobin (HbA1c), fasting blood glucose, fasting C-peptide, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and albumin were differed among different IR-index groups (all P value < 0.05). In models 1 and 2, no or some confounding factors were adjusted for, and we found that there was no relationship between 25OHD and the IR index. In model 3, when all confounding factors (DM course, insulin use, BMI, HbA1c, TG, HDL-C, ApoA1, albumin and other bone turnover markers) were adjusted for, the IR index was increased by 5.6% when 25OHD levels increased by 1 ng/mL (odds ratio: 1.056; 95% confidence interval: 1.009, 1.105).Conclusion: Vitamin D is independently associated with IR in patients with T2DM.Keywords: diabetes mellitus, type 2, vitamin D, insulin resistance

Xiaobo Dong,* Lei Wang,* Guangrong Song, Xu Cai, Wenxin Wang, Jiaqi Chen, Gesheng Wang The Third Department of Encephalopathy, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 100078, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gesheng WangThe Third Department of Encephalopathy, Dongfang Hospital Beijing University of Chinese Medicine, No. 6 Zone 1 Fangxingyuan, Fangzhuang, Fengtai District, Beijing 100078, People’s Republic of ChinaEmail wanggesh@sina.comBackground: Ischemic stroke (IS) is characterized by the rapid loss of brain function due to ischemia. Physcion has been found to have a neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the mechanism by which physcion regulates cerebral I/R injury remains largely unknown.Methods: An oxygen-glucose deprivation/reperfusion (OGD/R) model in SH-SY5Y cells and a rat cerebral ischemia-reperfusion (I/R) model were established, respectively. CCK-8 and flow cytometry assays were used to detect the viability and apoptosis of SH-SY5Y cells. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of SOD, MDA, GSH-Px, TNF-α, IL-1β, IL-6 and IL-10 in the supernatant of SH-SY5Y cells. Meanwhile, Western blot assay was used to detect the expressions of TLR4, p-p65 and p-IκB in SH-SY5Y cells and I/R rats.Results: In this study, physcion treatment significantly rescued OGD/R-induced neuronal injury. In addition, physcion decreased inflammatory response in SH-SY5Y cells after OGD/R insult, as shown by the decreased levels of the pro-inflammatory factors TNF-α, IL-1β, IL-6 and IL-10. Moreover, physcion attenuated the oxidative stress in OGD/R-treated SY-SY5Y cells, as evidenced by the increased SOD and GSH levels and the decreased ROS and MDA levels. Meanwhile, physcion significantly reduced cerebral infarction, attenuated neuronal injury and apoptosis in I/R rats. Furthermore, physcion markedly decreased the expressions of TLR4, p-NF-κB p65 and p-IκB in the brain tissues of rats subjected to I/R and in SH-SY5Y cells exposed to OGD/R.Conclusion: In conclusion, our study indicated that physcion protected neuron cells against I/R injury in vitro and in vivo by inhibition of the TLR4/NF-kB pathway; thus, physcion might serve as a promising therapeutic candidate for IS.Keywords: stroke, ischemia-reperfusion injury, physcion, NF-κB

Lifei Ma,1,2 Guiqin Song,1 Meiyu Li,3 Xiuqing Hao,4 Yong Huang,1 Jinping Lan,1 Siqian Yang,5 Zetian Zhang,6 Guohui Zhang,3 Jiao Mu3,7 1College of Laboratory Medicine, Hebei North University, Zhangjiakou, Hebei 075000, People’s Republic of China; 2State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, People’s Republic of China; 3Department of Forensic Medicine, Hebei North University, Zhangjiakou, Hebei 075000, People’s Republic of China; 4Department of Pathology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, People’s Republic of China; 5College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, People’s Republic of China; 6Department of Gastroenterology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei 075000, People’s Republic of China; 7Department of Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, People’s Republic of ChinaCorrespondence: Jiao Mu; Guohui Zhang Department of Forensic Medicine, Zhangjiakou, Hebei 075000, People’s Republic of ChinaTel +86-18931315882; +86-18931316008 Email jiaomu@hebeinu.edu.cn; 18931316008@163.comBackground: Triple-negative breast cancer (TNBC) is the most common and aggressive type of breast cancer with an unfavourable outcome worldwide. Novel therapeutic targets are urgently required to explore this malignancy. This study explored the ceRNA network and the important genes for predicting the therapeutic targets.Methods: It identified the differentially expressed genes of mRNAs, lncRNAs and miRNAs between TNBC and non-TNBC samples in four cohorts (TCGA, GSE38959, GSE45827 and GSE65194) to explore the novel therapeutic targets for TNBC. Downstream analyses, including functional enrichment analysis, ceRNA network, protein–protein interaction and survival analysis, were then conducted by bioinformatics analysis. Finally, the potential core protein of the ceRNA network in TNBC was validated by immunohistochemistry.Results: A total of 1,045 lncRNAs and 28 miRNAs were differentially expressed in the TCGA TNBC samples, and the intersections of 282 mRNAs (176 upregulations and 106 downregulations) between the GEO and TCGA databases were identified. A ceRNA network composed of 7 lncRNAs, 62 mRNAs, 12 miRNAs and 244 edges specific to TNBC was established. The functional assay showed dysregulated genes, and GO, DO and KEGG enrichment analysis were performed. Survival analysis showed that mRNA LIFR and lncRNA AC124312.3 were significantly correlated with the overall survival of patients with TNBC in the TCGA databases (P < 0.05). Finally, the LIFR protein was validated, and immunohistochemical results showed the upregulated expression of LIFR in TNBC tissues.Conclusion: Thus, our study presents an enhanced understanding of the ceRNA network in TNBC, where the key gene LIFR may be a new promising potential therapeutic target for patients with TNBC.Keywords: triple-negative breast cancer, ceRNA network, overall survival, novel biomarkers, leukemia inhibitory factor receptor

Gang Wang,* Guobin Song,* Yuanhong Xu Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanhong Xu Email xyhong1964@163.comBackground: Klebsiella pneumoniae is a common opportunistic pathogen and its production of extended-spectrum β-lactamases (ESBL) and carbapenemases leads to drug resistance. Clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated genes (Cas) are widespread in the genome of many bacteria and are a defense mechanism against foreign invaders such as plasmids and viruses.Purpose: To investigate the prevalence of the CRISPR/Cas system in wild type strains of K. pneumoniae in the hospital and its association with drug resistance.Materials and Methods: A total of 136 strains were collected and characterized their susceptibility to antimicrobial agents. The prevalence of CRISPR/Cas system was detected by PCR and DNA sequencing was analyzed by CRISPRFinder. The statistical analysis of the results was performed by SPSS.Results: We found that 50/136 (37%) isolates produced ESBL and 30/136 (22%) isolates were resistant to carbapenems. These isolates were liable to be multidrug resistant against β-lactams, quinolones, and aminoglycosides. Among the carbapenem-resistant isolates, blaKPC was the main drug resistance-associated gene and different types of ESBL and AmpC genes were present. Resistance to β-lactams, quinolones, aminoglycosides, tetracyclines, and β-lactams/enzyme inhibitor were higher in absence of the CRISPR/Cas system. Eighteen spacers within the CRISPR arrays matched with the genomes of plasmids or phages, some of which carried drug resistance genes.Conclusion: ESBL-producing and carbapenem-resistant K. pneumoniae are more likely to develop multidrug resistance and show an inverse correlation between drug resistance and CRISPR/Cas system. Absence of CRISPR/Cas modules allow for the acquisition of external drug resistance genes.Keywords: CRISPR/Cas, Klebsiella pneumoniae, extended-spectrum β-lactamases, carbapenemases, drug resistance

Hang Zhao,1 Cuijuan Qi,1 Chong Zheng,2 Kexin Gan,1 Luping Ren,1,* Guangyao Song1,* 1Endocrinology Department, Hebei General Hospital, Hebei 050051, People’s Republic of China; 2Pediatric Orthopaedics, Shijiazhuang the Third Hospital, Hebei 050011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Luping Ren Email renluping1122@163.comPurpose: We aimed to determine the relationship between the levels of glycated hemoglobin (HbA1c) and biomarkers of bone metabolism in patients with type 2 diabetes mellitus (T2DM), and whether HbA1c independently influences any of these biomarkers.Patients and Methods: A cohort study of 240 patients with T2DM was performed. Serum was obtained and used to measure HbA1c, total cholesterol (TC), triglycerides, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total protein, albumin, blood urea nitrogen (BUN), creatinine, serum 25-hydroxyvitamin D (25OHD), osteocalcin (OC), β-C-terminal cross-linked telopeptide of type I collagen (β-CTX), procollagen type 1 N-terminal propeptide (P1NP), or parathyroid hormone (PTH) concentrations. The participants were divided into three study groups according to HbA1c level: < 7%, 7– 9% and ≥ 9%. Chi-square testing and one-way analysis of variance were used to compare groups. The relationships between HbA1c and bone metabolism biomarker values were analyzed using linear correlation analysis and multiple linear regression analysis.Results: Age, duration of T2DM, and the concentrations of TC, LDL-C, apolipoprotein B, albumin, and BUN showed significant difference among the < 7%, 7– 9% and ≥ 9% HbA1c groups. Of the bone metabolism biomarkers, there were significant differences in serum 25-hydroxyvitamin D (25OHD) and osteocalcin (OC) among the groups. The correlation coefficients (r) for the relationships of HbA1c with 25OHD and OC were − 0.200 and − 0.183, respectively (P < 0.05). Regardless of adjustment for none, some, or all of the confounding factors (age, sex, and duration of T2DM), the 25OHD and OC concentrations were significantly lower in the HbA1c ≥ 9% group than in the HbA1c < 7% group. HbA1c showed no relationship with β-CTX, PINP, or PTH.Conclusion: T2DM patients with poorer glycemic control had lower concentrations of serum 25OHD and OC, suggesting that HbA1c is an independent risk factor for low 25OHD and OC.Keywords: diabetes mellitus type 2, bone metabolism, glycated hemoglobin

Yi Zhang,1,2 Song Cao,2,3 Jie Yuan,2,3 Ganjun Song,2,4 Tian Yu,2 Xiaoli Liang5 1Department of Anesthesiology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi 563002, Guizhou, People’s Republic of China; 2Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, People’s Republic of China; 3Department of Pain Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 4Department of Radiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of China; 5Department of Anesthesiology, Zunyi Medical University, Zunyi 563002, Guizhou, People’s Republic of ChinaCorrespondence: Xiaoli LiangDepartment of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, Guizhou, People’s Republic of ChinaTel +8613648521600Email 17799870@qq.comObjective: Multimodal magnetic resonance imaging (MRI) was used to detect whether 6 months after pain relieving, the structural and functional abnormalities in the brain of postherpetic neuralgia (PHN) patients are changeable.Methods: Fifteen successfully treated PHN patients were enrolled; the brain activity and structural abnormalities were detected and compared before and 6 months after treatment. The functional parameters were evaluated with resting-state functional MRI technique, i.e., the regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF). Structural changes were detected with voxel-based morphometry (VBM) and diffusion kurtosis imaging (DKI).Results: Six months after pain relieving, PHN brain showed different ReHo and fALFF values in the frontal lobe, caudate, supramarginal gyrus, anterior cingulate cortex (ACC), cuneus, middle temporal gyrus, and cerebellum. In addition, VBM intensity in the cerebellum increased; DKI values decreased in the thalamus and increased in the temporal lobe after successful treatment.Conclusion: Six months after pain relieving, functional and structural changes exist in PHN brain. Changes in some differential areas in PHN brain, such as ACC, frontal lobe, thalamus, and temporal lobe indicate that the central plasticity may be reversible after chronic pain relieving.Keywords: postherpetic neuralgia, PHN, functional magnetic resonance imaging, regional homogeneity, ReHo, fractional amplitude of low-frequency fluctuation, fALFF

The relationships between climate and forest dynamics can help us to interpret patterns of ecosystem carbon and to predict how forests react to climatic changes. We report mass dynamics of deadwood (necromass) from tropical forest ecosystems subject to some of the highest frequency of tropical cyclones in the world and to regular, persistent seasonal monsoon winds. Plots that are influenced by typhoons but exposed to different degrees of monsoon winds were monitored. We expected that stocks and inputs of necromass would reflect the seasonal intensity of wind events and be higher in the high wind exposure forest than in the low wind exposure forest, especially for fallen woody debris. The results showed that necromass input was indeed influenced by the magnitude of typhoons and aggravated by monsoon winds. However, while there was no significant difference in stock of necromass between plots, inputs of standing necromass were significantly higher in the high wind exposure plot; these were mostly derived from dead resprouts. Both our forests had very low values of total necromass stocks (3.47–4.32 Mg C ha−1) and inputs (2.1–2.5 Mg C ha−1 y−1) compared with tropical forests worldwide. Our results show that both monsoon and typhoon winds shape these tropical forests, favouring low stature individuals and trees with ability to resprout and that these strategies provide these forests with remarkable resistance and resilience to wind disturbances. Our findings from some of the most wind-affected forests in the world indicate how woody carbon dynamics and forest structure in other regions may respond to future changes in the frequency and intensity of winds.

Additional file 2: Supplementary materials.

Preliminary estimations of shaft resistance of rock-socketed piles are usually conducted using empirical formulations which relate to the uniaxial compressive strength (í µí¼ í µí±) of the weaker material involved (intact rock or pile). However, there are other factors, such as the degree of socket roughness, that could affect the shaft resistance of rock-socketed piles. In this paper, results from geotechnical centrifuge tests are presented to demonstrate the effect of socket roughness on the pile shaft resistance. Aluminum model piles with different degrees of shaft roughness were fabricated and embedded within an artificial rock mixture composed of sand, cement, bentonite and water. Pile loading tests were conducted within the centrifuge and axial forces along the model piles were measured using fiber Bragg grating (FBG) sensing technology. Results are used to demonstrate that centrifuge testing provides a suitable experimental method to study and quantify the effect of socket roughness on the shaft shearing mechanism of rock-socketed piles. Finally, the centrifuge test measurements are compared with several formulations published in the literature, suggesting that centrifuge measurements tend to agree with the overall trend, despite the variability of predictions obtained with different formulations.

Linyi Shu, 1, 2 Hang Zhao, 2 Wenli Huang, 1, 2 Guangsen Hou, 1, 2 Guangyao Song, 1, 2 Huijuan Ma 1–3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People’s Republic of China; 2Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of China; 3Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of ChinaCorrespondence: Guangyao SongEndocrinology Department, Hebei General Hospital, 348, Heping West Road, Shijiazhuang, Hebei 050051, People’s Republic of ChinaTel +86 311 8598 8556Email guangyaosong123@163.comPurpose: This study aimed to investigate how resveratrol (RSV) improves high-fat diet (HFD)-induced hepatic insulin resistance in mice via microRNA (miRNA) mmu-miR-363-3p in vitro and in vivo.Materials and Methods: C57BL/6J mice were fed a HFD for 8 weeks to establish an insulin resistance model. The model mice were treated or not with RSV for 6 weeks. Differential miRNA expression in mouse liver tissues was analyzed by high-throughput sequencing. Mouse HepG2 cells were treated with palmitic acid (PA) to establish a cell model of insulin resistance. HepG2 cells were transfected with mmu-miR-363-3p inhibitor or mimic, and the expression of PI3K-Akt signaling pathway-related proteins was analyzed.Results: Based on the high-throughput sequencing analysis, mmu-miR-363-3p was identified as a major miRNA involved in the action of RSV on insulin resistance. Based on KEGG pathway enrichment analysis, PI3K-Akt signaling was found to be significantly enriched among differentially expressed miRNAs, and this pathway is closely related to insulin resistance. RSV treatment reduced the expression of FOXO1 and G6PC, which are downstream of the PI3K-Akt pathway. In the cell model, mmu-miR-363-3p inhibitor significantly suppressed p-Akt and p-PI3K levels, but enhanced those of FOXO1 and G6PC. In contrast, mmu-miR-363-3p mimic significantly enhanced the p-Akt and p-PI3K levels, but suppressed FOXO1 and G6PC expression, which was similar to the effect of RSV.Conclusion: RSV improves insulin resistance by upregulating miRNA mmu-miR-363-3p via the PI3K-Akt pathway.Keywords: insulin resistance, resveratrol, microRNA, high-throughput sequencing, PI3K-Akt pathway

Hang Zhao,1 Linyi Shu,2 Wenli Huang,2 Wenzhao Wang,2 Guangyao Song1 1Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of China; 2Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People’s Republic of ChinaCorrespondence: Guangyao SongEndocrinology Department, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei 050051, People’s Republic of ChinaTel +86 311 85988556Email guangyaosong123@163.comIntroduction: Despite the increasingly young age at diabetes onset and the increasing number of deaths caused by type 2 diabetes mellitus (T2DM), why some patients develop macrovascular complications but others develop microvascular complications remains controversial and unclear. Notably, some patients have good glucose control but still develop vascular complications, whereas some patients have retinopathy with neither nephropathy nor neuropathy. This study will be performed to explore the risk factors for T2DM complications in Chinese patients.Methods and analysis: Patients with T2DM and healthy people will be recruited from Hebei General Hospital from September 2019 to September 2020. The subjects will be grouped into a control group, T2DM without vascular complications group, T2DM with macrovascular complications group, and T2DM with microvascular complications group; they will then be further subgrouped. The following data will be collected after admission: demographic information such as age, sex, and education; relevant medical history such as duration of diabetes, family history of first-degree relatives with diabetes, and age at diagnosis of diabetes; and anthropometric and blood indicators such as weight, waist circumference, fasting blood glucose level, C-peptide level, total cholesterol level, and triglyceride level. The statistical analysis will be performed using SPSS 22.0 (IBM Corp., Armonk, NY, USA). A P value of

Hang Zhao,1,2 Yunjia Zhang,1 Linyi Shu,1,2 Guangyao Song,1,2 Huijuan Ma1–31Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, People’s Republic of China; 2Endocrinology Department, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of China; 3Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei 050051, People’s Republic of ChinaPurpose: The aim of the study was to examine the effects of resveratrol upon hepatic endoplasmic reticulum stress (ERS) and insulin sensitivity in vivo and in vitro.Material and methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, and insulin resistance was evaluated by the intraperitoneal glucose tolerance test (IPGTT). Mice were then treated with resveratrol for 12 weeks and blood and liver samples collected. Blood biochemical indicators were determined by kits, liver protein expression was determined by western blot, and morphological changes were observed by histological staining. Palmitic acid (PA)-induced insulin-resistant HepG2 cells were established. Cells were exposed to 100, 50 or 20 μM resveratrol for 24 hrs, and proliferation/cytotoxicity was determined. Cells were divided into five groups: control, PA, PA + Rev (100 μM), PA + Rev (50 μM) and PA + Rev (20 μM) groups. After 24 hrs of treatment, cellular proteins were analyzed the same way as animal tissues.Results: The IPGTT confirmed that the insulin resistance model was established successfully. After resveratrol treatment, fasting blood glucose and cholesterol levels declined and the quantitative insulin sensitivity check index increased. Western-blot results showed that resveratrol-treated HFD mice had reduced hepatic levels of p-PERK, ATF-4 and TRIB3, and increased the levels of ATF-6, p-AKT and p-GSK3β. In the cell model, resveratrol with 100 and 50 μM enhanced ERS and insulin resistance, whereas 20 μM had beneficial effects, similar to the animal model.Conclusion: Resveratrol reduced hepatic ERS, thereby improving insulin sensitivity and glucose levels. However, high doses of resveratrol had harmful effects on cells, elevating ERS and insulin resistance. The safe dose of resveratrol needs further investigation.Keywords: blood glucose, insulin resistance, endoplasmic reticulum stress, resveratrol &nbsp

We propose the construction of LEGEND-1000, the ton-scale Large Enriched Germanium Experiment for Neutrinoless $\beta \beta$ Decay. This international experiment is designed to answer one of the highest priority questions in fundamental physics. It consists of 1000 kg of Ge detectors enriched to more than 90% in the $^{76}$Ge isotope operated in a liquid argon active shield at a deep underground laboratory. By combining the lowest background levels with the best energy resolution in the field, LEGEND-1000 will perform a quasi-background-free search and can make an unambiguous discovery of neutrinoless double-beta decay with just a handful of counts at the decay $Q$ value. The experiment is designed to probe this decay with a 99.7%-CL discovery sensitivity in the $^{76}$Ge half-life of $1.3\times10^{28}$ years, corresponding to an effective Majorana mass upper limit in the range of 9-21 meV, to cover the inverted-ordering neutrino mass scale with 10 yr of live time.

We propose the construction of LEGEND-1000, the ton-scale Large Enriched Germanium Experiment for Neutrinoless $\beta \beta$ Decay. This international experiment is designed to answer one of the highest priority questions in fundamental physics. It consists of 1000 kg of Ge detectors enriched to more than 90% in the $^{76}$Ge isotope operated in a liquid argon active shield at a deep underground laboratory. By combining the lowest background levels with the best energy resolution in the field, LEGEND-1000 will perform a quasi-background-free search and can make an unambiguous discovery of neutrinoless double-beta decay with just a handful of counts at the decay $Q$ value. The experiment is designed to probe this decay with a 99.7%-CL discovery sensitivity in the $^{76}$Ge half-life of $1.3\times10^{28}$ years, corresponding to an effective Majorana mass upper limit in the range of 9-21 meV, to cover the inverted-ordering neutrino mass scale with 10 yr of live time.

Rationally designed protein subunit vaccines are being developed for a variety of viruses including influenza, RSV, SARS-CoV-2, and HIV. These vaccines are based on stabilized versions of the primary targets of neutralizing antibodies on the viral surface, namely, viral fusion glycoproteins. While these immunogens display the epitopes of potent neutralizing antibodies, they also present epitopes recognized by non-neutralizing or weakly neutralizing ("off-target") antibodies. Using our recently developed electron microscopy polyclonal epitope mapping approach, we have uncovered a phenomenon wherein off-target antibodies elicited by HIV trimer subunit vaccines cause the otherwise highly stabilized trimeric proteins to degrade into cognate protomers. Further, we show that these protomers expose an expanded suite of off-target epitopes, normally occluded inside the prefusion conformation of trimer, that subsequently elicit further off-target antibody responses. Our study provides critical insights for further improvement of HIV subunit trimer vaccines for future rounds of the iterative vaccine design process.

Clarifying key factors dominating the immune heterogeneity from non-survivors to survivors is crucial for therapeutics and vaccine developments against COVID-19. The main difficulty is to quantitatively analyze the multi-level clinical data of viral dynamics, immune response, and tissue damages. Here, we adopt top-down modeling to quantify key functional aspects and their dynamical interplays in the virus-immune system battle, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses demonstrates T cells dominant role in the virus clearance relative to antibodies, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely cytokine inhibition rate and tissue repair rate also have positive correlations with T cell number, and are significantly suppressed in non-survivors. Simulations show that impaired immune functions of T cells leads to greater inflammation (thus dominates the death), explaining the monotonous increase of COVID-19 mortality with age and higher mortality for males. We conclude that T cells play the role of crucial immunity that saves the death from COVID-19, which points out a new direction to advance current prevention and treatment by incorporating the vaccines, drugs and health care activities that aim to improve T cells number and functions.

In order to improve our understanding of dissolved organic nitrogen (DON) variation characteristics in the biological aerated filter (BAF) for drinking water treatment, this study focused on gas-water ratio, a controlling factor of BAF operation, to study spectral characteristics of DON under different gas-water ratio conditions (0, 0.5:1, 2:1 and 10:1). The variations of dissolved organic carbon (DOC) and DON concentrations showed that DOC removal efficiency was consistent with DON concentration, both of which increased with the increase of gas-water ratio, but the increase gradually reduced and was certain limited. Three-dimensional excitation–emission matrix (3D-EEM) spectroscopy combined with parallel factor (PARAFAC) model and fluorescence regional integration (FRI) technique were applied to analyze the effect of gas-water ratio on spectral characteristics of DON, PARAFAC analysis results identified the main component of DON were tryptophan and protein related substances. The resistances of various fluorescent substances in the FRI technique under the influence of gas-water ratio were shown as: protein substances > humic acid and fulvic acid substances ≈ SMPs-like substances. Correlation analysis showed that the variation of FIS from PARAFAC model was consistent with corresponding normalized integration volume in FRI analysis under different gas-water ratios.

The low bandwidth Pr0.9Ca0.1MnO3 (PCMO) thin films prepared by sol-gel method were suffered tensile and compressive stress grown on SrTiO3 and LaAlO3 substrates. The hysteresis loops at different temperatures show that the coercivity field with tensile stress is larger due to the much stronger pinning potential of ferromagnetism motion. The temperature dependence of the ZFC and FC magnetizations indicates that the stress significantly affects the ferromagnetic (FM) and antiferromagnetic (AFM) transition temperature of PCMO, and the Curie temperature (TC) decreases with tensile stress. The films show strong anisotropy properties that the magnetization increases much faster with the magnetic field when H⊥c, but the coercive field and saturation magnetization do not change significantly. In addition, the persistent photoinduced magnetization is investigated, and significant improvement of the ferromagnetic ordering was observed in low temperature.

Siyang Song,1,2,* Hongzhe Fu,2,* Bing He,2 Dan Wang,3 Mengmeng Qin,2 Dan Yang,1,2 Dechun Liu,2 Ge Song,2 Yujie Shi,2 Hua Zhang,2 Xueqing Wang,2 Wenbing Dai,2 Qiang Zhang1,2 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; 2Beijing Key Laboratory of Molecular Pharmaceutics and the State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; 3Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China *These authors contributed equally to this work Introduction: Endocytosis of nanomaterials is the first step of nano-bio interaction and current regulation is mostly by nanomaterials but seldom by intracellular signaling proteins. Materials and methods: Herein, we synthesized tubular nanocarbon (oxMWCNT) and lamellar-like nanocarbon (oxGRAPHENE) and formulated their aqueous dispersion. A549 and Caco-2 cells were selected as the models of tumor and intestinal epithelial cells, respectively. After knocking down three members of Rho GTPases (Cdc42, Rac1, RhoA) in these two cell lines, their silencing effects on the uptake pathways of nanomaterials with different morphologies were investigated. Results: An unexpected finding was that the knock-down led to opposite uptake trends in different types of cells. The endocytosis of carbon nanomaterials increased in Caco-2 cells when Rho GTPases were inactivated, while that in A549 cells decreased. For nanomaterials with different shapes, the involved GTPase member of Rho family, or regulating protein molecule, was different. Concretely, Cdc42 and Rac1 were involved in oxMWCNT endocytosis, while all three GTPases participated in oxGRAPHENE internalization. More interestingly, such difference induced different uptake pathways, namely, the cellular uptake of oxMWCNT was clathrin-mediated and oxGRAPHENE was caveolin-modulated, both with the involvement of dynamin. Conclusion: In conclusion, this study provides new insights for the potential intervention in nano-bio interplay. Keywords: shape, cellular uptake, intracellular distribution, nanomaterials, Rho GTPases

Yong Huang,1,* Guiqin Song,1,* Xiaotong Chang,1 Zhenhui Wang,2 Xuejiao Zhang,1 Shuguang Han,3 Zhuobin Su,4 Hejie Yang,5 Dongdong Yang,6 Xiaojun Zhang7 1College of Lab Medicine, Hebei North University, Zhangjiakou, China; 2Department of Nuclear Medicine, People’s Liberation Army No 251 Hospital, Zhangjiakou, China; 3Institute of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China; 4The First Affiliated Hospital, Hebei North University, Zhangjiakou, China; 5State Key Laboratory for Mechanical Behavior of Materials, Xi’an Jiaotong University, Xi’an, China; 6School of Physics and Optoelectronic Engineering, Ludong University, Yantai, China; 7Department of Physics, Fourth Military Medical University, Xi’an, China *These authors contributed equally to this work Background: Poor mechanical properties, undesirable fast dissolution rate, and lack of antibacterial activity limit the application of hydroxyapatite (HA) as an implant coating material. To overcome these limitations, a hybrid coating of Ag+-substituted fluorhydroxyapatite and titania nanotube (TNT) was prepared.Methods: The incorporation of silver into the HA-TiO2 hybrid coating improves its antimicrobial properties. The addition of F as a second binary element increases the structural stability of the coating. The TNT/F-and-Ag-substituted HA (FAgHA) bilayer coating on the Ti substrate was confirmed by X-ray diffraction, scanning electron microscope, energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS).Results: The results indicate that the FAgHA/TNT nanocomposite coating has a dense and uniform morphology with a nano-rod-like structure. The solubility measurement result shows that the substitution of F- ions into the AgHA structure has a positive effect on the dissolution resistance of HA. The adhesion strength of FAgHA/TNT has significantly increased because of the interlocking of the roughened surface with nano-rod-like particles that entered into the voids of the TiO2 nanotubes. Compared with that of the bare Ti, the corrosion current density of FAgHA/TNT-coated Ti substrate decreased from 3.71 to 0.18 µA, and its corrosion resistance increased by almost two orders of magnitude. Moreover, despite pure HA, the FAgHA killed all viable Staphylococcus aureus after 24 hours of incubation. Although the fabricated FAgHA/TNT coating is hydrophobic, it induced deposition of the typical spherical apatite when immersed in a simulated body fluid (SBF); the osteoblasts spread very well on the surface of the coating. In addition, in vitro cell culture tests demonstrated cell viability and alkaline phosphatase (ALP) similar to pure HA, which indicated good cytocompatibility. Interestingly, compared with bare Ti, FAgHA/TNT-coated Ti surface was innocent for cell vitality and even more beneficial for cell osteogenesis in vitro.Conclusion: Enhancing the osseointegration and preventing infection in implants, the FAgHA/TNT-coated Ti makes implants more successful. Keywords: titania nanotube, silver, fluorhydroxyapatite, bactericidal effects, osteoin­ductivity

Qianling Lu,1,* Xinyu Dai,1,* Peng Zhang,1,* Xiao Tan,2 Yuejiao Zhong,3 Cheng Yao,4 Mei Song,4 Guili Song,4 Zhenghai Zhang,4 Gang Peng,5 Zhirui Guo,6 Yaoqi Ge,7 Kangzhen Zhang,7 Yuntao Li7 1Department of Neurology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 2Department of Emergency, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 3Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; 4Office of Academic Research, Kizilsu Kirghiz Autonomous Prefecture People’s Hospital, Atush, China; 5Department of Neurosurgery, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 6Department of Geratology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 7Department of General Practice, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Background: Thermoresponsive nanoparticles have become an attractive candidate for designing combined multimodal therapy strategies because of the onset of hyperthermia and their advantages in synergistic cancer treatment. In this paper, novel cetuximab (C225)-encapsulated core-shell Fe3O4@Au magnetic nanoparticles (Fe3O4@Au-C225 composite-targeted MNPs) were created and applied as a therapeutic nanocarrier to conduct targeted magneto-photothermal therapy against glioma cells. Methods: The core-shell Fe3O4@Au magnetic nanoparticles (MNPs) were prepared, and then C225 was further absorbed to synthesize Fe3O4@Au-C225 composite-targeted MNPs. Their morphology, mean particle size, zeta potential, optical property, magnetic property and thermal dynamic profiles were characterized. After that, the glioma-destructive effect of magnetic fluid hyperthermia (MFH) combined with near-infrared (NIR) hyperthermia mediated by Fe3O4@Au-C225 composite-targeted MNPs was evaluated through in vitro and in vivo experiments. Results: The inhibitory and apoptotic rates of Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group were significantly higher than other groups in vitro and the marked upregulation of caspase-3, caspase-8, and caspase-9 expression indicated excellent antitumor effect by inducing intrinsic apoptosis. Furthermore, Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group exhibited significant tumor growth suppression compared with other groups in vivo. Conclusion: Our studies illustrated that Fe3O4@Au-C225 composite-targeted MNPs have great potential as a promising nanoplatform for human glioma therapy and could be of great value in medical use in the future. Keywords: Fe3O4@Au-C225 composite-targeted magnetic nanoparticles, U251 cells, human glioma therapy, magnetic fluid hyperthermia, near-infrared hyperthermia

The aim of the present study was to perform comprehensive prenatal diagnosis using various detection techniques on a fetus in a high‑risk pregnant woman, and to provide genetic counseling for the patient and her family so as to avoid birth defects. The routine karyotype analysis via amniocentesis, fluorescence in situ hybridization, and whole genome microarray technique were performed for the prenatal diagnosis of the fetus. The fetal karyotype was 46,X,ish der(X) inv(X)(p22.3q28)t(X;Y)(q28;q11.2)(XYqter+,SRY‑,DXZ1+, RP11‑64L19+,STS+,XYpter+); namely, one fetal X chromosome belonged to the derivative imbalanced chromosome and this chromosome demonstrated complex chromosomal rearrangements involving inversion, translocation and deletion. Notably, pericentric inversion between Xp22.3 and Xq28 was identified, and the chromosomal microarray technique confirmed that the long arm q28 of the derivative X chromosome had a 1.241‑Mb deletion in Xq28, which included Online Mendelian Inheritance in Man genes such as coagulation factor VIII, glucose‑6‑phosphate dehydrogenase, inhibitor of nuclear factor‑κB kinase subunit γ, trimethyllysine hydroxylase e, Ras‑related protein Rab‑39B and chloride intracellular channel 2. In addition, this chromosome also exhibited the local translocation of fragment Yq11.21‑q11.23, which did not include the sex determining region Y gene. This fetus demonstrated deletion, inversion and translocation syndrome, and may exhibit the corresponding clinical phenotypes (e.g., intellectual disability or general delayed development) (1) of such chromosome abnormalities after birth. Therefore, in prenatal diagnosis, a variety of genetic diagnostic techniques should be comprehensively used based on specific clinical situations, which may accurately reveal the nature, sources and manifestations of the derivative chromosome abnormalities and avoid the birth of children with defects.

Ge Song,1,2,* Wang Jing,3,* Song Xue,1,2 Hongbo Guo,4 Jinming Yu1,2 1Department of Radiation Oncology, School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated with Shandong University, Jinan, 3Department of Radiation Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 4Department of Thoracic Surgery, Shandong Cancer Hospital Affiliated with Shandong University, Jinan, China *These authors contributed equally to the work Purpose: This study aimed to investigate the incidence of nodal skip metastasis (NSM) to identify the risk factors that influence NSM and to assess the prognostic value of NSM in patients with thoracic esophageal squamous cell carcinoma (ESCC).Patients and methods: Between January 2009 and December 2013, 285 patients with ESCC with positive lymph nodes who underwent complete resection were enrolled.Results: For the entire group, NSM occurred in 32.3% (92/285) of patients. The median survival time and 5-year survival rate in the NSM group were 28 months and 12.0%, respectively, compared with 36.3 months and 25.0%, respectively, in the non-NSM group (P=0.008). Both N stage (P=0.001) and T stage (P=0.014) were associated with the incidence of NSM. NSM (P=0.008), T stage (P=0.000), and N stage (P=0.000) were independent prognostic factors for survival. In the NSM group, T stage (P=0.014) and N stage (P=0.000) were independent prognostic factors for survival.Conclusion: It was concluded that NSM is common in ESCC and is associated with poor survival. Keywords: esophageal squamous cell carcinoma, surgery, nodal skip metastasis, incidence, risk factors, prognosis

Wen Shen,1,* Jia Liu,2,* Guohou Zhao,1 Minjuan Fan,1 Gao Song,3 Yang Zhang,1 Zhiying Weng,3 You Zhang4 1Department of Respiratory Medicine, 2Department of Experimental Zoology, The Second Affiliated Hospital of Kunming Medical University, 3School of Pharmaceutical Science, Kunming Medical University, 4Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, People’s Republic of China *These authors contributed equally to this work Background: Smoking is the leading cause of COPD. Exploring molecular markers and understanding the pathogenic mechanisms of smoking-related COPD are helpful for early clinical diagnosis and treatment of the disease. This study aims to identify specific circulating microRNAs (miRNAs) from the blood of COPD patients with a long history of smoking.Methods: Blood samples from four different groups were collected, and miRNA microarray was performed. Differential expression of miRNAs was verified by quantitative polymerase chain reaction. In vitro, THP-1 cells were cultured and stimulated with cigarette smoke extract (CSE) or transfected with miR-149-3p inhibitor/mimics. Protein levels of Toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB) were detected using Western blot and immunofluorescence. Interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were determined by an enzyme-linked immunosorbent assay.Results: miRNA profiling revealed that the expression of 56 miRNAs was changed between the four groups. Expression of miR-149-3p in group C (non-smoker non-COPD) was higher than in group S (smoker non-COPD), S-COPD (smoker with stable COPD) and AE-COPD (smoker with acute exacerbation COPD). CSE stimulation down-regulated the expression of miR-149-3p and up-regulated the TLR-4 and NF-κB levels in THP-1 cells. Transfecting miR-149-3p inhibitors in THP-1 cells also increased the expression of its target genes. Furthermore, overexpression of miR-149-3p inhibited the TLR-4/NF-κB signaling pathways and reduced the secretion of IL-1β and TNF-α.Conclusion: This study found that smoking can induce differential expression of circulating miRNAs, such as down-regulation of miR-149-3p. Reducing miR-149-3p may increase the inflammatory response in COPD patients through the regulation of the TLR-4/NF-κB signaling pathway. Keywords: smoking, COPD, microRNA-149-3p, Toll-like receptor 4, nuclear factor κB

Although agricultural robots are intended to move in straight lines in fields, they may yaw off the track because of tire slippage, surface unevenness, uneven weight distribution, or other factors. Many position-guiding technologies have been developed for agricultural robots, but their high costs have resulted in limited real-world use. Moreover, the use of large farming machinery in conjunction with the enormous tractors that are used to perform farm work can result in the destruction of cultivated land. This article presents the design and implementation of a low-cost planting robot with the capability of high-precision straight-line navigation. A two-stage guidance control scheme is proposed to regulate the robot‘s heading angle and minimize the lateral error in straigh

Guoqi Song,1 Huiyun Ni,1 Linqing Zou,2 Shukui Wang,3 Fuliang Tian,4 Hong Liu,1 William C Cho5 1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 2Department of Human Anatomy, Nantong University, Nantong, 3Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, 4Maternal and Child Health Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 5Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Objectives: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).Design and methods: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.Results: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB) type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS) and progression-free survival (PFS) in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. Keywords: CD40, diffuse large B-cell lymphoma, R-CHOP, prognostic factor

Real-time functional magnetic resonance imaging (rtfMRI) suffers from known issues related to T2*-weighted single-echo echo-planar imaging (EPI). These include image dropout in areas with increased local magnetic susceptibility susceptibility gradients; suboptimal whole-brain blood oxygen level-dependent (BOLD) contrast due to average T2*-weighting; and confounders like subject motion and physiology. During fMRI neurofeedback a metric calculated from real-time brain activity is presented visually to the subject in the scanner. To prevent sham feedback, new methods should focus on improving BOLD signal quality in real-time. In this work, presented as a poster at the 11th annual meeting of the ISMRM Benelux chapter (17 January 2019), we present our work on real-time multi-echo fMRI and its usefulness in increasing the temporal signal-to-noise ratio (tSNR) of rtfMRI., Funding received from Health Holland, LSH-TKI: grant LSHM16053-SGF

A CaO‐Bi2O3‐Al2O3‐B2O3 glass system was studied as a sealant for sodium‐sulfur battery. The thermal properties such as thermal expansion coefficient, glass transition, and softening temperature were determined by dilatometry and differential scanning calorimetry. Selected glasses, based on the thermal properties, were bonded with a‐alumina substrate followed by aging in air at 400°C for 100 hours and in sodium vapor at 350°C for 100 hours. The interfacial compatibility and resistance to sodium vapor corrosion of the bonded and aged samples were evaluated by structural and microstructural analysis using X‐ray diffractometer (XRD) and scanning electron microscope (SEM) attached with energy dispersive spectroscope (EDS). Helium leakage test was performed at room temperature to examine the sealing ability of the select glass. It is found that Bi2O3 increases the thermal expansion coefficient, decreases the glass transition and softening temperature, shows excellent interfacial compatibility and thermal cycling resistance, improves sealing ability, and degrades sodium corrosion resistance.

G protein-coupled receptors (GPCRs) represent the largest class of cell surface proteins and thus constitute an important family of therapeutic targets. Therefore, significant effort has been put towards the identification of novel ligands that can modulate the activity of a GPCR target with high efficacy and selectivity. However, due to limitations inherent to the most common techniques for GPCR ligand discovery, there is a pressing need for more efficient and effective ligand screening methods especially for the identification of potential allosteric modulators. Here we present a high-throughput, label-free and unbiased screening approach for the identification of small molecule ligands towards GPCR targets based on affinity mass spectrometry. This new approach features the usage of target-expressing cell membranes rather than purified proteins for ligand screening and allows the detection of both orthosteric and allosteric ligands targeting specific GPCRs. Screening a small compound library with this approach led to the rapid discovery of an antagonist for the 5-HT receptor and four positive allosteric modulators for GLP-1 receptor that were not previously reported. © 2018 The Royal Society of Chemistry.

Carbon stored in woody debris is a key carbon pool in forest ecosystems. The most widely-used method to convert woody debris volume to carbon is by first multiplying field-measured volume with wood density to obtain necromass, and then assuming that a fixed proportion (often 50%) of the necromass is carbon. However, this crucial assumption is rarely tested directly, especially in the tropics. The aim of this study is to verify the field carbon concentration values of living trees and woody debris in two distinct tropical forests in Taiwan. Wood from living trees and woody debris across five decay classes was sampled to measure density and carbon concentrations. We found that both wood density and carbon concentration (carbon mass/total mass) declined significantly with the decay class of the wood. Mean (±SE) carbon concentration values for living trees were 44.6 ± 0.1%, while for decay classes one to five they were respectively 41.1 ± 1.4%, 41.4 ± 1.0%, 37.7 ± 1.3%, 30.5 ± 2.0%, and 19.6 ± 2.2%. Total necromass carbon stock was low, only 3.33 ± 0.55 Mg C ha−1 in the windward forest (Lanjenchi) and 4.65 ± 1.63 Mg C ha−1 in the lowland forest (Nanjenshan). Applying the conventional 50% necromass carbon fraction value would cause a substantial overestimate of the carbon stocks in woody debris of between 17% and 36%, or about 1 Mg of carbon per hectare. The decline in carbon concentration and the increase of variances in the heavily decayed class suggest that in high-diversity tropical forests there are diverse decomposition trajectories and that assuming a fixed carbon fraction across woody pieces is not justified. Our work reveals the need to consider site-specific and decay class-specific carbon concentrations in order to accurately estimate carbon stocks and fluxes in forest ecosystems. If the marked decline in carbon content with necromass decay is typical of tropical forests, the dead wood carbon pool in the biome needs revision and is likely to be overestimated

Social influence is a fundamental issue in social network analysis and has attracted tremendous attention with the rapid growth of online social networks. However, existing research mainly focuses on studying peer influence. This paper introduces a novel notion of structural influence and studies how to efficiently discover structural influence patterns from social streams. We present three sampling algorithms with theoretical unbiased guarantee to speed up the discovery process. Experiments on a big microblogging dataset show that the proposed sampling algorithms can achieve a 10 times speedup compared to the exact influence pattern mining algorithm, with an average error rate of only 1.0%. The extracted structural influence patterns have many applications. We apply them to predict retweet behavior, with performance being significantly improved.

Objective Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. Methods The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15–99years) diagnosed with ovarian cancer during 1995–2009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from 67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated age-standardised 5-year net survival by stage at diagnosis (localised or advanced). Results Survival from type I epithelial ovarian tumours for women diagnosed during 2005–09 ranged from 40 to 70%. Survival from type II epithelial tumours was much lower (20–45%). Survival from germ cell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). Conclusions There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology.

Yuanyue Li,1 Congjie Dai,2 Juan Li,3 Weiwei Wang,3 Gang Song31Fisheries College, Jimei University, Fujian, China; 2School of Chemical and Life Science, Quanzhou Normal University, Fujian, China; 3Cancer Research Center, Medical College of Xiamen University, Xiamen, ChinaBackground: Growing evidence supports BH3-interacting domain death agonist (Bid) playing a dual role in DNA damage response. However, the effects of Bid on hepatocellular carcinoma (HCC) cell proliferation in response to etoposide-induced DNA damage have not been sufficiently investigated.Methods: Using a stable Bid-overexpression HCC cell line, Bid/PLC/PRF/5, overexpression of Bid promoted loss of viability in response to etoposide-induced DNA damage. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]- and BrdU (5'-bromo-2'-deoxyuridine)-labeling assays revealed that etoposide-inhibited HCC cells grew in concentration- and time-dependent manners. The phosphorylations of Akt and mitogen-activated protein kinases (MAPKs) in response to etoposide-induced DNA damage were analyzed by Western blotting.Results: The survival rates of 100 µM etoposide on the cells with control vector and Bid/PLC/PRF/5 at 48 hours amounted to 71% ± 0.75% and 59% ± 0.60% with MTT assay, and similar results of 85% ± 0.08% and 63% ± 0.14% with BrdU-labeling assay respectively. Moreover, overexpression of Bid sensitized the cells to apoptosis at a high dose of etoposide (causing irreparable damage). However, it had little effect on the proliferation at a low dose of etoposide (repairable damage). Furthermore, the phosphorylation status of Akt and MAPKs were investigated. Overexpression of Bid suppressed the activation of Akt with respect to etoposide-induced DNA damage. Similar to Akt, the levels of phosphorylated p38 and phosphorylated c-Jun were attenuated by Bid-overexpression. On the contrary, the level of phosphorylated ERK1/2 was sustained at a high level, especially in Bid/PLC/PRF/5 cells.Conclusion: Taken together, these results suggest that overexpression of Bid suppressed the activation of Akt, p38, and c-Jun, and promoted the activation of ERK1/2 induced by etoposide, suggesting that the promotion of ERK1/2 activation may have a negative effect on Bid-mediated HCC DNA damage induced by etoposide.Keywords: HCC, mitogen-activated protein kinases, BH3-interacting domain death agonist

MicroRNAs (miRNAs) are important epigenetic regulators of gene expression. Although several miRNAs have been implicated in osteosarcoma, their role in regulation of osteosarcoma cancer stem cells (CSCs) remains unknown. Here we demonstrated that miR-26a is downregulated in osteosarcoma CSCs when derived by either sarcosphere generation, chemodrug or aldehyde dehydrogenase (ALDH) activity selection. Lentiviral overexpression of miR-26a in ZOS and 143B osteosarcoma cells decreases the expression of stem cell markers and suppresses sarcosphere formation, as well as ALDH activity. Moreover, miR-26a overexpression inhibits the tumor cell growth both in vitro and in vivo. We further demonstrate that miR-26a directly target Jagged1, one of the Notch ligand, and that its tumor suppressive effects are mediated through inhibition of Jagged1/Notch signaling. Importantly, reduced miR-26a expression, as determined by in situ hybridization in patient tumors (n=92), is associated with lung metastasis and poor overall survival of osteosarcoma patients. Together, these data suggest the essential role of miR-26a/Jagged1/Notch pathway in regulating the stem cell-like traits of osteosarcoma cells and provide a potential target for osteosarcoma therapy.