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CdSiP2 is an outstanding mid-infrared nonlinear optical crystal material with high thermal conductivity. However, the microscopic physics behind its thermal transport behavior is still unclear. In this study, we have investigated the source of the thermal conductivity of CdSiP2 based on anharmonicity lattice dynamics (ALD) and the first-principle calculation. The results are well accordance with the experimental measurement in a wide temperature range. Based on our results, the acoustic phonon lifetime of CdSiP2 is higher than that of the thermoelectric and semiconducting materials reported in previous studies, which is induced by the low lattice anharmonicity demonstrated by CdSiP2. The mode-dependent thermal conductivity is obtained with the contribution of optical phonons being significant (27%) above 300 K; this is mainly due to the high phonon group velocity and relatively long phonon lifetime of low-energy optical phonons (80–200 cm−1). A high lifetime of acoustic phonons and remarkable contribution of low-energy optical phonons can be responsible for the high thermal conductivity of CdSiP2.

Background The aim of this study was to explore the potential genes and transcription factors involved in postoperative cognitive dysfunction (POCD) via bioinformatics analysis. Material/Methods GSE95070 miRNA expression profiles were downloaded from Gene Expression Omnibus database, which included five hippocampal tissues from POCD mice and controls. Moreover, the differentially expressed miRNAs (DEMs) between the two groups were identified. In addition, the target genes of DEMs were predicted using Targetscan 7.1, followed by protein-protein interaction (PPI) network construction, functional enrichment analysis, pathway analysis, and prediction of transcription factors (TFs) targeting the potential targets. Results A total of eight DEMs were obtained, and 823 target genes were predicted, including 170 POCD-associated genes. Furthermore, potential key genes in the network were remarkably enriched in focal adhesion, protein digestion and absorption, ECM-receptor interaction, and Wnt and MAPK signaling pathways. Conclusions Most potential target genes were involved in the regulation of TFs, including LEF1, SP1, and AP4, which may exert strong impact on the development of POCD.

With the advantages of high power generation efficiency, low pollution and noise, Proton exchange membrane fuel cell (PEMFC) is regarded as a promising energy source for electric vehicles and stationary power stations. However, performance degradation is inevitable when PEMFC is in operating, which makes the estimation of remaining useful life (RUL) a crucial problem to assure the stability and security of PEMFC. In this paper, the RUL of PEMFC is estimated by stochastic fusion filtering approach with the dataset provided in IEEE PHM 2014 Data Challenge. The total voltage dataset as well as each cell degradation dataset are fused to get more accurate results. The simulation results demonstrate the good characteristics of this method.

Objectives To evaluate the effectiveness of iodine-125 (125I) seed implantation for pancreatic cancer (PC), and preliminarily evaluate the clinical value of a self-developed three-dimensional (3D) visualized seed planning and navigation system in 125I seed implantation for treatment of PC. Patients and methods Our team retrospectively reviewed 25 PC patients who underwent 125I seed implantation between December 2010 and November 2016. The patients were divided into two groups: 3D visualization preoperative planning group (12 patients, 13 lesions) and two-dimensional (2D) regular group (13 patients, 14 lesions). We compared and analyzed the parameters of the two groups, such as number of needle insertions, one-time treatment success rate, proportion of added seeds, local control rate, rate of complications, rate of pain relief, and the survival rate and risk factors of the two groups. There was no significant difference in clinical data of the two groups. Results 125I seed implantation was performed successfully in all PC patients, with no occurrence of serious complications during and after the procedure. The one-time treatment success rate of 3D group (80%) was higher than that of 2D group (45.5%) (P

Immune checkpoint inhibitors (ICIs) have greatly improved the treatment of advanced non-small-cell lung cancer, including lung adenocarcinoma (LUAD). Patients treated with ICIs can have long-term clinical outcomes; however, acquired resistance to ICI therapy has been frequently observed. To date, little is known about the underlying mechanisms. In this study, we report the case of a male smoker with metastatic LUAD who initially received multi-line radiotherapy and chemotherapy and achieved stable disease (SD) for almost 10 years. The patient was treated with nivolumab for about 15 months. However, the disease later progressed rapidly. A genetic profile of the patient revealed the homozygous deletion of the human leukocyte antigen (HLA)-B gene, which may have conferred the acquired resistance. Our study is the first to describe the homozygous deletion of the HLA-B gene as an acquired-resistance mechanism to programmed cell death protein 1 (PD-1) blockade in a patient with LUAD. This evidence suggests that tumor cells can selectively lose HLA-A, B, and C to survive under strong immune pressure. This discovery enriches and develops our understanding of the mechanism of drug resistance in ICI therapy in LUAD. However, further investigations are urgently needed to be conducted to determine how this resistance can be overcome.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that leads to respiratory failure, and for which there is no effective treatment. Apolipoprotein A-1 (ApoA-1) has been reported to ameliorate the bleomycin (BLM)-induced IPF model. Methods To examine the function of D-4F, an ApoA-1 mimetic polypeptide, in IPF, we used an in-vivo BLM-induced model. We assigned mice into the following 3 groups: the Blank Group (BLK Group), the Bleomycin Treatment Group (Model Group), and the D-4F Interference Group (Inter Group). The BLM-induced fibrosis was examined by hematoxylin and eosin, Masson's trichrome (M-T) staining and immunohistochemical staining. An untargeted lipidomic and transcriptomic analysis were used to examine the function of D-4F. Results There were 35 differentially altered lipids (DALs) in the BLK, Model and Inter Groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that glycerophospholipid metabolism was the most highly enriched of the 35 DALs. There were 99 differentially expressed genes (DEGs) in the BLK, Model and Inter Groups. The enriched KEGG pathway analysis showed that the mitogen-activated protein kinase (MAPK) pathway was 1 of the top 10 pathways. The results of the untargeted lipidomic and transcriptomic analysis showed that phospholipase A2 group 4c (Pla2g4c) was a crucial gene in both the MAPK pathway and glycerophospholipid metabolism. Pla2g4c was increased in the Model Group but decreased in the Inter Group. Conclusions It may be that D-4F prevented the BLM-induced pulmonary fibrosis model by inhibiting the expression of pla2g4c. Our findings suggest that D-4F may be a potential treatment of IPF.

The aim of this study was to determine the prevalence and transmission mechanism(s) of mcr-1 in the gut flora of children. Faecal samples (n = 173) were obtained from non-diarrhoea patients at the Children's Hospital of Zhejiang University (Hangzhou, China). PCR-based analysis indicated that 17 isolates from 9.8% of the samples were positive for mcr-1, comprising 16 Escherichia coli and 1 Citrobacter freundii. Nine mcr-1-bearing isolates co-expressed extended-spectrum β-lactamase (ESBL) genes, but plasmid-mediated quinolone resistance (PMQR) genes were not detected. Transconjugation followed by Southern hybridisation analysis revealed that 14 of the E. coli isolates were able to transfer their colistin-resistant phenotype to E. coli EC600. All 14 of these E. coli strains contained a major mcr-1-containing conjugative plasmid with a size of ca. 33 kb or 55 kb. All but two of the E. coli isolates presented distinct pulsed-field gel electrophoresis (PFGE) patterns. Multilocus sequence typing (MLST) analysis revealed 11 sequence types (STs) among the E. coli 16 isolates, with ST117 being the most common. The finding of a high prevalence of mcr-1 in the intestinal flora of children, with the majority of mcr-1-positive isolates being E. coli, highlights the need for more rational use of polymyxins to prevent polymyxin resistance from becoming disseminated among different microbial pathogens. Given the high detection rate of mcr-1 in children, we recommend that polymyxin is no longer used as a last-resort antimicrobial agent and that alternative strategies are developed to treat infections caused by such pathogens.

A series of YAG:Ce 3+ /Eu 3+ , YAG:Ce 3+ /Eu 3+ /Bi 3+ and YAG:Ce 3+ /Gd 3+ phosphors were synthesized by a co-precipitation method. The results suggest that all of phosphors have the cubic phase and nearly spherical morphology. However, the red emission can be produced by codoping Eu 3+ and Eu 3+ /Bi 3+ ions in YAG:Ce 3+ , and the codoped Gd 3+ ions can induce the red-shift of Ce 3+ emission. These results suggest that the Eu 3+ , Eu 3+ /Bi 3+ and Gd 3+ ions can be used to decrease the correlated color temperature and increase the color-rendering index of white light-emitting diodes based on InGaN blue chip and YAG:Ce 3+ phosphors.

The threat of antibiotic resistance has increased dramatically in recent years. Fosfomycin, an old antibiotic agent, has been re-introduced to fight infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP). However, the trend of fosfomycin resistance among KPC-KP strains is increasing. In this study, 80 KPC-KP clinical isolates were collected from three teaching hospitals during 2014-2017 in China and were subjected to whole-genome sequencing (WGS). The fosfomycin resistance phenotype and resistance mechanisms were investigated by antimicrobial susceptibility testing and carbon source growth test, respectively. Among all KPC-KP strains, 80.0% (64/80) were resistant to fosfomycin and 36.3% (29/80) were positive for the mobile fosfomycin resistance gene fosA3. Among the 63 strains that were unable to grow in M9 basic medium with glycerol-3-phosphate (G3P) as the sole carbon source (mediated by mutation of the target gene glpT), there was no significant difference regarding the MIC distribution of fosfomycin between fosA3-positive and fosA3-negative strains (P = 0.577). Among the 50 strains that were negative for fosA3 but positive for fosA, the fosfomycin MICs of strains unable to grow in M9 basic medium with G3P as the sole carbon source were significantly higher (P0.001) than in strains that were able to grow in M9 basic medium with G3P as the sole carbon source. Our findings indicate that fosfomycin resistance among KPC-KP in China is an emerging problem and the two major mechanisms of resistance identified were plasmid-mediated fosfomycin resistance gene fosA3 and mutation of the target gene glpT.

Background The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we introduced a model to describe and monitor the immune status of sepsis and explored its prognostic value. Methods A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at day 1 and 3. Serum cytokines levels (TNF-α, IL-2R, IL-6, IL-8 and IL-10) and CD14 + monocyte HLA-DR expression were measured to serve as immune markers. Cut-off values were acquired from ROC curves and serum cytokine level higher than or HLA-DR level lower than cut point was defined as “positive”, otherwise defined as “negative”. Classification of each immune status, namely SIRS, CARS and MARS, was defined by numbers of positive immune markers levels. Changes of immune status from day 1 to 3 were classified into four groups which were Stabilization (SB), Deterioration (DT), Remission (RM) and Non-remission (NR). Results A total of 174 septic patients were enrolled including 50 non-survivors. In univariate analysis, serum levels of TNF-α, IL-2R, IL-6, IL-8 and IL-10 and HLA-DR expression at day 1 and 3 were associated with prognosis. Multivariate analysis discovered IL-10 and HLA-DR expression at day 3 were independent prognostic factors. Patients with MARS at day 1 had the highest mortality rate up to 58.7% among three immune status classifications, so did the patient with MARS at day 3 with mortality rate up to 69.2%. Immune status of 46.1% patients changed from day 1 to 3. Among four groups of immune status changes, DT had the highest mortality rate up to 77.8% followed by NR, RM and SB with mortality rate of 64.7%, 42.9% and 11.2% respectively. Conclusions Patients with severe immune disorder defined as MARS or deterioration of immune status defined as DT have the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers levels has prognostic values and worthy of further investigation. Trail Registration: ChiCTR-OCC-14005202 (Chinese Clinical Trial Registry), Registered 09 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=4373

Nanorod and nanosphere ${{\rm Gd}_2}{{\rm O}_3}\!:\!{{\rm Tb}^{3 + }}$Gd

Background Secondary infection has a higher incidence in septic patients and affects clinical outcomes. This study aims to investigate the clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis. Methods A four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between January, 2014 and January, 2018. Clinical data were acquired from medical records. CD14+ monocyte human leukocyte antigen-D related (HLA-DR) expression and serum cytokines levels were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA) respectively. Results A total of 297 septic patients were enrolled, 92 of whom developed 150 cases of secondary infections. Respiratory tract was the most common site of secondary infection (n = 84, 56%) and Acinetobacter baumanii the most commonly isolated pathogen (n = 40, 31%). Urinary and deep venous catheterization increased the risk of secondary infection. Lower HLA-DR expression and elevated IL-10 level were found in secondary infection group. The expected prolonged in-hospital stay owing to secondary infection was 4.63 ± 1.87 days. Secondary infection was also associated with higher in-hospital, 30-day and 90-day mortality. Kaplan-Meier survival analysis and Log-rank test revealed that secondary infection group had worse survival between day 15 and day 90. Conclusions Urinary and deep venous catheterization increased the risk of secondary infection, in which underlying immunosuppression might also play a role. Secondary infection affected the prognosis of septic patients and prolonged in-hospital length of stay.

A recently developed S. aureus subtyping module for rapidly differentiate methicillin-resistant Staphylococcus aureus (MRSA) from methicillin-susceptible S. aureus (MSSA) had been introduced into China. The principle of this method was to identify the methicillin resistance through detection of a specific phenol soluble modulin-mec peak (PSM-mec) by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). A total of 347 non-duplicated S. aureus strains were collected from the Second Affiliated Hospital of Zhejiang University School of Medicine during January 2014 to February 2019. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the automated subtyping module in identifying MRSA were evaluated. The specificity and PPV of this method were both 100%, and the sensitivity was 60.2%. PSM-bearing MRSA was reported with different prevalence from different parts of the world, our sample collection has the highest percentage so far. The repeatability showed that 1.7% (6/347) and 18.4% (64/347) were reported differently in the intra- and inter-batch analysis, respectively, which demonstrated that the threshold of this method could be further optimized to increase the sensitivity of MRSA detection. Overall, Bruker™ MALDI Biotyper can detect S. aureus isolates with a quite high specificity and expedite the identification of MRSA isolates without using extra reagent, labor, or time. The reduced turnaround time of MRSA identification is essential for appropriate therapeutic management and timely intervention for infection control.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a public health concern worldwide, but comprehensive analysis of risk factors for CRPA remains limited in China. We conducted a retrospective observational study of carbapenem resistance in 71,880 P. aeruginosa isolates collected in Zhejiang Province during 2015–2017. We analyzed risk factors for CRPA, including the type of clinical specimen; the year, season, and region in which it was collected; patient information, including age, whether they were an outpatient or inpatient, and whether inpatients were in the intensive care unit or general ward; and the level of hospital submitting isolates. We found CRPA was more prevalent among isolates from patients >60 years of age and in inpatients, especially in intensive care units. In addition, specimen types and seasons in which they were collected were associated with higher rates of CRPA. Our findings can help hospitals reduce the spread of P. aeruginosa and optimize antimicrobial drug use.

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In this study, a CRISPR/Cas9-mediated genome editing method was used to study the functions of the mgrB , tetA , and ramR genes in mediating colistin and tigecycline resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP). Inactivation of the tetA or ramR gene or the mgrB gene by CRISPR/Cas9 affected bacterial susceptibility to tigecycline or colistin, respectively.

T cell-mediated destruction of tumors and virus-infected cells is restricted by co-inhibitory receptors such as programmed cell death protein 1 (PD-1). Monoclonal antibodies blocking PD-1 have produced impressive clinical activity against human cancers, but durable response is limited to a minority of patients. Previous results suggest that B and T lymphocyte attenuator (BTLA), a co-inhibitory receptor structurally related to PD-1, may contribute to the resistance to PD-1 targeted therapy and co-blockade of BTLA can enhance the efficacy of anti-PD-1 immunotherapy. However, the biochemical mechanism by which BTLA represses T cell activity and to what extent the mechanism differs from that of PD-1 is unknown. Here we examine differences in the ability of BTLA and PD-1 to recruit effector molecules and regulate T cell signaling. We show that PD-1 and BTLA recruit different tyrosine phosphatases to regulate either CD28 or T cell antigen receptor (TCR)-signaling cascades. Our data reveal unexpected disparities between two structurally related immune checkpoints and two phosphatase paralogs.

A recently developed S. aureus subtyping module for rapidly differentiate methicillin-resistant Staphylococcus aureus (MRSA) from methicillin-susceptible S. aureus (MSSA) had been introduced into China. The principle of this method was to identify the methicillin resistance through detection of a specific phenol soluble modulin-mec peak (PSM-mec) by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). A total of 347 non-duplicated S. aureus strains were collected from the Second Affiliated Hospital of Zhejiang University School of Medicine during January 2014 to February 2019. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the automated subtyping module in identifying MRSA were evaluated. The specificity and PPV of this method were both 100%, and the sensitivity was 60.2%. PSM-bearing MRSA was reported with different prevalence from different parts of the world, our sample collection has the highest percentage so far. The repeatability showed that 1.7% (6/347) and 18.4% (64/347) were reported differently in the intra- and inter-batch analysis, respectively, which demonstrated that the threshold of this method could be further optimized to increase the sensitivity of MRSA detection. Overall, Bruker™ MALDI Biotyper can detect S. aureus isolates with a quite high specificity and expedite the identification of MRSA isolates without using extra reagent, labor, or time. The reduced turnaround time of MRSA identification is essential for appropriate therapeutic management and timely intervention for infection control.

Background Gram-positive bacteria are dangerous and challenging agents of infection due to their increasing resistance to antibiotics. We aim to analyse the epidemiology and risk factors of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) in Zhejiang China. Methods Gram-positive bacteria (including S. aureus, Enterococcus faecalis and Enterococcus faecium) were collected from eighty-six hospitals of eleven cities in Zhejiang China from 2015 to 2017. The detection rates of MRSA and VRE infection were calculated for the non-duplicated isolate according to year, region, hospital level, patient age, specimen type and patient category. Meanwhile, the detected resistances of MRSA, E. faecalis and E. faecium to different antibiotics from 2015 to 2017 were compared. The risk factors and the differences in MRSA and VRE detection rates were compared using odds ratio (OR) with 95% confidence interval (95% CI) and Chi-square test respectively. Results From 2015 to 2017, the detection rates of MRSA and VRE decreased gradually. The cities with the highest MRSA and VRE detection rates tended to be adjacent; for example, the neighbouring cities Hangzhou and Quzhou had simultaneously high rates of MRSA and VRE infection. Patients from IIIA hospital who were older than 75 years and in the intensive care unit (ICU) were most at risk. No vancomycin-resistant isolate was found in MRSA. Resistance of E. faecalis and E. faecium to vancomycin and linezolid decreased slightly and then maintained a low level. Conclusions The detection rates of MRSA and VRE stayed at moderate and low levels during the three year period of this study, while local dissemination was found in MRSA and VRE isolates. Sustained surveillance is necessary to prevent the spread or clonal dissemination of drug-resistant strains in Zhejiang China.

Circular RNAs (circRNAs) are endogenous non‑coding RNAs implicated in atherosclerosis. The aim of the present study was to explore the function of circRNA‑0044073 in atherosclerosis. Reverse transcription quantitative polymerase chain reaction assays were used to measure the expression levels of circRNA‑0044073, microRNA (miRNA/miR)‑107, janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), B‑cell lymphoma 2 (Bcl‑2) and v‑myc avian myelocytomatosis viral oncogene homolog (c‑myc) in in blood cells from patients with atherosclerosis. RNA pull‑down and luciferase reporter assays were then used to determine the association between circRNA and miR expression, and miR and gene expression, respectively. Matrigel invasion assay and flow cytometry were used to analyze cell invasion and cell cycle. Western blot analysis and ELISA were used to evaluate the expression levels of proteins. It was identified that the expression of circRNA‑0044073 was upregulated and the expression of miR‑107 was downregulated in atherosclerotic blood cells. Overexpression of circRNA‑0044073 promoted the proliferation of human vascular smooth muscle cells (HUVSMCs) and human vascular endothelial cells (HUVECs), while overexpression of miR‑107 inhibited their proliferation. In addition, circRNA‑0044073 suppressed the levels of miR‑107 via a sponge mechanism. Lipopolysaccharide (LPS) affected the proliferation of HUVSMCs and HUVECs, and also resulted in changes in circRNA‑0044073 expression levels. CircRNA‑0044073 promoted the proliferation and invasion of HUVSMCs and HUVECs in spite of the opposite effect observed with LPS treatment. The JAK/STAT signaling pathway was activated in patients with atherosclerosis. CircRNA‑0044073 favored the activation of the JAK/STAT signaling pathway and inflammation in HUVSMCs and HUVECs. These data indicate that circRNA‑0044073 is upregulated in atherosclerosis and promotes the proliferation and invasion of cells by targeting miR‑107 and activating the JAK/STAT signaling pathway, potentially offering a target for novel treatment strategies against atherosclerosis.

The metastable zone width and induction period of ZTS solution have been measured to investigate the influence of H3PO4 on solution stability, and it could be improved by adding phosphoric acid. Pure and H3PO4 doped ZTS crystals have been successfully grown using the slow-cooling method in aqueous solution. Several crystal samples were characterized by XRD, FTIR, TG, DTA, DTG, UV-VIS and SHG. The results show that some changes have taken place on external morphology and internal structure after H3PO4-doping. Thermostability, light transmittance and SHG efficiency of ZTS crystals are also affected by H3PO4, and all of them become better than undoped crystal, which are meaningful for practical applications of crystals.

Summary Background Bacterial translocation (BT) plays a vital role in the development of liver cirrhosis (LC); however, little is known regarding the role of gut innate immunity in cirrhosis. Aims To observe the influence of BT on multiple vital organs in LC and changes in the gut toll-like receptor-4 and nod-like receptor family pyrin domain containing-3 innate pathways in liver cirrhosis rats with bacterial translocation. Methods Wistar rats were divided into control and liver cirrhosis with and without bacterial translocation groups. Functional analysis was conducted using peripheral serum. Hematoxylin-eosin staining was performed to evaluate morphological changes in vital organs. Immunohistochemistry was performed to identify the distribution of toll-like receptor-4, nuclear factor-κ-gene binding-p65, nod-like receptor family pyrin domain containing-3, and its adaptor molecule Asc in the ileum. An enzyme-linked immunosorbent assay was conducted to measure tumor necrosis factor-α, interleukin-1β and interleukin-18 levels. Results A significant decrease in the serum albumin level and an increase in the serum ammonia level were detected in the BT-positive rats compared with the BT-negative rats. Pathological injuries of the intestines and livers of the BT-positive rats were greatly increased compared with the BT-negative rats. The cirrhotic rats with bacterial translocation exhibited increased expression of toll-like receptor-4, nuclear factor-κ-gene binding-p65, nod-like receptor family pyrin domain containing-3, Asc and tumor necrosis factor-α in the intestines compared with the negative group. There were no significant differences of interleukin-1β and interleukin-18 in the intestines between these two groups. Conclusions Excessive activation of nuclear factor-κ-gene binding-p65/tumor necrosis factor-α and impaired activation of nod-like receptor family pyrin domain containing-3/Asc/interleukin-1β, interleukin-18 in the intestinal mucosa were observed in the cirrhotic rats with BT. Regulation of innate immunity in the intestinal mucosa may represent a novel strategy for the prevention and treatment of LC and its complications.

// Zejun Fang 1 , Aifen Lin 2 , Jiaoe Chen 1 , Xiaomin Zhang 1 , Hong Liu 3 , Hongzhang Li 1 , Yanyan Hu 1 , Xia Zhang 2 , Jiangang Zhang 2 , Lanlan Qiu 1 , Lingming Mei 1 , Jimin Shao 4 , Xiang Chen 1 1 Central Laboratory, Sanmen People’s Hospital of Zhejiang, Sanmen, Zhejiang, 317100, China 2 Human Tissue Bank, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, 317000, China 3 Zhejiang Normal University - Jinhua People’s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004, China 4 Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China Correspondence to: Xiang Chen, email: sychenxiang@126.com Jimin Shao, email: shaojimin@zju.edu.cn Keywords: CREB1, ribonucleotide reductase small subunit M2, aggressiveness, colorectal cancer Received: March 16, 2016 Accepted: October 17, 2016 Published: October 27, 2016 ABSTRACT As the small subunit of Ribonucleotide reductase (RR), RRM2 displays a very important role in various critical cellular processes such as cell proliferation, DNA repair, and senescence, etc. Importantly, RRM2 functions like a tumor driver in most types of cancer but little is known about the regulatory mechanism of RRM2 in cancer development. In this study, we found that the cAMP responsive element binding protein 1 (CREB1) acted as a transcription factor of RRM2 gene in human colorectal cancer (CRC). CREB1 directly bound to the promoter of RRM2 gene and induced its transcriptional activation. Knockdown of CREB1 decreased the expression of RRM2 at both mRNA and protein levels. Moreover, knockdown of RRM2 attenuated CREB1-induced aggressive phenotypes of CRC cells in vitro and in vivo . Analysis of the data from TCGA database and clinical CRC specimens with immunohistochemical staining also demonstrated a strong correlation between the co-expression of CREB1 and RRM2. Decreased disease survivals were observed in CRC patients with high expression levels of CREB1 or RRM2. Our results indicate CREB1 as a critical transcription factor of RRM2 which promotes tumor aggressiveness, and imply a significant correlation between CREB1 and RRM2 in CRC specimens. These may provide the possibility that CREB1 and RRM2 could be used as biomarkers or targets for CRC diagnosis and treatment.

The effects of polycarboxylic acid (PC), naphthalene sulfonate (NS), and aliphatic (AH) superplasticizers on the carbonation of concrete were investigated. These three kinds of superplasticizers can improve anti-carbonation performance of concrete, and their order according to magnitude of effect are as follows PC > AH > NS. The mechanism behind this phenomenon was investigated using mercury intrusion porosimetry of the concrete, thermogravimetric analysis, X-ray diffraction, scanning electron microcopy, and X-ray photoelectron spectrometry of synthetic hydrated products. The effects of superplasticizers on carbonation resistance are associated not only with pore structure but also with the morphology of hydrated products.

A first-principles calculation is applied to perform a study of the Cu: KTaO3 system. The defect formation energy, the doping induced lattice distortion and the electronic structure properties have been calculated. The defect formation energy found that Cu is prefer to substitute K (CuK) at corresponding defect charge state +3( Cu K 3 + ), +1( Cu K 1 + ) and 0 ( Cu K 0 ) with Fermi energy increase; The doping of Cu leads to an obvious distortion of the oxygen octahedron, along with the change of ionic bond characteristics; Further research on electronic structure shows that the doped Cu atom mainly occupies the top of the valence band, resulting in the decrease of the band gap.

Neurocysticercosis is a parasitic disease that results from the larvae of Taenia solium. While neurocysticercosis is considered as the most common parasitic infection of the nervous system, spinal neurocysticercosis is rare. The present case study investigated a 59-year-old woman, who was admitted to our hospital with pain in the bilateral lower limbs and urinary complaints in the form of straining of micturition with increasing frequency. Magnetic resonance imaging revealed an intradural extramedullary lesion extending from L1/2 to S1 of the spine. Subsequently, a laminectomy from L1 to S1 was performed 3 days post-presentation. Intraoperatively, a thin-walled cyst with clear fluid was identified, extending from L2 to S1. The exposed, white and mucoid cysticerci was removed completely. Which on pathological examination was identified to be cysticercosis.

In this study, we grew CuO doped potassium tantalum niobate (Cu:KTN) crystals with a uniform superlattice structure by the off-center top-seeded solution growth (TSSG) method. The process of crystal superlattice structure formation was observed under a polarizing microscope at variable temperatures. It was found that the formation of the superlattice structure in the crystal was closely related to the formation process of the domain structure in the crystal. The 90° domain structure in the crystal promoted the formation of the superlattice structure in the crystal. The purpose of the formation of the superlattice structure is to enable the crystal to reach a more stable state. The clear diffraction effect of the crystal superlattice structure is similar to the x-ray diffraction phenomenon of low-temperature crystals, and it exists in the crystal in a three-dimensional structure.

Gd2O3: Tb3+nanocrystal co-doped with Mg2+ and Mn2+ ions were prepared by polyol method. The size, morphology, structure, fluorescence and relaxation properties of the nanoparticles were characterized, and the biocompatibility of Gd2O3: Tb3+ nanoparticles was evaluated by MTT toxicity test. The results showed that the fluorescence emission intensity of Gd2O3: Tb3+ nanocrystals was the highest with the Mg2+ doping concentration of 0.05 mmol, and the longitudinal relaxivity (r1) decreased with the increase of Mg2+ concentration, while the transverse relaxivity (r2) increased slightly. The fluorescence emission intensity of Gd2O3: Tb3+ nanoparticles were decreased after Mn2+ doping, whereas the longitudinal and transverse relaxivity were improved. The nanoparticles showed good biocompatibility with Gd concentration ranging from 0.05 and 0.2 mM. The results indicated that the synthesized Gd2O3: Tb3+ nanoparticles were expected to be used in fluorescence-MRI dual-mode biological detection.

SrLaGa3O7:Eu3+ and SrLaGa3O7:Tb3+ fluorescent powders were synthesized using solid sintering procedure. The crystal structure and luminescence of the synthesized fluorescent powders were surveyed. XRD patterns of the synthesized fluorescent powders demonstrate that they have the single tetragonal phase. Under excitation at 392 nm, SrLaGa3O7:Eu3+ fluorescent powders exhibit photoluminescence bands rooting in 5D0 → 7F0, 1, 2, 3, 4 transitions of Eu3+. In SrLaGa3O7, La3+ ions are surrounded octahedrally by eight ions and there is only one mirror plane paralleling to c axis in these distorted octahedrons. This characteristic induces the existence of photoluminescence band resulting from 5D0 → 7F0 transition and the strongest photoluminescence band resulting from 5D0 → 7F2 transition. Under excitation at 265 nm, SrLaGa3O7:Tb3+ fluorescent powders show photoluminescence bands resulting from 5D3 → 7F3 and 5D4 → 7F6, 5, 4, 3 transitions of Tb3+. The band resulting from 5D4 → 7F5 transition is strongest because that this transition has the largest probability for both electric-dipole and magnetic-dipole transitions. The decay curves of SrLaGa3O7:Eu3+ and SrLaGa3O7:Tb3+ fluorescent powders show a single exponential characteristic.

Pre-stressed high-strength concrete piles (PHCP) are widely used in the building industry in China. The main aim of our research was to investigate the utilization of quartz powder, fly ash, and blast furnace slag as mineral additives to prepare PHCP mortar. The samples were prepared using steam and autoclaving steaming. The influence of minerals on the sulfate resistance of mortar was analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM) and mercury intrusion porosimetry (MIP) tests. The results showed that when compared to single doped quartz powder samples, samples prepared using fly ash or blast furnace slag improved the sulfate resistance of the PHCP mortar. Furthermore, the resistance to sulfate attack of samples with dual doped quartz powder, fly ash, and blast furnace slag also improved. MIP tests showed that mineral additives can change the pore size distribution after autoclave curing. However, the number of aching holes increased after mixing with 20% quartz powder and caused a decrease in the sulfate resistance.

Multifunctional Gd2O3:Tb3+ nanoparticles doped with different concentrations of K+/Co2+ were synthesized by polyol method. The samples were characterized by X-ray diffractometer (XRD), Fourier transform infrared spectrometer (FTIR), field emission scanning electron microscope (SEM), X-ray energy spectrometer (EDS), Malvern laser particle size analyzer, transmission electron microscope (TEM), photoluminescence spectrometer (PL), vibrating sample magnetometer (VSM) and magnetic resonance imager (MRI). The results showed that the synthesized spherical particles were cubic crystals with a diameter of 12–15 nm. Significant increase in fluorescence intensity was observed for Gd2O3:Tb3+ doped with K+/Co2+ ions. The optimal doped ion concentrations were found to be 3 mol% K+ ions and 4 mol% Co2+ ions, and the corresponding absolute quantum yields (QYs) were 7.21% and 5.90%. The maximum magnetization was obtained for the sample doped with 3 mol% K+/Co2+ ions. The ion-doped samples showed enhanced r1 relaxivity of water protons. Therefore, the multifunctional nanoparticles Gd2O3:Tb3+ doped with K+/Co2+ ions can potentially be used in displays, luminescence and MR bimodal imaging, sensors, magnetic separat, and other applications.

We present the continuous-wave (CW) and passively Q-switched laser operation of disordered Nd:ABC3O7 crystals including Nd:SrLaGa3O7, Nd:SrGdGa3O7, and Nd:BaLaGa3O7. Among the Nd:ABC3O7 group members, Nd:SrLaGa3O7 exhibits superior laser properties. A maximum output power reaches 3.88 W under an absorbed pump power of 29.01 W, which is the highest CW output power using LD as the pump source for Nd:SrLaGa3O7 gain medium. Using a Cr4+:YAG crystal as a saturable absorber, the LD pumped passively Q-switched laser is also realized. With Nd:SrLaGa3O7, the shortest pulse width, the largest pulse energy, and the highest peak power are observed to be 10.6 ns, 60.3 μJ, and 5.3 kW, respectively. In the CW laser operation, wavelength tunings are also reported. The center wavelength of this Nd: SrGdGa3O7 laser shifts from 1062.48 to 1063.91 nm by changing the temperature from 60 °C to 135 °C.

Background: Secondary infection in hospital was found to have a higher incidence in septic patients and affect clinical outcomes. This study aimed to investigate the clinical characteristics, risk factors, prognosis and immune status of secondary infection of sepsis. Methods: A four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between 2014 January and 2018 January. Data were acquired from medical records. The flow cytometry was performed to measure the CD14+ monocyte human leukocyte antigen-D related (HLA-DR) expression. Serum cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA) method. Results: A total of 297 septic patients were enrolled, 92 of whom developed 150 cases of secondary infections. Respiratory tract was the most common site of secondary infection (n = 84, 56%) and Acinetobacter baumanii the most commonly isolated pathogen (n = 38, 32%). Urinary and deep venous catheterization increased the risk of developing secondary infection. Lower HLA-DR expression and elevated IL-10 level were found in secondary infection group. The expected prolonged in-hospital length of stay owing to secondary infection was 4.63 days. Secondary infection was also associated with higher in-hospital, 30-day and 90-day mortality. Kaplan-Meier survival curves and Log-rank test revealed secondary infection group had a worse survival between day 15 and day 90. Conclusions: Urinary and deep venous catheter indwelling increased the risk of developing secondary infection. Secondary infection influenced outcomes of septic patients and prolonged in-hospital length of stay. Immunosuppression led to a higher tendency to developing secondary infection. Keywords: Sepsis, Secondary infection, Immunosuppression, HLA-DR, Cytokine

Supplementary tables. Table S1. Results of quality assessment of included studies using Newcastle-Ottawa Scale. Table S2. Summary of the studies with changed results after sensitivity analysis. Table S3. Results of meta-analysis on non-adults after excluding two studies discussing elder children. Table S4. Results of meta-analysis after including the study by Reiman. (DOCX 22 kb)

Additional file 3: Table S2. Results of the comparison of the change of HLA-DR expression and serum cytokines levels.

Supplementary figures. The figures of pool analysis, eggerâ s test, sensitivity analysis and trial sequential analysis of each study were summarized. (DOCX 9463 kb)

Relatively low theoretical capacity and poor rate capability of commercial anode materials made traditional lithium-ion batteries (LIBs) difficult to satisfy the ever-increasing requirements in electric devices. Seeking for novel advanced substituted anode materials has been a great challenge. Herein, porous V2O3 particles composed of three-dimensional cut-through framework are produced as high-performance anode materials. The crystallinity of produced V2O3 was in pure rhombohedral phase. The porous V2O3 anode has a high specific capacity of 140 mA h g−1 at the density rate of 100 mA h g−1, and exhibits appreciable rate capability and excellent long-term cycling stability without apparent capacity fading after 50 cycles.

KTN single crystals have some excellent optoelectronic properties and it’s been difficult to manufacture. This paper analyzes the applicable and suitable growth process parameters for KTN crystal, and the influence of Cu-doping on crystal structure and processibility. Large-sized and high-quality KTa0.65Nb0.35O3 crystals with different Cu-doping contents have been grown by the Czochralski method. The results reveal that lattice parameters increase slightly along with the increase of Cu-doping in KTN crystals. And 1.5 mol% of Cu doped KTN crystal has higher hardness, larger density and better thermostability than pure, 1 mol% and 3 mol% of Cu doped crystals due to its fine quality and no macroscopic defects during growth process.

Purpose. Bloodstream infections are major causes of morbidity and mortality among hospitalized patients worldwide. Early identification of micro-organisms from blood culture can facilitate earlier optimization of treatment. The objective of this study was to assess an in-house method based on a new matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platform (Clin-TOF MS) for direct organism identification. Methodology. We studied the performance of the in-house method for direct identification and the conventional sub-culture method in parallel. Identification from subcultures was analysed with Bruker MS as the reference method. Results. A total of 666 blood cultures with a single micro-organism that flagged positive after no more than a 3-day incubation period were collected. The identification accuracy of the in-house Clin-TOF MS method for direct identification and the sub-culture method was 88.6 and 100 %, respectively. The in-house method exhibited better performance for Gram-negative bacteria than for Gram-positive bacteria (93.3 vs 81.6 %). The accuracy rate for anaerobes was 100 % (3/3). The lowest accurate identification rate was for yeast; this was only 20 %. Lytic Anaerobic/F (LAF) and Plus Aerobic/F (PAF) provided the highest accurate identification rates, and it was noteworthy that the accuracy rate for FAN Aerobic (FA) was 82 %, which is higher than previously reported and showed that the method was effective. Conclusion. Our study provides an effective sample preparation method for the direct identification of pathogens from positive blood culture vials via Clin-TOF MS at a very low cost of about $0.5 per sample and with a short turnaround time of about 20 min. This will help clinicians make precise diagnoses and provide targeted prescriptions, reducing the risk of the potential development of resistance.

Gastrointestinal carriage is regarded as a major reservoir of K. pneumoniae infections, especially in intensive care patients. A total of 101 (95.3%) KPC-producing carbapenem-resistant K. pneumoniae (CRKP) isolates were identified among 106 CRKP isolates collected from stool samples of inpatients performing active rectal screening for carbapenem-resistant Enterobacteriaceae during hospitalization in the ICUs of a tertiary hospital between 2016 and 2017. Among them, six KPC-producing CRKP isolates from three patients (two isolates for each patient) were identified with distinct antibacterial susceptibility. Our findings showed that: (1) blaKPC–2 gene is predominant in CRKP strains isolated from the intensive care patients and can be incorporated into various plasmids that are transmissible among multiple bacterial hosts in the human gastrointestinal tract; (2) the human gastrointestinal tract has a capacity to dynamically colonize multiple clones of CRKP strains with varied plasmids, diverse antimicrobial resistance genes and virulence genes. K. pneumoniae colonization is an important step in progression to extraintestinal infection, which provides the rationale for establishing intervention measures to prevent subsequent infection. Thus, close surveillance on CRKP colonization, together with effective infection prevention and control measures, should be put into practice.