bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel heavy metal resistance gene clusters are present in the genome of Cupriavidus neocaledonicus STM 6070, a new species of Mimosa pudica microsymbiont isolated from heavy-metal-rich mining site soil
Authors: Klonowska Agnieszka , Moulin Lionel , Ardley Julie Kaye , Braun Florence , Gollagher Margaret Mary , Zandberg Jaco Daniel , Marinova Dora Vasileva , Huntemann Marcel , Reddy T.B.K. , Varghese Neha Jacob , Woyke Tanja , Ivanova Natalia , Seshadri Rekha , Kyrpides Nikos , Reeve Wayne Gerald
Published: February 2020

Background Cupriavidus strain STM 6070 was isolated from nickel-rich soil collected near Koniambo massif, New Caledonia, using the invasive legume trap host Mimosa pudica. STM 6070 is a heavy metal-tolerant strain that is highly effective at fixing nitrogen with M. pudica. Here we have provided an updated taxonomy for STM 6070 and described salient features of the annotated genome, focusing on heavy metal resistance (HMR) loci and heavy metal efflux (HME) systems.Results The 6,771,773 bp high-quality-draft genome consists of 107 scaffolds containing 6,118 protein-coding genes. ANI values show that STM 6070 is a new species of Cupriavidus. The STM 6070 symbiotic region was syntenic with that of the M. pudica-nodulating Cupriavidus taiwanensis LMG 19424T. In contrast to the nickel and zinc sensitivity of C. taiwanensis strains, STM 6070 grew at high Ni2+ and Zn2+ concentrations. The STM 6070 genome contains 55 genes, located in 12 clusters, that encode HMR structural proteins belonging to the RND, MFS, CHR, ARC3, CDF and P-ATPase protein superfamilies. These HMR molecular determinants are putatively involved in arsenic (ars), chromium (chr), cobalt-zinc-cadmium (czc), copper (cop, cup), nickel (nie and nre), and silver and/or copper (sil) resistance. Seven of these HMR clusters were common to symbiotic and non-symbiotic Cupriavidus species, while four clusters were specific to STM 6070, with three of these being associated with insertion sequences. Within the specific STM 6070 HMR clusters, three novel HME-RND systems (nieIC cep nieBA, czcC2B2A2, and hmxB zneAC zneR hmxS) were identified, which constitute new candidate genes for nickel and zinc resistance.Conclusions STM 6070 belongs to a new Cupriavidus species, for which we have proposed the name Cupriavidus neocaledonicus sp. nov.. STM6070 harbours a pSym with a high degree of gene conservation to the pSyms of M. pudica-nodulating C. taiwanensis strains, probably as a result of recent horizontal transfer. The presence of specific HMR clusters, associated with transposase genes, suggests that the selection pressure of the New Caledonian ultramafic soils has driven the specific adaptation of STM 6070 to heavy-metal-rich soils via horizontal gene transfer.
CD45dimCD34+CD38-CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia .
Authors: Heo Sook-Kyoung , Noh Eui-Kyu , Ju Lan Jeong , Sung Jun Young , Jeong Yoo Kyung , Cheon Jaekyung , Koh SuJin , Min Young Joo , Choi Yunsuk , Jo Jae-Cheol
Published: February 2020

Background: Leukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies regarding the detection of LSCs and the development of novel therapies for targeting them are extensive. The identification of LSCs and targeting therapies for them has been continuously under investigation.

Methods: We examined the levels of CD45 dim CD34 + CD38 - CD133 + cells in bone marrow samples from patients with hematological malignancies and healthy controls, using four-color flow cytometry.

Results: Interestingly, the CD45 dim CD34 + CD38 - CD133 + cells were highly expressed in the bone marrow of patients with AML compared to that in healthy controls (HC). Moreover, the proportions of CD45 dim CD34 + CD38 - CD133 + cells were also examined in diverse hematological malignancies, including AML, CML, DLBCL, MM, MDS, HL, ALL, and CLL. LSCs were prominently detected in the BMCs isolated from patients with AML and CML, but rarely in BMCs isolated from patients with DLBCL, MM, MDS, ALL, CLL, and HL. Additionally, the high CD45 dim CD34 + CD38 - CD133 + cell counts in AML patients served as a significantly poor risk factor for overall and event free survival.

Conclusions: Therefore, our results suggest that CD45 dim CD34 + CD38 - CD133 + cells in AML might potentially serve as LSCs. In addition, this cell population might represent a novel therapeutic target in AML.
Dietary patterns of Brazilian farmers and their relation with sociodemographic, labor, and lifestyle conditions
Authors: Cattafesta Monica , Petarli Glenda Blaser , Luz Tamires Conceição da , Zandonade Eliana , Bezerra Olívia Maria de Paula Alves , Salaroli Luciane Bresciani
Published: February 2020

Background: The eating habits have changed in the last few decades, but few studies prioritize the food consumption of farmers and the rural population. Therefore, the objective of this study was to define the dietary patterns of farmers in a Brazilian municipality and evaluate their association with sociodemographic, occupational and lifestyle factors. Methods: This is a cross-sectional epidemiological study of 740 farmers (51.5%, n=381 males; 48.5%, n=359 females) from a municipality in Southeastern Brazil. Food intake data were obtained by applying multipass 24-hour recall and dietary intake was presented in dietary patterns determined by Principal Component Analysis with varimax orthogonal rotation. Results: Three dietary patterns were identified. The first pattern, “local traditional”, was associated with sociodemographic and labor variables, being considered typical of the region's farmer as white race/color (p=0.003), not extra-physical activity (p=0.014) and cultivating 5 or more crops (p=0.005). The permanence of a “traditional Brazilian” pattern and the occurrence of an “industrialized” pattern were also observed. Farmers working in non-conventional agriculture were 54% less adhere to “traditional Brazilian” pattern (OR 0.46, 95% CI 0.25–0.86, p=0.014). Individuals aged 50 and over years were 82% less likely (OR 0.18, 95% CI 0.10–0.30) to adhere to “industrialized” pattern. Still, individuals of lower socioeconomic class were 52% less likely to adhere to this pattern (OR 0.48, 95% CI 0.24–0.96). Farmers who spent R$ 200 or more per capita to buy food were more than twice as likely to adhere to this food pattern (OR 2.22, 95% CI 1.32–3.73), and who had the habit of frequently eating out were 1.62 as likely adhere to “industrialized” pattern (95% CI 1.11–2.36). Conclusions: The findings indicate changes in dietary patterns in rural areas of the country, maintaining a traditional Brazilian pattern, as well as a local and an industrialized pattern. This last pattern demonstrates that the contemporary rural population also opts for a diet with ultra-processed products, being associated with the characteristic habits of a more urbanized rural region.
The effect of a pre- and post- operative exercise programme versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (The PERIOP-OG Trial): Study protocol for a randomised controlled trial.
Authors: Tully Roisin , Loughney Lisa , Bolger Jarlath C , Sorensen Jan , Mcanena Oliver J , Collins Chris G , Carroll Paul A , Arumugasamy Mayilone , Murphy Thomas J , Robb William B
Published: February 2020

Background: Advances in peri-operative oncological treatment, surgery and peri-operative care have improved survival for patients with oesophagogastric cancers. Neoadjuvant cancer treatment (NCT) reduces physical fitness, which may reduce both compliance and tolerance of NCT as well as compromising post-operative outcomes. This is particularly detrimental in a patient group where malnutrition is common and surgery is demanding. The aim of this trial is to assess the effect on physical fitness and clinical outcomes of a comprehensive exercise training programme in patients undergoing NCT and surgical resection for oesophagogastric malignancies. Methods: The PERIOP-OG trial is a pragmatic, multi-centre, randomised controlled trial comparing a programme of peri-operative exercise with standard care in patients with oesophagogastric cancers treated with NCT and surgery. The intervention group undergo a formal exercise training programme and the usual care group receive standard clinical care (no formal exercise advice). The training programme is initiated at cancer diagnosis, continued during NCT, between NCT and surgery, and then resumed again after surgery. All participants undergo assessments at: baseline, post-NCT, pre-surgery and at 4 and 10 weeks after surgery. The primary endpoint is cardiorespiratory fitness measured by demonstration of a 15% difference in 6-minute walk test assessed at the pre-surgery time point. Secondary endpoints include measures of physical health (upper and lower body strength tests), body mass index, frailty, activity behavior, psychological and health related quality of life outcomes. Exploratory endpoints include a health economics analysis, assessment of clinical health by post-operative morbidity scores, hospital length of stay, nutritional status, immune and inflammatory markers, and response to NCT. Rates of NCT toxicity, tolerance and compliance will also be assessed. Discussion: The PERIOP-OG trial will determine whether, when compared to usual care, exercise training initiated at diagnosis and continued during NCT, prior to surgery and then during recovery, can maintain or improve cardiorespiratory fitness and other physical, psychological and clinical health outcomes. This trial will inform both the prescription of exercise regimes as well as the design of a larger prehabilitation and rehabilitation trial to investigate whether exercise in combination with nutritional and psychological interventions elicit greater benefits.
Association of serum apolipoprotein B with cerebrospinal fluid Alzheimer’s disease biomarkers in patients with subjective cognitive decline
Authors: Hu Hao , Tan Lan , Bi Yan-Lin , Xu Wei , Tan Lin , Shen Xue-Ning , Hou Xiao-He , Ma Ya-Hui , Dong Qiang , Yu Jin-Tai
Published: February 2020

Background The preclinical stage of Alzheimer's disease (AD) has become a key target stage for future AD prevention trials. Serum apolipoprotein, an important lipid-related factor, has been found to be involved in the pathogenesis of AD. This study was to examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1) or the ratio of ApoB and ApoA1 (ApoB/A1) were associated with early changes of cerebrospinal fluid (CSF) AD biomarkers in elderly adults with subjective cognitive decline. Methods This study included 201 cognitive normal (CN) elderly adults and 101 participants with subjective cognitive decline (SCD) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. The Kruskall-Wallis test and Chisquare test were applied in the intergroup comparisons. Multiple linear regression models were used to examine the cross-sectional associations of serum ApoB, ApoA1 and ApoB/A1 levels with CSF AD-related biomarkers. Results Compared with the control group, SCD participants with significant AD biological characteristics had lower ApoB levels. In the total participants, higher level of serum ApoB was associated with increases in CSF Aβ42 (p = 0.0009) and Aβ42/40 (p = 0.0038) as well as decreases in CSF t-tau/Aβ42 (p < 0.0001) and p-tau/Aβ42 (p < 0.0001), independent of APOEɛ4 status. In the further subgroup analysis, these associations were much more significant in the SCD participants. In addition, higher levels of serum ApoB were also found associated with decreases in CSF t-tau (p = 0.0224), p-tau (p = 0.0086) and Aβ40 (p = 0.0297) in the SCD subgroup. Furthermore, we found that these protective associations between serum ApoB and CSF AD core biomarkers were much more significant in the overweight participants. Results showed no association between ApoA1 and all CSF biomarkers in either total participants or subgroups. Conclusions This study is the first to find protective associations of serum ApoB, but not ApoA1, with CSF AD core biomarkers in elderly adults, and these associations were more significant in SCD individuals. This finding indicated that ApoB may play a protective role in the preclinical stage of AD. Identifying the underlying mechanisms may contribute to the discovery of new pathogenic mechanisms and therapeutic targets.
Sevoflurane inhibits Human umbilical vein endothelial cells migration by up-regulating VE-cadherin expression
Authors: Sun Yuanqing , Xu Zifeng , Xu Tao , Xu Hui
Published: February 2020

Background

Sevoflurane is a commonly used inhalation anesthesia and is famous for rapid onset of action, less metabolism in vivo and fast recovery. The aim of this study is to elaborate whether sevoflurane inhibits Human umbilical vein endothelial cells (HUVECs) migration function.

Methods

In vitro experiments, the HUVECs were divided into four groups randomly, and were exposed to 2% sevoflurane, refer to 1.6 minimal alveolar concentration (MAC), respectively for 0.5h, 1h, 2h and the first group was the control group which exposed to the same gas environment with other three groups but only without sevoflurane. After sevoflurane exposure, HUVECs were conducted the scratch assay.

Results

The results suggested that the HUVECs exposed to 2% sevoflurane for 2 h were more obviously inhibited on the migration distance during 12 h after scratched than the control group. Quantitative PCR results suggested that the HUVECs exposed to 2% sevoflurane for 2 h expressed more vascular endothelial cadherin (VE-cadherin) than the control group, with statistic difference. However, other scratch assay and quantitative trials suggested that the HUVECs which were transfected with VE-cadherin siRNA and exposed to 2% sevoflurane for 2 h had no significant difference with the control group on the migration distance and the expression of VE-cadherin.

Conclusion

These results suggested that sevoflurane inhibited the HUVECs migration function by up-regulating VE-cadherin expression, and may have an adverse effect on the normal functions of vascular endothelial cells.
Effectiveness of digital technologies to support nursing care: results of a scoping review
Authors: Huter Kai , Krick Tobias , Domhoff Dominik , Seibert Kathrin , Wolf-Ostermann Karin , Rothgang Heinz
Published: February 2020

Background The field of digital technologies being developed or applied to support nursing care is very extensive. The aim of this scoping review is to provide an overview on technologies for which results on positive or negative effects on persons in need of care, caregivers or care institutions are available – and to appraise the reliability of these results. An additional focus is put on the question which care settings and target groups have been addressed by the research so far. Methods A scoping review design has been used to identify studies focussing on the effectiveness of digital technologies in nursing care for persons in need of care, caregivers or care institutions. The screening process included 19.510 scientific publications from 9 databases. Results A total of 123 single studies and 31 reviews were subjected to the analysis. The range of technologies that is researched to support nursing care is wide. The included technologies comprise nursing and health information technologies, such as assistive devices, information and communication technologies (including decision support systems, electronic health records, hospital and nursing home information systems), sensors and robotic technologies. The results show that there are many studies that demonstrate positive effects of the technologies, but the level of evidence is mostly low and study sizes are often small. Hardly any technology has been researched intensively enough to produce conclusive results. Studies on a high level of evidence (RCTs) lack for nearly all technological areas. Heterogeneous results in some areas indicate that effects may depend strongly on the mode and and specific context into which the technologies are introduced. Most studies are situated in inpatient care settings. Conclusion Due to the limited evidence on effectiveness of digital technologies in nursing care, it is not surprising that care institutions are reluctant to put innovative technologies into practice. The scoping review indicates technology areas that should be subject to future research with higher quality studies. Research on outpatient care settings, informal care arrangements and cross-sectoral care should be intensified to further exploit the potential of digital technologies to improve independence of care-recipients and unburden formal an informal carers.
Intensive immunochemotherapy improves prognosis of young patients with double-expressor lymphoma comparison to non-double-expressor lymphoma: a single-center retrospective cohort study
Authors: Zhan Jing , Zhang Wei , Zhou Daobin , Zhang Yan , Wang Wei , Wei Chong
Published: February 2020

Background Double-expressor lymphoma (DEL), defined as cases with concurrent MYC and BCL2 proteins overexpression, is associated with poor prognosis when treated with R-CHOP alone. Prognostic data on DEL treated with intensive treatment are limited and controversial.Methods We retrospectively report our experiences about 221 consecutive de-novo diffuse large B cell lymphoma patients and analyze the role of intensive therapies for 65 patients with DEL.Results No significant difference in clinical characteristics and survival outcomes between DEL and non-DEL was observed. Overall, 32 (76.2%) and 20 (87.0%) patients with DEL received R-CHOP and intensive treatment achieved partial response or complete response, respectively. Intensive therapies may improve the prognosis over R-CHOP in patients with DEL (P = 0.029 for PFS, P = 0.026 for OS). Subgroup analysis according to clinical characteristics showed intensive therapies resulted in better prognosis than R-CHOP regimen in DEL patients aged under 60 years (P = 0.004 for PFS; P =0.090 for OS), whereas no significant superiority was found in DEL patients aged over 60 years (P = 0.646 for PFS; P = 0.361 for OS).Conclusions This second Chinese cohort study suggests that intensive immunochemotherapy may have the ability to improve the prognosis of young patients with DEL.
Screening and Quantification of Antiquorum-Sensing Activity of Actinobacteria Isolates Against Gram-Positive and Gram-Negative Biofilm Associated Bacteria
Authors: Wijaya Marco , Delicia Dea , Waturangi Diana Elizabeth
Published: February 2020

Objectives: The purpose of the study is to screen antiquorum sensing activity compound from actinobacteria using Chromobacterium violaceum as indicator and quantify the antibiofilm activity against several biofilm-forming pathogenic bacteria, such as Staphylococcus aureus ATCC 29213, Bacillus cereus ATCC 14579, Enterococcus faecalis ATCC 33186, Vibrio cholerae , Salmonella typhimurium , Pseudomonas aeruginosa ATCC 27853.Results: Crude extracts from marine actinobacteria isolated from Indonesia were promising for treating biofilm-related diseases. Out of 40 isolates 10 were found to have great quorum quenching activity against C. violaceum. Moreover, these isolates were able to inhibit biofim formation by Gram positive and Gram negative pathogenic bacteria. Quorum quenching agents in extracts of 1AC, 14PM, 16PM, 18PM, and CW17 isolates were predicted as proteins or enzymes.
Nationwide survey on the use of local antibiotics during anterior cruciate ligament reconstruction in Norway
Authors: Sailer Monica Alessandria , Skråmm Inge , Sivertsen Einar Andreas , Lygre Stein Håkon , Årøen Asbjørn
Published: February 2020

Objective: The use of local antibiotics in surgical reconstruction of the anterior cruciate ligament (ACLR) in Europe and Scandinavia is increasing.We wanted to survey the scope of this practice in Norway. In cooperation with the Norwegian cruciate ligament registry we contacted all institutions in Norway performing ACLR to find out.Results: The results showed that the practice of local antibiotics in ACLR is not widely used in Norway.
Anti- Toxoplasma gondii effect of Lumefantrine in vitro and in vivo
Authors: Wang Dawei , Xing Mengen , El-Ashram Saeed , Ding Yingying , Sang Xiaoyu , Feng Ying , Chen Ran , Wang Xinyi , Jiang Ning , Chen Qijun , Yang Na
Published: February 2020

Background: Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulfadiazine and pyrimethamine. However, both drugs have serious side effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-Toxoplasma drugs with high potency and less or no side-effects. Methods: The cytotoxicity of sulfadiazine and lumefantrine to Vero cells was evaluated by the methyl thiazolyl tetrazolium (MTT) assay. And MTT assay was also used to detect the inhibitory effects of lumefantrine on parasites invasion and proliferation. Flow cytometry was conducted to further verify parasites proliferation. qPCR was performed to evaluate the parasite load in the mice after lumefantrine treatment. In order to determine whether lumefantrine treatment enhances Th1 or Th2 cytokine response, IFN-γ, IL-4, and IL-10 levels in the serum of mice were determined. Results: Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its replication and invasion of Vero cells in vitro without being toxic to the cells. Furthermore, lumefantrine protected mice with acute toxoplasmosis from death to a certain extent and reduced the parasite burden in mouse tissues in vivo. In addition, a significant increase in IFN-γ production was observed in high dose lumefantrine-treated mice while IL-10 and IL-4 levels increased in low dose lumefantrine-treated mice. Conclusions: The results of this study demonstrated that lumefantrine may be a promising agent to treat toxoplamosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.Key words: Toxoplasma gondii, Lumefantrine, anti-Toxoplasma gondii, Invasion, Proliferation
Factors affecting perioperative ∆ALB and short term complications in pediatric patients undergoing major gastroenterology surgery
Authors: Gao Kai , Liu Qingshuang , guo chunbao
Published: February 2020

Background: Albumin is considered a negative acute-phase protein because its concentration decreases during injury and sepsis. The decrease in serum albumin might be important for perioperative morbidity, even in patients with normal preoperative levels in pediatric population. We here intend to determine the perioperative factors associated with the reduction in serum albumin within 2 postoperative days compared with the preoperative level (∆ALB) and its influence on the perioperative outcome in a pediatric general surgical cohort. Methods: This single-center retrospective review included 939 patients who underwent Roux-en-Y hepaticojejunostomy between August 2010 and Aug 2019. Based on the median ∆ALB (14.6%), patients were separated into two groups, including a high ∆ALB group (≥14.6%) and a low ∆ALB group (<14.6%). Multivariable logistic regression analyses were performed to determine the independent risk factors for the reduction in serum albumin. Propensity score matching was performed to adjust for any potential selection bios for the two groups. In 366 matched patients, influences of operating time on perioperative outcomes, including postoperative recovery, complications measurement, length of hospital stay between the two groups were analyzed. Results: For all 996 patients reviewed, 939 patient records were enrolled into the final analysis. Controlling for other factors, multivariate analysis showed that the high CRP on POD 3 or 4 (OR =2.36 [95% CI, 1.51-3.86]; p =0.007), presence of Charcot's triad (OR=1.73[95% CI, 1.05-2.83]; p = 0.031), the longer operating time (OR=1.18[95% CI, 1.00 -1.53]; p=0.014) were factors that predicted the high ∆ALB level. The high ∆ALB level was associated with postoperative gastrointestinal functional recovery, reflected by the first defecation (p= 0.013) and first bowel movement (p=0.019) and the high occurrence of postoperative complications (16.1% vs 10.9%, RR, 1.57; 95 %CI, 1.02-2.41, P=0.0026). The mean length of postoperative stay was longer than that of patients with ∆ALB < 14.0% group, although no statistic significant was stained (p=0.057). Conclusions: We showed that change in albumins was associated with postoperative outcomes. The risk factors for ∆ALB could be intervened in the perioperative period to permit patients gain a safe recovery and discharge after major abdominal operations
Early targeted DNA methylation profiling of CD04+/CD08+ T cells reveals pathogenic mechanisms in different stages of impaired glucose homeostasis Cardiovascular Diabetology
Authors: Benincasa Giuditta , Franzese Monica , Schiano Concetta , Marfella Raffaele , Miceli Marco , Infante Teresa , Mura Nunzia Della , Luongo Marco , Sardu Celestino , Zanfardino Mario , Affinito Ornella , Mansueto Gelsomina , Sommese Linda , Nicoletti Giovanni Francesco , Salvatore Marco , Paolisso Giuseppe , Napoli Claudio
Published: February 2020

Background: Despite current intensive treatments, hyperglycemic patients have an unfavorable prognosis due to severe CHD and development of complications. The interplay between hyperglycemia and systemic inflammation can modify patterns of gene expression mainly affecting DNA methylation in promoter regions and, thus, endothelial damage. However, DNA methylome of CD04+ and CD08+ T cells, which play a relevant role in endothelial dysfunction has not been studied, especially during increasing hyperglycemia.Purpose: To identify differentially methylated regions (DRMs) in CD04 + and CD08 + T cells by comparing healthy subjects (HS) to Pre-Diab and type 2 (T2D) patients. This approach would investigate possible biomarkers useful to identify vascular damage already at Pre-Diab state.Methods: In this pilot study, we enrolled a subgroup of patients from our ongoing PIRAMIDE clinical trial (NCT03792607) including a total of 14 individuals classified in HS (n=2), Pre-Diab (n=6), and T2D (n=6). The DMRs were identified by using the reduced representation bisulfite sequencing platform (RRBS) which captures the majority of promoters and CpG islands. Big data analysis was performed by using the R package and ChromHMM algorithms.Results: Most of the total DMRs (30-35%) were in the promoter regions in increasing hyperglycemia vs HS. A global analysis of DMR-related genes overlapping between Pre-Diab and T2D patients showed a prevalence of DNA hypermethylation in both T cells. Interestingly, the secreted protein acidic and cysteine rich (SPARC) gene was annotated to the most hypomethylated-DMR in Pre-Diab and its methylation level gradually decreased in T2D patients.Conclusions: Preliminary data indicated that hypomethylation of the SPARC promoter may be a useful biomarker of vascular complications in Pre-Diab patients with a possible role for primary prevention. However, larger multicenter trials are needed to validate our epigenetic data in the clinical arena.
Deficiency in interleukin-18 ameliorated glial activation and neuroinflammation after traumatic brain injury in mice
Authors: Dong Wenwen , Wang Linlin , Chen Ziyuan , Guo Xiangshen , Wang Pengfei , Cheng Hao , Zhang Fuyuan , Yang Bei , Wang Shuaibo , Qi Ruiqun , Wang Jiawen , Guan Dawei , Zhao Rui
Published: February 2020

Background: Neuroinflammation is recognized as one of the main pathological mechanisms of secondary injury caused by traumatic brain injury (TBI). It has been reported that interleukin (IL)-18 is expressed in glial cells and involved in the regulation of neuroinflammation. Further studies have revealed that IL-18 expression is upregulated and may contribute to pathogenesis in the later phases of TBI; however, the mechanism underlying the effect of IL-18 on TBI remains unclear. Our present study assessed the roles of IL-18 in inflammatory and neurodegenerative pathology in mice subjected to TBI.Methods: A controlled cortical impact (CCI) injury model was conducted to mimic TBI, and brains were collected at 3 and 7 days post TBI (dpi). The levels of IL-18 were detected by qRT-PCR and immunofluorescence staining. In addition, neurological severity score (NSS) was used to assess neurological deficits after TBI. Furthermore, neuronal cell death, glial activation, and inflammatory cytokine and chemokine secretion were evaluated in wild-type ( WT ) and Il18-knockout ( Il18 -KO) mice to explore the role of IL-18 in TBI.Results: IL-18 levels were upregulated post TBI, accompanied by reactive glial activation. Il-18 deficiency significantly ameliorated glial activation and improved neuronal cell death and neurological deficits. In addition, Il-18 deficiency reduced the TBI-induced M1-like microglia frequency. Interestingly, the levels of all pro- and anti-inflammatory cytokines, including IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL17A, G-CSF, GM-CSF, IFN-γ, and TNF-α, were downregulated in Il18 -KO mice. The deletion of Il-18 attenuated the levels of most chemokines induced by TBI, including CCL2, CCL3, CCL4, CCL5, CCL7, CCL12, CCL20, CXCL1, CXCL2, CXCL10, CXCL12, CXCL13, and CXCL16.Conclusions: These data demonstrated that IL-18 is involved in TBI induced neuroinflammation, which suggests that IL-18 is important for the development of secondary injury induced by TBI.
cGAS-STING signaling regulates control of microglia polarization in cerebral ischemic stroke
Authors: Jiang Guoliang , Yang Xinglong , Zhou Houjun , Long Jiang , Zhang Linming , Lu Di
Published: February 2020

Background Cerebral ischemic stroke is a highly debilitating disease, in which inflammation is well document to play a pivotal role in its pathophysiology. Microglia are the the major immuncompetent cells of the brain involved in different neuropathologies. Recent discovery of cyclic GMP-AMP synthase(cGAS) activation and its induction of the downstream signaling protein stimulator of interferon genes (STING) is increasingly recognized as a crucial determinant of neuropathophysiology. Although cGAS-STING pathway has been reported to play an important role in inflammatory response in myocardial infarction (MI), its mechanism in inflammatory response in ischemic stroke (IS) has remained to be fully explored.Methods In light of the above, this study sought to explore the roles of cGAS-STING pathway in inflammatory reaction in IS. It is hoped that the results would provide new insights for designing of therapeutic strategies targeting at IS. We used HT22 cells to establish an oxygen-glucose deprivation (OGD) cell model. The supernatant derived from this and which contained OGD-induced DAMPs(OIDs) was used to stimulate the BV2 microglia. Additionally, we used siRNA technology to interfere with cGAS gene expression to observe changes in downstream cytokines. Furthermore, we established middle cerebral artery occlusion (MCAO) mouse model and performed cGAS-siRNA lentivirus infection to further elucidate the mechanism of cGAS-STING pathway in vivo.Results We show here that OIDs strongly activated the cGAS-STING pathway and triggered accumulation of a plethora of proinflammatory factors in activated Microglia. Of note, the cascade reaction was successfully inhibited by cGAS-siRNA. Furthermore, we extended the study of cGAS-STING in a mouse MCAO model, which showed that inhibiting cGAS-STING pathway can effectively diminish MIDs(MCAO-induced DAMPs)-induced neuronal apoptosis and ultimately functional improvement.Conclusion The present results have shown GAS-STING signaling pathway controls the polarity transformation of microglia. The underlying mechanisms of cGAS-STING triggering microglial inflammatory response is now better clarified which made the pathway a potential therapeutic target of IS.
TRPM7 ameliorates the blue light-induced apoptosis of RPE cells involving PKC/ERK
Authors: Hu Luping , Xu Guoxing
Published: February 2020

Background Blue light triggers apoptosis of retinal pigment epithelium (RPE) cells and causes retinal damage. The aim of this study was to elucidate the protective role of TRPM7 in photo-damaged RPE cells. Methods RPE cells isolated from Sprague-Dawley (SD) rats were cultured in vitro , and exposed to varying intensities of blue light (500-5000 Lux). Cell proliferation and viability were respectively assessed by BrdU incorporation and MTT assays. Real-time PCR and Western blotting were used to analyze the mRNA and protein expression levels of TRPM7, PKC, ERK and Bax/Bcl-2. The cells were transfected with TRPM7 siRNA to knockdown its mRNA levels, or transduced with TRPM7–overexpressing lentiviruses. Pigment epithelium-derived factor (PEDF) was used in combination to detect the anti apoptosis effect. Results Blue light inhibited the proliferation and viability of RPE cells in an intensity-de pendent manner when compared to non-irradiated controls ( P <0.05). Compared to the control, photo-damaged RPE cells showed decreased levels of TRPM7, PKC, ERK and Bax, increased in Bcl-2 ( P <0.01) . Forced expression of TRPM7 partially ameliorated the reduction of proliferation and viability of RPE cells( P <0.01), alleviated the downregulation of TRPM7, PKC, ERK and Bax expression levels( P <0.01), induced by blue light irradiation, while TRPM7 knockdown had opposite effects( P <0.01). TRPM7 and PEDF synergistically alleviated the damaging effects of blue light. Conclusions The apoptosis of RPE cells induced by blue light was positively correlated with the expression of TRPM7. Forced expression of TRPM7 partially attenuated the deleterious effects of blue-light-demaged RPE cells and showed a synergistic protective effect with PEDF, involving PKC/ERK signaling pathway.
Co-expression of CMTM6 and PD-L1: a novel prognostic indicator of gastric cancer
Authors: Zhang Chao , An Wen , Tan Yuen , Xu Huimian
Published: February 2020

Background CKLF Like MARVEL Transmembrane Domain Containing 6 (CMTM6) is involved in the epigenetic regulation of genes and tumorigenesis. Programmed cell death ligand 1 (PD-L1) is closely related to the prognosis of some human cancers. CMTM6 is a key regulator of PD-L1 in many cancers. The purpose of this study was to investigate the expressions of these proteins in gastric cancer and the correlations with clinicopathological features and survival. Methods The expression levels of CMTM6 and PD-L1 were examined in 185 gastric cancer specimens by immunohistochemistry. Chi-square test was used to analyze the relationship between CMTM6 and PD-L1 expressions and clinicopathological characteristics. Kaplan-Meier method and log-rank test were used to analyze the survival data of patients.Results The positive expression rates of CMTM6 and PD-L1 were 78.38% (145/185) and 75.68% (140/185), respectively. High expression of CMTM6 and PD-L1 was correlated with Borrmann type ( P < 0.001), N stage ( P = 0.002), peritoneal metastasis ( P = 0.007) and TNM stage ( P = 0.038). The expression of CMTM6 and PD-L1 in gastric cancer tissues was positively correlated (Pearson's coefficient test, r = 0.260; P < 0.001). High expression of CMTM6 was correlated with poor prognosis (HR = 1.668; 95% CI = 1.032–2.695; P = 0.037). High expression of both CMTM6 and PD-L1 could be used as an independent factor for overall survival (HR = 1.554; 95% CI = 1.011–2.389; P = 0.044). Conclusions The combined detection of CMTM6 and PD-L1 may be used as an indicator for judging the prognosis of gastric cancer.
Clinical characteristics and predictors of mortality in critically ill influenza adult patients
Authors: Hsu Jui-Chi , Lee Ing-Kit , Huang Wen-Chi , Chen Yi-Chun , Tsai Ching-Yen
Published: February 2020

Background Severe influenza is associated with high morbidity and mortality. The aim of this study was to investigate the factors affecting the clinical outcomes of critically ill influenza patients. Methods In this retrospective study, we enrolled critically ill adult patients with influenza at the Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated the demographic, clinical, and laboratory findings and examined whether any of these measurements correlated with mortality. We then created an event-based algorithm as a simple predictive tool using 2 variables with statistically significant associations with mortality. Results Between 2015 and 2018, 102 critically ill influenza patients (median age, 62 years) were assessed; among them, 41 (40.1%) patients died. Of the 94 patients who received oseltamivir therapy, 68 (72.3%) began taking oseltamivir 48 hours after the onset of illness. Of the 102 patients, the major influenza-associated complications were respiratory failure (97%), pneumonia (94.1%), acute kidney injury (65.7%), adult respiratory distress syndrome (ARDS) (51%), gastrointestinal bleeding (35.3%), and bacteremia (16.7%). In the multivariate regression model, high lactate levels, ARDS, acute kidney injury, and gastrointestinal bleeding were independent predictors of mortality in critically ill influenza patients. The optimal lactate level cutoff for predicting mortality was 33 mg/dL with an area under curve of 0.728. We constructed an event-associated algorithm that included lactate and ARDS. Fifteen (75%) of 20 patients with lactate levels ≥33 mg/dL and ARDS died, compared with only 1 (7.7%) of 13 patients with normal lactate levels and without ARDS. Conclusions We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of critically ill influenza patients. Identification of these prognostic markers could be improved to prioritize key examinations that might be useful in determining patient outcomes.
Maternal 25-hydroxyvitamin D correlates with weight gain and bone metabolism during pregnancy
Authors: Luo Lianmei , Wu Nan , Xu Dan , Wang Lijiao , Zhang Jun , Yang Dong
Published: February 2020

Background: Vitamin D is involved in the regulation of 3% of the human genome, which encode proteins affecting bone health, immune system and other systems. The status of maternal vitamin D may program neonatal skeletal development. Besides, vitamin D is associated with obesity during pregnancy. Obesity has a detrimental effect on bone metabolism and the level of several hormones related to bone metabolism．Methods: This cross-sectional study recruited 103 families who visited Anzhen Hospital from January 2017 to June 2017. The age of included pregnant women ranged from 21 to 42 years old. Patients were assigned to different groups according to their body mass index (BMI) and weight gain during pregnancy. The level of 25-hydroxyvitamin D (25-(OH)D) in serum, parathyroid hormone (PTH), total procollagen type 1 N-terminal propeptide (P1NP), osteocalcin (OC), and C-terminal telopeptides type I collagen (CTX) from mothers and neonates were compared.Results: The results showed that the average level of 25-(OH) D in serum from mothers was 15.09ng/ml during pregnancy and 16.23ng/ml in the umbilical cord. The maternal P1NP increased significantly when the weight gain increased during pregnancy (P<0.01), as well as the fetal weight (P<0.05).Conclusions: Vitamin D deficiency is prevalent during pregnancy and led to more weight gain during pregnancy, also influence the fetal bone health. Obesity negatively correlates with 25-(OH)D level in serum and has a detrimental effect on bone metabolism.
Multiple Parameters and Target Optimization of Splitter Blades for Blood Pumps Using CFD and Neural Networks
Authors: Yu Zheqin , Tan Jianping , Wang Shuai
Published: February 2020

Background: The splitter blade is an improved structure effective in traditional pumps. However, applying splitter blades to blood pumps is a complex optimization problem with multiple parameters and objectives, because structural parameters, blood circulation dynamics, and blood damage need to be considered simultaneously. This study aims to obtain the performance impact of the splitter blade and make it well used in blood pumps through CFD and neural networks.Results: This study combines CFD and neural networks. And hydraulic experiments and PIV technology were used. In the optimization study, the number of blades, axial length, and circumferential offset are optimization parameters, and hydraulic performance and hemolytic prediction index are optimization targets. The study analyzes the influence of each parameter on performance and completes the optimization of the parameters. In the results, the optimal parameters of the number of blades, axial length ratio, and circumferential offset are 2, 6 °, and 0.41, respectively. Under optimized parameters, hydraulic performance can be significantly improved. And the results of hemolysis prediction and micro PIV experiments reflect that there is no increase in the risk of hemolytic damage.Conclusion: This study provides a method and ideas for improving the structure of the blood pump. The established optimization method can be effectively applied to the design and research of blood pumps with complex, high precision, and multiple parameters and targets.
Structural basis for receptor recognition by the novel coronavirus from Wuhan
Authors: Shang Jian , Ye Gang , Shi Ke , Wan Yushun , Luo Chuming , Aihara Hideki , Geng Qibin , Auerbach Ashley , Li Fang
Published: February 2020

A novel SARS-like coronavirus (2019-nCoV) recently emerged from Wuhan, China and is quickly spreading in humans. A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infection, pathogenesis, and host range. 2019-nCoV and SARS-CoV recognize the same host receptor ACE2. Here we determined the crystal structure of 2019-nCoV receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex of human ACE2.Compared with SARS-CoV, an ACE2-binding ridge in 2019-nCoV RBD takes more compact conformations, causing structural changes at the RBD/ACE2 interface. Adaptive to these structural changes, several mutations in 2019-nCoV RBD enhance ACE2- binding affinity, contributing to the high infectivity of 2019-CoV. These mutations also reveal the molecular mechanisms of the animal-to-human transmission of 2019-nCoV. Alarmingly, a single N439R mutation in 2019-nCoV RBD further enhances its ACE2- binding affinity, indicating possible future evolution of 2019-nCoV in humans. This study sheds light on the epidemiology and evolution of 2019-nCoV, and provides guidance for intervention strategies targeting receptor recognition by 2019-nCoV.
Diffusely Adhering Escherichia Coli
Authors: Turniak Michał , Sobieszczańska Beata
Published: February 2020

Diffusely adhering E. coli strains (DAEC) is one of the seven pathovars of pathogenic E. coli causing intestinal infections in humans. DAEC is a diverse group of strains producing fimbrial or afimbrial adhesins that are responsible for their pathogenicity specific diffuse adherence pattern for epithelial cells. DAEC isolates are detected not only in humans, but also in various groups of animals (dogs, calves, cattle, poultry, pigs). A large variation in the genes that encode the adhesins contributes to the omission of DAEC in the routine diagnosis of gastrointestinal and urinary tract infections.

1. Introduction. 2. The Afa/Dr family of adhesins. 3. The division of DAEC strains. 4. Other virulence factors of DAEC. 5. The pathogenicity of DAEC. 5.1. Urinary tract infections. 5.2. Gastrointestinal tract infections. 6. Immunological response in DAEC infections. 7. The pathomechanism of infections caused by DAEC. 7.1. The internalization of DAEC. 8. The epidemiology of DAEC. 9. Diagnosis. 10. Summary
Quality Assurance In The Medical Microbiology Laboratory
Authors: Młodzińska Ewa , Hryniewicz Waleria
Published: February 2020

In each laboratory, a quality assurance program should be developed in order to obtain reliable results and to fulfil the requirements of quality standards in the field of microbiological laboratory tests. Microbiological diagnostics makes it possible to determine the etiological agent of infection and allow the selection of an appropriate therapy. The quality of test results are affected by pre-laboratory, laboratory and post-laboratory steps, which should be checked regularly. Constant internal quality control of performance in the laboratory and participation in external quality control programmes may ensure the quality of results. Internal quality control of the tests at all stages of routine microbiological diagnostics in the laboratory facilitates constant monitoring of the quality of results. Participation in interlaboratory external quality control programmes permits the quality of performance of tests routinely used in a laboratory to be assessed.

1. Introduction. 2. Quality assurance programme. 2.1. Factors affecting quality. 3. Internal quality control. 3.1. Quality control of identification tests. 3.2. Internal quality control of antimicrobial susceptibility testing and detecting resistance mechanisms. 3.3. Internal quality control of automated systems for identification and susceptibility testing. 4. External quality control. 4.1. External quality assurance programme participation rules. 5. Summary
The Role Of The Stringent Components In The Regulation Of Virulence
Authors: Krause Klaudyna , Milewska Klaudia , Szalewska-Pałasz Agnieszka
Published: February 2020

The aim of the existence of every organism is to survive and replicate its genetic material. The pathogen, after infection of the host, has to overcome the host’s defensive barrier. For this, bacterial pathogens use virulence-related factors, such as cell and tissue invasion, adhesion to the surface and toxin production. Numerous pathogenic microorganisms combine their virulence pathways with general mechanisms that allow their adaptation to changing environmental conditions. For this purpose, many bacteria use the global mechanisms of reaction to a stress condition, the stringent response. Here we discuss how the components of stringent response influence the virulence of pathogenic bacteria.

1. Introduction. 2. Metabolism of (p)ppGpp. 2.1. Regulatory targets of (p)ppGpp. 3. Virulence and adaptation to adverse environmental conditions. 4. The role of stringent response in the virulence of Gram-negative bacteria 4.1. Escherichia coli EHEC. 4.2. Escherichia coli UPEC. 4.3. Shigella flexneri. 4.4. Vibrio cholerae. 4.5. Salmonella enterica. 4.6. Pseudomonas aeruginosa. 4.7. Francisella tularensis. 4.8. Bordetella pertussis. 5. The role of stringent response in the virulence of Gram-positive bacteria. 5.1. Enterococcus faecalis. 5.2. Bacillus anthracis. 5.3. Staphylococcus aureus. 5.4. Streptococcus pyogenes. 5.5. Listeria monocytogenes. 6. The effect of the stringent response on the virulence of Mycobacterium tuberculosis. 7. Summary