Investigation into the Antibacterial Mechanism of Biogenic Tellurium Nanoparticles and Precursor Tellurite.

Antibacterial tellurium nanoparticles have the advantages of high activity and biocompatibility. Microbial synthesis of Te nanoparticles is not only a green technology but builds new ecological relationships in diverse environments. However, the antibacterial mechanism of Te nanoparticles is largely unclear. In this study, we report the bacterial synthesis of rod-shaped Te nanoparticles (BioTe) with high antibacterial activity against Escherichia coli. Morphology and permeability examination indicates that membrane damage is the primary reason for the antibacterial activity of BioTe, rather than ROS production and DNA damage. Moreover, a comparison of transcriptome and relative phenotypes reveals the difference in antibacterial mechanisms between BioTe and tellurite. Based on our evidence, we propose an antibacterial mode of rod-shaped BioTe, in which positively charged BioTe interact with the cell membrane through electrostatic attraction and then penetrate the membrane by using their sharp ends. In contrast, tellurite toxicity might be involved in sulfur metabolism.

YgfY Contributes to Stress Tolerance in Shewanella oneidensis Neither as an Antitoxin Nor as a Flavinylation Factor of Succinate Dehydrogenase.

YgfY(SdhE/CptB) is highly conserved while has controversial functions in bacteria. It works as an antitoxin and composes a type IV toxin-antitoxin system with YgfX(CptA) typically in Escherichia coli, while functions as an flavinylation factor of succinate dehydrogenase and fumarate reductase typically in Serratia sp. In this study, we report the contribution of YgfY in Shewanella oneidensis MR-1 to tolerance of low temperature and nitrite. YgfY deficiency causes several growth defects of S. oneidensis MR-1 at low temperature, while YgfX do not cause a growth defect or morphological change of S. oneidensis MR1-1 and E. coli. YgfY do not interact with FtsZ and MreB nor with YgfX examined by bacterial two-hybrid assay. YgfY effect on growth under low temperature is not attributed to succinate dehydrogenase (SDH) because a mutant without SDH grows comparably with the wild-type strain in the presence of succinate. The ygfY mutant shows impaired tolerance to nitrite. Transcription of nitrite reductase and most ribosome proteins is significantly decreased in the ygfY mutant, which is consistent with the phenotypes detected above. Effects of YgfY on growth and nitrite tolerance are closely related to the RGXXE motif in YgfY. In summary, this study demonstrates pleiotropic impacts of YgfY in S. oneidensis MR-1, and sheds a light on the physiological versatility of YgfY in bacteria.

SREBP1 site 1 protease inhibitor PF-429242 suppresses renal cell carcinoma cell growth.

Renal cell carcinoma (RCC) cells have increased lipogenesis and cholesterol synthesis. Sterol regulatory element-binding protein-1 (SREBP1) is cleaved by site 1 protease (S1P) to release the transcriptionally active amino-terminal domain. PF-429242 is a potent and competitive S1P inhibitor. We here tested its activity in RCC cells. In established and primary human RCC cells, PF-429242 potently inhibited cell proliferation, migration, and invasion. The S1P inhibitor provoked apoptosis activation in RCC cells. Furthermore, shRNA-mediated S1P silencing or CRISPR/Cas9-induced S1P knockout led to RCC cell growth inhibition and apoptosis activation. Conversely, ectopic overexpression of SREBP1 or S1P augmented RCC cell proliferation and migration. Daily i.v. injection of a single dose of PF-429242 robustly inhibited RCC xenograft growth in severe combined immunodeficiency mice. Additionally, intratumoral injection of S1P shRNA lentivirus inhibited RCC xenograft growth in mice. SREBP1, S1P, and its target gene low density lipoprotein receptor (LDLR) were significantly elevated in human RCC tissues. These results suggest that targeting S1P by PF-429242 inhibited RCC cell growth in vitro and in vivo.

Pyruvate accelerates palladium reduction by regulating catabolism and electron transfer pathway in Shewanella oneidensis.

Shewanella oneidensis is a model strain of the electrochemical active bacteria (EAB) because of its strong capability of extracellular electron transfer (EET) and genetic tractability. In this study, we investigated the effect of carbon sources on EET in S. oneidensis by using reduction of palladium ions (Pd(II)) as a model and found that pyruvate greatly accelerated the Pd(II) reduction compared with lactate by resting cells. Both Mtr pathway and hydrogenases played a role in Pd(II) reduction when pyruvate was used as a carbon source. Furthermore, in comparison with lactate-feeding S. oneidensis, the transcriptional levels of formate dehydrogenases involving in pyruvate catabolism, Mtr pathway, and hydrogenases in pyruvate-feeding S. oneidensis were up-regulated. Mechanistically, the enhancement of electron generation from pyruvate catabolism and electron transfer to Pd(II) explains the pyruvate effect on Pd(II) reduction. Interestingly, a 2-h time window is required for pyruvate to regulate transcription of these genes and profoundly improve Pd(II) reduction capability, suggesting a hierarchical regulation for pyruvate sensing and response in S. oneidensis IMPORTANCE The unique respiration of EET is crucial for the biogeochemical cycling of metal elements and diverse applications of EAB. Although a carbon source is a determinant factor of bacterial metabolism, the research into the regulation of carbon source on EET is rare. In this work, we reported the pyruvate-specific regulation and improvement of EET in S. oneidensis and revealed the underlying mechanism, which suggests potential targets to engineer and improve the EET efficiency of this bacterium. This study sheds light on the regulatory role of carbon sources in anaerobic respiration in EAB, providing a way to regulate EET for diverse applications from a novel perspective.

Laboratory data analysis of novel coronavirus (COVID-19) screening in 2510 patients.

BACKGROUND: Novel coronavirus (COVID-19) is highly infectious and requires early detection, isolation, and treatment. We tried to find some useful information by analyzing the covid-19 screening data, so as to provide help for clinical practice. METHOD: We collected nucleic acid and hematology data from 2510 patients for COVID-19 infection for retrospective analysis. RESULT: COVID-19 and influenza A and B infection rates were 1.3%, 3%, and 3%, respectively. COVID-19 nucleic acid was detected in stool but not in tear samples from 8 positive patients. Among the 32 patients with COVID-19, 15 (47%) and 16 (50%) patients showed decreased lymphocyte count and lymphocyte ratio, 21(66%) and 24(75%) patients showed decreased eosinophil count and eosinophil ratio, and 18 (56%) patients showed increased C-reactive protein. Ten hematological indicators significantly differed in the blood of patients with COVID-19 and those with influenza A and B (P < 0.05). Eighteen hematological indicators significantly differed between patients with COVID-19 and negative patients (P < 0.05). CONCLUSION: The positive rate of influenza A and B infection was higher than that of COVID-19. When pharyngeal swab collection may cause infection, fecal samples can be examined. Evaluation of pharyngeal swab and fecal samples can improve the positive rate of nucleic acid detection. The COVID-19 can cause some hematological indices changes.

Reference Intervals for Serum Creatinine with Jaffe's Method in Healthy Chinese Geriatric Population.

BACKGROUND: Reliable reference intervals (RIs) for the serum creatinine (SCr), assayed by Jaffe's method and categorized in small intervals, are still lacking in elderly population. The study aims to establish RIs for SCr with Jaffe's method in healthy geriatric population of China. METHODS: Eight hundred twenty cases from six representative geographical regions in China (including 369 male cases and 374 female cases) of apparently healthy Chinese elderly aged 60 - 90 years were recruited. SCr were analyzed by an ARCHITECT c8000 biochemical analyzer with Jaffe's method, and RIs for Scr with Jaffe's method were determined following CLSI C28-A3 guidelines using a nonparametric method. RESULTS: In apparently healthy Chinese geriatric population of China, the RIs for Scr with Jaffe's method were 69.4 ~ 113.1, 74.1 ~ 122.1, 75.2 ~ 126.9 µmol/L, respectively, for males aged 61 - 70, 71 - 80, 81 - 90 years and 60.7 ~ 91.6, 62.2 ~ 102.5, 86.5 ~ 107.2 µmol/L, respectively, for females aged 61 - 70, 71 - 80, 81 - 90 years. CONCLUSIONS: The RIs for Scr using Jaffe's method were established within apparently healthy geriatric Chinese population according to CLSI C28-A3 document, providing a reference for clinical practice.

Trimester-specific reference intervals for kaolin-activated thromboelastography (TEG®) in healthy Chinese pregnant women.

OBJECTIVE: There has been little published work about the reference intervals of thromboelastography (TEG®) tests in pregnancy. Our aim was to establish the trimester-specific reference intervals of TEG tests for healthy pregnant women. METHODS: After excluding outliers, a total of 753 apparently healthy pregnant women aged from 19 to 44 years including 252 first trimester women, 340 second trimester women and 161 third trimester women were enrolled in our study. Non-fasting venous blood samples were collected. TEG tests were done on kaolin activated samples and processed on TEG 5000 Hemostasis Analyzer. Nonparametric 2.5th-97.5th percentile intervals were used to define the reference intervals. RESULTS: There were significant differences for TEG tests in pregnant women compared with non-pregnant women. The reference intervals for R, K, Angle, MA, Ly30 and CI were 4.1-10.4 min, 0.9-3.1 min, 53.6-75.9°, 46.1-69.8 mm, 0-10.7% and -5.5-2.5 respectively at first trimester; 3.9-9.7 min, 0.8-2.4 min, 56.7-78.0°, 49.8-72.1 mm, 0-9.7% and -3.7-2.9 at second trimester; 3.8-9.0 min, 0.8-2.5 min, 57.6-79.3°, 49.4-75.9 mm, 0-8.8% and -3.0-2.6 at third trimester. CONCLUSIONS: We established trimester-specific reference intervals of TEG® tests for healthy pregnant women. It's critical to accurate assessment of global haemostatic status during pregnancy and in pregnancy complications.

Long non-coding RNA expressed in macrophage co-varies with the inflammatory phenotype during macrophage development and polarization.

Advances in microarray, RNA-seq and omics techniques, thousands of long non-coding RNAs (lncRNAs) with unknown functions have been discovered. LncRNAs have presented a diverse perspective on gene regulation in diverse biological processes, especially in human immune response. Macrophages participate in the whole phase of immune inflammatory response. They are able to shape their phenotype and arouse extensive functional activation after receiving physiological and pathological stimuli. Emerging studies indicated that lncRNAs participated in the gene regulatory network during complex biological processes of macrophage, including macrophage-induced inflammatory responses. Here, we reviewed the existing knowledges of lncRNAs in the processes of macrophage development and polarization, and their roles in several different inflammatory diseases. Specifically, we focused on how lncRNAs function in macrophage, which might help to discover some potential therapeutic targets and diagnostic biomarkers.

The reference intervals for CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1.

Tumor markers are noninvasive diagnostic tools for cancer. Their abnormal expression often occurs earlier than clinical symptoms or other detection signals. Appropriate reference intervals (RIs) of tumor markers are important for health evaluation, cancer diagnosis, therapy monitoring and prognosis assessment. In this study, we aimed to establish the RIs of cancer antigen 125 (CA125), CA15-3, CA19-9, CA72-4, alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in apparently healthy Henan population. A total of 1705 apparently healthy participants (21-89 years) were recruited from five representative geographical regions in Henan province. Nonparametric 95th percentile intervals were used to define the RIs of CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1. The test results of CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1 can traceable to reference measurement procedures. The age- and gender-specific RIs of the tumor markers were established. We established age- and gender-specific RIs for CA125, CA15-3, CA19-9, CA72-4, AFP, CEA, NSE and CYFRA21-1. The newly established RIs should be more suitable for Henan population. It will be valuable for clinicians to make a medical diagnosis, therapeutic management decision and other physiological assessment.

Changes of serum homocysteine levels during pregnancy and the establishment of reference intervals in pregnant Chinese women.

BACKGROUD: Reference intervals (RIs) of clinical laboratory indexes are important basis for interpretation of corresponding test results. While elevated homocysteine (HCY) level is a risk factor of some severe gestational diseases, HCY RIs for pregnant women have not been reported so far. The current use of HCY RIs established for general population in pregnant women may challenge clinicians' judgment. This study aims to investigate the changes of serum HCY levels during pregnancy and establish the RIs of serum HCY in healthy pregnant Chinese women to provide valuable data to clinicians and enable the provision of more appropriate therapy. METHODS: 354 healthy pregnant Chinese women were randomly selected and divided into three groups according to gestational age: 114 in first trimester (1-13 week), 120 in second trimester (14-27 week) and 120 in third trimester (≥28 week). 120 healthy non-pregnant Chinese women were randomly selected as the non-pregnant control group. Serum HCY levels were determined on automatic biochemical analyzer with enzymatic cycling method. The RIs of serum HCY for healthy pregnant women were established using a nonparametric method. RESULTS: the RIs of serum HCY for healthy pregnant women is 5.79-11.86 µmol/L in first and second trimester (combined) and 6.13-16.75 µmol/L in third trimester. Besides, the RIs of serum HCY for healthy non-pregnant women is 8.25-22.92 µmol/L. CONCLUSIONS: Rigorously according to CLSI C28-A3 guidelines, the authoritative document of RIs establishment, the RIs of serum HCY for healthy pregnant Chinese women were established, which will provide a valuable reference for clinical work and laboratory researches.

The role of lncRNAs in signaling pathway implicated in CC.

Cervical cancer (CC) is the second most common malignancy in females. Owing to poor diagnosis, resistance to the systemic therapies, and high recurrence rate, patients with CC have a relatively poor prognosis. The role of a signaling pathway in CC has always been the focus among worldwide researchers. As reported before, aberrant expression of proteins associated with signaling pathways, such as phosphatidylinositol 3-kinase(PI3K), EGF-R, ß-catenin, and Erk and Bcl-2 was discovered in CC. Therefore, aberrant molecular signaling pathways are significant parts of cervical carcinogenesis. Recently discovered long noncoding RNAs (lncRNAs) as a new regulator player of molecular biology in CC have always been reported. In this review, we highlighted the role of lncRNA in signaling pathway implicated in CC and outlined the molecular mechanism of lncRNA in it. All of these present an opportunity for developing diagnosis and therapies against CC.

Inhibition of constructed SEC3-ES lentiviral vector to proliferation, migration of Hela cells.

AIM: To construct a lentiviral vector with endostatin (ES) and staphylococcal enterotoxin C3(SEC3) gene, and investigate its capacities of inhibition on proliferation and migration of Hela cells. METHODS: By inserting ES and SEC3 gene into the plasmid and then transfect 293 T cell, the co-expressed (SEC3-ES) vector were constructed. A series of experiments in vitro were carried out to detect its anti-tumor capacity. RESULTS: SEC3 expression of the vector is about 3 times of GV365-SEC3 vector, and ES expression is over 22.5-fold compared with GV365-ES vector. Moreover, OD490 value of CO group (1.212 ± 0.003) was notably lower than NC (negative control) group (1.124 ± 0.01) (P < 0.05) in MTT assay. Cell cycle analysis showed it could block Hela cells in S phase. Meanwhile, in wound healing assay, cells of CO group migrated at a slower rate (0.59 ± 0.02) compared with NC group (0.65 ± 0.02)(P < 0.01). CONCLUSION: The successful construction of co-expressed vector lays the foundation for further studies in vivo. These promising results suggest a new strategy to treating cervical cancer.

Assessment of a combination of Serum Proteins as potential biomarkers to clinically predict Schizophrenia.

Schizophrenia (SZ) is a devastating psychiatric disorder. Validation of potential serum biomarkers during first-episode psychosis (FEP) is especially helpful to understand the onset and prognosis of this disorder. To address this question, we examined multiple blood biomarkers and assessed the efficacy to diagnose SZ. The expression levels of Neuregulin1 (NRG1), ErbB4, brain-derived neurotrophic factor (BDNF), DNA methyltransferases 1 (DNMT1) and ten-eleven translocation 1 (TET1) proteins in peripheral blood of 53 FEP patients and 57 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression including biomarker concentration as covariates was used to predict SZ. Differentiating performance of these five serum protein levels was analyzed by Receiver Operating Characteristic (ROC) curve analysis. We found that patients with SZ present a higher concentration of DNMT1, and TET1 in peripheral blood, but a lower concentration of NRG1, ErbB4 and BDNF than controls. Multivariable logistic regression showed that ErbB4, BDNF and TET1 were independent predictors of SZ, and when combined, provided high diagnostic accuracy for SZ. Together, our findings highlight that altered expression of NRG1, ErbB4, BDNF, DNMT1 and TET1 are involved in schizophrenia development and they may serve as potential biomarkers for the diagnosis of the schizophrenia. Therefore, our study provides evidence that combination of ErbB4, BDNF and TET1 biomarkers could greatly improve the diagnostic performance.

Reference intervals for serum progastrin-releasing peptide in healthy Chinese adults with electrochemiluminescence immunoassay.

BACKGROUND: Reliable reference intervals for serum progastrin-releasing peptide (ProGRP) in healthy Chinese adults with electrochemiluminescence immunoassay (ECLIA) are still lacking in the Chinese population. OBJECTIVES: The study aims to establish reference intervals for ProGRP with ECLIA in apparently healthy Chinese adults. METHODS: A total of 384 apparently healthy individuals from six representative geographical regions in China were enrolled: 200 males and 184 females with a mean age of 43.4±12.2 years, and an age range from 21 to 85 years. Serum ProGRP levels were analyzed on Cobas e601 automatic immunoassay analyzer with ECLIA. Reference intervals for serum ProGRP with ECLIA were determined following CLSI C28-A3 guidelines using a nonparametric method. RESULTS: In an apparently healthy Chinese population, the reference intervals for serum ProGRP with ECLIA were ⩽53.92 ng/L for adults aged 21-70 years and ⩽75.69 ng/L for adults aged >70 years, respectively. CONCLUSIONS: The reference values for serum ProGRP with ECLIA in an apparently healthy Chinese population were established according to the CLSI C28-A3 document, providing a reference for the clinical work.

Wnt signaling in cervical cancer?

Cervical cancer (CC) is the second most common malignant cancer in women. CC is difficult to diagnose, has a high recurrence rate, and is resistant to systemic therapies; as a result, CC patients have a relatively poor prognosis. One potential link to CC is the Wnt signaling pathway and its downstream effectors, which regulate cell differentiation, proliferation, migration, and fate. The aberrant activation of Wnt signaling is associated with various cancers, including CC. Recent studies have shown that activating or inhibiting the intracellular signal transduction in this pathway can regulate cancer cell growth and viability. This review will summarize the experimental evidence supporting the significance of the Wnt signaling pathway in CC, and will also discuss the current clinical role of Wnt signaling in CC diagnosis, therapy, and prognosis.

Establishing reference intervals for ALT, AST, UR, Cr, and UA in apparently healthy Chinese adolescents.

BACKGROUND: The current child-specific reference intervals (RIs) are inadequate or even unavailable for many analyses in China. Many of the RIs used in Chinese laboratories were derived from Chinese adult standards or from foreign studies. The aim of this study was to establish specific RIs for alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (UR), creatinine (Cr) and uric acid (UA) for apparently healthy Chinese adolescents. METHODS: Overall, 1682 apparently healthy adolescents were enrolled. Serum ALT, AST, UR, Cr and UA were measured by an ARCHITECT C-8000 automated chemistry analyzer. The 2.5th and 97.5th percentile RIs were determined using non-parametric methods. RESULTS: The established reference intervals for ALT, AST, UR, CR and UA were 7.5-42.8 U/L, 12.8-40.2 U/L, 3.12-6.38 mmol/L, 42.7-91.2 µmol/L, and 180.2-409.6 µmol/L in boys and 6.5-32.8 U/L, 10.4-32.5 U/L, 3.05-6.47 mmol/L, 40.2-88.8 µmol/L and 176.5-394.0 µmol/L in girls, respectively. The median and upper and lower limits for the RIs of ALT, AST, Cr and UA were higher in boys than they were in girls (P < 0.05). CONCLUSION: RIs based on adult criteria are not applicable to adolescents. It was necessary to establish specific, accurate and suitable RIs for Chinese adolescents. We have established reference intervals of ALT, AST, UR, Cr and UA that are defined specifically for Chinese adolescents and are appropriate for universal use among Chinese laboratories.

Reference intervals for serum bilirubin, urea, and uric acid in healthy Chinese geriatric population.

OBJECTIVES: The study aims to establish the reference intervals (RIs) for total bilirubin (TBIL), direct bilirubin (DBIL), urea (UR), and uric acid (UA) in healthy Chinese geriatric population. METHODS: Eight hundred and twenty cases from six representative geographical regions in China (including male 413 cases and female 407 cases) of apparently healthy individuals aged 60-96 years were recruited. Serum TBIL, DBIL, UR, and UA were analyzed by automatic biochemical analyzer and RIs were determined following CLSI C28-A3 guidelines using a non-parametric method. RESULTS: In apparently healthy Chinese geriatric population of China, the RIs of TBIL, DBIL, UR, and UA were 6.6~21.8 µmol/L, 1.9~8.0 µmol/L, 3.60~9.51 mmol/L, 179.2~460.9 µmol/L in males and 6.1~20.0 µmol/L, 1.8~7.1 µmol/L,3.35~8.89 mmol/L, 130.2~443.4 µmol/L in females, respectively. CONCLUSIONS: The RIs of TBIL, DBIL, UR, and UA were established within apparently healthy geriatric Chinese population according to CLSIC28-A3 document, providing a reference for the clinical.

Up-regulated expression of oxytocin mRNA in peripheral blood lymphocytes from first-episode schizophrenia patients.

Schizophrenia (SZ) is a severe neuropsychiatric disorder with significant social cognition impairment. Increasing evidence has suggested that neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are important mediators of complex social cognition and behavior associates with SZ. In the present study, forty-three first-episode schizophrenia (FES) patients and forty-seven healthy controls (HC) were included. The peripheral mRNA expression of OXT, OXT receptor (OXTR), AVP, AVP 1a receptor (AVPR1a) and CD38 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The FES patients have a relatively higher mRNA level of OXT and OXTR genes and lower expression of AVP and CD38 genes than HC. No difference was found for AVPR1a between FES patients and HC. As for the sex difference, the mRNA expression of OXT and OXTR showed no difference in both male and female FES patients compared to HC group. The AVP and CD38 genes in female FES patients showed decreased mRNA expression than female HC. Our findings support disrupted OXT and AVP systems in the FES patients.

In vitro effects of Staphylococcus aureus enterotoxin C3 on T cell activation, proliferation and cytokine production.

The present study aimed to investigate the effects of Staphylococcus aureus enterotoxin C3 (SEC3), including recombinant (r)SEC3 protein and lentivirus­mediated SEC3, on the activation, proliferation and cytokine production of human T cells. HeLa cells were infected with SEC3 lentiviral vector (LV­SEC3) and viability was determined using the Cell Counting Kit­8 (CCK­8) assay. Subsequently, infected cells or rSEC3 protein were co­cultured with human peripheral blood mononuclear cells (PBMCs) for 10 days, after which the culture supernatant and T cells were incubated with untreated HeLa cells, which were subjected to a CCK­8 assay to determine cytotoxicity. In addition, IL­6 and IFN­Î³ expression was detected by chemiluminescence and enzyme­linked immunospot analyses, respectively. Subpopulations of activated T cells were sorted by flow cytometry. The results demonstrated that, following infection with LV­SEC3 or negative control lentiviral vector (LV­NC), >80% of HeLa cells presented green fluorescent protein­positive signals. All five groups of co­cultured T cells exhibited proliferation. Co­culture of PBMCs with rSEC3 protein or LV­SEC­infected cells resulted in elevated IL­6 and IFN­Î³ secretion. In addition, rSEC3­activated and monocultured T cells were predominantly cluster of differentiation (CD)4+ (62.7 and 59.6%, respectively) whereas phytohemagglutinin­stimulated T cells were predominantly CD8+ (57.8%). Compared with the LV­NC group, T cells and culture supernatants from the LV­SEC3 group significantly attenuated proliferation of HeLa cells. These results suggest that rSEC3 protein, and LV­SEC3­infected HeLa cells, are able to potently activate T cells, increasing cytokine production and amplify the antitumor immune response.