Exogenous Glucose Interferes with Antimicrobial-Mediated ROS Accumulation and Bacterial Death.

Glucose is widely used in the reconstitution of intravenous medications, which often include antimicrobials. How glucose affects antimicrobial activity has not been comprehensively studied. The present work reports that glucose added to bacteria growing in a rich medium suppresses the bactericidal but not the bacteriostatic activity of several antimicrobial classes, thereby revealing a phenomenon called glucose-mediated antimicrobial tolerance. Glucose, at concentrations corresponding to blood-sugar levels of humans, increased survival of Escherichia coli treated with quinolones, aminoglycosides, and cephalosporins with little effect on minimal inhibitory concentration. Glucose suppressed a ROS surge stimulated by ciprofloxacin. Genes involved in phosphorylated fructose metabolism contributed to glucose-mediated tolerance, since a pfkA deficiency, which blocks the formation of fructose-1,6-bisphosphate, eliminated protection by glucose. Disrupting the pentose phosphate pathway or the TCA cycle failed to alter glucose-mediated tolerance, consistent with an upstream involvement of phosphorylated fructose. Exogenous sodium pyruvate or sodium citrate reversed glucose-mediated antimicrobial tolerance. Both metabolites bypass the effects of fructose-1,6-bisphosphate, a compound known to scavenge hydroxyl radical and chelate iron, activities that suppress ROS accumulation. Treatment with these two compounds constitutes a novel way to mitigate the glucose-mediated antimicrobial tolerance that may exist during intravenous antimicrobial therapy, especially for diabetes patients.

Identification of pneumococcal serotypes with individual recognition of vaccine types by a highly multiplexed real-time PCR-based MeltArray approach.

BACKGROUND: Pneumococcus serotyping is important for monitoring serotype epidemiology, vaccine-induced serotypes replacement and emerging pathogenic serotypes. However, the lack of high-resolution serotyping tools has hindered its widespread implementation. METHODS: We devised a single-step, multiplex real-time polymerase chain reaction (PCR)-based MeltArray approach termed PneumoSero that can identify 92 serotypes with individual recognition of 54 serotypes, including all 24 currently available vaccine types. The limit of detection (LOD) and the ability to coexisting serotypes were studied, followed by analytical evaluation using 92 reference pneumococcal strains and 125 non-pneumococcal strains, and clinical evaluation using 471 pneumococcus isolates and 46 pneumococcus-positive clinical samples. RESULTS: The LODs varied with serotypes from 50 to 100 copies per reaction and 10 % of the minor serotypes were detectable in samples containing two mixed serotypes. Analytical evaluation presented 100 % accuracy in both 92 reference pneumococcal strains and 125 non-pneumococcal strains. Clinical evaluation of 471 pneumococcus isolates displayed full concordance with Sanger sequencing results. The 46 clinical specimens yielded 45 typeable results and one untypeable result. Of the 45 typeable samples, 41 were of a single serotype and four were of mixed serotypes, all of which were confirmed by Sanger sequencing or separate PCR assays. CONCLUSION: We conclude that the PneumoSero assay can be implemented as a routine tool for pneumococcal serotyping in standard microbiology laboratories and even in clinical settings.

Thermal reaction products and formation pathways of two monoterpenes under in situ thermal desorption conditions that mimic vaping coil temperatures.

Vaping has become more popular and different brands and types of vaping devices have rapidly emerged. However, little is known about the potential health risks of human inhalation exposures to the volatile chemicals in the vapour, which includes both directly vaporised components of vaping liquid and their reaction products formed during vaping processes. This study investigated reaction products of two monoterpenes (α-pinene and terpinolene) that are used as flavouring agents in vaping liquids with a focus on the identification of reaction products and their formation pathways. The thermal desorption was conducted under an in situ condition that is in the range of heating coil temperature in vaping by thermally desorbing the chemicals at a temperature range of 100-300 °C. Additional clean air was introduced during the thermal desorption. 36 and 29 reaction products were identified from α-pinene and terpinolene, respectively, at a relative concentration of 0.01% and greater in the desorbed mixture. 3-Carene was the dominant reaction product of α-pinene, while reaction products of terpinolene was dominated by p-isopropenyltoluene. Several reaction pathways including ring opening, allylic oxidation, cyclo-etherification, Wagner-Meerwein rearrangement, epoxidation, cleavage and removal of partial structure, and dehydration were involved in the formation of various reaction products. These pathways and resulting relative concentrations of residual parent compound and reaction products were influenced by both temperature and amount of air present during thermal desorption. The study results demonstrate possible existence of reaction products from thermally labile chemicals like monoterpenes in vaping aerosols and can help inform policies regulating vaping devices and products to protect public health.

Treponema pallidum membrane protein Tp47 induced autophagy and inhibited cell migration in HMC3 cells via the PI3K/AKT/FOXO1 pathway.

The migratory ability of microglia facilitates their rapid transport to a site of injury to kill and remove pathogens. However, the effect of Treponema pallidum membrane proteins on microglia migration remains unclear. The effect of Tp47 on the migration ability and autophagy and related mechanisms were investigated using the human microglial clone 3 cell line. Tp47 inhibited microglia migration, the expression of autophagy-associated protein P62 decreased, the expression of Beclin-1 and LC3-II/LC3-I increased, and the autophagic flux increased in this process. Furthermore, autophagy was significantly inhibited, and microglial cell migration was significantly increased after neutralisation with an anti-Tp47 antibody. In addition, Tp47 significantly inhibited the expression of p-PI3K, p-AKT, and p-mTOR proteins, and the sequential activation of steps in the PI3K/AKT/mTOR pathways effectively prevented Tp47-induced autophagy. Moreover, Tp47 significantly inhibited the expression of p-FOXO1 protein and promoted FOXO1 nuclear translocation. Inhibition of FOXO1 effectively suppressed Tp47-induced activation of autophagy and inhibition of migration. Treponema pallidum membrane protein Tp47-induced autophagy and inhibited cell migration in HMC3 Cells via the PI3K/AKT/FOXO1 pathway. These data will contribute to understanding the mechanism by which T. pallidum escapes immune killing and clearance after invasion into the central nervous system.

Enhancement of ß-Lactam-Mediated Killing of Gram-Negative Bacteria by Lysine Hydrochloride.

Widespread bacterial resistance among Gram-negative bacteria is rapidly depleting our antimicrobial arsenal. Adjuvants that enhance the bactericidal activity of existing antibiotics provide a way to alleviate the resistance crisis, as new antimicrobials are becoming increasingly difficult to develop. The present work with Escherichia coli revealed that neutralized lysine (lysine hydrochloride) enhances the bactericidal activity of ß-lactams in addition to increasing bacteriostatic activity. When combined, lysine hydrochloride and ß-lactam increased expression of genes involved in the tricarboxylic acid (TCA) cycle and raised reactive oxygen species (ROS) levels; as expected, agents known to mitigate bactericidal effects of ROS reduced lethality from the combination treatment. Lysine hydrochloride had no enhancing effect on the lethal action of fluoroquinolones or aminoglycosides. Characterization of a tolerant mutant indicated involvement of the FtsH/HflkC membrane-embedded protease complex in lethality enhancement. The tolerant mutant, which carried a V86F substitution in FtsH, exhibited decreased lipopolysaccharide levels, reduced expression of TCA cycle genes, and reduced levels of ROS. Lethality enhancement by lysine hydrochloride was abolished by treating cultures with Ca2+ or Mg2+, cations known to stabilize the outer membrane. These data, plus damage observed by scanning electron microscopy, indicate that lysine stimulates ß-lactam lethality by disrupting the outer membrane. Lethality enhancement of ß-lactams by lysine hydrochloride was also observed with Acinetobacter baumannii and Pseudomonas aeruginosa, thereby suggesting that the phenomenon is common among Gram-negative bacteria. Arginine hydrochloride behaved in a similar way. Overall, the combination of lysine or arginine hydrochloride and ß-lactam offers a new way to increase ß-lactam lethality with Gram-negative pathogens. IMPORTANCE Antibiotic resistance among Gram-negative pathogens is a serious medical problem. The present work describes a new study in which a nontoxic nutrient increases the lethal action of clinically important ß-lactams. Elevated lethality is expected to reduce the emergence of resistant mutants. The effects were observed with significant pathogens (Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa), indicating widespread applicability. Examination of tolerant mutants and biochemical measurements revealed involvement of endogenous reactive oxygen species in response to outer membrane perturbation. These lysine hydrochloride-ß-lactam data support the hypothesis that lethal stressors can stimulate the accumulation of ROS. Genetic and biochemical work also revealed how an alteration in a membrane protease, FtsH, abolishes lysine stimulation of ß-lactam lethality. Overall, the work presents a method for antimicrobial enhancement that should be safe, easy to administer, and likely to apply to other nutrients, such as arginine.

Red Blood Cell Lysis Pretreatment Can Significantly Improve the Yield of Treponema pallidum DNA from Blood.

PCR can be a supplement to Treponema serological testing. However, its sensitivity is not satisfactory for blood sample testing. The aim of this study was to investigate whether pretreatment with red blood cell (RBC) lysis could enhance the yield of Treponema pallidum subsp. pallidum DNA extraction from blood. We developed and verified the efficacy of a quantitative PCR (qPCR) assay that utilizes TaqMan technology to specifically detect T. pallidum DNA by targeting the polA gene. Simulation media with 106 to 100 treponemes/mL were prepared in normal saline (NS), whole blood, plasma, and serum, and RBC lysis pretreatment was performed on a portion of whole blood. Then, blood samples drawn from 50 syphilitic rabbits were divided in parallel into five groups, labeled whole blood, whole blood/lysed RBCs, plasma, serum, and blood cells/lysed RBCs. DNA extraction and qPCR detection were performed. The detection rate and copy number were compared among different groups. The polA assay showed good linearity and an excellent amplification efficiency of 102%. In the simulated blood samples, the detection limit of the polA assay reached 1 × 102 treponemes/mL in whole blood/lysed RBCs, plasma, and serum. However, the detection limit was only 1 × 104 treponemes/mL in NS and whole blood. Among the blood samples from syphilitic rabbits, whole blood/lysed RBCs showed the best detection rate (82.0%), while the detection rate for whole blood was only 6%. The copy number of whole blood/lysed RBCs was higher than that of whole blood. RBC lysis pretreatment can significantly improve the yield of T. pallidum DNA from whole blood, and the yield is better than that from whole blood, plasma, serum, and blood cells/lysed RBCs. IMPORTANCE Syphilis is a sexually transmitted disease caused by T. pallidum that can spread into the blood. T. pallidum DNA can be detected in blood by PCR but with low sensitivity. Few studies have applied RBC lysis pretreatment to blood T. pallidum DNA extraction. This study shows that the detection limit, detection rate, and copy number of whole blood/lysed RBCs were better than those of whole blood, plasma, and serum. After RBC lysis pretreatment, the yield of low concentrations of T. pallidum DNA was improved, and the low sensitivity of blood-based T. pallidum PCR was improved. Therefore, whole blood/lysed RBCs are the ideal sample for acquiring blood T. pallidum DNA.

Serum Ubiquitin C-Terminal Hydrolase-L1, Glial Fibrillary Acidic Protein, and Neurofilament Light Chain Are Good Entry Points and Biomarker Candidates for Neurosyphilis Diagnosis Among Patients Without Human Immunodeficiency Virus to Avoid Lumbar Puncture.

BACKGROUND: Laboratory tests to diagnose neurosyphilis using cerebrospinal fluid (CSF) are currently disadvantageous as a lumbar puncture is required, which may result in patients with neurosyphilis missing an opportunity for early diagnosis. Thus, blood biomarker candidates that are more convenient and minimally invasive to collect for diagnosing neurosyphilis is urgently needed. METHODS: This observational study aimed to analyze serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) levels in 153 patients without human immunodeficiency virus (HIV) and to evaluate their diagnostic performance in neurosyphilis compared with CSF. RESULTS: Serum UCH-L1, GFAP, and NF-L levels were significantly higher in patients with neurosyphilis compared with patients with uncomplicated syphilis or non-syphilis. For the diagnosis of neurosyphilis, serum UCH-L1, GFAP, and NF-L revealed sensitivities of 90.20%, 80.40%, and 88.24%, and specificities of 92.16%, 78.43%, and 80.39%, respectively, at cutoff levels of 814.50 pg/mL, 442.70 pg/mL, and 45.19 pg/mL, respectively. In patients with syphilis, serum UCH-L1, GFAP, and NF-L levels correlated strongly or moderately with those in the CSF, with similar or better diagnostic performance than those in the CSF. The testing algorithms' sensitivity and specificity increased to 98.04% and 96.08%, respectively, when subjected to parallel and combination testing, respectively. CONCLUSIONS: To avoid lumbar puncture, each serum UCH-L1, GFAP, and NF-L is a good entry point and biomarker candidate for the diagnosis of neurosyphilis among patients without HIV. These proteins used in concerto can further improve the diagnostic sensitivity and specificity.

Treponema pallidum protein Tp0136 promoting MMPs/TIMPs imbalance via PI3K, MAPK and NF-κB signalling pathways in HDVSMCs.

The invasive capability of Treponema. pallidum is central to its infection process. Matrix metalloproteinases (MMPs), which are specifically inhibited by the tissue inhibitors of metalloproteinases (TIMPs), play a pivotal role in promoting pathogenic invasion by destroying tissue barriers within the body. This study aimed to explore the effect of T. pallidum protein Tp0136 on the balance of MMPs/TIMPs in human dermal vascular smooth muscle cells (HDVSMCs) and the related underlying mechanisms. A number of in vitro studies were conducted to access the impact of recombinant Tp0136 protein on the balance of MMPs/TIMPs in HDVSMCs. The involvement of the PI3K, MAPK, and NF-κB signaling pathways in this process was also investigated. Tp0136 induced the mRNA and protein expressions of MMP1 in HDVSMCs in a concentration-dependent way. In addition, MMP1/TIMP1 and MMP1/TIMP2 ratios were also increased. Furthermore, the study demonstrated that treatment of HDVSMCs with Tp0136 activated the PI3K, MAPK, and NF-κB signaling pathways. Inhibition of PI3K, JNK, P38, and NF-κB, suppressed MMP1 expression and reduced the induction of MMP1/TIMP1 and MMP1/TIMP2 ratios by Tp0136. These findings demonstrate that Tp0136 enhanced the expression of MMP1 involving the PI3K, MAPK, and NF-κB signaling pathways in HDVSMCs, and thus generated the unbalance of MMPs/TIMP, which could contribute to the early spread of T. pallidum and pathogenesis of syphilis.

Evaluation of the efficacy of four anti-SARS-CoV-2 antibodies after vaccination using kits from two manufacturers: A prospective, longitudinal, cohort study at 11 serial time points within 160 days.

PURPOSE: The accuracy of level of anti- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is a great concern. We aimed to compare the efficacy of anti-SARS-CoV-2 antibody detection kits from two manufacturers in evaluating the efficacy of SARS-CoV-2 vaccines. METHODS: The immune responses and consistency of four anti-SARS-CoV-2 antibodies were evaluated using two manufacturers' antibody kits (A and B) in 61 subjects within 160 days after vaccination with the CoronaVac vaccine. RESULTS: The total seropositivity rates of neutralizing antibodies and IgM antibodies detected by kit A were higher than those detected by kit B (P = 0.003 and P < 0.001, respectively). Conversely, the total seropositivity rates of total antibodies and IgG antibodies were higher in kit B than kit A (P < 0.001 and P < 0.001, respectively). The consistency rates showed less than 90% agreement between the kits for the detection of the four antibodies, and the κ score showed moderate or substantial consistency. The half-lives of neutralizing antibodies, total antibodies, and IgG antibodies within 160 days after vaccination, detected by kit A were 63.88 days, 80.50 days, and 63.70 days, respectively and by kit B were 97.06 days, 65.41 days, and 77.99 days, respectively. CONCLUSION: The efficacy of antibody detection differed between the two commercial anti-SARS-CoV-2 antibody kits, although there was moderate consistency, which may affect the clinical application and formulation of the vaccine strategy.

Membrane location of cardiolipin antigen in Treponema pallidum: further study on the origin of nontreponemal antibodies.

Aim: The present study examined the membrane location of cardiolipin antigen in treponemes. Materials & methods: The authors used different methods to disrupt the outer membrane of treponemes, detected the location of the cardiolipin antigen and analyzed the immune response in rabbits immunized with various antigens. Results: All organisms were labeled with nontreponemal antibodies on immunoelectron and fluorescence microscopy, except the citrate buffer-treated group, which is a method leading to relatively complete removal. Except for citrate buffer-treated spirochetes, all treponemes produced low-titer, nontreponemal antibodies in immunized rabbits. Conclusion: These findings indicated that the cardiolipin antigen was localized in the outer membrane of spirochetes. This study provided further evidence of the origin of nontreponemal antibodies during Treponema pallidum infection.

A broadly applicable, stress-mediated bacterial death pathway regulated by the phosphotransferase system (PTS) and the cAMP-Crp cascade.

Recent work indicates that killing of bacteria by diverse antimicrobial classes can involve reactive oxygen species (ROS), as if a common, self-destructive response to antibiotics occurs. However, the ROS-bacterial death theory has been challenged. To better understand stress-mediated bacterial death, we enriched spontaneous antideath mutants of Escherichia coli that survive treatment by diverse bactericidal agents that include antibiotics, disinfectants, and environmental stressors, without a priori consideration of ROS. The mutants retained bacteriostatic susceptibility, thereby ruling out resistance. Surprisingly, pan-tolerance arose from carbohydrate metabolism deficiencies in ptsI (phosphotransferase) and cyaA (adenyl cyclase); these genes displayed the activity of upstream regulators of a widely shared, stress-mediated death pathway. The antideath effect was reversed by genetic complementation, exogenous cAMP, or a Crp variant that bypasses cAMP binding for activation. Downstream events comprised a metabolic shift from the TCA cycle to glycolysis and to the pentose phosphate pathway, suppression of stress-mediated ATP surges, and reduced accumulation of ROS. These observations reveal how upstream signals from diverse stress-mediated lesions stimulate shared, late-stage, ROS-mediated events. Cultures of these stable, pan-tolerant mutants grew normally and were therefore distinct from tolerance derived from growth defects described previously. Pan-tolerance raises the potential for unrestricted disinfectant use to contribute to antibiotic tolerance and resistance. It also weakens host defenses, because three agents (hypochlorite, hydrogen peroxide, and low pH) affected by pan-tolerance are used by the immune system to fight infections. Understanding and manipulating the PtsI-CyaA-Crp­mediated death process can help better control pathogens and maintain beneficial microbiota during antimicrobial treatment.

In-situ TD-GCMS measurements of oxidative products of monoterpenes at typical vaping temperatures: implications for inhalation exposure to vaping products.

Vaping is gaining in popularity. However, there is still much that remains unknown about the potential risk and harms of vaping. Formation of oxidative products is one of such areas that are not well understood. In this study, we used an in-situ thermal desorption GC/MS method to investigate the formation of oxidative products of several monoterpenes at or below typical vaping temperatures. Among the five tested monoterpenes, the unchanged portion of the parent compound in the vapour varied from 97 to 98% for myrcene to 11-28% for terpinolene. The majority of formed oxidative products in the vapour have a molecular weight of 134 (loss of two hydrogens), 150 (insertion of one oxygen and loss of two hydrogen atoms) or 152 (insertion of one oxygen atom). Three products, likely to be p-(1-propenyl)-toluene, ß-pinone and fenchol were also observed. This is the first in-situ thermal desorption GC/MS study to investigate the possible formation of oxidative products of monoterpenes, one of the major components in vaping liquids, at temperatures that are relevant to the vaping process. Although the toxicity of inhaling these oxidative products is not clear yet, allergic and irritation reactions associated with oxidized monoterpene oils are well documented. Therefore, potential adverse effects of inhaling these oxidative products during vaping could be investigated to help support human risk assessment.

A 14+7 day quarantine period and a dual nucleic acid testing reagent strategy detect potentially indiscoverable Coronavirus disease 2019 infections in Xiamen, China.

BACKGROUND: Determining what quarantine period and detection strategy are more effective and sustainable remains a challenge for further prevention and social stability. METHODS: From October 2020 to December 2021, 290,547 inbound overseas travelers were subject to government quarantine in Xiamen, China. The detection rate of COVID-19 during different quarantine periods using dual or single nucleic acid testing reagents. RESULTS: The COVID-19 positive rate was 1.79% (519/290,547). The detection rates during the 7-day, 14-day and 14+7-day quarantine periods using the dual reagents were 78.4%, 91.7%, and 100%, respectively. The detection rate of the 7-day, 14-day and 14+7-day quarantine periods were 73.99%, 86.51%, and 94.22%, respectively, using the Liferiver reagent and 72.25%, 84.59%, and 91.91%, respectively, using the Daan reagent. Based on the 14+7 day strategy, dual nucleic acid testing reagent strategy detected all imported cases, but 30 cases (5.78%) were not detected via Liferiver reagent and 42 (8.09%) cases not detected via Daan reagent. CONCLUSION: A 14+7-day quarantine period and dual nucleic acid testing reagent strategy are effective screening methods for COVID-19 among inbound overseas travelers. The superior detection rate of these strategies reduce the risk of secondary transmission of the SARS-CoV-2 virus.

Anti-Receptor-Binding Domain Immunoglobulin G Antibody as a Predictor of Seropositivity for Anti-SARS-CoV-2 Neutralizing Antibody.

CONTEXT.­: Neutralizing antibody detection can assess the incidence of COVID-19 and the effectiveness of vaccines. However, commercial reagents for neutralizing antibodies were developed after the anti-SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies. Therefore, some laboratories did not perform neutralizing antibody testing services because of multiple factors. OBJECTIVE.­: To find a fast, accurate, and economic alternative for the detection of neutralizing antibodies for the development of COVID-19 screening programs. DESIGN.­: The response and correlation of 3 antibodies (anti-spike protein neutralizing antibody, total anti-receptor-binding domain [RBD] antibody, and anti-RBD IgG) were determined by observing the dynamics in 61 participants for 160 days after vaccination. RESULTS.­: The levels of neutralizing and anti-RBD IgG antibodies reached their peak values on day 42 after vaccination (120.75 IU/mL and 14.38 signal-to-cutoff ratio [S/CO], respectively). The total antibody levels peaked at 138.47 S/CO on day 35 after vaccination. The strongest correlation was found between neutralizing and anti-RBD IgG antibody levels (r = 0.894, P < .001). The area under the receiver operating characteristic curve for total antibody levels for the prediction of seropositivity for neutralizing antibodies was 0.881 (P < .001), and that for anti-RBD IgG antibody levels was 0.937 (P < .001). CONCLUSIONS.­: Neutralizing and anti-RBD IgG antibody levels were strongly correlated, and thus anti-RBD IgG antibody levels can be used for the accurate assessment of immunity following SARS-CoV-2 infection or vaccination.

Mechanisms of Dendrobium officinale polysaccharides in repairing gastric mucosal injuries based on mitogen-activated protein kinases (MAPK) signaling pathway.

The present study aimed to investigate the protective effects and molecular mechanisms of Dendrobium officinale polysaccharides on gastric mucosal injuries. Following one week of continuous intragastric administration, a gastric mucosal injury model was established using intragastric administration of anhydrous ethanol. The area of gastric ulcer was measured, the contents of interleukin- 6 (IL-6), epidermal growth factor receptor (EGFR), and thyroid transcription factor 1 (TFF-1) in serum were detected by enzyme linked immunosorbent assay (ELISA), and the expressions of EGFR, TFF-1, IL-6, Raf-2, MAP kinase kinase 1 (MEK1), MEK2, and ERK1 in the gastric tissue were determined utilizing qPCR, Western blotting and immunohistochemistry. Simultaneously, Dendrobium officinale polysaccharides and anhydrous ethanol were added to the gastric mucosal cells (GES1) cultured in vitro, and the protective effects of Dendrobium officinale polysaccharides on cell viability was detected using Cell Counting Kit (CCK)-8. The addition of Dendrobium officinale polysaccharides markedly improved the gastric epithelial defect, inflammatory cell infiltration, and redness and swelling stemmed from gastric mucosal injuries and greatly reduced the area of gastric ulcer. The inhibition rates of gastric ulcer were 48.12 ± 2.98, 42.95 ± 1.52, and 27.96 ± 2.05% in the high, medium, and low concentration Dendrobium officinale polysaccharide groups, respectively. Dendrobium officinale polysaccharides could increase the expressions of EGFR and TFF-1 and decrease the expressions of IL-6, Raf-2, MEK1, MEK2, and ERK1. Dendrobium officinale polysaccharides could reduce the level of inflammatory factors and protect gastric mucosa by inhibiting the expression of MAPK pathway genes and proteins.

Kinetic and reaction mechanism of generated by-products in a photocatalytic oxidation reactor: Model development and validation.

Photocatalytic oxidation is a promising technology to control air pollution. However, the formation of hazardous by-products hinders the commercialization application of this technology. This paper reports the development of a novel by-products predictive model considering the mass transfer of the pollutant in the gas phase and kinetic reaction in the solid phase. Two challenge compounds from ketone group (acetone and methyl ethyl ketone) were examined for model validation in a continuous Photocatalytic Oxidation (PCO) reactor with TiO2 coated on silica fiber felts. A possible reaction pathway for degradation of each challenge compound was proposed based on identified by-products using analytical methods (GC-MS and HPLC). Formaldehyde, Acetaldehyde, Propionaldehyde, Ethanol, and acetic acid were detected as by-products of the Acetone and Methyl Ethyl Ketone in the PCO reactor. Different possible reaction rate scenarios were evaluated to find the best expression fitted to experimental data at the steady-state condition. The obtained reaction coefficients were then used to validate the model under various operating conditions, namely concentration, relative humidity, irradiation, and velocity variations. Higher concentration and irradiation, as well as lower relative humidity and velocity, resulted in more by-products generation. It was also observed that with enhancing residence time, mineralization efficiency (or CO2 formation) and by-products generation increases through PCO reaction. The model validation provided acceptable accuracy for both steady-state and transient conditions. Finally, the Health Risk Index was used to investigate the implications of generated by-products on human health under varying operating conditions.

A review on the analytical procedures of halogenated flame retardants by gas chromatography coupled with single quadrupole mass spectrometry and their levels in human samples.

Halogenated flame retardants (HFRs) market is continuously evolving and have moved from the extensive use of polybrominated diphenyl ether (PBDE) to more recent introduced mixtures such as Firemaster 550, Firemaster 680, DP-25, DP-35, and DP-515. These substitutes are mainly composed of non-PBDEs HFRs such as 2-ethyl-hexyl tetrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), 1,2-bis-(2,4,6-tribromophenoxy) ethane (BTBPE) and decabromodiphenyl ethane (DBDPE). Other HFRs commonly being monitored include Dechlorane Plus (DP), Dechlorane 602 (Dec602), Dechlorane 603 (Dec603), Dechlorane 604 (Dec604), 5,6-dibromo-1,10, 11, 12,13,13-hexachloro- 11-tricyclo[8.2.1.02,9]tridecane (HCDBCO) and 4,5,6,7-tetrabromo-1,1,3-trimethyl-3-(2,3,4,5-tetrabromophenyl)-2,3-dihydro-1H-indene (OBTMPI). This review aims at highlighting the advances in the past decade (2010-2020) on both the analytical procedures of HFRs in human bio-specimens using gas chromatography coupled with single quadrupole mass spectrometry and synthesizing the information on the levels of these HFRs in human samples. Human specimen included in this review are blood, milk, stool/meconium, hair and nail. The review summarizes the analytical methods, including extraction and clean-up techniques, used for measuring HFRs in biological samples, which are largely adopted from those for analysing PBDEs. In addition, new challenges in the analysis to include both PBDEs and a wide range of other HFRs are also discussed in this review. Review of the levels of HFRs in human samples shows that PBDEs are still the most predominant HFRs in many cases, followed by DP. However, emerging HFRs are also being detected in human despite of the fact that both their detection frequencies and levels are lower than PBDEs and DP. It is clearly demonstrated in this review that people working in the industry or living close to the industrial areas have higher HFR levels in their bodies.

Genome-wide long noncoding RNA and mRNA expression profiles demonstrate associations between exposure to inorganic elements and the risk of developing hepatocellular carcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) are closely associated with the development of hepatocellular carcinoma (HCC). The present study conducted a genome-wide microarray analysis and qPCR validation to obtain comprehensive insights into this issue. METHODS: Thirty male HCC patients with chronic HBV infection were included in the present study. Primary HCC tissue and normal tissue were collected. Double-stranded complementary DNA synthesized from 10 pairs of samples was labeled and hybridized to a microarray chip. Further analyses, such as hierarchical clustering, gene ontology (GO) and pathway analyses, were performed. In addition, qPCR validation was performed on tissue samples and additional serum samples. RESULTS: The microarray analysis identified 946 upregulated and 571 downregulated lncRNAs and 1720 upregulated and 1106 downregulated mRNAs. Among these RNAs, ENST00000583827.1 (fold change: 21) and uc010isf.1 (fold change: 18) were the most over- and underexpressed lncRNAs in the HCC tissues, respectively. For the mRNAs, KIF20A (fold change: 26) and HEPACAM (fold change: 50) were the most over- and underexpressed in the HCC tissues, respectively. The GO analysis demonstrated that the most differentially expressed mRNAs were related to the response of metal ions. The pathway analysis also suggested that the most enriched pathway was mineral absorption. CONCLUSIONS: The subsequent qPCR validation exhibited high consistency with the microarray analysis, except for three lncRNAs. The qPCR analysis also demonstrated that TCONS_00008984 had a 767-fold overexpression level in HCC tissues when compared with normal tissues, and this finding was confirmed in the serum samples; therefore, TCONS_00008984 has the potential to serve as a diagnostic marker or prognostic indicator. The GO and pathway analyses indicated that exposure to inorganic elements may be involved in HCC risk.