Redox Reactions of Organic Molecules Using Rotating Magnetic Field and Metal Rods.

In recent years, redox reactions have harnessed light or mechanical energy to enable the formation of chemical bonds. We postulated a complementary approach that electromagnetic induction could promote the redox reaction of organic molecules using a rotating magnetic field and metal rods. Here, we report that electromotive force activates the redox-active trifluoromethylating reagents. This magnetoredox system can be applied to the trifluoromethylation of heteroarenes with high regioselectivity and hydrotrifluoromethylation of alkenes without the need for catalysts and organic additives.

TAZ reverses the inhibitory effects of LPS on the osteogenic differentiation of human periodontal ligament stem cells through the NF-κB signaling pathway.

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are important candidate seed cells for periodontal tissue engineering, but the presence of lipopolysaccharide(LPS) in periodontal tissues inhibits the self-renewal and osteogenic differentiation of hPDLSCs. Our previous studies demonstrated that TAZ is a positive regulator of osteogenic differentiation of hPDLSCs, but whether TAZ can protect hPDLSCs from LPS is still unknown. The present study aimed to explore the regulatory effect of TAZ on the osteogenic differentiation of hPDLSCs in an LPS-induced inflammatory model, and to preliminarily reveal the molecular mechanisms related to the NF-κB signaling pathway. METHODS: LPS was added to the culture medium of hPDLSCs. The influence of LPS on hPDLSC proliferation was analyzed by CCK-8 assays. The effects of LPS on hPDLSC osteogenic differentiation were detected by Alizarin Red staining, ALP staining, Western Blot and qRT-PCR analysis of osteogenesis-related genes. The effects of LPS on the osteogenic differentiation of hPDLSCs with TAZ overexpressed or knocked down via lentivirus were analyzed. NF-κB signaling in hPDLSCs was analyzed by Western Blot and immunofluorescence. RESULTS: LPS inhibited the osteogenic differentiation of hPDLSCs, inhibited TAZ expression, and activated the NF-κB signaling pathway. Overexpressing TAZ in hPDLSCs partly reversed the negative effects of LPS on osteogenic differentiation and inhibited the activation of the NF-κB pathway by LPS. TAZ knockdown enhanced the inhibitory effects of LPS on osteogenesis. CONCLUSION: Overexpressing TAZ could partly reverse the inhibitory effects of LPS on the osteogenic differentiation of hPDLSCs, possibly through inhibiting the NF-κB signaling pathway. TAZ is a potential target for improving hPDLSC-based periodontal tissue regeneration in inflammatory environments.

Longitudinal Profiling of Plasma Cytokines and Its Association With Postoperative Delirium in Elderly Patients Undergoing Major Lower Limb Surgery: A Prospective Observational Study.

BACKGROUND: Surgery is accompanied by a systemic inflammatory response that may presage delirium in susceptible individuals. Little is known about the trajectory of plasma proinflammatory cytokines and their potential associations with postoperative delirium (POD). The current study longitudinally assessed both pro and anti-inflammatory plasma cytokine response and development of POD in older surgical patients to investigate associations with individual and/or clusters of cytokines that may indicate pathogenic mechanisms. METHODS: A prospective longitudinal study sought to enroll patients >60 years old who were scheduled for major lower limb surgery under general anesthesia. Blood was obtained preoperatively and postoperatively from day 1 through postoperative day 4 for measurement of plasma interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, soluble IL-6 receptor (sIL-6R), IL-10, and tumor necrosis factor-α (TNF-α). Participants were assessed for POD twice daily for 4 days using the confusion assessment method. Trajectory of postoperative changes in plasma cytokines was determined by a group-based trajectory modeling analysis that was informed by distinct cytokines identified by time-dependent Cox regression model. RESULTS: One hundred eighty-eight patients were assessed for eligibility of whom 129 underwent major surgery and 126 had complete datasets for final analysis. POD was diagnosed in 31 of 126 patients (24.6%). Time-dependent Cox regression model identified that higher IL-6 and sIL-6R levels were associated with higher risk of developing POD. A two-cluster model (stable lower and fluctuating higher levels) was considered to be the most statistically appropriate model for IL-6 and sIL-6R trajectory. More participants with fluctuating higher IL-6 were delirious (73.3% vs 18.0%, P = .001) as were those with fluctuating higher sIL-6R (81.3% vs 16.4%, P = .001). CONCLUSIONS: As higher IL-6 and sIL-6R levels were significantly associated with higher risk of POD and the combination is required for IL-6 trans-signaling, it is possible that activation of this pathway may be associated with POD. Furthermore, it will be important to determine whether high levels of the combination of IL-6 and sIL-6R can be an early biomarker for the subsequent development of POD.

A stochastic dynamical model for nosocomial infections with co-circulation of sensitive and resistant bacterial strains.

Nosocomial infections (hospital-acquired) has been an important public health problem, which may make those patients with infections or involved visitors and hospital personnel at higher risk of worse clinical outcomes or infection, and then consume more healthcare resources. Taking into account the stochasticity of the death and discharge rate of patients staying in hospitals, in this paper, we propose a stochastic dynamical model describing the transmission of nosocomial pathogens among patients admitted for hospital stays. The stochastic terms of the model are incorporated to capture the randomness arising from death and discharge processes of patients. Firstly, a sufficient condition is established for the stochastic extinction of disease. It shows that introducing randomness in the model will result in lower potential of nosocomial outbreaks. Further, we establish a threshold criterion on the existence of stationary distribution and ergodicity for any positive solution of the model. Particularly, the spectral radius form of stochastic threshold value is calculated in the special case. Moreover, the numerical simulations are conducted to both validate the theoretical results and investigate the effect of prevention and control strategies on the prevalence of nosocomial infection. We show that enhancing hygiene, targeting colonized and infected patients, improving antibiotic treatment accuracy, shortening treatment periods are all crucial factors to contain nosocomial infections.

Evaluation of effects of 3% diquafosol ophthalmic solution on preocular tear film stability after trabeculectomy.

OBJECTIVES: To determine the potential effects of 3% diquafosol (DQS) on tear film stability after glaucoma surgery. METHODS: We retrospectively reviewed consecutive patients who underwent glaucoma surgery at the glaucoma division of the Henan Eye Institute from January 2020 to January 2021. Clinical parameters, including age, sex, intraocular pressure, and number of glaucoma medications, were tested. Tear film parameters, such as tear meniscus height (TMH), first and average noninvasive tear break-up time (FBUT and ABUT, respectively), and tear film lipid layer grade (TFLL), were evaluated using the Oculus Keratograph 5M. We investigated the differences in clinical and tear film parameters pre- and postoperatively. We compared the baseline and different time points after surgery between the DQS and HA groups and identified the factors associated with changes in the tear film at 8 weeks postoperatively. RESULTS: A total of 101 eyes were included. Early administration of DQS increased TMH, FBUT, ABUT, and TFLL after trabeculectomy (all p < 0.05). In addition, the DQS group showed significantly higher ABUT than the HA group (p < 0.05). DQS use served as an associated parameter for better TMH, FBUT, ABUT, and the TFLL (p < 0.05). DQS and preoperative FBUT were significant independent parameters of postoperative FBUT (p < 0.05). CONCLUSIONS: The present study showed that postoperative TMH, FBUT, ABUT, and TFLL significantly increased after early application of DQS, and the efficacy of ABUT was better than that of HA at the early stage in 8 weeks after trabeculectomy (p < 0.05).

Antibiotic Stewardship Strategies and Their Association With Antibiotic Overuse After Hospital Discharge: An Analysis of the Reducing Overuse of Antibiotics at Discharge (Road) Home Framework.

BACKGROUND: Strategies to optimize antibiotic prescribing at discharge are not well understood. METHODS: In fall 2019, we surveyed 39 Michigan hospitals on their antibiotic stewardship strategies. The association of reported strategies with discharge antibiotic overuse (unnecessary, excess, suboptimal fluoroquinolones) for community-acquired pneumonia (CAP) and urinary tract infection (UTI) was evaluated in 2 ways: (1) all strategies assumed equal weight and (2) strategies were weighted based on the ROAD (Reducing Overuse of Antibiotics at Discharge) Home Framework (ie, Tier 1-Critical infrastructure, Tier 2-Broad inpatient interventions, Tier 3-Discharge-specific strategies) with Tier 3 strategies receiving the highest weight. RESULTS: Between 1 July 2017 and 30 July 2019, 39 hospitals with 20 444 patients (56.5% CAP; 43.5% UTI) were included. Survey response was 100%. Hospitals reported a median (interquartile range [IQR]) 12 (9-14) of 34 possible stewardship strategies. On analyses of individual stewardship strategies, the Tier 3 intervention, review of antibiotics prior to discharge, was the only strategy consistently associated with lower antibiotic overuse at discharge (adjusted incident rate ratio [aIRR] 0.543, 95% confidence interval [CI]: .335-.878). On multivariable analysis, weighting by ROAD Home tier predicted antibiotic overuse at discharge for both CAP and UTI. For diseases combined, having more weighted strategies was associated with lower antibiotic overuse at discharge (aIRR 0.957, 95% CI: .927-.987, per weighted intervention); discharge-specific stewardship strategies were associated with a 12.4% relative decrease in antibiotic overuse days at discharge. CONCLUSIONS: The more stewardship strategies a hospital reported, the lower its antibiotic overuse at discharge. However, Tier 3, or discharge-specific strategies, appeared to have the largest effect on antibiotic prescribing at discharge.

Interleukin-6 trans-signalling in hippocampal CA1 neurones mediates perioperative neurocognitive disorders in mice.

BACKGROUND: Interleukin-6 (IL-6), a pleiotropic cytokine with both degenerative and regenerative properties, is necessary and sufficient to provoke perioperative neurocognitive disorders after aseptic trauma in mice. IL-6 initiates its actions after binding to either membrane-bound IL-6 receptor α (mIL-6Rα) through classical signalling, or soluble IL-6 receptor (IL-6R) through trans-signalling; both signalling pathways require the transducer gp130. We investigated the site and type of IL-6 signalling that pertains in a tibial fracture aseptic trauma model of perioperative neurocognitive disorder. METHODS: Wild-type or genetically altered adult mice that lacked molecules unique to either classical or trans-IL-6 signalling underwent tibial fracture under isoflurane anaesthesia. In separate cohorts, we assessed postoperative memory using a trace fear conditioning paradigm (72 h postoperatively), and post-receptor IL-6 signalling (24 h postoperatively) using phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in CA1 hippocampal neurones. Fracture healing was assessed at postoperative day 15 after inhibiting either both forms of IL-6 signalling with BE0047 or only trans-signalling with sgp130Fc. RESULTS: The surgical phenotype of memory decline (decrease in freezing in trace fear conditioning) and upregulated IL-6 signalling (pSTAT3) did not occur after pretreatment before surgery with either BE0047 or sgp130Fc, or after depleting gp130 from CA1 neurones. The surgical phenotype still occurred when IL-6Rα was depleted in either CA1 hippocampal neurones (freezing time, 38.9% [11.5%] vs 58.4% [12.3%]; pSTAT+ CA1 neurones, 31.7 [4.9] vs 7.0 [3.1]) or microglia (freezing time, 40.1% [13.9%] vs 65.2% [12.6%]; pSTAT+ CA1 neurones, 30.1 [5.5] vs 7.9 [3.2]). In global IL-6Rα-/- mice, hyper-IL-6, the trans-signalling agonist, produced the surgical phenotype when administered i.c.v. (freezing time, 42.4% [8.8%] vs 59.7% [10.4%]; pSTAT+ cells, 29.3 [4.3] vs 10.0 [4.4]). Bone-fracture healing (% of fracture callus comprised of new collagen) was significantly greater with sgp130Fc than with BE0047 (52.2% [8.3%] vs 39.7% [7.9%]). CONCLUSIONS: After orthopaedic trauma, IL-6 produces perioperative neurocognitive disorders through IL-6 trans-signalling in mouse CA1 neurones. Druggable targets of the trans-signalling pathway should be sought to reduce perioperative neurocognitive disorders while allowing the healing properties of classical IL-6 signalling.

Remote Ischemic Preconditioning Reduces Acute Kidney Injury After Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery. METHODS: PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis. RESULTS: A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis. CONCLUSIONS: This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.

Dynamical Behavior of SEIR-SVS Epidemic Models with Nonlinear Incidence and Vaccination.

For some infectious diseases such as mumps, HBV, there is evidence showing that vaccinated individuals always lose their immunity at different rates depending on the inoculation time. In this paper, we propose an age-structured epidemic model using a step function to describe the rate at which vaccinated individuals lose immunity and reduce the age-structured epidemic model to the delay differential model. For the age-structured model, we consider the positivity, boundedness, and compactness of the semiflow and study global stability of equilibria by constructing appropriate Lyapunov functionals. Moreover, for the reduced delay differential equation model, we study the existence of the endemic equilibrium and prove the global stability of equilibria. Finally, some numerical simulations are provided to support our theoretical results and a brief discussion is given.

Perioperative dexmedetomidine and 5-year survival in patients undergoing cardiac surgery.

BACKGROUND: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery. METHODS: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 µg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models. RESULTS: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010). CONCLUSION: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.

miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression.

Psoriasis is considered as a common chronic and relapsing inflammatory skin disease. MicroRNAs (miRNAs) were found to be related with psoriasis pathogenesis. Nevertheless, the function of miR-617 in psoriasis is still unclear. The miR-617 RNA level was detected using quantitative reverse transcription-PCR (qRT-PCR). Western blot analysis examined the protein level. Cell proliferation was analyzed via cell counting kit-8 (CCK-8) assay. Flow cytometry analysis detected cell cycle and apoptosis. The relationship between miR-617 and forkhead box protein O4 (FOXO4) was confirmed through dual luciferase assay. The miR-617 was up-regulated in psoriatic skin tissues and interleukin-22 (IL-22)-stimulated immortalized human keratinocyte HaCaT cells. Moreover, miR-617 mimics promoted proliferation, cell cycle, and suppressed apoptosis in IL-22-stimulated HaCaT cells. However, miR-617 inhibitor showed opposite effects. Additionally, FOXO4 was a target of miR-617. FOXO4 was down-regulated in psoriatic skin tissues and IL-22-stimulated HaCaT cells. Negative correlation between miR-617 and FOXO4 was identified. FOXO4 overexpression alleviated the effects of miR-617 proliferation, cell cycle and apoptosis in the IL-22-stimulated HaCaT cells. These results demonstrate that miR-617 increases the growth of IL-22-stimulated keratinocytes through targeting FOXO4, which provides a new therapeutic target for psoriasis.

Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia: A double-blind, randomised clinical trial.

BACKGROUND: Dexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce. OBJECTIVE: To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA). DESIGN: A randomised, double-blind, placebo-controlled trial. SETTING: Single-centre, tertiary care hospital, November 2016 to September 2018. PATIENTS: Eligible patients (n = 177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, n = 87) or dexmedetomidine with TIVA (DEX-TIVA, n = 90). INTERVENTIONS: Patients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4 µg kg-1), over 15 min, followed by a continuous infusion at a rate of 0.1 µg kg-1 h-1 until 1 h before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol. OUTCOME MEASURES: The primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile. RESULTS: All randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (P = 0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, P = 0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (P < 0.0001). CONCLUSION: Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile. TRIAL REGISTRATION: Chinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881.

Blocking Kv1.3 potassium channels prevents postoperative neuroinflammation and cognitive decline without impairing wound healing in mice.

BACKGROUND: Postoperative cognitive decline (PCD) requires microglial activation. Voltage-gated Kv1.3 potassium channels are involved in microglial activation. We determined the role of Kv1.3 in PCD and the efficacy and safety of inhibiting Kv1.3 with phenoxyalkoxypsoralen-1 (PAP-1) in preventing PCD in a mouse model. METHODS: After institutional approval, we assessed whether Kv1.3-deficient mice (Kv1.3-/-) exhibited PCD, evidenced by tibial-fracture surgery-induced decline in aversive freezing behaviour, and whether PAP-1 could prevent PCD and postoperative neuroinflammation in PCD-vulnerable diet-induced obese (DIO) mice. We also evaluated whether PAP-1 altered either postoperative peripheral inflammation or tibial-fracture healing. RESULTS: Freezing behaviour was unaltered in postoperative Kv1.3-/- mice. In DIO mice, PAP-1 prevented postoperative (i) attenuation of freezing behaviour (54 [17.3]% vs 33.4 [12.7]%; P=0.03), (ii) hippocampal microglial activation by size (130 [31] pixels vs 249 [49]; P<0.001) and fluorescence intensity (12 000 [2260] vs 20 800 [5080] absorbance units; P<0.001), and (iii) hippocampal upregulation of interleukin-6 (IL-6) (14.9 [5.7] vs 25.6 [10.4] pg mg-1; P=0.011). Phenoxyalkoxypsoralen-1 neither affected surgery-induced upregulation of plasma IL-6 nor cartilage and bone components of the surgical fracture callus. CONCLUSIONS: Microglial-mediated PCD requires Kv1.3 activity, determined by genetic and pharmacological targeting approaches. Phenoxyalkoxypsoralen-1 blockade of Kv1.3 prevented surgery-induced hippocampal microglial activation and neuroinflammation in mice known to be vulnerable to PCD. Regarding perioperative safety, these beneficial effects of PAP-1 treatment occurred without impacting fracture healing. Kv1.3 blockers, currently undergoing clinical trials for other conditions, may represent an effective and safe intervention to prevent PCD.

Dexmedetomidine Prevents Cognitive Decline by Enhancing Resolution of High Mobility Group Box 1 Protein-induced Inflammation through a Vagomimetic Action in Mice.

BACKGROUND: Inflammation initiated by damage-associated molecular patterns has been implicated for the cognitive decline associated with surgical trauma and serious illness. We determined whether resolution of inflammation mediates dexmedetomidine-induced reduction of damage-associated molecular pattern-induced cognitive decline. METHODS: Cognitive decline (assessed by trace fear conditioning) was induced with high molecular group box 1 protein, a damage-associated molecular pattern, in mice that also received blockers of neural (vagal) and humoral inflammation-resolving pathways. Systemic and neuroinflammation was assessed by proinflammatory cytokines. RESULTS: Damage-associated molecular pattern-induced cognitive decline and inflammation (mean ± SD) was reversed by dexmedetomidine (trace fear conditioning: 58.77 ± 8.69% vs. 41.45 ± 7.64%, P < 0.0001; plasma interleukin [IL]-1ß: 7.0 ± 2.2 pg/ml vs. 49.8 ± 6.0 pg/ml, P < 0.0001; plasma IL-6: 3.2 ± 1.6 pg/ml vs. 19.5 ± 1.7 pg/ml, P < 0.0001; hippocampal IL-1ß: 4.1 ± 3.0 pg/mg vs. 41.6 ± 8.0 pg/mg, P < 0.0001; hippocampal IL-6: 3.4 ± 1.3 pg/mg vs. 16.2 ± 2.7 pg/mg, P < 0.0001). Reversal by dexmedetomidine was prevented by blockade of vagomimetic imidazoline and α7 nicotinic acetylcholine receptors but not by α2 adrenoceptor blockade. Netrin-1, the orchestrator of inflammation-resolution, was upregulated (fold-change) by dexmedetomidine (lung: 1.5 ± 0.1 vs. 0.7 ± 0.1, P < 0.0001; spleen: 1.5 ± 0.2 vs. 0.6 ± 0.2, P < 0.0001), resulting in upregulation of proresolving (lipoxin-A4: 1.7 ± 0.2 vs. 0.9 ± 0.2, P < 0.0001) and downregulation of proinflammatory (leukotriene-B4: 1.0 ± 0.2 vs. 3.0 ± 0.3, P < 0.0001) humoral mediators that was prevented by α7 nicotinic acetylcholine receptor blockade. CONCLUSIONS: Dexmedetomidine resolves inflammation through vagomimetic (neural) and humoral pathways, thereby preventing damage-associated molecular pattern-mediated cognitive decline.

Analysis of a Dengue Model with Vertical Transmission and Application to the 2014 Dengue Outbreak in Guangdong Province, China.

There is evidence showing that vertical transmission of dengue virus exists in Aedes mosquitoes. In this paper, we propose a deterministic dengue model with vertical transmission in mosquitoes by including aquatic mosquitoes (eggs, larvae and pupae), adult mosquitoes (susceptible, exposed and infectious) and human hosts (susceptible, exposed, infectious and recovered). We first analyze the existence and stability of disease-free equilibria, calculate the basic reproduction number and discuss the existence of the disease-endemic equilibrium. Then, we study the impact of vertical transmission of the virus in mosquitoes on the spread dynamics of dengue. We also use the model to simulate the reported infected human data from the 2014 dengue outbreak in Guangdong Province, China, carry out sensitivity analysis of the basic reproduction number in terms of the model parameters, and seek for effective control measures for the transmission of dengue virus.

Development and validation of a subcritical 1,1,1,2-tetrafluoroethane extraction technique: Gas chromatography-mass spectrometry method for the simultaneous determination of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and polybrominated biphenyl ethers in aquatic products.

A simple, rapid, and green method was developed for the simultaneous analysis of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and polybrominated biphenyl ethers in aquatic products using subcritical 1,1,1,2-tetrafluoroethane extraction coupled with gas chromatography and mass spectrometry. Effects of the extraction temperature, pressure, and cosolvent volume on the extraction efficiency were investigated by extracting spiked oyster samples. The results show that the maximum extraction efficiency was obtained at 40°C, 12 MPa, and a cosolvent (dichloromethane) volume of 5.0 mL. Under these conditions, the calibration curves had good linearity with square of the correlation larger than 0.998 in the concentration range of 5-800 ng/mL; limit of detection and limit of quantitation were 0.16-2.83 and 0.55-9.43 ng/g, respectively. At spiked levels of 10, 30, and 50 ng/g, the average recoveries were 70.4-80.4% for polycyclic aromatic hydrocarbons, 74.0-83.6% for polychlorinated biphenyls, and 66.9-78.0% for polybrominated biphenyl ethers, with average relative standard deviations of less than 16.3%. The established method has no significant differences in recovery compared to traditional methods and is suitable for the analysis of real samples.

Metal-Free Radical Oxidative Annulation of Ynones with Alkanes To Access Indenones.

The benzoyl peroxide (BPO) promoted carboannulation of ynones with alkanes is developed, affording a series of 2-alkyl-3-aryl indenones in moderate to good yields. The procedure involves direct functionalization of alkane C(sp(3))-H and arene C(sp(2))-H bonds under metal-free conditions, providing a favorable approach for indenone synthesis.

Ghrelin inhibits proinflammatory responses and prevents cognitive impairment in septic rats.

OBJECTIVES: A novel stomach-derived peptide, ghrelin, is down-regulated in sepsis and its IV administration decreases proinflammatory cytokines and mitigates organ injury. In this study, we wanted to investigate the effects of ghrelin on proinflammatory responses and cognitive impairment in septic rats. DESIGN: Prospective, randomized, controlled experiment. SETTING: Animal basic science laboratory. SUBJECTS: Sprague-Dawley rats, weighing 250-300 g. INTERVENTIONS: Sepsis was induced by cecal ligation and puncture. Animals were randomly divided into four groups: sham, sham + ghrelin, cecal ligation and puncture, and cecal ligation and puncture + ghrelin. Saline was given subcutaneously (30 mL/kg) at 4 and 16 hours after surgery for all rats. Septic rats were treated with ceftriaxone (30 mg/kg) and clindamycin (25 mg/kg) subcutaneously at 4 and 16 hours after surgery. Ghrelin (80 µg/kg) was administrated intraperitoneally 4 and 16 hours after surgery in sham + ghrelin group and cecal ligation and puncture + ghrelin group. MEASUREMENTS AND MAIN RESULTS: The levels of proinflammatory cytokines in hippocampus were measured by enzyme-linked immunosorbent assay, and cleaved caspase-3 was detected by Western blot 24 hours after surgery. Neuronal apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining 48 hours after surgery. Additional animals were monitored to record survival and body weight changes for 10 days after surgery. Survival animals underwent behavioral tasks 10 days after surgery: open-field, novel object recognition, and continuous multiple-trial step-down inhibitory avoidance task. Ghrelin significantly decreased the levels of proinflammatory cytokines and inhibited the activation of caspase-3 in the hippocampus after cecal ligation and puncture. The density of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive apoptotic neurons was significantly lowered by ghrelin. In addition, ghrelin improved the survival rates after cecal ligation and puncture. There were no differences in the distance and move time between groups in open-field task. However, the survivors after cecal ligation and puncture were unable to recognize the novel object and required more training trials to reach the acquisition criterion. All these long-term impairments were prevented by ghrelin. CONCLUSIONS: Ghrelin inhibited proinflammatory responses, improved the survival rate, and prevented cognitive impairment in septic rats.

Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice.

We previously found that human mesenchymal stem cells (MSC) or its conditioned medium restored lung protein permeability and reduced alveolar inflammation following Escherichia coli endotoxin-induced acute lung injury (ALI) in an ex vivo perfused human lung in part through the secretion of soluble factors such as keratinocyte growth factor (KGF). Recently, MSC were found to release microvesicles (MVs) that were biologically active because of the presence of mRNA or miRNA with reparative properties. MVs are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes. These studies were designed to determine if MVs released by human bone marrow derived MSCs would be effective in restoring lung protein permeability and reducing inflammation in E. coli endotoxin-induced ALI in C57BL/6 mice. The intratracheal instillation of MVs improved several indices of ALI at 48 hours. Compared to endotoxin-injured mice, MVs reduced extravascular lung water by 43% and reduced total protein levels in the bronchoalveolar lavage (BAL) fluid by 35%, demonstrating a reduction in pulmonary edema and lung protein permeability. MVs also reduced the influx of neutrophils and macrophage inflammatory protein-2 levels in the BAL fluid by 73% and 49%, respectively, demonstrating a reduction in inflammation. KGF siRNA-pretreatment of MSC partially eliminated the therapeutic effects of MVs released by MSCs, suggesting that KGF protein expression was important for the underlying mechanism. In summary, human MSC-derived MVs were therapeutically effective following E. coli endotoxin-induced ALI in mice in part through the expression of KGF mRNA in the injured alveolus.

Application of response surface methodology to optimise microbial inactivation of shrimp and conch by supercritical carbon dioxide.

BACKGROUND: Supercritical carbon dioxide (SC-CO2 ) has been shown to have a good pasteurising effect on food. However, very few research papers have investigated the possibility to exploit this treatment for solid foods, particularly for seafood. Considering the microbial safety of raw seafood consumption, the study aimed to explore the feasibility of microbial inactivation of shrimp (Metapenaeus ensis) and conch (Rapana venosa) by SC-CO2 treatment. RESULTS: Response surface methodology (RSM) models were established to predict and analyse the SC-CO2 process. A 3.69-log reduction in the total aerobic plate count (TPC) of shrimp was observed by SC-CO2 treatment at 53°C, 15 MPa for 40 min, and the logarithmic reduction in TPC of conch was 3.31 at 55°C, 14 MPa for 42 min. Sensory scores of the products achieved approximately 8 (desirable). The optimal parameters for microbial inactivation of shrimp and conch by SC-CO2 might be 55°C, 15 MPa and 40 min. CONCLUSION: SC-CO2 exerted a strong bactericidal effect on the TPC of shrimp and conch, and the products maintained good organoleptic properties. This study verified the feasibility of microbial inactivation of shrimp and conch by SC-CO2 treatment.