Sepsis-associated encephalopathy (SAE) is a common complication that leads to long-term cognitive impairments and increased mortality in sepsis survivors. The mechanisms underlying this complication ...remain unclear and an effective intervention is lacking. Accumulating evidence suggests the nucleotide-binding domain-like receptor protein3 (NLRP3)/caspase-1 pathway is involved in several neurodegenerative diseases. Thus, we hypothesized that the NLRP3/caspase-1 pathway is involved in NLRP3-mediated pyroptosis, maturation and release of inflammatory cytokines, and cognitive deficits in SAE. We used the NLRP3 inhibitor MCC950 and the caspase-1 inhibitor Ac-YVAD-CMK to study the role of the NLRP3/caspase-1 pathway in pyroptosis and cognitive deficits in a mouse model of SAE. Mice were randomly assigned to one of six groups: sham+saline, sham+MCC950, sham+Ac-YVAD-CMK, cecal ligation and puncture (CLP)+saline, CLP+MCC950, and CLP+Ac-YVAD-CMK. Surviving mice underwent behavioral tests or had hippocampal tissues collected for histochemical analysis and biochemical assays. Our results show that CLP-induced hippocampus-dependent memory deficits are accompanied by increased NLRP3 and caspase-1 positive cells, and augmented protein levels of NLRP3, caspase-1, gasdermin-D, and pro-inflammatory cytokines in the hippocampus. In addition, administration of MCC950 or Ac-YVAD-CMK rescues cognitive deficits and ameliorates increased hippocampal NLRP3-mediated neuronal pyroptosis and pro-inflammatory cytokines. Our results suggest that the NLRP3/caspase-1 pathway-induced pyroptosis mediates cognitive deficits in a mouse model of SAE.
Dendrite growth of alkali metal anodes limited their lifetime for charge/discharge cycling. Here, we report near-perfect anodes of lithium, sodium, and potassium metals achieved by electrochemical ...polishing, which removes microscopic defects and creates ultra-smooth ultra-thin solid-electrolyte interphase layers at metal surfaces for providing a homogeneous environment. Precise characterizations by AFM force probing with corroborative in-depth XPS profile analysis reveal that the ultra-smooth ultra-thin solid-electrolyte interphase can be designed to have alternating inorganic-rich and organic-rich/mixed multi-layered structure, which offers mechanical property of coupled rigidity and elasticity. The polished metal anodes exhibit significantly enhanced cycling stability, specifically the lithium anodes can cycle for over 200 times at a real current density of 2 mA cm
with 100% depth of discharge. Our work illustrates that an ultra-smooth ultra-thin solid-electrolyte interphase may be robust enough to suppress dendrite growth and thus serve as an initial layer for further improved protection of alkali metal anodes.
Purpose
We aim to investigate associations of maternal serum anti-thyroperoxidase autoantibody (TPOAb) with duration of gestation. We aim to investigate whether maternal TPOAb positivity is ...associated with the risk of premature or early term birth.
Methods
This was a prospective birth cohort study performed in an iodine sufficient area of China. Serum samples were collected from 2931 women at both the first and second trimesters of pregnancy. Thyrotropin (TSH), free thyroxine (FT4), and TPOAb levels were measured. Data on gestational age at birth was obtained from delivery records.
Results
The prevalence of early term birth was 23.8%, while the prevalence of premature birth was 4.2%. The prevalence of TPOAb positivity was 12.1% in the first trimester and was 7.2% in the second trimester. Gestational age at birth was inversely associated with lgTPOAb both in the first trimester (
β
, −0.283, 95% CI −0.408, −0.158;
P
< 0.001) and in the second trimester (
β
, −0.174, 95% CI −0.319, −0.030;
P
= 0.018), after adjustment for potential confounding factors. There was a positive association of TPOAb positivity with the risk of early term birth both in the first (OR = 1.691, 95% CI 1.302, 2.197) and second trimesters (OR = 1.644, 95% CI 1.193, 2.264), after adjustment for potential confounding factors. TPOAb positivity in the second trimester was associated with a 1.863-fold higher risk of premature birth (OR = 1.863, 95% CI 1.009, 3.441), after adjustment for potential confounding factors.
Conclusions
Our results show that TPOAb is associated with shorter duration of gestation and with higher risk of premature and early term birth.
Background
Several studies have shown that scorpion venom peptide BmK AGAP has an analgesic activity. Our previous study also demonstrated that intraplantar injection of BmK AGAP ameliorates ...formalin-induced spontaneous nociceptive behavior. However, the effect of intrathecal injection of BmK AGAP on nociceptive processing is poorly understood.
Methods
We investigated the effects of intrathecal injection of BmK AGAP on spinal nociceptive processing induced by chronic constrictive injury or formalin. Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and the von Frey filaments test. Formalin-induced spontaneous nociceptive behavior was also investigated. C-Fos expression was assessed by immunohistochemistry. Phosphorylated mitogen-activated protein kinase (p-MAPK) expression was monitored by Western blot assay.
Results
Intrathecal injection of BmK AGAP reduced chronic constrictive injury-induced neuropathic pain behavior and pain from formalin-induced inflammation, accompanied by decreased expression of spinal p-MAPKs and c-Fos protein. The results of combining low doses of different MAPK inhibitor (U0126, SP600125, or SB203580; 0.1 µg for each inhibitor) with a low dose of BmK AGAP (0.2 µg) suggested that BmK AGAP could potentiate the effects of MAPK inhibitors on inflammation-associated pain.
Conclusion
Our results demonstrate that intrathecal injection of BmK AGAP produces a sensory-specific analgesic effect via a p-MAPK-dependent mechanism.
Summary
Objective
Hypertensive disorders of pregnancy (HDP) have been associated with adverse health outcomes for both mothers and children. Previous studies examining associations of maternal ...thyroid autoantibodies with HDP indicate conflicting results. The objective of this study was to examine associations of maternal thyroid autoantibody positivity in the first and the second trimesters with the risk of HDP.
Design, Participants and Measurements
In the Ma'anshan Birth Cohort study, a population‐based prospective study in China, a total of 3474 pregnant women were enrolled between May 2013 and September 2014. Thyroid autoantibodies, including antithyroperoxidase autoantibody (TPOAb) and antithyroglobulin autoantibody (TgAb), as well as thyroid function tests, were measured in both the first and the second trimesters in 2893 pregnant women. Multivariate logistic regression analyses were conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for the associations between thyroid autoantibodies and HDP.
Results
Multivariate logistic regression analyses showed that TPOAb positivity in the first trimester was associated with a 1.80 (95% CI = 1.17‐2.78) increased odds of HDP after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.93, 95% CI = 1.17‐3.18). In addition, TgAb positivity in the first trimester was associated with a higher risk of HDP (OR = 1.78, 95% CI = 1.16‐2.73) after adjustment for confounders, which was mainly due to an increased risk of gestational hypertension (OR = 1.89, 95% CI = 1.15‐3.11). These associations were also seen among euthyroid women. Women with positive TPOAb in the second trimester seemed to have a higher risk of gestational hypertension (OR = 1.87, 95% CI = 1.02‐3.43) after adjustment for confounders. However, among euthyroid women, TPOAb positivity in the second trimester was not associated with HDP. The TgAb status in the second trimester was not associated with HDP.
Conclusions
Our results show that TPOAb positivity and TgAb positivity in the first trimester are associated with an increased risk of HDP. These data demonstrate that these associations are even seen among euthyroid women.
Aerobic granular sludge technology has great potential for the treatment of petroleum refinery wastewater. However, strategies to shorten the granulation time and improvement the stability still need ...to be developed. In this work, biochar was prepared from waste petroleum activated sludge (biochar-WPS) and used in a sequencing batch reactor for the treatment of petroleum refinery wastewater. Biochar-WPS presented the surface area of 229.77 m
2
/g, pore volume of 0.28 cm
3
/g, H/C and O/C atomic ratios of 0.42 and 0.21, respectively. The porous structure and a high degree of hydrophilicity were found to facilitate microbial colonization and adhesion as well as particle aggregation. Application of biochar-WPS resulted in the formation of more substantial and stable aerobic granules (~ 66% of granules > 0.46 mm diameter) 15 days earlier compared with the control. The addition of biochar-WPS enhanced the average removal efficiency of chemical organic demand (~ 3%), oil (~ 4%) and total nitrogen (~ 10%) over the control. Increased microbial richness and diversity were observed within the formed granules and had an increased (~ 4%) proportion of denitrifying bacteria. These results indicate that an aerobic granulation mechanism using biochar-WPS is a feasible option for the treatment of petroleum refinery wastewater.
Possible H-bond interactions between cellulose and AMMorOAc.
Display omitted
•The morpholinium-based ILs were synthesized for dissolution of cellulose.•The Morpholinium ILs showed high dissolving ...ability compared to imidazolium ILs.•The N-methyl-N-allyl-morpholinium acetate exhibited the highest dissolving ability among ILs.•The morpholinium-based ILs showed appropriate viscosity and conductivity.•Offered a cost-efficient and “green” strategy for dissolution of cellulose.
The effective dissolution of cellulose prepares for its subsequently full utilization. Ionic liquids (ILs) are attractive options for “green” dissolution of cellulose. A series of morpholinium-based ILs were synthesized and applied in dissolution of cellulose. The ultrasonic assisted saturated calcium chloride solution was used to activate cellulose. The remarkable decrease (from 87% to 65%) in crystallinity of cellulose facilitated dissolution process. The type of head-corn cations significantly increased polarity (ET(30)) and hydrogen bond acidity (α) of ILs. N-Allyl-N-methylmorpholinium-based ILs showed the highest ET(30) and α (59.11kcalmol−1 and 0.51) compared to 1-Allyl-3-methylimidazolium-based ILs (57.41kcalmol−1 and 0.46) and 1-Allyl-3-methylpyridinium-based ILs (49.36kcalmol−1 and 0.33) owing to the electron-rich center of oxygen in the morpholine ring. The type of anions dominated the ability to accept hydrogen bond of ILs. Formate, acetate and bisulfate contributed more hydrogen bond basicity (β) (0.84, 0.88 and 0.91) for N-allyl-N-methylmorpholinium-based ILs in comparison with other anions. Additionally, morpholinium-based ILs exhibited appropriate viscosity. Above-mentioned performances jointly improved the dissolution of cellulose in morpholinium-based ILs. This study demonstrated the potential of using morpholinium-based ILs as a class of efficient solvents to dissolve cellulose.
Novel Mn–Fe–Mg- and Mn–Fe–Ce-loaded alumina (Mn–Fe–Mg/Al
2
O
3
and Mn–Fe–Ce/Al
2
O
3
) were developed to catalytically ozonate reverse osmosis concentrates generated from petroleum refinery ...wastewaters (PRW-ROC). Highly dispersed 100–300-nm deposits of composite multivalent metal oxides of Mn (Mn
2+
, Mn
3+
, and Mn
4+
), Fe (Fe
2+
and Fe
3+
) and Mg (Mg
2+
), or Ce (Ce
4+
) were achieved on Al
2
O
3
supports. The developed Mn–Fe–Mg/Al
2
O
3
and Mn–Fe–Ce/Al
2
O
3
exhibited higher catalytic activity during the ozonation of PRW-ROC than Mn–Fe/Al
2
O
3
, Mn/Al
2
O
3
, Fe/Al
2
O
3
, and Al
2
O
3
. Chemical oxygen demand removal by Mn–Fe–Mg/Al
2
O
3
- or Mn–Fe–Ce/Al
2
O
3
-catalyzed ozonation increased by 23.9% and 23.2%, respectively, in comparison with single ozonation. Mn–Fe–Mg/Al
2
O
3
and Mn–Fe–Ce/Al
2
O
3
notably promoted ·OH generation and ·OH-mediated oxidation. This study demonstrated the potential use of composite metal oxide-loaded Al
2
O
3
in advanced treatment of bio-recalcitrant wastewaters.
This study evaluated the safety and efficacy of stereotactic radiation therapy (SRT) for the treatment of patients with oligometastases or oligorecurrence within mediastinal lymph nodes (MLNs) ...originating from different tumors.
Between October 2006 and May 2015, patients with MLN oligometastases or oligorecurrence were enrolled and treated with SRT at our hospital. The primary endpoint was MLN local control (LC). Secondary endpoints were time to symptom alleviation, overall survival (OS) after SRT, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).
Eighty-five patients with 98 MLN oligometastases or oligorecurrences were treated with SRT. For the entire cohort, the 1-year and 5-year actuarial LC rates were 97% and 77%, respectively. Of 53 symptomatic patients, symptom alleviation was observed in 47 (89%) after a median of 5 days (range, 3-30 days). The median OS was 27.2 months for all patients. For patients with non-small cell lung cancer, univariate and multivariate analyses revealed that a shorter interval between diagnosis of primary tumors and SRT and larger MLN SRT volume were associated with worse OS. CTCAE v4.0 ≥ Grade 3 toxicities occurred in six patients (7%), with Grade 5 in three patients (all with RT history to MLN station 7).
SRT is a safe and efficacious treatment modality for patients with oligometastases or oligorecurrence to MLNs originating from different tumors, except for patients who received radiotherapy to MLN station 7. Further investigation is warranted to identify the patients who benefit most from this treatment modality.
To evaluate the safety and efficacy of stereotactic radiotherapy (SRT, both stereotactic body RT SBRT and fractionated stereotactic RT FSRT) in the treatment of patients with recurrent or second ...primary mediastinal lymph node metastases (R/SP-MLNMs) originating from non-small cell lung cancer (NSCLC).
Between 10/2006 and 7/2013, patients with R/SP-MLNMs originating from NSCLC were enrolled and treated with SRT at our hospital; their data was stored in prospectively-collected database. The enrolled patients were divided into Group A (without prior RT) and Group B (with prior RT). The primary end-point was overall survival (OS). The secondary end-points were the MLNM local control (LC), the time to symptom alleviation, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).
Thirty-three patients were treated (16 in Group A with 19 R/SP-MLNMs and 17 in Group B with 17 R/SP-MLNMs). For the entire cohort, the median OS was 25.5 months with a median follow-up of 20.9 months (range, 3.2-82). The 1-year and 3-year actuarial LC rates were 100% and 86%, respectively. Symptom alleviation was observed in 52% of patients, after a median of 6 days (range, 3-18). CTCAE v4.0 ≥ Grade 3 toxicities occurred in 5 patients (15%; all in Group B); among them, Grade 5 in 2 patients.
We recommend exercising extreme caution in using SRT for R/SP-MLNMs in patients who received prior RT (particularly to LN station 7). For patients without previous RT, SRT appears to be safe and efficacious treatment modality; prospective studies are warranted.
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