Preeclampsia (PE) remains one of the leading causes of maternal and perinatal morbidity and mortality. However, the exact pathophysiology of PE is still unclear. The recent widely accepted notion ...that successful pregnancy relies on maternal immunological adaptation is of utmost importance. Moreover, salt-inducible kinase 3 (SIK3) is an AMP-activated protein kinase-related kinase, and it has reported a novel regulator of energy and inflammation, and its expression related with some diseases. To explore whether SIK3 expression correlated with PE, we analyzed SIK3 gene expression and its association with PE through GEO datasets. We identified that SIK3 was significantly downregulated in PE across four datasets (
< 0.05), suggesting that SIK3 participated in the pathogenesis of PE. We initially demonstrated the significant downregulation of SIK3 in trophoblast cells of PE. SIK3 downregulation was positively correlated with the increased number of CD204(+) cells in in vivo and in vitro experiments. The increased number of CD204(+) cells could inhibit the migration and invasion of trophoblast cells. We then clarified the potential mechanism of PE with SIK3 downregulation: M2 skewing was triggered by trophoblast cells derived via the CCL24/CCR3 axis, leading to an increase in CD204(+) cells, a decrease in phagocytosis, and the production of IL-10 at the maternal-fetal interface of the placenta with PE. IL-10 further contributed to a reduction in the migration and invasion of trophoblast cells. It also established a feedback loop wherein trophoblast cells increased CCL24 production to maintain M2 dominance in the placental environments of PE.
Hypertriglyceridemia is the third most common cause of acute pancreatitis, but whether the level of triglyceride (TG) is related to severity of pancreatitis is unclear.
To evaluate the effect of TG ...level on the severity of hypertriglyceridemic pancreatitis (HTGP).
Retrospective cohort study.
We reviewed the records of 144 patients with HTGP from 1999 to 2013 at Tri-Service General Hospital. Patients with possible etiology of pancreatitis, such as gallstones, those consuming alcohol or drugs, or those with infections were excluded. The classification of severity of pancreatitis was based on the revised Atlanta classification. We allocated the patients into high-TG and low-TG groups based on the optimal cut-off value (2648 mg/dL), which was derived from the receiver operating characteristic (ROC) curve between TG level and severity of HTGP. We then compared the clinical characteristics, pancreatitis severity, and mortality rates of the groups.
There were 66 patients in the low-TG group and 78 patients in the high-TG group. There was no significant difference in the age, sex ratio, body mass index, and comorbidity between the 2 groups. The high-TG group had significantly higher levels of glucose (P = 0.022), total cholesterol (P = 0.002), and blood urea nitrogen (P = 0.037), and lower levels of sodium (P = 0.003) and bicarbonate (P = 0.002) than the low-TG group. The incidences of local complication (P = 0.002) and severe and moderate form of pancreatitis (P = 0.004) were significantly higher in the high-TG group than in the low-TG group. The mortality rate was higher in the high-TG group than in the low-TG group (P = 0.07).
Higher TG level in patients with HTGP may be associated with adverse prognosis, but randomized and prospective studies are needed in the future verify this relationship.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Organic wastes are now increasingly viewed as a resource of energy that can be harvested by suitable biotechnologies. One promising technology is microbial fuel cells (MFC), which can generate ...electricity from the degradation of organic pollutants. While the environmental benefits of MFC in waste treatment have been recognized, their potential as an energy producer is not fully understood. Although progresses in material and engineering have greatly improved the power output from MFC, how to efficiently utilize the MFC's energy in real-world scenario remains a challenge. In this review, fundamental understandings on the energy-generating capacity of MFC from real waste treatment are provided and the challenges and opportunities are discussed. The limiting factors restricting the energy output and impairing the long-term reliability of MFC are also analyzed. Several energy storage and
in situ
utilization strategies for the management of MFC's energy are proposed, and future research needs for real-world application of this approach are explored.
Energy generated from wastes by using MFC technology could be effectively stored and utilized for real-world applications.
Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and exacerbation of hepatic steatosis but their combined impacts ...and the potential mechanisms remain to be further elucidated. Here, we showed that exposure to AFB1 impaired mitochondrial dynamics and increased intracellular lipid droplets (LDs) in the liver of HBV‐transgenic mice in vivo and the hepatitis B virus X protein (HBx)‐expressing human hepatocytes both ex vivo and in vitro. HBx combined with AFB1 exposure also up‐regulated receptor interaction protein 1 (RIP1), receptor interaction protein 3 (RIP3) and activated mixed lineage kinase domain like protein (MLKL), providing evidence of necrosome formation in the hepatocytes. The shift of the mitochondrial dynamics towards imbalance of fission and fusion was rescued when MLKL was inhibited in the HBx and AFB1 co‐treated hepatocytes. Most importantly, based on siRNA or CRISPR/Cas9 system, we found that the combination of HBx and AFB1 exposure increased cyclooxygenase‐2 (COX‐2) to mediate up‐regulation of RIP3 and dynamin‐related protein 1 (Drp1), which in turn promoted location of RIP3‐MLKL necrosome on mitochondria, subsequently exacerbated steatosis in hepatocytes. Taken together, these findings advance the understanding of mechanism associated with HBx and AFB1‐induced hepatic necrosome formation, mitochondrial dysfunction and steatosis and make COX‐2 a good candidate for treatment.
Immune checkpoint blockade therapy has revolutionized non-small cell lung cancer treatment. However, not all patients respond to this therapy. Assessing the tumor expression of immune checkpoint ...molecules, including programmed death-ligand 1 (PD-L1), is the current standard in predicting treatment response. However, the correlation between PD-L1 expression and anti-PD-1/PD-L1 treatment response is not perfect. This is partly caused by tumor heterogeneity and the common practice of assessing PD-L1 expression based on limited biopsy material. To overcome this problem, we developed a novel method that can make formalin-fixed, paraffin-embedded tissue translucent, allowing three-dimensional (3D) imaging. Our protocol can process tissues up to 150 μm in thickness, allowing anti-PD-L1 staining of the entire tissue and producing high resolution 3D images. Compared to a traditional 4 μm section, our 3D image provides 30 times more coverage of the specimen, assessing PD-L1 expression of approximately 10 times more cells. We further developed a computer-assisted PD-L1 quantitation method to analyze these images, and we found marked variation of PD-L1 expression in 3D. In 5 of 33 needle-biopsy-sized specimens (15.2%), the PD-L1 tumor proportion score (TPS) varied by greater than 10% at different depth levels. In 14 cases (42.4%), the TPS at different depth levels fell into different categories (< 1%, 1-49%, or ≥ 50%), which can potentially influence treatment decisions. Importantly, our technology permits recovery of the processed tissue for subsequent analysis, including histology examination, immunohistochemistry, and mutation analysis. In conclusion, our novel method has the potential to increase the accuracy of tumor PD-L1 expression assessment and enable precise deployment of cancer immunotherapy.
Background
Controversy still exists in which subtype of non-small-cell lung cancer squamous cell carcinoma (SCC) or adenocarcinoma is more likely to have lymph node (LN) metastasis. The aim of this ...study is to compare the pattern of LN metastasis in two cohorts of matched patients surgically treated for SCC or adenocarcinoma.
Methods
A retrospective analysis of patients undergoing lobectomy or segmentectomy with systematic lymphadenectomy without preoperative treatment for lung SCC or adenocarcinoma was conducted in this study. Data for analysis consisted of age, gender, tumor size, lobe-specific tumor location, tumor location (peripheral or central), and pathologic findings. We conducted the propensity score-matched (PSM) analysis to eliminate potential bias effects of possible confounding factors.
Results
From January 2015 to December 2016 in our department, we finally included a total of 387 patients (including 63 patients with SCC and 324 patients with adenocarcinoma) for analysis. For the unmatched cohort, there was no sufficient evidence of significantly different number of positive LNs (
P
= 0.90) and rate of LN metastasis (
P
= 0.23) between SCC patients and adenocarcinoma patients. However, potential confounding factors, for example gender, tumor size, tumor location, tumor differentiation, and total number of dissected LNs, were significantly different between patients with SCC and those with adenocarcinoma. In the analysis of matched cohort after PSM analysis, those above confounding factors were comparable between the two groups. However, patients with adenocarcinoma had significantly more mean positive LNs (2.2 and 0.7;
P
= 0.008) and a higher rate of LN metastasis (53% and 29%;
P
= 0.016) than those with SCC.
Conclusions
Lung adenocarcinoma had a higher risk of LN metastasis than SCC, suggesting that different therapeutic modalities may be indicated for the two different subtypes of lung cancer.
Marine biofouling is a severe problem with a wide‐reaching impact on ship maintenance, the economy, and ecosystem safety, among others. Inspired by complex multifunctional frogskins, wrinkled ...slippery coatings are created that exhibit remarkable antifouling, anti‐icing, and self‐cleaning properties through a combination of degradable di‐block copolymer self‐assembly i.e., polystyrene‐b‐polylactide (PS‐b‐PLA) and hydrolysis‐driven dynamic release‐induced surface wrinkling. Microwrinkled patterns can generate curved surfaces that are resistant to biofouling. Gyroid‐forming PS‐b‐PLA can be used to produce nanoporous templates with cocontinuous nanochannels, which generate strong capillary forces for trapping and storing infiltrated lubricants. In this study, block‐copolymer‐derived hierarchically wrinkled slippery liquid‐infused nanoporous surfaces (i.e., micro wrinkles with nanochannels infused with slippery fluids) are successfully fabricated after silicone oil infiltration. The antibiofouling performance of these surfaces is examined against different foulers under various conditions. The produced coatings exhibited flexible, stable, transparent, and easily tunable antibiofouling characteristics. In particular, the formation of an eco‐friendly silicon‐based lubricant layer without the use of fluorinated compounds and costly material precursors is an advantage in industrial practice that can be adopted in various applications, such as fuel transport, self‐cleaning windows, anticorrosion protection, nontoxic coatings for medical devices, and optical instruments.
Inspired by complex multifunctional frogskins, wrinkled slippery coatings are created that exhibit remarkable antifouling, anti‐icing, and self‐cleaning properties through a combination of degradable di‐block copolymer self‐assembly (i.e., polystyrene‐b‐polylactide) and hydrolysis‐driven dynamic release‐induced surface wrinkling. The formation of an eco‐friendly silicon‐based lubricant layer with flexible, stable, transparent, and easily tunable antibiofouling characteristics is an advantage in industrial practice.
Lipid metabolic dysregulation and liver inflammation have been reported to be associated with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain unclear. Hepatitis B virus x ...protein (HBx) is a risk factor for NASH. Based on metabolomic and transcriptomic screens and public database analysis, we found that HBx-expressing hepatocyte-derived prostaglandin E2 (PGE2) induced macrophage polarization imbalance via prostaglandin E2 receptor 4 (EP4) through in vitro, ex vivo, and in vivo models. Here, we revealed that the M1-type polarization of macrophages induced by endoplasmic reticulum oxidoreductase-1-like protein α (ERO1α)-dependent endoplasmic reticulum stress was associated with the HBx-related hepatic NASH phenotype. Mechanistically, HBx promoted Niemann–Pick type C1 (NPC1)/oxysterol-binding protein-related protein 5 (ORP5)-mediated cholesterol transport from the lysosome to the endoplasmic reticulum via mammalian target of rapamycin (mTOR) activation. This study provides a novel basis for screening potential biomarkers in the macrophage mTOR–cholesterol homeostasis–polarization regulatory signaling pathway and evaluating targeted interventions for HBx-associated NASH.
Many favorable anticancer treatments owe their success to the induction immunogenic cell death (ICD) in cancer cells, which results in the release of endogenous danger signals along with tumor ...antigens for effective priming of anticancer immunity. We describe a strategy to artificially induce ICD by delivering the agonist of stimulator of interferon genes (STING) into tumor cells using hollow polymeric nanoshells. Following intracellular delivery of exogenous adjuvant, subsequent cytotoxic treatment creates immunogenic cellular debris that spatiotemporally coordinate tumor antigens and STING agonist in a process herein termed synthetic immunogenic cell death (sICD). sICD is indiscriminate to the type of chemotherapeutics and enables colocalization of exogenously administered immunologic adjuvants and tumor antigens for enhanced antigen presentation and anticancer adaptive response. In three mouse tumor models, sICD enhances therapeutic efficacy and restrains tumor progression. The study highlights the benefit of delivering STING agonists to cancer cells, paving ways to new chemo-immunotherapeutic designs.
Redox from the holes at the O2p orbitals is a well‐known phenomenon in Li‐rich Mn‐based batteries. However, such an anionic redox process results in the formation of O2, leading to structural ...instability owing to unstable O2p holes. Herein, a swing‐like non‐isothermal sintering technique is used to stabilize the lattice oxygen by suppressing the formation of O2 during charging. It reduces both the number of intrinsic oxygen vacancies of the Li‐rich Mn‐based oxides and the formation of O2 during charging as compared with traditional constant high‐temperature sintering. Consequently, the number of holes generated during charging in the O2p orbitals increases, whereas the number of unstable O2p holes forming O2 decreases. Therefore, the sample prepared via swing‐like non‐isothermal sintering exhibited considerably slower voltage fading and better cycling stability. This study provides valuable guidelines for stabilizing the lattice oxygen and improving the structural stability of the oxide cathodes for electrochemical energy storage.
This study adopts a swing‐like non‐isothermal sintering technique to stabilize the lattice oxygen of the Li1.2Mn0.54Ni0.13Co0.13O2 cathode. The as‐prepared cathode exhibits high cycling stability. Such enhancement is mainly attributed to the reduced oxygen vacancy concentration during sintering, and facile oxygen reversible oxidation but suppressed O2 release during charging, thereby alleviating the structural transformation.
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