In this work, we designed a novel multifunctional Pickering emulsion stabilized by lignin-based nanoparticles. We utilized the industrial waste lignin to prepare thermoresponsive lignin copolymer by ...grafting poly(N-isopropylacrylamide) (PNIPAM) onto lignin via atom transfer radical polymerization (ATRP) and then formed self-assembled nanoparticles (AL-g-PNIPAM NPs). AL-g-PNIPAM NPs well stabilized trans-resveratrol (trans-RSV)-containing palm oil emulsion droplets in water. Thanks to the abundant UV chromophoric groups of lignin, the light stability of trans-RSV was significantly improved by the protecting of the AL-g-PNIPAM NPs layer. Moreover, the emulsion properties and release behavior strongly depend on the temperature and nanoparticles size: decreasing temperature induced deformation of AL-g-PNIPAM NPs at the interface, an increase in droplet size, and the accelerated release of trans-RSV. These results showed the great potential of this approach of a green functional lignin-based nanoparticles stabilized Pickering emulsion for storage and thermal-controlled release of light-unstable and poorly water-soluble drugs.
Background
Cadherin 5 (CDH5) functions critically in maintaining cell adhesion and integrity of endothelial and vascular cells. The expression of CDH5 is abnormal in tumor cells, which may have great ...potential to serve as a new immune checkpoint. The current pan-cancer analysis was performed to better understand the role of CDH5 in tumor.
Methods
The clinical significance and immunological function of CDH5 in pan-cancers were comprehensively analyzed based on the correlations between CDH5 and clinicopathologic features, prognosis values, tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration and immune response genes using 33 datasets from The Cancer Genome Atlas (TCGA). We further confirmed the expression of CDH5 in bladder cancer (BCa) tissues and cell lines. The CD8
+
T cells were screened from peripheral blood of healthy controls and activated. BCa cell-CD8
+
T cell co-culture assay and ELISA assay were carried out to verify the immunological function of CDH5.
Results
The expression of CDH5 was down-regulated in 8 types of tumors including in BCa but up-regulated in 4 types of tumors. CDH5 was significantly correlated with tumor stage in 6 types of tumors. In addition, CDH5 was positively or negatively correlated with tumor prognosis. Furthermore, CDH5 was closely associated with TMB in 15 types of tumors and with MSI in 9 types of tumors. KEGG-GSEA and Hallmarks-GSEA analyses results indicated that CDH5 was positively related to immune response in most tumor types. In many tumors, CDH5 showed a positive correlation with immune cell infiltration. Enrichment analyses demonstrated that CDH5 was significantly related to the expression of many immunomodulators and chemokines. Further experiments showed that CDH5 was low-expressed in BCa tissues and cell lines in comparison to adjacent normal tissues and normal urothelial cell line, but it was positively associated with a better prognosis of BCa patients. The results of
in vitro
co-culture assay and ELISA assay demonstrated that CDH5 could promote the function of CD8
+
T cells in TME of BCa.
Conclusion
In summary, CDH5 was positively associated with a favorable prognosis and effective immune response in tumors, showing a great potential to serve as a novel tumor biomarker and immune checkpoint.
Single crystal X-ray diffraction is arguably the most definitive method for molecular structure determination, but the inability to grow suitable single crystals can frustrate conventional X-ray ...diffraction analysis. We report herein an approach to molecular structure determination that relies on a versatile toolkit of guanidinium organosulfonate hydrogen-bonded host frameworks that form crystalline inclusion compounds with target molecules in a single-step crystallization, complementing the crystalline sponge method that relies on diffusion of the target into the cages of a metal-organic framework. The peculiar properties of the host frameworks enable rapid stoichiometric inclusion of a wide range of target molecules with full occupancy, typically without disorder and accompanying solvent, affording well-refined structures. Moreover, anomalous scattering by the framework sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. An ever-expanding library of organosulfonates provides a toolkit of frameworks for capturing specific target molecules for their structure determination.
To compare the effects of intrathecal dexmedetomidine and intrathecal morphine as supplements to bupivacaine in cesarean sections under spinal anesthesia. Full-term parturients (n=120) undergoing ...elective cesarean sections under spinal anesthesia were randomly allocated into three groups: Group B received 10 mg bupivacaine, Group BD received 10 mg bupivacaine plus 5 µg dexmedetomidine, and Group BM received 10 mg bupivacaine plus 100 µg morphine. The onset and regression time of sensory and motor blockade, postoperative analgesia, and side effects were recorded. Group BD showed quicker onset time and a longer sensory and motor blockade than other groups (BD vs. B and BD vs. BM, p<0.05). The mean time of sensory regression to the S1 segment was 253.21±42.79 min in group BD, 192.50±40.62 min in group BM and 188.33±37.62 min in group B (p<0.001). Group BD showed an analgesia duration (time to requirement of first rescue analgesic) (17.59±6.23 h) similar to that of group BM (16.78±5.90 h) but longer than that of group B (3.53±1.68 h) (p<0.001). The incidence of pruritus was significantly higher in group BM compared with groups BD and B (p<0.001). Less shivering was observed in group BD than in groups BM and B (p=0.009). So intrathecal dexmedetomidine (5 µg) prolonged the motor and sensory blockade, provided a similar analgesic effect and reduced pruritus and shivering compared with morphine (100 µg) in cesarean sections.
Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by Toxoplasma gondii ...infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during T. gondii infection. The expression of Tim-3 in decidual MDSCs was significantly downregulated following T. gondii infection. The proportion of monocytic MDSCs population, the inhibitory effect of MDSCs on T-cell proliferation, the levels of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs were all decreased in T. gondii-infected pregnant Tim-3 gene knockout (Tim-3KO) mice compared with infected pregnant WT mice. After treatment with Tim-3-neutralizing Ab in vitro, the expression levels of Arg-1, IL-10, C/EBPβ, and p-STAT3 were decreased, the interaction between Fyn and Tim-3 or between Fyn and STAT3 was weakened, and the binding ability of C/EBPβ to the promoters of ARG1 and IL10 was decreased in human decidual MDSCs with T. gondii infection, while opposite results were observed following treatment with galectin-9 (a ligand for Tim-3). Inhibitors of Fyn and STAT3 also downregulated the expression of Arg-1 and IL-10 in decidual MDSCs and exacerbated adverse pregnancy outcomes caused by T. gondii infection in mice. Therefore, our studies discovered that the decrease of Tim-3 after T. gondii infection could downregulate the functional molecules of Arg-1 and IL-10 expression in decidual MDSCs through the Fyn-STAT3-C/EBPβ signaling pathway and weaken their immunosuppressive function, which eventually contribute to the development of adverse pregnancy outcomes.
Abstract Commonly used anesthetic agents, e.g. ketamine, may be neurotoxic to the developing brain but there has been little attention to the neurobehavioral consequences for offspring when used for ...maternal anesthesia. We hypothesize that treatment of pregnant rats with ketamine during the second trimester would affect brain development of the offspring. Pregnant rats on gestational day 14, about equal to midtrimester pregnancy in humans, received a sedative dose of ketamine intravenously for 2 h. Brain hippocampal morphology of their pups at postnatal days 0 (P0) and P30 was examined by Nissl-staining and the characteristics of dendrites were determined using the Golgi-Cox staining, while cell proliferation in subventricular zone (SVZ) and dentate gyrus (DG) was labeled with bromodeoxyuridine (BrdU). Their neurobehavioral functions were tested at P25–30 after which the NR1 and NR2 subunits of N-methyl- d -aspartate (NMDA) receptor, brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD-95) in the hippocampus were analyzed by western blot. When pregnant rats were exposed to ketamine, there was neuronal loss, pyramidal neuronal abnormality and reduced cell proliferation in the hippocampus of offspring. These morphological abnormalities were associated with depression- and anxiety-like behaviors, and impaired memory up to young adult age. The treatment further caused NR2A receptor subunit up-regulation and NR2B receptor subunit, BDNF and PSD-95 down-regulation. These data suggest that maternal anesthesia with ketamine during the fetal brain development period can cause fetal brain damage and subsequent neurobehavioral abnormality, which is likely associated with the imbalanced expression of NMDA receptor subunits.
Guilin is a famous karst area, and currently the view that the disintegration of red clay will cause soil cave collapse is increasingly recognized. In order to study the influence of the coupling ...effect of moisture content and void ratio on the disintegration of red clay, different moisture contents and void ratios of Guilin red clay were placed on a self-made disintegration apparatus to record the real-time disintegration amount and observe the disintegration phenomenon. Images of the structural characteristics of soil were obtained by a scanning electron microscope (SEM). Additionally, nuclear magnetic resonance (NMR) was applied to analyze the distribution of water in both natural and saturated states. The results show that the disintegration rate of red clay decreases as the initial moisture content increases, but increases with the increase of void ratio. Both moisture content and void ratio affect the structural characteristics of red clay. When the moisture content remains constant, the soil changes from a three-peak to a two-peak structure as the void ratio increases. The total area and secondary peak area of the T2 spectrum increase, while the starting T2 value of the main peak shifts to the right and the area decreases. Meanwhile, the starting T2 value of the secondary peak shifts to the right and the area increases. When the void ratio remains constant, the starting T2 value of the main peak gradually shifts to the left and the area decreases as the moisture content increases. However, the starting T2 value of the secondary peak shifts to the right and the area decreases or first decreases and then increases. The disintegration rate does not exhibit a significant relationship with either pore volume or macropore volume. The combined water saturation shows a bilinear relationship with both the moisture content and void ratio, where it increases as the initial moisture content increases, but decreases as the void ratio increases, with a correlation coefficient of 0.9929. The disintegration rate has an exponential relationship with the combined water saturation, and it decreases as the combined water saturation increases, with a correlation coefficient of 0.9934.
The methylene-bridged triphenylamine 2 has been oxidized to planar radical cation 2 •+ by B(C6F5)3 or Ag+. Further reaction of 2 •+ Al(ORF)4− and 2 with trace amounts of silver salt resulted in ...dication 3 2+, providing a rare example of structurally characterized bis(triarylamine) “bipolarons”. 3 2+ can be directly prepared by the reaction of 3 with 2 equiv of Ag+. X-ray structural analysis together with theoretical calculation shows that 3 2+ has singlet diradical character and is analogous to Chichibabin’s hydrocarbons.
Objective
α2‑agonists and opioids have been used as intrathecal adjuvants to local anesthetics for several years, but the effect of intrathecal dexmedetomidine (Dex) or sufentanil combined with ...epidural ropivacaine in labor analgesia is not fully understood.
Methods
A total of 108 parturient women receiving combined spinal-epidural labor analgesia were randomly divided into three groups. Group C received l mL saline (0.9%) intrathecally, Group D received 5 µg Dex intrathecally, and Group S received 5 µg sufentanil intrathecally. All parturient women then received 0.1% epidural ropivacaine and 0.2 µg/mL sufentanil for patient-controlled epidural analgesia with standard settings. The visual analog scale score, onset time, duration of intrathecal injection, local anesthetic requirements, and side effects were recorded.
Results
The labor analgesia effects in Groups D and S were better than those in Group C. Groups D and S displayed significantly shorter onset times, longer durations of intrathecal injection, and reduced local anesthetic requirements compared with Group C. The incidence of shivering and pruritus in Group D was lower than that in Group S.
Conclusion
Intrathecal administration of 5 µg Dex could improve epidural labor analgesia effects.
This randomized controlled clinical trial was registered with the Chinese Clinical Registry Center (ChiCTR-1800014943, http://www.chictr.org.cn/).
Due to the limitations of traditional microbiological detection techniques in evaluating complicated infections in ICU patients, it is necessary to explore novel and effective methods to improve the ...clinical detection of ICU patients’ infections.
This study aimed to evaluate the efficiency and specificity of mNGS in screening pathogens in the blood, deep phlegm, urine, and other sample types of ICU patients exploring an effective method for infection detection.
A total of 56 ICU patients with 131 samples were included in this study. The sample types included blood, deep phlegm, urine, drainage, anal swabs, and other types. Samples were analyzed by both conventional detection method and mNGS tests. The diagnosis efficiency and consistency of the two methods were compared. The distribution of the identified pathogens was analyzed. Moreover, the clinical features of patients with mNGS-positive or mNGS-negative results were compared.
The positive rate of mNGS was 81.7% (107/131) including 3.1% (4/131) weakly positive, while the positive rate of traditional detection was only 30.5%, including 29 strong positive results and 11 weak positive results. Additionally, there were 41 patients chose to adjust anti-infection strategies according to the results of mNGS, which significantly saved treatment costs. The mNGS-positive patients showed a shorter ICU hospitalization and higher intention to adjust anti-infection strategies than the mNGS-negative patients.
mNGS is of great potential for the pathogen detection of ICU patients, and has a higher detection rate than traditional detection methods. Further clinical application investigations can be carried out to expand the application of mNGS.
•mNGS showed higher detection efficacy for ICU patients than traditional detection methods.•The clinical application of mNGS can be expanded.•mNGS provided reference for the anti-infection therapy of ICU patients.
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