Abstract
Existing therapeutics for autoimmune diseases remain problematic due to low efficacy, severe side effects, and difficulties to reach target tissues. Herein, we design multifunctional fusion ...nanovesicles that can target lesions for the treatment of autoimmune skin diseases. The grapefruit‐derived exosome‐like nanovesicles (GEVs) with anti‐inflammatory and antioxidant effects are first encapsulated with CX5461, an immunosuppressant with anti‐proliferative properties to form GEV@CX5461. In order to enhance therapeutic efficiency and safety, GEV@CX5461 are then fused with CCR6+ nanovesicles derived from membranes of engineered gingiva‐derived mesenchymal stem cells (GMSCs). The resulting FV@CX5461 not only maintain the bioactivity of GEVs, CX5461, and GMSC membranes but also home to inflamed tissues rich in chemokine CCL20 through the chemotaxis function of CCR6 on FVs. Moreover, FV@CX5461 reduce the secretion of inflammatory factors, calm down Th17 cell activation, and induce Treg cell infiltration. Finally, impressive therapeutic efficiency in both psoriasis and atopic dermatitis disease models is demonstrated using FV@CX5461 to reshape the unbalanced immune microenvironment. A nanotherapeutic drug delivery strategy is developed using fusion nanovesicles derived from plant and animal cells with high clinical potential.
Background: Accurate neonatal pain assessment (NPA) is the key to neonatal pain management, yet it is a challenging task for medical staff. This study aimed to analyze the clinical practicability of ...the artificial intelligence based NPA (AI-NPA) tool for real-world blood sampling. Method: We performed a prospective study to analyze the consistency of the NPA results given by a self-developed automated NPA system and nurses’ on-site NPAs (OS-NPAs) for 232 newborns during blood sampling in neonatal wards, where the neonatal infant pain scale (NIPS) was used for evaluation. Spearman correlation analysis and the degree of agreement of the pain score and pain grade derived by the NIPS were applied for statistical analysis. Results: Taking the OS-NPA results as the gold standard, the accuracies of the NIPS pain score and pain grade given by the automated NPA system were 88.79% and 95.25%, with kappa values of 0.92 and 0.90 (p < 0.001), respectively. Conclusion: The results of the automated NPA system for real-world neonatal blood sampling are highly consistent with the results of the OS-NPA. Considering the great advantages of automated NPA systems in repeatability, efficiency, and cost, it is worth popularizing the AI technique in NPA for precise and efficient neonatal pain management.
Abstract
A novel nano‐ternary spinel oxides of Zn−Ni‐Co−O are synthesized via the coprecipitation method and used for detection towards Cu(II). The Zn doping effect on morphologies and ...microstructures of Zn
x
Ni
1‐x
Co
2
O
4
(x=0, 0.2, 0.4, 0.6, 0.8, 1.0) is systematically characterized and investigated. At the x of 0.4, the prepared Zn
0.4
Ni
0.6
Co
2
O
4
modified electrode nanomaterials can realize electrochemical ultratrace detection of Cu(II), which shows the lowest detection limit of 1.96 nM with a linear range of 0.1 μM∼1.0 μM and the highest sensitivity of 15.2 μA/μM. Meanwhile, Zn
0.4
Ni
0.6
Co
2
O
4
modified electrodes exhibit excellent repeatability (relative standard deviation (RSD) of 0.34 %), reproducibility (RSD of 0.3 %), stability (RSD of 3.0 %) as well as anti‐interference analysis, which has been successfully applied in the actual water environment. These results indicate that Zn
x
Ni
1‐x
Co
2
O
4
nanoparticles as a promising modified electrode materials for the electrochemical detection Cu(II).
This study aimed to investigate the effects of unilateral labyrinthectomy (UL) on monoamine neurotransmitters in the medial vestibular nucleus (MVN) of rats.
Adult Sprague-Dawley rats were utilized ...for the vestibular impaired animal model through UL. The success of the model establishment and the recovery process were evaluated using vestibular behavioral tests, including spontaneous nystagmus, postural asymmetry, and balance beam test. Additionally, the expression levels of c-Fos protein in the MVN were assessed by immunofluorescence. Furthermore, changes in the expression levels of monoamine neurotransmitters, including 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), and histamine in the MVN, were analyzed using high-performance liquid chromatography (HPLC) at different time points after UL (4 h, 8 h, 1 day, 2 days, 4 days, and 7 days).
Compared to the sham control group, the UL group exhibited the most pronounced vestibular impairment symptoms at 4 h post-UL, which significantly decreased at 4 days and almost fully recovered by 7 days. Immunofluorescence results showed a notable upregulation of c-Fos expression in the MVN subsequent to the UL-4 h, serving as a reliable indicator of heightened neuronal activity. In comparison with the sham group, HPLC analysis showed that the levels of 5-HT and NE in the ipsilesional MVN of the UL group were significantly elevated within 4 days after UL, and peaked on 1 day and 2 days, respectively. DA showed an increasing trend at different time points up to 7 days post-UL, while histamine levels significantly increased only at 1 day post-UL.
UL-induced dynamic changes in monoamine neurotransmitters during the early compensation period in the rat MVN may be associated with the regulation of the central vestibular compensation mechanism by the MVN.
In order to reduce the failure accidents of conventional packers, a kind of sealing structure of retrievable packers is designed, which can provide reference for optimizing the sealing performance ...and pressure capacity of packers. And theoretical calculation and experimental research on their sealing performance and pressure capacity are carried out through the finite element analysis on the contact with large deformation based on Abaqus and experimental study. The results show that the upper packer is subjected to greater stress and mainly plays a sealing role in the sealing process. In order to improve the sealing performance of the packer, the height of the upper and lower packer should be preferentially selected about 60 mm, the height of the middle rubber cylinders should be about 50 mm, and the thickness of the packer should be about 21 mm. The newly designed rubber cylinders can meet 150°C. The newly designed rubber cylinders can meet the sealing function and pressure bearing function under the condition of 10,000 Psi and 150°C. The newly designed rubber cylinder can satisfy the function of sealing and pressure-bearing under 140°C and 10,000 Psi. The whole experiment shows that the capacity of bearing pressure and sealing is stable, which can better meet the requirements of field use.
Glaucoma is an irreversible and blinding neurodegenerative disease that is characterized by progressive loss of retinal ganglion cells. The current animal models of glaucoma fail to provide a chronic ...elevated intraocular pressure and cannot maintain the optical media clarity for a long time, which brings some difficulties to the study of glaucoma. Here, we developed a new chronic ocular hypertension model of mice induced by cross-linking hydrogel intracameral injection.
C57BL/6J mice aged 6-8 weeks were randomly divided into the control group and the operation group. The mice of the operation group were injected with cross-linking hydrogel to induce ocular hypertension. Intraocular pressure was measured preoperatively, 3 days after surgery, and weekly until the end of the study. Flash visual evoked potential (F-VEP) was used to observe optic nerve function at different times (preoperatively and 2, 4, and 6 weeks) after chronic ocular hypertension (COH). Retinal TNF-α, IL-1β, and IL-17A protein expression were measured by western blotting in the control group and in mice at 2, 4, and 6 weeks after COH. Microglial cell activation was evaluated by immunofluorescence staining and western blotting. Apoptosis and loss of retinal ganglion cells after 2, 4, and 6 weeks of intracameral injection of cross-linking hydrogel were observed by the TUNEL assay and Brn3a protein labeling. The loss of optic nerve axons in COH mice was evaluated by neurofilament heavy polypeptide protein labeling.
Intracameral injection of the cross-linking hydrogel induces increased intraocular pressure (IOP) to a mean value of 19.3 ± 4.1 mmHg, which was sustained for at least 8 weeks. A significant difference in IOP was noted between COH mice and sham-operation mice (
< 0.0001). The success rate was 75%. The average amplitude of F-VEP in mice with COH was reduced (
= 0.0149, 0.0012, and 0.0009 at 2, 4, and 6 weeks after COH vs. the control group, respectively), and the average latent period in mice with COH was longer (
= 0.0290, <0.0001, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively) compared with that in the control group. TNF-α, IL-1β, IL-17A, Iba-1, and CD68 protein expression increased in COH mice. During the processing of COH, the number of microglial cells increased along with cellular morphological changes of rounder bodies and thicker processes compared with the control group. Apoptosis of retinal ganglion cells (RGCs) was clearly observed in mice at 2, 4, and 6 weeks after COH (
= 0.0061, 0.0012, <0.0001, and 0.0371 at 2, 4, and 6 weeks after COH vs. the control group, respectively). The RGC density decreased significantly in the COH mice compared with the control group (
= 0.0042, 0.0036, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively). There was a significant loss of optic nerve axons in mice after intracameral injection of cross-linking hydrogel (
= 0.0095, 0.0002, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively).
A single intracameral injection of cross-linking hydrogel can effectively induce chronic ocular hypertension in mice, which causes progressive loss of retinal ganglion cells, increased expression levels of inflammatory cytokines and microglial cell activation, and deterioration of optic nerve function.
•The exotic Sonneratia apetala were used for mangrove afforestation in China.•Three native species were planted at the understory of different aged plantations.•Species performance was related to ...their occurrence in natural mangroves.•Shading had the least impact on Bruguiera but strongest impact on Sonneratia.•Introducing native mangroves to enhance Sonneratia monocultures is possible.
In China, large-scale mangrove afforestation has been performed over the last two decades using introduced species. The large areas occupied by the introduced Sonneratia apetala have generated some concerns of biological invasion. The aim of this study was to investigate the feasibility of planting native mangrove species under the canopy of S. apetala plantations and the best species to acclimate under low light conditions in the understory. A 360-day experiment was conducted with four dominant mangrove species in southern China (S. apetala, and three native species Kandelia obovata, Aegiceras corniculatum, and Bruguiera gymnorhiza) in four habitats (i.e., bare mudflat, two-year plantation, six-year plantation, and eight-year plantation) with different light irradiance conditions. Results showed that in terms of propagule germination and seedling survival, the low light irradiance condition impeded the early growth of S. apetala, but had less impact on B. gymnorhiza. With decrease in light irradiance, increments in stem height, basal area, and leaf area, and relative growth rate decreased the most for S. apetala and the least for B. gymnorhiza among the four species. In terms of the physiological response parameters of net photosynthesis rate, stomatal conductance, and transpiration rate, B. gymnorhiza exhibited more adaptability than S. apetala under dense canopies. With respect to the response of early growth of seedlings over 12months, B. gymnorhiza was the most adaptable species to the understory low light condition, while S. apetala was the most adversely affected species. The information from this study should be useful for the introduction of native species into plantations of introduced mangrove species to improve their conservation value.
A novel solid-solution garnet Yb3+ doped Y3Al5O12Mn3Al2(SiO4)3 (Yb:YAG-MnASG) has been designed and grown for the first time. The polycrystalline materials, crystal growth, crystal structures, ...absorption and emission spectra, energy level schema, fluorescence lifetime and laser performance parameters were investigated in detail. Owing to the inhomogeneity in the local environment of Yb3+ caused by the cationic substitutions of Mn2+ for Y3+, Si4+ for Al3+ and high crystal-field strengths caused by distorted host sites, both of the absorption and emission spectral bandwidth of Yb:YAG-MnASG crystal are broadened compared with Yb:YAG. The maximal full width at half maximum (FWHM) of absorption spectra around 940 nm and emission spectra around 1030 nm for Yb:YAG-MnASG crystal are almost 1.2 and 2.5 times larger than those of Yb:YAG crystal, respectively. The results reveal that the novel solid-solution garnet Yb:YAG-MnASG is an excellent candidate for ultrafast pulse laser crystal.
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•A novel solid-solution garnet Yb:YAG-MnASG was grown for the first time.•The spectral bandwidth of Yb:YAG-MnASG crystal are larger than those of Yb:YAG.•Yb:YAG-MnASG is more suitable for LD pumping and generation of femtosecond lasers.
Rationale
The research area of ion clusters has helped to enrich the study of chemical bonding theory, clarify the crystal nucleation process and investigate the cluster ion–molecule reactions. The ...mass spectrometry (MS) technique, especially high‐resolution MS, is an important method for investigating ion clusters in the gas phase. As polyoxometalates (POMs) have been attracting considerable interest in biochemistry, medicine and materials science due to their excellent structural and electronic features it is important to characterize these clusters by MS.
Methods
Singly negatively charged molybdenum‐containing and tungsten‐containing ion clusters with different matrices were produced by Keggin‐type silicopolyoxometalate anions under matrix‐assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI‐FTICR MS) conditions.
Results
The matrices displayed an obvious influence on the formation of ion clusters. It was found that the molybdenum‐containing ion species (HSiO3)(MoO3)n−, (SiO2)m(MoO3)n(H2O)x −•, (OH)(MoO3)n−•, (MoO3)n‐•, and HxSiMoyOz− were the main ion series in the mass spectra. For the tungsten‐containing ion clusters, (HSiO3)(WO3)n−, (C8H5Om)(WO3)n(H2O)x−, (OH)(WO3)n−, and (WO3)n‐• were the main ion species in the mass spectra, and a series of organic–inorganic hybrid tungsten‐containing ion clusters (C8H5Om)(WO3)n(H2O)x− were generated by the interaction of DHAP and THAP matrices with tungstate anions. Furthermore, the most abundant species (magic number) in each ion series indicated that they might adopt more stable structures than other relevant clusters.
Conclusions
Keggin‐type silicopolyoxometalate anions can produce several series of singly charged molybdenum‐containing/tungsten‐containing ion clusters in negative‐ion generating mode under MALDI conditions. It is proposed that the “Lucky Survivors” hypothesis may be used to illustrate the generation of ion clusters in the gas phase during the early stages of plume expansion. In addition, clear evidence of hydrogen transfer and electron capture to POMs was found in the obtained MALDI mass spectra. These results highlight the utility of the MALDI‐FT method for obtaining novel ion clusters and also show the stability of these clusters.
Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, exhibits strong cancer plasticity. We find that ALK rearrangement is detectable in 5.1-7.5% of ...human LUAS, and transgenic expression of EML4-ALK drives lung adenocarcinoma (LUAD) formation initially and squamous transition at late stage. We identify club cells as the main cell-of-origin for squamous transition. Through recapitulating lineage transition in organoid system, we identify JAK-STAT signaling, activated by EML4-ALK phase separation, significantly promotes squamous transition. Integrative study with scRNA-seq and immunostaining identify a plastic cell subpopulation in ALK-rearranged human LUAD showing squamous biomarker expression. Moreover, those relapsed ALK-rearranged LUAD show notable upregulation of squamous biomarkers. Consistently, mouse squamous tumors or LUAD with squamous signature display certain resistance to ALK inhibitor, which can be overcome by combined JAK1/2 inhibitor treatment. This study uncovers strong plasticity of ALK-rearranged tumors in orchestrating phenotypic transition and drug resistance and proposes a potentially effective therapeutic strategy.
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