Although the differentiation of CD4
T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell ...(DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4
T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4
T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4
T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1-p38MAPK signalling pathway in directing Th17 differentiation.
ObjectivesLittle study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a ...China birth cohort while adjusting by multiple factors.DesignCohort study.SettingChina birth cohort study conducted from 2017 to 2021.ParticipantsThe study finally included 114 672 singleton pregnancies in the 6–14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases).Primary and secondary outcome measuresAssociation between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively.ResultsThe first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation.Conclusions and relevanceAlthough the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.
Clinical studies have continually referred to the involvement of drug carrier having dramatic negative influences on the biocompatibility, biodegradability, and loading efficacy of hydrogel. To ...overcome this deficiency, researchers have proposed to directly self-assemble natural herbal small molecules into a hydrogel without any structural modification. However, it is still a formidable challenge due to the high requirements on the structure of natural molecules, leading to a rarity of this type of hydrogel. Mangiferin (MF) is a natural polyphenol of C-glucoside xanthone with various positive health benefits, including the treatment of diabetic wounds, but its poor hydrosolubility and low bioavailability significantly restrict the clinical application. Inspired by these, with heating/cooling treatment, a carrier-free hydrogel (MF-gel) is developed by assembling the natural herbal molecule mangiferin, which is mainly governed through hydrogen bonds and intermolecular π–π stacking interactions. The as-prepared hydrogel has injectable and self-healing properties and shows excellent biocompatibility, continuous release ability, and reversible stimuli-responsive performances. All of the superiorities enable the MF-based hydrogel to serve as a potential wound dressing for treating diabetic wounds, which was further confirmed by both the vitro and vivo studies. In vitro, the MF-gel could promote the migration of healing-related cells from peripheral as well as the angiogenesis and displays the capacity of mediating inflammation response by scavenging the intracellular ROS. In vivo, the MF-gel accelerates wound contraction and healing via inflammatory adjustment, collagen deposition, and angiogenesis. This study provides a facile and effective method for diabetic wound management and emphasizes the direct self-assembly hydrogel from natural herbal small molecule.
Abstract The destruction of alveolar bone is a crucial manifestation of severe chronic periodontitis, which stem cell-based bioengineered therapies are expected to cure. Therefore, a cost-effective, ...reproducible, quantifiability and easier to administrate animal model that mimics human periodontitis is of great importance for further endeavor. In this study, we created periodontitis rat models in silk ligation group, bone defect group and bone defect/silk ligation group, respectively. Obvious periodontal inflammation but slight alveolar bone resorption was observed in the ligation group, while surgical trauma was not robust enough to continually worsen the constructed bone defect area in the bone defect group. In the bone defect/ligature group, significant and stable periodontal inflammation was the most enduring with similar evolving pathological patterns of human periodontitis. It also exhibited enhanced clinical similarity and confirmed its superiority in quantitativeness. The present rat model is the first study to reproduce a pathological process similar to human periodontitis with reliable stability and repeatability, manifesting a priority to previous methods. Day 9-12 is the best time for reproducing severe periodontitis syndromes with vertical bone resorption in this model.
•Citric acid, an organic acid, was used in direct hydrolysis extraction method.•Both free and conjugated PSs were recovered from hickory husk by the new method.•Conductivity could be a good index to ...indicate the extraction rate of PSs.•Four PSs and one triterpenoid were firstly identified from hickory husk.•The new method was more effective than traditional solvent extraction.
This study investigated the direct citric acid hydrolysis extraction method to optimize phytosterols extraction from hickory husk. Single factor experiments followed by a three-level three-factor Box-Behnken experiments were performed. The optimal extraction parameters were determined as: pH of 2.0, liquid-to-solid ratio of 17.12: 1 mL/g, and temperature of 55.81 °C. Practical experiments were carried out in triplicate, and subsequently yielded phytosterols of 912.452 ± 17.452 μg/g DW, in good consistence with the predicted extraction yield of 902.874 μg/g DW. The conductivity of the extract was also found to play effective role under direct citric acid hydrolysis and recorded 36.30 ± 1.08 μs/cm at optimum extraction condition. β-Sitosterol stigmasterol, campsterol, ergosterol and lupeol were detected as main PSs and triterpenoids in hickory husk using UPLC-Triple-TOF/MS. Finally, the comparison between direct hydrolysis extraction and traditional solvent extraction showed that this new method was more effective and eco-friendlier to extract both free and conjugated phytosterols.
•Co-expressing Rad52 enhances CRISPR/Cas9-mediated HDR on surrogate reporters.•Rad52-Cas9 fusion enhances HDR at the surrogate reporter level.•HDR-based genome editing in human HEK293T cells can be ...enhanced by Rad52 co-expression and Rad52-Cas9 fusion.•Rad52-Cas9 fusion enhances the HDR-based modification of the IGF2 gene in porcine PK15 cells.
Precise genome editing with desired point mutations can be generated by CRISPR/Cas9-mediated homology-directed repair (HDR) and is of great significance for gene function study, gene therapy and animal breeding. However, HDR efficiency is inherently low and improvements are necessitated. Herein, we determined that the HDR efficiency could be enhanced by expressing Rad52, a gene that is involved in the homologous recombination process. Both the Rad52 co-expression and Rad52-Cas9 fusion strategies yielded approximately 3-fold increase in HDR during the surrogate reporter assays in human HEK293T cells, as well as in the genome editing assays. Moreover, the enhancement effects of the Rad52-Cas9 fusion on HDR mediated by different (plasmid, PCR and ssDNA) donor templates were confirmed. We found that the HDR efficiency could be significantly improved to about 40% by the combined usage of Rad52 and Scr7. In addition, we also applied the fusion strategy for modifying the IGF2 gene of porcine PK15 cells, which further demonstrated a 2.2-fold increase in HDR frequency. In conclusion, our data suggests that Rad52-Cas9 fusion is a good option for enhancing CRISPR/Cas9-mediated HDR, which may be of use in future studies involving precise genome editing.
Under the guidance of global natural product social molecular networking, three new indolocarbazoles named streptocarbazoles F–H (
1
-
3
), along with staurosporine (
4
) were isolated from the ...marine-derived
Streptomyces
sp. OUCMDZ-5380. Structures of streptocarbazoles F–H were, respectively, determined as
N
-demethyl-
N
-hexanoylstaurosporine (
1
),
N
-demethyl-
N
-(2-methyl-3-methoxypyridin-4-yl) staurosporine staurosporine (
2
), and 4-(
N
-demethylstaurosporine-
N
-yl)-1,2-dimethyl-3-methoxypyridinium (
3
) by spectroscopic analysis and electronic circular dichroism comparison with staurosporine. Compared with staurosporine (
4
), streptocarbazoles F–H (
1
-
3
) showed a selective antiproliferation of the acute myeloid leukemia cell line MV4-11 with the IC
50
values of 0.81, 0.55, and 1.88 μM, respectively.
Efficient electron transmission is an important step in the process of CO2 photoreduction. In this paper, a multi-interface-contacted In2S3/Au/reduced graphene oxide (rGO) photocatalyst with the ...fluorescence resonance energy transfer (FRET) mechanism has been successfully prepared by the solvothermal, self-assembly, and hydrothermal reduction processes. Photocatalytic CO2 reduction experiments showed that the In2S3/Au/rGO (IAr-3) composite exhibited excellent photoreduction performance and photocatalytic stability. The yields of CO and CH4 obtained after the photoreduction process with IAr-3 as the catalyst were around 4 and 6 times higher than those of pure In2S3, respectively. Photoelectrochemical analysis showed that the multi-interface contact and FRET mechanism greatly improved the generation, transmission, and separation efficiency of carriers photogenerated within the photocatalyst. In situ FTIR test was applied to analyze the photocatalytic CO2 reduction process. 13C isotope tracer test confirmed that the carbon source of CO and CH4 was the CO2 molecules in the photoreduction process rather than the decomposition of catalyst or TEOA. A potential enhanced photocatalytic mechanism has been discussed in total.
This paper analyzes the security of an image encryption algorithm based on a two-dimensional hyperchaotic map. This encryption algorithm generated chaotic sequences through a combination of two ...one-dimensional chaotic maps and used them as the permutation and diffusion key. Then, the image was encrypted by using the structure of row-column permutation, forward-diffusion, and backward-diffusion. The proposer claimed that the above algorithm was secure. However, it was found through cryptanalysis that the algorithm cannot withstand the chosen plaintext attack. Although the forward-diffusion and backward-diffusion of the original algorithm use two different diffusion keys and there is a ciphertext feedback mechanism, the analysis of the diffusion by iterative optimization showed that it can be equivalent to global diffusion. In addition, the generation of chaotic sequences in the encryption process is independent of the plaintext image, so the equivalent diffusion and permutation key stream can be obtained by adjusting the individual pixel values of the chosen plaintexts. Aiming at the security loopholes in the encryption algorithm, the theoretical and experimental results are presented to support the efficiency of the proposed attack and suggestions for improvement are given. Finally, compared with the performance analysis of the existing cracking algorithm, our cryptanalysis greatly improved the cracking efficiency without increasing the complexity of the data.
A facile approach using SDT method under uniform temperature have been applied to synthesize high yield, high purity and high-quality BP crystals. In addition, uniform and controllable doping of ...various elements are also achieved with the same method.
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Black phosphorus (BP) has recently attracted significant interest due to its unique electronic and optical properties. Doping is an effective strategy to tune a material’s electronic properties, however, the direct and controllable growth of BP with a high yield and its doping remain a great challenge. Here we report an efficient short-distance transport (SDT) growth approach and achieve the controlled growth of high quality BP with the highest yield so far, where 98% of the red phosphorus is converted to BP. The doping of BP by As, Sb, Bi, Se and Te are also achieved by this SDT growth approach. Spectroscopic results show that doping systematically changes BP’s electronic structures including band gap, work function, and energy band position. As a result, we have found that the air-stability of doped BP samples (Sb and Te-doped BP) improves compared with pristine BP, due to the downshift of the conduction band minimum with doping. This work reports a new method to grow BP and doped BP with tunable electronic structures and improved stability, and should extend the uses of these class of materials in various areas.
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