Abstract
Available therapies for chronic hepatitis B virus (HBV) infection are not satisfying, and interleukin‐21 (IL‐21) and checkpoint inhibitors are potential therapeutic options. However, the ...mechanism underlying IL‐21 and checkpoint inhibitors in treating chronic HBV infection is unclear. To explore whether IL‐21 and checkpoint inhibitors promote HBV clearance by modulating the function of natural killer (NK) cells, we measured the phenotypes and functions of NK cells in chronic HBV‐infected patients and healthy controls on mRNA and protein levels. We found that chronic HBV infection disturbed the transcriptome of NK cells, including decreased expression of
KLRK1, TIGIT, GZMA, PRF1
, and increased expression of
CD69
. We also observed altered phenotypes and functions of NK cells in chronic HBV‐infected patients, characterized by decreased NKG2D expression, increased TIGIT expression and impaired interferon‐gamma (IFN‐γ), tumor necrosis factor‐alpha (TNF‐α) production. Furthermore, these alterations cannot be restored by telbivudine treatment but can be partially restored by IL‐21 and anti‐TIGIT stimulation. IL‐21 upregulated the expression of activating receptor CD16, CD69, and NKG2D on NK cells, enhanced IFN‐γ production, cytolysis, and proliferation of NK cells, while anti‐TIGIT promoted IFN‐γ production in CD56
dim
subset exclusively in chronic HBV infected patients. Additionally, IL‐21 was indispensable for anti‐TIGIT in HBsAg clearance in mice bearing HBV. It enhanced IFN‐γ production in splenic NK cells rather than intrahepatic NK cells, indicating a brand‐new mechanism of IL‐21 in HBV clearance when combined with anti‐TIGIT. Overall, our findings contribute to the design of immunotherapy through enhancing the antiviral efficacy of NK cells in chronic HBV infection.
Judicious interfacial-, crystalline- and structural-engineering of plasmonic metal-semiconductor nanocomposites is key to harnessing their plasmonic functions for enhancing solar energy conversion. ...In this work, metal@semiconductor core-shell nanocrystals with atomically organized interface, quasi-monocrystalline shell and diverse controllable structures/morphologies, which are hardly tractable by conventional synthetic strategies, are accessed by developing an aqueous cation exchange method. The combined studies including Mid-IR femtosecond transient absorption spectroscopy measurements show that the superior metal-semiconductor interface attained by the presented method can greatly promote the extraction of hot electrons from metal to semiconductor (the quantum yield of hot electron injection was estimated at ~ 48%) in comparison with the nanostructures bearing unoptimized interfaces. Thus produced metal@semiconductor nanocrystals give 2–3 orders of magnitude enhancement in photocatalytic H2 evolution activity relative to their counterparts accessed by conventional methods.
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•Aqueous cation exchange-facilitated nonepitaxial growth of Au@CdS core-shell nanocrystals (NCs) is developed.•The NCs feature atomically clean interface, quasi-monocrystalline shell and independently tailored structures at nanoscale.•The quantum yield of hot electron injection from Au plasmon to CdS conduction band in these NCs is estimated around ~ 48%.•2-3 orders of magnitude increase in photocatalytic H2 evolution is achieved than the Au@CdS NCs accessed by other methods.
This study aimed to reveal the anti-fibrotic effects of Botrychium ternatum (Thunb.) Sw. (BT) against idiopathic pulmonary fibrosis (IPF) and to preliminarily analyze its potential mechanism on ...bleomycin-induced IPF rats.
The inhibition of fibrosis progression in vivo was assessed by histopathology combined with biochemical indicators. In addition, the metabolic regulatory mechanism was investigated using 1H-nuclear magnetic resonance-based metabolomics combined with multivariate statistical analysis.
Firstly, biochemical analysis revealed that BT notably suppressed the expression of hydroxyproline and transforming growth factor-β1 in the pulmonary tissue. Secondly, Masson's trichrome staining and hematoxylin and eosin showed that BT substantially improved the structure of the damaged lung and significantly inhibited the proliferation of collagen fibers and the deposition of extracellular matrix. Finally, serum metabolomic analysis suggested that BT may exert anti-fibrotic effects by synergistically regulating tyrosine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and synthesis and degradation of ketone bodies.
Our study not only clarifies the potential anti-fibrotic mechanism of BT against IPF at the metabolic level but also provides a theoretical basis for developing BT as an effective anti-fibrotic agent.
Er3+ ions and ZnO QDs codoped amorphous silica thin films are prepared by the modified sol-gel spin-coating technique. By introducing the ZnO QDs as sensitizers, the PL emission intensity of Er3+ ...ions is enhanced by more than two orders of magnitude. With the increasing annealing temperature, the lengthening PL emission lifetime indicates the gradual passivation of the non-radiative trap states. The thermal quenching behavior of PL emission intensity is analyzed by the temperature-dependent PL spectra. With the increasing annealing temperature, the decrease of activation energy suggests the narrowing of energy level difference between the excited state of Er3+ ions and the defect state of ZnO QDs. The gradually improved phonon-assisted energy transfer efficiency results in the greatly enhanced PL efficiency of Er3+ ions. These results will be a starting point for further research on the sensitization mechanisms in the rare earth ions and wide-bandgap QDs codoped amorphous silica.
•The ZnO QDs with the uniform size were formed inside amorphous silica film by the restricted crystallization process.•The diffusion of partial Er3+ ions from silica into ZnO QDs contributes to the reduced energy transfer distance.•Boosting energy transfer efficiency contributes to the greatly enhanced characteristic emission of Er3+ ions.
Abstract
This paper demonstrates the ability of a CuCo
2
S
4
–reduced graphene oxide (rGO) composite to perform robust electrochemical performances applying to supercapacitors (SCs) and lithium ion ...batteries (LIBs). The first‐principle calculation based on density functional theory is conducted to study the electronic property of CuCo
2
O
4
and CuCo
2
S
4
and provide a theoretical basis for this work. Then, the 3D spinel‐structured CuCo
2
O
4
and CuCo
2
S
4
microflowers are synthesized and compared as electrodes for both SCs and LIBs. The CuCo
2
S
4
microflowers can provide a larger specific surface area, which enlarges the contact area between the electrode material and the electrolyte and contributes to high‐efficiency electrochemical reactions. The reduced graphene oxides are coated on the CuCo
2
S
4
microflowers, therefore effectively increasing the conductivity, and further absorbing the stress produced in the reaction process. As an electrode of a symmetric supercapacitor, the optimized CuCo
2
S
4
–rGO composite exhibits an energy density of 16.07 Wh kg
−1
and a maximum power density of 3600 W kg
−1
. Moreover, the CuCo
2
S
4
–rGO composite can also be used as an anode for lithium ion batteries, exhibiting a reversible capacity of 1050 mAh g
−1
after 140 cycles at the current density of 200 mA g
−1
. The galvanostatic intermittence titration techniques also reveal superior Li‐ion diffusion behavior of the CuCo
2
S
4
–rGO composite during redox reactions.
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•Coupled effect of CO2 attack and tensile stress on well cement under CCS condition is studied.•A higher tensile stress will facilitate the generation and propagation of ...micro-cracks.•The tensile stress can accelerate the failure of well cement.•The carbonation rate of cement was faster in CO2-saturated brine.
In carbon capture and storage (CCS) wells, the well cement is attacked by CO2-rich fluids, coupled with tensile stress. In this study, well cement samples were designed to be exposed to humid CO2 gas and CO2 saturated brine and simultaneously subjected to external tensile stresses with load levels of 25%, 50%, and 75% of the initial tensile strength. The experimental results showed that a higher external tensile stress (50% and 75%) facilitated the generation and propagation of micro-cracks in the tension zone of loaded samples. Hence, the aggressive CO2-rich medium found direct paths to penetrate further into the core, significantly accelerating the rate of carbonation and failure of the well cement. As a result of the faster ion exchange and transfer, the carbonation rate was faster and the onset of failure in samples immersed in CO2-saturated brine occurred earlier than in the supercritical CO2 scenario. Findings from this study provide new, important information for understanding the integrity of well cement sheath under actual CCS well conditions, thereby promoting superior cement system design and safer operation.
Glytrexate, developed by our team, as a novel multitarget folate antagonist, has inhibitory effects on a variety of cancer cell types, especially KB tumor cells (IC
50
0.078 nM), and thus has ...antitumor drug development prospects. However, its pharmacokinetics and plasma protein binding properties remain unknown. In this study a selective and sensitive liquid chromatography-tandem mass spectrometry (LC‒MS/MS) method was developed and verified to facilitate biological analysis. The bioanalysis method was applied to evaluate the stability, plasma protein binding, and pharmacokinetics of glytrexate. Glytrexate is more stable in human plasma than in rat plasma and in human liver microsomes. The binding of glytrexate to human plasma proteins was higher than that to rat plasma proteins, both of which were less than 30%, suggesting that glytrexate may be at a higher concentration at the pharmacologic target receptor(s) in tissues. Pharmacokinetic characteristics were determined by noncompartmental analysis after administration of single oral (12.5, 25 and 50 mg/kg) and intravenous (2 mg/kg) doses in rats. According to the rat oral pharmacokinetic characteristics, glytrexate had linear dynamics in a dose range of 12.5–50 mg/kg and a poor oral bioavailability of 0.57–1.15%. The investigation revealed that the intravenous half-life, AUC, and C
max
of glytrexate were higher than those of pemetrexed. Pemetrexed is generally produced as an injection preparation. This provides ideas for the development of glytrexate formulations. Therefore, glytrexate injection has clinical application prospects compared to oral administration. This study provides a basis for further investigations into the pharmacological effects and clinical uses of glytrexate.
Iatrogenic tracheoesophageal fistula (TEF) is a rare but life-threatening condition. No consensus has been reached regarding TEF treatment, though, stenting has been gaining popularity for less ...invasiveness than thoracic surgery. The airway management during stent placement for TEF could be challenging.
We report a patient who suffered from TEF after cardiac surgery with symptoms of persistent coughing and aspiration. He who was admitted for stent placement but ended up in failure and referred to our institution for further treatment. We successfully took advantage of the supraglottic jet oxygenation and ventilation (SJOV) during stent placement.
This is the first case so far describing SJOV in complicated stenting treatment. This demonstrates that SJOV can be applied for stent placement in TEF patients with restricted airways.
Allogeneic bone marrow mesenchymal stem cell (allo-BMSC)-based tissue-engineered bone (TEB) has great potential for bone defect repair. However, the immunogenicities and biological roles of ...allo-BMSCs are still controversial. In this study, we established an animal model of critical-sized mandibular defect in beagle dogs and compared the repairing effects of allo-BMSC-based TEB with autogenic BMSC (auto-BMSC)-based TEB without the administration of immunosuppressants. During the first 2 weeks postimplantation, a transient immune response in the allo-BMSC group was detected with an increase in proinflammation cytokines TNF-α, IFN-γ, and IL-2, a declination of anti-inflammation cytokine IL-10, and an increase in percentages of CD4+ and CD8+ T-cell subsets in peripheral blood. Nevertheless, there was no significant difference in bone union achievement, bone mineral density, and biomechanical properties between the two groups at 12 and 24 weeks postimplantation. Further subcutaneous implantation of allo-BMSCs/scaffold also exhibited the similar transient immune responses in the first 2 weeks postimplantation but followed by a decreased bone formation at 4 and 8 weeks postimplantation. These findings indicate that allo-BMSCs can induce a transient immunoreaction, which may temporally delay the osteogenesis of allo-BMSC/scaffold complex in early stage of in vivo implantation, whereas the long-term engineered bone formation was not affected.
China's older population is facing serious health challenges, including malnutrition and multiple chronic conditions. There is a critical need for tailored food recommendation systems. Knowledge ...graph-based food recommendations offer considerable promise in delivering personalized nutritional support. However, the integration of disease-based nutritional principles and preference-related requirements needs to be optimized in current recommendation processes.
This study aims to develop a knowledge graph-based personalized meal recommendation system for community-dwelling older adults and to conduct preliminary effectiveness testing.
We developed ElCombo, a personalized meal recommendation system driven by user profiles and food knowledge graphs. User profiles were established from a survey of 96 community-dwelling older adults. Food knowledge graphs were supported by data from websites of Chinese cuisine recipes and eating history, consisting of 5 entity classes: dishes, ingredients, category of ingredients, nutrients, and diseases, along with their attributes and interrelations. A personalized meal recommendation algorithm was then developed to synthesize this information to generate packaged meals as outputs, considering disease-related nutritional constraints and personal dietary preferences. Furthermore, a validation study using a real-world data set collected from 96 community-dwelling older adults was conducted to assess ElCombo's effectiveness in modifying their dietary habits over a 1-month intervention, using simulated data for impact analysis.
Our recommendation system, ElCombo, was evaluated by comparing the dietary diversity and diet quality of its recommended meals with those of the autonomous choices of 96 eligible community-dwelling older adults. Participants were grouped based on whether they had a recorded eating history, with 34 (35%) having and 62 (65%) lacking such data. Simulation experiments based on retrospective data over a 30-day evaluation revealed that ElCombo's meal recommendations consistently had significantly higher diet quality and dietary diversity compared to the older adults' own selections (P<.001). In addition, case studies of 2 older adults, 1 with and 1 without prior eating records, showcased ElCombo's ability to fulfill complex nutritional requirements associated with multiple morbidities, personalized to each individual's health profile and dietary requirements.
ElCombo has shown enhanced potential for improving dietary quality and diversity among community-dwelling older adults in simulation tests. The evaluation metrics suggest that the food choices supported by the personalized meal recommendation system surpass autonomous selections. Future research will focus on validating and refining ElCombo's performance in real-world settings, emphasizing the robust management of complex health data. The system's scalability and adaptability pinpoint its potential for making a meaningful impact on the nutritional health of older adults.
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