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In situ tumor vaccines (ISTVs) hold great potential in tumor immunotherapy, however, three major obstacles, including inadequate endogenous antigen uptake by dendritic cells (DCs), weak T‐cell immune responses, and stubborn immunosuppressive tumor microenvironment (TME), still need to be fully addressed. Herein, a trifecta nanovaccine (TriNV) with TME‐responsive transformable ability is developed to tri‐boost antitumor immunity. First, sufficient endogenous tumor‐associated antigens (TAAs) are liberated in situ after immunogenic cell death is induced via TriNV‐based photoimmunotherapy. In the TME, soft‐transformed TriNV improves the uptake of TAAs by DCs to enhance acquired immunity. Second, the self‐adjuvating TriNV and the TME‐responsive released Mn2+ synergistically promote DC maturation and macrophage M1 polarization by augmenting the stimulator of interferon genes activation to further amplify T‐cell immune responses. Moreover, the decomposition of MnO2 within the core of TriNV exhausts glutathione and facilitates O2 release to alleviate hypoxia in the TME, thereby overcoming the chemical obstacles of the TME to further mitigate immunosuppression. Thus, TriNV remarkably eradicates primary tumors and inhibits distant metastasis, thus demonstrating great potential as a feasible and effective ISTV nanoplatform for combating poorly immunogenic solid tumors. [ABSTRACT FROM AUTHOR]

A broken-gap heterojunction is a bright approach for designing tunneling field-effect transistors (TFETs) due to its distinct quantum tunneling mechanisms. In this study, we investigate the electronic structure and transport characteristics of a SiC/Ti2CO2 heterojunction, as well as the impacts of electric field and strain on the electronic properties via density functional theory. We determine that the interfacial atoms of the heterojunction are covalently bonded, forming a type-III heterojunction with a broken-gap. There exists band-to-band tunneling (BTBT) from the valence band (VB) of SiC to the conduction band (CB) of Ti2CO2. The creation of the heterojunction also enhances the carrier mobility arising from the large elastic modulus and the decrease of deformation potential. The current–voltage (I–V) characteristics of the device demonstrate a pronounced negative differential resistance (NDR) effect, along with a current that is about ten times greater than that of the vdW type-III heterojunction. Moreover, the tunneling window of SiC/Ti2CO2 is only slightly altered when subjected to an external electric field and vertical strain, demonstrating the remarkable stability of its type-III band alignments. Our results indicate that the SiC/Ti2CO2 heterojunction is useful to construct high-performance TFETs, and also introduces new ideas to design TFETs by using type-III covalent-bond heterojunctions. [ABSTRACT FROM AUTHOR]

Z-scheme van der Waals heterojunctions are very attractive photocatalysts attributed to their excellent reduction and oxidation abilities. In this paper, we designed InN/XS2 (X = Zr, Hf) heterojunctions and explored their electronic structure properties, photocatalytic performance, and light absorption systematically using first-principles calculations. We found that the valence-band maximum (VBM) and conduction-band minimum (CBM) of the InN/XS2 (X = Zr, Hf) heterojunctions are contributed by InN and XS2, respectively. Photo-generated carriers transferring along the Z-path can accelerate the recombination of interlayer electron–hole pairs. Therefore, the photogenerated electrons in the CBM of the InN layer can be maintained making the hydrogen evolution reaction occur continuously, while photogenerated holes in the VBM of the Ti2CO2 layer make the oxygen evolution reaction occur continuously. The band edge positions of heterojunctions can straddle the required water redox potentials, while pristine InN and XS2 (X = Zr, Hf) can only be used for photocatalytic hydrogen evolution or oxygen evolution, respectively. Furthermore, the HER barriers can be tuned by transition metal doping. With Cr doping, the hydrogen evolution reaction (HER) barriers decrease to −0.12 for InN/ZrS2 and −0.05 eV for InN/HfS2, very close to the optimal value (0 eV). In addition, the optical absorption coefficient is as high as 105 cm−1 in the visible and ultraviolet regions. Therefore, the InN/XS2 (X = Zr, Hf) heterojunctions are expected to be excellent photocatalysts for water splitting. [ABSTRACT FROM AUTHOR]

BACKGROUND: The inadequacy samples caused by the internal characteristic structure of thyroid nodules are difficult to be solved. OBJECTIVE: To evaluate the ultrasound features affecting the sample adequacy after fine-needle aspiration (FNA) of thyroid nodules with different risk stratification. METHODS: 592 thyroid nodules that underwent ultrasound-guided FNA were included in this retrospective study. The sample obtained by FNA were classified as inadequacy and adequacy according to the cytopathological results. Ultrasound features (ie., size, position, cystic predominance, composition, echo, shape, margin, and superficial annular calcification status) of the nodules were recorded and compared between the inadequacy sample group and adequacy sample group. RESULTS: Multiple logistic regression shows that preponderant cystic proportion (OR, 0.384; P = 0.041), extremely hypoechogenicity and hypoechogenicity (OR, 6.349; P = 0.006) were the independent influencing factors of inadequate samples after FNA in benign expected nodules. In addition, nodule size ≤10 mm (OR, 1.960; P = 0.010) and superficially annular calcification (OR, 4.600; P < 0.001) were independent influencing factors for inadequate samples after FNA in malignant expected nodules. CONCLUSION: The ultrasound features of hypoechogenicity or high cystic proportion in benign expected nodules and that of small size or annular calcification in malignant expected nodules were the risk factors for inadequacy samples by US-guided FNA. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is a serious, potentially malignant oral disorder. It is histopathologically characterized by chronic inflammation and atrophic epithelium accompanied by the accumulation of collagen fibers in the lamina propria. The molecular mechanisms leading to atrophic epithelium remain poorly understood. Therefore, the present study investigated the role of autophagy and apoptosis in atrophic epithelium in OSF. The expression of Caspase-3 and autophagy-related proteins (LC3 and P62) in OSF epithelial tissues was quantified by immunohistochemistry. The analysis demonstrated that, compared with normal oral mucosal tissues, autophagy and apoptosis increased with the progression of OSF. Flow cytometry and Western blotting showed that arecoline induces apoptosis in human oral keratinocytes (HOKs) in a time-dependent manner in vitro. Arecoline-induced autophagy was confirmed by transmission electron microscopy and Western blotting. When chloroquine was used as an inhibitor of autophagy, the apoptosis rate and Caspase-3 expression decreased compared with the use of arecoline alone. Thus, autophagy and apoptosis may be involved in atrophic epithelium in OSF, and arecoline-induced autophagy promotes apoptosis in HOKs. [ABSTRACT FROM AUTHOR]

Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the in vitro tumor penetration and the in vivo anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity. Liposomes with tunable rigidity were constructed conveniently by varying the contents of cholesterol. It is revealed that liposomes with moderate rigidity gained improved tumor penetration and enhanced anti-tumor effects compared to their soft and hard counterparts. fx1 [ABSTRACT FROM AUTHOR]

• Autophagy in HUVECs could be induced by arecoline both in vivo and in vitro. • Oral submucous fibrosis samples showed a higher level of autophagy compared with normal samples. • A proper level of autophagy played a protective role in HUVECs via promoting angiogenesis. • Arecoline could induce uncontrolled autophagy in HUVECs, which led to abnormal endothelial cell function and inhibited angiopoiesis. • Autophagy activation mediated by arecoline might be one pathogenic mechanism in OSF by regulating angiogenesis. To detect the expression of protein light chain 3 (LC3) and p62-SQSTM1 (p62) in the lamina propria of oral submucous fibrosis (OSF) and to determine the association of autophagy with OSF. To investigate the role of autophagy in angiogenesis of human umbilical vein endothelial cells (HUVECs) and to assess whether this effect was induced by arecoline. LC3 and p62 expression was detected in OSF tissue through immunohistochemistry (IHC). Transmission electron microscopy (TEM) and Western blot were used to investigate the expression of autophagy in HUVECs. The role of autophagy in angiogenesis in HUVECs was investigated using the Matrigel assay. 1: LC3 expression was upregulated in OSF samples. In contrast, p62 was downregulated in early and intermediate stages but upregulated in advanced stages of OSF. 2: HUVECs treated with arecoline exhibited increased autophagosomes, LC3 expression and reduced p62 expression, when co-treated with chloroquine (CQ), which is a specific autophagy inhibitor, revealed the opposite trend. 3: Autophagy inhibited angiogenesis in HUVECs. Our findings suggest that arecoline induces autophagy in HUVECs. The high level of autophagy could reduce cell viability and inhibit angiogenesis in HUVECs, potentially promoting the development of OSF. [ABSTRACT FROM AUTHOR]

A multi-period, multi-product, multi-echelon, bi-objective, and dynamic closed-loop supply chain network model with fuzzy parameters is put forward in this article. In order to make the model realistic, the uncertainties of capacity, demand, and price are integrated into the model. Thus, a fuzzy bi-objective mixed integer model is developed to maximize the total profit and minimize the wastes of facilities. To deal with the proposed model, a solution method is put forward by incorporating four methods. Computational experiments demonstrate that the proposed hybrid method can find efficient solutions based on CLSC network managers’ risk preferences. And the proposed models and methods in this paper have important managerial implications for decision-makers. [ABSTRACT FROM AUTHOR]

Hydration kinetics for the principal phases of Portland cement blends have been incorporated in thermodynamic modeling (GEMS package), utilizing degrees of hydration from 29 Si MAS NMR. An empirical relationship for the reaction of these phases is established which includes three variable parameters that all can be estimated from the degrees of hydration. This approach is compared with thermodynamic equilibrium modeling (full hydration) for white Portland cement–metakaolin (0–30 wt.%) blends and for ternary blends of white Portland cement (65 wt.%)–metakaolin–limestone. The predicted phase assemblages have been compared with the phases identified by XRD, 27 Al and 29 Si MAS NMR which reveals that the incorporation of hydration kinetics improves the agreement between modeling and experiments. The results show also that the formation of strätlingite depends critically on the quantity of charge-balancing anions in the AFm phases, especially carbonate and sulfate anions, and on the degree of hydration for metakaolin. [ABSTRACT FROM AUTHOR]

Due to governmental, environmental, and economic concerns, the closed-loop supply chain network has attracted the attention of researchers. In this article, a multiproduct, multi-echelon, and multi-objective closed-loop supply chain network model in a fuzzy environment is proposed. The forward supply chain network includes raw material suppliers, virgin material suppliers, plants, distribution centers, and customer zones, while the reverse supply chain network is composed of customer zones, collection centers, refurbishing centers, dismantling centers, and decomposition centers. The objectives of this model are to minimize the total cost, waste, carbon dioxide, and risks. In order to solve the proposed model, a fuzzy multi-objective optimization method is used. A numerical example validates and verifies the practicability of the fuzzy model and solution method, and demonstrates the proposed model and method can be applied to solve real world problems. [ABSTRACT FROM AUTHOR]

Risks control has become a hot research area in supply chain management field. Risks indicate the reduction in revenue and profit or additional costs. Therefore, risks should be avoided as far as possible. This paper integrates risks into the design of closed-loop supply chain network and proposes a multi-period, multi-echelon, and bi-objective closed-loop supply chain network model in a fuzzy environment. The forward supply chain network includes component suppliers, assemblers, distribution centers, and customer zones. While the reverse supply chain network is composed of customer zones, recovery centers, and dismantling centers. The objectives of this model are to minimize the risks and total costs. In order to handle this model with risks caused by fuzziness, fuzzy set theory and posteriori method (compromise programming approach) are used. Computational experiments verify the practicability and validation of the fuzzy model and the solution method. The model and the method in this paper provide decision-makers with an effective tool. [ABSTRACT FROM PUBLISHER]

The composition and structure of the calcium-silicate-hydrate (C-S-H) phases formed by hydration of white portland cement-metakaolin ( MK) blends have been investigated using 27 Al and 29 Si MAS NMR. This includes blends with 0, 5, 10, 15, 20, 25, 30 wt% MK, following their hydration from 1 d to 1 yr. 29 Si MAS NMR reveals that the average Al/ Si ratio for the C-S-H phases, formed by hydration of the portland cement- MK blends, increases almost linearly with the MK content but is invariant with the hydration time for a given MK content. Correspondingly, the average aluminosilicate chain lengths of the C-S-H increase with increasing MK content, reflecting the formation of a C-S-H with a lower Ca/ Si ratio. The increase in Al/ Si ratio with increasing MK content is supported by 27 Al MAS NMR which also allows detection of strätlingite and fivefold coordinated aluminum, assigned to AlO5 sites in the interlayer of the C-S-H structure. Strätlingite is observed after prolonged hydration for MK substitution levels above 10 wt% MK. This is at a somewhat lower replacement level than expected from thermodynamic considerations which predict the formation of strätlingite for MK contents above 15 wt% after prolonged hydration for the actual portland cement- MK blends. The increase in fivefold coordinated Al with increasing MK content suggests that these sites may contribute to the charge balance of the charge deficit associated with the incorporation of Al3+ ions in the silicate chains of the C-S-H structure. [ABSTRACT FROM AUTHOR]

Aim We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder ( MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex ( ACC), and cerebellar hemisphere before and after antidepressant treatment. Methods Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. Results At baseline, N-acetyl aspartate ( NAA), total glutamine plus glutamate ( Glx) and myo-inositol ( MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls ( P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Conclusion Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas. [ABSTRACT FROM AUTHOR]