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Photosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment of malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency of photodynamic therapy (PDT). Herein, a molecular‐targeting photosensitizer QTANHOH is rationally designed for histone deacetylases (HDACs‐targeting photo‐immunotherapy application. The PS QTANHOH displays excellent type‐I/II PDT performance, exhibiting significant phototoxicity toward cancer cells with half maximal inhibitory concentration (IC50) less than 10 nm in both normoxia and hypoxia conditions under blue laser irradiation. Moreover, the bioactive compound could inhibit HDACs and activate the immune microenvironment to boost PDT efficacy on the immunocompetent BALB/c mice with breast cancer, leading to the eradication of solid tumor and inhibition of metastasis. Notably, the molecular‐targeting photosensitizer introduces an alternative strategy to achieve superior phototherapy for cancer therapy. [ABSTRACT FROM AUTHOR]

Stimulator of interferon genes (STING) agonists can improve the anticancer efficacy of immune checkpoint blockade by amplifying tumor immunogenicity. However, the clinical translation of cyclic dinucleotides (CDNs) as STING agonists is hindered by their poor drug-like properties. In this study, we investigated the design criteria for DOTAP/cholesterol liposomes for the systemic delivery of ADU-S100 and delineated the impact of key formulation factors on the loading efficiency, serum stability, and STING agonistic activity of ADU-S100. Our findings demonstrate that the cationic liposomal formulation of ADU-S100 can be optimized to greatly potentiate STING activation in antigen-presenting cells. [ABSTRACT FROM AUTHOR]

Background: The optimum timing to wean is crucial to avoid negative outcomes for mechanically ventilated patients. The rapid shallow breathing index (RSBI), a widely used weaning index, has limitations in predicting weaning outcomes. By replacing the tidal volume of the RSBI with diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) assessed by ultrasonography, we calculated two weaning indices, the diaphragmatic excursion rapid shallow breathing index (DE-RSBI, respiratory rate [RR]/DE) and the diaphragm thickening fraction rapid shallow breathing index (DTF-RSBI, RR/DTF). The aim of this study was to evaluate the predictive values of DTF-RSBI, DE-RSBI and traditional RSBI in weaning failure.Methods: This prospective observational study included patients undergoing mechanical ventilation (MV) for > 48 h and who were readied for weaning. During a pressure support ventilation (PSV) spontaneous breathing trial (SBT), right hemidiaphragmatic excursion and DTF were measured by bedside ultrasonography as well as RSBI. Weaning failure was defined as: (1) failing the SBT and (2) SBT success but inability to maintain spontaneous breathing for more than 48 h without noninvasive or invasive ventilation. A receiver operator characteristic (ROC) curve was used for analyzing the diagnostic accuracy of RSBI, DE-RSBI, and DTF-RSBI.Results: Of the 110 patients studied, 37 patients (33.6%) failed weaning. The area under the ROC (AUROC) curves for RSBI, DE-RSBI, and DTF-RSBI for predicting failed weaning were 0.639, 0.813, and 0.859, respectively. The AUROC curves for DE-RSBI and DTF-RSBI were significantly higher than for RSBI (P = 0.004 and P < 0.001, respectively). The best cut-off values for predicting failed weaning were RSBI > 51.2 breaths/min/L, DE-RSBI > 1.38 breaths/min/mm, and DTF-RSBI > 78.1 breaths/min/%.Conclusions: In this study, two weaning indices determined by bedside ultrasonography, the DE-RSBI (RR/DE) and DTF-RSBI (RR/DTF), were shown to be more accurate than the traditional RSBI (RR/VT) in predicting weaning outcome during a PSV SBT. [ABSTRACT FROM AUTHOR]

Patients with sepsis are prone to fluid overload (FO) due to fluid resuscitation, irrespective of stage of acute kidney injury (AKI). The aim of our study was to analyze the association between FO at continuous renal replacement therapy (CRRT) initiation and 28‐day mortality in patients with sepsis associated AKI (S‐AKI). In this retrospective study, data for patient characteristics were collected and 28‐day mortality were studied. We also analyze association of variables, including FO degrees with 28‐day mortality. Earlier commencement of CRRT showed better outcome. Non‐survivors had higher FO than survivor (9.17% vs. 5.20%; p = 0.016). Survival in patients with FO > 10% over 28 days was significantly worse compared to those with FO ≤ 10% (p = 0.006). Multivariate analysis showed, FO > 10% (95%CI [1.721, 17.195], p = 0.004) was significantly associated with increased 28‐day mortality. In S‐AKI requiring CRRT, FO > 10% at CRRT initiation was independently associated with 28‐day mortality. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resistance in CRC. The patients with higher expression of ATP7A tended to have platinum drug resistance. While the lower expression of ATP7A by siRNA knockdown resulted in enhancement of OXA sensitivity and increased OXA-induced apoptosis. Further, we demonstrated a novel and safe strategy to increase CRC chemosensitivity by delivering siRNA into tumor cells via a novel nanoparticle, DAN. In summary, our study provided a novel nanocarrier-based delivery of ATP7A to interfere in a key gene of chemo-resistance in CRC, which may be a novel therapeutic strategy to overcome chemotherapy resistance in CRC. [ABSTRACT FROM AUTHOR]

BACKGROUND Roasted peanut is widely loved as a kind of food with rich taste. However, peanut allergy is one of the major threats to human health, which affects about 5% of children and 1.4–2% of adults in the world. RESULTS: To evaluate the sensitization mechanism of peanut allergen Ara h 3, Caco‐2 cells as the model, which has the similar structure and function to differentiated small intestinal epithelial cells. Compared with Ara h 3‐raw (purified from raw peanut) group, more significant results such as the inhibited Caco‐2 cell viability and proliferation, the increased secretion of reactive oxygen species (ROS) and the decreased transepithelial electrical resistance were obtained in Ara h 3‐roasted (purified from roasted peanut) group. Accordingly, oxidative stress and NF‐κB signaling pathway were more imbalanced, which lead to the increased of thymic stromal lymphopoietin (TSLP), interleukin 6 (IL‐6), IL‐8 and monocyte chemotactic protein 1 (MCP‐1). Then, the gene expression of tight junction proteins ZO‐1, occludin and JAM‐1 were reduced, which proved that the integrity of the Caco‐2 monolayer barrier is severely damaged. CONCLUSION: These finding identify the mechanisms of the allergenicity of roasted peanut allergy proteins are probably associated with intestinal uptake and cytokine dependent allergies. The aggravated allergic reaction might be caused by the increment of TSLP, IL‐6, IL‐8 and MCP‐1 due to the activated NF‐κB signaling pathway, and the enhanced transport of Ara h 3‐roasted protein by Caco‐2 monolayer. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock worldwide. Russia is a big agricultural country with a wide geographical area where FMD outbreaks have become an obstacle for the development of the animal and animal products trade. In this study, we aimed to assess the export risk of FMD from Russia. Results: After simulation by Monte Carlo, the results showed that the probability of cattle infected with FMD in the surveillance zone (Surrounding the areas where no epidemic disease has occurred within the prescribed time limit, the construction of buffer areas is called surveillance zone.) of Russia was 1.29 × 10− 6. The probability that at least one FMD positive case was exported from Russia per year in the surveillance zone was 6 %. The predicted number of positive cattle of the 39,530 - 50,576 exported from Russia per year was 0.06. A key node in the impact model was the probability of occurrence of FMD outbreaks in the Russian surveillance zone. By semi-quantitative model calculation, the risk probability of FMD defense system defects was 1.84 × 10− 5, indicating that there was a potential risk in the prevention and control measures of FMD in Russia. The spatial time scan model found that the most likely FMD cluster (P < 0.01) was in the Eastern and Siberian Central regions. Conclusions: There was a risk of FMDV among cattle exported from Russia, and the infection rate of cattle in the monitored area was the key factor. Understanding the export risk of FMD in Russia and relevant epidemic prevention measures will help policymakers to develop targeted surveillance plans. [ABSTRACT FROM AUTHOR]

The transcutaneous oxygen challenge test (OCT) is associated with central venous oxygen saturation and cardiac output index, and has predictive value for prognosis. Whether the change of transcutaneous oxygen pressure (PtcO2)-related variables can reflect lactate clearance in sepsis patients is worth studying. We conducted a prospective observational study of 79 patients with sepsis or septic shock in the ICU. Immediately after enrollment, PtcO2 monitoring was continuously performed for 6 h. The OCT was performed at enrollment (T0) and the sixth hour (T6). The correlation between lactate clearance and PtcO2-related variables such as PtcO2 at T6, ΔPtcO2 (PtcO2 at T6 − PtcO2 at T0), ΔPtcO2 index (PtcO2/PaO2 at T6 − PtcO2/PaO2 at T0), 10 OCT [(PtcO2 after 10 min on FiO2 of 1.0) − (PtcO2 at baseline)], Δ10 OCT (10 OCT at T6 − 10 OCT at T0) was analyzed. The difference of PtcO2-related variables was compared between the high and low lactate clearance groups. PtcO2 at T6 (r = 0.477, p < 0.001), ΔPtcO2 (r = 0.592, p < 0.001), ΔPtcO2 index (r = 0.553, p < 0.001) and Δ10 OCT (r = 0.379, p = 0.001) were significantly correlated with the lactate clearance. To discriminate low lactate clearance, the area under the ROC curve was largest for ΔPtcO2, which was 0.804. PtcO2 at T6, PtcO2 index, ΔPtcO2, ΔPtcO2 index and Δ10 OCT were significantly different between the two different lactate clearance groups. Low lactate clearance in the initial 6 h of resuscitation of septic shock was associated to lower improvements in PtcO2-related variables. [ABSTRACT FROM AUTHOR]

Nanotechnology is an innovative science and technology that has the most opportunity to be applied in the market, and its intrinsic value is immeasurable. Some developed countries have invested a lot in research activities. The purpose of this paper is to explore the biomechanical principle of the skeletal muscle of the molecular motor and its application in the active rehabilitation of the lower limbs. In this paper, based on the force generation mechanism and biomechanical model of skeletal muscle, and guided by the mechanical principle equation of skeletal muscle contraction of the collective operation mechanism of a molecular motor, and combined with the experiment of active rehabilitation design of human lower limbs, it is demonstrated in the results that the angle error after yaw angle fitting can be controlled within −1° − 1°, which has a strong effect, and in the rehabilitation effect in fruit, the swing phase accounts for about 40% and the support phase accounts for about 60%. It can be concluded that the accuracy of rehabilitation data collection and the effectiveness of gait parameters detection in the process of human rehabilitation, as well as the actual recognition effect of lower limb movement pattern recognition, is good and efficient. Molecular materials play an important role in biology or medicine. With the development of technology, they contribute to the recovery of skeletal muscle. [ABSTRACT FROM AUTHOR]

Evidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease. [ABSTRACT FROM AUTHOR]

In this work, nonstoichiometric MgTiO3 ceramics were prepared by the sol–gel method. The crystalline structure, morphology, and microwave dielectric properties of the MgTi0.98O2.96 ceramics were investigated in detail. Compared to the samples prepared by the solid state method, the nonstoichiometric ceramics also had a high-density (~94.33% of the theoretical density) and high-quality factor (Q × f of 46,400 GHz). Meanwhile, the sintering characteristic was dramatically improved, making the densification sintering temperature reduce by 300 °C, from 1420 to 1120 °C. The lower temperature densification sintering can be ascribed to the high activity of the ceramic powders from the sol–gel process, the distortion of the octahedron, and the volume reduction of the unit cell. This study indicates that the sol–gel method is a promising way to prepare microwave materials, which can be applied in the efficient transmission of 5G wireless networks. Highlights: Non-stoichiometric MgTiO3 ceramics were synthesized by sol–gel method. The samples prepared by the sol–gel method had smaller grain size and unit cell volume. Sol–gel method can significantly improve the sintering characteristics and reduce the densification sintering temperature. [ABSTRACT FROM AUTHOR]

BACKGROUND Ara h 1 is a major food allergen in peanuts. Recently, many studies have revealed that the Maillard reaction (MR) affects the allergenicity of food proteins. RESULTS: To investigate the influence of the MR on the allergenicity of Ara h 1, R‐Ara h 1 was processed with glucose in dry heating conditions for different periods. The extent of the MR was assessed by four methods. The changes in secondary and tertiary structures were characterized through spectroscopy assays. Advanced glycation end products (AGE) structures were identified by protein sample dry heating for 60 min, indicating the formation of AGE‐Ara h 1. Simulated gastric fluid (SGF) digestion analysis showed that AGE‐Ara h 1 has higher resistance to peptic digestion than R‐Ara h 1. The BALB/c mouse model was also utilized to explore the effect of the MR on the allergenicity of Ara h 1, and the results showed that the Th2‐type cytokines, antibodies, and histamine content increased, and there was a greater degree of degranulation of rat basophilic leukemia (RBL) cells in the AGE‐Ara h 1 group compared with the R‐Ara h 1 group. CONCLUSION: During the process of dry heating, proteins participated in the MR with changes in secondary and tertiary structures. The condition applying a temperature of 100 °C for 60 min caused the formation of AGE‐Ara h 1. Simulated gastric fluid digestion analysis showed that AGE‐Ara h 1 had a greater resistance to peptic digestion than R‐Ara h 1. The BALB/c mouse model showed that AGE‐Ara h 1 had more allergenicity, indicating that the MR could enhance the allergenicity of Ara h 1. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

BACKGROUND Peanut allergy is one of the most common food allergies worldwide. Studies have shown that the incidence of peanut allergies in Western‐born Asians is higher than that in Asia‐born Asians. Notably, Europeans and Americans mostly eat roasted peanuts, whereas Asians mostly eat boiled or fried peanuts. RESULTS: BALB/c mice were sensitized using purified protein from raw, roasted or boiled peanuts, then fed the same by oral gavage. The relevant allergic reactions were studied using BALB/c mice model, including a rat basophilic leukemia (RBL) cell model, simulated gastric fluid experiments, and ultraviolet (UV) and circular dichroism (CD) spectral analysis. Serological studies showed increased levels of immunoglobulin E, interleukin‐4 and interleukin‐5, and pathological studies showed mast cell degranulation and inflammatory changes in jejunal tissues, with an increase in thymic stromal lymphopoietin (TSLP) gene expression in all treatment groups compared with the control group (phosphate‐buffered saline). Compared with the raw peanut group, sera from the roasted peanut group produced a significant increase in RBL β‐hexosaminidase A release in vitro, and roasted peanuts showed increased resistance to digestion in simulated gastric fluid experiments. Ultraviolet and CD spectral analyses showed that the roasting and boiling processes altered the structure of the major peanut allergens, which may have contributed to the differences observed in peanut allergenicity. CONCLUSION: Our findings indicate that peanut allergies are related to peanut thermal processing methods. In our mouse model, the raw, roasted and boiled peanuts elicited different degrees of allergic response. Compared with raw peanut, roasted peanuts show a higher allergenicity, whereas the boiled peanuts show a lower allergenicity. © 2018 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Biological products such as protein-based biopharmaceuticals are playing an important role in the healthcare and pharmaceutical industry. The interaction between biological products and packaging materials has become the focus of many studies since it can reduce the effectiveness of biological products. These interactions are heavily influenced by the surface properties and physicochemical nature of the therapeutic agents and the packaging materials. Therefore, it is critical to understand the interactions between packaging materials and biological products in order to design biocompatible packaging materials and develop approaches to minimize adverse interactions. We describe the interactions that occur when using several common packaging materials, including glass and polymer. We discuss the interaction between these materials and biological products such as blood, blood derivatives, recombinant proteins, monoclonal antibodies, and gene therapeutics. We also summarize approaches for overcoming these interactions. Understanding the interactions between biological materials and packaging materials is critical for the development of novel packaging materials that improve the safety of pharmaceutical products. [ABSTRACT FROM AUTHOR]

Chemoresistance, colorectal cancer, oxaliplatin, siRNA delivery, ATP7A Keywords: oxaliplatin; chemoresistance; siRNA delivery; colorectal cancer; ATP7A EN oxaliplatin chemoresistance siRNA delivery colorectal cancer ATP7A 1 2 2 06/30/22 20220627 NES 220627 In the original article, there was a mistake in Figure 3 as published. [Extracted from the article]

We introduce a novel method for making breath figure arrays (BFAs) on polyvinyl butyral (PVB) films under humidity by putting the dip coated samples inside a chamber filled with supersaturated salt solutions. With the increase in humidity or retention time, multiple porous films with bigger pore sizes and wider size distributions are generally obtained, resulting from the coalescence of the following-up water drops. The presence of nitrogen flow accelerates the evaporation of solvents and vapor, thus increases the elastic interaction among water droplets such that films with smaller pores can be obtained. Compared to PVB/ethyl acetate solution, it is easier to obtain a film with regular honeycomb pattern by using PVB/chloroform solution. Its lower boiling point makes it evaporate faster to increase temperature gradient between film surface and the atmosphere; while its higher density makes it provide stronger support to maintain the shape of water droplets. In this study, the solubility of polymer in solvents is initially proposed to explain the BFAs formation. Higher mobility of polymer chains in a good solvent increases chances of its polar groups to interact with water droplets, thus increases the possibility of regular arrangements of water droplets on the film. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]