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[Display omitted] Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated T H 2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. Real-time reverse transcription–quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5 -knockout mice were used to establish a nasal polyp model with T H 2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5 -deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions. [ABSTRACT FROM AUTHOR]

This study aimed to clarify whether the extent of thyroidectomy (total thyroidectomy vs thyroid lobectomy) influences survival in adults with localized medullary thyroid cancer. Patients with localized medullary thyroid cancer were identified using the Surveillance, Epidemiology, and End Results database (2000–2018). An independent cohort of patients with localized medullary thyroid cancer were retrospectively reviewed from three medical centers in China from 2010 to 2020. The patients were grouped by the extent of surgery (total thyroidectomy vs thyroid lobectomy). Primary end points were overall survival and disease-specific survival. From 1,686 patients with medullary thyroid cancer identified in SEER, 1,122 patients met inclusion for matching, with a median follow-up of 99 months. After propensity score matching, 122 patients underwent a total thyroidectomy and 122 patients underwent a thyroid lobectomy. The 10-year overall survival was 85.2% (77.9%–90.7%) and 83.1% (75.5%–90.7%) in total thyroidectomy group and in thyroid lobectomy group, respectively. The 10-year disease-specific survival was 100% and 96.8% (93.1%–100%) in total thyroidectomy group and in thyroid lobectomy group, respectively. There was no statistically significant difference in overall survival or disease-specific survival in patients with localized medullary thyroid cancer undergoing total thyroidectomy or thyroid lobectomy (hazard ratio = 0.83, 95% confidence interval 0.44–1.57, P =.57 and hazard ratio = 0.49, 95% confidence interval 0.10–2.41, P =.39, respectively). Forty-seven patients with localized medullary thyroid cancer were identified in an independent Chinese cohort (n = 29 in total thyroidectomy group vs n = 18 in thyroid lobectomy group). After a median follow-up of 47 months, there was no mortality observed in either group. This study suggests that the extent of thyroidectomy does not influence survival for patients with early-stage localized medullary thyroid cancer and that thyroid lobectomy might be adequate in this patient population. [ABSTRACT FROM AUTHOR]

The thermal behavior in aluminum-air battery has prominent effect on its operation performance, however, the investigations to the battery thermal behavior are still scarce. In this paper, an alkaline vehicular traction aluminum-air battery was designed and its thermal behavior was experimentally investigated. The impacts of various parameters were examined, including the ambient temperature, electrolyte concentration, and discharge current density on the battery's temperature-rise, outgoing heat-flux, heat generation rate, and discharge efficiency, etc. It is shown that the battery's temperature-rise, outgoing heat-flux, and heat generation rate increase with the ambient temperature decreases and the electrolyte concentration increases. Furthermore, the battery heat generation rate decreases over the discharge time, particularly it decreases drastically at the first half of discharge. The discharge efficiency of the battery increases with the increases of operating temperature and discharge current density. The battery discharge efficiency varies with the electrolyte concentration, which approaches 78 % under the electrolyte concentration of 3.0 mol L−1, but less than 60 % under the concentrations of 1.0 mol L−1 and 6.0 mol L−1. The present study compensates a vacancy of the thermal behavior characterization for a vehicular traction aluminum-air battery, and the results are of significance in understanding the aluminum-air battery's thermal behavior. • An alkaline Al-air battery is devised. • Proposes a measurement method to characterize the Al-air battery thermal behavior. • Impacts of thermal behavior on Al-air battery operating performance is studied. [ABSTRACT FROM AUTHOR]

A working model of Cucurbitacin B suppressing AKT/mTORC1 and LXRα/SREBP1 lipogenic pathways. [Display omitted] • Cucurbitacin B mitigates aberrant lipid accumulation and hepatic steatosis in AKT-triggered NAFLD mice. • Cucurbitacin B ameliorates liver function in AKT-injected mice. • Cucurbitacin B impairs AKT/mTORC1 and lipogenic cascades in mice. • Cucurbitacin B restrains AKT-driven lipogenic pathway in vitro. • Cucurbitacin B ameliorates AKT-driven fatty liver disease in mice by suppressing AKT/mTORC1 and LXRα/SREBP1 lipogenic pathways. Dysregulated de novo lipogenesis (DNL) is an essential characteristic of nonalcoholic fatty liver disease (NAFLD). Cucurbitacin B (CuB) is a triterpenoid found in the edible plants of Cucurbitaceae with a broad spectrum of beneficial effects. Here, we investigate the in vivo anti-steatotic efficacy of CuB in an AKT-driven NAFLD mouse model established using hydrodynamic injection. Hepatocyte lines with artificial activation of AKT were used for in vitro experiments. The results demonstrate that CuB effectively attenuates the content of triglyceride and total cholesterol (P < 0.05) and hepatocyte injury (P < 0.01) in the AKT-injected mice. Mechanically, CuB directly represses AKT/mTORC1 and LXRα/SREBP1 signaling, leading to the downregulation of key lipogenic enzymes, acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Taken together, CuB attenuates AKT-driven hepatic steatosis by retarding DNL, indicating that CuB may be beneficial for the treatment of NAFLD, especially in the subset displaying activated AKT/mTORC1 and lipogenic cascades. [ABSTRACT FROM AUTHOR]

To investigate the correlation between the contrast-enhanced mammography (CEM) imaging characteristics and different molecular subtypes of breast cancer (BC). We retrospectively included 313 eligible female patients who underwent CEM examination and surgery in our hospital from July 2017 to July 2021. Their lesions were confirmed on histopathological examination and immunohistochemical analysis. BC was divided into luminal A, luminal B, HER2-enriched, and triple-negative BC (TNBC) subtypes according to immunohistochemical markers. Nine features were extracted from CEM images, including tumor shape, margins, spiculated mass, lobulated mass, malignant calcification, lesion conspicuity, internal enhancement pattern, multifocal mass, and swollen axillary lymph nodes. Statistical analysis was performed using SPSS 25.0. Univariate analysis and binomial regression were used to analyze the correlation between CEM imaging features and BC molecular subtypes. There were 184 (58.8 %) Luminal A, 44 (14.1 %) Luminal B, 47 (15.0 %) HER-2-enriched and 38 (12.1 %) TNBC, respectively. Molecular subtypes were significantly related to the tumor shape, margins, spiculated mass, internal enhancement pattern, malignant calcification and swollen axillary lymph nodes. Spiculated and calcified tumors were associated with Luminal subtypes, especially Luminal B (P < 0.05). Irregular tumor shape and malignant calcification were associated with HER-2-enriched subtype (P < 0.05). Oval or round tumor shape, rim enhancement, and swollen axillary lymph nodes were associated with TNBC (P < 0.05). CEM imaging features could distinguish BC molecular subtypes. In particular, TNBC showed oval or round tumor shape, rim enhancement, and swollen axillary lymph nodes, providing insights into the diagnosis and prognosis of TNBC. • Spiculated margins on tumor masses may indicate Luminal B. • Compared to TNBC, Luminal B and HER-2 enriched showed malignant calcification (P < 0.05). • Luminal A showed homogenous enhancement compared to TNBC (OR = 937.77, P < 0.001). • Luminal B showed homogenous enhancement compared to TNBC (OR = 143.946, P < 0.001). • TNBC showed oval shape, rim enhancement, and swollen axillary lymph nodes. [ABSTRACT FROM AUTHOR]

It is seen from this figure that the maximum temperature rise of the cell module decreases as the increasing rate of fluid flow. The maximum temperature rise of the cell module is under 40 °C and 36 °C respectively since the flow rate is 0.40 × 10−3 L·s−1 and 1.20 × 10−3 L·s−1, indicating that increasing flow rate increases the cooling capability of the LCP. • A new cooling plate is developed for controlling undesirable cell temperature field. • Inlet and outlet of cooling plate have big impact on cell temperature distribution. • Increasing flow rate decreases cell temperature rise markedly. • Cooling plate channel width has weak impact on cell temperature distribution. • Channel width has great effect on ratio of power consumption of cooling plate. The thermal management for a lithium ion battery cell plays a pivotal role in enhancing the cell performance and reliability for electric vehicles. In this work, a novel serpentine-channel liquid cooling plate with double inlets and outlets is developed for better managing an undesirable temperature distribution of a cell module. With a simplified model for the cell module, numerical analyses are implemented using the software of FloEFD to study effects of flow directions, flow rates and channel widths of the cooling plate on cell temperature distribution under different operating conditions; Likewise, a ratio of power consumption as a non-dimensional number is defined to analyze the hydraulic performance of the developed cooling plate. Results show that locations of the inlet and the outlet as well as flow directions have great impacts on the cell temperature distribution and the ratio of power consumption of the cooling plate. Increasing fluid flow rate substantially decreases the maximum temperature rise of the cell module while it has little effect on the temperature distribution. Moreover, the channel width of the cooling plate has a strong influence on its ratio of power consumption as well as the cell temperature distribution but it has a weak influence on the cell maximum temperature rise. Interestingly, the developed serpentine-channel cooling plate offers one a new method to design a lithium ion battery thermal management system for controlling temperature distribution of a cell module. [ABSTRACT FROM AUTHOR]

It is seen from these two figures that the battery temperature and SOC have a minor effect on its thermal conductivity. Battery thermal conductivity vary with the battery types heavily. • A novel method for determining thermal parameters of lithium ion cells is presented. • Temperature has a linear effect on thermal conductivity and specific heat of cells. • Cell temperature has a higher effect on its specific heat than thermal conductivity. • Cells' thermal conductivity and specific heat vary with the battery types. • The method is more effective to test thermal conductivity and specific heat of cells. Characterizing thermal parameters of a lithium ion battery is a key step to predict the temperature distribution of battery cell modules. In this work, a novel method is developed based on the quasi-steady state heat transfer analysis to determine the thermal conductivity and the specific heat simultaneously. Both prismatic lithium iron phosphate cells and pouch cells with different electrode materials are used in this experimental test. A constant heat flux is applied to the cell surface whereas the heat loss is estimated based upon the temperature drop curve. As such, the quasi-steady state heat transfer can be attained to determine cell thermal parameters. It is observed that cell thermal parameters increase linearly with the increase of the operating temperature. Furthermore, the operating temperature has a more significant influence on the cell specific heat than the thermal conductivity, while the effect of the state of charge has a minimal effect on these two parameters. The current method demonstrates an effective and practical way to determine the thermal conductivity and specific heat of the cell simultaneously. [ABSTRACT FROM AUTHOR]

• CZ48 was incorporated into PLA microbubbles via a double emulsion technique. • The encapsulation efficiency and drug-loading content were ˜85.73% and 26.07%. • The half-life time of CZ48 and CPT of CZ48-loaded microbubbles was enhanced. • Controlled release of CZ48–loaded microbubbles was achieved in vitro and in vivo. CZ48, a prodrug of camptothecin (CPT) with derivative resistant to lactone hydrolysis, suffers from limited application for cancer treatment due to poor water-solubility, thus causing its low bioavailability and absorption in vivo. To echo this problem, CZ48 was incorporated into poly (lactic acid) (PLA) microbubbles via a double emulsion technique (W/O/W), and the successful loading was confirmed by X-ray diffraction (XRD) patterns and confocal laser scanning microscope (CLSM). The obtained CZ48-loaded microbubbles had a diameter ranging from 0.5 to 6.7 μm, and the encapsulation efficiency and drug-loading content were as high as 85.73 ± 2.41% and 26.07 ± 0.76%, respectively. The in vitro drug release demonstrated that only about 55% of CZ48 was released for CZ48-loaded PLA microbubbles in 48 h. In contrast, over 90% of CZ48 was released for free CZ48 crystals sample in only 5 h. Besides, in vivo pharmacokinetic studies further revealed that the availability of both CZ48 and its metabolite CPT were obviously enhanced after the incorporation of CZ48 into PLA microbubbles. To be noted, the value of AUC 0-∞ of the CZ48-loaded microbubbles was about 5-fold higher than that of free CZ48 suspension, implying a much higher anticancer effect of the CZ48-loaded microbubbles. The half-life time (T 1/2) of both CZ48 and CPT of the CZ48-loaded microbubbles were also significantly longer than that of the free CZ48, indicating a delayed release time for the microbubbles. Hence, this work promotes a promising drug carrier system for the controlled release of CZ48 as well as other drugs with poor water-solubility. [ABSTRACT FROM AUTHOR]

We report fabrication and photovoltaic properties of flexible dye-sensitized solar cells (FDSSCs) based on stainless steel mesh (SSM)-supported core-shell ZnO/TiO 2 nanorods photoanode and Pt nanoparticles- coated SSM counter electrode (Pt/SSM CE). The core-shell ZnO/TiO 2 structures were prepared via simple chemical bath deposition, and optimal conversion efficiency of 2.84% was achieved. When aluminum foil membrane was introduced on the back of the FDSSCs as reflecting film (Rf) for improving utilization of sunlight, the conversion efficiency of FDSSCs was increased from 2.84% to 3.12%. The relative improvement of 218% was achieved in conversion efficiency compared with similar device without TiO 2 buffer layer and reflecting film (0.98%). Meanwhile, the Pt CE based on SSM possessed of higher catalytic ability and longer stability compared with ITO/PET-based Pt CE. [ABSTRACT FROM AUTHOR]

• Vitamin D catabolism via Cyp24a1 modulates postnatal and pregnancy-associated mammary gland development. • Cyp24a1 gene deletion in the mammary epithelium inhibits luminal epithelial proliferation but not apoptosis. • Luminal mammary epithelial cells are more sensitive to 1,25(OH)2D with the ablation of Cyp24a1 activity. Active vitamin D (1,25(OH)2D) has been shown to regulate numerous cell processes in mammary cells. Degradation of 1,25(OH)2D is initiated by the mitochondrial enzyme, 25-hydroxyvitamin D 24-hydroxylase (CYP24 A1), and provides local control of 1,25(OH)2D bioactivity. Several reports of the association between elevated CYP24 A1 activity and breast cancer incidence, suggest that CYP24 A1 may be a target for therapeutic intervention. Whether CYP24 A1 activity within the mammary epithelium regulates 1,25(OH)2D levels and mammary gland development is yet to shown. We have used a conditional knockout of the Cyp24a1 gene specifically in the mammary epithelium to demonstrate reduced terminal end bud number, ductal outgrowth and branching during puberty and alveologenesis at early pregnancy, by inhibiting proliferation but not apoptosis in both basal and luminal MECs. In vitro study showed increased sensitivity of luminal MECs to lower levels of 1,25(OH)2D with the ablation of Cyp24a1 activity. In summary, Cyp24a1 within MECs plays an important role in modulating postnatal and pregnancy-associated mammary gland development which provides support for inhibiting CYP24 A1 as a potential approach to activating the vitamin D pathway in breast cancer prevention and therapy. [ABSTRACT FROM AUTHOR]

Abstract The purpose of present HUVE cells and mice study was to investigate the combined effects of carnosine and asiatic acid (AA) against diabetic progression. In HUVE cells, high glucose decreased cell viability, reduced Bcl-2 mRNA expression and increased Bax mRNA expression. The co-treatment of 0.5 μM carnosine plus 0.5 μM AA led to greater cell viability and Bcl-2 mRNA expression than 1 μM carnosine or 1 μM AA treatment alone. This combination more significantly decreased the production of DNA fragmentation, tumor necrosis factor (TNF)-alpha, reactive oxygen species (ROS), and nuclear factor kappa B binding activity than carnosine or AA treatment alone. In diabetic mice, the combination of 0.25% carnosine plus 0.25% AA in diet resulted in higher final body weight, and lower levels of plasma glucose and triglyceride than 0.5% carnosine or 0.5% AA treatment alone. Carnosine and AA combination caused more reduction in renal levels of leukin-6, TNF-alpha and ROS than carnosine or AA treatment alone. This combination also more significantly limited renal cyclooxygenase-2 activity and p-p38 phosphorylation than carnosine or AA treatment alone. These novel findings support that this combination is a more powerful remedy for diabetic control. Graphical abstract Effects of carnosine (Car) and/or AA upon NF-κB p50/65 binding activity (OD value/mg protein). HUVE cells were pre-treated with 1 μM Car, 1 μM AA or 0.5 μM Car+0.5 μM AA for 24 h incubation at 37 °C. Then, cells were treated with DMEM containing high glucose (33 mM), and followed by incubating for another 24 h at 37 °C. Normal group had no Car, AA, or high glucose. Control group had no Car or AA, but with high glucose. Data are mean ± SD (n = 6). Values with different alphabet among bars are significantly different at P < 0.05 as analyzed by Dunnett's t -test. Image 1 Highlights • HUVE cell line and diabetic mice were used to examine the combined effects of carnosine and asiatic acid (AA). • Co-treatment of carnosine plus AA led to grater HUVE cell viability and Bcl-2 mRNA expression. • In diabetic mice, carnosine and AA combination caused more reduction in renal IL-6, TNF-alpha and ROS generation. • This combination led to more decrease in renal cyclooxygenase-2 activity and p-p38 phosphorylation. • These findings support that this combination is a powerful remedy for diabetic control. [ABSTRACT FROM AUTHOR]

Graphical abstract It is found that the average heat generation rate of the lithium-ion battery cell has a quadratic relationship with the operating temperatures and operating currents. Tested results of the heat generation rate show a good agreement with results calculated as per widely used Bernardi's heat generation model. Highlights • Reveals a method for testing specific heat and heat generation of a Lithium ion cell. • Increasing temperature linearly increases the specific heat of Lithium ion cell. • Heat generation of Lithium ion cell quadratically increases with increasing current. • Tested results of heat generation via new method and Bernardi model are consistent. Abstract The specific heat and the heat generation rate are the key thermal properties for lithium ion battery cells. Nonetheless, there exists large scattering in data of thermal properties due to factors such as battery temperature nonuniformity during experimental measurement. In this work, a novel calorimetric method for measuring thermal properties of a lithium ion battery cell is proposed by introducing a temperature even out process to minimize the effect of the temperature difference across the battery. Through this method, the specific heat and the heat generation rate can be characterized for the electrochemical batteries. Thermal parameters of a prismatic lithium iron phosphate battery cell are determined for the wide temperature range at varying operating currents. It is found that the specific heat of the lithium ion battery cell has a linear relationship with the operating temperature, whereas the heat generation rate has a quadratic relationship with the operating current. The measured heat generation rate shows a good agreement with calculated results as per Bernardi's heat generation model. This new method allows one to obtain thermal properties of lithium ion battery cells at a lower cost and in a shorter time. [ABSTRACT FROM AUTHOR]

Abstract With growing demand for economic, eco-friendly, easy-manufacturing and renewable portable power source, flexible dye-sensitized solar cells (FDSSCs) exhibit a promising potential in the field of portable power sources. However, FDSSCs surfer from low conversion efficiency and poor stability, which hinder their applications. In this work, we have summarized recent development and challenges according to respective functions of their vital components (substrate, semiconductor film, sensitizer, electrolytes and counter electrode) as well as their effects on photoelectric conversion efficiency. Meanwhile, typical fabrication approaches have been analyzed for increasing the incident photon to current efficiency (IPCE). The approaches in rigid dye-sensitized solar cells (DSSCs) for improving performance are also introduced to provide the favorable direction for accelerating FDSSCs' application in field of potable power source. [ABSTRACT FROM AUTHOR]

Low soil water availability in the dry season substantially influences the survival of native tree species planted in subtropical degraded hilly lands in South China. In this study, we investigated the survival and hydraulic-related traits of 16 native tree species from a six-year-old mixed plantation, to investigate whether the survival ratios of species are associated with their drought tolerance and hydraulic efficiency. Our results showed that the six-year survival ratios ranged from 1% to 96% among the 16 species, with less 25% survival for four species. Across species, the survival ratio was significantly correlated with xylem vulnerability to cavitation, hydraulic safety margin, and leaf turgor loss point. It was not correlated with sapwood density and hydraulic conductivity. These results indicated that drought tolerance was the determinant of species survival in the mixed plantation. Additionally, we found that a large proportion of high survival species were non-pioneers, indicating that mixed plantations consisted of pioneers and non-pioneers are effective and would decrease the time required for the succession from plantation to mature forest. Considering that drought is one of the most important stress factors that affect the success of forest restoration, and increases in frequency and severity in the subtropical region, we suggest drought-tolerance traits are valuable for identification of native tree species suitable for restoration projects. [ABSTRACT FROM AUTHOR]

The biologically active form of vitamin D 3 (1,25(OH) 2 D) regulates epithelial cell differentiation, proliferation, and apoptosis, lending weight to clinical evidence linking vitamin D 3 insufficiency to breast cancer incidence and mortality. Local dysregulation of vitamin D 3 metabolism has been identified in patients with breast cancer, implying that disruption of 1,25(OH) 2 D signaling may contribute to breast cancer development in an autocrine or paracrine manner. Mouse mammary glands express the critical enzymes responsible for 1,25(OH) 2 D synthesis (Cyp2r1 and Cyp27b1), degradation (Cyp24a1), as well as the vitamin D 3 receptor (Vdr), and genetically modified mouse models have revealed a great deal about the role of vitamin D 3 in cancer initiation and progression. Ablation of Vdr or Cyp27b1 in murine models of mammary cancer reduces the anti-tumor effects of vitamin D 3 , while elevation of Cyp24a1 levels increases degradation of 1,25(OH) 2 D, leading to diminished anti-tumor effects. This review discusses the recent transgenic mouse models of vitamin D 3 metabolism and the Vdr signaling network, and how these contribute to mammary gland development, and cancer tumorigenesis and progression. Collectively, these mouse models have helped clarify mechanisms of action of vitamin D 3 signaling and suggest that activation or restoration of the vitamin D 3 regulated pathway is a potential approach for human breast cancer prevention. [ABSTRACT FROM AUTHOR]

• Two flow regimes were observed in membrane assisted reactive crystallization (MARC). • Reversible transitions between liquid layer and droplet can be achieved on membrane surface. • Controllable mixing and ions diffusion conditions were achieved via MARC. • Crystals with narrow nano/micro size distribution were obtained via MARC. Herein, membrane-assisted reactive crystallization (MARC) with effective interfacial flow regimes was proposed to achieve the effective mass transfer control during reactive crystallization. Three tube-shell side solution systems (EtOH-H 2 O, Butanol-H 2 O and H 2 O-H 2 O) were chosen to form different flow regimes on the membrane surface, including the microscale liquid layer and the uniform droplets. The fundamental mechanisms of 'rising and falling tide' phenomenon, and flexible layer thickness control were uncovered. A force analysis model was established to illustrate the transition behavior of the droplet and liquid layer on the membrane surface. Molecular simulations additionally demonstrated that MARC implemented various ion diffusion conditions in different solution systems. Compared to the conventional reactive crystallization, MARC with multiple flow regimes can achieve effective control of CaCO 3 crystal size ranging from 700 nm to 3 μm and obtain uniform size distribution (coefficient of variation less than 15.1 %), which shed light on the advanced material manufacture with reactive crystallization process. [ABSTRACT FROM AUTHOR]

Ethanol was used to induce acute hepatotoxicity in mice. Effects of cinnamic acid (CA) and syringic acid (SA) post-intake for hepatic recovery from alcoholic injury was investigated. Ethanol treated mice were supplied by CA or SA at 40 or 80 mg/kg BW/day for 5 days. Results showed that ethanol stimulated protein expression of CYP2E1, p47 phox , gp91 phox , cyclooxygenase-2 and nuclear factor kappa B in liver. CA or SA post-intake restricted hepatic expression of these molecules. Ethanol suppressed nuclear factor erythroid 2-related factor (Nrf2) expression, and CA or SA enhanced Nrf2 expression in cytosolic and nuclear fractions. Ethanol increased the release of reactive oxygen species, oxidized glutathione, interleukin-6, tumor necrosis factor-alpha, nitric acid and prostaglandin E 2 . CA or SA lowered hepatic production of these oxidative and inflammatory factors. Histological data revealed that ethanol administration caused obvious foci of inflammatory cell infiltration, and CA or SA post-intake improved hepatic inflammatory infiltration. These findings support that cinnamic acid and syringic acid are potent nutraceutical agents for acute alcoholic liver disease therapy. However, potential additive or synergistic benefits of cinnamic and syringic acids against ethanol-induced hepatotoxicity need to be investigated. [ABSTRACT FROM AUTHOR]

Multiple epidemiological studies have shown that high vitamin D 3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D 3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN , SERPINB1 , EFTUD1 , and KLK6 were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN , SERPINB1 , and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1 , and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D 3 levels may improve breast cancer outcome. [ABSTRACT FROM AUTHOR]

Digestive system cancers account for nearly half of all cancers around the world and have a high mortality rate. Cell culture and animal models represent cornerstones of digestive cancer research. However, their ability to enable cancer precision medicine is limited. Cell culture models cannot retain the genetic and phenotypic heterogeneity of tumors and lack tumor microenvironment (TME). Patient-derived xenograft mouse models are not suitable for immune-oncology research. While humanized mouse models are time- and cost-consuming. Suitable preclinical models, which can facilitate the understanding of mechanisms of tumor progression and develop new therapeutic strategies, are in high demand. This review article summarizes the recent progress on the establishment of TME by using tumor organoid models and microfluidic systems. The main challenges regarding the translation of organoid models from bench to bedside are discussed. The integration of organoids and a microfluidic platform is the emerging trend in drug screening and precision medicine. A future prospective on this field is also provided. [ABSTRACT FROM AUTHOR]