Abstract
Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in ...metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in
IL-10
-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction.
Chronic inflammation of white adipose tissue is a key link between obesity and the associated metabolic syndrome. Transient receptor potential melastatin-like 7 (TRPM7) is known to be related to ...inflammation; however, the role of TRPM7 in adipocyte phenotype and function in obesity remains unclear. Here, we observe that the activation of adipocyte TRPM7 plays an essential role in pro-inflammatory responses. Adult male mice are used in our experiments. Adipocyte-specific deficiency in TRPM7 attenuates the pro-inflammatory phenotype, improves glucose homeostasis, and suppresses weight gain in mice fed a high-fat diet. Mechanistically, the pro-inflammatory effect of TRPM7 is dependent on Ca
signaling. Ca
influx initiated by TRPM7 enhances transforming growth factor-β activated kinase 1 activation via the co-regulation of calcium/calmodulin-dependent protein kinase II and tumor necrosis factor receptor-associated factor 6, leading to exacerbated nuclear factor kappa B signaling. Additionally, obese mice treated with TRPM7 inhibitor are protected against obesity and insulin resistance. Our results demonstrate TRPM7 as a factor in the development of adipose inflammation that regulates insulin sensitivity in obesity.
Pyroptosis, a form of caspase-1-dependent cell death, also known as inflammation-dependent death, plays a crucial role in diseases such as stroke, heart disease, or tumors. Since its elucidation, ...pyroptosis has attracted widespread attention from various sectors. Reactive oxygen species (ROS) can regulate numerous cellular signaling pathways. Through further research on ROS and pyroptosis, the level of ROS has been revealed to be pivotal for the occurrence of pyroptosis, establishing a close relationship between the two. This review primarily focuses on the molecular mechanisms of ROS and pyroptosis in tumors and inflammatory diseases, exploring key proteins that may serve as drug targets linking ROS and pyroptosis and emerging fields targeting pyroptosis. Additionally, the potential future development of compounds and proteins that influence ROS-regulated cell pyroptosis is anticipated, aiming to provide insights for the development of anti-tumor and anti-inflammatory drugs.
As an environmentally friendly and efficient method, successive two-step fermentation has been applied for extracting chitin from shrimp shells. To screen out the microorganisms for fermentation, a ...protease-producing strain,
Exiguobacterium profundum
, and a lactic acid-producing strain,
Lactobacillus acidophilus
, were isolated from the traditional fermented shrimp paste. Chitin was extracted by successive two-step fermentation with these two strains, and 85.9 ± 1.2% of protein and 95 ± 3% of minerals were removed. The recovery and yield of chitin were 47.82 and 16.32%, respectively. Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy (SEM) were used to characterize the chitin. The crystallinity index was 54.37%, and the degree of deacetylation was 3.67%, which was lower than that of chitin extracted by the chemical method. These results indicated that successive two-step fermentation using these two bacterial strains could be applied to extract chitin. This work provides a suitable strategy for developing an effective method to extract chitin by microbial fermentation.
The orally disintegrating tablets (ODTs) are especially suitable for elders and children with dysphagia, who need to be given customized dosages.
This study aimed to prepare orally disintegrating ...tablets (ODTs) which can be customized as drug content by using semi-solid 3D printing pressure extrusion technology, with water insoluble and thermally unstable drug loratadine.
The influence of binder concentration, disintegrating agent dosage and ratio mannitol: cellulose on formability and disintegration time was investigated. The properties of orally disintegrating tablets were investigated by ATR-FTIR, XRPD, DSC and SEM. The correlation formula between tablet bottom area and drug content was established.
The formulation was optimized, and contained loratadine 3 g, cellulose 4 g, mannitol 2 g, carboxy methyl starch sodium 1g, 6% PVP K30 16 ml. The disintegration time was less than 60 s with infilling percentage of 60%, and the disintegration time was less than 30 s with infilling percentage of 40%. There was no detectable interaction between loratadine and the selected excipients by the analysis of ATR-FTIR, DSC and XRPD. The structure of the tablets was porous, and the drug was dissolved completely within 10 min. The drug content (x) of the tablet and the bottom area (y) of the tablet showed a linear fitting relationship, y = 3.8603x - 0.7176, r
= 0.9993.
Semi-solid extrusion of 3D printing technology was applied to prepare loratadine orally disintegrating tablets with customized drug content, which provides an alternative method for the research of customized preparation.
A novel nanomaterial of two-dimensional holey CuCo
2
O
4
(2D HCCO) nanosheets was synthesized via a general template-directed method and employed for the first time to construct an effective ...electrochemical platform for H
2
O
2
sensing with the combination of cerium oxide (CeO
2
). During the electrocatalytic reduction of H
2
O
2
, the synergetic catalysis of CeO
2
/HCCO/MWCNTs/GCE owing to the naturally holey frameworks and the mediator of CeO
2
results in the ultra-sensitive detection of H
2
O
2
. The current was greatly enhanced owing to the unique holey structure that can minimize the charge transfer distance and provide more active sites to boost the signals, and the dual oxidation state of Ce
3+
/Ce
4+
on the surface of 2D HCCO nanosheets can promote the in situ production of Cu
2+
/Cu
+
and Cu
+
/Cu and further amplify the detection signal. The CeO
2
/HCCO/MWCNTs/GCE showed a wide linear range from 1 μM to 7.31 mM using chronoamperometry at the potential of − 0.25 V and a relatively low detection limit of 0.16 μM in physiological environment, which was also utilized for tracking the trace H
2
O
2
released from Hela cells. This study shows great promise for the emerging application of holey HCCO-based biosensors in bioanalysis and early cancer diagnosis.
Graphical abstract
Radar waveform design is of great importance for radar system performances and has drawn considerable attention recently. Constant modulus is an important waveform design consideration, both from the ...point of view of hardware realization and to allow for full utilization of the transmitter's power. In this paper, we consider the problem of constant-modulus waveform design for extended target detection with prior information about the extended target and clutter. At first, we propose an arbitrary-phase unimodular waveform design method via joint transmitter-receiver optimization. We exploit a semi-definite relaxation technique to transform an intractable non-convex problem into a convex problem, which can then be efficiently solved. Furthermore, quadrature phase shift keying waveform is designed, which is easier to implement than arbitrary-phase waveforms. Numerical results demonstrate the effectiveness of the proposed methods.
Digital game-based learning has received increased attention in education. As the key stakeholders in education, students, parents, and teachers may have different perceptions and attitudes towards ...game-based learning, which have a great impact on its adoption and dissemination. However, there is a lack of research examining how the perceptions of different stakeholders towards digital educational games may differ and influence each other. This study aimed to address the gap by investigating the perceptions of students, parents and teachers towards digital educational games, the differences and relationships between their perceptions, and possible sources of their perceptions. The study was conducted with 415 participants in China, a country that has tension between play and learning in its traditional values. The results reveal that most students, parents and teachers have certain experience playing mobile games, but with limited knowledge about educational digital games. Students have more positive perceptions towards digital educational games than teachers and parents, and the perceptions of teachers and parents are correlated with each other. After an introduction to an educational digital game, students’ and parents’ intention to recommend game-based learning increased, which, however, was not the case for teachers. Implications of the findings were discussed.
Metastatic colorectal cancer (mCRC) patients are predisposed to venous thromboembolism (VTE). This study aimed to (1) evaluate the efficacy of 4 existing cancer-specific VTE models in predicting VTE ...incidence among hospitalized mCRC patients, and (2) examine the influence of incorporating mCRC molecular subtypes into these models. We conducted an evaluation of 4 cancer-specific VTE models, including Khorana, Vienna CATS, Protecht, and CONKO in a dataset involving 1392 mCRC patients. To evaluate the predictive performance, we utilized receiver operating characteristic (ROC) curves for both the original models and the modified models that incorporated microsatellite instability status or KRAS/NRAS/BRAF mutations. Moreover, we computed the net reclassification improvement (NRI) to quantify the enhancements made to the modified VTE risk models. All models demonstrated a moderate area under the ROC curve (ROC-AUC) when predicting the occurrence of VTE: Khorana (0.550), Vienna CATS (0.671), Protecht (0.652), and CONKO (0.578). The incorporation of KRAS and BRAF mutations significantly improved the ROC-AUC of all 4 existing models (modified Khorana: 0.796, modified Vienna CATS: 0.832, modified Protecht: 0.834, and modified CONKO: 0.809). After dichotomizing the risk using a threshold of 3 points and comparing them with the original models, NRI values for the 4 modified models were 0.97, 0.95, 1.11, and 0.98, respectively. All 4 cancer-specific VTE models exhibit moderate performance when identifying mCRC patients at high risk of VTE. Incorporating KRAS and BRAF mutations may enhance the prediction of VTE in hospitalized mCRC patients.
Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of ...directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active
not only conferred cytoprotection of H
O
-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds,
exhibited higher cytoprotective and neuroprotective potential
and
Overall, our findings showed compound
could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.
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