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The hypoxic microenvironment in esophageal carcinoma is an important factor promoting the rapid progression of malignant tumor. This study was to investigate the lactylation of Axin1 ...on glycolysis in esophageal carcinoma cells under hypoxia exposure. Hypoxia treatment increases pan lysine lactylation (pan-kla) levels of both TE1 and EC109 cells. Meanwhile, ECAR, glucose consumption and lactate production were also upregulated in both TE1 and EC109 cells. The expression of embryonic stem cell transcription factors NANOG and SOX2 were enhanced in the hypoxia-treated cells. Axin1 overexpression partly reverses the induction effects of hypoxia treatment in TE1 and EC109 cells. Moreover, lactylation of Axin1 protein at K147 induced by hypoxia treatment promotes ubiquitination modification of Axin1 protein to promote glycolysis and cell stemness of TE1 and EC109 cells. Mutant Axin1 can inhibit ECAR, glucose uptake, lactate secretion, and cell stemness in TE1 and EC109 cells under normal or hypoxia conditions. Meanwhile, mutant Axin1 further enhanced the effects of 2-DG on inhibiting glycolysis and cell stemness. Overexpression of Axin1 also inhibited tumor growth in vivo, and was related to suppressing glycolysis. In conclusion, hypoxia treatment promoted the glycolysis and cell stemness of esophageal carcinoma cells, and increased the lactylation of Axin1 protein. Overexpression of Axin1 functioned as a glycolysis inhibitor, and suppressed the effects of hypoxia exposure in vitro and inhibited tumor growth in vivo. Mechanically, hypoxia induces the lactylation of Axin1 protein and promotes the ubiquitination of Axin1 to degrade the protein, thereby exercising its anti-glycolytic function.
Mesenchymal stem cells (MSCs) are important cell sources in cartilage tissue development and homeostasis, and multiple strategies have been developed to improve MSCs chondrogenic differentiation with ...an aim of promoting cartilage regeneration. Here we report the effects of combining nanosecond pulsed electric fields (nsPEFs) followed by treatment with ghrelin (a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs. nsPEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs, and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined, which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats. We further found that nsPEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway. Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway, and RNA-seq results indicated 243 genes were regulated, and JAK-STAT signaling pathway was involved. Interestingly, the sequential order of applying these two stimuli is critical, with nsPEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo, but not vice versa. This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies.
Flexible wearable hydrogel devices show great potential for applications in human health monitoring. However, facile preparation procedures, reliability when defects are present, and the realization ...of actual wearable devices are still severe challenges. This work presents a facile method to prepare a reliable nanocomposite organohydrogel (NCO hydrogel) strain sensor and the corresponding flexible wearable device for long-term monitoring of outdoor human motion. The NCO hydrogel was facilely prepared through the
in situ
free radical polymerization of acrylic acid in a clay suspension, followed by immersion of the hydrogel in glycerol. The hydrogel shows excellent notch insensitivity, universal adhesion and environmental tolerance. More importantly, the hydrogel strain sensor with different notch lengths can still output steady electrical signals similar to that of the unnotched sensor, which shows favorable reliability required in actual applications. We designed a portable wearable device by attaching the NCO hydrogel to the substrate and connecting it to a Bluetooth module for the long-term outdoor monitoring of human motion. Various human physical motions can be recorded by the device and real-time displayed through an APP on a mobile phone. A two-level fully connected neural network (FCNN) was used to perform the classification and recognition of different motions through deep learning with a classification accuracy of 87%. The accuracy does not decrease even with a notch on the hydrogel sensor. We have provided a new approach to prepare actual reliable wearable devices through functional hydrogels for long-term outdoor human motion monitoring and recognition in the human health field.
A notch-insensitive and environment tolerant PAA-clay-glycerol organohydrogel strain sensor was facilely prepared and assembled to obtain an integrated wearable device for long-term human motion monitoring and classification.
As with the continuous improvement of the workshop automation rate and the importance in energy consumption, more and more enterprises not only need to make scheduling decision on production ...equipment, but also need to consider whether the scheduling of transportation equipment supports scheduling decisions on workshop production. At the same time, because both workshop production scheduling decision and transportation scheduling decision are NP-hard problems, it is necessary to design an efficient algorithm to improve productivity of the workshop. In order to solve this problem, firstly, based on the analysis of the problem structure, production environment and optimization objectives, a "manufacturing-transportation" multi-objective joint scheduling optimization mathematical model is established. By converting the energy consumption into the total transportation time objective of the transportation equipment, both total transportation time and makespan are taken as the optimization objectives. Secondly, based on the design idea of memetic algorithm (MA), non-dominated sorting genetic algorithm-Ⅱ(NSGA-II) is employed as the basis framework of our new developed algorithm. An effective discrete encoding scheme of MO-MA, a new initialization method for initial population and a neighborhood search mechanism based on critical path are incorporated into our new proposed algorithm. Then the parameter design of the algorithm is completed through variance analysis. Finally, the proposed algorithm is compared and analyzed with other algorithms in the dimension of hypervolume and Set Coverage (SC), and advantages of the algorithm in solving this problem are verified.
Molecular Sierpiński triangles (STs), a family of elegant and well-known fractals, can be prepared on surfaces with atomic precision. Up to date, several kinds of intermolecular interactions such as ...hydrogen bond, halogen bond, coordination, and even covalent bond have been employed to construct molecular STs on metal surfaces. Herein a series of defect-free molecular STs have been fabricated via electrostatic attraction between potassium cations and electronically polarized chlorine atoms in 4,4″-dichloro-1,1':3',1″-terphenyl (DCTP) molecules on Cu(111) and Ag(111). The electrostatic interaction is confirmed both experimentally by scanning tunneling microscopy and theoretically by density functional theory calculations. These findings illustrate that electrostatic interaction can serve as an efficient driving force to construct molecular fractals, which enriches our toolbox for the bottom-up fabrication of complex functional supramolecular nanostructures.
Electrons not only serve as a “reactant” in redox reactions but also play a role in “catalyzing” some chemical processes. Despite the significance and ubiquitousness of electron-induced chemistry, ...many related scientific issues still await further exploration, among which is the impact of molecular assembly. In this work, microscopic insights into the vital role of molecular assembly in tweaking the electron-induced surface chemistry are unfolded by combined scanning tunneling microscopy and density functional theory studies. It is shown that the selective dissociation of a C–Cl bond in 4,4″-dichloro-1,1′:3′,1′′-terphenyl (DCTP) on Cu(111) can be efficiently triggered by an electron injection via the STM tip into the unoccupied molecular orbital. The DCTP molecules are embedded in different assembly structures, including its self-assembly and coassemblies with Br adatoms. The energy threshold for the C–Cl bond cleavage increases as more Br adatoms stay close to the molecule, indicative of the sensitive response of the electron-induced surface reactivity of the C–Cl bond to the subtle change in the molecular assembly. Such a phenomenon is rationalized by the energy shift of the involved unoccupied molecular orbital of DCTP that is embedded in different assemblies. These findings shed new light on the tuning effect of molecular assembly on electron-induced reactions and introduce an efficient approach to precisely steer surface chemistry.
The current study was performed to evaluate the possible protective effects of fucoidan (F) and sodium alginate (SA) against lead-induced oxidative damage in vivo, and to identify relevant underlying ...mechanisms. Health Sprague Dawley (SD) rats were divided into nine groups of ten rats each and treated orally with lead acetate (5 mg/kg, Pb2+) for 4 weeks, then gavaged with DMSA (Meso-2, 3-dimercaptosuccinic acid, 25 mg/kg), F (50, 100, 200 mg/kg) and SA (50, 100, 200 mg/kg) individually after successful modelling. We found that the administration of both F or SA resulted in a beneficial effect by significantly decreasing lead levels (p < 0.05) in the kidneys from 2.85 mg/kg to 0.79 mg/kg and improving antioxidant status (SOD, GSH, and CAT) thereby alleviating lead-induced damage and injury of the liver and kidneys (AST, BUN, and Cr). Both natural extracts exerted dose-dependent effects. Protective effects were further demonstrated by histopathology. Our results demonstrate that the F and SA are effective natural extracts for lead-eliminating, and that they can ameliorate oxidative damage induced by lead toxicity.
•Effects of fucoidan (F) and sodium alginate (SA) on lead-induced oxidative damage studied•Administration of F and SA alleviated lead-induced oxidative damage.•Administration of F and SA ameliorated diminished liver and kidney function.•F and SA are promising antioxidants against lead-induced oxidative stress in rats.
The emergence of COVID-19 and the implementation of preventive measures and behavioral changes have led to a significant decrease in the prevalence of other respiratory viruses. However, the manner ...in which seasonal viruses will reemerge in the absence of COVID-19-related restrictions remains unknown. Starting from October 2021, a substantial increase in the number of patients visiting the designated fever clinics in Beijing was observed, with this trend continuing until January 2022. COVID-19 tests conducted on these patients yielded negative results, while the positivity rate for influenza rose from approximately 8% in October 2021 to over 40% by late January 2022. The cases started to decline after this peak. Data from China CDC confirmed that influenza B is a major pathogen during the season. Sequencing of the viral strain revealed the presence of the Victoria-like lineage of the influenza B strain, with minor variations from the Florida/39/2018 strain. Analysis of the hospitalized patients' characteristics indicated that severe cases were relatively more prevalent among younger individuals, with an average age of 40.9 + or - 24.1 years. Among the seven patients who succumbed to influenza, the average age was 30 + or - 30.1 years. These patients exhibited secondary infections involving either bacterial or fungal pathogens and displayed elevated levels of cell death markers (such as LDH) and coagulation pathway markers (D-dimer). Influenza B represents a significant infection threat and can lead to substantial morbidity and mortality, particularly among young patients. To mitigate morbidity and mortality rates, it is imperative to implement appropriate vaccination and other preventive strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutation of ACAT1 that affects both isoleucine catabolism and ketolysis. There is little information ...available regarding the incidence, newborn screening (NBS), and mutational spectrum of BKTD in China.
We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published data from Chinese BKTD patients. A total of 16,088,190 newborns were screened and 14 patients were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. In total, twenty-nine patients were genetically diagnosed with BKTD, 12 of which were newly identified. Most patients exhibited typical blood acylcarnitine and urinary organic acid profiles. Interestingly, almost all patients (15/16, 94%) showed elevated 3-hydroxybutyrylcarnitine (C4OH) levels. Eighteen patients presented with acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of nine patients were triggered by infections, diarrhea, or an inflammatory response to vaccination. Approximately two-thirds of patients had favorable outcomes, one showed a developmental delay and three died. Twenty-seven distinct variants were identified in ACAT1, among which five were found to be novel.
This study presented the largest series of BKTD cohorts in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by the addition of C4OH to the current panel of 3-hydroxyisovalerylcarnitine and tiglylcarnitine markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in the Chinese population were expanded with five newly identified variants.
In studies on arthritis pain, mice are the most important and frequently-used experimental animal models. Currently, in mouse pain assessment, the artificial observation is highly subjective, and ...common automatic analysis systems utilize single-view video from which the extracted features are not diverse. Therefore, this study aims to develop an efficient mouse arthritis pain assessment system by combining dual-view fusion pose estimation and multi-type motion feature extraction.
First, a video acquisition device is designed and videos of mice with arthritis pain are collected. After mouse image annotation, a dual-view fusion framework for pose estimation is proposed to accurately locate the mouse keypoints. Then, outliers in motion trajectories are detected and corrected through a two-stage search method. On this basis, multi-type motion features are extracted to construct an efficient arthritis pain evaluation system. Finally, the effectiveness of constructed system is verified by evaluating the pain status of experimental mice.
The dual-view fusion pose estimation achieves an average precision of 0.83 and 0.87 in vertical and upward view, respectively. Statistical analysis shows that after arthritis modeling surgery, features with significant differences increases over time, which account for 100% at the 12th week after surgery.
The proposed pain evaluation system obtains a highest classification accuracy of 0.8, indicating its effectiveness in measuring the mouse arthritis pain status.
The development of automated pain assessment system is promising to help promote the research of pain pathology mechanisms and the development of therapeutic drugs.
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