Annealing effects on the structure characteristics and the digestibility of corn starch (CS)/corn oil (oil)/lysine mixture were investigated. The objective of this study was to provide guidance for ...designing higher slowly digestible starch. Confocal laser confirmed that lysine adhered to granules surface. The interactions among starch, corn oil and lysine were further investigated by using X-ray diffraction (XRD), differential scanning calorimetry (DSC) and rapid visco analyzer (RVA). After annealing treatment, in vitro digestion studies showed that the content of slowly digestible starch increased in the mixture blended with corn oil and lysine. The physical barrier of lysine, amylose-lipid complex and starch-oil-lysine three-dimensional network can provide resistance to digestive enzymes. Annealing with corn oil and lysine can be a good prospect for the efficient modification of in vitro digestibility of starch.
Current approaches to fabrication of nSC composites for bone tissue engineering (BTE) have limited capacity to achieve uniform surface functionalization while replicating the complex architecture and ...bioactivity of native bone, compromising application of these nanocomposites for in situ bone regeneration. A robust biosilicification strategy is reported to impart a uniform and stable osteoinductive surface to porous collagen scaffolds. The resultant nSC composites possess a native‐bone‐like porous structure and a nanosilica coating. The osteoinductivity of the nSC scaffolds is strongly dependent on the surface roughness and silicon content in the silica coating. Notably, without the use of exogenous cells and growth factors (GFs), the nSC scaffolds induce successful repair of a critical‐sized calvarium defect in a rabbit model. It is revealed that topographic and chemical cues presented by nSC scaffolds could synergistically activate multiple signaling pathways related to mesenchymal stem cell recruitment and bone regeneration. Thus, this facile surface biosilicification approach could be valuable by enabling production of BTE scaffolds with large sizes, complex porous structures, and varied osteoinductivity. The nanosilica‐functionalized scaffolds can be implanted via a cell/GF‐free, one‐step surgery for in situ bone regeneration, thus demonstrating high potential for clinical translation in treatment of massive bone defects.
A biosilicification strategy is developed to provide a uniform and robust osteoinductive surface on porous natural collagen scaffolds. The resultant nanosilica–collagen (nSC) scaffolds possess topographical and chemical cues for superior in situ bone defect repair, without the use of exogenous cells or growth factors. This novel preparation of biomimetic bone scaffolds shows promising clinical applications in the treatment of bone defects.
Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the ...relationship between AF and serum electrolytes remains unclear.
A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association.
In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively.
Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Identifying the authenticity of library intelligence has consistently posed a significant challenge in intelligence management. This paper aims to optimize the D-S evidence theory to address the ...issues of uncertainty, imprecision, and high conflict in library intelligence evidence fusion. To achieve this, DSmT is employed to extend the D-S evidence theory by eliminating the process of assigning conflicting information with normalization coefficients. Then, through the fuzzy information pseudo-feature analysis method, the library intelligent intelligence information entropy feature quantity is extracted, and semantic feature matching is used to construct the library intelligent intelligence true and false information recognition system. Finally, the recognition performance of the system is examined using a dataset to analyze the intelligence authenticity recognition of mis-spliced bacterial colony genomic data from a biological experiment that has been entered into the library intelligence database. Finally, it was found that the average recognition rate of this paper's system in the four classical datasets is 96.57%, which is higher than the 89.61% and 90.02% of the two evidence fusion classification schemes. The results of this paper's algorithm for high-conflict evidence are 0.9506, 0.0558, and 0.0097, reflecting the accuracy of the evidence support results. Finally, 35 colony genome splicing error intelligence were identified, of which 32 were genuine errors, with a precision rate of 91% and a recall rate of 94%. The library intelligence authenticity recognition system designed in this paper has excellent performance and provides an effective path and usable algorithmic model for library intelligence authentication.
Abstract
Oxidative allylic C–H functionalization is a powerful tool to streamline organic synthesis as it minimizes the need for functional group activation and generates alkenyl-substituted products ...amenable to further chemical modifications. The intramolecular variants can be used to construct functionalized ring structures but remain limited in scope and by their frequent requirement for noble metal catalysts and stoichiometric chemical oxidants. Here we report an oxidant-free, electrocatalytic approach to achieve intramolecular oxidative allylic C–H amination and alkylation by employing tailored cobalt-salen complexes as catalysts. These reactions proceed through a radical mechanism and display broad tolerance of functional groups and alkene substitution patterns, allowing efficient coupling of di-, tri- and even tetrasubstituted alkenes with N- and C-nucleophiles to furnish high-value heterocyclic and carbocyclic structures.
Osteocytes, entrapped within the mineralized bone matrix, has been found to have numerous functions such as acting as an orchestrator of bone remodeling through regulation of both osteoclast and ...osteoblast activity and also functioning as an endocrine cell. Due to a specialized morphology and surrounding structure, osteocytes are more tolerant to hypoxia during osteoporosis, fracture, osteoarthritis, and orthodontic–orthognathic combination therapy. Hypoxia‐inducible factor‐1α (HIF‐1α) is one of the master regulators of hypoxia reactions, playing an important role in bone modeling, remodeling, and homeostasis. This study aimed to investigate the pivotal functional role of HIF‐1α in osteocytes initiating of bone remodeling under hypoxia. In the present study, the osteoclasts formation induced by RAW264.7 was significantly promoted in conditioned media (CM) from osteocytic MLO‐Y4 exposed to hypoxia in vitro. Therefore, hypoxic MLO‐Y4 cells simulated by 100 μmol/L CoCl2 or 2% O2 stably expressed HIF‐1α proteins and upregulated the expression of receptor activator of nuclear factor‐κB ligand (RANKL) at both the messenger RNA (mRNA) and protein level. Furthermore, with the Knockdown of HIF‐1α, the expression of RANKL mRNA and protein decreased after transient transfection. In addition, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription (STAT3) was also correlated with HIF‐1α and RANKL levels under hypoxia. Then AG490, a JAK2 inhibitor, inhibited p‐JAK2, p‐STAT3 and RANKL expression. It was possible that AG490 disturbed the contact of HIF‐1α and RANKL by JAK2/STAT3 pathway, influencing osteoclastogenesis. Our findings suggested that HIF‐1α promoted the expression of RANKL by activating JAK2/STAT3 pathway in MLO‐Y4 cells, and enhanced osteocyte‐mediated osteoclastic differentiation in vitro.
Recent studies have revealed a role for macrophages and neutrophils in limiting chemotherapy efficacy; however, the mechanisms underlying the therapeutic benefit of myeloid-targeting agents in ...combination with chemotherapy are incompletely understood. Here, we show that targeting tumour-associated macrophages by colony-stimulating factor-1 receptor (CSF-1R) blockade in the K14cre;Cdh1
;Trp53
transgenic mouse model for breast cancer stimulates intratumoural type I interferon (IFN) signalling, which enhances the anticancer efficacy of platinum-based chemotherapeutics. Notably, anti-CSF-1R treatment also increased intratumoural expression of type I IFN-stimulated genes in patients with cancer, confirming that CSF-1R blockade is a powerful strategy to trigger an intratumoural type I IFN response. By inducing an inflamed, type I IFN-enriched tumour microenvironment and by further targeting immunosuppressive neutrophils during cisplatin therapy, antitumour immunity was activated in this poorly immunogenic breast cancer mouse model. These data illustrate the importance of breaching multiple layers of immunosuppression during cytotoxic therapy to successfully engage antitumour immunity in breast cancer.
Computerized detection of voice disorders has attracted considerable academic and clinical interest in the hope of providing an effective screening method for voice diseases before endoscopic ...confirmation. This study proposes a deep-learning-based approach to detect pathological voice and examines its performance and utility compared with other automatic classification algorithms.
This study retrospectively collected 60 normal voice samples and 402 pathological voice samples of 8 common clinical voice disorders in a voice clinic of a tertiary teaching hospital. We extracted Mel frequency cepstral coefficients from 3-second samples of a sustained vowel. The performances of three machine learning algorithms, namely, deep neural network (DNN), support vector machine, and Gaussian mixture model, were evaluated based on a fivefold cross-validation. Collective cases from the voice disorder database of MEEI (Massachusetts Eye and Ear Infirmary) were used to verify the performance of the classification mechanisms.
The experimental results demonstrated that DNN outperforms Gaussian mixture model and support vector machine. Its accuracy in detecting voice pathologies reached 94.26% and 90.52% in male and female subjects, based on three representative Mel frequency cepstral coefficient features. When applied to the MEEI database for validation, the DNN also achieved a higher accuracy (99.32%) than the other two classification algorithms.
By stacking several layers of neurons with optimized weights, the proposed DNN algorithm can fully utilize the acoustic features and efficiently differentiate between normal and pathological voice samples. Based on this pilot study, future research may proceed to explore more application of DNN from laboratory and clinical perspectives.
After an infection, pathogen-specific tissue-resident memory T cells (TRM cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create TRM ...cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how TRM cells provide such pathogen protection. Here, we demonstrate that activated TRM cells in mouse skin profoundly alter the local tissue environment by inducing a number of broadly active antiviral and antibacterial genes. This “pathogen alert” allows skin TRM cells to protect against an antigenically unrelated virus. These data describe a mechanism by which tissue-resident memory CD8⁺ T cells protect previously infected sites that is rapid, amplifies the activation of a small number of cells into an organ-wide response, and has the capacity to control escape variants.
The KRAS oncoprotein, a critical driver in 33% of lung adenocarcinoma (LUAD), has remained an elusive clinical target due to its perceived undruggable nature. The identification of dependencies borne ...through common co-occurring mutations are sought to more effectively target KRAS-mutant lung cancer. Approximately 20% of KRAS-mutant LUAD carry loss-of-function mutations in KEAP1, a negative regulator of the antioxidant response transcription factor NFE2L2/NRF2. We demonstrate that Keap1-deficient Kras
lung tumors arise from a bronchiolar cell-of-origin, lacking pro-tumorigenic macrophages observed in tumors originating from alveolar cells. Keap1 loss activates the pentose phosphate pathway, inhibition of which, using 6-AN, abrogated tumor growth. These studies highlight alternative therapeutic approaches to specifically target this unique subset of KRAS-mutant LUAD cancers.