Discovery of a novel flavonol O-methyltransferase possessing sequential 4'- and 7-O-methyltransferase activity from Camptotheca acuminata Decne.

The biosynthetic route for flavonol in Camptotheca acuminata has been recently elucidated from a chemical point of view. However, the genes involved in flavonol methylation remain unclear. It is a critical step for fully uncovering the flavonol metabolism in this ancient plant. In this study, the multi-omics resource of this plant was utilized to perform flavonol O-methyltransferase-oriented mining and screening. Two genes, CaFOMT1 and CaFOMT2 are identified, and their recombinant CaFOMT proteins are purified to homogeneity. CaFOMT1 exhibits strict substrate and catalytic position specificity for quercetin, and selectively methylates only the 4'-OH group. CaFOMT2 possesses sequential O-methyltransferase activity for the 4'-OH and 7-OH of quercetin. These CaFOMT genes are enriched in the leaf and root tissues. The catalytic dyad and critical substrate-binding sites of the CaFOMTs are determined by molecular docking and further verified through site-mutation experiments. PHE181 and MET185 are designated as the critical sites for flavonol substrate selectivity. Genomic environment analysis indicates that CaFOMTs evolved independently and that their ancestral genes are different from that of the known Ca10OMT. This study provides molecular insights into the substrate-binding pockets of two new CaFOMTs responsible for flavonol metabolism in C. acuminata.

Proteomic Profiling of SGLT-2 Inhibitor Canagliflozin in a Swine Model of Chronic Myocardial Ischemia.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to be cardioprotective independent of glucose control, but the mechanisms of these benefits are unclear. We previously demonstrated improved cardiac function and decreased fibrosis in a swine model of chronic myocardial ischemia. The goal of this study is to use high-sensitivity proteomic analyses to characterize specific molecular pathways affected by SGLT-2 inhibitor canagliflozin (CAN) therapy in a swine model of chronic myocardial ischemia. METHODS: Chronic myocardial ischemia was induced in sixteen Yorkshire swine via the placement of an ameroid constrictor to the left circumflex coronary artery. After two weeks of recovery, swine received either 300 mg of CAN daily (n = 8) or a control (n = 8). After five weeks of therapy, the group of swine were euthanized, and left ventricular tissue was harvested and sent for proteomic analysis. RESULTS: Total proteomic analysis identified a total of 3256 proteins between the CAN and control groups. Three hundred and five proteins were statistically different. This included 55 proteins that were downregulated (p < 0.05, fold change <0.5) and 250 that were upregulated (p < 0.05, fold change >2) with CAN treatment. Pathway analysis demonstrated the upregulation of several proteins involved in metabolism and redox activity in the CAN-treated group. The CAN group also exhibited a downregulation of proteins involved in motor activity and cytoskeletal structure. CONCLUSIONS: In our swine model of chronic myocardial ischemia, CAN therapy alters several proteins involved in critical molecular pathways, including redox regulation and metabolism. These findings provide additional mechanistic insights into the cardioprotective effects of canagliflozin.

Wearable and interactive multicolored photochromic fiber display.

Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human-machine integration.

Association of the visceral adiposity index with femur bone mineral density and osteoporosis among the U.S. older adults from NHANES 2005-2020: a cross-sectional study.

Background: The visceral adiposity index (VAI) is a marker of abdominal fat distribution and adipose tissue function. However, the association between VAI and femur bone mineral density (BMD) and osteoporosis is unclear among the U.S. older adults. Methods: Cross-sectional data for adults aged 60 years and older from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included. Multivariable linear and logistic regression were used to evaluate the association between VAI and femur BMD and osteoporosis. We used the smooth curve fitting to address nonlinearity. Moreover, a two-piecewise linear regression model was used to explain the nonlinearity further. Results: The findings of the multivariable logistic regression models showed that as the VAI value increased by one unit, the prevalence of osteoporosis decreased by 1.2% after adjusting for covariates associated with osteoporosis. The multivariable linear regression models demonstrated that VAI was positively correlated with femur BMD. Further analysis revealed an inverted L-shaped and inverted U-shaped relationship between VAI and femur BMD at different sites. Conclusions: Our findings indicated that an increased VAI is independently linked to a higher prevalence of osteoporosis among the U.S. older adults. Further analysis reveals that once VAI reaches a certain threshold, femur BMD no longer increases and may even decrease. This suggests that a moderate accumulation of visceral fat may be beneficial for bone health, while excessive visceral fat could potentially have detrimental effects.

Visible-light-enabled cascade cross-dehydrogenative-coupling/cyclization to construct α-chromone substituted α-amino acid derivatives.

Organophotocatalytic cascade cross-dehydrogenative-coupling/cyclization reaction of o-hydroxyarylenaminones with α-amino acid derivatives for the construction of α-chromone substituted α-amino acid derivatives was developed. Various N-arylglycine esters, amides and dipeptides underwent the cascade cyclization reaction well with o-hydroxyarylenaminones to afford the corresponding 3-aminoalkyl chromones in good to excellent yields. This approach consists of visible-light-promoted oxidation of α-amino acid derivatives, the Mannich reaction, and intramolecular nucleophilic cyclization under acidic conditions, and features a wide reaction scope, a simple operation and mild reaction conditions, which may have the potential to be used for the synthesis of bioactive molecules.

A novel RNA modification prognostic signature for predicting the characteristics of the tumor microenvironment in gastric cancer.

Gastric cancer (GC) is one of the most common neoplastic malignancies, which permutes a fourth of cancer-related mortality globally. RNA modification plays a significant role in tumorigenesis, the underlying molecular mechanism of how different RNA modifications directly affect the tumor microenvironment (TME) in GC is unclear. Here, we profiled the genetic and transcriptional alterations of RNA modification genes (RMGs) in GC samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Through the unsupervised clustering algorithm, we identified three distinct RNA modification clusters and found that they participate in different biological pathways and starkly correlate with the clinicopathological characteristics, immune cell infiltration, and prognosis of GC patients. Subsequently, univariate Cox regression analysis unveiled 298 of 684 subtype-related differentially expressed genes (DEGs) are tightly interwoven to prognosis. In addition, we conducted the principal component analysis to develop the RM_Score system, which was used to quantify and predict the prognostic value of RNA modification in GC. Our analysis indicated that patients with high RM_Score were characterized by higher tumor mutational burden, mutation frequency, and microsatellite instability which were more susceptible to immunotherapy and had a favorable prognosis. Altogether, our study uncovered RNA modification signatures that may have a potential role in the TME and prediction of clinicopathological characteristics. Identification of these RNA modifications may provide a new understanding of immunotherapy strategies for gastric cancer.

Reduction in Nitrogen Rate and Improvement of Nitrogen Use Efficiency without Loss of Peanut Yield by Regional Mean Optimal Rate of Chemical Fertilizer Based on a Multi-Site Field Experiment in the North China Plain.

It is important to quantify nutrient requirements and optimize fertilization to improve peanut yield and fertilizer use efficiency. In this study, a multi-site field trial was conducted from 2020 to 2021 in the North China Plain to estimate nitrogen (N), phosphorus (P), and potassium (K) uptake and requirements of peanuts, and to evaluate the effects of fertilization recommendations from the regional mean optimal rate (RMOR) on dry matter, pod yield, nutrient uptake, and fertilizer use efficiency. Results show that compared with farmer practice fertilization (FP), optimal fertilization (OPT) based on the RMOR increased peanut dry matter by 6.6% and pod yield by 10.9%. The average uptake rates of N, P, and K were 214.3, 23.3, and 78.4 kg/ha, respectively, with 76.0% N harvest index, 59.8% P harvest index, and 41.4% K harvest index. The OPT treatment increased N, P, and K uptake by 19.3%, 7.3%, and 11.0% compared with FP, respectively. However, the average of yield, nutrition uptake, and harvest indexes of N, P, and K were not significantly affected by fertilization. The peanut required 42.0 kg N, 4.6 kg P, and 15.3 kg K to produce 1000 kg of pods. The OPT treatment significantly improved the N partial factor productivity and N uptake efficiency but decreased the K partial factor productivity and K uptake efficiency. The present study demonstrates that fertilizer recommendations from RMOR improve N use efficiency, and reduce N and P fertilizer application without yield loss in regions with smallholder farmers, and the corresponding estimation of nutrient requirements helps to make peanut fertilization recommendations.

Prospective assessment of pancreatic ductal adenocarcinoma diagnosis from endoscopic ultrasonography images with the assistance of deep learning.

BACKGROUND: Endosonographers are highly dependent on the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to develop a deep-learning radiomics (DLR) model based on endoscopic ultrasonography (EUS) images for identifying PDAC and to explore its true clinical benefit. METHODS: A retrospective data set of EUS images that included PDAC and benign lesions was used as a training cohort (N = 368 patients) to develop the DLR model, and a prospective data set was used as a test cohort (N = 123 patients) to validate the effectiveness of the DLR model. In addition, seven endosonographers performed two rounds of reader studies on the test cohort with or without DLR assistance to further assess the clinical applicability and true benefits of the DLR model. RESULTS: In the prospective test cohort, DLR exhibited an area under the receiver operating characteristic curves of 0.936 (95% confidence interval [CI], 0.889-0.976) with a sensitivity of 0.831 (95% CI, 0.746-0.913) and 0.904 (95% CI, 0.820-0.980), respectively. With DLR assistance, the overall diagnostic performance of the seven endosonographers improved: one endosonographer achieved a significant expansion of specificity (p = .035,) and another achieved a significant increase in sensitivity (p = .038). In the junior endosonographer group, the diagnostic performance with the help of the DLR was higher than or comparable to that of the senior endosonographer group without DLR assistance. CONCLUSIONS: A prospective test cohort validated that the DLR model based on EUS images effectively identified PDAC. With the assistance of this model, the gap between endosonographers at different levels of experience narrowed, and the accuracy of endosonographers expanded.

Activity and mechanism of vanadium sulfide for organic contaminants oxidation with peroxymonosulfate.

Transition metal sulfides have been demonstrated to be effective for peroxymonosulfate (PMS) activation towards wastewater treatment. However, the activity of vanadium sulfide (VS4) and the role of the chemical state of V have not been revealed. Here, three types of VS4 with various morphologies and chemical states of V were synthesized by using methanol (M-VS4, nanosphere composed of nanosheets), ethanol (E-VS4, sea urchin like nanosphere) and ultrapure water (U-VS4, compact nanosphere) as hydrothermal solvent, respectively, and used as heterogeneous catalysts to activate PMS for the degradation of refractory organic pollutants. The effects of PMS concentration, temperature, pH, inorganic ions, and humic acid (HA) on the degradation efficiency of VS4/PMS system were investigated systematically. The results indicated that the highest specific surface area and lowest ratio of V5+ enable E-VS4/PMS system possessed the highest performance in degrading tetracycline hydrochloride (TCH), in which 100% TCH was removed after operating 10 min (0.805 min-1) under a relatively low concentration of PMS (1 mM) and catalyst (100 mg/L). It also revealed that the system exhibited a typical radical process in TCH degradation, which could be attributed to the redox cycles between V5+, V4+ and V3+ in the presence of PMS to generate various radicals. This radical process enabled the E-VS4/PMS system with a high activity in wide reaction conditions and high mineralization ratios in degrading various refractory organic pollutants within 10 min. In addition, the E-VS4/PMS system exhibited favorable reusability and stability with very less V and S ions leaching, and showed excellent performance in real water purification.

Metabolite Profiling of Wheat Response to Cultivar Improvement and Nitrogen Fertilizer.

Both genetic improvement and the application of N fertilizer increase the quality and yields of wheat. However, the molecular kinetics that underlies the differences between them are not well understood. In this study, we performed a non-targeted metabolomic analysis on wheat cultivars from different release years to comprehensively investigate the metabolic differences between cultivar and N treatments. The results revealed that the plant height and tiller number steadily decreased with increased ears numbers, whereas the grain number and weight increased with genetic improvement. Following the addition of N fertilizer, the panicle numbers and grain weights increased in an old cultivar, whereas the panicle number and grain number per panicle increased in a modern cultivar. For the 1950s to 2010s cultivar, the yield increases due to genetic improvements ranged from -1.9% to 96.7%, whereas that of N application ranged from 19.1% to 81.6%. Based on the untargeted metabolomics approach, the findings demonstrated that genetic improvements induced 1.4 to 7.4 times more metabolic alterations than N fertilizer supply. After the addition of N, 69.6%, 29.4%, and 33.3% of the differential metabolites were upregulated in the 1950s, 1980s, and 2010s cultivars, respectively. The results of metabolic pathway analysis of the identified differential metabolites via genetic improvement indicated enrichment in 1-2 KEGG pathways, whereas the application of N fertilizer enriched 2-4 pathways. Our results provide new insights into the molecular mechanisms of wheat quality and grain yield developments.

Formulation and Characterisation of Carbamazepine Orodispersible 3D-Printed Mini-Tablets for Paediatric Use.

One of the main challenges to paediatric drug administration is swallowing difficulties, hindering the acceptability of the medicine and hence clinical outcomes. This study aims at developing a child-appropriate dosage form, the orodispersible mini-tablet (ODMT), using the model drug carbamazepine (CBZ). This dosage form was prepared and 3D-printed via a semi-solid extrusion technique. Design of Experiment methods were applied for optimising the formulation. The formulation with 40% (w/w) of SSG (superdisintegrant) and 5% (w/w) of PVP K30 (binder) was selected and loaded with CBZ. The drug-loaded tablets were characterised by a mean hardness of 18.5 N and a disintegrating time of 84 s, along with acceptable friability. The mean drug loading ratio of the tablets was tested as 90.56%, and the drug release rate in 0.1 M HCl reached 68.3% at 45 min. Excipients showed proper compatibility with the drug in physical form analysis. Taste assessment via an E-tongue was also conducted, where the drug did not show bitter taste signals at a low concentration in the taste assessment, and the sweetener also blocked bitterness signals in the testing. To this end, ODMTs were found to be potential candidates for child-appropriate dosage forms delivering CBZ.

Constructing Escherichia coli co-display systems for biodegradation of polyethylene terephthalate.

BACKGROUND: The accumulation of fast-growing polyethylene terephthalate (PET) wastes has posed numerous threats to the environments and human health. Enzymatic degradation of PET is a promising approach for PET waste treatment. Currently, the efficiency of various PET biodegradation systems requires further improvements. RESULTS: In this work, we engineered whole cell systems with co-display of strong adhesive proteins and the most active PETase for PET biodegradation in E. coli cells. Adhesive proteins of cp52k and mfp-3 and Fast-PETase were simultaneously displayed on the surfaces of E. coli cells, and the resulting cells displaying mfp-3 showed 50% increase of adhesion ability compared to those without adhesive proteins. Consequently, the degradation rate of E. coli cells co-displaying mfp-3 and Fast-PETase for amorphous PET exceeded 15% within 24 h, exhibiting fast and thorough PET degradation. CONCLUSIONS: Through the engineering of co-display systems in E. coli cells, PET degradation efficiency was significantly increased compared to E. coli cells with sole display of Fast-PETase and free enzyme. This feasible E. coli co-display system could be served as a convenient tool for extending the treatment options for PET biodegradation.

Imperceptible, designable, and scalable braided electronic cord.

Flexible sensors, friendly interfaces, and intelligent recognition are important in the research of novel human-computer interaction and the development of smart devices. However, major challenges are still encountered in designing user-centered smart devices with natural, convenient, and efficient interfaces. Inspired by the characteristics of textile-based flexible electronic sensors, in this article, we report a braided electronic cord with a low-cost, and automated fabrication to realize imperceptible, designable, and scalable user interfaces. The braided electronic cord is in a miniaturized form, which is suitable for being integrated with various occasions in life. To achieve high-precision interaction, a multi-feature fusion algorithm is designed to recognize gestures of different positions, different contact areas, and different movements performed on a single braided electronic cord. The recognized action results are fed back to varieties of interactive terminals, which show the diversity of cord forms and applications. Our braided electronic cord with the features of user friendliness, excellent durability and rich interaction mode will greatly promote the development of human-machine integration in the future.

Fabric computing: Concepts, opportunities, and challenges.

With the advent of the Internet of Everything, people can easily interact with their environments immersively. The idea of pervasive computing is becoming a reality, but due to the inconvenience of carrying silicon-based entities and a lack of fine-grained sensing capabilities for human-computer interaction, it is difficult to ensure comfort, esthetics, and privacy in smart spaces. Motivated by the rapid developments in intelligent fabric technology in the post-Moore era, we propose a novel computing approach that creates a paradigm shift driven by fabric computing and advocate a new concept of non-chip sensing in living spaces. We discuss the core notion and benefits of fabric computing, including its implementation, challenges, and future research opportunities.

Combining Enzyme and Photoredox Catalysis for the Construction of 3-Aminoalkyl Chromones.

Herein, we reported a practical and efficient strategy combining photoredox and enzyme catalysis for the construction of 3-aminoalkyl chromones from o-hydroxyaryl enaminones and N-arylglycine esters. A variety of 3-aminoalkyl chromones were synthesized with good yields under mild conditions in one pot. This synthetic protocol consists of sequential enzymatic hydrolysis and photoredox decarboxylation of N-arylglycine esters, oxidation of aminoalkyl radicals, Mannich reaction, and intramolecular nucleophilic cyclization, which affords a convenient pathway for the preparation of various 3-substituted chromones.

Characterization of pyruvate metabolism and citric acid cycle patterns predicts response to immunotherapeutic and ferroptosis in gastric cancer.

BACKGROUND: Gastric cancer is one of the most common malignancies of the digestive system with a high lethal rate. Studies have shown that inherited and acquired mutations in pyruvate metabolism and citric acid cycle (P-CA) enzymes are involved in tumorigenesis and tumor development. However, it is unclear how different P-CA patterns affect the tumor microenvironment (TME), which is critical for cancer progression. METHODS: This study mainly concentrated on investigating the role of the P-CA patterns in multicellular immune cell infiltration of GC TME. First, the expression levels of P-CA regulators were profiled in GC samples from The Cancer Genome Atlas and Gene Expression Omnibus cohorts to construct a consensus clustering analysis and identify three distinct P-CA clusters. GSVA was conducted to reveal the different biological processes in three P-CA clusters. Subsequently, 1127 cluster-related differentially expressed genes were identified, and prognostic-related genes were screened using univariate Cox regression analysis. A scoring system was then set up to quantify the P-CA gene signature and further evaluate the response of the patients to the immunotherapy. RESULTS: We found that GC patients in the high P-CA score group had a higher tumor mutational burden, higher microsatellite instability, and better prognosis. The opposite was observed in the low P-CA score group. Interestingly, we demonstrated P-CA gene cluster could predict the sensitivity to immunotherapy and ferroptosis-induced therapy. CONCLUSION: Collectively, the P-CA gene signature in this study exhibits potential roles in the tumor microenvironment and predicts the response to immunotherapeutic. The identification of these P-CA patterns may significantly accelerate the strategic development of immunotherapy for GC.

Development of a novel autophagy-related gene model for gastric cancer prognostic prediction.

Gastric cancer (GC) is a major global health issue and one of the leading causes of tumor-associated mortality worldwide. Autophagy is thought to play a critical role in the development and progression of GC, and this process is controlled by a set of conserved regulators termed autophagy-related genes (ATGs). However, the complex contribution of autophagy to cancers is not completely understood. Accordingly, we aimed to develop a prognostic model based on the specific role of ATGs in GC to improve the prediction of GC outcomes. First, we screened 148 differentially expressed ATGs between GC and normal tissues in The Cancer Genome Atlas (TCGA) cohort. Consensus clustering in these ATGs was performed, and based on that, 343 patients were grouped into two clusters. According to Kaplan-Meier survival analysis, cluster C2 had a worse prognosis than cluster C1. Then, a disease risk model incorporating nine differentially expressed ATGs was constructed based on the least absolute shrinkage and selection operator (LASSO) regression analysis, and the ability of this model to stratify patients into high- and low-risk groups was verified. The predictive value of the model was confirmed using both training and validation cohorts. In addition, the results of functional enrichment analysis suggested that GC risk is correlated with immune status. Moreover, autophagy inhibition increased sensitivity to cisplatin and exacerbated reactive oxygen species accumulation in GC cell lines. Collectively, the results indicated that this novel constructed risk model is an effective and reliable tool for predicting GC outcomes and could help with individual treatment through ATG targeting.

Associations of Abdominal Visceral Fat Content and Plasma Adiponectin Level With Intracranial Atherosclerotic Stenosis: A Cross-Sectional Study.

Background: Abdominal obesity and adipocytokines are closely related to atherosclerosis, and adiponectin level is considered one of the important clinical indicators. This study aimed to analyze the associations of abdominal visceral fat content and adiponectin level with intracranial atherosclerotic stenosis (ICAS). Methods: A total of 186 patients were enrolled in this study. Patients were distributed into ICAS and non-ICAS by the degree of artery stenosis. Plasma adiponectin levels and the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) were measured. The related factors of intracranial atherosclerotic stenosis were determined using multivariable logistic regression analysis. Results: The VAT/SAT ratio (OR, 26.08; 95% CI, 5.92-114.83; p < 0.001) and adiponectin (OR, 0.61; 95% CI, 0.44-0.84; p = 0.002) were found to be the independent predictors of ICAS in a multivariable logistic regression analysis. The prevalence of ICAS increased (T1: 27.4%; T2: 50.0%; T3: 75.8%) as the VAT/SAT ratio tertile increased (p < 0.001). The prevalence of ICAS decreased (T1: 72.6%; T2: 54.8%; T3: 25.8%) as the adiponectin tertile increased (p < 0.001). In ROC curves analysis, VAT/SAT ratio had a sensible accuracy for the prediction of ICAS. The optimal cut-off value of VAT/SAT ratio to predict ICAS in this study was 1.04 (AUC: 0.747; p < 0.001; sensitivity: 67.4%; specificity: 74.7%). The optimal adiponectin cutoff was 3.03 ug/ml (AUC: 0.716; p < 0.001; sensitivity:75.8%; specificity: 61.5%). Conclusion: Higher VAT/SAT ratio and lower plasma adiponectin levels were closely related to the increased risk of intracranial atherosclerotic stenosis.