Regulatory roles of long non-coding RNAs in short-term heat stress in adult worker bees.

Long non-coding RNAs (lncRNAs) are crucial modulators of post-transcriptional gene expression regulation, cell fate determination, and disease development. However, lncRNA functions during short-term heat stress in adult worker bees are poorly understood. Here, we performed deep sequencing and bioinformatic analyses of honeybee lncRNAs. RNA interference was performed by using siRNA targeting the most highly expressed lncRNA. The silencing effect on lncRNA and the relative expression levels of seven heat shock protein (HSP) genes, were subsequently examined. Overall, 7,842 lncRNAs and 115 differentially expressed lncRNAs (DELs) were identified in adult worker bees following heat stress exposure. Structural analysis revealed that the overall expression abundance, length of transcripts, exon number, and open reading frames of lncRNAs were lower than those of mRNAs. GO analysis revealed that the target genes were mainly involved in "metabolism," "protein folding," "response to stress," and "signal transduction" pathways. KEGG analysis indicated that the "protein processing in endoplasmic reticulum" and "longevity regulating pathway-multiple species" pathways were most enriched. Quantitative real-time polymerase chain reaction (qRT-PCR) detection of the selected DELs confirmed the reliability of the sequencing data. Moreover, the siRNA experiment indicated that feeding siRNA yielded a silencing efficiency of 77.51% for lncRNA MSTRG.9645.5. Upon silencing this lncRNA, the expression levels of three HSP genes were significantly downregulated (p < 0.05), whereas those of three other HSP genes were significantly upregulated (p < 0.05). Our results provide a new perspective for understanding the regulatory mechanisms of lncRNAs in adult worker bees under short-term heat stress.

Enzyme-Activatable Near-Infrared Photosensitizer with High Enrichment in Tumor Cells Based on a Multi-Effect Design.

Enzyme-activatable near-infrared (NIR) fluorescent probes and photosensitizers (PSs) have emerged as promising tools for molecular imaging and photodynamic therapy (PDT). However, in living organisms selective retention or even enrichment of these reagents after enzymatic activation at or near sites of interest remains a challenging task. Herein, we integrate non-covalent and covalent retention approaches to introduce a novel "1-to-3" multi-effect strategy-one enzymatic stimulus leads to three types of effects-for the design of an enzyme-activatable NIR probe or PS. Using this strategy, we have constructed an alkaline phosphatase (ALP)-activatable NIR fluorogenic probe and a NIR PS, which proved to be selectively activated by ALP to switch on NIR fluorescence or photosensitizing ability, respectively. Additionally, these reagents showed significant enrichment (over 2000-fold) in ALP-overexpressed tumor cells compared to the culture medium, accompanied by massive depletion of intracellular thiols, the major antioxidants in cells. The investigation of this ALP-activatable NIR PS in an in vivo PDT model resulted in complete suppression of HeLa tumors and full recovery of all tested mice. Encouragingly, even a single administration of this NIR PS was sufficient to completely suppress tumors in mice, demonstrating the high potential of this strategy in biomedical applications.

Ion Addition by Electrolysis to Improve the Quantitative Analysis of Bacteria with MALDI-TOF MS.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is commonly applied to the identification of bacteria but rarely used for quantitative detection due to the inhomogeneous crystallization of the matrix leading to the unsatisfactory linear relationship between the sample amount and the mass spectrum signals. Herein, we proposed a noninterference ion addition (NIA) method by electrolysis to improve homogeneous crystallization during the evaporation progress of sample droplets on the target plates. The active metal wire was inserted in the droplet as the anode electrode, and metal ions were released through electrolysis. The directional migration of metal ions under the electric field can hinder the migration of matrix molecules to the boundary and homogenize the matrix crystals by forming spherical crystals. Simultaneously, trace cationic surfactant was added to the droplet for pinning the contact surface to define the circle crystallization region. The metal ions from the anode electrode wire were deposited on the surface of the target plates which served as the cathode. Therefore, ion addition has no interference effect on ionization during MALDI-MS detection. This NIA method benefits the homogeneous crystallization and so improves the quantitative analysis. NIA is suitable for biological samples with different matrices, and bacterial samples could be quantitatively analyzed.

Denoising brain networks using a fixed mathematical phase change in independent component analysis of magnitude-only fMRI data.

Brain networks extracted by independent component analysis (ICA) from magnitude-only fMRI data are usually denoised using various amplitude-based thresholds. By contrast, spatial source phase (SSP) or the phase information of ICA brain networks extracted from complex-valued fMRI data, has provided a simple yet effective way to perform the denoising using a fixed phase change. In this work, we extend the approach to magnitude-only fMRI data to avoid testing various amplitude thresholds for denoising magnitude maps extracted by ICA, as most studies do not save the complex-valued data. The main idea is to generate a mathematical SSP map for a magnitude map using a mapping framework, and the mapping framework is built using complex-valued fMRI data with a known SSP map. Here we leverage the fact that the phase map derived from phase fMRI data has similar phase information to the SSP map. After verifying the use of the magnitude data of complex-valued fMRI, this framework is generalized to work with magnitude-only data, allowing use of our approach even without the availability of the corresponding phase fMRI datasets. We test the proposed method using both simulated and experimental fMRI data including complex-valued data from University of New Mexico and magnitude-only data from Human Connectome Project. The results provide evidence that the mathematical SSP denoising with a fixed phase change is effective for denoising spatial maps from magnitude-only fMRI data in terms of retaining more BOLD-related activity and fewer unwanted voxels, compared with amplitude-based thresholding. The proposed method provides a unified and efficient SSP approach to denoise ICA brain networks in fMRI data.

Successful non-operative management of atrioesophageal fistula after combined therapy of catheter ablation and left atrial appendage closure for atrial fibrillation: A case report.

Atrioesophageal fistula (AEF) is a rare but devastating complication of radiofrequency ablation (RFCA) for atrial fibrillation (AF) and is associated with high mortality rates. Whereas most cases of AEF are treated by emergency surgical interventions, we report a case of paroxysmal AF with AEF after combined therapy of catheter ablation and percutaneous left atrial appendage closure (LAAC), which was treated successfuly without major surgery or esophageal stenting. He was presented 18 days after the procedure, suffering chest pain, fever, and a transient loss of consciousness. Computed tomography (CT) of the chest disclosed a small accumulation of air in the region of the left atrium adjacent to the esophagus, suggesting AEF. Supported by early aggressive antibiotic therapy, pericardial drainage and a fasting state with adequate parenteral nutrition, resulted in improvement of his condition with no recurrence of symptoms. Subsequent chest CT scans confirmed disappearance of the leaked air and the patient was discharged home 28 days after admission with no neurological compromise. Early detection, rapid treatment and constant awareness of potential fatal consequences are prerequisites for successful treatment of this complication and prevention of fatal outcome.

Advances in Biological Control and Resistance Genes of Brassicaceae Clubroot Disease-The Study Case of China.

Clubroot disease is a soil-borne disease caused by Plasmodiophora brassicae. It occurs in cruciferous crops exclusively, and causes serious damage to the economic value of cruciferous crops worldwide. Although different measures have been taken to prevent the spread of clubroot disease, the most fundamental and effective way is to explore and use disease-resistance genes to breed resistant varieties. However, the resistance level of plant hosts is influenced both by environment and pathogen race. In this work, we described clubroot disease in terms of discovery and current distribution, life cycle, and race identification systems; in particular, we summarized recent progress on clubroot control methods and breeding practices for resistant cultivars. With the knowledge of these identified resistance loci and R genes, we discussed feasible strategies for disease-resistance breeding in the future.

Screening of Oral Potential Angiotensin-Converting Enzyme Inhibitory Peptides from Zizyphus jujuba Proteins Based on Gastrointestinal Digestion In Vivo.

Plant proteins are a good source of active peptides, which can exert physiological effects on the body. Predicting the possible activity of plant proteins and obtaining active peptides with oral potential are challenging. In this study, the potential activity of peptides from Zizyphus jujuba proteins after in silico simulated gastrointestinal digestion was predicted using the BIOPEP-UWM™ database. The ACE-inhibitory activity needs to be further investigated. The actual peptides in mouse intestines after the oral administration of Zizyphus jujuba protein were collected and analyzed, 113 Zizyphus jujuba peptides were identified, and 3D-QSAR models of the ACE-inhibitory activity were created and validated using a training set (34 peptides) and a test set (12 peptides). Three peptides, RLPHV, TVKPGL and KALVAP, were screened using the 3D-QSAR model and were found to bind to the active sites of the ACE enzyme, and their IC50 values were determined. Their values were 6.01, 3.81, and 17.06 µM, respectively. The in vitro digestion stabilities of the RLPHV, TVKPGL, and KALVAP peptides were 82%, 90%, and 78%. This article provides an integrated method for studying bioactive peptides derived from plant proteins.

Isomer-specific biomarker discovery in multiple myeloma with dual-derivatized N-glycans.

As one of the most important post-translational modifications, protein glycosylation plays vital role in various physiological processes. With multitudinous glycosyltransferases, N-glycans present structural diversity in linkages and branching styles. Structure-specific glycan profiling may provide more potential biological information than compositional profiling. In this work, N-glycans released from human serum samples were derivatized with reduction and methylamination prior to profiling using nanoLC-ESI-MS with PGC as stationary phase. In addition, α 2-3 neuraminidase was also applied for distinguishing the linkage types of sialic acid corresponding to different isomers. Relative abundances of 280 isomeric N-glycans were compared and 20 isomers showed significant difference between multiple myeloma cases and healthy controls. ROC was performed to assess the significantly altered isomeric glycans and 6 AUCs have exceeded 0.80, providing high diagnostic accuracy for MM. PCA is also employed to establish the differences among sample sets. Furthermore, these specific isomers have also been used for early detection of multiple myeloma, presenting important clinical application value. Isomer-specific biomarker discovery in multiple myeloma with dual-derivatized N-glycans.

Discovery of 7-alkyloxy- [1,2,4] triazolo[1,5-a] pyrimidine derivatives as selective positive modulators of GABAA1 and GABAA4 receptors with potent antiepileptic activity.

A series of 7-alkoxy - [1,2,4] triazolo [1, 5-a] pyrimidine derivatives were designed and synthesized. Maximal electroshock (MES) and pentylenetetrazole (PTZ) tests were utilized to access their anticonvulsant activity. Most of the series of compounds exhibited significant anti-seizure effects. Further studies demonstrated that the anticonvulsant activity of these compounds mainly depended on their allosteric potentiation of GABAA receptors. Among them, compound 10c was picked for the mechanism study due to its potent activity. The compound is more sensitive to subunit configurations of synaptic α1ß2γ2 and extrasynaptic α4ß3δ GABAA receptors, but there were no effects on NMDA receptors and Nav1.2 sodium channels. Meanwhile, 10c acted on the sites of GABAA receptors distinct from commonly used anticonvulsants benzodiazepines and barbiturates. Furthermore, studies from native neurons demonstrated that compound 10c also potentiated the activity of native GABAA receptors and reduced action potential firings in cultured cortical neurons. Such structural compounds may lay a foundation for further designing novel antiepileptic molecules.

Inhibition Effect of Negative Air Ions on Adsorption between Volatile Organic Compounds and Environmental Particulate Matter.

This work focused on the chemisorption of volatile organic compounds (VOCs) on particulate matter of less than 2.5 µm (PM2.5). The detection results illustrated that VOCs on PM2.5 containing hydroxyl, carbonyl, and ester groups and CxHy on PM2.5 were sequentially decreased as 70.02, 21.35, 6.42, and 2.21%, respectively. The chemisorption mechanism showed that the stronger the electronegativity of oxygen-containing functional groups of VOCs, the easier it is to adsorb them on the silicate PM2.5 due to hydrogen bond formation. Strong electronegative oxygen-containing functional groups readily interacted through hydrogen bonds with silanol groups, which was the main component of PM2.5, resulting in VOC adsorption on PM2.5. Negative air ions (NAIs) can weaken the offset ability of the lone pair of electrons in oxygen-containing functional groups in VOCs, which could significantly weaken the possibility of forming hydrogen bonds with silanol groups. Therefore, NAIs can effectively inhibit the adsorption between VOCs and PM2.5, leading to a significant reduction in VOCs on the surface of PM2.5.

Rhein attenuates lipopolysaccharide-primed inflammation through NF-κB inhibition in RAW264.7 cells: targeting the PPAR-γ signal pathway.

Inflammation is a common inducer of numerous severe diseases such as sepsis. The NF-κB signaling pathway plays a key role in the inflammatory process. Its activation promotes the release of pro-inflammatory mediators like inducible nitric oxide synthase and tumor necrosis factor alpha. Peroxisome proliferator-activated receptor gamma (PPAR-γ) inactivates nuclear factor kappa B (NF-κB) and subsequently attenuates inflammation. Rhein, an agent isolated from rhubarb, has been known to have anti-inflammatory effects. However, its influence on PPAR-γ remains largely unknown. In this study, an inflammation model was constructed by stimulating RAW264.7 cells with lipopolysaccharide. Rhein was used as a therapeutic agent, while rosiglitazone (PPAR-γ activator) and GW9662 (PPAR-γ inhibitor) were used as disrupters for in depth studies. The results demonstrated that rhein inhibits NF-κB activation and inflammatory factor release. However, GW9662 significantly reduced this effect, indicating that PPAR-γ is a critical mediator in the rhein-mediated anti-inflammatory process. Additionally, positive modulation of PPAR-γ expression and activity by rosiglitazone correspondingly influenced the effects of rhein on inflammatory factors and NF-κB expression. We also found that rhein could enhance PPAR-γ, NF-κB, and histone deacetylase 3 (HDAC3) binding. These results indicate that rhein exerts its anti-inflammation function by regulating the PPAR-γ-NF-κB-HDAC3 axis.

Adipose tissue-derived stem cells inhibit hypertrophic scar (HS) fibrosis via p38/MAPK pathway.

OBJECTIVE: The current study was designed to investigate the effects and underlying mechanisms of adipose tissue-derived stem cells (ADSCs) on hypertrophic scar (HS) fibrosis. METHOD: Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot analysis were performed to detect the expression of collagen I (Col1), collagen III (Col3), and α-smooth muscle actin (α-SMA) after fibroblasts and cultured HS tissues were treated with ADSC medium. All data were analyzed by using SPSS17.0 software. Statistical analysis was performed by Student t tests. RESULTS: The in vitro study showed that ADSC medium decreased the expression of Col1, Col3, and α-SMA. In addition, the protein level of p-p38 was downregulated by ADSC medium treatment in a concentration dependent manner. CONCLUSION: The current study demonstrated that ADSC could decrease collagen deposition and scar formation in in vitro experiments. The regulation of the p38/MAPK signaling pathway might play an important role in the process.

Toll-like receptor 5-mediated IL-17C expression in intestinal epithelial cells enhances epithelial host defense against F4+ ETEC infection.

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. The IL-17 cytokine family is well known to play important roles in the host defense against bacterial infections at the mucosa. Previously, we reported the potential role of IL-17A in clearing an ETEC infection in piglets. IL-17C, another member of the IL-17 family, is highly expressed in the intestinal epithelium, however, its role during an ETEC infection is still unclear. In this study, we demonstrate that F4+ ETEC induce IL-17C mRNA and protein expression in intestinal tissues as well as in porcine intestinal epithelial cells (IPEC-J2). This IL-17C production is largely dependent on TLR5 signaling in IPEC-J2 cells. Both F4+ ETEC infection and exogenous IL-17C increased the expression of antimicrobial peptides and tight junction proteins, such as porcine beta-defensin (pBD)-2, claudin-1, claudin-2 and occludin in IPEC-J2 cells. Taken together, our data demonstrate that TLR5-mediated IL-17C expression in intestinal epithelial cells enhances mucosal host defense responses in a unique autocrine/paracrine manner in the intestinal epithelium against ETEC infection.

Circadian Blood Pressure Variations in Postmenopausal Females with Hypertension.

The abnormalities of blood pressure (BP) nocturnal decline have been found to be predictive for carotid plaque and lacunar infarction in patients with hypertension. In this study, BP dipping patterns in postmenopausal females with hypertension were investigated. The nocturnal decline of systolic BP (SBP) was evaluated using 24-hour ambulatory BP monitoring (ABPM). A total of 163 postmenopausal females were eventually included in our study. The prevalence of reverse-dipper BP pattern was 32.3% in females with menopause age in their 40s and 40% in their 50s. However, after multivariate logistic regression analysis, menopause age was shown to be an independent risk factor for BP reverse dipping (Odds ratio [OR] 1.148; 95%CI 1.020 - 1.292; P = 0.020). Moreover, menopause age was negatively correlated with the decline rate of nocturnal SBP (r = -0.159; P < 0.05) and diastolic BP (r = -0.161; P < 0.05). Our study suggested that the menopause age might serve as a risk factor for reverse-dipper BP pattern in postmenopausal females with hypertension.

Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot.

In this work we demonstrate that blood glucose can be controlled remotely through light stimulated release of insulin from an injected cutaneous depot. Human insulin was tethered to an insoluble but injectable polymer via a linker, which was based on the light cleavable di-methoxy nitrophenyl ethyl (DMNPE) group. This material was injected into the skin of streptozotocin-treated diabetic rats. We observed insulin being released into the bloodstream after a 2 min trans-cutaneous irradiation of this site by a compact LED light source. Control animals treated with the same material, but in which light was blocked from the site, showed no release of insulin into the bloodstream. We also demonstrate that additional pulses of light from the light source result in additional pulses of insulin being absorbed into circulation. A significant reduction in blood glucose was then observed. Together, these results demonstrate the feasibility of using light to allow for the continuously variable control of insulin release. This in turn has the potential to allow for the tight control of blood glucose without the invasiveness of insulin pumps and cannulas.

Fabrication of freestanding nanoparticle membranes over wells.

Freestanding nanoparticle membranes over circular wells are prepared by utilizing surface engineering. The crucial step of this method is the hydrophobic treatment of the substrate surface, which causes the water droplet to be suspended over wells during drying. Consequently, the nanoparticle monolayer self-assembled at the surface of the water droplet would drape itself over wells instead of being dragged into wells and ruptured into patches after the evaporation of water. This scenario was confirmed by the results of control experiments with changes in the hydrophobicity of the surface and the depth of wells. Moreover, the NaCl crystallization experiment provides additional evidence for the dynamic process of drying. Freestanding nanoparticle membranes with different nanoparticle core sizes and different lengths of ligands have been successfully prepared using the same route. The Young's modulus of one typical kind of prepared freestanding nanoparticle membrane was measured with force microscopy.

Eco-Friendly Spiking Approach Based on Microfluidics for Preparation of Matrix Reference Materials.

Medicated bath is the most common spiking method used in the development of matrix reference materials for aquatic products; however, the environmental issues caused by the treatment of waste liquid after medicated bath cannot be ignored. We proposed an environmentally friendly spiking method based on microfluidics, which significantly improved the drug utilization rate without the need for subsequent drug residue treatment. Finely processed minced fish samples were fully mixed with quinolone drugs, and minced fish gel microspheres were prepared by microfluidic technology, utilizing the gel's water-locking function to enhance the drug-loading capacity. The results showed that this method can significantly increase the drug-loading capacity of the matrix (2.33-4.03 times) compared with the traditional spiking methods. In addition, the matrix reference material prepared by this method has good stability, and the drug concentration was adjustable and controllable.

The global, regional, and national burden of stomach cancer attributed to smoking in 204 countries, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019.

INTRODUCTION: Understanding the current burden of stomach cancer linked to smoking and the variations in trends across different locations, is crucial for developing effective prevention strategies. In this study, we present findings on the age-standardized death rate (ASDR) and age-standardized disability-adjusted life years (DALYs) rate attributed to smoking in 204 countries and territories spanning 21 regions from 1990 to 2019. METHODS: The data for this study were obtained from the Global Burden of Disease Study (GBD) 2019, which assessed 369 diseases and injuries, as well as 87 risk factors in 204 countries and 21 regions. To assess the trend in ASDR and age-standardized DALYs rate, the estimated annual percentage change (EAPC) was utilized. RESULTS: Between 1990 and 2019, smoking was found to be associated with a decrease in ASDR (EAPC = -2.20) and age-standardized DALYs (EAPC = -2.42) rates for gastric cancer. As the sociodemographic index (SDI) increased, the decline in rates also increased gradually. However, the decline was smallest in regions with low SDI (EAPCASDR = -1.34; EAPCage-standardized DALYs rate = -1.38). In 21 regions, both ASDR and DALYs rates experienced a decline. The smallest decline in ASDR was observed in Western Sub-Saharan Africa, with an EAPC of -0.80, while the smallest decline in DALYs rate was found in Oceania, with an EAPC of -0.81. Among the 204 countries analyzed, the Dominican Republic showed the highest increase in ASDR and age-standardized DALYs rate (EAPCASDR = 1.19; EAPCage-standardized DALYs rate = 1.21), followed by Afghanistan (EAPCASDR = 1.09; EAPCage-standardized DALYs rate = 1.09) and Sao Tome and Principe (EAPCASDR = 1.05; EAPCage-standardized DALYs rate = 1.03). In the year 2019, the highest ASDR and age-standardized DALYs rate was observed in East Asia, with the highest rates occurring in Mongolia. CONCLUSIONS: The burden of stomach cancer worldwide, adjusted for age, and related to smoking, has shown a decline from 1990 to 2019. However, regional disparities have been identified, with some areas experiencing an increase in this burden. These regions with a higher burden emphasize the necessity for the implementation of strong tobacco control measures.

Improving and controlling the drug loading capacity of seven quinolones in minced fish matrix based on microfluidics.

Traditional spiking methods for preparing matrix reference material of aquatic products is difficult to control the drug content in the matrix, especially one matrix containing multiple drugs. Minced fish is commonly used for the preparation of matrix reference materials in aquatic products, which is a relatively complex matrix with stickiness and difficult handling. Drug loading capacity is a key factor affecting the effectiveness of matrix reference materials. Here, we proposed a new spiking approach to improve the drug loading capacity of seven quinolones based on microfluidics, simultaneously. Fresh grass carp tissue underwent grinding, fine filtration, centrifugation and reconstituted in distilled water to form a liquid sample, which was subsequently mixed with a sodium alginate solution (1 %) at a ratio of 1:1.2. The mixed solution was supplemented with seven quinolones of equal concentration, followed by the preparation of uniform fish gel microspheres using microfluidic technology. The results indicated that the recoveries of seven quinolones ranged from 82.54 % to 114.17 %, demonstrating a significant improvement in the drug loading capacity of these quinolones compared to traditional methods. Moreover, the drug concentration in the matrix can be precisely controlled. A strong linear relationship was observed between the concentration of seven quinolones in the matrix and its initial concentration, which could serve as a reference for the development of other matrix reference materials.

Estimation of complete mutual information exploiting nonlinear magnitude-phase dependence: Application to spatial FNC for complex-valued fMRI data.

BACKGROUND: Real-valued mutual information (MI) has been used in spatial functional network connectivity (FNC) to measure high-order and nonlinear dependence between spatial maps extracted from magnitude-only functional magnetic resonance imaging (fMRI). However, real-valued MI cannot fully capture the group differences in spatial FNC from complex-valued fMRI data with magnitude and phase dependence. METHODS: We propose a complete complex-valued MI method according to the chain rule of MI. We fully exploit the dependence among magnitudes and phases of two complex-valued signals using second and fourth-order joint entropies, and propose to use a Gaussian copula transformation with a lower bound property to avoid inaccurate estimation of joint probability density function when computing the joint entropies. RESULTS: The proposed method achieves more accurate MI estimates than the two histogram-based (normal and symbolic approaches) and kernel density estimation methods for simulated signals, and enhances group differences in spatial functional network connectivity for experimental complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with the simplified complex-valued MI and real-valued MI, the proposed method yields higher MI estimation accuracy, leading to 17.4 % and 145.5 % wider MI ranges, and more significant connectivity differences between healthy controls and schizophrenia patients. A unique connection between executive control network (EC) and right frontal parietal areas, and three additional connections mainly related to EC are detected than the simplified complex-valued MI. CONCLUSIONS: With capability in quantifying MI fully and accurately, the proposed complex-valued MI is promising in providing qualified FNC biomarkers for identifying mental disorders such as schizophrenia.