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.

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.

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.

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.

One step cleanup of 160 pesticides and veterinary drugs in aquatic products using melamine-based automatic pressure filtration purification method combined with HPLC-MS/MS.

A 15-channel pressure filtration purification method was presented for high throughput sample preparation of aquatic products. A cost-effective device was constructed and melamine sponge was selected as the cleanup sorbent. Upon interfacing with HPLC-MS/MS, the analytical procedure demonstrated its suitability for quantifying 160 pesticides and veterinary drug residues in aquatic products such as fish, shrimp, and crab. The method achieved sample recoveries ranging from 61.3 to 124.9 %. The detection limits were established between 0.5 and 1.0 µg/kg, while the quantitation limits were confirmed to be within the range of 1.0-2.0 µg/kg. The method was applied to quantify the pesticide and veterinary drug residues in mostly consumed aquatic products from five coastal provinces in China. The results showed significant differences between different aquatic products in the concentrations of pesticide and veterinary drug residues, implying the necessity of supervision for the accurate determination of pesticides and veterinary drugs.

Dynamic functional network connectivity based on spatial source phase maps of complex-valued fMRI data: Application to schizophrenia.

BACKGROUND: Dynamic spatial functional network connectivity (dsFNC) has shown advantages in detecting functional alterations impacted by mental disorders using magnitude-only fMRI data. However, complete fMRI data are complex-valued with unique and useful phase information. METHODS: We propose dsFNC of spatial source phase (SSP) maps, derived from complex-valued fMRI data (named SSP-dsFNC), to capture the dynamics elicited by the phase. We compute mutual information for connectivity quantification, employ statistical analysis and Markov chains to assess dynamics, ultimately classifying schizophrenia patients (SZs) and healthy controls (HCs) based on connectivity variance and Markov chain state transitions across windows. RESULTS: SSP-dsFNC yielded greater dynamics and more significant HC-SZ differences, due to the use of complete brain information from complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with magnitude-dsFNC, SSP-dsFNC detected additional and meaningful connections across windows (e.g., for right frontal parietal) and achieved 14.6% higher accuracy for classifying HCs and SZs. CONCLUSIONS: This work provides new evidence about how SSP-dsFNC could be impacted by schizophrenia, and this information could be used to identify potential imaging biomarkers for psychotic diagnosis.

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.

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.

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.

DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord.

Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.

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.

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.

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.

Molecular docking and antihypertensive effects of a novel angiotensin-I converting enzyme inhibitory peptide from yak bone.

A novel angiotensin-converting enzyme (ACE) inhibitory peptide ser-ala-ser-val-ile-pro-val-ser-ala-val-arg-ala (SASVIPVSAVRA) was purified and identified from yak bone by Electrospray Ionization-Time of Flight-Mass Spectrometry (ESI-TOF-MS). Results in vitro showed that the peptide exhibited strong ACE inhibition activities with an IC50 of 54.22 µM. Molecular docking results showed the binding between the peptide SASVIPVSAVRA and ACE mainly driven by van der Waals forces, hydrogen bonds and metal receptor. Interestingly, the ACE inhibition activities of the peptide increased about 19% after digestion, but none of its metabolites showed stronger activity than it. The in vivo experiment showed that the antihypertensive effect of peptide SASVIPVSAVRA at dose of 30 mg/kg is nearly equal to Captopril at dose of 10 mg/kg to spontaneously hypertensive rats (SHRs). The antihypertensive effect mechanism of SASVIPVSAVRA should be further studied through plasma metabolomics and bioanalysis. Structure analysis of amino acids and peptides produced during digestion may help better understand the antihypertensive effect of peptides.

Digital light processing (DLP) in tissue engineering: from promise to reality, and perspectives.

Tissue engineering technology provides a revolutionary strategy to completely restore the structure and function of damaged tissues or organs. Digital light processing (DLP), as a kind of three-dimensional (3D) printing technology, has great advantages in printing resolution and efficiency, with low requirements for bioinks. This review introduces DLP-based printing and its development, as well as the manufacturing processes and printable materials. We also focus on tissue engineering products such as bone, tooth, cartilage, nerve, blood vessel, and so on. This review expounds on the difficulties and shortcomings of DLP printing technology in tissue engineering today. Perspectives are given on the current outlook on DLP-based 3D printing tissue engineering.

Nickel Coated Polyester Sponge for Delaying the Specific Aggregation of Fine Particles Induced by Negative Air Ions.

Negative air ions (NAIs) produced by corona discharge is often used for indoor air purification; however, the specific aggregation of suspended particles caused by NAIs, especially fine particles (FPs), needs to be considered. Here, a nickel coated conductive sponge (NCCS) was used as the main adsorption interface for delaying the obstinate aggregation caused by NAIs on another surface. The specific aggregation of FPs is caused by the directional transfer of electric charge, and the oxidation characteristic of NAIs results in the surface reaction of FPs simultaneously. The conductivity and roughness of the adsorption interface determine the migration direction and enrichment number of FPs, respectively. Nickel coated conductive sponge with high conductivity and high specific surface area can effectively adsorb the FPs affected by NAIs and can effectively delay the specific aggregation on the surface of indoor objects.

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.

A novel [1,2,4]triazolo[1,5-a]pyrimidine derivative as a fluorescence probe for specific detection of Fe3+ ions and application in cell imaging.

The detection of metal ions is of particular importance for monitoring environmental pollution and life metabolic activities. However, it is still a challenge to achieve Fe3+ detection with specific sensitivity and rapid response, especially in the presence of chelating agents for Fe3+ ions. Herein, a novel fluorescence probe for Fe3+, i.e., amide derivative of [1,2,4]triazolo[1,5-a] pyrimidine (TP, Id), was synthesized, featuring specific Fe3+ selectivity, rapid quenching (5 s), low limit of detection (0.82 µM), good permeability and low cytotoxicity. More importantly, Id can be used to identify and detect Fe3+ in the presence of existing strong chelating agents (e.g., EDTA) for Fe3+ ions. The results show that the as-synthesized fluorescence probe is particularly suitable as a bioimaging reagent to monitor intracellular Fe3+ in living HeLa cells. Furthermore, we proposed the binding mode for Id with Fe3+ ions and the light-emitting mechanism through high-resolution mass spectra and density function theory calculations, respectively. An Id-based test paper can be used to rapidly identify Fe3+. These results are expected to improve the development of new sensitive and specific fluorescent sensors for Fe3+.

Aqueous humor dynamics in human eye: A lattice Boltzmann study.

This paper presents a lattice Boltzmann model to simulate the aqueous humor (AH) dynamics in the human eye by involving incompressible Navier-Stokes flow, heat convection and diffusion, and Darcy seepage flow. Verifying simulations indicate that the model is stable, convergent and robust. Further investigations were carried out, including the effects of heat convection and buoyancy, AH production rate, permeability of trabecular meshwork, viscosity of AH and anterior chamber angle on intraocular pressure (IOP). The heat convection and diffusion can significantly affect the flow patterns in the healthy eye, and the IOP can be controlled by increasing the anterior chamber angle or decreasing the secretion rate, the drainage resistance and viscosity of AH. However, the IOP is insensitive to the viscosity of AH, which may be one of the causes that the viscosity would not have been considered as a factor for controlling the IOP. It's interesting that all these factors have more significant influences on the IOP in pathologic eye than healthy one. The temperature difference and the eye-orientation have obvious influence on the cornea and iris wall shear stresses. The present model and simulation results are expected to provide an alternative tool and theoretical reference for the study of AH dynamics.