Diacylglycerol O-acyltransferase (DGAT) isoforms play a role in peridroplet mitochondrial fatty acid metabolism in bovine liver.

Hepatocellular lipid accumulation characterizes fatty liver in dairy cows. Lipid droplets (LD), specialized organelles that store lipids and maintain cellular lipid homeostasis, are responsible for the ectopic storage of lipids associated with several metabolic disorders. In recent years, non-ruminant studies have reported that LD-mitochondria interactions play an important role in lipid metabolism. Due to the role of diacylglycerol acyltransferase isoforms (DGAT1 and DGAT2) in LD synthesis, we explored mechanisms of mitochondrial fatty acid transport in ketotic cows using liver biopsies and isolated primary hepatocytes. Compared with healthy cows, cows with fatty liver had massive accumulation of LD and high protein expression of the triglyceride (TAG) synthesis-related enzymes DGAT1 and DGAT2, LD synthesis-related proteins perilipin 2 (PLIN2) and perilipin 5 (PLIN5), and the mitochondrial fragmentation-related proteins dynamin-related protein 1 (DRP1) and fission 1 (FIS1). In contrast, factors associated with fatty acid oxidation, mitochondrial fusion and mitochondrial electron transport chain complex were lower compared with those in the healthy cows. In addition, transmission electron microscopy revealed significant contacts between LD-mitochondria in liver tissue from cows with fatty liver. Compared with isolated cytoplasmic mitochondria, expression of carnitine palmitoyl transferase 1A (CPT1A) and DRP1 was lower, but mitofusin 2 (MFN2) and mitochondrial electron transport chain complex was greater in isolated peridroplet mitochondria from hepatic tissue of cows with fatty liver. In vitro data indicated that exogenous free fatty acids (FFA) induced hepatocyte LD synthesis and mitochondrial dynamics consistent with in vivo results. Furthermore, DGAT2 inhibitor treatment attenuated the FFA-induced upregulation of PLIN2 and PLIN5 and rescued the impairment of mitochondrial dynamics. Inhibition of DGAT2 also restored mitochondrial membrane potential and reduced hepatocyte reactive oxygen species production. The present in vivo and in vitro results indicated there are functional differences among different types of mitochondria in the liver tissue of dairy cows with ketosis. Activity of DGAT2 may play a key role in maintaining liver mitochondrial function and lipid homeostasis in dairy cows during the transition period.

ß-sitosterol alleviates high fatty acid-induced lipid accumulation in calf hepatocytes by regulating cholesterol metabolism.

A significant reduction in plasma concentration of cholesterol during early lactation is a common occurrence in high-yielding dairy cows. An insufficient synthesis of cholesterol in the liver has been linked to lipid accumulation caused by high concentrations of fatty acids during negative energy balance (NEB). As ruminant diets do not provide quantitative amounts of cholesterol for absorption, phytosterols such as ß-sitosterol may serve to mitigate the shortfall in cholesterol within the liver during NEB. To gain mechanistic insights, primary hepatocytes were isolated from healthy female 1-day old calves for in vitro studies with or without 1.2 mM fatty acids (FA) to induce metabolic stress. Furthermore, hepatocytes were treated with 50 µM ß-sitosterol with or without FA. Data were analyzed by one-way ANOVA with subsequent Bonferroni correction. Results revealed that calf hepatocytes treated with FA had greater content of non-esterified fatty acids (NEFA) and triacylglycerol (TAG), and greater mRNA and protein abundance of the lipid synthesis-related SREBF1 and FASN. In contrast, mRNA and protein of CPT1A (fatty acid oxidation) and the cholesterol metabolism-related targets SREBF2, HMGCR, ACAT2, APOA1, ABCA1 and ABCG5 was lower. Content of the antioxidant-related glutathione (GSH) and activities of superoxide dismutase (SOD) also was lower. Compared with FA challenge alone, 50 µM ß-sitosterol led to greater mRNA and protein abundance of SREBF2, HMGCR, ACAT2 and ABCG5, and greater content of GSH and activity of SOD. In contrast, compared with the FA group, the mRNA and protein abundance of SREBF1 and ACC1 and the content of TAG and NEFA in the ß-sitosterol + FA group were lower. Overall, ß-sitosterol can promote cholesterol metabolism and reduce oxidative stress while reducing lipid accumulation in hepatocytes challenged with high concentrations of fatty acids.

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Multi-modal ultrasound multistage classification of PTC cervical lymph node metastasis via DualSwinThyroid.

Objective: This study aims to predict cervical lymph node metastasis in papillary thyroid carcinoma (PTC) patients with high accuracy. To achieve this, we introduce a novel deep learning model, DualSwinThyroid, leveraging multi-modal ultrasound imaging data for prediction. Materials and methods: We assembled a substantial dataset consisting of 3652 multi-modal ultrasound images from 299 PTC patients in this retrospective study. The newly developed DualSwinThyroid model integrates various ultrasound modalities and clinical data. Following its creation, we rigorously assessed the model's performance against a separate testing set, comparing it with established machine learning models and previous deep learning approaches. Results: Demonstrating remarkable precision, DualSwinThyroid achieved an AUC of 0.924 and an 96.3% accuracy on the test set. The model efficiently processed multi-modal data, pinpointing features indicative of lymph node metastasis in thyroid nodule ultrasound images. It offers a three-tier classification that aligns each level with a specific surgical strategy for PTC treatment. Conclusion: DualSwinThyroid, a deep learning model designed with multi-modal ultrasound radiomics, effectively estimates the degree of cervical lymph node metastasis in PTC patients. In addition, it also provides early, precise identification and facilitation of interventions for high-risk groups, thereby enhancing the strategic selection of surgical approaches in managing PTC patients.

A luminescent organic cocrystal for detecting 2,4-dinitroaniline.

2,4-dinitroaniline (2,4DNBA), a significant hazardous chemical, is extensively used in industry and agriculture. The chemical accumulates in the environment for a long time, causing irreversible damage to the ecosystem. Currently, it is quite challenging to identify it by common analysis and detection techniques. Herein, a luminescent organic cocrystal (TCNB-8HQ) was prepared using 1,2,4,5-tetracyanobenzene (TCNB) as the electron acceptor and 8-hydroxyquinoline (8HQ) as the electron donor. The prepared TCNB-8HQ was used as a fluorescent probe with a fast and specific response to 2,4DNBA. This detection method possessed a linear range of 0.5-200 µmol/L with a detection limit as low as 0.085 µmol/L to detect 2,4DNBA in real samples with satisfactory spiking recovery. As revealed by fluorescence spectrum and UV-vis absorption spectrum, the detection mechanism involved competitive absorption between cocrystal material and 2,4DNBA. Moreover, the feasibility of the system was explored by preparing portable indicator strips for 2,4DNBA from organic cocrystal (TCNB-8HQ). This study not only provided an environmentally friendly gram-level preparation strategy to synthesize the fluorescent material but also investigated their application in chemical detection.

The economic effect of financial compensation in China's healthcare system: comprehensive insights regarding supply and demand factors.

OBJECTIVES: We aim to analyse the effects of government subsidies on residents' health and healthcare expenditure from the perspectives of supply and demand. DATA AND METHODS: According to the regional division adopted in the data query system of the National Bureau of Statistics, this study divides 31 provinces and cities into three regions: eastern, central, and western. The data used are from public databases, such as the "China Statistical Yearbook," "China Health Statistical Yearbook," and "Government Final Account Report". In this study, mathematical model derivation is used to construct a fixed effects model, and an empirical study based on cross-sectional data and general linear regression is conducted. To prevent endogeneity issues, this study introduces instrumental variables and uses 2SLS regression to further analyse the output results. RESULTS: For every 1% increase in supplementary funding on the supply side, the perinatal mortality rate decreases by 1.765%, while for every 1% increase in financial compensation on the demand side, per capita outpatient expenses increase by 0.225% and per capita hospitalization expenses increase by 0.196%. Regarding medical resources, for every 1% increase in the number of beds per 1,000 people, per capita hospitalization expenses decrease by 0.099%. In the central and eastern regions, where economic levels are higher, supply-side government funding is more effective than demand-side funding. In contrast, demand-side funding is more effective in the western region. CONCLUSIONS: The roles of multiple influencing factors and significant regional heterogeneity are clarified. Increasing financial compensation to providers positively impacts perinatal mortality but leads to higher per capita outpatient and hospital expenditures. Finally, this study provides targeted policy recommendations and solid theoretical support for policymakers.

The first two whole mitochondrial genomes for the genus Dactylis species: assembly and comparative genomics analysis.

BACKGROUND: Orchardgrass (Dactylis glomerata L.), a perennial forage, has the advantages of rich leaves, high yield, and good quality and is one of the most significant forage for grassland animal husbandry and ecological management in southwest China. Mitochondrial (mt) genome is one of the major genetic systems in plants. Studying the mt genome of the genus Dactylis could provide more genetic information in addition to the nuclear genome project of the genus. RESULTS: In this study, we sequenced and assembled two mitochondrial genomes of Dactylis species of D. glomerata (597, 281 bp) and D. aschersoniana (613, 769 bp), based on a combination of PacBio and Illumina. The gene content in the mitochondrial genome of D. aschersoniana is almost identical to the mitochondrial genome of D. glomerata, which contains 22-23 protein-coding genes (PCGs), 8 ribosomal RNAs (rRNAs) and 30 transfer RNAs (tRNAs), while D. glomerata lacks the gene encoding the Ribosomal protein (rps1) and D. aschersoniana contains one pseudo gene (atp8). Twenty-three introns were found among eight of the 30 protein-coding genes, and introns of three genes (nad 1, nad2, and nad5) were trans-spliced in Dactylis aschersoniana. Further, our mitochondrial genome characteristics investigation of the genus Dactylis included codon usage, sequences repeats, RNA editing and selective pressure. The results showed that a large number of short repetitive sequences existed in the mitochondrial genome of D. aschersoniana, the size variation of two mitochondrial genomes is due largely to the presence of a large number of short repetitive sequences. We also identified 52-53 large fragments that were transferred from the chloroplast genome to the mitochondrial genome, and found that the similarity was more than 70%. ML and BI methods used in phylogenetic analysis revealed that the evolutionary status of the genus Dactylis. CONCLUSIONS: Thus, this study reveals the significant rearrangements in the mt genomes of Pooideae species. The sequenced Dactylis mt genome can provide more genetic information and improve our evolutionary understanding of the mt genomes of gramineous plants.

Frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students.

AIM: To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students. METHODS: Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University. Their data were used to identify the different types of accommodation and non-strabismic binocular vision dysfunction and to determine their frequency. Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities. RESULTS: The results showed that 36.71% of the subjects had accommodation and non-strabismic binocular vision issues, with 8.86% being attributed to accommodation dysfunction and 27.85% to binocular abnormalities. Convergence insufficiency (CI) was the most common abnormality, accounting for 13.29%. Those with these abnormalities experienced higher levels of eyestrain (χ2=69.518, P<0.001). The linear correlations were observed between the difference of binocular spherical equivalent (SE) and the index of horizontal esotropia at a distance (r=0.231, P=0.004) and the asthenopia survey scale (ASS) score (r=0.346, P<0.001). Furthermore, the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range (r=-0.321, P<0.001), the convergence of negative fusion images at close range (r=-0.294, P<0.001), the vergence facility (VF; r=-0.234, P=0.003), and the set of negative fusion images at far range (r=-0.237, P=0.003). Logistic regression analysis indicated that gender, age, and the difference in right and binocular SE did not influence the emergence of these abnormalities. CONCLUSION: Binocular vision abnormalities are more prevalent than accommodation dysfunction, with CI being the most frequent type. Greater binocular refractive disparity leads to more severe eyestrain symptoms.

Characterization of thyroid metastasis from clear cell renal cell carcinoma on ultrasonography: a report of three cases and literature review.

Introduction: Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is relatively rare, so ultrasound doctors lack experience with the disease, which can easily lead to misdiagnosis. We describe three cases of thyroid metastasis from ccRCC detected 12, 8, and 7 years after nephrectomy. Case presentation: The first patient, a 78-year-old woman, was admitted to our institution for hoarseness and progressive dyspnea. Ultrasonography revealed bilateral thyroid nodules and abnormal cervical lymph nodes. Fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the thyroid was nondiagnostic. The other two patients, a 54-year-old man and a 65-year-old man, were admitted to our institution for a goiter pressing on the trachea. In each case, ultrasonography revealed a partially cystic nodule of the left lobe of the thyroid gland. Histological examination of three patients after thyroidectomy showed thyroid metastasis from ccRCC. Discussion/Conclusion: For patients with a history of ccRCC, long-term follow-up and routine thyroid ultrasonography should be performed. If a new thyroid nodule is found during the examination, metastases should be highly suspected. FNAB should be performed, even if benign ultrasound features seem to be in evidence. If the diagnosis of FNAB is incorrect and inconclusive, CNB should be performed.

m6A RNA demethylase AtALKBH9B promotes mobilization of a heat-activated long terminal repeat retrotransposon in Arabidopsis.

Transposons are mobile and ubiquitous DNA molecules that can cause vast genomic alterations. In plants, it is well documented that transposon mobilization is strongly repressed by DNA methylation; however, its regulation at the posttranscriptional level remains relatively uninvestigated. Here, we suggest that transposon RNA is marked by m6A RNA methylation and can be localized in stress granules (SGs). Intriguingly, SG-localized AtALKBH9B selectively demethylates a heat-activated retroelement, Onsen, and thereby releases it from spatial confinement, allowing for its mobilization. In addition, we show evidence that m6A RNA methylation contributes to transpositional suppression by inhibiting virus-like particle assembly and extrachromosomal DNA production. In summary, this study unveils a previously unknown role for m6A in the suppression of transposon mobility and provides insight into how transposons counteract the m6A-mediated repression mechanism by hitchhiking the RNA demethylase of the host.

A silver metal-organic cage with antibacterial activity for wound healing.

Bacterial infection is one of the most threatening diseases in humans and can result in tissue necrosis, inflammation, and so on. Although a large number of antibacterial materials have been developed, there are still some disadvantages in this field, including decreasing antibacterial activity in the aqueous solution or a short duration of time. Herein, a metal-organic cage named Ag-TBI-TPE with excellent antibacterial activity was prepared and applied in wound healing. Owing to the photosensitive production of the toxic ROS species and the positive charge of the surface, the Ag-TBI-TPE cage exhibits high antibacterial activity, especially under UV irradiation. It could accelerate the healing process of the infected wounds in vivo with satisfactory biocompatibility and bio-safety. The results indicated that after treatment with the Ag-TBI-TPE cage, with and without UV irradiation, the healing rates of wounds infected by E. coli and S. aureus were 89.59% and 93.05%, and 83.48% and 90.84%, respectively, which were much higher than those shown by the positive control group at 51.38% and 67.74%, respectively. This study not only sheds light on a design idea for a new antibacterial material but also further expands the potential application field of metal-organic cages.

Optical performance evaluation of an infrared system of a hypersonic vehicle in an aero-thermal environment.

At hypersonic velocities, the turbulent flow field generated by an aircraft, along with its temperature distribution, leads to significant aerodynamic optical effects that severely impede the performance of internal optical systems. This study proposes a method for analyzing the temporal characteristics of imaging degradation in a detector window infrared imaging system under different field angles of hypersonic velocity. Based on heat transfer theory, a method for solving the transient temperature field in the optical window of a high-speed aircraft is derived and established, considering unsteady thermal conduction-radiation coupling. Additionally, an optical window radiation tracing method is introduced, which directly determines the initial direction vector of light reaching the detector. This method reduces the workload of radiation transmission, significantly enhancing the efficiency of radiation calculations. The time characteristics of image degradation caused by aero-optical effects in high-speed aircraft are analyzed using metrics such as peak signal-to-noise ratio, wave aberration, and point diffusion function. The results demonstrate that as working time increases and the viewing angle widens, the impact of aero-optics on the aircraft imaging system becomes more severe. Moreover, compared to the aerodynamic light transmission effect, the aerodynamic thermal radiation effect has a more detrimental influence on imaging quality.

Circ-KATNAL1 Knockdown Reduces Neuronal Apoptosis and Alleviates Spinal Cord Injury Through the miR-98-5p/PRDM5 Regulatory Axis.

Spinal cord injury (SCI) is a common disease of the central nervous system. circRNAs play a crucial role in neurological disease. The purpose of this study was to investigate the role of circ-KATNAL1 in SCI and its regulatory mechanism. T9-L10 spinal segment of Sprague Dawley rats was compressed or contused after T10 laminectomy to establish the SCI rat model. Then, rats were divided into SCI group, si-NC group, si-circ-KATNAL1 group, si-circ-KATNAL1 + antagomir NC group, si-circ-KATNAL1 + miR-98-5p antagomir group, si-circ-KATNAL1 + oe-NC group, and si-circ-KATNAL1 + oe-PRDM5 group, with 6 rats in each group. There was another sham operation group that received no treatment. Basso, Beattie, and Bresnahan (BBB) scores were used to evaluate the neural function of rats. In addition to that, the pathological changes of spinal cord tissue, neuronal apoptosis, and inflammatory responses were correspondingly observed and analyzed. Quantitative measurements of circ-KATNAL1, miR-98-5p, and PRDM5 levels were conducted, as well as analyses of their interrelationship. Circ-KATNAL1 was up-regulated in the spinal cord tissue of SCI rats, and circ-KATNAL1 knockdown could improve neural function, alleviate pathological changes of spinal cord tissue, and inhibit neuronal apoptosis and inflammatory responses in SCI rats. For miR-98-5p, circ-KATNAL1 was an upstream factor, while PRDM5 was a downstream actor. miR-98-5p deficiency or PRDM5 restoration impaired the remission effect of circ-KATNAL1 knockdown on SCI. Circ-KATNAL1 knockdown reduces neuronal apoptosis and alleviates SCI through miR-98-5p/PRDM5 regulatory axis.

Lanthanide Metal-Organic Framework Isomers with Novel Water-Boosting Lanthanide Luminescence Behaviors.

Lanthanide metal-organic frameworks (Ln-MOFs) with exceptional optical performance and structural diversity offer a unique platform for the development of luminescent materials. However, Ln-MOFs often suffer from luminescence quenching by high-vibrating oscillators, especially in aqueous solution. Thus, multiple strategies have been adopted to improve the luminescence of Ln3+. Anomalous research about water-induced lanthanide luminescence enhancement of Ln-MOFs is in the primary stage. Here, two Eu-based metal-organic framework (Eu-MOF) isomers named QXBA-Eu-1 and QXBA-Eu-2 were constructed by using the same ligand under different solvent thermal conditions, which exhibited distinctive water- and methanol-boosting emission behaviors. As for QXBA-Eu-1, water and methanol molecules replaced the free N,N-dimethylacetamide (DMA) molecules in the framework, repressed the rotation or libration suppression of the QXBA linker, and formed hydrogen bonds with the coordinated water molecules, which suppressed the O-H high-energy vibrations, reduced nonradiative transitions, stabilized the T1 state, and facilitated the intersystem crossing (ISC) process. For QXBA-Eu-2, water molecules tended to replace the coordinated DMA ligands, which altered the S1 and T1 energy levels of the ligand and facilitated the ligand-to-metal energy transfer (LMET) process and strengthened the luminescence of Eu3+. Importantly, free solvent molecules and the hydroxylation of Eu3+ centers also restrained the rotation or libration of the QXBA linker, by which the nonradiative transition was further inhibited and the lanthanide luminescence enhanced. Thus, this work not only opened an unprecedented path to enhance lanthanide luminescence in aqueous solution but also expanded its application scope.

Regulation of cholesterol metabolism during high fatty acid-induced lipid deposition in calf hepatocytes.

Cholesterol in the circulation is partly driven by changes in feed intake, but aspects of cholesterol metabolism during development of fatty liver are not well known. The objective of this study was to investigate mechanisms of cholesterol metabolism in calf hepatocytes challenged with high concentrations of fatty acids (FA). To address mechanistic insights regarding cholesterol metabolism, liver samples were collected from healthy control dairy cows (n = 6; 7-13 d in milk) and cows with fatty liver (n = 6; 7-11 d in milk). In vitro, hepatocytes isolated from 3 healthy female calves (1 d old) were challenged with or without a mix of 1.2 mM FA to induce metabolic stress. In addition, hepatocytes were processed with 10 µmol/L of the cholesterol synthesis inhibitor simvastatin or 6 µmol/L of the cholesterol intracellular transport inhibitor U18666A with or without the 1.2 mM FA mix. To evaluate the role of cholesterol addition, hepatocytes were treated with 0.147 mg/mL methyl-ß-cyclodextrin (MßCD + FA) or 0.147 mg/mL MßCD with or without 10 and 100 µmol/L cholesterol before incubation with FA (CHO10 + FA and CHO100 + FA). In vivo data from liver biopsies were analyzed by 2-tailed unpaired Student's t-test. Data from in vitro calf hepatocytes were analyzed by one-way ANOVA. Compared with healthy cows, blood plasma total cholesterol and plasma low-density lipoprotein cholesterol content in cows with fatty liver was markedly lower, whereas the hepatic total cholesterol content did not differ. In contrast, compared with healthy controls, the triacylglycerol content in the liver and the content of FA, ß-hydroxybutyrate, and aspartate aminotransferase in the plasma of cows with fatty liver were greater. The results revealed that both fatty liver in vivo and challenge of calf hepatocytes with 1.2 mM FA in vitro led to greater mRNA and protein abundance of sterol regulatory element binding transcription factor 1 (SREBF1) and fatty acid synthase (FASN). In contrast, mRNA and protein abundance of sterol regulatory element binding transcription factor 2 (SREBF2), acyl coenzyme A-cholesterol acyltransferase, and ATP-binding cassette subfamily A member 1 (ABCA1) were lower. Compared with the FA group, the cholesterol synthesis inhibitor simvastatin led to greater protein abundance of microsomal triglyceride transfer protein and mRNA abundance of SREBF2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), ACAT2, and lower ABCA1 and FASN protein abundance. In contrast, compared with the FA group, the cholesterol intracellular transport inhibitor U18666A + FA led to greater total cholesterol concentration and greater protein and mRNA abundance of FASN. Compared with the MßCD + FA group, the addition of 10 µmol/L cholesterol led to greater concentration of cholesteryl ester and excretion of apolipoprotein B100, and greater protein and mRNA abundance of ABCA1 and microsomal triglyceride transfer protein, and lower concentration of malondialdehyde. Overall, a reduction in cholesterol synthesis promoted FA metabolism in hepatocytes likely to relieve the oxidative stress caused by the high FA load. The data suggest that maintenance of normal cholesterol synthesis promotes very low-density lipoprotein excretion and can reduce lipid accumulation and oxidative stress in dairy cows that experience fatty liver.

Ligand-free high loading capacity ursolic acid self-carried nanovesicles enable hepatocyte targeting via absorbing apolipoproteins.

Ursolic acid (UA), a natural pentacyclic terpenoid carboxylic acid that can exert a potent hepatoprotective activity, has been developed into various types of nanoparticles to improve its pharmacological effects, however, the phagocytosis of nanoparticles by Kupffer cells greatly limits its efficacy. Herein, UA/Tween 80 nanovesicles (V-UA) were constructed and despite its simple composition, it fulfills multiple functions simultaneously: UA served as not only an active ingredient in the nanovesicle drug delivery system, but also acts as part of the carrier to stabilize UA/Tween 80 nanostructure; with a molar ratio of UA to Tween 80 up to 2:1, the formulation possesses a significant advantage of higher drug loading capacity; relative to liposomal UA (Lipo-UA), a conditional cellular uptake and higher accumulation of V-UA in hepatocytes provide insights into the hepatocytes targeting mechanisms of this nanovesicles. Favorable hepatocyte targeting ability also facilitates the treatment of liver diseases, which was well validated in three liver disease models.

Novel Lanthanide-Based Metal-Organic Framework Isomer as a Double Ratiometric Fluorescent Probe for Vanillymandelic Acid.

The concentration of vanillymandelic acid (VMA) in urine is closely related with pheochromocytoma diagnosis. Thus, it is essential to develop more accurate and convenient fluorescence sensing strategies toward VMA. Until now, the design of double ratiometric detection methods for VMA was still in the unexplored stage. In this work, novel Ln3+-based metal-organic frameworks (QBA-Eu and QBA-Gd0.875Eu0.125) possessing dual emission peaks was fabricated successfully, which served as isomers of YNU-1 and exhibited more excellent water stability in fluorescence and structure than the ones of YNU-1. The formation of the complex between QBA ligands and VMA molecules via hydrogen bonds within QBA-Eu frameworks produced a new emission band centered at 450 nm and resulted in the decline of monomer emission intensity for QBA at 390 nm. Owing to the reduced energy gap [ΔE (S1 - T1)], the antenna effect was hampered and luminescence of Eu3+ ions also decreased. The developed double ratiometric (I615nm/I475nm, I390nm/I475nm) fluorescence sensors based on QBA-Eu and QBA-Gd0.875Eu0.125 possessed the advantages of fast response (4 min), low detection limits (0.58 and 0.51; 0.22 and 0.31 µM), and wide linear ranges (2-100 and 2-80 µM), which met the requirements of pheochromocytoma diagnosis. We also applied them to determine VMA in an artificial urine sample and diluted human urine sample and obtained satisfactory results. They will become prospective fluorescence sensing platforms for VMA.

Effect of Myricetin on Lipid Metabolism in Primary Calf Hepatocytes Challenged with Long-Chain Fatty Acids.

Triacylglycerol (TAG) accumulation and oxidative damage in hepatocytes induced by high circulating concentrations of fatty acids (FA) are common after calving. In order to clarify the role of myricetin on lipid metabolism in hepatocytes when FA metabolism increases markedly, we performed in vitro analyses using isolated primary calf hepatocytes from three healthy female calves (1 d old, 42 to 48 kg). Two hours prior to an FA challenge (1.2 mM mix), the hepatocytes were treated with 100 µM (M1), 50 µM (M2), or 25 µM (M3) of myricetin. Subsequently, hepatocytes from each donor were challenged with or without FA for 12 h in an attempt to induce metabolic stress. Data from calf hepatocyte treatment comparisons were assessed using two-way repeated-measures (RM) ANOVA with subsequent Bonferroni correction. The data revealed that hepatocytes challenged with FA had greater concentrations of TAG and nonesterified fatty acids (NEFA), oxidative stress-related MDA and H2O2, and mRNA and protein abundance of lipid synthesis-related SREBF1 and inflammatory-related NF-κB. In addition, the mRNA abundance of the lipid synthesis-related genes FASN, DGAT1, DGAT2, and ACC1; endoplasmic reticulum stress-related GRP79 and PERK; and inflammatory-related TNF-α also were upregulated. In contrast, the activity of antioxidant SOD (p < 0.01) and concentrations of GSH (p < 0.05), and the protein abundance of mitochondrial FA oxidation-related CPT1A, were markedly lower. Compared with FA challenge, 50 and 100 µM myricetin led to lower concentrations of TAG, NEFA, MDA, and H2O2, as well as mRNA and protein abundance of SREBF1, DGAT1, GRP78, and NF-κB. In contrast, the activity of SOD (p < 0.01) and mRNA and protein abundance of CPT1A were markedly greater. Overall, the results suggest that myricetin could enhance the antioxidant capacity and reduce lipotoxicity, endoplasmic reticulum stress, and inflammation. All of these effects can help reduce TAG accumulation in hepatocytes.

m6A RNA methylation impairs gene expression variability and reproductive thermotolerance in Arabidopsis.

Heat-imposed crop failure is often attributed to reduced thermotolerance of floral tissues; however, the underlying mechanism remains unknown. Here, we demonstrate that m6A RNA methylation increases in Arabidopsis flowers and negatively regulates gene expression variability. Stochastic gene expression provides flexibility to cope with environmental stresses. We find that reduced transcriptional fluctuation is associated with compromised activation of heat-responsive genes. Moreover, disruption of an RNA demethylase AtALKBH10B leads to lower gene expression variability, suppression of heat-activated genes, and strong reduction of plant fertility. Our work proposes a novel role for RNA methylation in the bet-hedging strategy of heat stress response.

Metal-Organic Framework with Near-Infrared Luminescence for "Switch-on" Determination of Kaempferol and Quercetin by the Antenna Effect.

The establishment of a reliable and sensitive method for the detection of flavonoids, such as kaempferol (Kae) and quercetin (Que), is important and challenging in food chemistry and pharmacology because numerous structural analogues may interfere with the detection. Until now, designing an efficient switch-on fluorescence sensing strategy for Kae and Que was still in the unachievable stage. In this work, a switch-on near-infrared (NIR) luminescence sensing assay for Kae and Que was fabricated based on a metal-organic framework (MOF) called IQBA-Yb for the first time. The fluorescence enhancing mechanism was that analytes served as additional "antenna" of Yb3+, leading to the efficient switch-on NIR emission under excitation at 467 nm. Meanwhile, the combination results of experiment and theoretical calculation revealed that there existed hydrogen bonds between Kae, Que, and the MOF skeleton, further promoting the energy transfer between the analyte and Yb3+ and facilitating fluorescence enhancement response. The developed probe possessed excellent sensing capability for Kae and Que, accompanied by a wide linear range (0.04-70, 0.06-90 µM), low detection limit (0.01, 0.06 µM), and short response time (20 min, 6 min), which was used to determine the Kae and Que contents in Green Lake and eatable Que samples with satisfactory results.