KN-93 promotes HDAC4 nucleus translocation to promote fatty acid oxidation in myocardial infarction.

Myocardial infarction (MI) is a potentially fatal disease that causes a significant number of deaths worldwide. The strategy of increasing fatty acid oxidation in myocytes is considered a therapeutic avenue to accelerate metabolism to meet energy demands. We conducted the study aiming to investigate the effect of KN-93, which induces histone deacetylase (HDAC)4 shuttling to the nucleus, on fatty acid oxidation and the expression of related genes. A mouse model of myocardial infarction was induced by isoprenaline administration. Heart damage was assessed by the detection of cardiac injury markers. The level of fatty acid oxidation level was evaluated by testing the expression of related genes. Both immunofluorescence and immunoblotting in the cytosol or nucleus were utilized to observe the distribution of HDAC4. The interaction between HDAC4 and specificity protein (SP)1 was confirmed by co-immunoprecipitation. The acetylation level of SP1 was tested after KN-93 treatment and HDAC4 inhibitor. Oxygen consumption rate and immunoblotting experiments were used to determine whether the effect of KN-93 on increasing fatty acid oxidation is through HDAC4 and SP1. Administration of KN-93 significantly reduced cardiac injury in myocardial infarction and promoted fatty acid oxidation both in vitro and in vivo. KN-93 was shown to mediate nuclear translocation of HDAC4. HDAC4 was found to interact with SP1 and reduce SP1 acetylation. HDAC4 or SP1 inhibitors attenuated the effect of KN-93 on fatty acid oxidation. In conclusion, KN-93 promotes HDAC4 translocation to the nucleus, thereby potentially enhancing fatty acid oxidation by SP1.

Genetic linkage map construction and QTL analysis for plant height in proso millet (Panicum miliaceum L.).

KEY MESSAGE: A genetic linkage map representing proso millet genome was constructed with SSR markers, and a major QTL corresponding to plant height was mapped on chromosome 14 of this map. Proso millet (Panicum miliaceum L.) has the lowest water requirements of all cultivated cereal crops. However, the lack of a genetic map and the paucity of genomic resources for this species have limited the utility of proso millet for detailed genetic studies and hampered genetic improvement programs. In this study, 97,317 simple sequence repeat (SSR) markers were developed based on the genome sequence of the proso millet landrace Longmi 4. Using some of these markers in conjunction with previously identified SSRs, an SSR-based linkage map for proso millet was successfully constructed using a large mapping population (316 F2 offspring). In total, 186 SSR markers were assigned to 18 linkage groups corresponding to the haploid chromosomes. The constructed map had a total length of 3033.42 centimorgan (cM) covering 78.17% of the assembled reference genome. The length of the 18 linkage groups ranged from 88.89 cM (Chr. 15) to 274.82 cM (Chr. 16), with an average size of 168.17 cM. To our knowledge, this is the first genetic linkage map for proso millet based on SSR markers. Plant height is one of the most important traits in crop improvement. A major QTL was repeatedly detected in different environments, explaining 8.70-24.50% of the plant height variations. A candidate gene affecting auxin biosynthesis and transport, and ROS homeostasis regulation was predicted. Thus, the linkage map and QTL analysis provided herein will promote the development of gene mining and molecular breeding in proso millet.

Radiomics using CT images for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma: a multi-centric study.

OBJECTIVES: To develop a CT-based radiomics model for preoperative prediction of lymph node (LN) metastasis in perihilar cholangiocarcinoma (pCCA). METHODS: The study enrolled consecutive pCCA patients from three independent Chinese medical centers. The Boruta algorithm was applied to build the radiomics signature for the primary tumor and LN. The k-means algorithm was employed to cluster the selected LNs based on the radiomics signature LN. Support vector machines were used to construct the prediction models. The diagnostic efficiency was measured by the area under the receiver operating characteristic curve (AUC). The optimal model was evaluated in terms of calibration, clinical usefulness, and prognostic value. RESULTS: A total of 214 patients were included in the study (mean age: 61.6 years ± 9.4; 130 male). The selected LNs were classified into two clusters, which were significantly correlated with LN metastasis in all cohorts (p < 0.001). The model incorporated the clinical risk factors, radiomics signature primary tumor, and the LN cluster obtained the best discrimination, with AUC values of 0.981 (95% CI: 0.962-1), 0.896 (95% CI: 0.810-0.982), and 0.865 (95% CI: 0.768-0.961) in the training, internal validation, and external validation cohorts, respectively. High-risk patients predicted by the optimal model had shorter overall survival than low-risk patients (median, 13.7 vs. 27.3 months, p < 0.001). CONCLUSIONS: The study proposed a radiomics model with good performance to predict LN metastasis in pCCA. As a noninvasive preoperative prediction tool, this model may help in patient risk stratification and personalized treatment. CLINICAL RELEVANCE STATEMENT: A CT-based radiomics model accurately predicts lymph node metastasis in perihilar cholangiocarcinoma patients. This noninvasive preoperative tool can aid in patient risk stratification and personalized treatment, potentially improving patient outcomes. KEY POINTS: • The radiomics model based on contrast-enhanced CT is a useful tool for preoperative prediction of lymph node metastasis in perihilar cholangiocarcinoma. • Radiomics features extracted from lymph nodes show great potential for predicting lymph node metastasis. • The study is the first to identify a lymph node phenotype with a high probability of metastasis based on radiomics.

Epidemiological study of pediatric nutritional deficiencies: an analysis from the global burden of disease study 2019.

BACKGROUND: Nutritional deficiencies (ND) continue to threaten the lives of millions of people around the world, with children being the worst hit. Nevertheless, no systematic study of the epidemiological features of child ND has been conducted so far. Therefore, we aimed to comprehensively assess the burden of pediatric ND. METHODS: We analyzed data on pediatric ND between 1990 and 2019 from the Global Burden of Disease study (GBD) 2019 at the global, regional, and national levels. In addition, joinpoint regression models were used to assess temporal trends. RESULTS: In 2019, the number of prevalent cases of childhood malnutrition increased to 435,071,628 globally. The global age-standardized incidence, prevalence, and DALY rates showed an increasing trend between 1990 and 2019. Meanwhile, the burden of child malnutrition was negatively correlated with sociodemographic index (SDI). Asia and Africa still carried the heaviest burden. The burden and trends of child malnutrition varied considerably across countries and regions. At the age level, we found that malnutrition was significantly more prevalent among children < 5 years of age. CONCLUSION: Pediatric ND remains a major public health challenge, especially in areas with low SDI. Therefore, primary healthcare services in developing countries should be improved, and effective measures, such as enhanced pre-school education, strengthened nutritional support, and early and aggressive treatment, need to be developed.

Triplet-Induced Singlet Oxygen Photobleaches Near-Infrared Dye-Sensitized Upconversion Nanosystems.

The rapid photobleaching of near-infrared (NIR) dye-sensitized upconversion nanosystems is one of the crucial problems that has blocked their technological applications. Uncovering the photophysical and photochemical pathways of NIR dyes would help to elucidate the photobleaching mechanism and thereby improve the photostability of the system. Here we investigate the triplet dynamics of NIR dyes and their interaction with triplet oxygen in the typically investigated IR806-sensitized upconversion nanoparticle (UCNP) nanosystem. Low-temperature fluorescence at 77 K provides direct proof of the generation of singlet oxygen (1O2) under 808 nm laser irradiation. Mass spectrometry indicates that all three double bonds in the structure of IR806 can be broken in the photochemical process. Coupling IR806 to the surface of UCNPs can accelerate its triplet dynamics, thus producing more 1O2 to photocleave IR806. Importantly, we find that the addition of ß-carotene can scavenge the generated 1O2, thereby providing a simple method to effectively inhibit photobleaching.

Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer.

BACKGROUND: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. METHODS: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation. The motility and invasiveness of breast cancer cells were examined in vitro using wound healing and transwell invasion assays. The orthotopic spontaneous metastasis and intra-venous experimental metastasis assays were used to test the formation of metastasis in vivo, respectively. RESULTS: HSP90α interacts with NME1 and increases NME1 lifetime by impeding its ubiquitin-proteasome-mediated degradation. HSP90α overexpression significantly inhibits the metastatic potential of breast cancer cells in vitro and in vivo. A novel cell-permeable peptide, OPT22 successfully mimics the HSP90α function and prolongs the life span of endogenous NME1, resulting in reduced metastasis of breast cancer. CONCLUSION: These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy.

Solving Anderson Impurity Model by the Effective Hamiltonian Theory.

We apply the Self-Consistent Effective Hamiltonian Theory (SCEHT), which uses a general variational Fermionic many-body wave function to generate an effective Hamiltonian in a quadratic form, to the Anderson impurity model. The chiral symmetry-breaking quadratic effective Hamiltonian is solved exactly for the single Fermion excitation spectrum. We validate the theory by numerically solving a model problem. The solution shows the correct Kondo resonance in the quasi-particle density of states.

Icariin alleviates ferroptosis-related atherosclerosis by promoting autophagy in xo-LDL-induced vascular endothelial cell injury and atherosclerotic mice.

Vascular endothelial cells (VECs) are located between the blood plasma and the vascular tissue, and the ferroptosis (iron-dependent programmed cell death) of VECs can lead to a range of cardiovascular diseases. Icariin is the main active ingredient of Epimedium brevicornum Maxim., which can improve endothelial cell dysfunction. In the present study, the protective effects of icariin on oxidised low-density lipoprotein (ox-LDL)-treated VECs and high-fat diet-fed Apolipoprotein E-deficient mice were investigated. Inflammatory fibrosis in tissues and inflammatory factors in serum and cell supernatants were detected, and mitochondrial membrane potential and the expression levels of ferroptosis-associated proteins were also detected. The results revealed that icariin reduced the endothelial atherosclerotic plaque area and collagen fibres in aortic sinus tissue, and increased the viability and mitochondrial membrane potential, whereas it reduced the reactive oxygen species levels of VECs. The nucleation of transcription factor EB (TFEB) and subsequent autophagy were negatively associated with ferroptosis in endothelial cells, and the more prominent the autophagy, the lower the levels of ferroptosis. Furthermore, by co-treating the cells with icariin and the two autophagy inhibitors, Bafilomycin A1 (blocking autophagosome and lysosome fusion) and 3-methyladenine (blocking autophagosome formation), respectively, the promoting effects of icariin on autophagy were found to be mediated through the process of autophagosome-lysosome fusion. In in vivo experiments, icariin reduced ferroptosis, alleviated atherosclerotic lesions and increased the rate of TFEB nucleation. Additionally, it was found that ARG304, THR308 and GLN311 were the optimal binding sites for the interaction between icariin and TFEB. Taken together, these results suggest that the fusion of autophagosomes and lysosomes promoted by icarrin enhances autophagy and thus reduces ferroptosis. Therefore, icariin may be a potential candidate for the prevention of ferroptosis of VECs and, thus, for the treatment of cardiovascular diseases.

Salvianolic Acid B Inhibits Ferroptosis and Apoptosis during Myocardial Ischemia/Reperfusion Injury via Decreasing the Ubiquitin-Proteasome Degradation of GPX4 and the ROS-JNK/MAPK Pathways.

Myocardial ischemia/reperfusion injury (MIRI) is related to ferroptosis and apoptosis elicited by reactive oxygen species (ROS). In this research, we investigated the protective effect of salvianolic acid B (SAB) as a natural antioxidant on ferroptosis and apoptosis in the MIRI process, and discussed the protective mechanism inhibiting ubiquitin-proteasome degradation of glutathione peroxidase 4 (GPX4) and the c-Jun N-terminal kinases (JNK) apoptosis signal pathway. We observed that ferroptosis and apoptosis occurred in the MIRI rat model in vivo and the H9c2 cardiomyocyte hypoxia/reoxygenation (H/R) damage model in vitro. SAB can alleviate tissue damage related to ROS, ferroptosis and apoptosis. Ubiquitin-proteasome degradation of GPX4 occurred in H/R models, and SAB reduced the ubiquitin-proteasome degradation of GPX4. SAB downregulates JNK phosphorylation and the expression of BCL2-Associated X (Bax)/B-cell lymphoma-2 (Bcl-2) and Caspase-3 to inhibit apoptosis. The role of GPX4 in the cardioprotection of SAB was further verified by the elimination effect of the GPX4 inhibitor RAS-selective lethal 3 (RSL3). This research shows that SAB may be used as a myocardial protective agent against oxidative stress, ferroptosis and apoptosis, and has potential clinical application prospects.

Chemical Variation and Environmental Influence on Essential Oil of Cinnamomum camphora.

Cinnamomum camphora is a traditional aromatic plant used to produce linalool and borneol flavors in southern China; however, its leaves also contain many other unutilized essential oils. Herein, we report geographic relationships for the yield and compositional diversity of C. camphora essential oils. The essential oils of 974 individual trees from 35 populations in 13 provinces were extracted by hydrodistillation and analyzed qualitatively and quantitatively by gas chromatography-mass spectrometry and gas chromatography-flame ionization detection, respectively. Oil yields ranged from 0.01% to 3.46%, with a significantly positive correlation with latitude and a significantly negative correlation with longitude. In total, 41 compounds were identified, including 15 monoterpenoids, 24 sesquiterpenoids, and two phenylpropanoids. Essential oil compositions varied significantly among individuals and could be categorized into various chemotypes. The six main chemotypes were eucalyptol, nerolidol, camphor, linalool, selina, and mixed types. The other 17 individual plants were chemotypically rare and exhibited high levels of methyl isoeugenol, methyl eugenol, δ-selinene, or borneol. Eucalyptol-type plants had the highest average oil yield of 1.64%, followed in decreasing order by linalool-, camphor-, mixed-, selina-, and nerolidol-type plants. In addition, the five main compounds exhibited a clear geographic gradient. Eucalyptol and linalool showed a significantly positive correlation with latitude, while selina-6-en-4-ol was significantly and negatively correlated with latitude. trans-Nerolidol and selina-6-en-4-ol showed significantly positive correlations with longitude, whereas camphor was significantly and negatively correlated with longitude. Canonical correspondence analysis indicated that environmental factors could strong effect the oil yield and essential oil profile of C. camphora.

Multi-process and multi-pollutant control technology for ultra-low emissions in the iron and steel industry.

The iron and steel industry is not only an important foundation of the national economy, but also the largest source of industrial air pollution. Due to the current status of emissions in the iron and steel industry, ultra-low pollutant emission control technology has been researched and developed. Liquid-phase proportion control technology has been developed for magnesian fluxed pellets, and a blast furnace smelting demonstration project has been established to use a high proportion of fluxed pellets (80%) for the first time in China to realize source emission reduction of SO2 and NOx. Based on the characteristics of high NOx concentrations and the coexistence of multiple pollutants in coke oven flue gas, low-NOx combustion coupled with multi-pollutant cooperative control technology with activated carbon was developed to achieve efficient removal of multiple pollutants and resource utilization of sulfur. Based on the characteristics of co-existing multiple pollutants in pellet flue gas, selective non-catalytic reduction (SNCR) coupled with ozone oxidation and spray drying adsorption (SDA) was developed, which significantly reduces the operating cost of the system. In the light of the high humidity and high alkalinity in flue gas, filter materials with high humidity resistance and corrosion resistance were manufactured, and an integrated pre-charged bag dust collector device was developed, which realized ultra-low emission of fine particles and reduced filtration resistance and energy consumption in the system. Through source emission reduction, process control and end-treatment technologies, five demonstration projects were built, providing a full set of technical solutions for ultra-low emissions of dust, SO2, NOx, SO3, mercury and other pollutants, and offering technical support for the green development of the iron and steel industry.

[Lianmei Qiwu Decoction relieves diabetic cardiac autonomic neuropathy by regulating AMPK/TrkA/TRPM7 signaling pathway].

This study investigated the effect of Lianmei Qiwu Decoction(LMQWD) on the improvement of cardiac autonomic nerve remodeling in the diabetic rat model induced by the high-fat diet and explored the underlying mechanism of LMQWD through the AMP-activated protein kinase(AMPK)/tropomyosin receptor kinase A(TrkA)/transient receptor potential melastatin 7(TRPM7) signaling pathway. The diabetic rats were randomly divided into a model group, an LMQWD group, an AMPK agonist group, an unloaded TRPM7 adenovirus group(TRPM7-N), an overexpressed TRPM7 adenovirus group(TRPM7), an LMQWD + unloaded TRPM7 adenovirus group(LMQWD+TRPM7-N), an LMQWD + overexpressed TRPM7 adenovirus group(LMQWD+TRPM7), and a TRPM7 channel inhibitor group(TRPM7 inhibitor). After four weeks of treatment, programmed electrical stimulation(PES) was employed to detect the arrhythmia susceptibility of rats. The myocardial cell structure and myocardial tissue fibrosis of myocardial and ganglion samples in diabetic rats were observed by hematoxylin-eosin(HE) staining and Masson staining. The immunohistochemistry, immunofluorescence, real-time quantitative polymerase chain reaction(RT-PCR), and Western blot were adopted to detect the distribution and expression of TRPM7, tyrosine hydroxylase(TH), choline acetyltransferase(ChAT), growth associated protein-43(GAP-43), nerve growth factor(NGF), p-AMPK/AMPK, and other genes and related neural markers. The results showed that LMQWD could significantly reduce the arrhythmia susceptibility and the degree of fibrosis in myocardial tissues, decrease the levels of TH, ChAT, and GAP-43 in the myocardium and ganglion, increase NGF, inhibit the expression of TRPM7, and up-regulate p-AMPK/AMPK and p-TrkA/TrkA levels. This study indicated that LMQWD could attenuate cardiac autonomic nerve remodeling in the diabetic state, and its mechanism was associated with the activation of AMPK, further phosphorylation of TrkA, and inhibition of TRPM7 expression.

Au-TiO2/Ti Hybrid Coating as a Liquid and Gas Diffusion Layer with Improved Performance and Stability in Proton Exchange Membrane Water Electrolyzer.

The liquid and gas diffusion layer is a key component of proton exchange membrane water electrolyzer (PEMWE), and its interfacial contact resistance (ICR) and corrosion resistance have a great impact on the performance and durability of PEMWE. In this work, a novel hybrid coating with Au contacts discontinuously embedded in a titanium oxidized layer was constructed on a Ti felt via facile electrochemical metallizing and followed by a pre-oxidization process. The physicochemical characterizations, such as scanning electron microscopy, energy dispersive spectrometer, and X-ray diffraction results confirmed that the distribution and morphology of the Au contacts could be regulated with the electrical pulse time, and a hybrid coating (Au-TiO2/Ti) was eventually achieved after the long-term stability test under anode environment. At the compaction force of 140 N cm-2, the ICR was reduced from 19.7 mΩ cm2 of the P-Ti to 4.2 mΩ cm2 of the Au-TiO2/Ti. The corrosion current density at 1.8 V (RHE) is 0.689 µA cm-2. Both the ICR and corrosion resistance results showed that the prepared protective coating could provide comparable ICR and corrosion resistance to a dense Au coating.

High-Sensitivity Sensing of Divalent Copper Ions at the Single Upconversion Nanoparticle Level.

Single-nanoparticle-level sensing allows us to measure individual molecular interactions and probe environmental stimuli at nanometer-scale resolution. Despite these premises, limited success has been met hitherto due to the demanding challenge to distinguish a dimmed signal from a noisy background. Here, we describe an approach for high-sensitivity single-nanoparticle-level sensing of divalent copper (Cu2+) ions through near-infrared-to-visible upconversion luminescence against a near-null background. This nanosensor utilizes ytterbium- (Yb3+) and erbium (Er3+)-doped sodium yttrium fluoride (NaYF4) upconversion nanoparticles (UCNPs) (maximal emission at 540 nm when excited at 980 nm) as an energy donor, of which the surface attaches Cu2+-dependent DNAzymes labeled with BHQ1 dye (Black Hole Quencher 1, maximal absorption at 548 nm) as energy acceptors. Adding a hint amount of Cu2+ ions resulted in the cleavage of a BHQ1-containing moiety in DNAzymes, thus turning on upconversion luminescence for sensitive detection. Indeed, this approach allows us to perform single-nanoparticle-level detection of Cu2+ ions with extraordinary signal-to-noise ratios (SNRs, >277) for all measured concentrations that cover 3 orders of magnitude (from sub-nM to µM). Importantly, a limit of detection of 220 pM was achieved, about sevenfold lower than the one at the ensemble level. Moreover, a stochastic particle-to-particle sensing behavior was also identified, featuring single-nanoparticle-level detection. This work untaps the usage of UCNPs for high-sensitivity single-nanoparticle-level biosensing.

Does public fear that bats spread COVID-19 jeopardize bat conservation?

With >1 400 species, bats comprise the second-largest order of mammals and provide critical ecological services as insect consumers, pollinators, and seed dispersers. Yet, bats are frequently associated with infectious human diseases such as SARS, MERS, and Ebola. As early as the end of January 2020, several virological studies have suggested bats as a probable origin for SARS-CoV-2, the causative agent of COVID-19. How does the public view the role of bats in COVID-19? Here we report pilot data collected shortly after the outbreak of COVID-19 using two online surveys, combined with a conservation intervention experiment, primarily on people who are receiving or have received higher education in China. We found that 84% of the participants of an online survey (n = 13 589) have misunderstood the relationship between bats and COVID-19, which strengthened negative attitudes towards bats. Knowledge of bats, gender, and education level of the participants affected their attitudes towards bats. Participants who indicated a better knowledge of bats had a more positive attitude towards bats. The proportion of female participants who had negative attitudes towards bats was higher than that of male participants. Participants with a higher education level indicated a more positive attitude towards bats after the outbreak of COVID-19. A specially prepared bat conservation lecture improved peoples' knowledge of bats and the positive attitudes, but failed to correct the misconception that bats transmit SARS-CoV-2 to humans directly. We suggest that the way virologists frame the association of bats with diseases, the countless frequently inaccurate media coverages, and the natural perceptual bias of bats carrying and transmitting diseases to humans contributed to the misunderstandings. This probably led to a rise in the events of evicting bats from dwellings and structures by humans and the legislative proposal for culling disease-relevant wildlife in China. A better understanding of the relationship between disease, wildlife and human health could help guide the public and policymakers in an improved program for bat conservation.

In vivo multivesicular bodies and their exosomes in the absorptive cells of the zebrafish (Danio Rerio) gut.

Intercellular communication of gut epithelial cells is critical to gut mucosal homeostasis. Exosomes are important intercellular mediators in communication between cell to cell. Although many literature focus on the immunologic roles in the gut by the exosomes, the biological process of exosomes in the absorptive cells remains unknown. Uncovering the distribution, classification and formation process of multivesicular bodies (MVBs) and their exosomes in the absorptive cells of the zebrafish gut, is urgently needed to establish a platform for immunological research of fish gut exosomes. The expression levels of CD63 and TSG101 were different among the three segments of the gut, and they were enriched at the apex of the mid gut villi. The characteristics of MVBs and their exosomes in the absorptive cells were further revealed by transmission electron microscopy (TEM). Early endosomes (ee) were mainly present in the apical and basal cytoplasm of absorptive cells. Late endosomes (le) were mostly distributed with the supranuclear part of these cells. "Heterogeneous" MVBs were detected underlying the apical membranes of absorptive cells. Many exosomes with some MVB-like structures occurred in the lumen, indicating that the release process was mainly through apical secretion. Various MVBs with exosomes and the endosome-heterogeneous MVB-exosome complex existed widely in the mid gut absorptive cells, concluding that zebrafish as a potential model for in vivo MVBs and their exosomes research. All the results were summarized in a schematic diagram illustrating the morphological characteristics of gut MVBs and their exosomes in zebrafish.

The dynamic distribution of duck Tembusu virus in the spleen of infected shelducks.

BACKGROUND: Duck Tembusu virus (DTMUV) is a novel member of Flavivirus. The isolated and purified DTMUV strain XZ-2012 was used as a strain model, to intramuscularly inject the six-month egg-laying shelducks with the infective dose of 104TCID50. The dynamic distribution of the virus in spleen at different time post-infection (pi) was studied using RT-PCR, RT-qPCR, ELISA, immunofluorescence and transmission electron microscopy (TEM). RESULT: The results showed that the virus occurred in the spleen after 2 hpi and lasted up to 18 dpi. The registered viral load increased from 2 hpi to 3 dpi, and then it diminished from 6 dpi to 18 dpi with a slight rise at 12 dpi. From 2 hpi to 6 dpi the DTMUV particles were mostly distributed in the periellipsoidal lymphatic sheath (PELS) of spleen white pulp, few being found in the sheathed capillary. From 9 dpi to 18 dpi, the DTMUV particles were migrating into periarterial lymphatic sheaths (PALS) around the central artery through the red pulp. Under TEM, the virus particles could be observed mostly in lymphocytes and macrophages. CONCLUSION: It was suggested that DTMUV invaded lymphocytes and macrophages of the spleen at 2 hpi and replicated significantly from 1 dpi to 3 dpi, being eliminated from 9 dpi to 18 dpi. This is the first study on the dynamic distribution of DTMUV from invasion to elimination in duck spleen conducted by molecular and morphological methods. It could provide theoretical basis for the occurrence, development and detoxification of the virus in the organs of the immune system.

Full-Length Transcriptome Sequencing and Different Chemotype Expression Profile Analysis of Genes Related to Monoterpenoid Biosynthesis in Cinnamomum porrectum.

Leaves of C. porrectum are rich in essential oils containing monoterpenes, sesquiterpenes and aromatic compounds, but the molecular mechanism of terpenoid biosynthesis in C. porrectum is still unclear. In this paper, the differences in the contents and compositions of terpenoids among three chemotypes were analyzed using gas chromatography mass spectrometry (GC/MS). Furthermore, the differential expression of gene transcripts in the leaf tissues of the three C. porrectum chemotypes were analyzed through a comparison of full-length transcriptomes and expression profiles. The essential oil of the three C. porrectum chemotypes leaves was mainly composed of monoterpenes. In the full-length transcriptome of C. porrectum, 104,062 transcripts with 306,337,921 total bp, an average length of 2944 bp, and an N50 length of 5449 bp, were obtained and 94025 transcripts were annotated. In the eucalyptol and linalool chemotype, the camphor and eucalyptol chemotype, and the camphor and linalool chemotype comparison groups, 21, 22 and 18 terpene synthase (TPS) unigenes were identified respectively. Three monoterpene synthase genes, CpTPS3, CpTPS5 and CpTPS9, were upregulated in the eucalyptol chemotype compared to the linalool chemotype and camphor chemotype. CpTPS1 was upregulated in the camphor chemotype compared to the linalool chemotype and the eucalyptol chemotype. CpTPS4 was upregulated in the linalool chemotype compared to the camphor chemotype and the eucalyptol chemotype. Different unigenes had different expression levels among the three chemotypes, but the unigene expression levels of the 2-C-methyl-D-erythritol 4phosphate (MEP) pathway were generally higher than those of the mevalonate acid (MVA) pathway. Quantitative reverse transcription PCR(qRT-PCR) further validated these expression levels. The present study provides new clues for the functional exploration of the terpenoid synthesis mechanism and key genes in different chemotypes of C. porrectum.

A "Lamellar structure" contributes to autophagosome biogenesis and mitophagy in zebrafish hepatocytes.

Despite many studies being conducted over the past few decades, the origin of autophagosomal membranes remains unclear. The present study aimed to uncover the formation process of autophagosomal membranes in hepatocytes of zebrafish (Danio rerio), a model organism in medical science. Immunohistochemistry of zebrafish hepatocytes indicated that light chain 3-like protein 2 (LC3-II) is highly active in some hepatocytes, but poorly expressed in others. Under transmission electron microscopy, the amount of autophagosomes (APs) varied in different hepatocytes. When the endoplasmic reticulum (ER) is dispersed in the cytoplasm, few isolation membranes (IMs) and APs were observed. Subsequently, when the ER assembles into a particular "lamellar structure" (LS), IMs arise from it and extend to enwrap the mitochondria. With further aggregation of the ER, the LS developed into an over twenty-layered structure, and mitophagy was more obvious in the hepatocytes and cavities appeared in mitochondria. Finally, most ERs were assembled into several LSs. At this point, mitophagy was most active in the hepatocytes. Thereafter, glycogen and lipid droplet increased gradually, while the LS degenerated and ER scatter increased. Then, the glycogen and lipid droplets dominated the hepatocellular cytoplasm. After suppressing the formation of autophagosomes using 3-Methyladenine (3-MA), the LS could no longer be visualized in the hepatocellular cytoplasm, and mitophagy decreased drastically. Taken together, the results suggested that this LS in the hepatocytes of zebrafish, might be another manifestation of a pre-autophagosomal structure in zebrafish liver, analogous to the omegasome in yeast or the ER-IM complex in mammalian cell lines. Furthermore, selective mitophagy and consequent cyclic utilization of its products were probably relevant to dynamic cycle of the hepatocellular cytoplasm.

Dye-sensitized lanthanide-doped upconversion nanoparticles.

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising for applications as wide as biological imaging, multimodal imaging, photodynamic therapy, volumetric displays, and solar cells. Yet, the weak and narrow absorption of lanthanide ions poses a fundamental limit of UCNPs to withhold their brightness, creating a long-standing hurdle for the field. Dye-sensitized UCNPs are emerging to address this performance-limiting problem, yielding up to thousands-fold brighter luminescence than conventional UCNPs without dye sensitization. In their configuration, organic dyes with spectrally broad and intense absorption are anchored to the surface of UCNPs to harvest the excitation light energy, which is then transferred via Förster and/or Dexter mechanisms across the organic/inorganic interface to the lanthanides incorporated in UCNPs (with or devoid of a shell) to empower efficient upconversion. This tutorial review highlights recent progress in the development of dye sensitized UCNPs, with an emphasis on the theory of energy transfer, the geometric classification of the dye sensitized core and core/shell nanocrystals, and their emerging photonic and biophotonic applications. Opportunities and challenges offered by dye sensitized UCNPs are also discussed.