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Since the first two novel coronavirus cases appeared in January of 2020, the outbreak of the COVID-19 epidemic seriously threatens the public health of Italy. In this article, the distribution characteristics and spreading of COVID-19 in various regions of Italy were analysed by heat maps. Meanwhile, spatial autocorrelation, spatiotemporal clustering analysis and kernel density method were also applied to analyse the spatial clustering of COVID-19. The results showed that the Italian epidemic has a temporal trend and spatial aggregation. The epidemic was concentrated in northern Italy and gradually spread to other regions. Finally, the Google Trends index of the COVID-19 epidemic was further employed to build a prediction model combined with machine learning algorithms. By using Adaboost algorithm for single-factor modelling,the results show that the AUC of these six features (mask, pneumonia, thermometer, ISS, disinfection and disposable gloves) are all >0.9, indicating that these features have a large contribution to the prediction model. It is also implied that the public's attention to the epidemic is increasing as well as the awareness of the need for protective measures. This increased awareness of the epidemic will prompt the public to pay more attention to protective measures, thereby reducing the risk of coronavirus infection.

Peste des Petits Ruminants (PPR) is an acute and highly contagious transboundary disease caused by the PPR virus (PPRV). The virus infects goats, sheep and some wild relatives of small domestic ruminants, such as antelopes. PPR is listed by the World Organization for Animal Health as an animal disease that must be reported promptly. In this paper, PPR outbreak data combined with WorldClim database meteorological data were used to build a PPR prediction model. Using feature selection methods, eight sets of features were selected: bio3, bio10, bio15, bio18, prec7, prec8, prec12, and alt for modeling. Then different machine learning algorithms were used to build models, among which the random forest (RF) algorithm was found to have the best modeling effect. The ACC value of prediction accuracy for the model on the training set can reach 99.10%, while the ACC on the test sets was 99.10%. Therefore, RF algorithms and eight features were finally selected to build the model in order to build the online prediction system. In addition, we adopt single-factor modeling and correlation analysis of modeling variables to explore the impact of each variable on modeling results. It was found that bio18 (the warmest quarterly precipitation), prec7 (the precipitation in July), and prec8 (the precipitation in August) contributed significantly to the model, and the outbreak of the epidemic may have an important relationship with precipitation. Eventually, we used the final qualitative prediction model to establish a global online prediction system for the PPR epidemic.

The flavonoid dihydromyricetin (DMY) is the main component of Ampelopsis grossedentata (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MSn. Of the 31 compounds detected, 29 were identified based on previous results. Then, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by 1H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.

The interaction between three flavonoids, i.e., Luteolin (LTL), Quercetin (QCT), and Naringenin (NGN) and bovine lactoferrin (BLF) at pH 7.4 was investigated by fluorescence quenching spectra, synchronous fluorescence spectra, and UV-visible absorption spectra. The results indicate the fluorescence of BLF quenched by Luteolin (LTL), Quercetin (QCT), and Naringenin (NGN) via static quenching. The main force between QCT and LTL with BLF was van der Waals interactions and hydrogen bonds. Electrostatic interactions played a major role in the binding process of interaction between NGN and BLF. Synchronous fluorescence was used to study the conformational changes of BLF. The values of binding constant (Ka) and number of binding sites (n) at different temperatures (300K, 305K, 310K) were also calculated, respectively. The results of corresponding thermodynamic parameters as well as binding distance between BLF and LTL, QCT, or GNG were obtained. These results implied that Luteolin (LTL), Quercetin (QCT), and Naringenin (NGN) could provide important guides for compound quantity (e.g., medicine dosage) and the design of new compounds (or drugs).

We previously reported unexpected apoptosis-like cell death induced by nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish. To assess whether the pore formation mechanism underlay the action of NV, the change in cell membrane permeability was studied in both chicken erythrocytes and human CNE-2 cells. Initially, paradoxical results were derived from osmoprotectant protection assays. Polyethylene glycol (PEG)2000, which completely inhibited the NV induced hemolysis, failed to protect CNE-2 cells. Detailed experiments showed that PEG protection from hemolysis is concentration dependent and indicated caution when estimating the pore size formed by NV with the osmotic protection method. NV-treated CNE-2 cells remained impermeable to dyes with various molecular weights (MWs) (622.6-40,000 Da). Furthermore, membrane depolarization and selective permeability to Na+ other than K+ were induced in CNE-2 cells. No oxidative damage to the cell membrane was detected. Amiloride, an inhibitor of Na+/H+ exchanger (NHE), substantially protected both CNE-2 cells and erythrocytes from NV. Combined with the previously reported increase in intracellular pH, we supposed that NV activated plasma membrane NHE without forming transmembrane pores. Interestingly, glutathione (GSH) showed significant protection to CNE-2 cells while potentiating the hemolytic power of NV. This finding may suggest a key role of reactive oxygen species (ROS) in the cytotoxicity of NV. To the best of our knowledge, this is the first report that a hemolytic jellyfish venom acts through NHE in a manner other than compromising membrane integrity. The current work provides new insight into the arsenal of toxic jellyfishes.

African swine fever (ASF) is a virulent infectious disease of pigs. As there is no effective vaccine and treatment method at present, it poses a great threat to the pig industry once it breaks out. In this paper, we used ASF outbreak data and the WorldClim database meteorological data and selected the CfsSubset Evaluator-Best First feature selection method combined with the random forest algorithms to construct an African swine fever outbreak prediction model. Subsequently, we also established a test set for data other than modelling, and the accuracy accuracy value range of the model on the independent test set was 76.02%-84.64%, which indicated that the modelling effect was better and the prediction accuracy was higher than previous estimates. In addition, logistic regression analysis was conducted on 12 features used for modelling and the ROC curves were drawn. The results showed that the bio14 features (precipitation of driest month) had the largest contribution to the outbreak of ASF, and it was speculated that the outbreak of the epidemic was significantly related to precipitation. Finally, we used this qualitative prediction model to build a global online prediction system for ASF outbreaks, in the hope that this study will help to decision-makers who can then take the relevant prevention and control measures in order to prevent the further spread of future epidemics of the disease.

Gynostemma pentaphyllum (Thunb.) Makino (GpM) and its derivatives, especially gypenosides (Gyps), are widely used as safe and convenient natural herbal drugs for the treatment of many diseases for a long time, and Gyps have different oral bioavailability (OB) values and low ability to cross the blood-brain barrier (BBB). The effects of GpM and isolates on fibrosis, inflammation, oxidation, proliferation and migration are proved. GpM shows bidirectional regulation effect on proliferation, oxidation and apoptosis in tumor and non-tumor cells. GpM and its extractions can resist proliferation, activate oxidation and apoptosis in tumor cells and have opposite effects on non-tumor cells. We succinctly present some current views of medicinal value and potential therapeutic mechanisms of GpM and its derivatives.

Protein arginine methyltransferase 5 interacts with and methylates apoptosis signal–regulating kinase 1 at arginine residue 89, thereby negatively regulating its activity by promoting the interaction between ASK1 and Akt and thus phosphorylating ASK1 at serine residue 83., We describe a novel functional interaction between ASK1 and PRMT5. We show that PRMT5 interacts with and methylates ASK1 at arginine residue 89 and thereby negatively regulates its activity by promoting the interaction between ASK1 and Akt and thus phosphorylating ASK1 at serine residue 83. Furthermore, the association between ASK1 and Akt is enhanced by VEGF stimulation, and PRMT5 is required for this association. Moreover, PRMT5-mediated ASK1 methylation impaired the H2O2-induced activity of ASK1, and this inhibitory effect of PRMT5 was abolished by replacement of arginine 89 with Trp or depletion of PRMT5 expression by RNA interference. Together the results demonstrate cross-talk between arginine methylation and serine phosphorylation in ASK1.

Rubusoside is a natural sweetener and the active component of Rubus suavissimus. The preventive and therapeutic effect of rubusoside on high-fat diet-induced (HFD) serum metabolite changes in golden hamsters was analyzed by 1H-NMR metabolomics to explore the underlying mechanism of lipid metabolism regulation. 1H-NMR serum metabolomics analyses revealed a disturbed amino acid-, sugar-, fat-, and energy metabolism in HFD animals. Animals supplemented with rubusoside can partly reverse the metabolism disorders induced by high-fat diet and exerted good anti-hypertriglyceridemia effect by intervening in some major metabolic pathways, involving amino acid metabolism, synthesis of ketone bodies, as well as choline and 4-hydroxyphenylacetate metabolism. This study indicates that rubusoside can interfere with and normalize high-fat diet-induced metabolic changes in serum and could provide a theoretical basis to establish rubusoside as a potentially therapeutic tool able to revert or prevent lipid metabolism disorders.

The present work investigated the in vitro cytotoxicity of nematocyst venom (NV) from Chrysaora helvola Brandt (C. helvola) jellyfish against human MCF-7 and CNE-2 tumor cell lines. Potent cytotoxicity was quantified using the MTT assay (LC50=12.07±3.13 and 1.6±0.22μg/mL (n=4), respectively). Apoptosis-like cell death was further confirmed using the LDH release assay and Annexin V/PI double staining-based flow cytometry analysis. However, only activation of caspase-4 was observed. It is possible that some caspase-independent pathways were activated by the NV treatment. Since no reference or antivenom is available, the effects of several commonly used antidotes on the cytotoxicity of NV were examined on more sensitive CNE-2 cells to determine the appropriate emergency measures for envenomation by C. helvola. The phospholipase A2 (PLA2) inhibitor para-bromophenacyl bromide (pBPB) showed no protective effect, while Mg(2+) potentiated cytotoxicity. Voltage-gated L-type Ca(2+) channel blockers (verapamil, nifedipine and felodipine) and Na-Ca(2+) exchanger inhibitor KB-R7943 also showed no effect. Assays using Ca(2+)-free culture media or the intracellular Ca(2+) chelator BAPTA also could not inhibit the cytotoxicity. Taken together, these results suggest that PLA2 and Ca(2+) are not directly involved in the cytotoxicity of NV from C. helvola. Our work also suggests caution regarding the choice for first aid for envenomation by C. helvola jellyfish.

The present work investigated the effects of the nematocysts venom (NV) from the Chrysaora helvola Brandt (C. helvola) jellyfish on the human nasopharyngeal carcinoma cell line, CNE-2. The medium lethal concentration (LC50), quantified by MTT assays, was 1.7 ± 0.53 μg/mL (n = 5). An atypical apoptosis-like cell death was confirmed by LDH release assay and Annexin V-FITC/PI staining-based flow cytometry. Interestingly, activation of caspase-4 other than caspase-3, -8, -9 and -1 was observed. Moreover, the NV stimuli caused a time-dependent loss of mitochondrial membrane potential (ΔΨm) as was an intracellular ROS burst. These results indicated that there was uncoupling of oxidative phosphorylation (UOP). An examination of the intracellular pH value by a pH-sensitive fluorescent probe, BCECF, suggested that the UOP was due to the time-dependent increase in the intracellular pH. This is the first report that jellyfish venom can induce UOP.