USP14-regulated allostery of the human proteasome by time-resolved cryo-EM.

Proteasomal degradation of ubiquitylated proteins is tightly regulated at multiple levels1-3. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating enzyme ubiquitin-specific protease 14 (USP14), which reversibly binds the proteasome and confers the ability to edit and reject substrates. How USP14 is activated and regulates proteasome function remain unknown4-7. Here we present high-resolution cryo-electron microscopy structures of human USP14 in complex with the 26S proteasome in 13 distinct conformational states captured during degradation of polyubiquitylated proteins. Time-resolved cryo-electron microscopy analysis of the conformational continuum revealed two parallel pathways of proteasome state transitions induced by USP14, and captured transient conversion of substrate-engaged intermediates into substrate-inhibited intermediates. On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate8-10, enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding. Dynamic USP14-ATPase interactions decouple the ATPase activity from RPN11-catalysed deubiquitylation11-13 and kinetically introduce three regulatory checkpoints on the proteasome, at the steps of ubiquitin recognition, substrate translocation initiation and ubiquitin chain recycling. These findings provide insights into the complete functional cycle of the USP14-regulated proteasome and establish mechanistic foundations for the discovery of USP14-targeted therapies.

Pathogenic bacteria exploit transferrin receptor transcytosis to penetrate the blood-brain barrier.

The human blood-brain barrier (BBB) comprises a single layer of brain microvascular endothelial cells (HBMECs) protecting the brain from bloodborne pathogens. Meningitis is among the most serious diseases, but the mechanisms by which major meningitis-causing bacterial pathogens cross the BBB to reach the brain remain poorly understood. We found that Streptococcus pneumoniae, group B Streptococcus, and neonatal meningitis Escherichia coli commonly exploit a unique vesicle fusion mechanism to hitchhike on transferrin receptor (TfR) transcytosis to cross the BBB and illustrated the details of this process in human BBB model in vitro and mouse model. Toll-like receptor signals emanating from bacteria-containing vesicles (BCVs) trigger K33-linked polyubiquitination at Lys168 and Lys181 of the innate immune regulator TRAF3 and then activate the formation of a protein complex containing the guanine nucleotide exchange factor RCC2, the small GTPase RalA and exocyst subcomplex I (SC I) on BCVs. The distinct function of SEC6 in SC I, interacting directly with RalA on BCVs and the SNARE protein SNAP23 on TfR vesicles, tethers these two vesicles and initiates the fusion. Our results reveal that innate immunity triggers a unique modification of TRAF3 and the formation of the HBMEC-specific protein complex on BCVs to authenticate the precise recognition and selection of TfR vesicles to fuse with and facilitate bacterial penetration of the BBB.

Single-cell transcriptomic signatures and gene regulatory networks modulated by Wls in mammalian midline facial formation and clefts.

Formation of highly unique and complex facial structures is controlled by genetic programs that are responsible for the precise coordination of three-dimensional tissue morphogenesis. However, the underlying mechanisms governing these processes remain poorly understood. We combined mouse genetic and genomic approaches to define the mechanisms underlying normal and defective midfacial morphogenesis. Conditional inactivation of the Wnt secretion protein Wls in Pax3-expressing lineage cells disrupted frontonasal primordial patterning, cell survival and directional outgrowth, resulting in altered facial structures, including midfacial hypoplasia and midline facial clefts. Single-cell RNA sequencing revealed unique transcriptomic atlases of mesenchymal subpopulations in the midfacial primordia, which are disrupted in the conditional Wls mutants. Differentially expressed genes and cis-regulatory sequence analyses uncovered that Wls modulates and integrates a core gene regulatory network, consisting of key midfacial regulatory transcription factors (including Msx1, Pax3 and Pax7) and their downstream targets (including Wnt, Shh, Tgfß and retinoic acid signaling components), in a mesenchymal subpopulation of the medial nasal prominences that is responsible for midline facial formation and fusion. These results reveal fundamental mechanisms underlying mammalian midfacial morphogenesis and related defects at single-cell resolution.

Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome.

The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate.

Temperature sensing using junctions between mobile ions and mobile electrons.

Sensing technology is under intense development to enable the Internet of everything and everyone in new and useful ways. Here we demonstrate a method of stretchable and self-powered temperature sensing. The basic sensing element consists of three layers: an electrolyte, a dielectric, and an electrode. The electrolyte/dielectric interface accumulates ions, and the dielectric/electrode interface accumulates electrons (in either excess or deficiency). The ions and electrons at the two interfaces are usually not charge-neutral, and this charge imbalance sets up an ionic cloud in the electrolyte. The design functions as a charged temperature-sensitive capacitor. When temperature changes, the ionic cloud changes thickness, and the electrode changes open-circuit voltage. We demonstrate high sensitivity (∼1 mV/K) and fast response (∼10 ms). Such temperature sensors can be made small, stable, and transparent. Depending on the arrangement of the electrolyte, dielectric, and electrode, we develop four designs for the temperature sensor. In addition, the temperature sensor has good linearity in the range of tens of Kelvin. We further show that the temperature sensors can be integrated into stretchable electronics and soft robots.

Molecular-scale axial localization by repetitive optical selective exposure.

We introduce an axial localization with repetitive optical selective exposure (ROSE-Z) method for super-resolution imaging. By using an asymmetric optical scheme to generate interference fringes, a <2 nm axial localization precision was achieved with only ~3,000 photons, which is an approximately sixfold improvement compared to previous astigmatism methods. Nanoscale three-dimensional and two-color imaging was demonstrated, illustrating how this method achieves superior performance and facilitates the investigation of cellular nanostructures.

Dynamics studies for the multi-well and multi-channel reaction of OH with C2H2 on a full-dimensional global potential energy surface.

The C2H2 + OH reaction is an important acetylene oxidation pathway in the combustion process, as well as a typical multi-well and multi-channel reaction. Here, we report an accurate full-dimensional machine learning-based potential energy surface (PES) for the C2H2 + OH reaction at the UCCSD(T)-F12b/cc-pVTZ-F12 level, based on about 475 000 ab initio points. Extensive quasi-classical trajectory (QCT) calculations were performed on the newly developed PES to obtain detailed dynamic data and analyze reaction mechanisms. Below 1000 K, the C2H2 + OH reaction produces H + OCCH2 and CO + CH3. With increasing temperature, the product channels H2O + C2H and H + HCCOH are accessible and the former dominates above 1900 K. It is found that the formation of H2O + C2H is dominated by a direct reaction process, while other channels belong to the indirect mechanism involving long-lived intermediates along the reaction pathways. At low temperatures, the C2H2 + OH reaction behaves like an unimolecular reaction due to the unique PES topographic features, of which the dynamic features are similar to the decomposition of energy-rich complexes formed by C2H2 + OH collision. The classification of trajectories that undergo different reaction pathways to generate each product and their product energy distributions were also reported in this work. This dynamic information may provide a deep understanding of the C2H2 + OH reaction.

Formation Mechanisms of Electronically Excited Nitrogen Molecules from N + N2 and N + N + N Collisions Revealed by Full-Dimensional Potential Energy Surfaces.

This work reports six new full-dimensional adiabatic potential energy surfaces (PESs) of the N3 system (four 4A″ states and two 2A″ states) at the MRCI + Q/AVQZ level of theory that correlated to N2(X1Σg+) + N(4S), N2(X1Σg+) + N(2D), N2(A3Σu+) + N(4S), N2(B3Πg) + N(4S), N2(W3Δu) + N(4S), and N(4S) + N(4S) + N(4S) channels. The neural networks with a proper account of the nuclear permutation invariant symmetry of N3 were employed to fit the PESs based on about 4000 ab initio points. The accuracy of the PESs was validated by excellent agreement on the equilibrium bond length, vertical excitation energy, and dissociation energy with experimental values. Two possible mechanisms of the formation of N2(A) were found. One is that the collision occurs between N2(X) and N(4S) in the 14A″ state, followed by a nonadiabatic transition through the conical intersection with the 24A″ PES, resulting in the formation of the N2(A) + N(4S) product. The other takes place in the collision among three N(4S) atoms in the adiabatic 24A″ state, and then, N2(A) + N(4S) is formed. This is the first systematical research of the N3 system focusing on the formation of the excited states of N2 via both adiabatic and nonadiabatic pathways.

Effect of lung isolation with different airway devices on postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery: a propensity score-matched study.

BACKGROUND: Postoperative pneumonia is one of the common complications after video-assisted thoracoscopic surgery. There is no related study on the effect of lung isolation with different airway devices on postoperative pneumonia. Therefore, in this study, the propensity score matching method was used to retrospectively explore the effects of different lung isolation methods on postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery. METHODS: This is A single-center, retrospective, propensity score-matched study. The information of patients who underwent VATS in Weifang People 's Hospital from January 2020 to January 2021 was retrospectively included. The patients were divided into three groups according to the airway device used in thoracoscopic surgery: laryngeal mask combined with bronchial blocker group (LM + BB group), tracheal tube combined with bronchial blocker group (TT + BB group) and double-lumen endobronchial tube group (DLT group). The main outcome was the incidence of pneumonia within 7 days after surgery; the secondary outcome were hospitalization time and hospitalization expenses. Patients in the three groups were matched using propensity score matching (PSM) analysis. RESULTS: After propensity score matching analysis, there was no significant difference in the incidence of postoperative pneumonia and hospitalization time among the three groups (P > 0.05), but there was significant difference in hospitalization expenses among the three groups (P < 0.05). CONCLUSIONS: There was no significant difference in the effect of different intubation lung isolation methods on postoperative pneumonia in patients undergoing thoracoscopic surgery.

Preparation of milk fat globule membrane ingredients enriched in polar lipids: Composition characterization and digestive properties.

In this study, milk fat globule membrane (MFGM) ingredients enriched in polar lipids were prepared using membrane filtration, including microfiltration, diafiltration, and ultrafiltration from butter serum powder. Polar lipids (phospholipids, sterols, and gangliosides) in prepared MFGM ingredients were analyzed by 31P nuclear magnetic resonance spectroscopy, GC-MS, and ultra-performance liquid chromatography (UPLC)-MS/MS, respectively. The lipolysis degree and microstructure of MFGM ingredient and soybean lecithin (SL) emulsions during in vitro digestion were also analyzed. Microfiltration showed higher concentration efficiency than ultrafiltration, which increased by 2.16% and 2.73% in phospholipids, respectively. Moreover, diafiltration concentrated more polar lipids (6.39% of phospholipids) than microfiltration. Milk fat globule membrane ingredients had high levels of sphingomyelin (1.27%-1.36%) and ratio of GD3 to GM3 is 9.25- to 9.88-fold. The different lipolysis behaviors between MFGM ingredient emulsions and SL emulsions were correlated with their different polar lipid compositions. Phospholipids from both MFGM ingredients and SL could help maintain the initial structure during the gastric digestion. These results could provide a scientific basis for developing high-polar-lipids food, particularly infant formulas and special functional foods.

Fabrication of Human Milk Fat Substitute: Based on the Similarity Evaluation Model and Computer Software.

We aimed to obtain the optimal formula for human milk fat substitute (HMFS) through a combination of software and an evaluation model and further verify its practicability through an animal experiment. The results showed that a total of 33 fatty acid (FA) and 63 triglyceride (TAG) molecular species were detected in vegetable oils. Palmitic acid, oleic acid, linoleic acid, 18:1/16:0/18:1, 18:2/16:0/18:2, 18:1/18:1/18:1 and 18:1/18:2/18:1, were the main molecular species among the FAs and TAGs in the vegetable oils. Based on the HMFS evaluation model, the optimal mixed vegetable oil formula was blended with 21.3% palm oil, 2.8% linseed oil, 2.6% soybean oil, 29.9% rapeseed oil and 43.4% maize oil, with the highest score of 83.146. Moreover, there was no difference in the weight, blood routine indices or calcium and magnesium concentrations in the feces of the mice between the homemade mixed vegetable oil (HMVO) group and the commercial mixed vegetable oil (CMVO) group, while nervonic acid (C24:1) and octanoic acid (C8:0) were absorbed easily in the HMVO group. Therefore, these results demonstrate that the mixing of the different vegetable oils was feasible via a combination of computer software and an evaluation model and provided a new way to produce HMFS.

A Novel Bifidobacterium/Klebsiella Ratio in Characterization Analysis of the Gut and Bile Microbiota of CCA Patients.

Cholangiocarcinoma (CCA) is a serious health problem worldwide. The gut and bile microbiota have not been clearly characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA need to be established. The aim of this study was to investigate the characteristics of the gut and bile microbiota in CCA patients. Forty-two CCA patients and 16 healthy normal controls (HNCs) were enrolled. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. We found that there were significant differences in the species diversity, structure, and composition of the microbial communities between the CCA group and the HNC grouAt the phylum level, compared with that in the HNC group, the relative abundance of Firmicutes and Actinobacteriota was significantly decreased in the CCA group, whereas Proteobacteria and Bacteroidota were significantly enriched. The Firmicutes/Bacteroidota (F/B) ratio significantly decreased in the CCA group compared to the HNC grouThe relative abundance of Klebsiella in the CCA group was significantly higher than that in the HNC group, while the relative abundance of Bifidobacterium was significantly decreased. The Bifidobacterium/Klebsiella (B/K) ratio was established as a novel biomarker and was found to be significantly decreased in the CCA group compared with the HNC grouOur findings provide evidence supporting the use of Klebsiella and Bifidobacterium as noninvasive intestinal microbiomarkers for improving the diagnosis of CCA.

Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length.

Previous studies have reported the immunotoxicity of per- and polyfluoroalkyl substances (PFASs), but it remains a significant challenge to assess over 10,000 distinct PFASs registered in the distributed structure-searchable toxicity (DSSTox) database. We aim to reveal the mechanisms of immunotoxicity of different PFASs and hypothesize that PFAS immunotoxicity is dependent on the carbon chain length. Perfluorobutanesulfonic acid (PFBA), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) representing different carbon chain lengths (4-9) at environmentally relevant levels strongly reduced the host's antibacterial ability during the zebrafish's early-life stage. Innate and adaptive immunities were both suppressed after PFAS exposures, exhibiting a significant induction of macrophages and neutrophils and expression of immune-related genes and indicators. Interestingly, the PFAS-induced immunotoxic responses were positively correlated to the carbon chain length. Moreover, PFASs activated downstream genes of the toll-like receptor (TLR), uncovering a seminal role of TLR in PFAS immunomodulatory effects. Myeloid differentiation factor 88 (MyD88) morpholino knock-down experiments and MyD88 inhibitors alleviated the immunotoxicity of PFASs. Overall, the comparative results demonstrate differences in the immunotoxic responses of PFASs due to carbon chain length in zebrafish, providing new insights into the prediction and classification of PFASs mode of toxic action based on carbon chain length.

A numerical model for water hydration on nanosurfaces: from friction to hydrophilicity and hydrophobicity.

Fluidic transport down to the nanometer scale is of great importance for a wide range of applications such as energy harvesting, seawater desalination, and water treatment and may help to understand many biological processes. In this work, we studied the interfacial friction of liquid water on a series of nanostructures through molecular dynamics (MD) simulations. Our results reveal that the friction coefficient of the water-solid interface cannot be described using a previously reported simple function of the free energy corrugation. Considering that the water-solid friction is firmly correlated with the microscopic water motion, we proposed a probability parameter P(d, t) to classify water motion modes on a surface. We demonstrate that this parameter can be used to accurately predict the water-solid friction by simply monitoring the water binding time on a nanosurface. More importantly, according to the relationship between P(d, t) and friction, we found that the friction coefficient can be used as an indicative criterion for quantitatively assessing hydrophobic or hydrophilic materials, where the borderline is roughly 2 × 105 N s m-3. That is if the water-solid friction is less than 2 × 105 N s m-3, the surface is considered hydrophobic. But if the friction is larger than this value, the surface is hydrophilic. The present findings could help to better understand fluidic transport at the nanoscale and guide the future design of functional materials, such as super-hydrophobic and super-hydrophilic surfaces by structure engineering.

Nonthermal plasma-irradiated polyvalent ferromanganese binary hydro(oxide) for the removal of uranyl ions from wastewater.

Nonthermal plasma (NTP) irradiation was employed to adjust the morphological structures and valence distribution of ferromanganese (Fe-Mn)-based binary hydro (oxide) to enhance the heterogeneous adsorption of uranyl ions. The output voltage and the liquid-plate distance played a more vital role among the NTP factors in the irradiation system in influencing the polyvalent Fe-Mn binary hydro (oxide) (poly-Fe-Mn). The formation of plates, flakes, and nanoscale nodules was specifically observed, which caused more pores and fractures in the poly-Fe-Mn binary hydro (oxide). The poly-Fe-Mn performed explicitly better in the adsorption of uranium ions in comparison with the counterpart of the Fe-Mn, which was appropriately fitted by the pseudofirst-order kinetic and Elovich models. Maximum equilibrium adsorption capacities of 663.92 and 923.45 mg/g were obtained for the Fe-Mn and poly-Fe-Mn binary hydro (oxides) toward U ions in the orthogonal design, respectively. The maximum monolayer adsorption capacity achieved by the fitting of the Langmuir model was 1091.10 mg/g. Both physisorption and chemisorption contributed to the heterogeneous process of the poly-Fe-Mn toward uranium ions. The employment of NTP irradiation changed the monolayer adsorption of the traditional Fe-Mn materials and diversified the reaction mechanisms between the interface of the Fe-Mn materials and uranium ions. The elements, including O, N, and U exhibited higher compatibility and overlapped in the samples. The highly effective capture of uranium ions from the solution by the poly-Fe-Mn binary hydro (oxide) was mainly related to the chemical deposition of O and N radicals.

Spatiotemporal effects of meteorological conditions on global influenza peaks.

BACKGROUND: Numerous studies have suggested that meteorological conditions such as temperature and absolute humidity are highly indicative of influenza outbreaks. However, the explanatory power of meteorological factors on the seasonal influenza peaks varied widely between countries at different latitudes. OBJECTIVES: We aimed to explore the modification effects of meteorological factors on the seasonal influenza peaks in multi-countries. METHODS: Data on influenza positive rate (IPR) were collected across 57 countries and data on meteorological factors were collected from ECMWF Reanalysis v5 (ERA5). We used linear regression and generalized additive models to investigate the spatiotemporal associations between meteorological conditions and influenza peaks in cold and warm seasons. RESULTS: Influenza peaks were significantly correlated with months with both lower and higher temperatures. In temperate countries, the average intensity of cold season peaks was stronger than that of warm season peaks. However, the average intensity of warm season peaks was stronfger than of cold season peaks in tropical countries. Temperature and specific humidity had synergistic effects on influenza peaks at different latitudes, stronger in temperate countries (cold season: R2=0.90; warm season: R2=0.84) and weaker in tropical countries (cold season: R2=0.64; warm season: R2=0.03). Furthermore, the effects could be divided into cold-dry and warm-humid modes. The temperature transition threshold between the two modes was 16.5-19.5 °C. During the transition from cold-dry mode to warm-humid mode, the average 2 m specific humidity increased by 2.15 times, illustrating that transporting a large amount of water vapor may compensate for the negative effect of rising temperatures on the spread of the influenza virus. CONCLUSION: Differences in the global influenza peaks were related to the synergistic influence of temperature and specific humidity. The global influenza peaks could be divided into cold-dry and warm-humid modes, and specific thresholds of meteorological conditions were needed for the transition of the two modes.

Transcriptional adaptor 3 influences the proliferative and invasive phenotypes of non-small cell lung cancer cells via regulating EMT.

Transcriptional adaptor 3 (TADA3/ADA3) is a conserved transcriptional co-activator and is dysregulated in many aggressive tumors. However, the role of TADA3 in non-small cell lung cancer (NSCLC) remains unknown. It was previously demonstrated that TADA3 expression correlates with poor prognosis in patients with NSCLC. In the present study, the expression and function of TADA3 were investigated in cells in vitro and in vivo. TADA3 expression was evaluated in clinical specimens and cell lines using reverse transcription-quantitative PCR and western blot analysis. The TADA3 protein level was significantly higher in human NSCLC specimens compared with matched normal tissues. In human NSCLC cell lines, short hairpin RNA-mediated silencing of TADA3 suppressed their proliferative, migratory and invasive abilities in vitro, and delayed G1 to S phase progression through the cell cycle. Consistent with this, TADA3 silencing increased expression of the epithelial marker E-cadherin and reduced expression of the mesenchymal markers, N-cadherin, Vimentin, Snail, and Slug. To verify the effect of TADA3 on tumor formation and growth in vivo, a mouse tumor xenograft model was established. TADA3 silencing slowed the growth of NSCLC tumor xenografts in nude mice, and excised tumors showed a similarly altered pattern of epithelial-mesenchymal transition (EMT) marker expression. The present results demonstrated the significance of TADA3 in regulating the growth and metastasis of NSCLC and may provide a theoretical basis for early diagnosis and targeted therapy of NSCLC.

Fatty acid, triglyceride, and kinetic properties of milk fat fractions made by the combination of dry fractionation and short-path molecular distillation.

In this study, we aimed to detect the physicochemical properties of distilled products (residue and distillate) obtained from anhydrous milk fat (AMF) and its dry fractionation products (liquid and solid fractions at 25°C [25 L and 25 S]). The results showed that the saturated fatty acids and low- and medium molecular-weight triglycerides were easily accumulated in the distillate, and the percentage of unsaturated fatty acid and high molecular-weight triglycerides in the residue were higher, and these components in 25 S and 25 L were influenced more significantly than those in the AMF. In addition, the distillate had larger melting ranges in comparison with the distilled substrate, while the melting ranges of residue was smaller. The triglycerides were presented as the mixture crystal forms (α, ß', and ß crystal) in 25 S, AMF, and their distilling products, and it was transformed gradually to a single form as the increasing of distilling temperature. Moreover, the accumulated pattern of triglycerides was double chain length in 25 S, AMF, and their distilling products. These results provide a new approach to obtain the milk fat fractions with different properties, and the findings of this study enrich the theoretical basis of milk fat separation in practical production.

Assessing the export trade risk of bluetongue virus serotypes 4 and 8 in France.

Bluetongue (BT) causes an economic loss of $3 billion every year in the world. After two serious occurrences of BT (bluetongue virus [BTV] occurrence in 2006 and 2015), France has been controlling for decades, but it has not been eradicated. As the largest live cattle export market in the world, France is also one of the major exporters of breeding animals and genetic materials in the world. The biosafety of its exported cattle and products has always been a concern. The scenario tree quantitative model was used to analyze the risk of BTV release from French exported live cattle and bovine semen. The results showed that with the increase in vaccination coverage rates, the risk decreased. If the vaccine coverage is 0%, the areas with the highest average risk probability of BTV-4 and BTV-8 release from exported live cattle were Haute-Savoie and Puy-de-Dôme, and the risk was 2.96 × 10-4 and 4.25 × 10-4 , respectively. When the vaccine coverage was 90%, the risk probability of BTV-4 and BTV-8 release from exported live cattle was 2.96 × 10-5 and 4.24 × 10-5 , respectively. The average probability of BTV-8 release from bovine semen was 1.09 × 10-10 . Sensitivity analysis showed that the probability of false negative polymerase chain reaction (PCR) test and the probability of BT infection in the bull breeding station had an impact on the model. The identification of high-risk areas and the discovery of key control measures provide a reference for decision makers to assess the risk of French exports of live cattle and bovine semen.

Epidemic threshold of a COVID-19 model with gaussian white noise and semi-Markov switching.

In this study, we investigate the COVID-19 propagation dynamics using a stochastic SIQR model with Gaussian white noise and semi-Markovian switching, focusing on the impacts of Gaussian white noise and semi-Markovian switching on the propagation dynamics of COVID-19. It is suggested that the fate of COVID-19 is entirely determined by the basic reproduction number R0, under mild extra conditions. By making sensitivity analysis on R0, we found that the effect of quarantine rate on R0 was more significant compared to transmission rate. Our results demonstrate that: (i) The presence of Gaussian white noise, while reducing the basic reproduction number R0 of COVID-19, also poses more challenges for the prediction and control of COVID-19 propagation. (ii) The conditional holding time distribution has a significant effect on the kinetics of COVID-19. (iii) The semi-Markov switching and Gaussian white noise can support irregular recurrence of COVID-19 outbreaks.