Rabies virus (RABV) is highly lethal and triggers severe neurological symptoms. The neuropathogenic mechanism remains poorly understood. Ras-related C3 botulinum toxin substrate 1 (Rac1) is a Rho-GTPase that is involved in actin remodeling and has been reported to be closely associated with neuronal dysfunction. In this study, by means of a combination of pharmacological inhibitors, small interfering RNA, and specific dominant-negatives, we characterize the crucial roles of dynamic actin and the regulatory function of Rac1 in RABV infection, dominantly in the viral entry phase. The data show that the RABV phosphoprotein interacts with Rac1. RABV phosphoprotein suppress Rac1 activity and impedes downstream Pak1-Limk1-Cofilin1 signaling, leading to the disruption of F-actin-based structure formation. In early viral infection, the EGFR-Rac1-signaling pathway undergoes a biphasic change, which is first upregulated and subsequently downregulated, corresponding to the RABV entry-induced remodeling pattern of F-actin. Taken together, our findings demonstrate for the first time the role played by the Rac1 signaling pathway in RABV infection and may provide a clue for an explanation for the etiology of rabies neurological pathogenesis.IMPORTANCEThough neuronal dysfunction is predominant in fatal rabies, the detailed mechanism by which rabies virus (RABV) infection causes neurological symptoms remains in question. The actin cytoskeleton is involved in numerous viruses infection and plays a crucial role in maintaining neurological function. The cytoskeletal disruption is closely associated with abnormal nervous symptoms and induces neurogenic diseases. In this study, we show that RABV infection led to the rearrangement of the cytoskeleton as well as the biphasic kinetics of the Rac1 signal transduction. These results help elucidate the mechanism that causes the aberrant neuronal processes by RABV infection and may shed light on therapeutic development aimed at ameliorating neurological disorders.
The hub-and-spoke theory of semantic representation fractionates the neural underpinning of semantic knowledge into two essential components: the sensorimotor modality-specific regions and a crucially important semantic hub region. Our previous study in patients with semantic dementia has found that the hub region is located in the left fusiform gyrus. However, because this region is located within the brain damage in patients with semantic dementia, it is not clear whether the semantic deficit is caused by structural damage to the hub region itself or by its disconnection from other brain regions. Stroke patients do not have any damage to the left fusiform gyrus, but exhibit amodal and modality-specific deficits in semantic processing. Therefore, in this study, we validated the semantic hub region from a brain network perspective in 79 stroke patients and explored the white matter connections associated with it. First, we collected data of diffusion-weighted imaging and behavioural performance on general semantic tasks and modality-specific semantic tasks (assessing object knowledge on form, colour, motion, sound, manipulation and function). We then used correlation and regression analyses to examine the association between the nodal degree values of brain regions in the whole-brain structural network and general semantic performance in the stroke patients. The results revealed that the connectivity of the left fusiform gyrus significantly predicted general semantic performance, indicating that this region is the semantic hub. To identify the semantic-relevant connections of the semantic hub, we then correlated the white matter integrity values of each tract connected to the left fusiform gyrus separately with performance on general and modality-specific semantic processing. We found that the hub region accomplished general semantic processing through white matter connections with the left superior temporal pole, middle temporal gyrus, inferior temporal gyrus and hippocampus. The connectivity between the hub region and the left hippocampus, superior temporal pole, middle temporal gyrus, inferior temporal gyrus and parahippocampal gyrus was differentially involved in object form, colour, motion, sound, manipulation and function processing. After statistically removing the effects of potential confounding variables (i.e. whole-brain lesion volume, lesion volume of regions of interest and performance on non-semantic control tasks), the observed effects remained significant. Together, our findings support the role of the left fusiform gyrus as a semantic hub region in stroke patients and reveal its crucial connectivity in the network. This study provides new insights and evidence for the neuroanatomical organization of semantic memory in the human brain.
Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control.
Typical small organic dyes exhibit excellent UV absorption capabilities and are commonly used as additives to shield plastic films from photoaging. However, their tendency to decompose easily and migrate rapidly within a polymer matrix limits their service life. Herein we prepared g-C3N4 nanosheets and fabricated g-C3N4/PBAT films to investigate the effects of g-C3N4 on UV shielding and plasticizing of a biodegradable PBAT film. Photophysical characterizations revealed that an improved UV light barrier performance was achieved on g-C3N4/PBAT films compared to pure PBAT. Furthermore, the photoaging results show that g-C3N4 can stably exist in the PBAT matrix, enabling the aged g-C3N4/PBAT films to maintain their effective UV shielding ability, whereas the aged benzophenone (UV-0)/PBAT film shows a substantial decrease in UV light absorption due to the photodecomposition of UV-0. Additionally, g-C3N4 acted as a reinforcing material for PBAT, as evidenced by the approximately 1.5-fold increase in longitudinal tear strength and 1.6-fold increase in tensile strength of g-C3N4/PBAT films compared to pure PBAT. Remarkably, even after 100 hours of photoaging, the aged g-C3N4/PBAT films retained their favorable mechanical properties. This study highlights the potential of g-C3N4 as a new type of UV shield additive for future practical applications in protecting biodegradable plastic from photoaging.
As an ultra-wide bandgap semiconductor, gallium oxide (Ga2O3) has been extensively applied in solar-blind photodetectors (PDs) owing to the absorbance cut-off wavelength of shorter than 280 nm, and the optimized technologies of detection performance is seriously essential for its further usages. Herein, a feasible thermal reorder engineering method was performed through annealing Ga2O3films in vacuum, O2and oxygen plasma atmospheres, realizing to tune solar-blind photosensing performance of Ga2O3PDs. Thermal treatment, in fact a crystal reorder process, significantly suppressed the noise in Ga2O3-based PDs and enhanced the photo-sensitivity, with the dark current decreasing from 154.63 pA to 269 fA and photo-to-dark current ratio magically raising from 288 to 2.85 × 104. This achievement is dependent of energy-band modulation in Ga2O3semiconductor, that is certified by first-principles calculation. Additionally, annealing in oxygen atmospheres notably reduces the concentration of oxygen vacancies in the surface of films, thereby improving the performance of the PDs; the oxygen vacancy is extremely concerned in oxide semiconductors in the view of physics of surface defects. In all, this work could display a promising guidance for modulating the performance of PDs based on wide bandgap oxide semiconductor, especially for hot Ga2O3issue.
Classical swine fever virus (CSFV), which is a positive-sense, single-stranded RNA virus with an envelope, is a member of the Pestivirus genus in the Flaviviridae family. CSFV causes a severe and highly contagious disease in pigs and is prevalent worldwide, threatening the pig farming industry. The detailed mechanisms of the CSFV life cycle have been reported, but are still limited. Some receptors and attachment factors of CSFV, including heparan sulfate (HS), laminin receptor (LamR), complement regulatory protein (CD46), MER tyrosine kinase (MERTK), disintegrin, and metalloproteinase domain-containing protein 17 (ADAM17), were identified. After attachment, CSFV internalizes via clathrin-mediated endocytosis (CME) and/or caveolae/raft-dependent endocytosis (CavME). After internalization, CSFV moves to early and late endosomes before uncoating. During this period, intracellular trafficking of CSFV relies on components of the endosomal sorting complex required for transport (ESCRT) and Rab proteins in the endosome dynamics, with a dependence on the cytoskeleton network. This review summarizes the data on the mechanisms of CSFV attachment, internalization pathways, and intracellular trafficking, and provides a general view of the early events in the CSFV life cycle.
Classical Swine Fever Virus , Classical Swine Fever , Pestivirus , Animals , Swine , Classical Swine Fever Virus/metabolism , Endocytosis
RATIONALE: Cases of respiratory dysfunction due to phrenic nerve sacrifice during resection of massive mediastinal tumor have rarely been studied in detail. Diaphragmatic dysfunction in such cases can lead to potentially fatal respiratory and circulatory disturbances. Therefore, timely diagnosis and intervention are important. Conservative rehabilitation therapy is the first choice for respiratory dysfunction due to diaphragmatic dysfunction. PATIENT CONCERNS, DIAGNOSES AND INTERVENTIONS: We present 3 patients with respiratory dysfunction due to phrenic nerve sacrifice during resection of massive mediastinal tumor. The diagnostic methods and therapeutic procedures for diaphragmatic dysfunction for each patient are described in detail. This study highlights the role of ventilator support combined with physical therapy in the treatment of respiratory dysfunction in such cases. The diagnosis of diaphragmatic dysfunction as well as the risk assessment of phrenic nerve involvement are also discussed. The modalities of ventilator support, including modes and parameters, are listed. OUTCOMES AND LESSONS: This study provides experiences of diagnosis and treatment of respiratory dysfunction due to phrenic nerve sacrifice during resection of massive mediastinal tumor. Timely diagnosis of diaphragmatic dysfunction primarily relies on clinical manifestations and radiography. Conservative rehabilitation therapy can improve or restore diaphragmatic function in majority of patients, and avert or delay the need for surgical intervention. Preoperative assessment of the risk of phrenic nerve involvement is important in such cases.
Mediastinal Neoplasms , Medicine , Humans , Mediastinal Neoplasms/complications , Mediastinal Neoplasms/surgery , Phrenic Nerve , Conservative Treatment , Diaphragm/surgery
We report a fully integrated digital microfluidic absorbance detection system with an enhanced sensitivity for online bacterial monitoring. Through a 100 µm gap in the chip, our optical detection system has a detection sensitivity for a BCA protein concentration of 0.1 mg mL-1. The absorbance detection limit of our system is 1.4 × 10-3 OD units, which is one order of magnitude better than that of the existing studies. The system's linear region is 0.1-7 mg mL-1, and the dynamic range is 0-25 mg mL-1. We measured the growth curves of wild-type and E. coli transformed with resistance plasmids and mixed at different ratios on chip. We sorted out the bacterial species including highly viable single cells based on the difference in absorbance data of growth curves. We explored the changes in the growth curves of E. coli under different concentrations of resistant media. In addition, we successfully screened for the optimal growth environment of the bacteria, in which the growth rate of PET30a-DH5α (in a medium with 33 µg mL-1 kanamycin resistance) was significantly higher than that of a 1 mg mL-1 resistance medium. In conclusion, the enhanced digital microfluidic absorbance detection system exhibits exceptional sensitivity, enabling precise bacterial monitoring and growth curve analysis, while also laying the foundation for DMF-based automated bioresearch platforms, thus advancing research in the life sciences.
Microfluidics , Optical Devices , Escherichia coli , Lab-On-A-Chip Devices , Cell Movement
Solar-blind UV photodetectors have outstanding reliability and sensitivity in flame detection without interference from other signals and response quickly. Herein, we fabricated a solar-blind UV photodetector based on a La2O3/ε-Ga2O3 p-n heterojunction with a typical type-II band alignment. Benefiting from the photovoltaic effect formed by the space charge region across the junction interface, the photodetector exhibited a self-powered photocurrent of 1.4 nA at zero bias. Besides, this photodetector demonstrated excellent photo-to-dark current ratio of 2.68 × 104 under 254 nm UV light illumination and at a bias of 5 V, and a high specific detectivity of 2.31 × 1011 Jones and large responsivity of 1.67 mA/W were achieved. Importantly, the La2O3/ε-Ga2O3 heterojunction photodetector can rapidly respond to flames in milliseconds without any applied biases. Based on the performances described above, this novel La2O3/ε-Ga2O3 heterojunction is expected to be a candidate for future energy-efficient fire detection.
Solar-driven electrochemical NO3- reduction reaction (NO3-RR) is a clean and sustainable strategy that can convert pollutant NO3- in wastewater to value-added NH3. In recent years, cobalt oxides-based catalysts have shown their intrinsic catalytic properties toward NO3-RR but still have room for improvement through catalyst design. Coupling metal oxides with noble metal has been demonstrated to improve electrochemical catalytic efficiency. Here, we use Au species to tune the surface structure of Co3O4 and improve the efficiency of NO3-RR to NH3. The obtained Au nanocrystals-Co3O4 catalyst exhibited an onset potential of 0.54 V vs RHE, NH3 yield rate of 27.86 µg/h·cm2, and Faradaic efficiency (FE) of 83.1% at 0.437 V vs RHE in an H-cell, which is much higher than Au small species (Au clusters or single atoms)-Co3O4 (15.12 µg/h·cm2) and pure Co3O4 (11.38 µg/h·cm2), respectively. Combined experiments with theory calculations, we attributed the enhanced performance of Au nanocrystals-Co3O4 to the reduced energy barrier of *NO hydrogenation to the *NHO and suppression of HER, which originated from the charge transfer from Au to Co3O4. Using an amorphous silicon triple-junction (a-Si TJ) as the solar cell and an anion exchange membrane electrolyzer (AME), an unassisted solar-driven NO3-RR to NH3 prototype was realized with a yield rate of 4.65 mg/h and FE of 92.1%.
Argyreiasubrotunda, a new species from Yunnan Province, China, is described and illustrated. The new species resembles A.fulvocymosa and A.wallichii, but differs from these in the flowers with an entire or shallowly lobed corolla, as well as smaller elliptic bracts, lax flat-topped cymes and shorter corolla tubes. An updated key to the species of Argyreia from Yunnan province is also provided.
Designing phosphors that are excited by blue light is extraordinarily important for white light-emitting diodes (w-LEDs). In the present study, a new Ruddlesden-Popper type of SZO:xEu3+ (x = 0.01~0.10) phosphors was developed using solid-state reactions. Interestingly, a Eu3+ doping-induced phase transformation from the Sr3Zr2O7 (cubic) to the SrZrO3 (orthorhombic) phase was observed, and the impact of the occupied sites of Eu3+ ions on the lifetime of Sr3Zr2O7:xEu3+ phosphors is discussed in detail. Diffuse reflectance spectroscopy results showed that the band gap of SZO:xEu3+ phosphors gradually increased from 3.48 eV for undoped Sr3Zr2O7 hosts to 3.67 eV for SZO:0.10Eu3+ samples. The fluorescence excitation spectrum showed that ultraviolet (300 nm), near-ultraviolet (396 nm) and blue light (464 nm) were all effective excitation pump sources of Sr3Zr2O7:xEu3+ phosphors, and the strongest emission at 615 nm originated from an electric dipole transition (5D0â7F2). CIE coordinates moved from orange (0.5969, 0.4267) to the reddish-orange region (0.6155, 0.3827), and the color purity also increased. The fabricated w-LED was placed on a 460 nm chip with a mixture of YAG:Ce3+ and SZO:0.1Eu3+ samples and showed "warm" white light with a color rendering index (CRI) of 81.8 and a correlation color temperature (CCT) of 5386 K, indicating great potential for application in blue chip white LEDs.
Nowadays, the impact ionization coefficient in the avalanche breakdown theory is obtained using 1-D PN junctions or SBDs, and is considered to be a constant determined by the material itself only. In this paper, the impact ionization coefficient of silicon in a 2D lateral power device is found to be no longer a constant, but instead a function of the 2D coupling effects. The impact ionization coefficient of silicon that considers the 2D depletion effects in real-world devices is proposed and extracted in this paper. The extracted impact ionization coefficient indicates that the conventional empirical impact ionization in the Fulop equation is not suitable for the analysis of 2D lateral power devices. The veracity of the proposed impact ionization coefficient is validated by the simulations obtained from TCAD tools. Considering the complexity of direct modeling, a new prediction method using deep neural networks is proposed. The prediction method demonstrates 97.67% accuracy for breakdown location prediction and less than 6% average error for the impact ionization coefficient prediction compared with the TCAD simulation.
Previous studies have shown that the pollutants in exhaust gas can cause performance deterioration in air-fuel oxygen sensors. Although the content of Pb in fuel oil is as low as 5 mg/L, the effect of long-term Pb accumulation on TiO2 oxygen sensors is still unclear. In this paper, the influence mechanism of Pb-containing additives in automobile exhaust gas on the response characteristics of TiO2 oxygen sensors was simulated and studied by depositing Pb-containing pollutants on the surface of a TiO2 sensitive film. It was found that the accumulation of Pb changed the surface gas adsorption state and reduced the activation energy of TiO2, thus affecting the steady-state response voltage and response speed of the TiO2-based oxygen sensor.
Live, inactivated Lactobacillus or their metabolites have various beneficial functions, which may alleviate food allergy. This study aimed to investigate the intervention effects of three forms of Lactobacillus delbrueckii subsp. bulgaricus (Ld) on cell degranulation, intestinal barrier function, and intestinal mucosal immunity against soybean allergy. First, the intervention effect of Ld on cell degranulation was investigated using the KU812 cell degranulation model. Then, the Caco-2 cell inflammation model was used to evaluate their anti-inflammatory capacity, and the cell monolayer model was constructed to test the protective effects of different forms of Ld on the intestinal barrier. Finally, mesenteric lymph node (MLN) cells from mice were used to assess the ability of different forms of Ld to regulate the balance of cytokines associated with food allergy in the immune tissue of the intestinal mucosa. Results showed that live bacteria and heat-inactivated bacteria could inhibit the degranulation of KU812 cells, mainly by significantly inhibiting the release of histamine, IL-6 and TNF-α. Both live bacteria and heat-inactivated bacteria could also suppress the increase of IL-6 and IL-8 in Caco-2 cells induced by lipopolysaccharide (LPS). The culture supernatant of bacteria and live bacteria showed better ability to maintain the integrity and permeability of the intestinal epithelial barrier. In addition, heat-inactivated bacteria could return the values of IFN-γ and IL-10 to normal levels and restore the balance of IFN-γ/IL-4, thereby reversing the immune deviation of MLN cells. Therefore, three forms of Ld have potential for the treatment of soybean allergy.
Anti-Allergic Agents , Hypersensitivity , Lactobacillus delbrueckii , Humans , Animals , Mice , Lactobacillus delbrueckii/metabolism , Anti-Allergic Agents/metabolism , Caco-2 Cells , Glycine max , Interleukin-6/metabolism , Bacteria
Although lactation mastitis (LM) has been extensively researched, the incidence rate of LM remains a salient clinical problem. To reduce this incidence rate and achieve a better prognosis, early and specific quantitative indicators are particularly important. It has been found that milk electrolyte concentrations (chloride, potassium, and sodium) and electrical conductivity (EC) significantly change in the early stages of LM in an animal model. Several studies have evaluated EC for the detection of subclinical mastitis in cows. EC, chloride, and sodium content of milk were more accurate for predicting infection status than were other variables. In the early stages of LM, lactic sodium, chloride, and EC increase, but potassium decreases. However, these indicators have not been reported in the diagnosis of LM in humans. This review summarizes the pathogenesis and the mechanism of LM in terms of milk electrolyte concentration and EC, and aim to provide new ideas for the detection of sub-clinical mastitis in humans.
Food allergy has become a major public health problem all over the world. Evidence showed that allergic reactions induced by food proteins often lead to disturbances in the gut microbiota (symbiotic bacteria). Gut microbiota plays an important role in maintaining the balance between intestinal immune tolerance and allergic reactions. Dietary intervention has gradually become an important method for the prevention and treatment of allergic diseases, and changing the composition of gut microbiota through oral intake of prebiotics and probiotics may serve as a new effective adjuvant treatment measure for allergic diseases. In this paper, the main mechanism of food allergy based on intestinal immunity was described firstly. Then, the clinical and experimental evidence showed that different prebiotics and probiotics affect food allergy by changing the structure and composition of gut microbiota was summarized. Moreover, the molecular mechanism in which the gut microbiota and their metabolites may directly or indirectly regulate the immune system or intestinal epithelial barrier function to affect food immune tolerance of host were also reviewed to help in the development of food allergy prevention and treatment strategies based on prebiotics and probiotics.
Maize is a globally valuable commodity and one of the most extensively studied genetic model organisms. However, we know surprisingly little about the extent and potential utility of the genetic variation found in wild relatives of maize. Here, we characterize a high-density genomic variation map from 744 genomes encompassing maize and all wild taxa of the genus Zea, identifying over 70 million single-nucleotide polymorphisms. The variation map reveals evidence of selection within taxa displaying novel adaptations. We focus on adaptive alleles in highland teosinte and temperate maize, highlighting the key role of flowering-time-related pathways in their adaptation. To show the utility of variants in these data, we generate mutant alleles for two flowering-time candidate genes. This work provides an extensive sampling of the genetic diversity of Zea, resolving questions on evolution and identifying adaptive variants for direct use in modern breeding.
Plant Breeding , Zea mays , Zea mays/genetics , Adaptation, Physiological/genetics , Base Sequence , Alleles , Genetic Variation/genetics
Although gastroesophageal reflux disease (GERD), a common chronic disease in clinical practice, has been widely studied, its potential adverse impact on patients is still a significant clinical concern. It is necessary to understand the pathogenesis of the disease and choose appropriate treatment according to its mechanism. The pathogenesis of GERD is diverse and complex. As the traditional treatment methods are expensive and ineffective in alleviating symptoms in some patients, new treatment options need to be explored. Our previous study suggested that the activation of nuclear factor-kappa beta (NF-κB) in esophageal mucosa may be related to the injury of epithelial barrier function caused by reflux. Based on the literature and our previous study results, it is speculated that inhibition of NF-κB activation may block the insult of GERD on the esophageal mucosal barrier. NF-κB may play an important role in the development of GERD. This article reviews the pathogenesis of GERD and the relationship between NF-κB and GERD, in order to provide new strategies for the treatment of GERD.
Induced pluripotent stem cells (iPSCs) offer an unlimited source for cartilage regeneration as they can generate a wide spectrum of cell types. Here, we established a tetracycline (tet) controlled bone morphogenetic protein-4 (BMP-4) expressing iPSC (iPSC-Tet/BMP-4) line in which transcriptional activation of BMP-4 was associated with enhanced chondrogenesis. Moreover, we developed an efficient and simple approach for directly guiding iPSC-Tet/BMP-4 differentiation into chondrocytes in scaffold-free cartilaginous pellets using a combination of transcriptional activation of BMP-4 and a 3D shaking suspension culture system. In chondrogenic induction medium, shaking culture alone significantly upregulated the chondrogenic markers Sox9, Col2a1, and Aggrecan in iPSCs-Tet/BMP-4 by day 21. Of note, transcriptional activation of BMP-4 by addition of tet (doxycycline) greatly enhanced the expression of these genes. The cartilaginous pellets derived from iPSCs-Tet/BMP-4 showed an oval morphology and white smooth appearance by day 21. After day 21, the cells presented a typical round morphology and the extracellular matrix was stained intensively with Safranin O, alcian blue, and type II collagen. In addition, the homogenous cartilaginous pellets derived from iPSCs-Tet/BMP-4 with 28 days of induction repaired joint osteochondral defects in immunosuppressed rats and integrated well with the adjacent host cartilage. The regenerated cartilage expressed the neomycin resistance gene, indicating that the newly formed cartilage was generated by the transplanted iPSCs-Tet/BMP-4. Thus, our culture system could be a useful tool for further investigation of the mechanism of BMP-4 in regulating iPSC differentiation toward the chondrogenic lineage, and should facilitate research in cartilage development, repair, and osteoarthritis.
