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Amidst growing demand for sophisticated energy storage solutions, lithium-selenium (Li-Se) batteries have emerged as a viable substitute for lithium-sulfur (Li-S) batteries, presenting advantages including superior energy density, cost efficiency, and eco-friendliness. However, the implementation of Li-Se batteries encounters several obstacles, such as low active material utilization, inadequate electrical conductivity, rapid capacity degradation, and the notorious lithium polyselenide (LiPSe) shuttle effect. In this study, we address these obstacles by introducing porous carbon derived from wheat grains (denoted as WGr) through a straightforward carbonization-KOH activation procedure. By optimizing the mass ratio of carbonized wheat grains to KOH in a 1:2 ratio, we obtained a carbon material WG2 with a unique hierarchical porous structure that effectively encapsulates selenium within its small pores. The microporous feature in the WG2 material promotes solid–solid reactions, mitigates the LiPSe shuttle effect, enhances electrical conductivity, and ensures high electrochemical utilization of selenium. The WG2 material exhibits a diverse porous carbon framework with a Brunauer–Emmett–Teller (BET) surface area of 497.8519 m2 g−1 and a cumulative pore volume of 0.250 cm3 g−1. Utilizing the WG2 carbon structure as a cathode host substrate in Li-Se batteries, the composite WG2@Se, with selenium loading of 43.13%, demonstrates impressive performance. After 600 cycles, it exhibits a reversible capacity of 384.6 mAh g−1 (at 1 C) and a remarkable rate performance of 311.7 mAh g−1 at 4 C. Furthermore, when applied in sodium-selenium (Na-Se) batteries, the WG2@Se cathode displays superior rate capabilities and stable cycling performance. The incorporation of wheat grain-derived hierarchical porous carbon structure into Li/Na-Se batteries paves the way for cost-effective and eco-friendly techniques in the development of confined selenium cathodes. The research offers valuable understanding of the design and development of cutting-edge cathode materials, contributing to the ongoing efforts within the realm of Li/Na-Se batteries. We utilized wheat grain-derived porous carbon (WG2), obtained through carbonization and KOH activation, to successfully encapsulate selenium within its pores, significantly enhancing electrical conductivity and cycle stability, and mitigating the polyselenide shuttle effect in selenium-based batteries. [ABSTRACT FROM AUTHOR]

The cathode in lithium-selenium (Li-Se) batteries has garnered extensive attention owing to its superior specific capacity and enhanced conductivity compared to sulfur. Nonetheless, the adoption and advancement of Li-Se batteries face significant challenges due to selenium's low reactivity, substantial volume fluctuations, and the shuttle effect associated with polyselenides. Single-atom catalysts (SACs) are under the spotlight for their outstanding catalytic efficiency and optimal atomic utilization. To address the challenges of selenium's low chemical activity and volume expansion in Li-Se batteries, through electrospun, we have developed a lotus root-inspired carbon nanofiber (CNF) material, featured internal multi-channels and anchored with molybdenum (Mo) single atoms (Mo@CNFs). Mo single atoms significantly enhance the conversion kinetics of selenium (Se), facilitating rapid formation of Li2Se. The internally structured multi-channel CNF serves as an effective host matrix for Se, mitigating its volume expansion during the electrochemical process. The resulting cathode, Se/Mo@CNF composite, exhibits a high discharge specific capacity, superior rate performance, and impressive cycle stability in Li-Se batteries. After 500 cycles at a current density of 1 C, it maintains a capacity retention rate of 82% and nearly 100% coulombic efficiency (CE). This research offers a new avenue for the application of single-atom materials in enhancing advanced Li-Se battery performance. [ABSTRACT FROM AUTHOR]

Assembly construction is extensively employed in bridge construction due to its ability to accelerate construction and improve quality. To speed the recovery of bridges after major earthquakes, this study proposes an assembled connection for precast piers and footings based on assembly construction. The precast piers are connected to the footings using ultra-high-performance concrete (UHPC) post-cast cupped sockets. Two specimens are tested with a 1:4 scale, namely, the cast-in-place (CIP) specimen and, the UHPC cupped socket pier specimen. Finite element models (FEM) of a continuous girder bridge with cupped socket connections are developed and verified by experimental results. The seismic fragility analysis is conducted to investigate the difference between the cupped socket connection and the CIP connection. The experimental results showed that the plastic hinge was formed on the precast piers and there was little damage to the UHPC sockets. The results of FEA indicate that UHPC cupped socket piers have slightly higher seismic fragility than the seismic fragility of cast-in-place piers. Then, some methods were proposed to reduce the seismic fragility of UHPC cupped socket piers, and their availability was confirmed by comparing them with the seismic fragility of CIP piers. Finally, an example bridge with this connection is introduced to illustrate replacing prefabricated piers after an earthquake. [ABSTRACT FROM AUTHOR]

Assembly of precast elements is a widely adopted technology for achieving accelerated bridge construction (ABC) owing to the increased construction speed and quality. Connection methods between precast structural members, if designed properly, can facilitate a convenient postearthquake replacement of damaged members and hence enable rapid function recovery of bridges. This study proposes a new precast bridge pier–footing connection using external sockets. The external sockets are prefabricated on the top of bridge footings and the precast piers can be directly inserted into the sockets with postgrouting. Quasi-static cyclic loading tests were conducted on four 1/4-scale pier–footing specimens, including three external socket pier specimens and a cast-in-place (CIP) specimen for comparison purposes. The experimental results show that the external sockets with normal design sizes are effective precast pier–footing connection methods, ensuring that plastic hinges are formed in the piers without damaging the external sockets and footings. Because of the shortened effective pier height, the socket piers show increased lateral stiffness and strength but decreased displacement capacity compared with the CIP pier. The measured peak horizontal forces for the precast socket pier specimens PCS-1, PCS-2, and PCS-3 are increased by 7.5%, 34.5%, and 51.4%, respectively. However, the ultimate displacements are reduced by 11.1%–22.0% compared with the CIP pier. The hysteretic energy dissipation of the socket piers is compared with that of the CIP pier, with a difference less than 20%. Postexperiment replacement of a tested precast pier was carried out, which demonstrates the feasibility of rapidly replacing damaged bridge piers when using the proposed external socket connections. A subsequent experiment reveals that the newly replaced pier specimen could show an equivalent seismic performance to the previous specimen. The maximum differences of the peak force and initial stiffness between the two piers are within 6.7%, and the difference of the dissipated energy is only 3.8%. The experimental results verified the effectiveness of the rapid replacement. [ABSTRACT FROM AUTHOR]

Trained immunity defines the long‐term memory of innate immunity based on innate immune signalling, metabolic changes and epigenetic rewiring of trained innate immune cells, which are characterised by elevated inflammatory responses towards secondary stimuli. The activation of this non‐specific protection‐mediated memory in innate immune cells was identified to benefit host defences as well as play a detrimental role in inflammatory diseases. In this review, we focused on summing up the current progress about the inducers, effector cells, molecular mechanisms and protective effects of trained immunity that have been identified in both mammals and teleost fish, and discussing the future research and application of trained immunity in aquaculture. Revealing the mechanisms of trained immunity will not only provide a novel aspect for understanding the evolution of innate immune memory and their longer‐term protections, but also contribute to the rational design and evaluation of immunopotentiators, adjuvants and potential vaccines in aquaculture. [ABSTRACT FROM AUTHOR]

Aims Pseudomonas plecoglossicida (P. plecoglossicida) is the causative agent of visceral granulomas disease in large yellow croaker (Larimichthys crocea) and it causes severe economic loss to its industry. Biofilm formation, related to intracellular cyclic bis (3′–5′) diguanylic acid (c-di-GMP) levels, is essential for the lifestyle of P. plecoglossicida. This research aims to investigate the role of YfiR—a key regulator of the diguanylate cyclase YfiN to regulate c-di-GMP levels and reveal its regulatory function of bacterial virulence expression in P. plecoglossicida. Methods and results A genetic analysis was carried out to identify the yfiBNR operon for c-di-GMP regulation in P. plecoglossicida. Then, we constructed a yfiR mutant and observed increased c-di-GMP levels, enhanced biofilm formation, increased exopolysaccharides, and diminished swimming and swarming motility in this strain. Moreover, through establishing a yolk sac microinjection infection model in zebrafish larvae, an attenuated phenotype of yfiR mutant that manifested as restored survival and lower bacterial colonization was found. Conclusions YfiR is the key regulator of virulence in P. plecoglossicida , which contributes to c-di-GMP level, biofilm formation, exopolysaccharides production, swimming, swarming motility, and bacterial colonization in zebrafish model. [ABSTRACT FROM AUTHOR]

This study aims to investigate the seismic behavior of concrete-filled steel tubular (CFST)-laced piers; after verifying the model through engineering tests, the simplified finite element models (S-FEM) and refined ones (R-FEM) with CFST-laced piers are developed in this manuscript, respectively. Through comparison, it is found that the S-FEM can effectively improve analyzing efficiency while meeting the requirements of engineering analysis accuracy. In addition, the seismic response of assembled flange-connected CFST-laced piers bridge was studied based on the S-FEM, and different structural parameters, including pier height, axial compression ratios, steel ratios of CFST columns, steel lacing tube arrangement, and longitudinal slope, are considered to optimize the bridge design scheme. Results indicate that the parameters of 0.1 axial pressure ratios and 1:30 longitudinal slope show superior seismic performance. Meanwhile, the peak axial force and peak bending moment of CFST column limbs occur at the pier bottom, and the flanges, which are subject to larger bending moments, are generally located at the two connection positions above the pier bottom. [ABSTRACT FROM AUTHOR]

This paper studies the load-bearing characteristics of two prestressed high-strength concrete (PHC) pipe piles constructed by the medium mid-digging and hammering methods. The ultimate load tests and numerical simulations of the pipe piles constructed by both methods were carried out to analyze the ultimate lateral resistance, and ultimate resistance performance characteristics of the two pipe piles and the influence of the wall thickness of the pipe piles on the bearing performance. The test results show that the pipe pile constructed by the middle inner digging method has a higher pile quality. The single pile bearing capacity of the pipe pile constructed by the middle inner digging method is 50% higher than that of the common hammering method. The enlarged part of the pile end has an obvious effect on improving the bearing capacity. The settlement of the pipe pile constructed by the middle inner digging method is smaller than that of the hammering method. The large diameter pipe pile constructed by the middle inner digging method usually shows characteristics of the end-bearing pile. The resistance of the pile end accounts for 40–50% of the top load. The numerical simulation results agree with the field test and are compared and discussed. The simulation results show that when the bearing capacity of the pile is provided by the pile side frictional resistance, the influence of the pile wall thickness on the bearing capacity is insignificant. When the top pile load is close to the bearing capacity of the pipe pile, the influence of the pipe pile wall thickness on the bearing capacity is greater. [ABSTRACT FROM AUTHOR]

The seismic performance of prefabricated hollow circular piers with socket and slot connection was evaluated through model tests and numerical simulations. The quasi-static tests with cyclic lateral load and constant axial load were conducted on three large pier specimens. The piers of these three specimens were cast by polyvinyl alcohol (PVA) fiber concrete, and the piers were connected to the cover beams by slotted connections and to the bearing platform by socketed connections. The seismic performance of the specimens was investigated in terms of failure modes, hysteresis curves, skeleton curves, stiffness degradation, energy dissipation, and residual deformation. The test results showed that, within a certain range, increasing the axial compression ratio is able to enhance the shear bearing capacity of prefabricated hollow piers and increase the cumulative energy dissipation, but it is not beneficial to the ductility. In addition, the increase in the shear span ratio significantly reduces the shear bearing capacity of piers and increases the residual deformation of the specimen, but the ductility is significantly improved. In addition, the numerical model of the prefabricated hollow pier was established by ABAQUS. The result of the numerical simulation was consistent and similar to the experimental result in terms of damage modes and load–displacement curves. Finally, the parametric analysis of the prefabricated hollow piers was carried out on the basis of the numerical model. [ABSTRACT FROM AUTHOR]

Long-wave infrared imaging systems are widely used in the field of environmental monitoring and imaging guidance. As the core components, the long-wave infrared lenses suffer the conditions of less available materials, difficult processing, large volume and mass. Metalens composed of sub-wavelength structures is one of the most potential candidates to achieve a lightweight and planar optical imaging systems. Meanwhile, it is essential to obtain large-aperture infrared lenses with high power and high resolution. However, it is difficult to use the finite-difference time-domain method to simulate a large-aperture metalens with the diameter of 201 mm due to the large amount of computational memory and computational time required. Here, to solve the mentioned problem, we firstly propose a simulation method for designing a large-aperture metalens, which combines the finite-difference time-domain algorithm and diffraction integration. The finite-difference time-domain algorithm is used to simulate the meta-atom’s transmitted complex amplitude and the one-dimensional simplification of the diffraction integral is to calculate the focused field distributions of the designed metalens. Furthermore, the meta-atom spatial multiplexing is applied to design the all-silicon metalenses with the aperture of 201 mm to realize dual-wavelength (10 and 11 μ m) achromatic focusing, super anomalous dispersion focusing and super normal dispersion focusing. The designed metalenses are numerically confirmed, which reveal the feasibility of all-silicon sub-wavelength structures to accomplish the multiwavelength dispersion control. The designed all-silicon metalenses have the advantage of lightweight and compact. The proposed method is effective for the development of large-aperture imaging systems in the long-wave infrared. [ABSTRACT FROM AUTHOR]

Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. Infection-induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic organ injury remains largely unknown. Here, through establishing an in vivo β-glucan training and lipopolysaccharide (LPS) challenge model in zebrafish larvae, we observe that induction of trained immunity could inhibit pyroptosis of hepatocytes to alleviate septic liver injury, with an elevated trimethyl-histone H3 lysine 4 (H3K4me3) modification that targets mitophagy-related genes. Moreover, we identify a C-type lectin domain receptor in zebrafish, named Dr Dectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring-mediated mitophagy activation and alleviating pyroptosis-engaged septic liver injury in vivo. Taken together, our results uncover tissue-resident trained immunity in maintaining liver homeostasis at the whole-animal level and offer an in vivo model to efficiently integrate trained immunity for immunotherapies. [Display omitted] • β-Glucan training protects zebrafish from LPS-induced liver injury • Dr Dectin-1-gated H3K4me3 rewiring of mitophagy-related genes in hepatocytes • Heightened mitophagy alleviates pyroptosis-engaged septic-liver injury in vivo Trained immunity initially describes the long-term functional reprogramming of innate immune cells. Here, Yang et al. reveal the mechanism of trained immunity in zebrafish hepatocytes. They uncover that β-glucan training induces Dr Dectin-1-gated H3K4me3 modification of mitophagy-related genes, inhibiting pyroptosis to protect the host from septic liver injury in vivo. [ABSTRACT FROM AUTHOR]

Xyloglucan is a quantitatively major polysaccharide in the primary cell walls of flowering plants and has been reported to affect plants' ability to tolerate toxic elements. However, it is not known if altering the amounts of xyloglucan in the wall influences the uptake and translocation of inorganic arsenic (As). Here, we identified two Nicotiana tabacum genes that encode xyloglucan-specific xylosyltransferases (XXT), which we named NtXXT1 and NtXXT2. We used CRISPR-Cas9 technology to generate ntxxt1 , ntxxt2 , and ntxxt1/2 mutant tobacco plants to determine if preventing xyloglucan synthesis affects plant growth and their ability to accumulate As. We show that NtXXT1 and NtXXT2 are required for xyloglucan biosynthesis because no discernible amounts of xyloglucan were present in the cell walls of the ntxxt1/2 double mutant. The tobacco double mutant (ntxxt1/2) and the corresponding Arabidopsis mutant (atxxt1/2) do not have severe growth defects but do have a short root hair phenotype and a slow growth rate. This phenotype is rescued by overexpressing NtXXT1 or NtXXT2 in atxxt1/2. Growing ntxxt mutants in the presence of AsIII or AsV showed that the absence of cell wall xyloglucan affects the accumulation and translocation of As. Most notably, root retention of As increased substantially and the amounts of As translocated to the shoots decreased in ntxxt1/2. Our results suggest that xyloglucan-deficient plants provide a strategy for the phytoremediation of As contaminated soils. [ABSTRACT FROM AUTHOR]

Programmed cell death plays an important role in modulating host immune defense and pathogen infection. Ferroptosis is a type of inflammatory cell death induced by intracellular iron-dependent accumulation of toxic lipid peroxides. Although ferroptosis has been associated with cancer and other sterile diseases, very little is known about the role of ferroptosis in modulating host-pathogen interactions. We show that accumulation of the secondary messenger bis-(3′,5′)-cyclic dimeric GMP (c-di-GMP) in the pathogenic bacterium Edwardsiella piscicida (E. piscicida) triggers a non-canonical ferroptosis pathway in infected HeLa cells. Moreover, we observed that the dysregulation of c-di-GMP in E. piscicida promotes iron accumulation, mitochondrial dysfunction, and production of reactive oxygen species, all of which that can be blocked by iron chelator. Importantly, unlike classical ferroptosis that is executed via excess lipid peroxidation, no lipid peroxidation was detected in the infected cells. Furthermore, lipoxygenases inhibitors and lipophilic antioxidants are not able to suppress morphological changes and cell death induced by E. piscicida mutant producing excess c-di-GMP, and this c-di-GMP dysregulation attenuates bacterial virulence in vivo. Collectively, our results reveal a novel non-canonical ferroptosis pathway mediated by bacterial c-di-GMP and provide evidence for a role of ferroptosis in the regulation of pathogen infection. [ABSTRACT FROM AUTHOR]

It is important that bacterium can coordinately deliver several effectors into host cells to disturb the cellular progress during infection, however, the precise role of effectors in host cell cytosol remains to be resolved. In this study, we identified a new bacterial virulence effector from pathogenic Edwardsiella piscicida, which presents conserved crystal structure to thioredoxin family members and is defined as a thioredoxin-like protein (Trxlp). Unlike the classical bacterial thioredoxins, Trxlp can be translocated into host cells, mimicking endogenous thioredoxin to abrogate ASK1 homophilic interaction and phosphorylation, then suppressing the phosphorylation of downstream Erk1/2- and p38-MAPK signaling cascades. Moreover, Trxlp-mediated inhibition of ASK1-Erk/p38-MAPK axis promotes the pathogenesis of E. piscicida in zebrafish larvae infection model. Taken together, these data provide insights into the mechanism underlying the bacterial thioredoxin as a virulence effector in downmodulating the innate immune responses during E. piscicida infection. [ABSTRACT FROM AUTHOR]

Inflammatory caspase-11/4/5 recognize cytosolic LPS from invading Gram-negative bacteria and induce pyroptosis and cytokine release, forming rapid innate antibacterial defenses. Since extracellular or vacuole-constrained bacteria are thought to rarely access the cytoplasm, how their LPS are exposed to the cytosolic sensors is a critical event for pathogen recognition. Hemolysin is a pore-forming bacterial toxin, which was generally accepted to rupture cell membrane, leading to cell lysis. Whether and how hemolysin participates in non-canonical inflammasome signaling remains undiscovered. Here, we show that hemolysin-overexpressed enterobacteria triggered significantly increased caspase-4 activation in human intestinal epithelial cell lines. Hemolysin promoted LPS cytosolic delivery from extracellular bacteria through dynamin-dependent endocytosis. Further, we revealed that hemolysin was largely associated with bacterial outer membrane vesicles (OMVs) and induced rupture of OMV-containing vacuoles, subsequently increasing LPS exposure to the cytosolic sensor. Accordingly, overexpression of hemolysin promoted caspase-11 dependent IL-18 secretion and gut inflammation in mice, which was associated with restricting bacterial colonization in vivo. Together, our work reveals a concept that hemolysin promotes noncanonical inflammasome activation via liberating OMVs for cytosolic LPS sensing, which offers insights into innate immune surveillance of dysregulated hemolysin via caspase-11/4 in intestinal antibacterial defenses. [ABSTRACT FROM AUTHOR]

Many bacterial pathogens inject effectors directly into host cells to target a variety of host cellular processes and promote bacterial dissemination and survival. Identifying the bacterial effectors and elucidating their functions are central to understanding the molecular pathogenesis of these pathogens. Edwardsiella piscicida is a pathogen with a wide host range, and very few of its effectors have been identified to date. Here, based on the genes significantly regulated by macrophage infection, we identified 25 intracellular translocation-positive candidate effectors, including all five previously reported effectors, namely EseG, EseJ, EseH, EseK, and EvpP. A subsequent secretion analysis revealed diverse secretion patterns for the 25 effector candidates, suggesting that multiple transport pathways were involved in the internalization of these candidate effectors. Further, we identified two novel type VI secretion system (T6SS) putative effectors and three outer membrane vesicles (OMV)-dependent putative effectors among the candidate effectors described above, and further analyzed their contribution to bacterial virulence in a zebrafish model. This work demonstrates an effective approach for screening bacterial effectors and expands the effectors repertoire in E. piscicida. [ABSTRACT FROM AUTHOR]

Bacterium usually utilises type III secretion systems (T3SS) to deliver effectors directly into host cells with the aids of chaperones. Hence, it is very important to identify bacterial T3SS effectors and chaperones for better understanding of host-pathogen interactions. Edwardsiella piscicida is an invasive enteric bacterium, which infects a wide range of hosts from fish to human. Given E. piscicida encodes a functional T3SS to promote infection, very few T3SS effectors and chaperones have been identified in this bacterium so far. Here, we reported that EseK is a new T3SS effector protein translocated by E. piscicida. Bioinformatic analysis indicated that escH and escS encode two putative class I T3SS chaperones. Further investigation indicated that EscH and EscS can enhance the secretion and translocation of EseK. EscH directly binds EseK through undetermined binding domains, whereas EscS binds EseK via its N-terminal α-helix. We also found that EseK has an N-terminal chaperone-binding domain, which binds EscH and EscS to form a ternary complex. Zebrafish infection experiments showed that EseK and its chaperones EscH and EscS are necessary for bacterial colonisation in zebrafish. This work identified a new T3SS effector, EseK, and its two T3SS chaperones, EscH and EscS, in E. piscicida, which enriches our knowledge of bacterial T3SS effector-chaperone interaction and contributes to our understanding of bacterial pathogenesis. [ABSTRACT FROM AUTHOR]

This study was performed to investigate the clinical manifestations, treatment methods, and prognosis of Rosai-Dorfman disease (RDD) with laryngeal involvement. Five clinical cases of RDD with laryngeal involvement diagnosed between 1986 and 2015 were retrospectively analyzed. The laryngeal lesions of these 5 patients mostly involved the glottis and subglottis, with the main symptoms being a hoarse voice and airway obstruction. In addition, the patients mostly exhibited a unilateral or asymmetric onset that was manifested by a laryngeal submucosal nodular mass. The patients were subjected to a regimen of hormone treatment combined with surgical resection. The median follow-up duration was 101 months (8–384 months). One case was lost, and the remaining 4 subjects are alive with disease. The follow-up examinations revealed that 4 subjects had stable laryngeal conditions, whereas one showed minor progression. RDD with laryngeal involvement is clinically rare and differs considerably from classical RDD in age of onset, gender composition, and extranodal involvement. The regimen of hormone treatment combined with surgical resection can stabilize the patient’s general condition and laryngeal lesion. Tracheotomies are recommended for patients with dyspnea. After their conditions stabilize, decannulation can be successfully performed in most cases. This therapeutic regimen generally delivers a good prognosis. [ABSTRACT FROM AUTHOR]

Edwardsiella piscicida, a bacterial pathogen in fish and humans, expresses a type III secretion system (T3SS) that is critical for pathogen virulence and disease development. However, little is known about the associated effectors and their functional importance. In this study, we identified the ETAE_1757 encoded protein, termed here E. piscicida secretion effector H (EseH) as a novel T3SS effector. We found that upon infection with E. piscicida, EseH is translocated into nucleus of host cells which required the T3SS. Homology modelling analysis suggests that EseH is an enzyme that belongs to the family of phosphothreothine lyases. Consistently, EseH inhibited phosphorylation of ERK1/2, p38α and JNK MAPK pathways in host cells, but had no effect on the NF-kB pathway. Furthermore, mutation of the critical amino acid residues predicted to confer phosphothreonine lyase activity abolished the ability of EseH to inhibit phosphorylation of ERK1/2, p38α and JNK MAPK pathways in host cells. In addition, we found an increase in transcript levels of TNF-α, IL-12, IL-10 and IFN-γ in zebrafish infected with the eseH mutant when compared with the wild type bacterium. Importantly, the virulence of E. piscicida deficient in EseH was highly attenuated in the zebrafish infection model which correlated with decreased loads of the mutant bacterium in both liver and kidney. Complementation of the E. piscicida mutant strain with EseH restored virulence in zebrafish. These results identified EseH as a critical T3SS effector that contributes to virulence by targeting MAPK signalling during E. piscicida infection. [ABSTRACT FROM AUTHOR]

To cross-culturally adapt the Questionnaire of olfactory disorders (QOD) into a Chinese version, and then evaluate its reliability and validity for testing patients with olfactory dysfunction. A Chinese version of the QOD was evaluated for test-retest reliability, split-half reliability, and internal consistency. The validity analysis included components of content validity and criterion-related validity, as well as comparisons between The Medical Outcomes Study's36-Item ShortForm Health Survey(SF-36)questionnaire and the WHO Quality of Life-BREF (WHOQOL-BREF)questionnaire. A total of 125 patients with olfactory dysfunction were tested, and 104 patients completed three different surveys (QOD, SF-36, and WHOQOL-BREF). The test-retest reliabilities of the QOD-Parosmia statements (QOD-P), QOD-Quality of life (QOD-QoL), and QOD-Visual simulation (QOD-VAS)sections were 0.802 ( P < 0.001), 0.797 ( P < 0.001), and 0.468 ( P < 0.001), respectively, and the Cronbach's α coefficients of internal consistency were 0.473, 0.814, and 0.882, respectively. The split-half reliability was 0.70. No correlation was found between the QOD-P section and the SF-36; however, there were statistically significant correlations between the QOD-QoL andQOD-VAS sections and the SF-36. The same results were observed for correlations between the QOD and WHOQOL-BREF. The Chinese version of the QOD was proven to be a generally reliable and valid questionnaire for use in evaluating mainland Chinese patients suspected of having olfactory dysfunction. However, the QOD-P section requires further modifications to properly evaluate patients with a Chinese cultural background and type of cognition. [ABSTRACT FROM AUTHOR]

Inorganic nanoparticles (NPs) are promising drug delivery carriers owing to their high drug loading efficiency, scalable preparation, facile functionalization, and chemical/thermal stability. However, the clinical translation of inorganic nanocarriers is often hindered by their poor biodegradability and lack of controlled pH response. Herein, a fully degradable and pH‐responsive DOX@ACC/PAA NP (pH 7.4–5.6) is developed by encapsulating doxorubicin (DOX) in poly(acrylic acid) (PAA) stabilized amorphous calcium carbonate (ACC) NPs. The DOX‐loaded NPs have small sizes (62 ± 10 nm), good serum stability, high drug encapsulation efficiency (>80%), and loading capacity (>9%). By doping proper amounts of Sr2+ or Mg2+, the drug release of NPs can be further modulated to higher pH responsive ranges (pH 7.7–6.0), which enables drug delivery to the specific cell domains of tissues with a less acidic microenvironment. Tumor inhibition and lower drug acute toxicity are further confirmed via intracellular uptake tests and zebrafish models, and the particles also improve pharmacokinetics and drug accumulation in mouse xenograft tumors, leading to enhanced suppression of tumor growth. Owing to the excellent biocompatibility, biodegradability, and tunable drug release behavior, the present hybrid nanocarrier may find broad applications in tumor therapy. [ABSTRACT FROM AUTHOR]

Inflammasomes are important innate immune components in mammals. However, the bacterial factors modulating inflammasome activation in fish, and the mechanisms by which they alter fish immune defences, remain to be investigated. In this work, a mutant of the fish pathogen Edwardsiella piscicida (E. piscicida), called 0909I, was shown to overexpress haemolysin, which could induce a robust pyroptotic‐like cell death dependent on caspase‐5‐like activity during infection in fish nonphagocyte cells. E. piscicida haemolysin was found to mainly associate with bacterial outer membrane vesicles (OMVs), which were internalised into the fish cells via a dynamin‐dependent endocytosis and induced pyroptotic‐like cell death. Importantly, bacterial immersion infection of both larvae and adult zebrafish suggested that dysregulated expression of haemolysin alerts the innate immune system and induces intestinal inflammation to restrict bacterial colonisation in vivo. Taken together, these results suggest a critical role of zebrafish innate immunity in monitoring invaded pathogens via detecting the bacterial haemolysin‐associated OMVs and initiating pyroptotic‐like cell death. These new additions to the understanding of haemolysin‐mediated pathogenesis in vivo provide evidence for the existence of noncanonical inflammasome signalling in lower vertebrates. [ABSTRACT FROM AUTHOR]

The noncanonical inflammasome is critical for cytosolic sensing of Gram-negative pathogens. Here, we show that bacterial infection induces caspy2 activation in zebrafish fibroblasts, which mediates pyroptosis via a caspase-5-like activity. Zebrafish caspy2 binds directly to lipopolysaccharide via the N-terminal pyrin death domain, resulting in caspy2 oligomerization, which is critical for pyroptosis. Furthermore, we show that caspy2 is highly expressed in the zebrafish gut and is activated during infection. Knockdown of caspy2 expression impairs the ability of zebrafish to restrict bacterial invasion in vivo, and protects larvae from lethal sepsis. Collectively, our results identify a crucial event in the evolution of pattern recognition into the death domain superfamily-mediated intracellular lipopolysaccharide-sensing pathway in innate immunity. In humans, caspase-5 is an LPS sensor that can induce gasdermin D cleavage and pyroptosis. Here, the authors show that zebrafish caspy2 is a functional homolog as it also senses cytosolic LPS to activate the noncanonical inflammasome and to protect against bacterial infection, but it does so via pyrin death domain interactions. [ABSTRACT FROM AUTHOR]