Crystal Field-Engineered Cr3+-Doped Gd3(MgxGa5-2xGex)O12 Phosphors for Near-Infrared LEDs and X-ray Imaging Applications.

Inorganic materials doped with chromium (Cr) ions generate remarkable and adjustable broadband near-infrared (NIR) light, offering promising applications in the fields of imaging and night vision technology. However, achieving high efficiency and thermal stability in these broadband NIR phosphors poses a significant challenge for their practical application. Here, we employ crystal field engineering to modulate the NIR characteristics of Cr3+-doped Gd3Ga5O12 (GGG). The Gd3MgxGa5-2xGexO12 (GMGG):7.5% Cr3+ (x = 0, 0.05, 0.15, 0.20, and 0.40) phosphors with NIR emission are developed through the cosubstitution of Mg2+ and Ge4+ for Ga3+ sites. This cosubstitution strategy also effectively reduces the crystal field strength around Cr3+ ions, which results in a significant enhancement of the photoluminescence (PL) full width at half-maximum (fwhm) from 97 to 165 nm, alongside a red shift in the PL peak and an enhancement of the PL intensity up to 2.3 times. Notably, the thermal stability of the PL behaviors is also improved. The developed phosphors demonstrate significant potential in biological tissue penetration and night vision, as well as an exceptional scintillation performance for NIR scintillator imaging. This research paves a new perspective on the development of high-performance NIR technology in light-emitting diodes (LEDs) and X-ray imaging applications.

Development of Monoclonal Antibody against PirB and Establishment of a Colloidal Gold Immunochromatographic Assay for the Rapid Detection of AHPND-Causing Vibrio.

Acute hepatopancreatic necrosis disease (AHPND) poses a significant threat to shrimp aquaculture worldwide, necessitating the accurate and rapid detection of the pathogens. However, the increasing number of Vibrio species that cause the disease makes diagnosis and control more difficult. This study focuses on developing a monoclonal antibody against the Photorhabdus insect-related (Pir) toxin B (PirB), a pivotal virulence factor in AHPND-causing Vibrio, and establishing a colloidal gold immunochromatographic assay for the enhanced early diagnosis and monitoring of AHPND. Monoclonal antibodies targeting PirB were developed and utilized in the preparation of colloidal-gold-labeled antibodies for the immunochromatographic assay. The specificity and sensitivity of the assay were evaluated through various tests, including antibody subclass detection, affinity detection, and optimal labeling efficiency assessment. The developed PirB immunochromatographic test strips exhibited a good specificity, as demonstrated by the positive detection of AHPND-causing Vibrio and negative results for non-AHPND-causing Vibrio. The study highlights the potential of the developed monoclonal antibody and immunochromatographic assay for the effective detection of AHPND-causing Vibrio. Further optimization is needed to enhance the sensitivity of the test strips for improved practical applications in disease prevention and control in shrimp aquaculture.

Nonstoichiometry-Induced Self-Activated Phosphors for Dynamic Anti-counterfeiting Applications.

Optical signals with distinctive properties, such as contactless, fast response, and high identification, are harnessed to realize advanced anti-counterfeiting. However, the simultaneous attainment of multi-color, -temporal, and -modal luminescence performance remains a compelling and imperative pursuit. In our work, a temperature/photon-responded dynamic self-activated luminescence originating from nonstoichiometric Zn2GeO4 is developed with the modulation of intrinsic defects. The increased concentration of oxygen vacancies (VO••) contributes to an enhanced recombination of ZnGe″-VO••, ultimately improving the self-activated luminescence performance. Additionally, the photoluminescence (PL) color of the representative Zn2.2GeO4 sample changes from green to blue-white with the increased ultraviolet (UV) irradiation time. Concurrently, the emission color undergoes a variation from blue to green as the ambient temperature raises from 280 to 420 K. Remarkably, green long persistent luminescence (LPL) and photostimulated luminescence (PSL) behaviors are observed. Herein, this study elucidates a sophisticated anti-counterfeiting approach grounded in the dynamic luminescent attributes of nonstoichiometric Zn2GeO4, presenting a promising frontier for the evolution of anti-counterfeiting technologies.

Meta-Transcriptomic Analysis Reveals Novel RNA Viruses in Polychaetes Perinereis.

Perinereis species are essential benthonic animals in coastal ecosystems and have significant roles as live feed in aquaculture, owing to their high-protein and low-fat nutritional profile. Despite their ecological importance, the viral communities associated with these organisms need to be better understood. In this study, we generated 2.6 × 108 reads using meta-transcriptomic sequencing and de novo assembled 5.3 × 103 virus-associated contigs. We identified 12 novel RNA viruses from two species, Perinereis aibuhitensis and P. wilsoni, which were classified into four major viral groups: Picobirnaviridae, Marnaviridae, unclassified Picornavirales, and unclassified Bunyavirales. Our findings revealed the hidden diversity of viruses and genome structures in Perinereis, enriching the RNA virosphere and expanding the host range of Picobirnaviridae, Marnaviridae, and Bunyavirales. This study also highlighted the potential biosecurity risk of the novel viruses carried by Perinereis to aquaculture.

Cuproptotic nanoinducer-driven proteotoxic stress potentiates cancer immunotherapy by activating the mtDNA-cGAS-STING signaling.

Proteotoxic stress, caused by the accumulation of abnormal unfolded or misfolded cellular proteins, can efficiently activate inflammatory innate immune response. Initiating the mitochondrial proteotoxic stress might go forward to enable the cytosolic release of intramitochondrial DNA (mtDNA) for the immune-related mtDNA-cGAS-STING activation, which however is easily eliminated by a cell self-protection, i.e., mitophagy. In light of this, a nanoinducer (PCM) is reported to trigger mitophagy-inhibited cuproptotic proteotoxicity. Through a simple metal-phenolic coordination, PCMs reduce the original Cu2+ with the phenolic group of PEG-polyphenol-chlorin e6 (Ce6) into Cu+. Cu+ thereby performs its high binding affinity to dihydrolipoamide S-acetyltransferase (DLAT) and aggregates DLAT for cuproptotic proteotoxic stress and mitochondrial respiratory inhibition. Meanwhile, intracellular oxygen saved from the respiratory failure can be utilized by PCM-conjugated Ce6 to boost the proteotoxic stress. Next, PCM-loaded mitophagy inhibitor (Mdivi-1) protects proteotoxic products from being mitophagy-eliminated, which allows more mtDNA to be released in the cytosol and successfully stimulate the cGAS-STING signaling. In vitro and in vivo studies reveal that PCMs can upregulate the tumor-infiltrated NK cells by 24% and enhance the cytotoxic killing of effector T cells. This study proposes an anti-tumor immunotherapy through mitochondrial proteotoxicity.

Dual-Epigenetically Relieving the MYC-Correlated Immunosuppression via an Advanced Nano-Radiosensitizer Potentiates Cancer Immuno-Radiotherapy.

Cancer cells can upregulate the MYC expression to repair the radiotherapy-triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC-transcriptional abnormality may intensively solve this clinical problem. Herein, 5-Aza (a DNA methyltransferase inhibitor) and ITF-2357 (a histone deacetylase inhibitor) are engineered into a tungsten-based nano-radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5-Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF-2357, which triggers cancer cellular type I interferon (IFN-I) signaling. Coupling 5-Aza with ITF-2357 ensures that PWAI does not evoke the treated model with high MYC-related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN-I signal-related proteins involving IFN-α and IFN-ß. Unlike the radiation treatment alone, PWAI-triggered immuno-radiotherapy remarkably enhances antitumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory-phenotype formation in 4T1 tumor-bearing mice. Downgrading the radiotherapy-induced MYC overexpression via the dual-epigenetic reprogramming strategy may elicit a robust immuno-radiotherapy.

Development of a Melting Curve-Based Triple Eva Green Real-Time PCR Assay for Simultaneous Detection of Three Shrimp Pathogens.

Infections with Enterocytozoon hepatopenaei (EHP), infectious hypodermal and hematopoietic necrosis virus (IHHNV), and Decapod iridescent virus 1 (DIV1) pose significant challenges to the shrimp industry. Here, a melting curve-based triple real-time PCR assay based on the fluorescent dye Eva Green was established for the simultaneous detection of EHP, IHHNV, and DIV1. The assay showed high specificity, sensitivity, and reproducibility. A total of 190 clinical samples from Shandong, Jiangsu, Sichuan, Guangdong, and Hainan provinces in China were evaluated by the triple Eva Green real-time PCR assay. The positive rates of EHP, IHHNV, and DIV1 were 10.5%, 18.9%, and 44.2%, respectively. The samples were also evaluated by TaqMan qPCR assays for EHP, DIV1, and IHHNV, and the concordance rate was 100%. This illustrated that the newly developed triple Eva Green real-time PCR assay can provide an accurate method for the simultaneous detection of three shrimp pathogens.

PhotoPyro-Induced cGAS-STING Pathway Activation Enhanced Anti-Melanoma Immunotherapy via a Manganese-Coordinated Nanomedicine.

Malignant melanoma is an aggressive skin cancer with a high metastatic and mortality rate. Owing to genetic alterations, melanoma cells are resistant to apoptosis induction, which reduces the efficacy of most adjuvant systemic anticancer treatments in clinical. Here, a noninvasive strategy for anti-melanoma immunotherapy based on a manganese-coordinated nanomedicine is provided. Supplemented with photoirradiation, photon-mediated reactive oxygen species generation by photosensitizer chlorin e6 initiates photon-controlled pyroptosis activation (PhotoPyro) and promotes antitumor immunity. Simultaneously, photoirradiation-triggered double-stranded DNA generation in the cytosol would activate the Mn2+ -sensitized cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which further augment the PhotoPyro-induced immune response. The syngeneic effect of these immunostimulatory pathways significantly benefits dendritic cell maturation by damage-associated molecular patterns and proinflammatory cytokines secretion, thereby activating T cells and remarkably eliciting a systemic antitumor immune response to inhibiting both primary and distant tumor growth. Collaboratively, the photoirradiation-triggered PhotoPyro and cGAS-STING pathway activation by nanomedicine administration could enhance the antitumor capacity of immunotherapy and serve as a promising strategy for melanoma treatment.

Diversity and connectedness of brine shrimp viruses in global hypersaline ecosystems.

Brine shrimp (Artemia) has existed on Earth for 400 million years and has major ecological importance in hypersaline ecosystems. As a crucial live food in aquaculture, brine shrimp cysts have become one of the most important aquatic products traded worldwide. However, our understanding of the biodiversity, prevalence and global connectedness of viruses in brine shrimp is still very limited. A total of 143 batches of brine shrimp (belonging to seven species) cysts were collected from six continents including 21 countries and more than 100 geographic locations worldwide during 1977-2019. In total, 55 novel RNA viruses were identified, which could be assigned to 18 different viral families and related clades. Eleven viruses were dsRNA viruses, 16 were +ssRNA viruses, and 28 were-ssRNA viruses. Phylogenetic analyses of the RNA-directed RNA polymerase (RdRp) showed that brine shrimp viruses were often grouped with viruses isolated from other invertebrates and fungi. Remarkably, most brine shrimp viruses were related to those from different hosts that might feed on brine shrimp or share the same ecological niche. A notable case was the novel brine shrimp noda-like virus 3, which shared 79.25% (RdRp) and 63.88% (capsid proteins) amino acid identity with covert mortality nodavirus (CMNV) that may cause losses in aquaculture. In addition, both virome composition and phylogenetic analyses revealed global connectedness in certain brine shrimp viruses, particularly among Asia and Northern America. This highlights the incredible species diversity of viruses in these ancient species and provides essential data for the prevalence of RNA viruses in the global aquaculture industry. More broadly, these findings provide novel insights into the previously unrecognized RNA virosphere in hypersaline ecosystems worldwide and demonstrate that human activity might have driven the global connectedness of brine shrimp viruses.

Visualized Stress-Temperature Sensor with the Zinc Sulfide and Perovskite Glass Ceramics Composite.

The visualized dual-modal stress-temperature sensing refers to the ability of a sensor to provide real-time and visible information about both stress and temperature and has indeed attracted significant interest in various fields. However, the development of convenient methods for achieving this capability remains a challenge. In this work, a dual-modal stress-temperature sensor is successfully fabricated using a ZnS/Cu@CsPbBr1.2I1.8 glass ceramics (GCs)/polydimethylsiloxane (PDMS) (ZCP) composite film. The tunable ML color is achieved by modulating the concentration of CsPbBr1.2I1.8 GCs in the ZCP composite films based on the light conversion process from ZnS/Cu to CsPbBr1.2I1.8 GCs. Additionally, the stress and temperature can be visualized simultaneously by integrating the ML intensity and ML color of the ZCP composite film. This feature allows for the real-time monitoring of automotive tire temperature by embedding the ZCP composite film on the tire surface, enabling a strong and stable response to both stress and temperature changes. Overall, this work offers a convenient, efficient, and repeatable approach for achieving visualized dual-modal stress-temperature sensing in the fields of mechanical engineering, structural health monitoring, and intelligent devices.

Multimode-Responsive Luminescence of Er3+ Single-Activated CaF2 Phosphor for Advanced Information Encryption.

The current optical anticounterfeit strategies that rely on multimode luminescence in response to the photon or thermal stimuli have significant importance in the field of anticounterfeiting and information encryption. However, the dependence on light and heat sources might limit their flexibility in practical applications. In this work, Er3+ single-doped CaF2 phosphors that show multistimuli-responsive luminescence have been successfully prepared. The as-obtained CaF2:Er3+ phosphor exhibits green photoluminescence (PL) and color-tunable up-conversation (UC) luminescence from red to green due to the cross-relaxation of Er3+ ions. Additionally, as-obtained CaF2:Er3+ phosphors also display green mechano-luminescence behavior, which is induced by the contact electrification between the CaF2 particles and PDMS polymers, enabling the phosphor to flexibly respond to mechanical stimuli. Moreover, feasible anticounterfeiting schemes with the capability of multistimuli-responsive and flexible decryption have been constructed, further expanding the application of optical materials in the field of advanced anticounterfeiting and information encryption.

Metal-Phenolic Nanomedicines Regulate T-Cell Antitumor Function for Sono-Metabolic Cancer Therapy.

Cancer cells outcompete tumor-infiltrating T lymphocytes (TILs) for glucose uptake, manipulating a glucose-deprived tumor microenvironment (TME) with high accumulation of lactate, which impairs CD8+ TIL effector function, however supports the immune suppression of regulatory T (Treg) cells. Aerobic glycolysis inhibition coupled with mitochondrial dysfunction in cancer cells may reprogram TME to destabilize Treg cells and, more importantly, facilitate CD8+ T cell activation and cytotoxic killing. Here, a sono-metabolic cancer therapy via hyaluronic acid (HA)-modified metal-phenolic nanomedicine (HPP-Ca@GSK) is proposed to accomplish the aforementioned goals. Abrogating lactate dehydrogenase A (LDHA) by delivering GSK2837808A (GSK, LDHA inhibitor) successfully suppresses aerobic glycolysis in cancer cells and creates high-glucose, low-lactate conditions, satisfying the glucose nutrition required by CD8+ TILs but destabilizing Treg cells. Meanwhile, depending on ultrasound-mediated oxidative stress, more than 3-fold of calcium (from HPP-Ca@GSK) is mitochondrion-overloaded, amplifying mitochondrial dysfunction and promoting the cancer cellular release of damage-associated molecular patterns for more CD8+ T cell activation and tumor infiltration. In vitro and in vivo studies demonstrate that HPP-Ca@GSK-based sono-metabolic treatment exhibits impressive anticancer activity. Cooperating with anticytotoxic T lymphocyte-associated protein-4 antibodies for enhanced Treg cell destabilization further improves therapeutic efficacy. These findings provide a metabolic intervention strategy for cancer immunotherapy.

Fueling sentinel node via reshaping cytotoxic T lymphocytes with a flex-patch for post-operative immuno-adjuvant therapy.

Clinical updates suggest conserving metastatic sentinel lymph nodes (SLNs) of breast cancer (BC) patients during surgery; however, the immunoadjuvant potential of this strategy is unknown. Here we leverage an immune-fueling flex-patch to animate metastatic SLNs with personalized antitumor immunity. The flex-patch is implanted on the postoperative wound and spatiotemporally releases immunotherapeutic anti-PD-1 antibodies (aPD-1) and adjuvants (magnesium iron-layered double hydroxide, LDH) into the SLN. Genes associated with citric acid cycle and oxidative phosphorylation are enriched in activated CD8+ T cells (CTLs) from metastatic SLNs. Delivered aPD-1 and LDH confer CTLs with upregulated glycolytic activity, promoting CTL activation and cytotoxic killing via metal cation-mediated shaping. Ultimately, CTLs in patch-driven metastatic SLNs could long-termly maintain tumor antigen-specific memory, protecting against high-incidence BC recurrence in female mice. This study indicates a clinical value of metastatic SLN in immunoadjuvant therapy.

Self-Degradable Nanogels Reshape Immunosuppressive Tumor Microenvironment via Drug Repurposing Strategy to Reactivate Cytotoxic CD8+ T Cells.

Intratumoral CD8+ T cells are crucial for effective cancer immunotherapy, but an immunosuppressive tumor microenvironment (TME) contributes to dysfunction and insufficient infiltration. Drug repurposing has successfully led to new discoveries among existing clinical drugs for use as immune modulators to ameliorate immunosuppression in TME and reactivate T-cell-mediated antitumor immunity. However, due to suboptimal tumor bioavailability, the full potential of immunomodulatory effects of these old drugs has not been realized. The self-degradable PMI nanogels carrying two repurposed immune modulators, imiquimod (Imi) and metformin (Met), are reported for TME-responsive drug release. It remodels the TME through the following aspects: 1) promoting dendritic cells maturation, 2) repolarizing M2-like tumor-associated macrophages, and 3) downregulating PD-L1 expression. Ultimately, PMI nanogels reshaped the immunosuppressive TME and efficiently promote CD8+ T cell infiltration and activation. These results support that PMI nanogels can potentially be an effective combination drug for enhancing the antitumor immune response of anti-PD-1 antibodies.

Coinfection with Yellow Head Virus Genotype 8 (YHV-8) and Oriental Wenrivirus 1 (OWV1) in Wild Penaeus chinensis from the Yellow Sea.

At present, there are few studies on the epidemiology of diseases in wild Chinese white shrimp Penaeus chinensis. In order to enrich the epidemiological information of the World Organisation for Animal Health (WOAH)-listed and emerging diseases in wild P. chinensis, we collected a total of 37 wild P. chinensis from the Yellow Sea in the past three years and carried out molecular detection tests for eleven shrimp pathogens. The results showed that infectious hypodermal and hematopoietic necrosis virus (IHHNV), Decapod iridescent virus 1 (DIV1), yellow head virus genotype 8 (YHV-8), and oriental wenrivirus 1 (OWV1) could be detected in collected wild P. chinensis. Among them, the coexistence of IHHNV and DIV1 was confirmed using qPCR, PCR, and sequence analysis with pooled samples. The infection with YHV-8 and OWV1 in shrimp was studied using molecular diagnosis, phylogenetic analysis, and transmission electron microscopy. It is worth highlighting that this study revealed the high prevalence of coinfection with YHV-8 and OWV1 in wild P. chinensis populations and the transmission risk of these viruses between the wild and farmed P. chinensis populations. This study enriches the epidemiological information of WOAH-listed and emerging diseases in wild P. chinensis in the Yellow Sea and raises concerns about biosecurity issues related to wild shrimp resources.

Enzyme and Reactive Oxygen Species-Responsive Dual-Drug Delivery Nanocomplex for Tumor Chemo-Photodynamic Therapy.

Introduction: Combination therapy is a promising approach to promote the efficacy and reduce the systemic toxicity of cancer therapy. Herein, we examined the potency of a combined chemo-phototherapy approach by constructing a hyaluronidase- and reactive oxygen species-responsive hyaluronic acid nanoparticle carrying a chemotherapy drug and a photosensitizer in a tumor-bearing mouse model. We hypothesized that following decomposition, the drugs inside the nanocomplex will be released in the tumors to provide effective tumor treatment. We aimed to design a smart drug delivery system that can improve traditional chemotherapy drug delivery and enhance the therapeutic efficacy in combination with photodynamic therapy. Methods: Hydrophilic hyaluronic acid (HA) was covalently modified with a hydrophobic 5ß-cholanic acid (CA) via an ROS-cleavable thioketal (tk) linker for a targeted co-deliver of 10-Hydroxy camptothecin (HCPT) and Chlorin e6 (Ce6) into tumors to improve the efficiency of combined chemo-photodynamic therapy. Results: The obtained HA-tk-CA nanoparticle carrying HCPT and Ce6, named HTCC, accumulated in the tumor through the enhanced permeable response (EPR) effect and HA-mediated CD44 targeting after intravenous administration. Upon laser irradiation and hyaluronidase degradation, HTCC was disrupted to release HCPT and Ce6 into the tumors. Compared to the monotherapy approach, HTCC demonstrated enhanced tumor growth inhibition and minimized systemic toxicity in a tumor-bearing mouse model. Conclusion: Our results suggested that controlled dual-drug release not only improved tumor drug delivery efficacy, but also reduced systemic side effects. In addition to HCPT and Ce6 delivery, the HA-tk-CA nanocomplex can be used to deliver other drugs in synergistic cancer therapy. Since most current combined therapy uses free drugs with distinct spatiotemporal distributions, the simultaneous co-delivery of dual drugs with a remote on-demand drug delivery nanosystem provides an alternative strategy for drug delivery design.

A platinum@polymer-catechol nanobraker enables radio-immunotherapy for crippling melanoma tumorigenesis, angiogenesis, and radioresistance.

Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis, angiogenesis, and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression. Interdicting melanoma intrinsic growth signals, including the blockade of PD-L1 and mTOR signaling concurrently, cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor encumbrance. Thence, we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody (aPD-L1) for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma eradication. The aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1: PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling; corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis, respectively. Further, high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal efficacy. Hereto, the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic efficacy. Such an ingenious tactic may provide substantial benefits to clinical melanoma patients.

A neuron-immune circuit regulates neurodegeneration in the hindbrain and spinal cord of Arf1-ablated mice.

Neuroimmune connections have been revealed to play a central role in neurodegenerative diseases (NDs). However, the mechanisms that link the central nervous system (CNS) and peripheral immune cells are still mostly unknown. We recently found that specific ablation of the Arf1 gene in hindbrain and spinal cord neurons promoted NDs through activating the NLRP3 inflammasome in microglia via peroxided lipids and adenosine triphosphate (ATP) releasing. Here, we demonstrate that IL-1ß with elevated chemokines in the neuronal Arf1-ablated mouse hindbrain and spinal cord recruited and activated γδ T cells in meninges. The activated γδ T cells then secreted IFN-γ that entered into parenchyma to activate the microglia-A1 astrocyte-C3-neuronal C3aR neurotoxic pathway. Remarkably, the neurodegenerative phenotypes of the neuronal Arf1-ablated mice were strongly ameliorated by IFN-γ or C3 knockout. Finally, we show that the Arf1-reduction-induced neuroimmune-IFN-γ-gliosis pathway exists in human NDs, particularly in amyotrophic lateral sclerosis and multiple sclerosis. Together, our results uncover a previously unknown mechanism that links the CNS and peripheral immune cells to promote neurodegeneration.

Conjugative Transfer of Acute Hepatopancreatic Necrosis Disease-Causing pVA1-Type Plasmid Is Mediated by a Novel Self-Encoded Type IV Secretion System.

The pathogenic pVA1-type plasmids that carry pirAB toxin genes are the genetic basis for Vibrio to cause acute hepatopancreatic necrosis disease (AHPND), a lethal shrimp disease posing an urgent threat to shrimp aquaculture. Emerging evidence also demonstrate the rapid spread of pVA1-type plasmids across Vibrio species. The pVA1-type plasmids have been predicted to encode a self-encoded type IV secretion system (T4SS). Here, phylogenetic analysis indicated that the T4SS is a novel member of Trb-type. We further confirmed that the T4SS was able to mediate the conjugation of pVA1-type plasmids. A trbE gene encoding an ATPase and a traG gene annotated as a type IV coupling protein (T4CP) were characterized as key components of the T4SS. Deleting either of these 2 genes abolished the conjugative transfer of a pVA1-type plasmid from AHPND-causing Vibrio parahaemolyticus to Vibrio campbellii, which was restored by complementation of the corresponding gene. Moreover, we found that bacterial density, temperature, and nutrient levels are factors that can regulate conjugation efficiency. In conclusion, we proved that the conjugation of pVA1-type plasmids across Vibrio spp. is mediated by a novel T4SS and regulated by environmental factors. IMPORTANCE AHPND is a global shrimp bacteriosis and was listed as a notifiable disease by the World Organization for Animal Health (WOAH) in 2016, causing losses of more than USD 7 billion each year. Several Vibrio species such as V. parahaemolyticus, V. harveyi, V. campbellii, and V. owensii harboring the virulence plasmid (designated as the pVA1-type plasmid) can cause AHPND. The increasing number of Vibrio species makes prevention and control more difficult, threatening the sustainable development of the aquaculture industry. In this study, we found that the horizontal transfer of pVA1-type plasmid is mediated by a novel type IV secretion system (T4SS). Our study explained the formation mechanism of pathogen diversity in AHPND. Moreover, bacterial density, temperature, and nutrient levels can regulate horizontal efficiency. We explore new ideas for controlling the spread of virulence plasmid and form the basis of management strategies leading to the prevention and control of AHPND.