Decolonising global health research: Shifting power for transformative change.

Recent debates on decolonizing global health have spurred interest in addressing the power asymmetries and knowledge hierarchies that sustain colonial ideas and relationships in global health research. This paper applies three intersecting dimensions of colonialism (colonialism within global health; colonisation of global health; and colonialism through global health) to develop a broader and more structural understanding of the policies and actions needed to decolonise global health research. It argues that existing guidelines and checklists designed to make global health research more equitable do not adequately address the underlying power asymmetries and biases that prevail across the global health research ecosystem. Beyond encouraging fairer partnerships within individual research projects, this paper calls for more emphasis on shifting the balance of decision-making power, redistributing resources, and holding research funders and other power-holders accountable to the places and peoples involved in and impacted by global health research.

Developing an agenda for the decolonization of global health.

Colonialism, which involves the systemic domination of lands, markets, peoples, assets, cultures or political institutions to exploit, misappropriate and extract wealth and resources, affects health in many ways. In recent years, interest has grown in the decolonization of global health with a focus on correcting power imbalances between high-income and low-income countries and on challenging ideas and values of some wealthy countries that shape the practice of global health. We argue that decolonization of global health must also address the relationship between global health actors and contemporary forms of colonialism, in particular the current forms of corporate and financialized colonialism that operate through globalized systems of wealth extraction and profiteering. We present a three-part agenda for action that can be taken to decolonize global health. The first part relates to the power asymmetries that exist between global health actors from high-income and historically privileged countries and their counterparts in low-income and marginalized settings. The second part concerns the colonization of the structures and systems of global health governance itself. The third part addresses how colonialism occurs through the global health system. Addressing all forms of colonialism calls for a political and economic anticolonialism as well as social decolonization aimed at ensuring greater national, racial, cultural and knowledge diversity within the structures of global health.

Le colonialisme, qui implique la domination systémique de terres, de marchés, de peuples, de ressources, de cultures ou d'institutions politiques dans le but d'exploiter, de détourner et d'extraire des richesses et des ressources, affecte la santé de nombreuses manières. Ces dernières années, la décolonisation de la santé mondiale a suscité un intérêt croissant, l'accent étant mis sur la correction des déséquilibres de pouvoir entre les pays à revenu élevé et les pays à faible revenu, ainsi que sur la remise en question des idées et des valeurs de certains pays riches qui façonnent la pratique de la santé mondiale. Nous soutenons que la décolonisation de la santé mondiale doit également aborder la relation entre les acteurs de la santé mondiale et les formes contemporaines de colonialisme, en particulier les formes actuelles de colonialisme d'entreprise et de colonialisme financiarisé qui opèrent par des systèmes mondialisés d'extraction de richesses et de profits. Nous présentons un programme d'action en trois parties destiné à décoloniser la santé mondiale. La première partie porte sur les asymétries de pouvoir existant entre les acteurs de la santé mondiale des pays à hauts revenus et historiquement privilégiés et leurs homologues des pays à faibles revenus et marginalisés. La deuxième partie concerne la colonisation des structures et des systèmes de la gouvernance mondiale de la santé elle-même. La troisième partie traite de la manière dont le colonialisme se manifeste à travers le système de santé mondial. La lutte contre toutes les formes de colonialisme nécessite un anticolonialisme politique et économique ainsi qu'une décolonisation sociale visant à garantir une plus grande diversité nationale, raciale, culturelle et des connaissances au sein des structures de la santé mondiale.

El colonialismo, que implica la dominación sistémica de tierras, mercados, pueblos, bienes, culturas o instituciones políticas para explotar, apropiarse indebidamente y extraer riqueza y recursos, afecta a la salud de muchas maneras. En los últimos años ha crecido el interés por descolonizar la salud mundial, en particular para corregir los desequilibrios de poder entre los países de ingresos altos y los de ingresos bajos, y para cuestionar las ideas y los valores de algunos países ricos que influyen en la práctica de la salud mundial. Sostenemos que la descolonización de la salud mundial también debe abordar la relación entre los actores de la salud mundial y las formas contemporáneas de colonialismo, en especial las formas actuales de colonialismo corporativo y financiarizado que operan a través de sistemas globalizados de extracción de riqueza y especulación. Presentamos un programa de acción dividido en tres partes para descolonizar la salud mundial. La primera parte se refiere a las asimetrías de poder que existen entre los actores de la salud mundial procedentes de países de ingresos altos e históricamente privilegiados y sus homólogos de entornos de ingresos bajos y marginados. La segunda parte se refiere a la colonización de las estructuras y sistemas de la propia gobernanza de la salud mundial. La tercera parte aborda cómo se produce el colonialismo a través del sistema sanitario mundial. Abordar todas las formas de colonialismo exige un anticolonialismo político y económico, así como una descolonización social destinada a garantizar una mayor diversidad nacional, racial, cultural y de conocimientos dentro de las estructuras de la salud mundial.

Shrimp SIRT4 promotes white spot syndrome virus replication.

In WSSV pathogenesis, the molecular mechanisms and the key host factors that regulate the viral replication and morphogenesis remain unclear. However, like most viruses, WSSV is known to induce metabolic reprogramming in several metabolic pathways including the host glutamine metabolism, and several recent reports have suggested that the sirtuins SIRT3, SIRT4, and SIRT5, which belong to a family of NAD+-dependent deacetylases, play an important role in this regulation. Here we focus on characterizing LvSIRT4 from Litopenaeus vannamei and investigate its role in regulating glutamine dehydrogenase (GDH), an important enzyme that promotes glutaminolysis and viral replication. We found that LvSIRT4 silencing led to significant decreases in both WSSV gene expression and the number of viral genome copies. Conversely, overexpression of LvSIRT4 led to significant increases in the expression of WSSV genes and the WSSV genome copy number. Immunostaining in Sf9 insect cells confirmed the presence of LvSIRT4 in the mitochondria and the co-localization of LvSIRT4 and LvGDH in the same cellular locations. In vivo gene silencing of LvSIRT4 significantly reduced the gene expression of LvGDH whereas LvSIRT4 overexpression had no effect. However, neither silencing nor overexpression had any effect on the protein expression levels of LvGDH. Lastly, although GDH activity in uninfected shrimp was unchanged, the GDH enzyme activity in WSSV-infected shrimp was significantly increased after both LvSIRT4 silencing and overexpression. This suggests that although there may be no direct regulation, LvSIRT4 might still be able to indirectly regulate LvGDH via the mediation of one or more WSSV proteins that have yet to be identified.

Machine Learning Elucidates Design Features of Plasmid DNA Lipid Nanoparticles for Cell Type-Preferential Transfection.

For cell and gene therapies to become more broadly accessible, it is critical to develop and optimize non-viral cell type-preferential gene carriers such as lipid nanoparticles (LNPs). Despite the effectiveness of high throughput screening (HTS) approaches in expediting LNP discovery, they are often costly, labor-intensive, and often do not provide actionable LNP design rules that focus screening efforts on the most relevant chemical and formulation parameters. Here we employed a machine learning (ML) workflow using well-curated plasmid DNA LNP transfection datasets across six cell types to maximize chemical insights from HTS studies and has achieved predictions with 5-9% error on average depending on cell type. By applying Shapley additive explanations to our ML models, we unveiled composition-function relationships dictating cell type-preferential LNP transfection efficiency. Notably, we identified consistent LNP composition parameters that enhance in vitro transfection efficiency across diverse cell types, such as ionizable to helper lipid ratios near 1:1 or 10:1 and the incorporation of cationic/zwitterionic helper lipids. In addition, several parameters were found to modulate cell type-preferentiality, including the ionizable and helper lipid total molar percentage, N/P ratio, cholesterol to PEGylated lipid ratio, and the chemical identity of the helper lipid. This study leverages HTS of compositionally diverse LNP libraries and ML analysis to understand the interactions between lipid components in LNP formulations; and offers fundamental insights that contribute to the establishment of unique sets of LNP compositions tailored for cell type-preferential transfection.

Gut microbiota of Pacific white shrimp (Litopenaeus vannamei) exhibits distinct responses to pathogenic and non-pathogenic Vibrio parahaemolyticus.

Acute hepatopancreatic necrosis disease (AHPND), a high-mortality-rate shrimp disease, is caused by specific Vibrio parahaemolyticus (Vp) strains with a plasmid encoding the PirABVp toxins. As a bacterial pathogen, the invasion of AHPND-causing Vp might impose pressure on commensal microbiota in the shrimp gut, while the relationship between the pathogenesis of AHPND and the dysbiosis of gut bacterial communities remains unclear. Here we explored the temporal changes of shrimp gut microbiota in response to AHPND-causing and non-AHPND-causing Vp strains, with the non-infected controls as a baseline of the shrimp gut microbiota. The diversity and composition of bacterial communities from 168 gut samples (covering three treatments at seven time points with eight individuals per set) were investigated using 16S rRNA gene metabarcoding with high-throughput sequencing. The results showed that (i) species diversity of gut bacterial communities declined in Vp-infected shrimp, independent of the strain pathogenicity; (ii) taxonomic compositions of gut bacterial communities were significantly different between shrimp infected by AHPND-causing and non-AHPND-causing Vp strains; (iii) short-term (within 6 hours) compositional shifts in the gut microbiota were found only in AHPND-causing Vp-infected shrimp; (iv) the gut microbiota of AHPND-causing Vp-infected shrimp was enriched with genera Photobacterium and Vibrio, with a decline in Candidatus Bacilliplasma; and (v) functional predictions suggested the loss of normal metabolism due to compositional shifts in the gut microbiota. Our work reveals distinct features of community dynamics in shrimp gut microbiota, associated with pathogenic versus non-pathogenic Vibrio infections, providing a new perspective of the pathogenesis of AHPND. IMPORTANCE Shrimp production is continually threatened by newly emerging diseases, such as AHPND, which is caused by specific Vp strains. Previous studies on the pathogenesis of AHPND have mainly focused on the histopathology and immune responses of the host. However, more attention needs to be paid to the gut microbiota, which acts as the first barrier to pathogen colonization. In this study, we revealed that shrimp gut microbiota responded differently to pathogenic and non-pathogenic Vp strains, with bacterial genera Photobacterium and Vibrio enriched in pathogenic Vp-infected shrimp, and Candidatus Bacilliplasma enriched in non-pathogenic Vp-infected shrimp. Moreover, functional predictions suggested that changes in taxonomic compositions would further affect normal metabolic functions, emphasizing the importance of sustaining an equilibrium in the gut microbiota. Several biomarkers associated with specific microbial taxa and functional pathways were identified in our data sets, which help predict the incidence of disease outcomes.

Systematic review of global hepatitis E outbreaks to inform response and coordination initiatives.

INTRODUCTION: Hepatitis E virus (HEV) is the most common cause of acute hepatitis. While symptoms are generally mild and resolve within weeks, some populations (e.g., pregnant women, immunocompromised adults) are at high-risk of severe HEV-related morbidity and mortality. There has not been a recent comprehensive review of contemporary HEV outbreaks, which limits the validity of current disease burden estimates. Therefore, we aimed to characterize global HEV outbreaks and describe data gaps to inform HEV outbreak prevention and response initiatives. METHODS: We performed a systematic review of peer-reviewed (PubMed, Embase) and gray literature (ProMED) to identify reports of outbreaks published between 2011 and 2022. We included (1) reports with ≥ 5 cases of HEV, and/or (2) reports with 1.5 times the baseline incidence of HEV in a specific population, and (3) all reports with suspected (e.g., clinical case definition) or confirmed (e.g., ELISA or PCR test) cases if they met criterium 1 and/or 2. We describe key outbreak epidemiological, prevention and response characteristics and major data gaps. RESULTS: We identified 907 records from PubMed, 468 from Embase, and 247 from ProMED. We screened 1,362 potentially relevant records after deduplication. Seventy-one reports were synthesized, representing 44 HEV outbreaks in 19 countries. The populations at risk, case fatalities, and outbreak durations were not reported in 66% of outbreak reports. No reports described using HEV vaccines. Reported intervention efforts included improving sanitation and hygiene, contact tracing/case surveillance, chlorinating boreholes, and advising residents to boil water. Commonly missing data elements included specific case definitions used, testing strategy and methods, seroprevalence, impacts of interventions, and outbreak response costs. Approximately 20% of HEV outbreaks we found were not published in the peer-reviewed literature. CONCLUSION: HEV represents a significant public health problem. Unfortunately, extensive data shortages and a lack of standardized reporting make it difficult to estimate the HEV disease burden accurately and to implement effective prevention and response activities. Our study has identified major gaps to guide future studies and outbreak reporting systems. Our results support the development of standardized reporting procedures/platforms for HEV outbreaks to ensure accurate and timely data distribution, including active and passive coordinated surveillance systems, particularly among high-risk populations.

Resilience and probiotic interventions to prevent and recover from shrimp gut dysbiosis.

To counter the recurrent outbreaks of bacterial (acute hepatopancreatic necrosis disease; AHPND) and viral (white spot disease; WSD) shrimp diseases, which still remain a threat to the global industry, shrimp gut microbiota research has been gaining more attention in recent years, and the use of probiotics in aquaculture has had promising results in improving shrimp gut health and immunity. In this review based on our studies on AHPND and WSD, we summarize our current understanding of the shrimp gastrointestinal tract and the role of the microbiota in disease, as well as effects of probiotics. We focus particularly on the concept of microbiota resilience, and consider strategies that can be used to restore shrimp gut health by probiotic intervention at a crucial time during gut microbiota dysbiosis. Based on the available scientific evidence, we argue that the use of probiotics potentially has an important role in controlling disease in shrimp aquaculture.

A bacterial binary toxin system that kills both insects and aquatic crustaceans: Photorhabdus insect-related toxins A and B.

Photorhabdus insect-related toxins A and B (PirA and PirB) were first recognized as insecticidal toxins from Photorhabdus luminescens. However, subsequent studies showed that their homologs from Vibrio parahaemolyticus also play critical roles in the pathogenesis of acute hepatopancreatic necrosis disease (AHPND) in shrimps. Based on the structural features of the PirA/PirB toxins, it was suggested that they might function in the same way as a Bacillus thuringiensis Cry pore-forming toxin. However, unlike Cry toxins, studies on the PirA/PirB toxins are still scarce, and their cytotoxic mechanism remains to be clarified. In this review, based on our studies of V. parahaemolyticus PirAvp/PirBvp, we summarize the current understanding of the gene locations, expression control, activation, and cytotoxic mechanism of this type of toxin. Given the important role these toxins play in aquatic disease and their potential use in pest control applications, we also suggest further topics for research. We hope the information presented here will be helpful for future PirA/PirB studies.

White spot syndrome virus (WSSV) modulates lipid metabolism in white shrimp.

In addition to the Warburg effect, which increases the availability of energy and biosynthetic building blocks in WSSV-infected shrimp, WSSV also induces both lipolysis at the viral genome replication stage (12 hpi) to provide material and energy for the virus replication, and lipogenesis at the viral late stage (24 hpi) to complete virus morphogenesis by supplying particular species of long-chain fatty acids (LCFAs). Here, we further show that WSSV causes a reduction in lipid droplets (LDs) in hemocytes at the viral genome replication stage, and an increase in LDs in the nuclei of WSSV-infected hemocytes at the viral late stage. In the hepatopancreas, lipolysis is triggered by WSSV infection, and this leads to fatty acids being released into the hemolymph. ß-oxidation inhibition experiment reveals that the fatty acids generated by WSSV-induced lipolysis can be diverted into ß-oxidation for energy production. At the viral late stage, WSSV infection leads to lipogenesis in both the stomach and hepatopancreas, suggesting that fatty acids are in high demand at this stage for virion morphogenesis. Our results demonstrate that WSSV modulates lipid metabolism specifically at different stages to facilitate its replication.

Multiple Nucleocapsid Structural Forms of Shrimp White Spot Syndrome Virus Suggests a Novel Viral Morphogenetic Pathway.

White spot syndrome virus (WSSV) is a very large dsDNA virus. The accepted shape of the WSSV virion has been as ellipsoidal, with a tail-like extension. However, due to the scarcity of reliable references, the pathogenesis and morphogenesis of WSSV are not well understood. Here, we used transmission electron microscopy (TEM) and cryogenic electron microscopy (Cryo-EM) to address some knowledge gaps. We concluded that mature WSSV virions with a stout oval-like shape do not have tail-like extensions. Furthermore, there were two distinct ends in WSSV nucleocapsids: a portal cap and a closed base. A C14 symmetric structure of the WSSV nucleocapsid was also proposed, according to our Cryo-EM map. Immunoelectron microscopy (IEM) revealed that VP664 proteins, the main components of the 14 assembly units, form a ring-like architecture. Moreover, WSSV nucleocapsids were also observed to undergo unique helical dissociation. Based on these new results, we propose a novel morphogenetic pathway of WSSV.

Losses along the tuberculosis sputum sample referral cascade for Mpongwe District, Zambia.

BACKGROUND: In resource limited-settings, timely tuberculosis (TB) diagnosis depends upon referral of sputum samples from non-diagnostic to diagnostic facilities for examination. The TB programme data for 2018 suggested losses in Mpongwe District's sputum referral cascade. AIM: This study aimed to identify the referral cascade stage where loss of sputum specimen occurred. SETTING: Primary health care facilities in Mpongwe District, Copperbelt Province, Zambia. METHODS: Data were retrospectively collected from one central laboratory and six referring health facilities between January and June 2019, using a paper-based tracking sheet. Descriptive statistics were generated in SPSS version 22. RESULTS: Of the 328 presumptive pulmonary TB patients found in presumptive TB registers at referring facilities, 311 (94.8%) submitted sputum samples and were referred to the diagnostic facilities. Of these, 290 (93.2%) were received at the laboratory, and 275 (94.8%) were examined. The remaining 15 (5.2%) were rejected for reasons such as 'insufficient sample'. Results for all examined samples were sent back and received at referring facilities. Referral cascade completion rate was 88.4%. Median turnaround time was six days (IQR = 1.8). CONCLUSION: Losses in the sputum referral cascade for Mpongwe District mainly occurred between dispatch of sputum samples and receipt at diagnostic facility. Mpongwe District Health Office needs to establish a system to monitor and evaluate the movement of sputum samples along the referral cascade to minimize losses and ensure timely TB diagnosis.Contribution: This study has highlighted, at primary health care level for resource limited settings, the stage in the sputum sample referral cascade where losses mainly occur.

Mortality among persons receiving tuberculosis treatment in Itezhi-Tezhi District of Zambia: A retrospective cohort study.

Itezhi-Tezhi District in southern Zambia has been reporting tuberculosis (TB) mortality rates that are fourfold higher than the national average of six percent. We conducted a retrospective cohort study to establish the demographic and clinical characteristics associated with mortality among persons under treatment for TB in Itezhi-Tezhi District, as well as the likely causes and time to death. We reviewed medical records for persons with TB registered in 19 public health facilities in Itezhi-Tezhi District between January 2015 and December 2018. Of the 506 persons with TB registered in the study period, 426 were included in the analysis. Of these, 71 (16.7%) died before completing treatment. The overall mortality rate was 31.8 per 1,000 person-months of observation. Most of the deaths (53 [74.7%]) occurred in the first month of treatment (median: 16 days; interquartile range: 5-52 days). In a multivariate Cox regression model, type of TB was found to be an independent predictor of mortality while on TB treatment. The risk of dying was more than twice higher for persons with clinically diagnosed PTB compared to those with bacteriologically confirmed PTB (adjusted hazard ratio = 2.2, 95% CI: 1.4-3.6). In a sub-analysis of persons with clinically diagnosed PTB, persons with TB who were on a community-based DOT plan were more than twice more likely to die compared to those on facility-based DOT plan (adjusted hazard ratio = 2.21, 95% CI: 1.1-4.8). Common likely causes of death were pulmonary TB disease (66.0%), anemia (12.8%), cardiac failure (4.3%), pneumocystis jiroveci pneumonia (4.3%), and gastroenteritis (4.2%). These findings show that most deaths occurred during the first month of treatment. Clinical evaluation at initiation of anti-TB treatment and during follow-up care, especially in persons with clinically diagnosed PTB, should include screening and treatment of other conditions.

Synthesis and Characterization of Curcumin Incorporated Multi Component Nano-Scaffold with Enhanced Anti-bacterial and Wound Healing Properties.

BACKGROUND: Wound healing is one of the major challenges in chronic diseases; the current treatment options are less effective with undesirable side effects and are expensive. Extensive research is carried out to develop cost-effective, natural, biodegradable wound dressings that can reduce oxidative stress and inflammation and prevent bacterial infections. Curcumin has a plethora of therapeutic applications; however, its low solubility limits its clinical use. OBJECTIVE: In this study, curcumin nanoparticles (Cur NP) and curcumin-chitosan nanoparticles (CCNP) were incorporated into the chitosan collagen vanillin scaffold, characterized, and investigated their potential wound healing properties. METHODS: The nano-scaffolds were prepared by freeze-drying method and were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, nanoparticle tracking analysis, and scanning electron microscopy. The drug release, antioxidant, antibacterial, and wound healing properties were assessed by in vitro assays. RESULTS: Cur nano-scaffolds showed particle sizes of 195.9 nm and 110.6 nm for Cur NP+VC and CCNP+VC, respectively. The curcumin encapsulated in the Cur NP+VC and CC+VC nano-scaffolds showed a release profile of > 60% and an improved antioxidant activity of greater than 80%. The nanoscaffolds were antagonistic against Escherichia coli and Staphylococcus aureus and enhanced wound healing capacity of 85.62 % and 77.05% in the murine cell line. CONCLUSION: The curcumin nano-scaffold is a biodegradable and effective drug delivery system for topical use that can act as an antioxidant, facilitate wound healing, as well as prevent bacterial infections.

Identification of a novel, MSC-induced macrophage subtype via single-cell sequencing: implications for intervertebral disc degeneration therapy.

Intervertebral disc (IVD) degeneration is a common pathological condition associated with low back pain. Recent evidence suggests that mesenchymal signaling cells (MSCs) promote IVD regeneration, but underlying mechanisms remain poorly defined. One postulated mechanism is via modulation of macrophage phenotypes. In this manuscript, we tested the hypothesis that MSCs produce trophic factors that alter macrophage subsets. To this end, we collected conditioned medium from human, bone marrow-derived STRO3+ MSCs. We then cultured human bone marrow-derived macrophages in MSC conditioned medium (CM) and performed single cell RNA-sequencing. Comparative analyses between macrophages cultured in hypoxic and normoxic MSC CM showed large overlap between macrophage subsets; however, we identified a unique hypoxic MSC CM-induced macrophage cluster. To determine if factors from MSC CM simulated effects of the anti-inflammatory cytokine IL-4, we integrated the data from macrophages cultured in hypoxic MSC CM with and without IL-4 addition. Integration of these data sets showed considerable overlap, demonstrating that hypoxic MSC CM simulates the effects of IL-4. Interestingly, macrophages cultured in normoxic MSC CM in the absence of IL-4 did not significantly contribute to the unique cluster within our comparison analyses and showed differential TGF-ß signaling; thus, normoxic conditions did not approximate IL-4. In addition, TGF-ß neutralization partially limited the effects of MSC CM. In conclusion, our study identified a unique macrophage subset induced by MSCs within hypoxic conditions and supports that MSCs alter macrophage phenotypes through TGF-ß-dependent mechanisms.

Materiomically Designed Polymeric Vehicles for Nucleic Acids: Quo Vadis?

Despite rapid advances in molecular biology, particularly in site-specific genome editing technologies, such as CRISPR/Cas9 and base editing, financial and logistical challenges hinder a broad population from accessing and benefiting from gene therapy. To improve the affordability and scalability of gene therapy, we need to deploy chemically defined, economical, and scalable materials, such as synthetic polymers. For polymers to deliver nucleic acids efficaciously to targeted cells, they must optimally combine design attributes, such as architecture, length, composition, spatial distribution of monomers, basicity, hydrophilic-hydrophobic phase balance, or protonation degree. Designing polymeric vectors for specific nucleic acid payloads is a multivariate optimization problem wherein even minuscule deviations from the optimum are poorly tolerated. To explore the multivariate polymer design space rapidly, efficiently, and fruitfully, we must integrate parallelized polymer synthesis, high-throughput biological screening, and statistical modeling. Although materiomics approaches promise to streamline polymeric vector development, several methodological ambiguities must be resolved. For instance, establishing a flexible polymer ontology that accommodates recent synthetic advances, enforcing uniform polymer characterization and data reporting standards, and implementing multiplexed in vitro and in vivo screening studies require considerable planning, coordination, and effort. This contribution will acquaint readers with the challenges associated with materiomics approaches to polymeric gene delivery and offers guidelines for overcoming these challenges. Here, we summarize recent developments in combinatorial polymer synthesis, high-throughput screening of polymeric vectors, omics-based approaches to polymer design, barcoding schemes for pooled in vitro and in vivo screening, and identify materiomics-inspired research directions that will realize the long-unfulfilled clinical potential of polymeric carriers in gene therapy.

Litopenaeus vannamei peritrophin interacts with WSSV and AHPND-causing V. parahaemolyticus to regulate disease pathogenesis.

Peritrophins are peritrophic membrane (PM) proteins that can interact with chitin fibers via chitin-binding domains. Peritrophins have essential roles in providing porosity and strength to the PM that lines the shrimp midgut. Acute hepatopancreatic necrosis disease (AHPND), caused by strains of V. parahaemolyticus, is known to initially colonize the shrimp stomach and simultaneously disrupt its structural barriers (e.g., cuticle or epithelial tissues) to reach the hepatopancreas. Although stomach and hepatopancreas were identified as target tissues involved in AHPND pathogenesis, our results indicated that peritrophin in peritrophic membrane has a crucial role in determining not only colonization of AHPND-causing bacteria but also their tissue distribution. As the interaction between LvPeritrophin (LvPT) and WSSV (white spot syndrome virus) is not well understood, we noted that LvPT expression was upregulated in shrimp stomach challenged with either WSSV or AHPND. In an in vitro pathogen binding assay, there was strong binding of recombinant LvPT WSSV and AHPND-causing V. parahaemolyticus, and various bacteria. Furthermore, dsRNA-mediated LvPT silencing inhibited WSSV gene expression and viral genome replication. However, downregulation of LvPT gene expression increased copies of AHPND-causing bacteria in shrimp digestive tract, and facilitated bacterial colonization in stomach. In conclusion, we speculated that LvPT might regulate bacterial colonization during AHPND, whereas in WSSV infection, LvPT silencing favored the host. Although recombinant LvPT had strong binding with WSSV, the precise role of LvPT in WSSV infection needs further investigation. These findings increased our understanding of host-pathogen interactions in AHPND and WSSV infection that can be applied in shrimp aquaculture for developing effective antibacterial and antiviral strategies.