Reduced Disease Severity Research Articles

Use of commercial fertilizers in an IPDM protocol to mitigate Olive Quick Decline Syndrome caused by Xylella fastidiosa subsp. pauca in Southern Italy.

Management of Xylella fastidiosa subsp. pauca (Xfp) presents significant challenges due to the lack of genetic resistance in major crops, pathogen variability and resistance development against the main antimicrobial compounds, and the lack of effective chemical compounds for control. Traditional bactericides in the EU are restricted, and copper-based products are increasingly limited due to environmental impacts. In this study the antibacterial side effects of some commercial fertilizers against Xfp were evaluated. These products, containing metal ions (mainly copper and/or zinc) complexed with phosphites and bioavailable silicon, show antimicrobial and bactericidal activities in vitro which suggest their possible use to control the pathogen, as well as enhanced plant resistance to biotic and abiotic stresses. Greenhouse and open field trials showed that they can significantly reduce disease severity and pathogen population, thus improving fruit yield. The integrated pest and disease management (IPDM) strategy, which combines these treatments with agronomic and phytosanitary vector-control measures, leads to a reduction of disease symptoms in treated plants compared to untreated ones. These findings highlight the potential of systemic fertilizers to mitigate Xfp symptoms by providing antimicrobial collateral effects and probably enhance plant defenses, since similar compounds are known to be plant defense inducers in other pathosystems. Therefore, these products offer a sustainable solution for managing plant pathogenic bacteria and improving crop health and yield. This approach is crucial for the sustainability of olive production in Xf-affected areas. However, further research is needed to optimize these strategies for long-term effectiveness under field conditions. Overall, the results emphasize the value of the collateral effects of some mineral fertilizers in a comprehensive strategy aimed at mitigating the symptoms of Xfp and safeguarding the agricultural productivity as well as the invaluable heritage of centuries-old Apulian olive trees.

Evaluation of Fungicides, Host-plant Defense Inducer, and Anti-transpirant in Management of Boxwood Blight

Boxwood, valued at over $140.9 million annually in the United States, faces a significant threat from boxwood blight disease. This study evaluated 24 treatment combinations involving three fungicides (Daconil Weatherstik, Postiva, and F6123-1), a disinfectant/fungicide (KleenGrow), a host-plant defense inducer (Actigard), and an anti-transpirant (Vapor Gard) for managing boxwood blight. Preventive applications were performed 24 h before pathogen inoculation, while curative treatments were applied at 14-d intervals, starting 14 d after inoculation. The disease severity (0% to 100% plant affected), area under disease progress curve (AUDPC), plant growth, defoliation (0% to 100%), and stem water potential (MPa) were assessed. All the applications significantly reduced disease severity and AUDPC compared with the non-treated, inoculated control. Preventative applications of Actigard alternated (alt.) with Vapor Gard and Actigard alone consistently reduced the disease progression, while Actigard alt. with Vapor Gard reduced the disease severity. Curative application of the low rate of Postiva exhibited the highest disease suppression, comparable to applications of F6123-1 alt. with Vapor Gard and the high rate of Postiva alt. with Vapor Gard. The preventative and curative application of the high rate of Postiva alt. with Vapor Gard was the most effective in reducing disease severity and slowing disease progression. Preventive and curative application of Daconil Weatherstik, KleenGrow, and Daconil Weatherstik alt. with KleenGrow were also effective. None of the preventive treatments significantly reduced defoliation. However, curative applications of F6123-1 alt. with Vapor Gard and preventive and curative treatments of the high rate of Postiva alt. with Vapor Gard consistently reduced the defoliation. Preventive application of Actigard alt. with Vapor Gard, curative application of the low rate of Postiva alt. Vapor Gard, and preventive and curative treatments of the high rate of Postiva alt. Vapor Gard, as well as Vapor Gard alone, resulted in the highest stem water potential among treated plants. A weak positive correlation was observed between stem water potential and disease development. The identified combinations and application strategies provide options for effective boxwood blight management when combined with other management strategies.

Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice.

Influenza infections are often complicated by secondary bacterial infections such as MRSA pneumonia, which increase morbidity and mortality. Viral infections lead to an inflammatory response that includes elevated levels of IL-6 and interferons. IL-6 activates the JAK/STAT signaling pathway, amplifying downstream inflammation. Given the clinical efficacy of the JAK inhibitor baricitinib in reducing disease severity in COVID-19, we evaluated its impact in a murine model of influenza, MRSA, and post-influenza MRSA pneumonia. Additionally, because IL-6 inhibitory therapies have improved outcomes during COVID-19, we evaluated the impact of IL-6 deletion on post-influenza MRSA pneumonia. In our studies, baricitinib effectively inhibited the JAK/STAT pathway in the lungs, as demonstrated by decreased interferon-stimulated genes (ISGs) and STAT3 phosphorylation. Despite this inhibition, baricitinib did not cause a global suppression of cytokines. Notably, baricitinib treatment did not impair either antiviral or antibacterial host immunity, inflammatory cell recruitment, or lung tissue injury. IL-6 deficiency did not alter weight loss, inflammatory cell recruitment, or bacterial burden during post-influenza MRSA pneumonia. These findings suggest that both JAK inhibition via baricitinib and IL-6 deletion do not enhance host defense or limit tissue injury in murine models of influenza and post-influenza MRSA pneumonia.

Comparing adalimumab biosimilars in the clinical practice of psoriatic patients.

Biologic drugs have revolutionized the treatment of psoriasis and other chronic inflammatory diseases. In recent years, numerous biosimilar molecules that target cytokines such as TNF-alpha or its receptors have been developed. The approval of biosimilars has made it possible to reduce the costs of biologic drugs, thereby increasing access to these therapies for more patients and enhancing psoriasis treatment globally. Imraldi and Idacio are both biosimilars of Adalimumab, approved for treating moderate to severe psoriasis. Our study aims to compare these two adalimumab biosimilars in psoriasis patients who have previously undergone treatment with other biologic drugs or systemic therapy in a real-life setting. Our cohort comprised 32 psoriatic patients. Of these patients, 15 were prescribed Imraldi, while the remaining were on Idacio. To assess the efficacy of these therapies, we utilized various measures including the Psoriasis Area and Severity Index, the Pruritus Visual Analog Scale, the Visual Analog Scale, the Dermatology Life Quality Index, and the Psoriasis Global Assessment, monitoring the patients over a 24-week period. Our results indicated that the use of Idacio led to greater decreases in all scores compared to Imraldi. However, in terms of safety and efficacy, the two drugs were found to be comparable. The findings of this study support the efficacy and safety of Idacio and Imraldi in managing psoriasis, with Idacio demonstrating superior efficacy in reducing disease severity. Future studies could benefit from expanding the patient cohort and conducting further analyses to evaluate individual responses to treatment.

Comparison of Contemporary and Historic Highly Pathogenic Avian Influenza A(H5N1) Virus Replication in Human Lung Organoids.

We compared virus replication and host responses in human alveolar epithelium infected with highly pathogenic avian influenza (HPAI) A(H5N1) viruses. A/Vietnam/1203/2004 replicated most efficiently, followed by A/Texas/37/2024, then A/bovine/Ohio/B24OSU-342/2024. Induction of interferon-stimulated genes was lower with A/Texas/37/2024 and A/bovine/Ohio/B24OSU-342/2024, which may indicate a reduced disease severity of those viruses.

P-1971. Patterns of T cell receptor usage reveal associations with COVID-19 severity

Abstract Background T cells are associated with viral clearance and improved outcomes in COVID-19, but also with immunopathology. Defining T cell diversity in response to SARS-CoV-2 infection enables implementation of T cells in prevention and treatment strategies. T cells recognize peptide sequences from pathogens upon presentation in major histocompatibility complexes (MHC). Human MHC molecule diversity results in a wide array of peptide recognition by T cells making viral escape difficult, but also challenging to measure. Methods Using the ImmunoSEQ Assay to sequence complementarity-determining regions in the β chains (CDR3β) of the T cell receptor (TCR) from peripheral blood collected from participants in the EPICC COVID-19 cohort study, we quantified and characterized patterns of TCR usage. Multiple bioinformatic pipelines were compared for analysis. Results Our study evaluated TCR repertoires from 39 participants who had mild (20 outpatient) versus severe (19 hospitalized) acute COVID-19, and either experienced unvaccinated primary infection (n = 15) or vaccine breakthrough infection (n = 24) (Table 1). From these four clinical groups, we used the ImmuneCODE database, VDJdatabase and healthy controls to identify CD8 TCR sequences and amino acid motifs in the CDR3β region specific for the SARS-CoV-2 proteome. We were surprised to find that vaccine breakthrough and primary infection participants exhibited similar frequencies of SARS-CoV-2-specific TCR sequences over 14-21 days post-symptom onset. Increased use of common TCR clones occurred in participants with older age and comorbidities, which correlated with more severe disease (Figure 1). Strikingly, an increased frequency of non-SARS-CoV-2 TCRs was significantly associated with severe disease in unvaccinated (p = 0.006) and vaccinated participants (p = 0.045). Conclusion In conclusion, our study highlights the opportunities and challenges of studying the complexity of T cell diversity and the utility of combining databases and bioinformatics for identification of patterns of TCR recognition. Interestingly, participants who were hospitalized were more likely to have circulating T cells non-specific for SARS-CoV-2 suggesting that vaccines that increase T cell specificity may reduce disease severity. Disclosures Simon Pollett, MBBS, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response

P-2053. Clinical Outcomes and Severity of Hospitalized COVID-19 Patients Among Partially and Fully Vaccinated Patients in Louisville, Kentucky

Abstract Background Despite COVID-19 vaccine availability, reducing disease severity and hospitalizations remains crucial. Persistent vaccine hesitancy necessitates studies comparing outcomes between partially and fully vaccinated individuals. Our study aims to evaluate clinical outcomes among hospitalized COVID-19 patients, distinguishing between partial and full vaccination. Multivariable logistic regression analysis for ICU admission among fully and partially vaccinated patients with COVID-19 CAP Methods We conducted a retrospective cohort study among hospitalized COVID-19 patients with community-acquired pneumonia (CAP) in Louisville, Kentucky. Clinical outcomes, including in-hospital mortality, cardiac events, ICU admission, and use of mechanical intubation and ventilation, were assessed. Statistical analyses included univariate and multivariable logistic regression to compare outcomes between vaccination statuses. Multivariable logistic regression analysis for Mechanical intubation and ventilation use among fully and partially vaccinated patients with COVID-19 CAP Results Of 142 eligible patients, 87% were fully vaccinated, with 13% partially vaccinated. The fully vaccinated group had less patients with a CURB-65 score >3 compared to the partially vaccinated group (63% vs. 53%, P=0.55). In addition, partially vaccinated patients exhibited increased rates of ARDS (6% vs 1%, P=0.61), septic shock (11% vs 3%, P=0.37), intubation (16% vs 8%, P=0.20) and mortality (21% vs 7%, P=0.09). Fully vaccinated patients exhibited lower rates of ICU admission compared to partially vaccinated patients (40% vs 15%, P=0.04). After adjusting for confounders, fully vaccinated patients had significantly lower odds of ICU admission (OR: 0.28, 95%CI: 0.15, 0.56) and intubation (OR: 0.22, 95%CI: 0.06, 0.81). However, fully vaccinated individuals had more in-hospital cardiac events (12% vs. 1%, P=0.61) and a lower odds of in-hospital mortality (OR: 0.18, 95%CI: 0.02, 1.66), but these were not statistically significant. Multivariable logistic regression analysis for in-hospital mortality among fully and partially vaccinated patients with COVID-19 CAP Conclusion This study highlights full vaccination's importance in reducing COVID-19 severity among hospitalized patients. Male gender and cancer were associated with higher mortality rates. Fully vaccinated patients had lower odds of ICU admission and intubation compared to partially vaccinated counterparts. Being fully vaccinated was not found to be associated with less cardiac events or mortality. These findings emphasize the need for comprehensive vaccination strategies and targeted public health initiatives. Disclosures All Authors: No reported disclosures

Long COVID and its risk factors in migrants: a nationwide register study from Sweden

BackgroundMany studies have found more severe COVID-19 outcomes in migrants and ethnic minorities throughout the COVID-19 pandemic, while recent evidence also suggests higher risk of longer-term consequences. We studied the risk of a long COVID diagnosis among adult residents in Sweden, dependent on country of birth and accounting for known risk factors for long COVID.MethodsWe used linked Swedish administrative registers between March 1, 2020 and April 1, 2023, to estimate the risk of a long COVID diagnosis in the adult population that had a confirmed COVID-19 infection. Poisson regressions were used to calculate incidence rate ratios (IRR) of long COVID by country/region of birth. The contribution of sex, preexisting health status, disease severity, vaccination status, and socioeconomic factors to differences in long COVID diagnosis by country/region of birth were further investigated.ResultsOf the 1,869,188 persons diagnosed with COVID-19 that were included, 7539 had received a long COVID diagnosis. Compared with residents born in Sweden, we found higher risks of long COVID among migrants from East Europe (IRR: 1.44 CI: 1.29–1.60), Finland (IRR: 1.36 CI: 1.15–1.61), South Asia (IRR: 1.28 CI: 1.03–1.59), Other Asia (IRR: 1.35 CI: 1.13–1.62), Other Africa (IRR: 1.48 CI: 1.17–1.87), and the Middle East (IRR: 1.43 CI: 1.27–1.63) in models adjusted for age and sex. We discovered that disease severity, i.e., whether the person was hospitalized (IRR: 18.6 CI: 17.3–20.0) or treated in an intensive care unit (IRR: 120.5 CI: 111.7–129.8), primarily contributed to the higher risk of long COVID found in migrants while the contribution of vaccinations and social conditions were moderate. Preexisting health problems did not contribute to the increased risk of long COVID in migrants.ConclusionsThe greater exposure and impact of the COVID-19 virus among migrants also affected longer-term consequences. Disease severity was the most important risk factor for long COVID in migrants. The findings emphasize the need for targeted health interventions for migrant communities during an infectious disease pandemic, such as strategic vaccination campaigns and extending social insurance schemes, focusing on reducing disease severity to mitigate the longer-term health consequences of an infection.

P0041 Assessment of real-world effectiveness of risankizumab in patients with moderate-severe Crohn’s disease in a global setting

Abstract Background The primary treatment goals in Crohn’s disease (CD) are to control symptoms, such as abdominal pain and diarrhea, and induce long-term endoscopic remission. The biologic risankizumab (RZB) was approved in 2022 for the treatment of adult patients with moderate-severe CD. As data on RZB utilization and effectiveness are limited, this study aimed to assess the impact of RZB on disease remission and symptom control for optimizing treatment outcomes in patients with CD. Methods Data were drawn from the Adelphi Real World CD Disease Specific Programme, a cross-sectional survey with retrospective data collection of gastroenterologists (GIs) in France, Germany, Italy, Spain, the UK, and the USA from Feb 2023–Oct 2024. GIs provided data on their consulting patients with subjectively classified at RZB initiation moderate-severe CD reported demographics, clinical characteristics and symptoms at RZB initiation and at most recent consultation. Analyses were descriptive, Wilcoxon signed rank and McNemar tests were used to compare severity and symptoms at RZB initiation and at most recent consultation, respectively. Results Overall, 206 GIs reported data on 333 patients with moderate-severe CD receiving RZB. Mean (standard deviation; SD) patient age was 40.8 (13.0), disease duration was 4.7 (5.8) years; 54% were advanced therapy (AT, comprising biologics and small molecule therapies) naïve and 46% AT experienced (Table 1). Among all patients, 85% received RZB as a monotherapy; 6% received RZB with corticosteroids and 9% with 5-aminosalicylates and/or immunomodulators for; mean (SD) time on RZB among those with a known treatment duration (n=299) was 7.5 (7.5) months. Among patients receiving RZB for >6 months (n=140), 55% were in GI-reported clinical remission at most recent consultation. Among all patients, GI-reported moderate-severe disease severity significantly reduced from RZB initiation (100% of patients) to most recent consultation (55%; p<0.0001; Fig 1A). Key symptoms experienced at RZB initiation (abdominal pain, 87%; bloody diarrhoea, 29%; non-bloody diarrhoea, 59%; fatigue, 54%; bowel urgency, 41%) significantly reduced at most recent consultation with continued RZB treatment (48%, 9%, 35%, 38%, 20%, respectively; p<0.0001; Fig 1B). Conclusion In a real-world global setting, patients with moderate-severe CD treated with RZB experienced a significant reduction in GI-reported disease severity and improvement in key symptoms, and over half of patients were in GI-reported clinical remission. The improvement in symptoms and severity were greater among patients who were treated for a longer duration with RZB. These results highlight the real-world effectiveness of RZB in managing disease activity and symptom burden among patients over time.

P0124 Therapeutic Potential of Adipose-Derived Extracellular Vesicles for Inflammation Modulation and Mucosal Healing in Crohn’s Disease

Abstract Background Crohn’s disease (CD) is a chronic, idiopathic inflammatory bowel disease characterised by discontinuous lesions and transmural inflammation that can affect the entire gastrointestinal tract. Despite recent therapeutic advancements, around 50% of patients with CD require at least one surgical intervention within ten years of diagnosis, with 80% of these patients developing new lesions following surgery.1 Emerging evidence highlights that the therapeutic efficacy of mesenchymal stem cells (MSCs) is predominantly attributed to the extracellular vesicles (EVs) they secrete.2 These nanovesicles have gained recognition as critical mediators of anti-inflammatory responses and tissue repair. This research seeks to develop MSC-derived EV-based acellular therapy to regulate the immune response, heal the intestinal mucosa, restore gut microbiota balance, and ultimately reduce disease severity and recurrence. Methods Inclusion criteria for selecting healthy donors for obtaining EVs derived from subcutaneous adipose tissue MSCs include sex, age <40 years, and BMI <25 kg/m². Exclusion criteria include smokers, alcohol consumers, and patients with cancer or other chronic conditions. EV isolation was performed using size-exclusion chromatography, and characterisation was conducted via flow cytometry and electron microscopy (Cryo-TEM). To assess the therapeutic properties of the EVs, biopsies of inflamed perilesional adipose tissue and intestinal mucosa from CD patients were treated with a dose of 150 µg/mL for 20 hours. Finally, the gene expression profile of pro-inflammatory markers (TNFα, IL1B, IL6, and CCL2) and anti-inflammatory markers (IL10) was analysed by qPCR. Results The isolation and characterization of EVs were successfully demonstrated, along with their functional efficacy in both adipose and intestinal explant models. Explants treatment with EVs resulted in a significant reduction in pro-inflammatory cytokines, with IL-1β and TNF-α expression decreased by up to 200-fold compared to untreated explants, while also promoting a notable increase in the anti-inflammatory marker IL-10. Conclusion Adipose tissue-derived EVs could regulate inflammation and promote the regeneration of the intestinal barrier, thus reducing the severity of CD and lowering the risk of post-surgical recurrence. References 1Golovics PA, Mandel MD, Lovasz BD, Lakatos PL. Inflammatory bowel disease course in Crohn’s disease: Is the natural history changing? World J Gastroenterol. 2014;20(12):3198-3207. 2.Zhou Y, Yamamoto Y, Xiao Z, Ochiya T. The immunomodulatory functions of mesenchymal stromal/stem cells mediated via paracrine activity. J Clin Med. 2019;8(1)

Efficacy of integrated cultural practices for dollar spot disease management on creeping bentgrass and bermudagrass

AbstractDollar spot, caused by Clarireedia spp., is one of the major challenges in golf course management. While individual cultural practices such as adequate nitrogen fertilization, thatch removal, aeration, and dew removal (DR) can reduce dollar spot severity, there are limited reports across multiple locations on the effectiveness of integrating multiple cultural practices for improved dollar spot suppression. Field studies were conducted in Wisconsin, Ohio, Pennsylvania, and Virginia to evaluate the efficacy of urea fertilizer, DR, and a plant growth regulator (PGR) in dollar spot management on golf course greens and fairways. Each of the three treatments had two levels including applied or not applied. Urea and early DR reduced dollar spot severity across several locations, while PGR did not affect disease suppression. In some locations, the two‐way and three‐way interaction effects were significant, where combining the treatments reduced disease severity compared to non‐treated plots or when only one treatment was applied. Overall, the urea application had the most notable and consistent impact on reducing disease severity, while the effectiveness of DR and PGR varied depending on the location and year. Results from this study provide insights into the development of an effective integrated management program for dollar spot.

The Utilization of Bacillus spp. as Endophytes in Enhancing Plant Resistance and Health Against Fusarium oxysporum : A Mini Review

Fusarium oxysporum is a destructive pathogen responsible for significant losses in chili (Capsicum spp.) and other crops. Traditional chemical control methods pose environmental and health risks, highlighting the need for sustainable alternatives. This review explores the role of Bacillus spp. as endophytic biocontrol agents in combating F. oxysporum. Species such as B. subtilis, B. mojavensis, and B. velezensis exhibit antifungal activity through the production of hydrolytic enzymes (e.g., glucanase, cellulase, and chitinase) and secondary metabolites like lipopeptides and antibiotics, which inhibit pathogen growth. Furthermore, these bacteria enhance plant health by inducing systemic resistance, promoting root development, and creating a rhizosphere environment unfavorable to pathogens. Their synergistic interactions with other beneficial microorganisms further bolster plant defense and productivity. Molecular and physiological analyses confirm the efficacy of Bacillus spp. in reducing disease severity and improving plant resilience. Continued research into their mechanisms and field application can support more sustainable agricultural practices.

Regulation of fibroblast phenotype in osteoarthritis using CDKN1A-loaded copper sulfide nanoparticles delivered by mesenchymal stem cells.

This study aimed to investigate the regulation of fibroblast phenotypes by mesenchymal stem cells (MSCs) delivering copper sulfide (CuS) nanoparticles (NPs) loaded with CDKN1A plasmids and their role in cartilage repair during osteoarthritis (OA). Single-cell RNA sequencing data from the GEO database were analyzed to identify subpopulations within the OA immune microenvironment. Quality control, filtering, principal component analysis (PCA) dimensionality reduction, and tSNE clustering were performed to obtain detailed cell subtypes. Pseudotime analysis was used to understand the developmental trajectory of fibroblasts, and GO/KEGG enrichment analyses highlighted biological processes related to fibroblast function. Transcriptomic data and WGCNA identified CDKN1A as a key regulatory gene. A biomimetic CuS@CDKN1A nanosystem was constructed and loaded into MSCs to create MSCs@CuS@CDKN1A. The characterization of this system confirmed its efficient cellular uptake by fibroblasts. In vitro experiments demonstrated that MSCs@CuS@CDKN1A significantly modulated fibroblast phenotypes and improved the structure, proliferation, reduced apoptosis, and enhanced migration of IL-1β-stimulated chondrocytes. In vivo, an OA mouse model was treated with intra-articular injections of MSCs@CuS@CDKN1A. Micro-CT scans revealed a significant reduction in osteophyte formation and improved joint space compared with control groups. Histological analysis, including H&E, Safranin O-Fast Green, and toluidine blue staining, confirmed improved cartilage integrity, whereas the International Osteoarthritis Research Society (OARSI) scoring indicated reduced disease severity. Immunofluorescence showed upregulated CDKN1A expression, decreased MMP13, and reduced α-SMA expression in fibroblast subtypes. Major organs exhibited no signs of toxicity, confirming the biocompatibility and safety of the treatment. These findings suggest that MSCs@CuS@CDKN1A can effectively regulate fibroblast activity and promote cartilage repair, providing a promising therapeutic strategy for OA treatment.NEW & NOTEWORTHY This study introduces MSCs@CuS@CDKN1A, a nanoengineered MSC platform that targets fibroblast phenotypes in osteoarthritis (OA). By modulating CDKN1A expression, this innovative approach not only enhances cartilage repair but also effectively mitigates fibroblast-driven inflammation, marking a significant advancement in OA therapeutics with demonstrated efficacy and biocompatibility.

CXCL12 ameliorates neutrophilia and disease severity in SARS-CoV-2 infection.

Neutrophils, particularly low-density neutrophils (LDNs), are believed to contribute to acute COVID-19 severity. Here, we showed that neutrophilia can be detected acutely and even months after SARS-CoV-2 infection in patients and mice, while neutrophil depletion reduced disease severity in mice. A key factor in neutrophilia and severe disease in infected mice was traced to the chemokine CXCL12 secreted by bone marrow cells and unexpectedly, endothelial cells. CXCL12 levels were negatively correlated with LDN numbers in longitudinal analyses of patient blood samples. CXCL12 blockade in SARS-CoV-2-infected mice increased blood/lung neutrophil numbers thereby accelerating disease progression without changing lung virus titers. The exaggerated mortality caused by CXCL12 blockade can be reversed by neutrophil depletion. In addition, blocking interactions between SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) reduced CXCL12 levels, suggesting a signal transduction from virus-mediated ACE2 ligation to increased CXCL12 secretion. Collectively, these results demonstrate a previously unappreciated role of CXCL12 in diminishing neutrophilia, including low density neutrophilia, and its deleterious effects in SARS-CoV-2 infections. The results also support the involvement of SARS-CoV-2-endothelial cell interactions in viral pathogenesis.

Piriformospora indica Enhances Rice Blast Resistance and Plant Growth

Rice blast disease, caused by Magnaporthe oryzae (M. oryzae), is a significant threat to global rice production. Conventional methods for disease management face limitations, emphasizing the importance of sustainable alternatives. In this study, two rice cultivars with different blast resistance abilities, the susceptible variety CO39 and the resistant variety Pi4b, were used as materials to study the effects of Piriformospora indica (Pi) on the resistance to M. oryzae infection and rice growth. The in vitro tests revealed no direct antagonistic interaction between Pi and M. oryzae. However, the in vivo experiments showed that Pi promoted plant growth by increasing root and shoot length, chlorophyll content, and nitrogen uptake, particularly in CO39 during pathogen infection. Pi inoculation also significantly reduced disease severity, which was indicated by smaller lesion areas and shorter lesion lengths in both cultivars but a more pronounced effect in CO39. This occurred due to the decreasing levels of MDA and the modulating activity of antioxidant enzymes in Pi-inoculated rice plants. At the early stage of M. oryzae infection, the expression of the ethylene signaling gene OsEIN2 and the gibberellin biosynthesis gene OsGA20ox1 in Pi-inoculated CO39 decreased but significantly increased in both rice cultivars at the later stage. The reverse was found for the pathogenesis-related (PR) genes OsPR10 and OsPBZ1 and the blast-resistant genes OsBRG1, OsBRG2, and OsBRW1, suggesting early growth suppression for rice resilience to blast followed by a later shift back to growth. Meanwhile, Pi inoculation increased OsCesA9 expression in rice to strengthen cell walls and establish the primary defense barrier against M. oryzae and upregulated the expression of OsNPR1 without a significant difference in CO39 but downregulated it in Pi4b to activate PR genes to enhance plant resistance. In summary, these results underscore the potential of Pi as a sustainable biological control agent for rice blast disease, which is particularly beneficial for blast-susceptible rice cultivars.

The effectiveness of arbuscular mycorrhizal fungal species (Funneliformis mosseae, Rhizophagus intraradices, and Claroideoglomus etunicatum) in the biocontrol of root and crown rot pathogens, Fusarium solani and Fusarium mixture in pepper.

This study evaluated the effectiveness of arbuscular mycorrhizal fungi (AMF) species, including Funneliformis mosseae (FM), Rhizophagus intraradices (RI), Claroideoglomus etunicatum (CE), and a Mycorrhizal mix (MM) comprising these three species, on pepper plants (Capsicum annuum L.) inoculated with two isolates of Fusarium solani (48-F. solani and 18-F. solani) and two isolates of Fusarium mix (50-F. mixture and 147-F. mixture). Analysis of variance (ANOVA)-Tukey statistics revealed that the effects of AMF inoculations on morphological parameters, disease severity, root colonization, and total spore numbers in pathogen-infected plants varied significantly depending on the AMF species and pathogen group. AMF colonization significantly reduced disease severity, with disease inhibition (DI) reaching up to 58%, depending on the specific pathogen. However, there were a few instances where the application of AMF did not lead to a reduction in disease severity. Single AMF species were more effective in enhancing the growth of pathogen-treated host plants and suppressing disease compared to the mixed AMF. The mixed AMF was only more effective in balancing pathogen-induced decreases in plant nutrients (Copper (Cu), Magnesium (Mg), Zinc (Zn), and Phosphorus (P)). Among the compared mycorrhizae, C. etunicatum (CE) was the most effective in disease suppression due to its relatively more positive effects on plant root structure, increasing root fresh weight by up to 49% in the CE+pathogen plant group compared to the control group. Root colonization rates were generally higher in plants treated with both mycorrhiza and pathogens compared to plants treated with mycorrhiza alone. Overall, the curative effects of AMFs on plants following pathogen application varied concurrently with disease severity rates caused primarily by pathogens. AMFs demonstrated greater efficacy in combating 18-F. solani, which causes less severe plant disease. However, the effectiveness of AMFs was comparatively lower against 48-F. solani and 147-F. mix., which cause more severe plant disease. This indicates that the efficacy of AMFs varies depending on the specific strain of Fusarium solani, with better results observed against strains that cause less severe plant disease.

Exploring the impact of climatic variations on infectious gastroenteritis and a review of current antiviral vaccines

Weather and seasonal changes are recognized contributors to the prevalence of infectious diseases, including gastroenteritis, particularly in developing countries. Infectious gastroenteritis, characterized by symptoms such as diarrhea, vomiting, and abdominal pain, is predominantly caused by pathogens like rotavirus and norovirus. Environmental changes, such as abrupt temperature drops and heavy rainfall, facilitate the proliferation and transmission of these pathogens. Studies reveal a significant correlation between low temperatures, increased rainfall, and higher hospitalization rates for rotavirus and norovirus infections. Developing countries face compounded challenges due to financial constraints, inadequate healthcare infrastructure, poor sanitation, and malnutrition, which exacerbate disease burden. Preventive measures, particularly vaccinations, have proven effective in mitigating viral gastroenteritis. Rotavirus vaccines, such as RotaTeq™ and Rotarix™, have demonstrated efficacy in reducing disease severity and hospitalization rates. However, norovirus vaccine development remains complex due to genetic diversity, rapid mutation rates, and the absence of standardized models for testing efficacy. Promising candidates like HIL-214, a bivalent VLP vaccine, and novel approaches such as plant-based vaccines and recombinant adenovirus platforms have shown potential in preclinical and early clinical trials. Notable advancements include immunization strategies employing double-stranded RNA adjuvants and the use of gnotobiotic pig models to study vaccine efficacy. This study underscores the urgent need for enhanced research into the interplay between weather patterns and gastroenteritis incidence. Addressing vaccine development challenges is crucial to mitigating the global health burden of infectious gastroenteritis in the face of climate change.

Therapeutic effect of oxidized bletilla striata polysaccharide-natamycin eye drops on fungal keratitis.

Fungal keratitis (FK) usually develops to a poor clinical prognosis due to the fungal invasion and excessive inflammatory reaction. In order to enhance the therapeutic effect of natamycin (NAT), we used the anti-inflammatory biological polysaccharide bletilla striata polysaccharide (BSP) combined with NAT to prepare a new eye drop -- oxidized bletilla striata polysaccharide-natamycin (OBN). UV-vis, FT-IR, and fluorescence spectroscopy were used to identify the synthesis of OBN. Biocompatibility of OBN was determined by CCK-8, scratch assay, and corneal toxicity test. RAW264.7 cells and C57BL/6 mice were stimulated with A. fumigatus and treated with PBS, OBN, or NAT. The anti-inflammatory activity of OBN was detected by RT-PCR and ELISA. In mice with FK, the clinical scores were used to evaluate the effect of OBN; HE staining was performed to assess the corneal pathological changes; MPO assay and immunofluorescence staining were used to investigate neutrophil infiltration. OBN was synthesized by combining oxidized bletilla striata polysaccharide (OBSP) with NAT through Schiff base reaction. OBN did not affect cell viability at a concentration of 160μg/mL in HCECs, RAW264.7 cells, and mouse corneas. OBN versus NAT significantly improved the prognosis of A. fumigatus keratitis by reducing disease severity, neutrophil infiltration, and expression of inflammatory factors in vivo. Additionally, OBN treatment down-regulated the mRNA and protein expression levels of inflammatory factors IL-1β, TNF-α, and IL-6 in RAW264.7 and mouse models. OBN is a compound prepared by covalently linking OBSP to the imino group of NAT through Schiff base reaction. OBN treatment down-regulated inflammation and improved the prognosis of mice with A. fumigatus keratitis.

Phocaeicola vulgatus shapes the long-term growth dynamics and evolutionary adaptations of Clostridioides difficile.

Clostridioides difficile can transiently or persistently colonize the human gut, posing a risk for infections. This colonization is influenced by complex molecular and ecological interactions with the human gut microbiota. By investigating C.difficile dynamics in human gut communities over hundreds of generations, we show patterns of stable coexistence, instability, or competitive exclusion. Lowering carbohydrate concentrations shifted a community containing C.difficile and the prevalent human gut symbiont Phocaeicola vulgatus from competitive exclusion to coexistence, facilitated by increased cross-feeding. In this environment, two key mutations in C.difficile altered its metabolic niche from proline to glucose utilization. These metabolic changes in C.difficile substantially impacted gut microbiota inter-species interactions and reduced disease severity in mice. In sum, interactions with P.vulgatus are crucial in shaping the long-term growth dynamics and evolutionary adaptations of C.difficile, offering key insights for developing anti-C.difficile strategies.

PEPITEM, its tripeptide pharmacophores and their peptidomimetic analogues regulate the inflammatory response through parenteral and topical dosing in models of peritonitis and psoriasis.

PEPITEM is an immune-modulatory peptide that effectively regulates inflammation and mitigates immune-mediated inflammatory diseases (IMIDs). Here, we identify two independently active tripeptide pharmacophores within PEPITEM and engineered peptidomimetics with enhanced pharmacodynamic properties. These peptidomimetics regulate T-cell trafficking in vitro and reduce T-cell, neutrophil and macrophage numbers in the inflamed peritoneal cavity in vivo. In a plaque psoriasis model, topical administration reduced disease severity, inflammation and immune cell infiltration, while regulating cytokine release in macrophages and fibroblasts, as well as keratinocyte proliferation. Th1 and Th17 cell abundance, along with their cytokines, was reduced in secondary lymphoid organs. This expanded functional repertoire of PEPITEM and its derivatives provides innovative tools for countering immune and stromal cell-induced pathology in IMIDs. Moreover, by identifying significantly smaller tripeptide pharmacophores of 14 amino acid PEPITEM, we may be able to deliver substantial financial advantages in synthesis and formulation. The order of magnitude increase in efficacy observed for some peptidomimetics may deliver agents with enhanced pharmacological characteristics compared to the parent PEPITEM sequence. Taken together with other reports on the efficacy of PEPITEM, this study paves the way for the development and translation of a novel class of anti-inflammatory agents which may have utility in a broad range of autoimmune and chronic inflammatory diseases.