Stages Of Infection Research Articles

Central Nervous System Effects of Early HIV Infection and Consequences of Antiretroviral Therapy Initiation during Acute HIV.

HIV infection is a multi-organ disease that involves the central nervous system (CNS). While devastating CNS complications such as HIV-associated dementia and CNS opportunistic infection typically manifest years after HIV acquisition, HIV RNA is readily detected in the cerebrospinal fluid in untreated neuroasymptomatic people with HIV, highlighting that HIV neuroinvasion predates overt clinical manifestations. Over the past two decades, increased awareness of HIV infection within the at-risk population, coupled with the accessibility of nucleic acid testing and modern HIV immunoassays, has made the detection of acute and early HIV infection readily achievable. This review aims to summarize research findings on CNS involvement during acute and early HIV infection, as well as the outcomes following the immediate initiation of antiretroviral therapy during this early stage of infection. The knowledge gap in long-term neuroprotection through early ART within the first year of infection will be discussed.

Influenza A defective viral genomes and non-infectious particles are increased by host PI3K inhibition via anti-cancer drug alpelisib.

RNA viruses produce abundant defective viral genomes during replication, setting the stage for interactions between viral genomes that alter the course of pathogenesis. Harnessing these interactions to develop antivirals has become a recent goal of intense research focus. Despite decades of research, the mechanisms that regulate the production and interactions of Influenza A defective viral genomes are still unclear. The role of the host is essentially unexplored; specifically, it remains unknown whether host metabolism can influence the formation of defective viral genomes and the particles that house them. To address this question, we manipulated host cell anabolic signaling activity and monitored the production of defective viral genomes and particles by A/H1N1 and A/H3N2 strains, using a combination of single-cell immunofluorescence quantification, third-generation long-read sequencing, and the cluster-forming assay, a method we developed to titer defective and fully-infectious particles simultaneously. Here we show that alpelisib (Piqray), a highly selective inhibitor of mammalian Class 1a phosphoinositide-3 kinase (PI3K) receptors, significantly changed the proportion of defective particles and viral genomes (specifically deletion-containing viral genomes) in a strain-specific manner, under conditions that minimize multiple cycles of replication. Alpelisib pre-treatment of cells led to an increase in defective particles in the A/H3N2 strain, while the A/H1N1 strain showed a decrease in total viral particles. In the same infections, we found that defective viral genomes of polymerase and antigenic segments increased in the A/H1N1 strain, while the total particles decreased suggesting defective interference. We also found that the average deletion size in polymerase complex viral genomes increased in both the A/H3N2 and A/H1N1 strains. The A/H1N1 strain, additionally showed a dose-dependent increase in total number of defective viral genomes. In sum, we provide evidence that host cell metabolism can increase the production of defective viral genomes and particles at an early stage of infection, shifting the makeup of the infection and potential interactions among virions. Given that Influenza A defective viral genomes can inhibit pathogenesis, our study presents a new line of investigation into metabolic states associated with less severe flu infection and the potential induction of these states with metabolic drugs.

Emergence and fixation of SARS-CoV-2 minority variants in a chronically infected patient receiving therapy in Denmark.

SARS-CoV-2 variants of concern (VOC), such as Delta and Omicron have harbored mutations, which increased viral infectivity or ability to evade neutralizing antibodies. Immunocompromised patients might be a source of some of these emerging variants. In this study, we sequenced 17 consecutive samples from an immunocompromised patient with a long-term SARS-CoV-2 infection with the pre-VOC era lineage B.1.177.35. We here describe the emergence of 73 nonsynonymous minority variants in this patient and show that 10 of these mutations became dominant in the viral population during the treatment period. Four of these were seen throughout the infection period and had a very low global prevalence, although three of them were also observed later in the Alpha, Delta, and Omicron lineages. We also found that two adjacent nsp12 variants (M785I and S786P) belonged to different quasi-species and competed during the early stages of infection and remdesivir administration. This emphasizes the importance of ongoing genome surveillance of SARS-CoV-2 among immunocpromised patients.

Computational Exploration of Potential Pharmacological Inhibitors Targeting the Envelope Protein of the Kyasanur Forest Disease Virus.

The limitations of the current vaccination strategy for the Kyasanur Forest Disease virus (KFDV) underscore the critical need for effective antiviral treatments, highlighting the crucial importance of exploring novel therapeutic approaches through in silico drug design. Kyasanur Forest Disease, caused by KFDV, is a tick-borne disease with a mortality of 3-5% and an annual incidence of 400 to 500 cases. In the early stage of infection, the envelope protein plays a crucial role by facilitating host-virus interactions. The objective of this research is to develop effective antivirals targeting the envelope protein to disrupt the virus-host interaction. In line with this, the 3D structure of the envelope protein was modeled and refined through molecular modeling techniques, and subsequently, ligands were designed via de novo design and pharmacophore screening, yielding 12 potential hits followed by ADMET analysis. The top five candidates underwent geometry optimization and molecular docking. Notably, compounds L4 (SA28) and L3 (CNP0247967) are predicted to have significant binding affinities of -8.91 and -7.58 kcal/mol, respectively, toward the envelope protein, based on computational models. Both compounds demonstrated stability during 200 ns molecular dynamics simulations, and the MM-GBSA binding free-energy values were -85.26 ± 4.63 kcal/mol and -66.60 ± 2.92 kcal/mol for the envelope protein L3 and L4 complexes, respectively. Based on the computational prediction, it is suggested that both compounds have potential as drug candidates for controlling host-virus interactions by targeting the envelope protein. Further validation through in-vitro assays would complement the findings of the present in silico investigations.

Characterization of the fungal genus Sphaerellopsis associated with rust fungi: species diversity, host-specificity, biogeography, and in-vitro mycoparasitic events of S. macroconidialis on the southern corn rust, Puccinia polysora

Sphaerellopsis species are putative hyperparasites of rust fungi and may be promising biological control agents (BCA) of rust diseases. However, few detailed studies limit potential BCA development in Sphaerellopsis. Here, we explored the biogeography, host-specificity, and species diversity of Sphaerellopsis and examined the early infection stage of one species, S. macroconidialis, to infer its trophic status. We randomly screened 5,621 rust specimens spanning 99 genera at the Arthur Fungarium for the presence of Sphaerellopsis. We identified 199 rust specimens infected with Sphaerellopsis species on which we conducted morphological and multi-locus phylogenetic analyses. Five Sphaerellopsis species were recovered, infecting a total of 122 rust species in 18 genera from 34 countries. Sphaerellopsis melampsorinearum sp. nov. is described as a new species based on molecular phylogenetic data and morphological features of the sexual and asexual morphs. Sphaerellopsis paraphysata was the most commonly encountered species, found on 77 rust specimens, followed by Sphaerellopsis macroconidialis on 56 and S. melampsorinearum on 55 examined specimens. The type species, Sphaerellopsis filum, was found on 12 rust specimens and Sphaerellopsis hakeae on a single specimen. We also recovered and documented for the first time, the sexual morph of S. macroconidialis, from a specimen collected in Brazil. Our data indicate that Sphaerellopsis species are not host specific and furthermore that most species are cosmopolitan in distribution. However, S. paraphysata is more abundant in the tropics, and S. hakeae may be restricted to Australia. Finally, we confirm the mycoparasitic strategy of S. macroconidialis through in-vitro interaction tests with the urediniospores of Puccinia polysora. Shortly after germination, hyphae of S. macroconidialis began growing along the germ tubes of P. polysora and coiling around them. After 12 days of co-cultivation, turgor loss was evident in the germ tubes of P. polysora, and appressorium-like structures had formed on urediniospores. The interaction studies indicate that Sphaerellopsis species may be more effective as a BCA during the initial stages of rust establishment.

Comparison of Immune Indicators Related to Phagocytosis of Five Species of Sea Urchins under Artificial Infection with the Pathogenic Bacterium of Black Mouth Disease.

To screen for immune indicators closely related to disease resistance, two species of sea urchin susceptible to black mouth disease (Strongylocentrotus intermedius, S. intermedius ♀ × Heliocidaris crassispina ♂) and three species of sea urchin resistant to black mouth disease (H. crassispina, H. crassispina ♀ × S. intermedius ♂ and Mesocentrotus nudus) were artificially infected with the black mouth pathogen Vibrio echinoideorum. The phagocytosis-related immune indices of the five sea urchin species were compared at different time points post-infection. The results demonstrated that the parameters such as apoptotic rate of phagocytes, mean contribution value (MCV) of single effective phagocyte on Acid Phosphatase (ACP), Reactive Oxygen Species (ROS), and Total Antioxidant Capacity (T-AOC) of the five sea urchin species first increased and then decreased after infection. The key time points were 3 h to 6 h and 48 h post-infection when the black mouth disease-resistant and susceptible sea urchins demonstrated differences. At 3 h or 6 h post-infection, the up-regulation folds in MCV of ACP, ROS and T-AOC of black mouth disease-resistant sea urchins were considerably higher than that of the susceptible sea urchins. At 6 h post-infection, the apoptosis rate and the phagocytic index (PI) of the black mouth disease-resistant sea urchins were significantly higher than those of the susceptible sea urchins (p < 0.05). At 48 h post-infection, the necrosis rate of phagocytes, MCV of ACP and MCV of ROS of the black mouth disease-resistant sea urchins were significantly lower than those of the susceptible sea urchins (p < 0.05). The apoptosis and necrosis rate of phagocytes, PI, and MCV on ACP, ROS may be used as indicators of disease resistance in sea urchins. Disease resistance standards in immune indices can be summarized as phagocytosis increases greatly in the early infection stage and decreases timely to a normal level after killing the pathogen in a short period.

Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection.

Human cytomegalovirus (HCMV) causes significant disease in individuals with impaired or immature immune systems, such as transplant patients and after congenital infection. Antiviral drugs that target the virus directly are toxic and are susceptible to antiviral drug resistance due to virus mutations. An alternate strategy is to target processes within host cells that are required by the virus for replication. Herein, we show that HCMV infection triggers a highly reactive molecule, peroxynitrite, during the initial stages of infection. Peroxynitrite was required for the initial entry of the virus into the cell and promotes virus replication in multiple cell types, suggesting a broad pro-viral function. Importantly, targeting peroxynitrite dramatically inhibited cytomegalovirus replication in cells in the laboratory and in mice, suggesting that therapeutic targeting of this molecule and/or the cellular functions it regulates could represent a novel strategy to inhibit HCMV infection.

Sac1 links phosphoinositide turnover to cryptococcal virulence.

Cryptococcus neoformans is an environmentally acquired fungal pathogen that causes over 140,000 deaths per year. Cryptococcal infection occurs when infectious particles are deposited into the lung, where they encounter host phagocytic cells. C. neoformans may be engulfed by these phagocytes, an important step of infection that leads to outcomes ranging from termination of infection to cryptococcal dissemination. To study this critical process, we screened approximately 4,700 cryptococcal gene deletion mutants for altered uptake, using primary mouse and human phagocytic cells. Among the hits of these two screens, we identified 93 mutants with perturbed uptake in both systems, as well as others with differences in uptake by only one cell type. We further screened the hits for changes in thickness of the capsule, a protective polysaccharide layer around the cell which is an important cryptococcal virulence factor. The combination of our three screens yielded 45 mutants, including one lacking the phosphatidylinositol-4-phosphate phosphatase Sac1. In this work, we implicate Sac1 in both host cell uptake and capsule production. We found that sac1 mutants exhibit lipid trafficking defects, reductions in secretory system function, and changes in capsule size and composition. Many of these changes occur specifically in tissue culture media, highlighting the role of Sac1 phosphatase activity in responding to the stress of host-like conditions. Overall, these findings show how genome-scale screening can identify cellular factors that contribute to our understanding of cryptococcal biology and demonstrate the role of Sac1 in determining fungal virulence.IMPORTANCECryptococcus neoformans is a fungal pathogen with significant impact on global health. Cryptococcal cells inhaled from the environment are deposited into the lungs, where they first contact the human immune system. The interaction between C. neoformans and host cells is critical because this step of infection can determine whether the fungal cells die or proliferate within the human host. Despite the importance of this stage of infection, we have limited knowledge of cryptococcal factors that influence its outcome. In this study, we identify cryptococcal genes that affect uptake by both human and mouse cells. We also identify mutants with altered capsule, a protective coating that surrounds the cells to shield them from the host immune system. Finally, we characterize the role of one gene, SAC1, in these processes. Overall, this study contributes to our understanding of how C. neoformans interacts with and protects itself from host cells.

Exploring the impression of TRIM25 gene expression on COVID-19 severity and SARS-CoV-2 viral replication

BackgroundThere are numerous human genes associated with viral infections, and their identification in specific populations can provide suitable therapeutic targets for modulating the host immune system response and better understanding the viral pathogenic mechanisms. Many antiviral signaling pathways, including Type I interferon and NF-κB, are regulated by TRIM proteins. Therefore, the identification of TRIM proteins involved in COVID-19 infection can play a significant role in understanding the innate immune response to this virus. MethodsIn this study, the expression of TRIM25 gene was evaluated in a blood sample of 330 patients admitted to the hospital (142 patients with severe disease and 188 patients with mild disease) as well as in 160 healthy individuals. The relationship between its expression and the severity of COVID-19 disease was assessed and compared among the study groups by quantitative Real-time PCR technique. The statistical analysis of the results demonstrated a significant reduction in the expression of TRIM25 in the group of patients with severe infection compared to those with mild infection. Furthermore, the impact of increased expression of TRIM25 gene in HEK-293 T cell culture was investigated on the replication of attenuated SARS-CoV-2 virus. ResultsThe results of Real-time PCR, Western blot for the viral nucleocapsid gene of virus, and CCID50 test indicated a decrease in virus replication in these cells. The findings of this research indicated that the reduced expression of the TRIM25 gene was associated with increased disease severity of COVID-19 in individuals. Additionally, the results suggested the overexpression of TRIM25 gene can impress the replication of attenuated SARS-CoV-2 and the induction of beta-interferon. ConclusionTRIM25 plays a critical role in controlling viral replication through its direct interaction with the virus and its involvement in inducing interferon during the early stages of infection. This makes TRIM25 a promising target for potential therapeutic interventions.

Analysis of spatiotemporal changes mechanism of cell wall biopolymers and monosaccharide components in kiwifruit during Botryosphaeria dothidea infection

To further reveal the interaction mechanism between plants and pathogens, this study used confocal Raman microscopy spectroscopy (CRM) combined with chemometrics to visualize the biopolymers distribution of kiwifruit cell walls at different infection stages at the cellular micro level. Simultaneously, the changes in the content of various monosaccharides in fruit were studied at the molecular level using high-performance liquid chromatography (HPLC). There were significant differences in the composition of various nutrient components in the cell wall structure of kiwifruit at different infection times after infection by Botryosphaeria dothidea. PCA could cluster samples with infection time of 0–9 d into different infection stages, and SVM was used to predict the PCA classification results, the accuracy >96 %. Multivariate curve resolution-alternating least squares (MCR-ALS) helped to identify single substance spectra and concentration signals from mixed spectral signals. The pure substance chemical imaging maps of low methylated pectin (LMP), high methylated pectin (HMP), cellulose, hemicellulose, and lignin were obtained by analyzing the resolved concentration data. The imaging results showed that the lignin content in the kiwifruit cell wall increased significantly to resist pathogens infection after the infection of B. dothidea. With the development of infection, B. dothidea decomposed various substances in the host cell walls, allowing them to penetrate the interior of fruit cells. This caused significant changes in the form, structure, and distribution of various chemicals on the fruit cell walls in time and space. HPLC showed that glucose was the main carbon source and energy substance obtained by pathogens from kiwifruit during infection. The contents of galactose and arabinose, which maintained the structure and function of the fruit cell walls, decreased significantly and the cell wall structure was destroyed in the late stage of pathogens infection. This study provided a new perspective on the cellular structure changes caused by pathogenic infection of fruit and the defense response process of fruit and provided effective references for further research on the mechanisms of host-pathogen interactions in fruit infected by pathogens.

Performance evaluation of the MAGLUMI Hepatitis B virus surface antigen chemiluminescence immunoassay.

A highly sensitive and reliable Hepatitis B virus surface antigen (HBsAg) measurement is essential to universal screening, timely diagnosis, and management of Hepatitis B virus (HBV) infection. This study aimed to evaluate the performance of MAGLUMI HBsAg chemiluminescence immunoassay (CLIA). MAGLUMI HBsAg (CLIA) was compared against ARCHITECT HBsAg. 411 HBsAg positive samples, including different stages of infection, genotypes, subtypes, mutants, and 30 seroconversion panels were tested to evaluate diagnostic sensitivity. Diagnostic specificity was evaluated by testing 205 hospitalized samples and 5101 blood donor samples. Precision, limit of blank (LoB), limit of detection (LoD), and linearity were also verified. The diagnostic sensitivity of the MAGLUMI HBsAg (CLIA) was 100% with better seroconversion sensitivity than ARCHITECT HBsAg. The MAGLUMI HBsAg (CLIA) has optimal detection efficacy for HBV subgenotypes samples. The analytical sensitivity is 0.039 IU/mL. The initial diagnostic specificity is 99.63% on blood donors and 96.59% on hospitalized samples. The verification data demonstrated high repeatability, a LoB of 0.02 IU/mL, LoD of 0.05 IU/mL and an excellent linearity of 0.050-250 IU/mL (R2 = 0.9946). The MAGLUMI HBsAg (CLIA) is proved a highly sensitive and reliable assay with optimal subgenotype detection efficacy.

Acute kidney injury in children with lymphoma.

To analyze the epidemiology of acute kidney injury (AKI) in children with lymphoma and to assess the incidence, risk profile of AKI, and effects on renal function in children with lymphoma during their first 30 days of hospitalization. This was a retrospective screen of electronic hospital and laboratory databases to select hospitalized children who were first diagnosed and treated for lymphoma at Beijing Children's Hospital between 2020 and 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. We analyzed the incidence and risk factors for AKI in children with lymphoma during their first 30 days of hospitalization. We also analyzed mortality rate and the incidence of kidney recovery over a 1-year follow-up period. Of the 295 children with lymphoma (which were all non-Hodgkin lymphoma), 42 (16.5%) experienced AKI events during the first their 30 days of hospitalization. The proportion of patients with lymphoma clinical stage 4 was higher in the AKI group than in the non-AKI group (66.7 vs. 43.7%, p<0.05). Tumor lysis syndrome (TLS), lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma. Severe AKI was associated with TLS, sepsis, and a higher need for intensive care. Over 1-year of follow-up, none of the survivors developed impaired renal function or proteinuria. However, the mortality of children in the AKI group was significantly higher than that in the non-AKI group (p<0.05). TLS, lung infection, and lymphoma clinical stage were identified as independent risk factors for AKI in children with lymphoma during the first 30 days of hospitalization. Clinicians should increase their awareness of AKI in hospitalized patients with lymphoma.

A Review of Syphilis Infection in Pediatric Patients

Nearly half of all sexually transmitted infections occur in adolescents and young adults. Among them, syphilis infections are on the rise in the United States. Sexually active adolescents, especially those who do not use condoms consistently or are men who have sex with men, are at particular risk for syphilis infection. With the rise in acquired syphilis infections, the incidence of congenital syphilis has also increased. Syphilis can have a variety of presentations based on infectious stage and central nervous system involvement. Careful physical examination and history can elicit the diagnosis. Screening with a nontreponemal test followed by treponemal testing can confirm the diagnosis, and staging is determined clinically. Testing for all sexually transmitted infections should be pursued because coinfections are common. Penicillin is the first-line treatment for syphilis, and duration of therapy depends on the presence of neurologic symptoms; all infants with possible congenital syphilis should receive treatment. Posttreatment monitoring is essential to confirm successful eradication of syphilis. All sexually active, at-risk patients, including pregnant persons, should be screened for syphilis, and those diagnosed as having syphilis should be counseled on disclosure to partners. Although not often found in a pediatric population, with the increasing incidence of syphilis infections in the United States, pediatric providers should have a low threshold for syphilis screening in adolescents and a high index of suspicion for congenital syphilis in infants.

Age, gender, and infectious status-wise assessments of hematological parameters among patients with dengue infection

BackgroundThe aim of this study was to examine the impact of different stages of dengue infection on immune cell counts among dengue patients and to compare them with cases of non-dengue febrile illness. MethodsThe recruited patients were divided into two groups: the first group served as a control (n = 55), representing non-dengue febrile illness, and the second group was identified as dengue febrile illness (n = 149), which was further divided into three groups based on infection stage. Blood samples were collected from the selected patients and subjected to blood cell component analysis. To find IgG and IgM as well as the dengue virus non-structural antigen-1 (NS1), an immunochromatographic test (ICT) kit was utilized. Additionally, a hematological analyzer was used to determine complete blood cell counts (CBC). Data was thoroughly analyzed using Graph Pad Prism 6 software. The differences in means of different groups were calculated by applying the student's t-test. ResultsThe findings revealed the presence of severe leucopenia and thrombocytopenia at stages 1 and 2, accompanied by lymphopenia at stage 1. Group comparisons indicated that only teenagers exhibited a significantly lower white blood cell count compared to older individuals, while no significant differences were observed in lymphocytes, platelets, and monocytes across all age groups. Comparing different age groups of normal individuals to dengue-infected patients, the results unveiled that leucopenia was most severe in adults, followed by teenagers and children, with no significant difference in the elderly. Furthermore, adults showed the greatest degree of thrombocytopenia, followed by teens and kids, with the elderly showing the greatest degree of thrombocytopenia. Adults and teens showed extreme neutrophilia, whereas young children and the elderly showed no discernible abnormalities. Elderly patients experienced a marked decrease in monocyte count, a phenomenon not observed in other age groups. ConclusionIn conclusion both, leucopenia & thrombocytopenia, are most severe in stages 1 and 2, whereas neutrophilia & lymphopenia are predominantly severe in stage 1. These results imply that the consequences associated with dengue infection are more severe in the early stages and tend to ameliorate as the patient progresses toward recovery.

The impact of travel distance in patient outcomes following revascularization for chronic limb-threatening ischemia

BackgroundPatient travel distance to the hospital is a key metric of individual and social disadvantage and its impact on the management and outcomes following intervention for chronic limb-threatening ischemia (CLTI) is likely underestimated. We sought to evaluate the effect of travel distance on outcomes in patients undergoing first-time lower extremity revascularization at our institution. MethodsWe retrospectively reviewed all consecutive patients undergoing first-time lower extremity revascularization, both endovascular and open, for CLTI from 2005 to 2014. Patients were stratified into 2 groups based on travel distance from home to hospital greater than or less than 30 miles. Outcomes included reintervention, major amputation, restenosis, primary patency, wound healing, length of stay, length of follow-up and mortality. Kaplan-Meier estimates were used to determine event rates. Logistic and cox regression was used to evaluate for an independent association between travel distance and these outcomes. ResultsOf the 1293 patients were identified, 38% traveled >30 miles. Patients with longer travel distances were younger (70 years vs 73 years; P = .001), more likely to undergo open revascularization (65% vs 41%; P < .001), and had similar Wound, Ischemia, foot Infection stages (P = .404). Longer distance travelled was associated with an increase in total hospital length of stay (9.6 days vs 8.6 days; P = .031) and shorter total duration of postoperative follow-up (2.1 years vs 3.0 years; P = .001). At 5 years, there was no definitive difference in the rate of restenosis (hzard ratio [HR], 1.3; 95% confidence interval [CI], 0.91-1.9; P = .155) or reintervention (HR, 1.4; 95% CI, 0.96-2.1; P = .065), but longer travel distance was associated with an increased rate of major amputation (HR, 2.1; 95% CI, 1.2-3.7; P = .011), and death (HR, 1.6; 95% CI, 1.2-2.2; P = .002). Longer travel distance was also associated with higher rate of nonhealing wounds (HR, 2.3; 95% CI, 1.5-3.5; P = .001). ConclusionsLonger patient travel distance was found to be associated with a lower likelihood of limb salvage and survival in patients undergoing first-time lower extremity revascularization for CLTI. Understanding and addressing the barriers to discharge, need for multidisciplinary follow-up, and appropriate postoperative wound care management will be key in improving outcomes at tertiary care regional specialty centers.

Promising Potential of Curcumin and Related Compounds for Antiviral Drug Discovery.

Viruses are acellular, microscopic, and mobile particles containing genetic particles, either DNA/RNA strands as nucleoproteins, responsible for 69,53,743 deaths till the year 2023. Curcumin and related compounds are among the areas of pivotal interest for researchers because of their versatile pharmacological profile. Chemically known as diferuloylmethane, which is a main constituent of turmeric along with demethoxycurcumin and bisdemethoxycurcumin, they have a broad spectrum of antiviral activity against viruses such as human immunodeficiency virus, herpes simplex virus, influenza virus (Avian influenza) and Hepatitis C virus HIV. The possible role of curcumin as an antiviral agent may be attributed to the activation of the 20S proteasome, a cellular machinery responsible for degrading unfolded or misfolded proteins in a ubiquitin-independent manner. It shows suppression of HBV entry at various infection stages by inhibiting cccDNA replication by inhibiting the Wnt/β-catenin signaling pathway to attenuate IAV-induced myocarditis.

Impact of Infrapopliteal Revascularisation Establishing In Line Flow to the Wound in Patients with Chronic Limb Threatening Ischaemia

This study aimed to determine the impact of infrapopliteal (IP) revascularisation establishing in line flow to the wound (IFW) on wound healing in chronic limb threatening ischaemia (CLTI), using a core laboratory assessment for wounds and in line flow. The Wound-directed Angiosome RevasculaRIzation apprOach to patients with cRitical limb iSchaemia (WARRIORS) multicentre observational study enrolled patients with CLTI with tissue loss undergoing IP revascularisation in Japan, with scheduled two year follow up. The primary outcome measure was complete wound healing, defined as achievement of complete epithelialisation of all wounds without major amputation. IP revascularisation establishing IFW was defined as revascularisation after which a tibiopedal artery that actually fed an injured pedal unit was patent. The incidence of wound healing was compared between the IFW and non-IFW groups using inverse probability of treatment weighting based on the propensity score. A total of 440 patients with CLTI (median age, 75 years; male, 64.1%; diabetes mellitus, 72.0%; dialysis, 57.7%) with tissue loss (Wound, Ischemia, and foot Infection stage 4, 66.4%) who underwent IP revascularisation (endovascular procedure, n = 304; bypass grafting, n = 136) between October 2017 and June 2020 were registered. During a median follow up of 23.6 months, 51.1% achieved wound healing. Successful IP revascularisation with IFW was achieved in 68.2%. After analysis, the IFW group had a higher incidence of wound healing than the non-IFW group (34.5 vs. 16.1 per 100 person years; p = .030). The association of IFW with wound healing was not statistically different between patients undergoing bypass grafting and those undergoing an endovascular procedure (p for interaction = .38). There was no statistically significant interaction effect between IFW and direct revascularisation for wound healing (p for interaction = .51). IP revascularisation establishing IFW was statistically significantly associated with a higher wound healing rate in patients with CLTI.

An improved bacterial mRNA enrichment strategy in dual RNA sequencing to unveil the dynamics of plant-bacterial interactions

BackgroundDual RNA sequencing is a powerful tool that enables a comprehensive understanding of the molecular dynamics underlying plant-microbe interactions. RNA sequencing (RNA-seq) poses technical hurdles in the transcriptional analysis of plant-bacterial interactions, especially in bacterial transcriptomics, owing to the presence of abundant ribosomal RNA (rRNA), which potentially limits the coverage of essential transcripts. Therefore, to achieve cost-effective and comprehensive sequencing of the bacterial transcriptome, it is imperative to devise efficient methods for eliminating rRNA and enhancing the proportion of bacterial mRNA. In this study, we modified a strand-specific dual RNA-seq method with the goal of enriching the proportion of bacterial mRNA in the bacteria-infected plant samples. The enriched method involved the sequential separation of plant mRNA by poly A selection and rRNA removal for bacterial mRNA enrichment followed by strand specific RNA-seq library preparation steps. We assessed the efficiency of the enriched method in comparison to the conventional method by employing various plant-bacterial interactions, including both host and non-host resistance interactions with pathogenic bacteria, as well as an interaction with a beneficial rhizosphere associated bacteria using pepper and tomato plants respectively.ResultsIn all cases of plant-bacterial interactions examined, an increase in mapping efficiency was observed with the enriched method although it produced a lower read count. Especially in the compatible interaction with Xanthmonas campestris pv. Vesicatoria race 3 (Xcv3), the enriched method enhanced the mapping ratio of Xcv3-infected pepper samples to its own genome (15.09%; 1.45-fold increase) and the CDS (8.92%; 1.49-fold increase). The enriched method consistently displayed a greater number of differentially expressed genes (DEGs) than the conventional RNA-seq method at all fold change threshold levels investigated, notably during the early stages of Xcv3 infection in peppers. The Gene Ontology (GO) enrichment analysis revealed that the DEGs were predominantly enriched in proteolysis, kinase, serine type endopeptidase and heme binding activities.ConclusionThe enriched method demonstrated in this study will serve as a suitable alternative to the existing RNA-seq method to enrich bacterial mRNA and provide novel insights into the intricate transcriptomic alterations within the plant-bacterial interplay.

Hyoid epiglottis combined with sternocleidomastoid muscle clavicle flap for repairing laryngeal defect after laryngeal trauma infection: a case report

The initial treatment of open laryngeal trauma must be implemented immediately, with the primary focus on saving lives. However, in the later stages, various factors may cause changes in the structure and function of the larynx, which requires special attention. This article reports on the treatment process of a patient with depression who suffered from laryngeal trauma. Due to the late stage of laryngeal infection causing laryngeal defects, a hyoid epiglottis combined with sternocleidomastoid muscle clavicular flap repair was performed. Additionally, personalized functional exercise was performed, ultimately resulting in recovery.

Isocitrate lyase promotes Puccinia striiformis f. sp. tritici susceptibility in wheat (Triticum aestivum) by suppressing accumulation of glyoxylate cycle intermediates.

Plant fungal parasites manipulate host metabolism to support their own survival. Among the many central metabolic pathways altered during infection, the glyoxylate cycle is frequently upregulated in both fungi and their host plants. Here, we examined the response of the glyoxylate cycle in bread wheat (Triticum aestivum) to infection by the obligate biotrophic fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Gene expression analysis revealed that wheat genes encoding the two unique enzymes of the glyoxylate cycle, isocitrate lyase (TaICL) and malate synthase, diverged in their expression between susceptible and resistant Pst interactions. Focusing on TaICL, we determined that the TaICL B homoeolog is specifically upregulated during early stages of a successful Pst infection. Furthermore, disruption of the B homoeolog alone was sufficient to significantly perturb Pst disease progression. Indeed, Pst infection of the TaICL-B disruption mutant (TaICL-BY400*) was inhibited early during initial penetration, with the TaICL-BY400* line also accumulating high levels of malic acid, citric acid, and aconitic acid. Exogenous application of malic acid or aconitic acid also suppressed Pst infection, with trans-aconitic acid treatment having the most pronounced effect by decreasing fungal biomass 15-fold. Thus, enhanced TaICL-B expression during Pst infection may lower accumulation of malic acid and aconitic acid to promote Pst proliferation. As exogenous application of aconitic acid and malic acid has previously been shown to inhibit other critical pests and pathogens, we propose TaICL as a potential target for disruption in resistance breeding that could have wide-reaching protective benefits for wheat and beyond.