Browse Articles

Genomic exploration of Bemisia tabaci microRNAs using predictive modeling and confirmation through experimental evidence

Prevalence, incidence and associated factors of pneumonia among severely malnourished children hospitalized in Mulago National Referral Hospital, Uganda

Background Pneumonia is still a burden in children hospitalized with severe acute malnutrition (SAM). However, there is limited published information on the magnitude and characteristics of those who present with or develop pneumonia during hospitalization. We determined the prevalence and incidence of pneumonia, and associated factors among children aged 6-59 months hospitalized with SAM. Methods This study employed 2 study designs; cross sectional for prevalence of pneumonia and single arm retrospective cohort design for incidence of pneumonia. We used secondary data collected as part of the ProbiSAM trial that assessed the effect of Probiotics on diarrhea in children with severe acute malnutrition conducted at Mwanamugimu Nutrition Unit Mulago Hospital. Children aged 6-59 months hospitalized with SAM were assessed for prevalence and incidence of pneumonia. Prevalence of pneumonia was the proportion of pneumonia cases at the time of enrolment or within the first 48 hours of admission. 2)Incidence of pneumonia was the proportion who developed clinical signs of pneumonia for the first time during hospitalization among those who did not have pneumonia at enrolment or within 48 hours after admission. Results 400 children were included in the study and of these, 58% were males. Most (87%) of the children were aged 24 months and below. The prevalence of pneumonia was 28% (95% CI: 24–33). In multivariable analysis, factors associated with prevalence of pneumonia include: female sex (Adjusted PR: 1.72, 95% CI: 1.20–2.45), stunting (Adjusted PR: 1.60, 95% CI: 1.12—2.30) and presumptive TB (Adjusted PR: 1.95, 95% CI: 1.34—2.82). Incident pneumonia was estimated at 356 (95% CI: 305—416) per 1000 hospital admissions of children with SAM. In multivariable analysis, children at risk of pneumonia were: young age 6 to 12 months (Adjusted RR: 1.89, 95% CI: 1.10–3.29), stunting (Adjusted RR: 1.59, 95% CI: 1.15–2.20), HIV infection (Adjusted RR: 1.59, 95% CI: 1.08–2.33), presumptive TB (Adjusted RR: 1.73, 95% CI: 1.23–2.43), used a nasogastric tube for feeding (RR: 1.38, 95% CI: 1.00–1.89) and prolonged hospitalization of 15 days or more (Adjusted RR: 2.16, 95% CI: 1.39—3.35). Conclusion and Significance This study identified that prevalence of pneumonia among children hospitalized with SAM is still high and similar to previous studies done in different settings in Uganda. In addition, this study showed that the risk of incident pneumonia among children hospitalized with SAM is high. These findings point out the need to develop guidelines to monitor, detect and treat incident pneumonia among children hospitalized with SAM. Stunting as factor associated with both prevalence and incidence of pneumonia underscores the importance of further research to evaluate how stunting relates to pneumonia.

A diverse family of bacterial deubiquitinases is defined by the <i>Coxiella burnetii</i> effector EmcB

The obligate intracellular pathogen Coxiella burnetii encodes a deubiquitinase called EmcB that prevents signaling by the host immune sensor Retinoic acid Inducible Gene I (RIG-I). The evolutionary relationship between EmcB and other deubiquitinases is currently unknown. Here, we show that EmcB defines a broad family of bacterial deubiquitinases divergently evolved from the eukaryotic Ovarian Tumor (OTU) family of deubiquitinases. Our data indicate that the emcB gene has an internal gene rearrangement that resulted in a circular permutation of the OTU fold. Proteins with a region homologous to the deubiquitinase domain of EmcB were identified in numerous members of the bacterial order Legionellales. Proteins with an EmcB-related deubiquitinase domain demonstrated cysteine protease activity that cleaved ubiquitin and ubiquitin-related modifiers. Most of the bacteria encoding EmcB-related proteins had components of the Dot/Icm Type IVB secretion system that delivers EmcB into host cells. Indeed, many of these EmcB-related proteins were translocated into eukaryotic cells by the Dot/Icm system of Legionella pneumophila , consistent with their predicted roles as bacterial effector proteins that target host pathways. Comparison of EmcB family deubiquitinases revealed a two-domain architecture of EmcB comprising a deubiquitinase domain and a ubiquitin binding module that confers enzyme specificity for certain polyubiquitin chains. This ubiquitin binding region in EmcB was found to be necessary for efficient inhibition of RIG-I signaling. Thus, these EmcB-related proteins represent a large family of deubiquitinating enzymes that arose by divergent evolution in Legionellales , likely enabling these bacteria to infect different host cells by targeting signaling pathways regulated by ubiquitin.

Advanced MRI based Alzheimer’s diagnosis through ensemble learning techniques

Correction: Foreign direct investment and domestic innovation: Roles of absorptive capacity, quality of regulations and property rights

Evolution under vancomycin selection drives divergent collateral sensitivity patterns in <i>Staphylococcus aureus</i>

Staphylococcus aureus bacteremia is typically treated empirically with vancomycin, with therapy later tailored based on susceptibility results. However, these tests occur before vancomycin exposure and do not account for adaptation during empiric treatment that can alter S. aureus ’ susceptibility to first-line drugs. To investigate these collateral drug responses, we experimentally evolved 18 methicillin-susceptible S. aureus (MSSA) populations under increasing vancomycin concentrations until they achieved intermediate resistance. Genomic sequencing revealed two distinct adaptive pathways characterized by mutations in the WalKR regulon, affecting cell wall metabolism, or rpsU , impacting translational stress responses. These pathways correlated with divergent collateral sensitivity profiles to first-line antibiotics. By developing a Collateral Response Score (CRS), we quantified the probability and magnitude of these responses, demonstrating that evolutionary dynamics critically influence resistance outcomes. Our findings suggest a probabilistic approach to antimicrobial therapy, advocating for rapid genomic diagnostics alongside susceptibility testing to better anticipate and respond to evolutionary changes.

Meta-analysis of biofertilizer effects of Bacillus species on tomato yield

Phyllostachyos Caulis in Taeniam extract stimulates longitudinal bone growth via IGF-1 and JAK2/STAT5 signaling in rats

Longitudinal bone growth, which is regulated by endocrine and paracrine factors, is a critical determinant of linear growth during childhood. This study investigated the effects of an aqueous extract of Phyllostachyos Caulis in Taeniam (PCE) on longitudinal bone growth and its regulatory effects on circulating insulin-like growth factor-1 (IGF-1) in rats. Twenty-eight adolescent rats were randomly assigned to four groups (n = 7 per group): control, recombinant human growth hormone (rhGH) 20 μg/kg, PCE 200 mg/kg, and 400 mg/kg. After 10 days of administration, the serum levels of growth hormone (GH), IGF-1, IGF binding protein 3 (IGFBP3), and osteocalcin, as well as tibial length, were measured. In addition, the mRNA expression levels of IGF-1 and IGFBP3 in liver tissue were quantified via real-time polymerase chain reaction (qRT-PCR), and the protein expression levels of Janus kinase 2 (JAK2), signal transducer and activator of transcription 5 (STAT5), and IGF-1 were assessed via western blotting. Compared with the control, 400 mg/kg PCE significantly increased the serum levels of GH, IGF-1, IGFBP3, and osteocalcin in rats by 486.6%, 73.7%, 22.5%, and 27.8%, respectively (P &lt; 0.01), and increased the tibial length by 7.4% (P &lt; 0.01). Compared with the control, 400 mg/kg PCE also increased the mRNA expression of IGF-1 and IGFBP3 in the liver by 5.2-fold (P &lt; 0.01) and 7.3-fold (P &lt; 0.05), respectively. Moreover, compared with the control, 400 mg/kg PCE increased hepatic IGF-1 protein expression by 2.76-fold (P &lt; 0.01) and promoted the phosphorylation of JAK2 and STAT5 by 1.13-fold (P &lt; 0.05) and 2.82-fold (P &lt; 0.01), respectively. These findings suggest that PCE promotes longitudinal bone growth in rats, potentially through GH-mediated IGF-1 regulation via the JAK2/STAT5 pathway.

Nonmuscle myosin 2 turnover in cells is synergistically controlled by the tail and the motor domain

Myosin 2, an actin-dependent motor, is universally responsible for cell contractility due to its ability to form bipolar filaments. Fast turnover of nonmuscle myosin 2 (NM2) filaments is necessary to keep up with cell motility and shape changes. The turnover mechanisms are not fully understood and differ for two main mammalian paralogs—NM2A and NM2B—whereas paralog copolymerization adds complexity to this process by enabling the intrinsically fast NM2A to dynamize the intrinsically slow NM2B. Here, we show that the nonhelical tail, the C-terminal phosphorylation sites, and surprisingly, the motor domain of the NM2A heavy chain synergistically accelerate the turnover of NM2B in trans and cell motility, suggesting that these three mechanisms collectively control NM2A’s own dynamics. Conversely, the phosphomimetic NM2B tail facilitates only local turnover of endogenous wild type NM2B but not its global redistribution unless the NM2A motor is combined with the phosphomimetic NM2B tail. Collectively, we reveal the cooperation between the motor activity and the NM2 tail-targeting turnover mechanisms in regulating the NM2 filament turnover in trans and cell motility.

Association between neutrophil-lymphocyte ratio and all-cause and cardiovascular mortality in osteoarthritis patients from the NHANES 1999–2018 cohort

Abstract This cross-sectional study aimed to investigate the correlation between the neutrophil-lymphocyte ratio (NLR) and all-cause mortality and cardiovascular mortality in osteoarthritis (OA) patients. We involved 3549 adults with OA from the National Health and Nutrition Examination Survey (NHANES) database (1999–2018). The optimal NLR threshold (2.53) was determined using maximally selected rank statistics. Kaplan-Meier (KM), weighted Cox regression, and restricted cubic spline (RCS) analyses were employed to assess the relationship between the NLR and mortality outcomes, with subgroup and sensitivity analyses evaluating the stability of the observed associations. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to evaluate the NLR prognostic accuracy for mortality across time points. During the 91-month median follow-up period, 843 patients died (256 from cardiovascular disease). Elevated NLR (≥ 2.53) was associated with increased risks of all-cause mortality (HR = 1.82) and cardiovascular mortality (HR = 2.50). Nonlinear correlations of the NLR with mortality outcomes were observed. ROC analysis demonstrated superior NLR predictive capability for all-cause and cardiovascular mortality compared to individual blood cell types. Elevated NLR is independently associated with increased risks of all-cause mortality and cardiovascular mortality in OA patients.

High throughput transcriptomics analysis of ovine mammary epithelial cells stimulated with Staphylococcus aureus in vitro

In sheep, the innate immune response of mammary epithelial cells (MECs) plays a central role in combating mastitis, yet our understanding of their resistance mechanisms remains limited. This study aimed to elucidate the gene expression profiles of ovine MECs following in vitro stimulation with Staphylococcus aureus (S. aureus) using RNA-Seq technology. Bioinformatics analysis identified a total of 175 differentially expressed genes (DEGs), including 172 up-regulated and 3 down-regulated genes in the stimulated group compared to the non-stimulated control group. Gene ontology annotation and functional pathway analysis indicated that these DEGs are primarily involved in ribosomal functions, which are essential for protein synthesis and first target of pathogens, as well as in immune response dysregulations, infection, phagocytosis, and bacterial invasion of epithelial cells. Validation via quantitative real-time PCR (qRT-PCR) confirmed the RNA-Seq results. Our results revealed that DEGs converged on innate immune pathways (TLR, NOD-like receptor, NF-κB, MAPK), cytoskeletal remodeling and translational control, indicating inflammatory activation and cell injury in oMECs and highlighting candidate targets for mastitis resistance selection against S. aureus. These findings significantly contribute to the understanding of how ovine MECs respond to S. aureus stimulation, providing a foundation for further research, particularly regarding the immune defense mechanisms, strategies and implications in dairy industry.

FGF21 acting on the noradrenergic nervous system protects against influenza virus infection

The hormone fibroblast growth factor 21 (FGF21) is induced in murine liver in response to both bacterial and viral infection. In this report, we show that FGF21 is induced by infection with influenza virus in both humans and mice. Mice lacking FGF21 had decreased food intake, body weight, and body temperature compared to wild-type mice following influenza virus inoculation, indicating reduced tolerance to the infection. Conversely, pharmacologic administration of FGF21 after viral infection protected mice against these pathologic changes. Pair feeding studies showed that neither the induction of FGF21 nor the hypothermia was secondary to decreased food intake. Notably, mice selectively lacking FGF21’s coreceptor protein, βKlotho, in noradrenergic neurons were also more susceptible to influenza virus infection, including hypothermia. We show that FGF21 acting on noradrenergic neurons, including those in the locus coeruleus region, stimulates energy expenditure and thermogenic gene expression in brown adipose tissue. Our findings reveal an FGF21-regulated neuronal pathway that protects mice against influenza infection and suggest the potential utility of using FGF21 pharmacologically to improve outcomes after influenza infection.

Individual training prescribed by heart rate variability, heart rate and well-being scores in experienced cyclists

Transcriptomic profiling of lung alveolar macrophages reveals distinct contribution of sterol metabolism in macrophage response to Cryptococcus gattii infection

Alveolar macrophages are well known as the first responders to pulmonary cryptococcosis; however, their dynamic molecular responses to Cryptococcus gattii infection in vivo remain limited. Here, we investigated the transcriptional profiles of lung alveolar macrophages purified from mice intranasally infected with C. gattii and compared them to those infected with C. neoformans using RNA sequencing analysis. Alveolar macrophages from C. gattii-infected mice exhibited distinct transcriptional alterations, particularly in genes associated with sterol biosynthesis, whereas those from C. neoformans-infected mice showed enrichment in interferon and cytokine signaling pathways. Treatment with the sterol biosynthesis inhibitor lovastatin significantly reduced cholesterol accumulation in C. gattii-infected RAW 264.7 cells. Furthermore, lovastatin treatment of C. gattii-infected RAW 264.7 and bone marrow-derived macrophages suppressed intracellular cryptococcal proliferation and augmented inflammatory response, as evidenced by increased expression of Nos2 and Il6. Lovastatin also potentiated the antifungal effect of fluconazole by promoting intracellular fungal clearance and increasing nitric oxide activity in macrophages. In C. gattii-infected mice, lovastatin treatment enhanced the efficacy of fluconazole, resulting in improved pulmonary fungal clearance, increased lung CD4 ⁺ T cell numbers, and elevated nitric oxide activity. Collectively, these findings reveal a unique macrophage response to C. gattii infection and highlight the role of sterol metabolism in modulating host defense, offering potential avenues for therapeutic intervention.

Structural insights into the dynamic mechanism of bornavirus polymerase

Borna disease virus 1 (BoDV-1), an emerging zoonotic pathogen from the Bornaviridae family, is neurotropic and can infect a variety of mammalian hosts, including humans. Linked to severe encephalitis and high mortality, BoDV-1 currently lacks licensed treatments or vaccines. The BoDV-1 polymerase complex, comprising the large (L) and phosphoprotein (P) subunits, is crucial for viral replication and transcription, making it a promising target for antiviral intervention. Here, we present the cryoelectron microscopy structure of the apo BoDV-1 L-P complex, revealing a unique “mitten-shaped” architecture. The structure characterizes key domains involved in RNA synthesis, including RNA-dependent RNA polymerase, polyribonucleotidyltransferase, and an inactive methyltransferase domain. While no RNA or NTPs were visible, we observed distinct conformational states, showing large-scale rearrangements of the P tetramer and L domains, as well as remodeling of the RNA template, nucleoside triphosphates, and nascent RNA entrances and/or exits, upon introducing RNA and NTPs. These findings highlight the dynamic structural changes probably associated with polymerase activity and advance the understanding of the BoDV-1 polymerase mechanisms, offering a basis for developing targeted antiviral strategies against this deadly pathogen.

T cell dysregulation reflects disease stage in hepatitis virus and alcohol-related liver disease

Abstract Liver cirrhosis is characterized by both immunodeficiency and an exaggerated immune response leading to systemic inflammation. In this study, we investigated the role of T cells in different stages of liver disease and therefore analyzed 72 patients stratified into those with and without cirrhosis and compensated and decompensated cirrhosis. Flow cytometry revealed that CD8+ T cells, but not CD4+ T cells were diminished in patients with decompensated liver cirrhosis and this further resulted in an increased CD4/CD8 T cell ratio in those patients. In addition, the phenotype of CD4+ and CD8+ T cells shifted towards activated and exhausted effector-memory and terminally differentiated cells in patients with compensated liver cirrhosis, which was parallelled by an impaired functional response upon stimulation with IL-12 + IL-18. Conversely, in patients with decompensated cirrhosis, CD4+ and CD8+ T cells exhibited heightened proliferative activity and showed a relative loss of activation and exhaustion marker expression compared with compensated cirrhosis. Furthermore, investigation of 64 soluble immune mediators revealed an inflammatory cytokine milieu in patients with decompensated liver cirrhosis. Taken together, these results indicate an association between phenotypic and functional changes in the T cell compartment and the different stages of liver disease.

Retraction: Strychnos pseudoquina modulates the morphological reorganization of the scar tissue of second intention cutaneous wounds in rats

Duplication of a conserved mitochondrial enzyme gene arms parasitoid wasps with venom cytotoxicity and oogenesis regulation

Gene duplication, followed by neofunctionalization, is a key mechanism driving the emergence of evolutionary novelties. Despite its significance, the molecular and functional processes underlying this phenomenon remain incompletely understood. By tracing the evolutionary history of cysteine-S-conjugate beta-lyase genes within the kynurenine aminotransferase family, we identified a gene duplication event in parasitoid wasps of the Chalcidoidea superfamily. Notably, a single-copy, highly conserved mitochondria-localized physiological gene underwent a significant duplication, resulting in one copy being recruited into the venom system and acquired cytotoxicity against wasps' hosts. Through this neofunctionalization process, we observed several key evolutionary changes, including loss of ancestral mitochondrial localization and enzyme activity, acquisition of a secretory signal peptide, shift in expression pattern, positive selection, and the establishment of evolutionary acquired protein–protein interactions. Additionally, we found that another duplicate copy was specialized in wasps' ovary and repurposed for oogenesis regulation. Our study offers a detailed insight into the genetic and molecular mechanisms that drive functional diversification during the evolution of gene families.

Removal of hexavalent chromium from contaminated synthetic groundwater via functionalized carbon nanomaterials modified with zinc and potassium

Abstract Chromium has been shown to be a significant contributor to water pollution, leading to cancer. This study aimed to investigate the potential of various functionalized carbon nanomaterials for removing Cr(VI) from synthetic groundwater. Functionalized carbon nanomaterials with layered and tube-like structures were designed on the basis of thermal methods (KOH-activated micrographite sheets) and impregnation methods by anchoring K and Zn on carbon nanotubes (CNTs), respectively, for the removal of Cr(VI) from contaminated synthetic groundwater. Several experimental parameters, including the concentration of the solution, pH, adsorbent dosage, and duration of contact, were systematically varied in a series of batch experiments. The optimal conditions were determined to be a 30 mg/20 mL adsorbent dosage (after the dosage test was 5–50 mg), a pH of 2 (tested at 1–240 min), and a constant agitation speed for all adsorbents. The maximum Cr(VI) removal by K-CNTs (83.04%) occurred at pH 4 and 25 °C and at a constant agitation speed. Zn-CNTs achieved up to 79% removal efficiency at pH 2. However, at neutral pH (8), only K-CNTs maintained a high removal capacity (97%), whereas the other adsorbents exhibited an approximately 53% decrease in removal efficiency. The Cr(VI) removal efficiency reached 95% and 32.7% after five adsorption/desorption cycle tests for K and Zn-CNTs, respectively, at pH = 8, and K-CNTs achieved 91% removal after six cycles, which is particularly noteworthy. Fourier transform infrared (FTIR) spectroscopy was employed to observe the adsorption processes in the polluted water samples, both before and after treatment. The results indicated an increase in the specific surface area and beneficial development of adsorption sites on the CNTs. To elucidate the adsorption mechanisms, the experimental data were analyzed via various isotherm models, namely, the Langmuir, Freundlich, Temkin, and Sips models. Additionally, the adsorption kinetics were examined via pseudo-first-order and pseudo-second-order kinetic models to characterize the temporal aspects of the adsorption process.

Comparison of time to death and its predictors among hospitalized children with and without severe acute malnutrition at Mulanje District Hospital, Southern Malawi

Introduction Severe acute malnutrition (SAM) is a major cause of child mortality in sub-Saharan Africa, yet recent data from Mulanje District Hospital, Malawi, showed higher mortality among non-SAM under-five children. This unexpected trend highlights a knowledge gap, as no studies in Malawi have compared time to death and its predictors between SAM and non-SAM children. This study aimed to fill that gap by examining and comparing mortality timing and predictors in both groups. Methods A retrospective cohort study was conducted using medical records of 454 randomly selected under-five children admitted to Mulanje District Hospital between January 2017 and February 2021. Data were collected using structured forms and analysed in STATA version 16. Cox proportional hazards regression was used to identify mortality predictors, with significance set at p &lt; 0.05. Results The overall mortality rate was 14.8%, with higher mortality in non-SAM children (21.2%) than SAM children (8.4%). The median time to death was 5 days (IQR: 2–8) for SAM and 1 day (IQR: 1–2) for non-SAM children. Among SAM children, not having received amoxicillin (AHR: 4.59; CI: 1.46–14.43) was a significant predictor of death. Among non-SAM children, facility referral (AHR: 2.66 (95% CI: 1.34–5.27)), oxygen therapy (AHR: 4.04 (95% CI: 2.11–7.71)), and not having received amoxicillin (AHR: 33.49 (95% CI: 4.47–250.7)) were significant predictors of mortality. Conclusion The higher mortality observed among non-SAM children reflected more acute disease presentations and delays in effective intervention, underscoring the need for rapid triage and treatment in this group.