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Abstract Background Namibia, a low malaria transmission country targeting elimination, has made substantial progress in reducing malaria burden through improved case management, widespread indoor residual spraying and distribution of insecticidal nets. The country's diverse landscape includes regions with varying population densities and geographical niches, with the north of the country prone to periodic outbreaks. As Namibia approaches elimination, malaria transmission has clustered into distinct foci, the identification of which is essential for deployment of targeted interventions to attain the southern Africa Elimination Eight Initiative targets by 2030. Geospatial modelling provides an effective mechanism to identify these foci, synthesizing aggregate routinely collected case counts with gridded environmental covariates to downscale case data into high-resolution risk maps. Methods This study introduces innovative infectious disease mapping techniques to generate high-resolution spatio-temporal risk maps for malaria in Namibia. A two-stage approach is employed to create maps using statistical Bayesian modelling to combine environmental covariates, population data, and clinical malaria case counts gathered from the routine surveillance system between 2018 and 2021. Results A fine-scale spatial endemicity surface was produced for annual average incidence, followed by a spatio-temporal modelling of seasonal fluctuations in weekly incidence and aggregated further to district level. A seasonal profile was inferred across most districts of the country, where cases rose from late December/early January to a peak around early April and then declined rapidly to a low level from July to December. There was a high degree of spatial heterogeneity in incidence, with much higher rates observed in the northern part and some local epidemic occurrence in specific districts sporadically. Conclusions While the study acknowledges certain limitations, such as population mobility and incomplete clinical case reporting, it underscores the importance of continuously refining geostatistical techniques to provide timely and accurate support for malaria elimination efforts. The high-resolution spatial risk maps presented in this study have been instrumental in guiding the Namibian Ministry of Health and Social Services in prioritizing and targeting malaria prevention efforts. This two-stage spatio-temporal approach offers a valuable tool for identifying hotspots and monitoring malaria risk patterns, ultimately contributing to the achievement of national and sub-national elimination goals.

Abstract Background Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children. Method We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children’s Hospital. Clinical characteristics, pathogens and management were analyzed. Results We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p

Background/purpose: No consensus has been established regarding the exact amount of bone grafting in maxillary sinus augmentation. The aim of this study was to estimate the minimum bone volume for sinus augmentation and to investigate the factors that influence the augmentation volume (AV). Materials and methods: This study included patients with cone-beam computed tomography scanning. Dome-shaped sinus augmentation was performed virtually at vertical heights (VH) of 3, 5, 7, and 9 mm in Group A (without implantation) and Group B (with implantation). The augmentation angle (AA) and the sinus width (SW) were measured. The AV was measured using the three-dimensional image processing program 3D Slicer. Univariable and multivariable analyses were conducted. Results: This study included 30 patients (120 subjects). In Group A, the mean AVs were 0.062, 0.271, 0.642, and 1.287 cc at VHs of 3, 5, 7, and 9 mm, respectively, in Group B, the mean AVs were 0.037, 0.230, 0.594, and 1.230 cc. Univariable analysis indicated that factors significantly associated with the AV in both groups included SW, AA, and VH (P

Abstract Background Malaria risk maps are crucial for controlling and eliminating malaria by identifying areas of varying transmission risk. In the Greater Mekong Subregion, these maps guide interventions and resource allocation. This article focuses on analysing changes in malaria transmission and developing fine-scale risk maps using five years of routine surveillance data in Laos (2017–2021). The study employed data from 1160 geolocated health facilities in Laos, along with high-resolution environmental data. Methods A Bayesian geostatistical framework incorporating population data and treatment-seeking propensity was developed. The models incorporated static and dynamic factors and accounted for spatial heterogeneity. Results Results showed a significant decline in malaria cases in Laos over the five-year period and a shift in transmission patterns. While the north became malaria-free, the south experienced ongoing transmission with sporadic outbreaks. Conclusion The risk maps provided insights into changing transmission patterns and supported risk stratification. These risk maps are valuable tools for malaria control in Laos, aiding resource allocation, identifying intervention gaps, and raising public awareness. The study enhances understanding of malaria transmission dynamics and facilitates evidence-based decision-making for targeted interventions in high-risk areas.

In this study, cattle bone collagen peptides–selenium chelate (CCP-Se) was prepared and its structure, oxidation resistance and stability were characterized. The selenium binding capacity was 33.65 ± 0.13 mg/g by optimized preparation conditions. Structural analysis showed that selenium ions bound mainly to the amino nitrogen, carboxyl oxygen and hydroxyl oxygen atoms of the cattle bone collagen peptide (CCP). The microstructure and particle size analyses showed that the particle size of CCP-Se was increased and formed a regular and compact crystal structure compared with CCP. Additionally, CCP-Se exhibited excellent antioxidant activity. Stability analysis showed that CCP-Se was stable in thermal processing, simulated in vitro digestion and acid/alkali tolerance tests. The intestinal selenium permeability of CCP-Se was significantly better than sodium selenite (p

Abstract Interferons (IFNs) activate JAK‐STAT pathways to induce downstream effector genes for host defense against invaded pathogens and tumors. Here both type I (β) and II (γ) IFNs are shown that can activate the transcription factor IRF3 in parallel with STAT1. IRF3‐deficiency impairs transcription of a subset of downstream effector genes induced by IFN‐β and IFN‐γ. Mechanistically, IFN‐induced activation of IRF3 is dependent on the cGAS‐STING‐TBK1 axis. Both IFN‐β and IFN‐γ cause mitochondrial DNA release into the cytosol. In addition, IFNs induce JAK1‐mediated tyrosine phosphorylation of cGAS at Y214/Y215, which is essential for its DNA binding activity and signaling. Furthermore, deficiency of cGAS, STING, or IRF3 impairs IFN‐β‐ or IFN‐γ‐mediated antiviral and antitumor activities. The findings reveal a novel IRF3 activation pathway parallel with the canonical STAT1/2 activation pathways triggered by IFNs and provide an explanation for the pleiotropic roles of the cGAS‐STING‐IRF3 axis in host defense.

Abstract Background Immunogenic cell death (ICD) is a crucial approach to turn immunosuppressive tumor microenvironment (ITM) into immune-responsive milieu and improve the response rate of immune checkpoint blockade (ICB) therapy. However, cancer cells show resistance to ICD-inducing chemotherapeutic drugs, and non-specific toxicity of those drugs against immune cells reduce the immunotherapy efficiency. Methods Herein, we propose cancer cell-specific and pro-apoptotic liposomes (Aposomes) encapsulating second mitochondria-derived activator of caspases mimetic peptide (SMAC-P)-doxorubicin (DOX) conjugated prodrug to potentiate combinational ICB therapy with ICD. The SMAC-P (AVPIAQ) with cathepsin B-cleavable peptide (FRRG) was directly conjugated to DOX, and the resulting SMAC-P-FRRG-DOX prodrug was encapsulated into PEGylated liposomes. Results The SMAC-P-FRRG-DOX encapsulated PEGylated liposomes (Aposomes) form a stable nanostructure with an average diameter of 109.1 ± 5.14 nm and promote the apoptotic cell death mainly in cathepsin B-overexpressed cancer cells. Therefore, Aposomes induce a potent ICD in targeted cancer cells in synergy of SMAC-P with DOX in cultured cells. In colon tumor models, Aposomes efficiently accumulate in targeted tumor tissues via enhanced permeability and retention (EPR) effect and release the encapsulated prodrug of SMAC-P-FRRG-DOX, which is subsequently cleaved to SMAC-P and DOX in cancer cells. Importantly, the synergistic activity of inhibitors of apoptosis proteins (IAPs)-inhibitory SMAC-P sensitizing the effects of DOX induces a potent ICD in the cancer cells to promote dendritic cell (DC) maturation and stimulate T cell proliferation and activation, turning ITM into immune-responsive milieu. Conclusions Eventually, the combination of Aposomes with anti-PD-L1 antibody results in a high rate of complete tumor regression (CR: 80%) and also prevent the tumor recurrence by immunological memory established during treatments. Graphical Abstract

Abstract Background Nitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes. Results Total N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar. Conclusions N deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.

Summary: Purpose: The coronavirus disease 2019 (COVID-19) pandemic has caused patients to suffer from various physical and psychological symptoms and social challenges, but the impact was harder for those COVID-19 patients receiving treatment in single-room isolation wards in South Korea. This study aimed to investigate resilience, anxiety, depression, and sleep quality of those patients and the relationships between those variables, and explore the patients’ experience of resilience during the COVID-19 treatment in single-room isolation wards. Methods: This study employed a mixed-methods approach, collecting quantitative data through surveys and qualitative data through semistructured interviews conducted between May and October 2022. Quantitative surveys encompassing disease-specific and demographic information, visual analog scales to assess anxiety, depression, and sleep quality, and the Connor–Davidson resilience scale were administered to patients (N = 153). Qualitative thematic analyses were conducted following interviews with a subset of patients (N = 13) belonging to the high-resilience group. Results: Resilience exhibited a negative correlation with anxiety and depression, while showing a positive correlation with sleep quality. Factors affecting resilience include having a spouse, educational attainment, and depression. The qualitative thematic analysis results were categorized into: (1) facing the reality of being isolated in a room; (2) struggling to accept and adapt to isolation; and (3) seeking connections in isolation. Conclusions: This research sheds light on the challenges faced by individuals in isolation and underscores the crucial role of resilience in overcoming such challenges. The resilience observed in these patients is grounded in both interpersonal and profound spiritual connections. These findings underscore the necessity for nurses to develop customized strategies to alleviate the impacts of social isolation.