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For geological carbon sequestration to work, we need a geospatial planning policy

HSD17B4 deficiency causes dysregulation of primary cilia and is alleviated by acetyl-CoA

Innovative liposomal coumarin: A promising solution for enhancing soft white cheese quality

Background Coumarin is a natural bioactive compound found in many plants and acquires antibacterial, antioxidant and anticoagulant activities. The antibacterial activity of coumarin has never been tested after being encapsulated in liposomes. This study was carried out to screen the main functional components of Rubus canescens DC crude extract (CE), develop a coumarin nanoliposome, and test its anti-bacterial and antioxidant properties. Methods R. canescens DC CE was screened for its main functional compounds using liquid chromatography-mass spectrometry (LC-MS). Pure commercial coumarin was loaded into liposomes and characterized in terms of surface morphology, hydrodynamic diameter, zeta potential, and encapsulation efficiency (EE). The antioxidant activity of coumarin was evaluated against ascorbic acid. The antibacterial activity of both coumarin alone and liposome-encapsulated coumarin against Staphylococcus aureus, Salmonella typhimurium, and Pseudomonas aeruginosa inoculated in soft white cheese (SWC) was also evaluated. Results The predominant natural constituent of R. canescens DC CE, was coumarin. Comparing the DPPH scavenging activity of coumarin to that of ascorbic acid, coumarin exhibited an insignificant effect (p ≥ 0.05). The minimum inhibitory concentration (MIC) values for coumarin against P. aeruginosa, E. coli, Staph. aureus, S. typhimurium, and L. monocytogenes were 2.5, 2.5, 2.5, 1.25, and 1.25 µg/ml, respectively. The minimum bactericidal concentration (MBC) values for coumarin against these microorganisms were 5, 5, 5, 2.5, and 2.5 µg/ml, respectively. Coumarin was successfully loaded into nanoliposomes, which had a polydispersity index (PDI) of 0.36 ±  0.35 Đ, hydrodynamic diameter of 127.8 ±  0.3 nm, zeta-potential of -61.03 ±  2.9 mV, and EE of 40.93 ±  0.2%. Both the coumarin alone and the liposome loaded with coumarin showed antibacterial effects against the inoculated bacterial strains in SWC over a 30-day storage period at 4°C. Conclusions Coumarin was successfully formulated into a nanoliposome, and showed antibacterial activity against P. aeruginosa, S. aureus, and S. typhimurium.

Relation-based self-distillation method for 2D object detection

SOS1 inhibitor BI-3406 shows in vivo antitumor activity akin to genetic ablation and synergizes with a KRAS ^G12D inhibitor in KRAS LUAD

We evaluated the in vivo therapeutic efficacy and tolerability of BI-3406-mediated pharmacological inhibition of SOS1 in comparison to genetic ablation of this universal Ras-GEF in various KRAS-dependent experimental tumor settings. Contrary to the rapid lethality caused by SOS1 genetic ablation in SOS2 KO mice, SOS1 pharmacological inhibition by its specific inhibitor BI-3406 did not significantly affect animal weight/viability nor cause noteworthy systemic toxicity. Allograft assays using different KRAS mut cell lines showed that treatment with BI-3406 impaired RAS activation and RAS downstream signaling and decreased tumor burden and disease progression as a result of both tumor-intrinsic and -extrinsic therapeutic effects of the drug. Consistent with prior genetic evidence and the KRAS mut allografts assays in immunocompromised mice, our analyses using an in vivo model of KRAS G12D -driven lung adenocarcinoma (LUAD) in immunocompetent mice showed that single, systemic BI-3406 treatment impaired tumor growth and downmodulated protumorigenic components of the tumor microenvironment comparably to SOS1 genetic ablation or to treatment with the specific KRAS G12D inhibitor MRTX1133. Furthermore, markedly stronger, synergistic antitumor effects were observed upon concomitant treatment with BI-3406 and MRTX1133 in the same in vivo LUAD mouse model. Our data confirm SOS1 as an actionable therapy target in RAS-dependent cancers and suggest that BI-3406 treatment may yield clinical benefit both as monotherapy or as a potential combination partner for multiple RAS-targeting strategies.

Intergenerational transmission of polygenic predisposition for neuropsychiatric traits on emotional and behavioural difficulties in childhood

Abstract Childhood emotional and behavioural difficulties tend to co-occur and often precede diagnosed neuropsychiatric conditions. Identifying shared and specific risk factors for early-life mental health difficulties is therefore essential for prevention strategies. Here, we examine how parental risk factors shape their offspring’s emotional and behavioural symptoms (e.g. feelings of anxiety, and restlessness) using data from 14,959 genotyped family trios from the Norwegian Mother, Father and Child Cohort Study (MoBa). We model maternal reports of emotional and behavioural symptoms, organizing them into general and specific domains. We then investigate the direct (genetically transmitted) and indirect (environmentally mediated) contributions of parental polygenic risk for neuropsychiatric-related traits and whether these are shared across symptoms. We observe evidence consistent with an environmental route to general symptomatology beyond genetic transmission, while also demonstrating domain-specific direct and indirect genetic contributions. These findings improve our understanding of early risk pathways that can be targeted in preventive interventions aiming to interrupt the intergenerational cycle of risk transmission.

Correction: A scoping review to examine health care professionals’ experiences as family caregivers

Measurement properties of the Polish version of the Cystic Fibrosis Questionnaire Revised 14+ in the adult population

Proteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis

Chronic infections with hepatitis E virus (HEV), especially those of genotype 3 (G3), frequently lead to liver fibrosis and cirrhosis in patients. However, the causation and mechanism of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we found that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin–proteasomal processing leading to formation of the H EV- D erived S MAD A ctivator (HDSA), a viral polypeptide lacking putative helicase and RNA polymerase domains. The HDSA is stable, non-HSP90-bound, localizes to the nucleus, and is abundant in G3 HEV-infected hepatocytes of various origins. Markedly, the HDSA in hepatocytes potentiates the fibrogenic TGF-β/SMAD pathway by forming compact complexes with SMAD3 to facilitate its promoter binding and coactivator recruitment, leading to significant fibrosis in HEV-susceptible gerbils. Virus infection–induced liver fibrosis in HEV-susceptible gerbils could be prevented by mutating the residues P989C, A990C, and A991C (PAA-3C) within ORF1, which are required for proteasomal processing. Thus, we have identified a viral protein derived from host proteasomal processing, defined its notable role in liver fibrosis and highlighted the nature of an unanticipated host–HEV interaction that facilitates hepatitis E pathogenesis.

Metabolomics strategy for diagnosing urinary tract infections

Perspectives of health workers on malaria case referral among pregnant women attending antenatal care in Savelugu Municipality, Ghana: A qualitative descriptive study

Background Malaria remains endemic in Africa, with pregnant women exposed to the dangers of complications, which require emergency referral for lifesaving interventions. This study explored the perspectives of health workers on malaria case referral among pregnant women attending antenatal care (ANC) at health facilities in Savelugu Municipality, northern Ghana. Methods The study employed a qualitative descriptive design with a constructivist grounded theory perspective. A semi-structured interview guide was used to collect information from thirteen health workers on face-to-face. The participants were purposefully sampled and interviewed. The data were transcribed verbatim. Content analysis was performed and the results were presented as themes and sub-themes. Results After the analysis, two main themes and six sub-themes emerged from the data: a robust referral system (patient awareness and consent, documentation, referral coordination, and post-referral feedback) and a referral mechanism (ambulance/nurse accompaniment, and transportation shortfalls/patients left to their fate). Participants described the referral system as robust but reported transport challenges as the main obstacle to its operation. The study also revealed that health workers do not accompany all referral cases. Conclusion A referral system exists in the Savelugu Municipality with transportation lapses causing delays. Health workers often failed to accompany referred cases to the referral facilities. Though an inter-sectoral approach is needed to tackle the referral transport challenges, facility managers need to ensure that all referred cases are accompanied by a designated health worker.

Molecular insights into supercritical water gasification process of polyoxymethylene plastics

Abstract Effective plastic management is crucial in addressing the growing environmental challenges posed by plastic pollution. Among various plastics, polyoxymethylene (POM) stands out as a widely used engineering thermoplastic with significant applications in industries . Innovative recycling solutions are essential to mitigate its environmental impact. This study investigates the supercritical water gasification (SCWG) of POM plastics at a molecular level using reactive molecular dynamics simulations. The research aims to provide insights into the factors influencing the SCWG process. Key findings reveal that temperature significantly affects reaction mechanisms, while the primary syngas products include hydrogen , carbon monoxide, and carbon dioxide. A notable trend observed is the increase in activation energy as water content increases, highlighting the importance of optimizing hydration levels for efficient conversion. The calculated activation energies range from 106 to 135 kJ/mol, aligning well with experimental findings (160 kJ/mol). The study validates the computational approach by demonstrating excellent agreement between simulation results and experimental findings on the molar fraction of gas and activation energy, underscoring its reliability as a predictive tool for process design and optimization. Furthermore, the research contributes to sustainable waste management by offering strategies to enhance SCWG efficiency.

iPSCs engrafted in allogeneic hosts without immunosuppression induce donor-specific tolerance to secondary allografts

Currently, most cell or tissue transplantations using induced pluripotent stem cells (iPSCs) are anticipated to involve allogeneic iPSCs. However, the immunological properties of iPSCs in an allogeneic setting are not well understood. We previously established a mouse transplantation model of MHC-compatible/minor antigen-mismatched combinations, assuming a hypoimmunogenic iPSC-setting. Here, we found that iPSCs subcutaneously inoculated into MHC-compatible allogeneic host mice resisted rejection and formed teratomas without immunosuppressant administration. Notably, when skin grafts were transplanted onto hosts more than 40 d after the initial iPSCs inoculation, only the skin of the same strain as the initial iPSCs was engrafted. Therefore, donor-specific immune tolerance was induced by a single iPSC inoculation. Diverse analyses, including single-cell RNA-sequencing after transplantation, revealed an increase in regulatory T cell (Treg) population, particularly CD25 + CD103 + effector Tregs within the teratoma and skin grafts. The removal of CD25 + or Foxp3 + cells suppressed the increase in effector Tregs and disrupted graft acceptance, indicating the importance of these cells in the establishment of immune tolerance. Within the teratoma, we observed an increase in TGF-β2 levels, suggesting an association with the increase in effector Tregs. Our results provide important insights for future applications of allogeneic iPSC-based cell or tissue transplantation.

Global gridded population datasets systematically underrepresent rural population

Abstract Numerous initiatives towards sustainable development rely on global gridded population data. Such data have been calibrated primarily for urban environments, but their accuracy in the rural domain remains largely unexplored. This study systematically validates global gridded population datasets in rural areas, based on reported human resettlement from 307 large dam construction projects in 35 countries. We find large discrepancies between the examined datasets, and, without exception, significant negative biases of −53%, −65%, −67%, −68%, and −84% for WorldPop, GWP, GRUMP, LandScan, and GHS-POP, respectively. This implies that rural population is, even in the most accurate dataset, underestimated by half compared to reported figures. To ensure equitable access to services and resources for rural communities, past and future applications of the datasets must undergo a critical discussion in light of the identified biases. Improvements in the datasets’ accuracies in rural areas can be attained through strengthened population censuses, alternative population counts, and a more balanced calibration of population models.

Smart IoT-driven precision agriculture: Land mapping, crop prediction, and irrigation system

As the world population is increasing day by day, so is the need for more advanced automated precision agriculture to meet the increasing demands for food while decreasing labor work and saving water for crops. Recently, there have been many studies done in this field, but very few discuss implementing smart technologies to present a combined sustainable farming system. In this article, we present a complete integrated design of a smart IoT-based suitable agricultural land and crop selection, along with an irrigation system using agricultural mapping, machine learning, and fuzzy logic for precision agriculture. Multi-spectral band images from Landsat-8 satellite images of a chosen land are employed from USGS Earth Resources Observation and Science (EROS) Center for extracting indices that are used for agricultural analysis, determining the vegetation index, water index, and salinity index of that land using K-means. Furthermore, crop yield is predicted using Linear Regression and Random Forest, achieving accuracies of 93.49% and 95.87%, respectively, while using RMSE (Root Mean Squared Error) as the loss function. The LSTM model is used for healthy vegetation area forecasting highlighting the changes of the vegetation area over time. Such analysis helps to decide whether that land is suitable for farming or not. Multiple soil-parameter measuring sensors are used to identify suitable crop and fertilizer requirements for that land using IoT and machine learning. The ML model-based crop prediction showed 97.35% accuracy utilizing random forest algorithm. Finally, a fuzzy logic-based solar-powered irrigation system is used to monitor the water requirements of those crops and irrigate them according to their needs. The experimental results demonstrated that fuzzy logic has faster calibration rate of 66.23% and helps to save around 61% water in comparison to average logic algorithm. The implementation of a fuzzy logic algorithm significantly optimized water usage compared to traditional manual irrigation methods. These findings highlight the effectiveness of advanced computational techniques in enhancing agricultural practices and resource management.

Predictors of optimal angiographic lesion outcomes in drug-coated balloon treatment for de novo coronary artery disease

<i>N</i> 6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins

N 6-methyladnosine (m 6 A) modification is present in both positive- and negative-strand RNA of influenza A virus (IAV) and affects the replication and pathogenicity of IAV. However, little is known about the regulatory mechanism of m 6 A in IAV RNA. In the present study, we identified the m 6 A methylation of the viral RNA of different IAV subtypes and confirmed that m 6 A modification promotes the polymerase activity and replication of IAV. By mutating m 6 A motifs on the multiple viral RNAs (vRNAs) of IAV, we revealed that m 6 A deficiency in vRNA suppresses the expression of viral genes and the replication of the virus in vitro. In addition, m 6 A deficiency in vRNA reduced the pathogenicity of IAV in a mouse model. Mechanistically, m 6 A deficiency in vRNA suppresses the assembly of the viral ribonucleoprotein (vRNP) complex by impairing the interaction between vRNA and vRNP proteins in an m 6 A methyltransferase-dependent manner, but not the m 6 A reader proteins. Together, our findings reveal an important role for m 6 A on viral RNAs in facilitating the activity of the polymerase complex and the replication and pathogenicity of IAV, which provides insights for the development of novel anti-influenza strategies.

The stomatin-like protein StlP organizes membrane microdomains to govern polar growth in filamentous actinobacteria under hyperosmotic stress

Sarcopenic obesity in predialysis chronic kidney disease: Muscle strength is a predictor of mortality and disease progression in a six-year prospective cohort

Introduction Sarcopenic obesity (SO) is a poorly defined physiological condition that is associated with increased morbimortality in the general population. The prevalence of SO has increased, making it an important public health issue; however, its effects when associated with other chronic conditions are still unclear. Therefore, it is necessary to comprehend the potential outcomes in chronic kidney disease (CKD) patients. Objective To assess the associations of predialysis CKD patients with SO and its components with death and disease progression to renal replacement therapy (RRT). Methods Prospective six-year cohort with 100 patients with predialysis CKD (stages one through five). Participants were older than 18 years and signed an informed consent form. The data were collected in an outpatient clinic specializing in predialysis care, and demographic, clinical, laboratory and inflammatory variable data were collected. A descriptive analysis was performed, and the SO and non-SO groups were compared with Student’s t test, Mann‒Whitney U test and Cox regression, taking into consideration all relevant confounding variables. Body composition variables utilized to diagnose SO were separately analyzed along with the outcomes. Results Sixteen percent of our sample were diagnosed with SO, but this was not associated with death or RRT, while lower BMI values were negatively associated with these outcomes. However, in an isolated analysis, handgrip strength was correlated with both RRT (p = 0.029) and death (p = 0.003). We recommend that health professionals pay greater attention to muscle strength, striving for earlier assessment, in an effort to better counsel patients and implement actions to increase or preserve strength through nonpharmacological treatment, such as resistance training.

Influence of dietary protein levels on nano-encapsulated Yucca schidigera extract and its effects on in vitro ruminal greenhouse gas production and fermentation dynamics

Abstract The influence of nano-encapsulated Yucca schidigera extract (YSE) on total gas (GP), ruminal methane (CH4), carbon monoxide (CO), hydrogen sulphide (H2S) production, and fermentation activities of diets based on two different protein levels were investigated. A completely randomized experimental design with a factorial arrangement (2 × 4 × 4) with three replications was used. Factor 1 was the dietary protein levels (14%and 18%), factor 2 was the types of extracts used (TE; negative control (without extract), positive control (empty chitosan nano-capsules), Y. schidigera extract nano-capsules, and crude Y. schidigera extract), and factor 3 the doses of each type of extract (ED; 0-, 0.25-, 0.5-, and 1.0- mL extract/g DM). Nano-chitosan reduced the GP production with a higher protein level by 24.9% after 48 h while the crude extract elevated it. At both crude protein levels, the interaction of crude extract at an ED of 0.25 mL extract/g DM generated a higher volume of CH4 at 6 h (p = 0.001 and 0.001 respectively) compared to the volume generated by the negative control. The 0.25 mL extract/g DM extract for both the crude extract and nano-extract elicited higher and lower CO production at 6 h (p &lt; 0.0001), respectively. Nano-chitosan at 0.25 mL extract/g DM resulted in less H2S produced at 6 h than when crude extract was used at the same dose and a higher protein level (p = 0.027). The ED did not significantly affect any of the parameters under consideration as used under lower protein levels. However, TE affected pH and dry matter degradability (p &lt; 0.0001) while the interaction of both TE and ED impacted both CH4:SCFA and CH4:ME (p = 0.045) with higher and lower values obtained for nano-chitosan and the negative control, respectively. In conclusion, nano-chitosan at a higher protein level proved its antimicrobial property, and although the production of CO increased at 14% protein, in vitro fermentation indicated its ability to minimize the production of GP, methane and hydrogen sulphide in the rumen, and to boost the degradability of DM and methane conversion efficiency.