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Background: Extremely preterm infants (EPIs) are at high-risk of white matter injury (WMI), leading to long-term neurodevelopmental impairments. We aimed to develop nomograms for WMI., Methods: The study included patients from 31 provinces, spanning ten years. 6074 patients before 2018 were randomly divided into a training and internal validation group (7:3). The external validation group comprised 1492 patients from 2019. Predictors were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression and nomograms were constructed. Models' performance was evaluated using receiver operating characteristic (ROC), decision curve analysis (DCA) and calibration curves., Results: The prenatal nomogram included multiple gestation, premature rupture of membranes (PROM), chorioamnionitis, prenatal glucocorticoids, hypertensive disorder complicating pregnancy (HDCP) and Apgar 1 min, with area under the curve (AUC) of 0.805, 0.816 and 0.799 in the training, internal validation and external validation group, respectively. Days of mechanical ventilation (MV), shock, patent ductus arteriosus (PDA) ligation, intraventricular hemorrhage (IVH) grade III-IV, septicemia, hypothermia and necrotizing enterocolitis (NEC) stage II-III were identified as postpartum predictors. The AUCs were 0.791, 0.813 and 0.823 in the three groups, respectively. DCA and calibration curves showed good clinical utility and consistency., Conclusion: The two nomograms provide clinicians with precise and efficient tools for prediction of WMI., Impact: This study is a large-sample multicenter study, spanning 10 years. The two nomograms are convenient for identifying high-risk infants early, allowing for reducing poor prognosis., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Land-use change is the main driver of carbon storage change in terrestrial ecosystems. Currently, domestic and international studies mainly focus on the impact of carbon storage changes on climate, while studies on the impact of land-use changes on carbon storage in complex terrestrial ecosystems are few. The Jialing River Basin (JRB), with a total area of ~ 160,000 km 2 , diverse topography, and elevation differences exceeding 5 km, is an ideal case for understanding the complex interactions between land-use change and carbon storage dynamics. Taking the JRB as our study area, we analyzed land-use changes from 2000 to 2020. Subsequently, we simulated land-use patterns for business-as-usual (BAU), cropland protection (CP), and ecological priority (EP) scenarios in 2035 using the PLUS model. Additionally, we assessed carbon storage using the InVEST model. This approach helps us to accurately understand the carbon change processes in regional complex terrestrial ecosystems and to formulate scientifically informed land-use policies. The results revealed the following: (1) Cropland was the most dominant land-use type (LUT) in the region, and it was the only LUT experiencing net reduction, with 92.22% of newly designated construction land originating from cropland. (2) In the JRB, total carbon storage steadily decreased after 2005, with significant spatial heterogeneity. This pattern was marked by higher carbon storage levels in the north and lower levels in the south, with a distinct demarcation line. The conversion of cropland to construction land is the main factor driving the reduction in carbon storage. (3) Compared with the BAU and EP scenarios, the CP scenario demonstrated a smaller reduction in cropland area, a smaller addition to construction land area, and a lower depletion in the JRB total carbon storage from 2020 to 2035. This study demonstrates the effectiveness of the PLUS and InVEST models in analyzing complex ecosystems and offers data support for quantitatively assessing regional ecosystem services. Strict adherence to the cropland replenishment task mandated by the Chinese government is crucial to increase cropland areas in the JRB and consequently enhance the carbon sequestration capacity of its ecosystem. Such efforts are vital for ensuring the food and ecological security of the JRB, particularly in the pursuit of the "dual-carbon" objective., (© 2024. The Author(s).)

Terrestrial planets and their moons have impact craters, contributing significantly to the complex geomorphology of planetary bodies in our Solar System. Traditional crater identification methods struggle with accuracy because of the diverse forms, locations, and sizes of the craters. Our main aim is to locate lunar craters using images from Terrain Mapping Camera-2 (TMC-2) onboard the Chandrayaan-II satellite. The crater-based U-Net model, a convolutional neural network frequently used in image segmentation tasks, is a deep learning method presented in this study. The task of crater detection was accomplished with the proposed model in two steps: initially, it was trained using Resnet18 as the backbone and U-Net based on Image Net as weights. Secondly, TMC-2 images from Chandrayaan-2 were used to detect craters based on the trained model. The model proposed in this study comprises a neural network, feature extractor, and optimization technique for lunar crater detection. The model achieves 80.95% accuracy using unannotated data and precision and recall are much better with annotated data with an accuracy of 86.91% in object detection with TMC-2 ortho images. 2000 images have been considered for the present work as manual annotation is a time-consuming process and the inclusion of more images can enhance the performance score of the model proposed., (© 2024. The Author(s).)

Naturally occurring human infections by zoonotic Plasmodium species have been documented for P. knowlesi, P. cynomolgi, P. simium, P. simiovale, P. inui, P. inui-like, P. coatneyi, and P. brasilianum. Accurate detection of each species is complicated by their morphological similarities with other Plasmodium species. PCR-based assays offer a solution but require prior knowledge of adequate genomic targets that can distinguish the species. While whole genomes have been published for P. knowlesi, P. cynomolgi, P. simium, and P. inui, no complete genome for P. brasilianum has been available. Previously, we reported a draft genome for P. brasilianum, and here we report the completed genome for P. brasilianum. The genome is 31.4 Mb in size and comprises 14 chromosomes, the mitochondrial genome, the apicoplast genome, and 29 unplaced contigs. The chromosomes consist of 98.4% nucleotide sites that are identical to the P. malariae genome, the closest evolutionarily related species hypothesized to be the same species as P. brasilianum, with 41,125 non-synonymous SNPs (0.0722% of genome) identified between the two genomes. Furthermore, P. brasilianum had 4864 (82.1%) genes that share 80% or higher sequence similarity with 4970 (75.5%) P. malariae genes. This was demonstrated by the nearly identical genomic organization and multiple sequence alignments for the merozoite surface proteins msp3 and msp7. We observed a distinction in the repeat lengths of the circumsporozoite protein (CSP) gene sequences between P. brasilianum and P. malariae. Our results demonstrate a 97.3% pairwise identity between the P. brasilianum and the P. malariae genomes. These findings highlight the phylogenetic proximity of these two species, suggesting that P. malariae and P. brasilianum are strains of the same species, but this could not be fully evaluated with only a single genomic sequence for each species., (© 2022. The Author(s).)

The EMT (epithelial-to-mesenchymal-transition) subtype of gastric cancer (GC) is associated with poor treatment responses and unfavorable clinical outcomes. Despite the broad physiological roles of the micro-RNA (miR)-200 family, they largely serve to maintain the overall epithelial phenotype. However, during late-stage gastric tumorigenesis, members of the miR-200 family are markedly suppressed, resulting in the transition to the mesenchymal state and the acquisition of invasive properties. As such, the miR-200 family represents a robust molecular marker of EMT, and subsequently, disease severity and prognosis. Most reports have studied the effect of single miR-200 family member knockdown. Here, we employ a multiplex CRISPR/Cas9 system to generate a complete miR-200 family knockout (FKO) to investigate their collective and summative role in regulating key cellular processes during GC pathogenesis. Genetic deletion of all miR-200s in the human GC cell lines induced potent morphological alterations, G1/S cell cycle arrest, increased senescence-associated β-galactosidase (SA-β-Gal) activity, and aberrant metabolism, collectively resembling the senescent phenotype. Coupling RNA-seq data with publicly available datasets, we revealed a clear separation of senescent and non-senescent states amongst FKO cells and control cells, respectively. Further analysis identified key senescence-associated secretory phenotype (SASP) components in FKO cells and a positive feedback loop for maintenance of the senescent state controlled by activation of TGF-β and TNF-α pathways. Finally, we showed that miR-200 FKO associated senescence in cancer epithelial cells significantly recruited stromal cells in the tumor microenvironment. Our work has identified a new role of miR-200 family members which function as an integrated unit serving to link senescence with EMT, two major conserved biological processes., (© 2021. The Author(s).)

Previous studies have suggested excess GH/IGF1 secretion in patients with acromegaly is protective for periodontal health. Diabetes is prevalent comorbidity in patients of acromegaly and is associated with worsening of periodontal disease. The present study evaluates the periodontal health and cytokines status in treatment-naive active acromegaly patients with and without diabetes. Eleven patients, each of acromegaly with and without diabetes and 20 healthy controls were enrolled. Periodontal parameters were assessed. GCF and blood samples for IL-6, TGF-β1, and PDGF were obtained. Serum GH, IGF1, HbA1c, pituitary hormones and MRI sella were performed in patients with acromegaly. There was no significant difference in periodontal status of patients with acromegaly and healthy controls. However, a significant increase in serum IL-6 (p = 0.019) and TGF-β1 (p = 0.025) levels in patients with acromegaly was observed and all patients had concurrent hypogonadism. Nevertheless, the patients with acromegaly having diabetes had modestly higher CAL and PD and serum IL-6 levels (p = 0.051), but it could not exert adverse effects on periodontal health in presence of GH/IGF1 excess. GH/IGF1 excess did not exert a protective effect on periodontal status in acromegaly, possibly due to concurrent hypogonadism and opposing cytokines; however, it could mask the ill-effects of diabetes on periodontal health.

In light of the declining global malaria burden attained largely due to insecticides, a deeper understanding of the factors driving insecticide resistance is needed to mitigate its growing threat to malaria vector control programs. Following evidence of microbiota-mediated insecticide resistance in agricultural pests, we undertook a comparative study of the microbiota in mosquitoes of differing insecticide resistance status. The microbiota of wild-caught Anopheles albimanus, an important Latin American malaria vector, that were resistant (FEN_Res) or susceptible (FEN_Sus) to the organophosphate (OP) insecticide fenitrothion were characterized and compared using whole metagenome sequencing. Results showed differing composition of the microbiota and its functions between FEN_Res and FEN_Sus, with significant enrichment of OP-degrading bacteria and enzymes in FEN_Res compared to FEN_Sus. Lower bacterial diversity was observed in FEN_Res compared to FEN_Sus, suggesting the enrichment of bacterial taxa with a competitive advantage in response to insecticide selection pressure. We report and characterize for the first time whole metagenomes of An. albimanus, revealing associations between the microbiota and phenotypic resistance to the insecticide fenitrothion. This study lays the groundwork for further investigation of the role of the mosquito microbiota in insecticide resistance.

A real time monitoring of fouling in liquid chromatography has been presented. The versatility of the approach has been proven by successful implementation in three case studies with an error <1%. The first application demonstrates the monitoring of protein A ligand density and foulant concentration for assessing performance of protein A chromatography resin during purification of monoclonal antibodies. The observations have been supported from LC-MS/MS studies that were independently performed. The second application involves monitoring of foulant deposition during multimode cation exchange chromatography based purification of human serum albumin. Finally, in the third application, monitoring of foulants during multimodal hydrophobic interaction chromatography of recombinant human granulocyte colony stimulating factor is demonstrated. In all three cases, it is observed that the fluorescence intensity consistently increases with resin reuse as more foulants are deposited over time. The proposed approach can be readily used for real time monitoring of fouling and process control.

Premature ovarian insufficiency (POI) is a frequent long-term complication of classic galactosemia. The majority of women with this disorder develop POI, however rare spontaneous pregnancies have been reported. Here, we evaluate the effect of D-galactose and its metabolites, galactitol and galactose 1-phosphate, on oocyte quality as well as embryo development to elucidate the mechanism through which these compounds mediate oocyte deterioration. Metaphase II mouse oocytes (n = 240), with and without cumulus cells (CCs), were exposed for 4 hours to D-galactose (2 μM), galactitol (11 μM) and galactose 1-phosphate (0.1 mM), (corresponding to plasma concentrations in patients on galactose-restricted diet) and compared to controls. The treated oocytes showed decreased quality as a function of significant enhancement in production of reactive oxygen species (ROS) when compared to controls. The presence of CCs offered no protection, as elevated ROS was accompanied by increased apoptosis of CCs. Our results suggested that D-galactose and its metabolites disturbed the spindle structure and chromosomal alignment, which was associated with significant decline in oocyte cleavage and blastocyst development after in-vitro fertilization. The results provide insight into prevention and treatment strategies that may be used to extend the window of fertility in these patients.

Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

Faithful transmission of the genome requires that a protein complex called cohesin establishes and maintains the regulated linkage between replicated chromosomes before their segregation. Here we report the unforeseen participation of Caenorhabditis elegans TIM-1, a paralogue of the Drosophila clock protein TIMELESS, in the regulation of chromosome cohesion. Our biochemical experiments defined the C. elegans cohesin complex and revealed its physical association with TIM-1. Functional relevance of the interaction was demonstrated by aberrant mitotic chromosome behaviour, embryonic lethality and defective meiotic chromosome cohesion caused by the disruption of either TIM-1 or cohesin. TIM-1 depletion prevented the assembly of non-SMC (structural maintenance of chromosome) cohesin subunits onto meiotic chromosomes; however, unexpectedly, a partial cohesin complex composed of SMC components still loaded. Further disruption of cohesin activity in meiosis by the simultaneous depletion of TIM-1 and an SMC subunit decreased homologous chromosome pairing before synapsis, revealing a new role for cohesin in metazoans. On the basis of comparisons between TIMELESS homologues in worms, flies and mice, we propose that chromosome cohesion, rather than circadian clock regulation, is the ancient and conserved function for TIMELESS-like proteins.