Search Results (589)

Methamphetamine (Meth), a psychostimulant drug of the amphetamine type, is widely abused and highly neurotoxic. Meth exposure leads to neuronal necroptosis, and the mitochondrial dysfunction may be involved. However, the underlying mechanisms remain poorly understood. Here, we found that Meth significantly elicited the formation of the RIPK1–RIPK3–MLKL necrosome complex. Intriguingly, the activated MLKL (p-MLKL) translocated to the mitochondrial membrane and displayed pore-forming activity, manifesting as the penetration of MLKL in the cell membranes of the mitochondria, which caused decreased mitochondrial membrane potential, ATP generation, and mitochondrial DNA (mtDNA) and increased mitochondrial ROS (mtROS) generation, which finalized neuronal necroptosis. Notably, MLKL activation and translocation seem to depend on the RIPK1–RIPK3 axis since these adverse effects can be substantially ameliorated by disruption of the necrosome complex formation by the necroptotic inhibitor 1 (Nec-1), which also markedly impeded the MLKL mitochondrial membrane translocation. Finally, to delineate the effects of pore formation-associated ROS generation, specific blockage of mtROS retarded the Meth-induced neuronal necroptosis. In conclusion, our study reveals for the first time that MLKL mitochondrial membrane translocation may be involved in Meth-induced neuronal necroptosis. Therefore, impeding MLKL translocation might provide a novel therapeutic strategy for Meth-induced neurotoxicity. Full article

Before colonization, Indigenous child protection looked like an interdependent community. Indigenous knowledges and relational actions kept all within its fold safe and well. Colonial dispossession of land, degradation of subsistence rights, boarding schools, ongoing child removal, capitalism, and systems of oppression attempted to disconnect Indigenous peoples from their language, lands, ceremonial practices, stories, dances, songs, family, community, and themselves. However, Indigenous communities have held on, persevered, and have begun to turn the tide of intergenerational trauma through the revival of Indigenous wellness and self-determination. We believe local-based Indigenous relational knowledges can end colonial harm and promote wellbeing for all families and children. Our work builds off an Indigenous Connectedness Framework that recognizes the importance of the interrelated wellbeing of a person, family, community, ancestors/future generations, and the Earth. This framework was adapted based on community feedback to better fit the Nome Eskimo Community (NEC) and Bering Strait regional context. This paper shares results of community focus groups that led to the creation of a NEC Piaġiq (wellness) Framework, and shares intentions for pilot implementation of a wellness curriculum and pilot intervention. We will offer insights and lessons learned. We believe self-determined Indigenous wellbeing efforts can lead to improved outcomes for our sacred children and families for generations to come. Full article

Global warming impacts agricultural production and food security, particularly in high-latitude regions with high temperature sensitivity. As a major grain-producing area in China and one of the fastest-warming regions globally, Northeast China (NEC) has received considerable research attention. However, the existing literature lacks sufficient exploration of the spatiotemporal heterogeneity in climate change impacts. Based on data on rice, corn, and soybean yields, as well as temperature, rainfall, and sunshine duration in NEC from 1993 to 2022, this study employs Sen’s slope estimation, the Mann–Kendall (MK) test, spatial autocorrelation analysis, and the Geographically and Temporally Weighted Regression (GTWR) model to analyze the spatiotemporal evolution of grain yields and their responses to climate change. The results show that ① 1993–2022 witnessed an overall rise in grain yields per unit area in NEC, with Liaoning growing fastest. Rice yields increased regionally; corn yields rose in Liaoning and Jilin, while soybean yields increased only in Liaoning. During the growing season, rainfall trended upward with fluctuations, temperatures rose steadily, and sunshine duration declined in Heilongjiang. ② Except for corn and soybeans in the early period, other crops exhibited significant yield spatial agglomeration. High–high agglomeration areas first expanded, then shrank, eventually shifting northward to the region of Jilin Province. ③ Climatic factors show marked spatiotemporal heterogeneity in impacts: positive effect areas of rainfall and temperature expanded northward; sunshine duration’s influence weakened, but its negative effect areas spread. ④ Differences in crop responses are closely linked to their physiological characteristics, regional climate evolution, and agricultural adaptation measures. This study provides a scientific basis for formulating region-specific agricultural adaptation strategies to address climate change in NEC. Full article

Background: Transcription factors have been linked to changes in various physiological processes, such as attractive and rewarding phenotypes during plant–pollinator interactions. In the genus Petunia, most species are pollinated by bees, but hawkmoth- and bird pollination are also observed. Here, we aimed to test the hypothesis that species with the same pollination syndrome evolved through convergence, while differences in pollinators indicate divergence. We selected six genes (MYB-FL, DFR, EOBII, ODO1, BPBT, and NEC1) involved in establishing pollination syndromes to explore the potential role of cis-regulatory elements in shifts among pollination syndromes, attracting and rewarding pollinators. Methods: We retrieved the genomic sequences of genes from the genomes of four Petunia species, which exhibit distinct pollination syndromes. We analyzed the cis-regulatory elements, focusing on the structure and composition of motifs, and inferred the functions of these transcription factors using Gene Ontology analysis. Results: All sequences were highly conserved among species, with variations in promoter motif structure and TF binding sites. The evolutionary relationships among the genes closely reflected the species’ phylogeny. Likewise, regulatory elements and gene structure mostly followed the species’ evolutionary history. However, different pollination syndromes are present, and there is an unexpected lack of convergence between the two bee-pollinated species. Conclusions: Our findings showed that the most recent common ancestor of these species better predicts relationships among gene regulatory elements than does the pollination syndrome. To fully understand the evolution of pollination syndromes in Petunia, additional studies are needed to analyze entire pathways and compare genomes and transcriptomes. Full article

The rainy season characteristics are directly modulated by atmospheric circulation and moisture transport dynamics. Focusing on the characteristics of the rainy season onset date (RSOD), this study aims to advance the understanding and prediction of climate change impacts on agricultural production and disaster mitigation strategies. Based on rainfall data from 66 meteorological stations in northeast China (NEC) from 1961 to 2020, this study determined the patterns of the RSOD in the region and established its mechanistic linkages with atmospheric circulation and water vapor transport mechanisms. This study identifies a climatic regime shift around 2000, with the RSOD transitioning from low to high interannual variability in NEC. Further analysis reveals a strong correlation between the RSOD and atmospheric circulation characteristics: cyclonic vorticity amplifies before the RSOD and dissipates afterward. Innovatively, this study reveals a significant transition in the water vapor transport paths during the early rainy season in NEC around 2000, shifting from eastern Mongolia–Sea of Japan to the northwestern Pacific region. Moreover, the advance or delay of the RSOD directly influences the water vapor transport intensity—an early (delayed) RSOD is associated with enhanced (weakened) water vapor transport. These findings provide a new perspective for predicting the RSOD in the context of climate change while providing critical theoretical underpinnings for optimizing agricultural strategies and enhancing disaster prevention protocols. Full article

Background/Objectives: The 2019 WHO classification redefined high-grade gastrointestinal neuroendocrine neoplasms (GI NENs), encompassing not only poorly differentiated neuroendocrine carcinomas (NECs), but also well-differentiated grade 3 neuroendocrine tumors (NETs G3). Since both subtypes share a Ki-67 index > 20%, distinguishing them based solely on morphology is challenging. Prior studies have shown TP53 alterations in NECs but not in NETs. This study aimed to evaluate clinico-morphological parameters and the immunohistochemical (IHC) expression of p53 in high-grade GI NENs to identify relevant correlations. Methods: Tumors were stratified by Ki-67 index into two groups: >20–50% and >50%. p53 IHC expression was assessed as “wild-type” (1–20% positive tumor cells) or “non-wild-type” (absence or >20% positivity). Correlations were analyzed between Ki-67, p53 status, and various pathological features. Results: Significant correlations were found between the Ki-67 index and maximum tumor size, pT stage, lymphovascular invasion, perineural infiltration, and diagnostic classification. Similarly, p53 immunohistochemical status was significantly associated with lymphovascular invasion, lymph node metastasis, and tumor classification (NET G3 versus NEC, including NEC components of MiNENs). Conclusions: The findings support the value of Ki-67 and p53 as complementary biomarkers in the pathological evaluation of high-grade GI NENs. Their significant associations with key morphological parameters support their utility in differentiating NETs G3 from NECs, particularly in cases showing overlapping histological features. The immunohistochemical profile of p53 may serve as a useful diagnostic adjunct in routine practice. Full article

Background and Objectives: Neonatal respiratory distress syndrome (NRDS), resulting from a deficiency of pulmonary surfactant (PS), can cause alveoli to collapse. Glucocorticoids reduce inflammation and are effective in reducing pulmonary swelling. This study aims to assess the effectiveness of the combination of PS and budesonide in the management of NRDS. Materials and Methods: Publications between 21 May and 24 November were screened through PubMed, Cochrane and Embase. Data analysis was performed on RevMan 5.3 software. Subgroup analysis was performed to evaluate the routes of administrations. Results: The use of budesonide along with pulmonary surfactant for treating NRDS revealed the following results: (1) a reduced duration of invasive mechanical ventilation (standardized mean difference (SMD) = −1.06, 95% confidence interval (CI) = −1.55 to −0.56, p < 0.0001); (2) reduced rate of bronchopulmonary dysplasia (BPD) occurrence (relative risk (RR) = 0.72, 95% CI = 0.60 to 0.86, p = 0.0003); (3) reduced duration for hospital admittance (SMD = −0.38, 95% CI = −0.64 to −0.11, p = 0.005). The occurrence of complications, i.e., sepsis, pneumothorax, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), rate of mortality, hyperglycemia and intraventricular hemorrhage (IVH), was not significantly different among the intervention and comparison group except for patent ductus arteriosus (PDA) and pulmonary hemorrhage, with their incidence being higher in the control group (p = 0.002 and p = 0.05, respectively). Conclusions: The combination of pulmonary surfactant and budesonide decreases the occurrence of BPD, duration of mechanical ventilation, length of hospital stay and risk of pulmonary hemorrhage and PDA. It does not increase the risk of complications and death and is clinically safe. Full article

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease and a major cause of morbidity and mortality among preterm infants. Traditional diagnostic methods such as abdominal radiography have limited sensitivity in early disease stages, prompting interest in bowel ultrasound (BUS) as a complementary imaging modality. Objective: This scoping review aims to synthesize existing literature on the role of ultra sound in the early detection, diagnosis, and management of NEC, with emphasis on its diagnostic performance, integration into clinical care, and technological innovations. Methods: Following PRISMA-ScR guidelines, a systematic search was conducted across PubMed, Embase, Cochrane Library, and Google Scholar for studies published between January 2000 and December 2025. Inclusion criteria encompassed original research, reviews, and clinical studies evaluating the use of bowel, intestinal, or Doppler ultrasound in neonates with suspected or confirmed NEC. Data were extracted, categorized by study design, population characteristics, ultrasound features, and diagnostic outcomes, and qualitatively synthesized. Results: A total of 101 studies were included. BUS demonstrated superior sensitivity over radiography in detecting early features of NEC, including bowel wall thickening, portal venous gas, and altered peristalsis. Doppler ultrasound, both antenatal and postnatal, was effective in identifying perfusion deficits predictive of NEC onset. Neonatologist-performed ultrasound (NEOBUS) showed high interobserver agreement when standardized protocols were used. Emerging tools such as ultra-high-frequency ultrasound (UHFUS) and artificial intelligence (AI)-enhanced analysis hold potential to improve diagnostic precision. Point-of-care ultrasound (POCUS) appears feasible in resource-limited settings, though implementation barriers remain. Conclusions: Bowel ultrasound is a valuable adjunct to conventional imaging in NEC diagnosis. Standardized protocols, validation of advanced technologies, and out come-based studies are essential to guide its broader clinical adoption. Full article

Purpose: Neuroendocrine carcinomas (NECs) are aggressive tumors treated with cisplatin-based chemotherapy, though responses vary. As DNA damage response (DDR) pathways influence cisplatin sensitivity, this single-center retrospective study evaluates the efficacy of first-line cisplatin in recurrent or metastatic NEC based on DDR mutation status. Materials and Methods: This study analyzed patients with grade 3 recurrent or metastatic NEC treated with first-line etoposide plus cisplatin at Samsung Medical Center between January 2019 and September 2023. All patients underwent next-generation sequencing to determine DDR mutation status, defined by pathogenic alterations in major DNA repair pathways. Clinical outcomes were assessed per RECIST v1.1. Survival analyses were conducted using Kaplan–Meier methods and Cox regression models, with significance set at p ≤ 0.05. Results: A total of 40 patients with NEC were included in this study. There were 16 patients with DDR wild-type (WT) and 24 patients with DDR mutant type (MT). The most common primary tumor sites were the pancreas (25.0%), stomach (20.0%), and gallbladder/duct (12.5%). Among 40 patients, those with DDR mutations (n = 24) showed significantly higher objective response (58.3% vs. 12.5%) and disease control rates (91.7% vs. 50.0%) compared to patients with DDR WT (n = 16). The median progression-free survival (PFS) showed the favorable trend in the DDR mutant group (8.0 vs. 4.3 months; p = 0.15), with similar trends observed across homologous recombination repair (HRR), Fanconi anemia (FA), and mismatch repair (MMR) subgroups. Conclusions: This study revealed that patients with DDR mutations had significantly higher response to first-line etoposide–cisplatin, suggesting DDR mutation status as a potential predictive marker to guide treatment and improve outcomes in recurrent or metastatic NEC. Full article

Existing methods for detecting cotton boll diseases frequently exhibit high rates of both false negatives and false positives under complex field conditions (e.g., lighting variations, shadows, and occlusions) and struggle to achieve real-time performance on edge devices. To address these limitations, this study proposes an enhanced YOLOv11n model (YOLOv11n-ECS) for improved detection accuracy. A dataset of cotton boll diseases under different lighting conditions and shooting angles in the field was constructed. To mitigate false negatives and false positives encountered by the original YOLOv11n model during detection, the EMA (efficient multi-scale attention) mechanism is introduced to enhance the weights of important features and suppress irrelevant regions, thereby improving the detection accuracy of the model. Partial Convolution (PConv) is incorporated into the C3k2 module to reduce computational redundancy and lower the model’s computational complexity while maintaining high recognition accuracy. Furthermore, to enhance the localization accuracy of diseased bolls, the original CIoU loss is replaced with Shape-IoU. The improved model achieves floating point operations (FLOPs), parameter count, and model size at 96.8%, 96%, and 96.3% of the original YOLOv11n model, respectively. The improved model achieves an mAP@0.5 of 85.6% and an mAP@0.5:0.95 of 62.7%, representing improvements of 2.3 and 1.9 percentage points, respectively, over the baseline YOLOv11n model. Compared with CenterNet, Faster R-CNN, YOLOv8-LSW, MSA-DETR, DMN-YOLO, and YOLOv11n, the improved model shows mAP@0.5 improvements of 25.7, 21.2, 5.5, 4.0, 4.5, and 2.3 percentage points, respectively, along with corresponding mAP@0.5:0.95 increases of 25.6, 25.3, 8.3, 2.8, 1.8, and 1.9 percentage points. Deployed on a Jetson TX2 development board, the model achieves a recognition speed of 56 frames per second (FPS) and an mAP of 84.2%, confirming its suitability for real-time detection. Furthermore, the improved model effectively reduces instances of both false negatives and false positives for diseased cotton bolls while yielding higher detection confidence, thus providing robust technical support for intelligent cotton boll disease detection. Full article

Background and Clinical Significance: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2. Cardiac rhabdomyoma is a common prenatal finding and can be associated with severe complications, including pericardial effusion. We administered prenatal sirolimus to mitigate pericardial effusion, which led to postnatal complications. Case Presentation: A 28-year-old pregnant woman with no significant family history underwent routine fetal ultrasound at 28.1 weeks of gestation, which identified a large right ventricular mass consistent with rhabdomyoma. Further fetal brain MRI revealed cortical-subcortical tubers and subependymal nodules, leading to a clinical diagnosis of TSC. At 30.4 weeks, oral sirolimus (3 mg/day) was started due to the significant pericardial effusion. The effusion remained after treatment, requiring pericardiocentesis at 33.6 weeks. The sirolimus dosage was raised to 6 mg/day at 35.6 weeks, reaching a plasma level of 3.76 ng/mL, but there was no discernible improvement because of the continued fluid accumulation. The mother did not experience any adverse side effects from the procedure. Genetic testing confirmed a pathogenic variant in TSC2 (c.1372C>T). After birth, the neonate received a single dose of sirolimus but subsequently developed necrotizing enterocolitis (NEC), highlighting the potential adverse effects and the need for cautious consideration of treatment options. Conclusions: This case illustrates the complexities of managing prenatal tuberous sclerosis complex (TSC). While sirolimus has been explored for fetal cardiac rhabdomyoma and associated complications, its effectiveness in resolving pericardial effusion remains uncertain. Additionally, the development of NEC postnatally raises concerns about the safety of mTOR inhibitors in this context. Further studies are necessary to assess the risks and benefits of this approach in fetal therapy. Full article

Research in the field of stem cells in necrotizing enterocolitis has primarily focused on the curative role of specific cells—mostly bone marrow and amniotic fluid stem cells. The impact of stem cells on reducing inflammatory cytokine levels in the necrotizing enterocolitis (NEC) model has been studied in accordance with the effects they pose on histopathology. Taking into consideration the possible paracrine mechanism of action of stem cells, our group hypothesized that lowering the initial levels of proinflammatory cytokines may be one of the mechanisms affecting the clinical outcome. A self-modified rat NEC model was used to show the effect of intraperitoneal administration of adipose derived stem cells on the initial levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alfa) in comparison with the interleukin levels in NEC animals and control animals without adipose–derived stem cells (ADSCs) injection. We showed a statistically significant difference in the levels of interleukins when comparing an ADSC injected group and an NEC group. This suggests that one of the mechanisms in which stem cells impact the clinical outcomes in NEC may be by alleviating the initial levels of proinflammatory cytokines. Full article

Background: Vitamin D is increasingly recognized not only for its role in skeletal development but also for its immunomodulatory and gastrointestinal effects. Maternal and neonatal vitamin D deficiency (VDD) has been associated with alterations in gut microbiota, impaired intestinal barrier integrity, and increased susceptibility to inflammatory conditions in neonates. However, the exact mechanisms linking perinatal vitamin D status to neonatal gastrointestinal morbidity remain incompletely understood. Methods: This review synthesizes current evidence (2015–2024) from clinical studies, animal models, and mechanistic research on the impact of VDD during pregnancy and the neonatal period on gastrointestinal health. Databases such as PubMed, Scopus, and Web of Science were systematically searched using keywords, including “vitamin D”, “neonate”, “gut microbiome”, “intestinal barrier”, and “necrotizing enterocolitis”. Results: Emerging data suggest that VDD in utero and postnatally correlates with dysbiosis, increased intestinal permeability, and elevated inflammatory responses in neonates. Notably, low 25(OH)D levels in mothers and newborns have been linked with a higher incidence of necrotizing enterocolitis (NEC), delayed gut maturation, and altered mucosal immunity. Vitamin D appears to modulate the expression of tight junction proteins, regulate antimicrobial peptides, and maintain microbial diversity through the vitamin D receptor (VDR). Conclusions: Understanding the gastrointestinal implications of early-life VDD opens a potential window for preventive strategies in neonatal care. Timely maternal supplementation and targeted neonatal interventions may mitigate gut-related morbidities and improve early-life health outcomes. Further longitudinal and interventional studies are warranted to clarify causality and optimal intervention timing. Full article

Background/Objective: We sought to address ongoing gaps in understanding the relationship between first-week percent maximal weight loss (MWL) and average first-week total fluid intake (TFI), enteral intake, and parenteral intake among premature newborns with adverse in-hospital outcomes born in low- and middle-income countries (LMICs). Methods: We evaluated newborns born <34 weeks gestation or <1500 g who survived at least 7 days at the St. Paul’s Hospital Millennium Medical College (SPHMMC) neonatal intensive care unit in Ethiopia. We performed univariate and multivariate regression models analyzing the first-week MWL, average TFI, parenteral, and enteral intake and their relationships with adverse in-hospital outcomes. Results: Among N = 490 moderately and very preterm newborns, multivariate regression models demonstrated that >13% MWL was associated with significantly increased odds of suspected necrotizing enterocolitis (NEC), culture-positive sepsis, retinopathy of prematurity (ROP), and a longer length of stay (LOS). An average enteral intake of >60 mL/kg/day was significantly associated with reduced odds of all-cause mortality, suspected NEC, culture-positive sepsis, ROP, and a shorter LOS, whereas an average parenteral intake of >60 mL/kg/day was associated with increased odds of in-hospital mortality, culture-positive sepsis, ROP, and a longer LOS. Conclusions: In moderately and very preterm neonates in an LMIC setting, >13% MWL is associated with adverse health outcomes. Increasing the average parenteral intake over the first week after birth among moderately and very preterm neonates is significantly associated with adverse in-hospital outcomes whereas increasing the average enteral intake is associated with improved outcomes. Full article

Necrotizing enterocolitis (NEC) is a serious GI disease of premature infants, marked by intestinal inflammation and necrosis. Recent research has highlighted the potential role of oxidative stress (OS) and ferroptosis in its pathogenesis. We previously identified a deficiency in Glutathione Peroxidase (GPX) 4 and lipid radical accumulation, prompting further investigation. Human intestinal tissue from a prior study was processed, and it underwent RNA and protein isolation, Immunohistochemistry, Immunofluorescence, and acid digestion for iron and selenium analysis via Inductively coupled mass spectrometry (ICP-MS). NEC was induced in human enteroids using lipopolysaccharide (LPS) and hypoxia, followed by RNA/protein isolation and lipidomic analysis. Humans with NEC had significantly higher levels of GPX2 (p = 0.0003). Enteroids exposed to NEC conditions had significantly decreased amounts of NADPH compared to initial controls (p = 0.0091), but similar levels compared to post-24 h controls (p = 0.3520). Patients with NEC had significantly higher levels of iron compared to controls via the bathophenanthroline-based assay (p = 0.0102) and with ICP-MS (p = 0.0148). There were several significant alterations in lipid distribution between NEC and control patients, but not in the fatty acid profiles. Our study suggests that oxidative stress, iron dysregulation, and altered lipid metabolism contribute to NEC pathogenesis. Full article