Delayed sustained lung inflation for preterm neonates in neonatal intensive care unit: a randomized controlled trial.

INTRODUCTION: Sustained lung inflation (SLI) right after birth to decrease the use of mechanical ventilation of preterm infants is controversial because of potential harm. This randomized controlled trial was conducted to evaluate the effectiveness and safety of delayed SLI in neonatal intensive care unit (NICU). METHODS: Preterm neonates requiring continuous positive airway pressure after birth were eligible for enrollment. In the experimental group, SLI with 20 cm H2O for 15 s was conducted by experienced staff in the NICU between 30 min and 24 h after birth. RESULTS: A total of 45 neonates were enrolled into this study, including 24 in the experimental group and 21 in the control group. There was no significant difference in the birth condition between the experimental and control groups, including gestational age (p = 0.151), birth weight (p = 0.692), and Apgar score at 1 min (p = 0.410) and 5 min (p = 0.518). The results showed the duration of respiratory support was shorter in the experimental group than the control group (p = 0.044). In addition, there was no significant difference in the other outcomes, such as pneumothorax, patent ductus arteriosus, and bronchopulmonary dysplasia. CONCLUSION: Our findings indicate that sustained inflation conducted by experienced staff in the NICU is safe. The data suggest that SLI conducted by experienced staff in the NICU after stabilization could serve as an alternative management for preterm infants with respiratory distress. However, the reduction in use of respiratory support should be interpreted cautiously as a result of limited sample size. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000052797 (retrospectively registered).

Impact of Clinical Use of Probiotics on Preterm-Related Outcomes in Infants with Extremely Low Birth Weight.

Background: Preterm birth significantly contributes to mortality and morbidities, with recent studies linking these issues to gut microbiota imbalances. Probiotic supplementation shows promise in mitigating adverse outcomes in preterm infants, but optimal timing and guidelines remain unclear. This study assesses the benefits of probiotic supplementation for preterm infants without consistent guidelines. Methods: This retrospective study examined extremely low-birth-weight (ELBW) infants in neonatal intensive care units from 2017 to 2021. Mortality and preterm-related outcomes were compared between infants receiving probiotics and those not. Subgroup analyses based on probiotic initiation timing were conducted: early (≤14 days), late (>14 days), and non-probiotic groups. Results: The study included 330 ELBW infants: 206 received probiotics (60 early, 146 late), while 124 did not. Probiotic supplementation was associated with lower overall mortality (adjusted OR 0.22, 95% CI 0.09-0.48) and decreased mortality from necrotizing enterocolitis (NEC) or late-onset sepsis (LOS) (adjusted OR 0.12, 95% CI 0.03-0.45). Early probiotics reduced overall mortality, NEC/LOS-related mortality, and NEC/LOS-unrelated mortality. Late probiotics decreased overall mortality and NEC/LOS-related mortality. Early probiotic use also expedited full enteral feeding achievement. Conclusions: Probiotic supplementation reduces mortality and improves feeding tolerance in preterm infants. Establishing guidelines for probiotic use in this population is crucial.

Discovery and Optimization of Aryl Piperidinone Ureas as Selective Formyl Peptide Receptor 2 Agonists.

We report the discovery and optimization of aryl piperidinone urea formyl peptide receptor 2 (FPR2) agonists from a weakly active high-throughput screening (HTS) hit to potent and selective agonists with favorable efficacy in acute in vivo models. A basis for the selectivity for FPR2 over FPR1 is proposed based on docking molecules into recently reported FPR2 and FPR1 cryoEM structures. Compounds from the new scaffold reported in this study exhibited superior potency and selectivity and favorable ADME profiles. Furthermore, select compounds were evaluated in an acute rat lipopolysaccharide (LPS) inflammation model and demonstrated robust dose-dependent induction of IL10, a marker for inflammation resolution, providing a valuable proof of concept for this class of FPR2 agonists.

Expression of Iron Metabolism Genes Is Potentially Regulated by DOF Transcription Factors in Dendrocalamus latiflorus Leaves.

Transcription factors (TFs) are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of TFs with extensive roles in plant growth and development. Our previous research indicated that iron content varies among bamboo leaves of different colors. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism related (IMR) genes in bamboo and determined the TFs that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF TFs in D. latiflorus.

Disruption and Improvisation: Experiences of Loneliness for People With Chronic Illness.

Chronic illness can disrupt many aspects of life, including identity, social relationships, and anticipated life trajectories. Despite significant scholarship on chronic illness, we know less about the ways in which chronic illness impacts feelings of loneliness and how people with chronic illness deal with loneliness. Drawing on concepts of biographical disruption and liminality and data from walking and photo-elicitation interviews with 14 people, we aimed to explore how people with chronic illness experience loneliness in their everyday lives. Tracing how past and present illness experiences are implicated in the lived experience of loneliness and the strategies people use to manage loneliness, our findings illustrated that being caught in a liminal state where participants struggled to maintain and adapt to a new normality in life with chronic illness was a central thread woven throughout their experience of loneliness. Although participants drew on their personal agency and adopted strategies to account for, manage, and limit disruptions from chronic illness and loneliness, they found that their strategies were not completely effective or satisfactory. Chronic illness and loneliness continue to be largely considered as an individual's problem, limiting opportunities for people with chronic illness who experience loneliness to seek support and social connection. Our research highlighted that chronic illness and loneliness need to be acknowledged as both a personal and collective problem, with multi-level responses that involve individuals, communities, and society.

The impact of gut microbiota on morbidities in preterm infants.

The gut microbiota undergoes substantial development from birth, and its development in the initial years of life has a potentially lifelong effect on the health of the individual. However, various factors can disrupt the development of the gut microbiota, leading to a condition known as dysbiosis, particularly in preterm infants. Current studies involving adults have suggested that the gut microbiota not only influences the gut but also has multidimensional effects on remote organs; these pathways are often referred to as the gut-organ axis. Imbalance of the gut microbiota may lead to the development of multiple diseases. Recent studies have revealed that gut dysbiosis in preterm infants may cause several acute morbidities-such as necrotizing enterocolitis, late-onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity-and it may also influence long-term outcomes including neurodevelopment and somatic growth. This review mainly presents the existing evidence regarding the relationships between the gut microbiota and these morbidities in preterm infants and explores the role of the gut-organ axis in these morbidities. This paper thus offers insights into the future perspectives on microbiota interventions for promoting the health of preterm infants.

DHX9 SUMOylation is required for the suppression of R-loop-associated genome instability.

RNA helicase DHX9 is essential for genome stability by resolving aberrant R-loops. However, its regulatory mechanisms remain unclear. Here we show that SUMOylation at lysine 120 (K120) is crucial for DHX9 function. Preventing SUMOylation at K120 leads to R-loop dysregulation, increased DNA damage, and cell death. Cells expressing DHX9 K120R mutant which cannot be SUMOylated are more sensitive to genotoxic agents and this sensitivity is mitigated by RNase H overexpression. Unlike the mutant, wild-type DHX9 interacts with R-loop-associated proteins such as PARP1 and DDX21 via SUMO-interacting motifs. Fusion of SUMO2 to the DHX9 K120R mutant enhances its association with these proteins, reduces R-loop accumulation, and alleviates survival defects of DHX9 K120R. Our findings highlight the critical role of DHX9 SUMOylation in maintaining genome stability by regulating protein interactions necessary for R-loop balance.

CircATF6 inhibits hepatocellular carcinoma progression by suppressing calreticulin-mediated Wnt/ß-catenin signaling pathway.

Circular RNAs (circRNAs) are covalently closed, single-stranded RNAs that play critical roles in various biological processes and diseases, including cancers. However, the functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) need further clarification. Here, we identified and confirmed that circATF6 is downregulated in HCC tissues and negatively associated with the overall survival of HCC patients. Ectopic overexpression of circATF6 inhibits malignant phenotypes of HCC cells in vitro and in vivo, while knockdown of circATF6 had opposite effects. Mechanistically, we found that circATF6 bound to calreticulin (CALR) protein and acted as a scaffold to enhance the interaction of CALR with calpain2 (CAPN2), which promoted the degradation of CALR by its enzymatic activity. Moreover, we found that circATF6 inhibited HCC cells by suppressing CALR-mediated wnt/ß-catenin signaling pathway. Taken together, our findings suggest that circATF6 is a potential prognostic biomarker and therapeutic target for HCC.

Multi-objectives optimization on microwave-assisted-biological-based biogas upgrading and bio-succinic acid production.

This study represents the first investigation of bio-succinic acid (bio-SA) production with methane enrichment using carbon-dioxide-fixating bacteria in the co-culture of ragi tapai and macroalgae, Chaetomorpha. Microwave irradiation has also been introduced to enhance the biochemical processes as it could provide rapid and selective heating of substrates. In this research, microwave irradiation was applied on ragi tapai as a pre-treatment process. Factors such as microwave irradiation dose on ragi tapai, Chaetomorpha ratio in the co-culture, and pH value were studied. Optimal conditions were identified using Design-Expert software, resulting in optimal experimental biomethane and bio-SA production of 85.7 % and 0.65 g/L, respectively, at a microwave dose of 1.45 W/g, Chaetomorpha ratio of 0.9 and pH value of 7.8. The study provides valuable insights into microwave control for promoting simultaneous methane enrichment and bio-SA production, potentially reducing costs associated with CO2 capture and storage and biogas upgrading.

Evaluation of the Fetal Alcohol Spectrum Disorder Hub Australia website.

INTRODUCTION: To evaluate use and utility of the Fetal Alcohol Spectrum Disorder (FASD) Hub Australia website. METHODS: Online REDCap user survey incorporating the Website Evaluation Questionnaire, open ended questions, Google metrics data and an accessibility audit. RESULTS: Seventy-six participants: researchers (32%), health professionals (29%) and policymakers/advocates (16%) completed the survey. Most were from Australia (95%) and were likely or very likely to recommend the FASD Hub to colleagues (92%), friends (74%) and patients (72%). The mean Website Evaluation Questionnaire score was at least 3.45/5 for all dimensions (ease of use, hyperlinks, structure, relevance, comprehension, completeness, layout, search option); range 3.45 (search option) to 4.04 (relevance). Participants found the content trustworthy (92%) but wanted more information for, and to support, Aboriginal and Torres Strait Islander peoples, and improved search capacity. Google metrics identified 25,534 unique users over 6 months (82% new users); 83% aged 18-44 years, 72% female and 35% international. CONCLUSIONS: Users found the FASD Hub accessible, authoritative and useful and suggested improvements.

Four-Level Cervical Disc Arthroplasty.

BACKGROUND: Multilevel anterior cervical discectomy and fusion inevitably yields a higher chance of pseudarthrosis or require more reoperations than single-level procedures. Therefore, multilevel cervical disc arthroplasty (CDA) could be an alternative surgery for cervical spondylosis, as it (particularly 3- and 4-level CDA) could preserve more functional motility than single-level disc diseases. This study aimed to investigate the clinical and radiological outcomes of 4-level CDA, a relatively infrequently indicated surgery. METHODS: The medical records of consecutive patients who underwent 4-level CDA were retrospectively reviewed. These highly selected patients typically had multilevel disc herniations with mild spondylosis. The inclusion criteria were symptomatic cervical spondylotic myelopathy, radiculopathy, or both, that were medically refractory. The clinical outcomes were assessed. The radiographic outcomes, including global and individual segmental range of motion (ROM) at C3-7, and any complications were also analyzed. RESULTS: Data from a total of 20 patients (mean age: 56 ± 8 years) with an average follow-up of 34 ± 20 months were analyzed. All patients reported improved clinical outcomes compared with that of preoperation, and the ROMs at C3-7 were not only preserved but also trended toward an increase (35 ± 8 vs 37 ± 10 degrees, pre- vs postoperation, P = 0.271) after the 4-level CDA. However, global cervical alignment remained unchanged. There was one permanent C5 radiculopathy, but no other neurological deteriorations or any reoperations occurred. CONCLUSION: For these rare but unique indications, 4-level CDA yielded clinical improvement and preserved segmental motility with low rates of complications. Four-level CDA is a safe and effective surgery, maintaining the ROM in patients with primarily disc herniations and mild spondylosis. CLINICAL RELEVANCE: For patients with mild spondylosis, whose degeneration at the cervical spine is not so severe, CDA is more suitable.

Energetically Favored 2D to 3D Transition: Why Silicene Cannot Be Grown on Ag(111).

Silicene, a two-dimensional (2D) Si monolayer with properties similar to those of graphene, has attracted considerable attention because of its compatibility with existing technology. Most growth efforts to date have focused on the Ag(111) substrate, with a 3 × 3 phase widely reported below one monolayer (ML). As the coverage increases, a √3 × âˆš3 pattern frequently emerges, which has been proposed by various experimental investigations as a Si(111)-3×3-Ag reconstructed structure. We report first-principles calculations to understand this series of observations. A major finding from our energetics studies is that Si growth on Ag(111) beyond one ML will switch to the Volmer-Weber mode, forming three-dimensional sp3 films. Combining with the condition that the 3 × 3 monolayer on Ag(111) does not have the correct buckling pattern of freestanding silicene, we conclude that silicene cannot be grown on Ag(111) and that a 2D to 3D transition is energetically favored beyond one ML.

Topological Quantum Well States in Pb/Sb Thin-Film Heterostructures.

Composite topological heterostructures, wherein topologically protected states are electronically tuned due to their proximity to other matter, are key avenues for exploring emergent physical phenomena. Particularly, pairing a topological material with a superconductor such as Pb is a promising means for generating a topological superconducting phase with exotic Majorana quasiparticles, but oft-neglected is the emergence of bulklike spin-polarized states that are quite relevant to applications. Using high-resolution photoemission spectroscopy and first-principles calculations, we report the emergence of bulk-like spin-polarized topological quantum well states with long coherence lengths in Pb films grown on the topological semimetal Sb. The results establish Pb/Sb heterostructures as topological superconductor candidates and advance the current understanding of topological coupling effects required for realizing emergent physics and for designing advanced spintronic device architectures.

TRIM29 modulates proteins involved in PTEN/AKT/mTOR and JAK2/STAT3 signaling pathway and suppresses the progression of hepatocellular carcinoma.

Tripartite motif-containing 29 (TRIM29), also known as the ataxia telangiectasia group D-complementing (ATDC) gene, has been reported to play an oncogenic or tumor suppressive role in developing different tumors. So far, its expression and biological functions in hepatocellular carcinoma (HCC) remain unclear. We investigated TRIM29 expression pattern in human HCC samples using quantitative RT-PCR and immunohistochemistry. Relationships between TRIM29 expression level, clinical prognostic indicators, overall survival (OS), and disease-free survival (DFS) were evaluated by Kaplan-Meier analysis and Cox proportional hazards model. A series of in vitro experiments and a xenograft tumor model were conducted to detect the functions of TRIM29 in HCC cells. RNA sequencing, western blotting, and immunochemical staining were performed to assess the molecular regulation of TRIM29 in HCC. We found that the mRNA and protein levels of TRIM29 were significantly reduced in HCC samples, compared with adjacent noncancerous tissues, and were negatively correlated with poor differentiation of HCC tissues. Survival analysis confirmed that lower TRIM29 expression significantly correlated with shorter OS and DFS of HCC patients. TRIM29 overexpression remarkably inhibited cell proliferation, migration, and EMT in HCC cells, whereas knockdown of TRIM29 reversed these effects. Moreover, deactivation of the PTEN/AKT/mTOR and JAK2/STAT3 pathways might be involved in the tumor suppressive role of TRIM29 in HCC. Our findings indicate that TRIM29 in HCC exerts its tumor suppressive effects through inhibition of the PTEN/AKT/mTOR and JAK2/STAT3 signaling pathways and may be used as a potential biomarker for survival in patients with HCC.

HOTAIR/miR-1277-5p/FBN2 signaling axis is involved in recurrent spontaneous abortion by regulating the growth, migration, and invasion of HTR-8/SVneo cells†.

OBJECTIVE: This study aimed to explore the specific pathways by which HOX transcript antisense intergenic RNA contributes to the pathogenesis of unexplained recurrent spontaneous abortion. METHODS: Real-time quantitative PCR was employed to assess the differential expression levels of HOX transcript antisense intergenic RNA in chorionic villi tissues from unexplained recurrent spontaneous abortion patients and women with voluntarily terminated pregnancies. HTR-8/SVneo served as a cellular model. Knockdown and overexpression of HOX transcript antisense intergenic RNA in the cells were achieved through siRNA transfection and pcDNA3.1 transfection, respectively. Cell viability, migration, and invasion were evaluated using cell counting kit-8, scratch, and Transwell assays, respectively. The interaction among the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 axis was predicted through bioinformatics analysis and confirmed through in vitro experiments. Furthermore, the regulatory effects of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis on cellular behaviors were validated in HTR-8/SVneo cells. RESULTS: We found that HOX transcript antisense intergenic RNA was downregulated in chorionic villi tissues from unexplained recurrent spontaneous abortion patients. Overexpression of HOX transcript antisense intergenic RNA significantly enhanced the viability, migration, and invasion of HTR-8/SVneo cells, while knockdown of HOX transcript antisense intergenic RNA had the opposite effects. We further confirmed the regulatory effect of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis in unexplained recurrent spontaneous abortion. Specifically, HOX transcript antisense intergenic RNA and fibrillin 2 were found to reduce the risk of unexplained recurrent spontaneous abortion by enhancing cell viability, migration, and invasion, whereas miR-1277-5p exerted the opposite effects. CONCLUSION: HOX transcript antisense intergenic RNA promotes unexplained recurrent spontaneous abortion development by targeting inhibition of miR-1277-5p/fibrillin 2 axis.

Variability in Leaf Color Induced by Chlorophyll Deficiency: Transcriptional Changes in Bamboo Leaves.

The diversity of leaf characteristics, particularly leaf color, underscores a pivotal area of inquiry within plant science. The synthesis and functionality of chlorophyll, crucial for photosynthesis, largely dictate leaf coloration, with varying concentrations imparting different shades of green. Complex gene interactions regulate the synthesis and degradation of chlorophyll, and disruptions in these pathways can result in abnormal chlorophyll production, thereby affecting leaf pigmentation. This study focuses on Bambusa multiplex f. silverstripe, a natural variant distinguished by a spectrum of leaf colors, such as green, white, and green-white, attributed to genetic variations influencing gene expression. By examining the physiological and molecular mechanisms underlying chlorophyll anomalies and genetic factors in Silverstripe, this research sheds light on the intricate gene interactions and regulatory networks that contribute to leaf color diversity. The investigation includes the measurement of photosynthetic pigments and nutrient concentrations across different leaf color types, alongside transcriptomic analyses for identifying differentially expressed genes. The role of key genes in pathways such as ALA biosynthesis, chlorophyll synthesis, photosynthesis, and sugar metabolism is explored, offering critical insights for advancing research and plant breeding practices.

Two somatic mutations in the androgen receptor N-terminal domain are oncogenic drivers in hepatocellular carcinoma.

The androgen receptor (AR) plays an important role in male-dominant hepatocellular carcinoma, and specific acquired somatic mutations of AR have been observed in HCC patients. Our previous research have established the role of AR wild type as one of the key oncogenes in hepatocarcinogenesis. However, the role of hepatic acquired somatic mutations of AR remains unknown. In this study, we identify two crucial acquired somatic mutations, Q62L and E81Q, situated close to the N-terminal activation function domain-1 of AR. These mutations lead to constitutive activation of AR, both independently and synergistically with androgens, making them potent driver oncogene mutations. Mechanistically, these N-terminal AR somatic mutations enhance de novo lipogenesis by activating sterol regulatory element-binding protein-1 and promote glycogen accumulation through glycogen phosphorylase, brain form, thereby disrupting the AMPK pathway and contributing to tumorigenesis. Moreover, the AR mutations show sensitivity to the AMPK activator A769662. Overall, this study establishes the role of these N- terminal hepatic mutations of AR as highly malignant oncogenic drivers in hepatocarcinogenesis and highlights their potential as therapeutic targets for patients harboring these somatic mutations.

Association between cooking patterns and the prevalence of hyperlipidemia in Eastern China.

BACKGROUND: Hyperlipidemia is a major risk factor for many diseases. Previous studies have shown that diet is closely associated with hyperlipidemia. However, the relationship between cooking methods and hyperlipidemia remains unclear. The objective of this study was to identify the major cooking patterns existing in the Eastern Chinese population and evaluate their association with the prevalence of hyperlipidemia. METHODS: We interviewed 4,710 residents in Eastern China regarding the consumption frequency of each cooking method when they prepare food at home or when eating out and regarding the prevalence of hyperlipidemia. Factor analysis, Chi-square tests, analysis of variance, and binary logistic regression analysis were used to identify the cooking patterns and analyze the characteristics of participants' categories of cooking patterns and the relationship between different cooking patterns and prevalence of hyperlipidemia. RESULTS: Three major cooking patterns were identified: Traditional Chinese, Bland (little or no oil is used to process the food), and High-temperature cooking patterns. After controlling for potential confounders, participants in the highest quartile of the Bland cooking pattern had lower odds of hyperlipidemia than those in the lowest quartile. Nevertheless, no significant associations were observed between the Traditional Chinese and High-temperature cooking patterns and the prevalence of hyperlipidemia. CONCLUSIONS: This study confirms the association between cooking patterns and the prevalence of hyperlipidemia and indicates that the Bland cooking pattern is associated with a reduced prevalence of hyperlipidemia.

The complete mitochondrial genome of the red-footed tortoise (Chelonoidis carbonarius Spix 1824).

In this study, we report the complete mitochondrial genome of the red-footed tortoise (Chelonoidis carbonarius). The compete mitochondrial genome of C. carbonarius is 16,639 bp in length, including 13 protein-coding genes, 22 tRNA genes, and two rRNA genes. The mitogenome was deposited in NCBI GenBank under the accession number OQ789392. Furthermore, we also constructed a phylogenetic tree of Chelonoidis using eight species. These results will aid the conservation of Chelonoidis from the perspective of genetic evolution.