Why did the world's largest green tides occur exclusively in the southern Yellow Sea?

The world's largest green tide, caused by the nuisance green algae Ulva prolifera, has occurred in the southern Yellow Sea for 16 consecutive years. It is puzzling why the extensive floating green tide occurs exclusively in the southern Yellow Sea, rather than other waters. We speculate that the transition of U. prolifera from a sessile state to a surface-floating one is the underlying cause of the floating green tide. Here we founded that the floating of U. prolifera was attributed to detachment from substrata and appropriate desiccation. The convergence of unreasonable green algae disposal, geographical features and farming patterns of Porphyra (economic red algae) in Subei Shoal contributed to mass production of floating U. prolifera, resulting in the exclusive occurrence of the floating green tides. Inducing the natural inactivation of green algae to prevent the floating of U. prolifera may effectively mitigate the extensive Ulva bloom at zero cost.

Knocking down EGR1 inhibits nucleus pulposus cell senescence and mitochondrial damage through activation of PINK1-Parkin dependent mitophagy, thereby delaying intervertebral disc degeneration.

Mitophagy plays a crucial role in maintaining the homeostasis of intervertebral disc (IVD). Early Growth Response 1 (EGR1), a conservative transcription factor, is commonly upregulated under oxidative stress conditions and participates in regulating cellular senescence, apoptosis, and inflammatory responses. However, the specific role of EGR1 in nucleus pulposus (NP) cell senescence and mitophagy remains unclear. In this study, through bioinformatics analysis and validation using human tissue specimens, we found that EGR1 is significantly upregulated in IVD degeneration (IDD). Further experimental results demonstrate that knockdown of EGR1 inhibits TBHP-induced NP cell senescence and mitochondrial dysfunction while promoting the activation of mitophagy. The protective effect of EGR1 knockdown on NP cell senescence and mitochondrion disappears upon inhibition of mitophagy with mdivi1. Mechanistic studies reveal that EGR1 suppresses NP cell senescence and mitochondrial dysfunction by modulating the PINK1-Parkin dependent mitophagy pathway. Additionally, EGR1 knockdown delays acupuncture-induced IDD in rats. In conclusion, our study demonstrates that under TBHP-induced oxidative stress, EGR1 knockdown mitigates NP cell senescence and mitochondrial dysfunction through the PINK1-Parkin dependent mitophagy pathway, thereby alleviating IDD.

The predictive value of TyG and lipid ratios on the development of complications and hyperuricemia in patients with type 2 diabetes mellitus.

Investigate the predictive value of TyG and lipid ratios on the development of complications and HUA in patients with T2DM. A retrospective cross-sectional study involving 9488 T2DM patients was conducted. They were divided into HUA and NUA group base on SUA level and divided into with and without complications groups according to the diagnosis of the endocrinologist. Necessary information and biochemical parameters were recorded during outpatient visit. TyG index and lipid ratios were calculated, and statistical analysis was carried out to correlate the calculated values and HUA using SPSS version 26.0 for Windows. TyG and lipid ratios were significantly higher in T2DM with HUA or with complications than those with NUA or without complications (p < 0.05). Regression analysis adjusting for confounding factors found TyG (adjusted OR = 1.54; 95% CI: 1.31-1.82; p < 0.05), TG/HDL-C (adjusted OR = 1.21; 95% CI: 1.04-1.40; p < 0.05) and TC/HDL (adjusted OR = 1.36; 95% CI: 1.17-1.57; p < 0.05) was risk factor of HUA in T2DM patients. TyG (adjusted OR = 1.21; 95% CI: 1.02-1.44; p < 0.05), TG/HDL (adjusted OR = 1.19; 95% CI: 1.03-1.38; p < 0.05) and Apo A/Apo B (adjusted OR = 1.41; 95% CI: 1.26-1.58; p < 0.05) was risk factor of complications in T2DM patients. TyG, TG/HDL-C, and TC/HDL can be used as early sensitive target in the occurrence of HUA in T2DM patients and TyG was the most influential risk factor. TyG, TG/HDL-C, and Apo A/Apo B can be used as early sensitive target in the occurrence of complications in T2DM patients and Apo A/Apo B was the most influential risk factor.

GA-GBLUP: leveraging the genetic algorithm to improve the predictability of genomic selection.

Genomic selection (GS) has emerged as an effective technology to accelerate crop hybrid breeding by enabling early selection prior to phenotype collection. Genomic best linear unbiased prediction (GBLUP) is a robust method that has been routinely used in GS breeding programs. However, GBLUP assumes that markers contribute equally to the total genetic variance, which may not be the case. In this study, we developed a novel GS method called GA-GBLUP that leverages the genetic algorithm (GA) to select markers related to the target trait. We defined four fitness functions for optimization, including AIC, BIC, R2, and HAT, to improve the predictability and bin adjacent markers based on the principle of linkage disequilibrium to reduce model dimension. The results demonstrate that the GA-GBLUP model, equipped with R2 and HAT fitness function, produces much higher predictability than GBLUP for most traits in rice and maize datasets, particularly for traits with low heritability. Moreover, we have developed a user-friendly R package, GAGBLUP, for GS, and the package is freely available on CRAN (https://CRAN.R-project.org/package=GAGBLUP).

An advanced three-dimensional phenotypic measurement approach for extracting Ginkgo root structural parameters based on terrestrial laser scanning.

The phenotyping of plant roots is essential for improving plant productivity and adaptation. However, traditional techniques for assembling root phenotyping information are limited and often labor-intensive, especially for woody plants. In this study, an advanced approach called accurate and detailed quantitative structure model-based (AdQSM-based) root phenotypic measurement (ARPM) was developed to automatically extract phenotypes from Ginkgo tree root systems. The approach involves three-dimensional (3D) reconstruction of the point cloud obtained from terrestrial laser scanning (TLS) to extract key phenotypic parameters, including root diameter (RD), length, surface area, and volume. To evaluate the proposed method, two approaches [minimum spanning tree (MST)-based and triangulated irregular network (TIN)-based] were used to reconstruct the Ginkgo root systems from point clouds, and the number of lateral roots along with RD were extracted and compared with traditional methods. The results indicated that the RD extracted directly from point clouds [coefficient of determination (R 2) = 0.99, root-mean-square error (RMSE) = 0.41 cm] outperformed the results of 3D models (MST-based: R 2 = 0.71, RMSE = 2.20 cm; TIN-based: R 2 = 0.54, RMSE = 2.80 cm). Additionally, the MST-based model (F1 = 0.81) outperformed the TIN-based model (F1 = 0.80) in detecting the number of first-order and second-order lateral roots. Each phenotyping trait fluctuated with a different cloud parameter (CP), and the CP value of 0.002 (r = 0.94, p < 0.01) was found to be advantageous for better extraction of structural phenotypes. This study has helped with the extraction and quantitative analysis of root phenotypes and enhanced our understanding of the relationship between architectural parameters and corresponding physiological functions of tree roots.

Prolonged premature rupture of membranes with increased risk of infection is associated with gut accumulation of Pseudomonas from the environment.

Background: Preterm premature rupture of membranes (PPROM) contributes to over one-third of preterm births, and PPROM infants are more susceptible to infections. However, the risk factors remain poorly understood. We here aim to investigate the association of duration of premature rupture of membranes (PROM) and environmental microbiota with the gut microbiota and infection in PPROM infants. Methods: Forty-six premature infants were recruited from two hospitals, and infant fecal and environmental samples were collected. 16 s rRNA sequencing was performed to analyze the fecal and environmental microbiome. Human inflammatory cytokines in cord vein plasma were measured. Results: The gut microbiota composition of PPROM infants was different from that of non-PPROM infants, and the microbiome phenotypes were predicted to be associated with a higher risk of infection, further evidenced by the significantly increased levels of IL-6 and IL-8 in cord vein plasma of PPROM infants. The diversity of the gut microbiota in PPROM infants increased significantly as the duration of PROM excessed 12 h, and Pseudomonas contributed significantly to the dynamic changes. The Pseudomonas species in the gut of PPROM infants were highly homologous to those detected in the ward environment, suggesting that prolonged PROM is associated with horizontal transmission of environmental pathogens, leading to a higher risk of infection. Conclusions: This study highlights that the duration of PROM is associated with the accumulation of environmental pathogens in the gut of PPROM infants, which is a risk factor for nosocomial infections. Improving environmental hygiene could be effective in optimizing the clinical care of PPROM infants.

Synergistic Assistance of Ir Clusters and NiCo2O4 Nanosheets Interfaces in Direct O-O Coupling for High-Efficiency Alkaline Oxygen Evolution.

Adopting noble metals on non-noble metals is an effective strategy to balance the cost and activity of electrocatalysts. Herein, a thorough analysis of the synergistic OER is conducted at the heterogeneous interface formed by Ir clusters and NiCo2O4 based on DFT calculations. Specifically, the electrons spontaneously bring an eg occupancy of interfacial Ir close to unity after the absorbed O, providing more transferable electrons for the conversion of the absorbed O-intermediates. Besides, the diffuse distribution of electrons in the Ir 5d orbital fills the antibonding orbital after O is absorbed, avoiding the desorption difficulties caused by the stronger Ir-O bonds. The electrons transfer from Ir to Co atoms at the heterogeneous interface and fill the Co 3d band near the Fermi level, stimulating the interfacial Co to participate in the direct O-O coupling (DOOC) pathway. Experimentally, the ultrathin-modulated NiCo2O4 nanosheets are used to support Ir clusters (Ircluster-E-NiCo2O4) by the electrodeposition method. The as-synthesized Ircluster-E-NiCo2O4 catalyst achieves a current density of 10 mA cm-2 at an ultralow overpotential of 238 mV and works steadily for 100 h under a high current of 100 mA cm-2, benefiting from the efficient DOOC pathway during the OER.

Spotlight on necroptosis: Role in pathogenesis and therapeutic potential of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the leading cause of low back pain, which is one of the major factors leading to disability and severe economic burden. Necroptosis is an important form of programmed cell death (PCD), a highly regulated caspase-independent type of cell death that is regulated by receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL)-mediated, play a key role in the pathophysiology of various inflammatory, infectious and degenerative diseases. Recent studies have shown that necroptosis plays an important role in the occurrence and development of IDD. In this review, we provide an overview of the initiation and execution of necroptosis and explore in depth its potential mechanisms of action in IDD. The analysis focuses on the connection between NP cell necroptosis and mitochondrial dysfunction-oxidative stress pathway, inflammation, endoplasmic reticulum stress, apoptosis, and autophagy. Finally, we evaluated the possibility of treating IDD by inhibiting necroptosis, and believed that targeting necroptosis may be a new strategy to alleviate the symptoms of IDD.

Aging in chronic lung disease: Will anti-aging therapy be the key to the cure?

Chronic lung disease is the third leading cause of death globally, imposing huge burden of death, disability and healthcare costs. However, traditional pharmacotherapy has relatively limited effects in improving the cure rate and reducing the mortality of chronic lung disease. Thus, new treatments are urgently needed for the prevention and treatment of chronic lung disease. It is particularly noteworthy that, multiple aging-related phenotypes were involved in the occurrence and development of chronic lung disease, such as blocked proliferation, telomere attrition, mitochondrial dysfunction, epigenetic alterations, altered nutrient perception, stem cell exhaustion, chronic inflammation, etc. Consequently, senescent cells induce a series of pathological changes in the lung, such as immune dysfunction, airway remodeling, oxidative stress and regenerative dysfunction, which is a critical issue that needs special attention in chronic lung diseases. Therefore, anti-aging interventions may bring new insights into the treatment of chronic lung diseases. In this review, we elaborate the involvement of aging in chronic lung disease and further discuss the application and prospects of anti-aging therapy.

Pulmonary and renal long COVID at two-year revisit.

This study investigated host responses to long COVID by following up with 89 of the original 144 cohorts for 1-year (N = 73) and 2-year visits (N = 57). Pulmonary long COVID, characterized by fibrous stripes, was observed in 8.7% and 17.8% of patients at the 1-year and 2-year revisits, respectively, while renal long COVID was present in 15.2% and 23.9% of patients, respectively. Pulmonary and renal long COVID at 1-year revisit was predicted using a machine learning model based on clinical and multi-omics data collected during the first month of the disease with an accuracy of 87.5%. Proteomics revealed that lung fibrous stripes were associated with consistent down-regulation of surfactant-associated protein B in the sera, while renal long COVID could be linked to the inhibition of urinary protein expression. This study provides a longitudinal view of the clinical and molecular landscape of COVID-19 and presents a predictive model for pulmonary and renal long COVID.

Novel multi-functional microsphere scaffold with shape memory function for bone regeneration.

Irregular bone defects caused by trauma and bone diseases provide a complex implant environment for surgery. Traditional implants often fail to integrate well with the surrounding bone defect interface, therefore, developing an artificial bone scaffold that can adapt to irregular bone defect boundaries is of significant importance for bone defect repair. This study successfully utilized a shape memory ternary copolymer polylactic acid-trimethylene carbonate-hydroxyacetic acid (PLLA-TMC-GA) and dopamine-modified nano-hydroxyapatite (PHA) composite to construct a temperature-responsive bone repair scaffold (PTG/PHA), thereby enhancing the interface compatibility between the implant and the surrounding environment. The addition of PHA has effectively improved the hydrophilicity of the stent and significantly increased its mechanical strength. Furthermore, the Sodium alginate (SA) hydrogel loaded with Icariin (Ica) coated on the stent surface promotes the growth and differentiation of bone cells through the drug-scaffold synergistic effect. Both in vivo and in vitro experiments have shown that the synergistic effect of the composite stent with Icariin significantly enhances the repair of bone defects. This study provides a promising tissue engineering method for the repair of irregular bone defects.

Circulating tumor cells are a good predictor of tumor recurrence in clinical patients with gastric cancer.

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101-0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169-8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071-0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28-80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.

A generic causality-informed neural network (CINN) methodology for quantitative risk analytics and decision support.

In this paper, we develop a generic framework for systemically encoding causal knowledge manifested in the form of hierarchical causality structure and qualitative (or quantitative) causal relationships into neural networks to facilitate sound risk analytics and decision support via causally-aware intervention reasoning. The proposed methodology for establishing causality-informed neural network (CINN) follows a four-step procedure. In the first step, we explicate how causal knowledge in the form of directed acyclic graph (DAG) can be discovered from observation data or elicited from domain experts. Next, we categorize nodes in the constructed DAG representing causal relationships among observed variables into several groups (e.g., root nodes, intermediate nodes, and leaf nodes), and align the architecture of CINN with causal relationships specified in the DAG while preserving the orientation of each existing causal relationship. In addition to a dedicated architecture design, CINN also gets embodied in the design of loss function, where both intermediate and leaf nodes are treated as target outputs to be predicted by CINN. In the third step, we propose to incorporate domain knowledge on stable causal relationships into CINN, and the injected constraints on causal relationships act as guardrails to prevent unexpected behaviors of CINN. Finally, the trained CINN is exploited to perform intervention reasoning with emphasis on estimating the effect that policies and actions can have on the system behavior, thus facilitating risk-informed decision making through comprehensive "what-if" analysis. Two case studies are used to demonstrate the substantial benefits enabled by CINN in risk analytics and decision support.

Airway epithelial-derived exosomes induce acute asthma exacerbation after respiratory syncytial virus infection.

Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2-mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell-derived exosomes (AEC-Exos), which potentially influence the development of asthma. However, the specific role of AEC-Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC-Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC-Exos thorough transportation of hsa-miR-155-5p-Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa-miR-155-5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC-Exos promote the enhanced Th2 inflammation through transportation of increased hsa-miR-155-5p, which was mediated partly through SIRT1-mediated pathway. hsa-miR-155-5p is a potential biomarker for early prediction of acute asthma exacerbation.

LEUTX regulates porcine embryonic genome activation in somatic cell nuclear transfer embryos.

Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.

Characterization and dynamics of intestinal microbiota in patients with Clostridioides difficile colonization and infection.

Gut microbiota dysbiosis increases the susceptibility to Clostridioides difficile infection (CDI). In this study, we monitored C. difficile colonization (CDC) patients from no CDC status (CDN) to CDC status (CDCp) and CDI patients from asymptomatic status before CDI (PRECDI), CDI status (ONCDI), to asymptomatic status after CDI (POSTCDI). Based on metagenomic sequencing, we aimed to investigate the interaction pattern between gut microbiota and C. difficile. There was no significant difference of microbiota diversity between CDN and CDCp. In CDCp, Bacteroidetes and short-chain fatty acid (SCFA)-producing bacteria increased, with a positive correlation between SCFA-producing bacteria and C. difficile colonization. Compared with PRECDI, ONCDI and POSTCDI showed a significant decrease in microbiota diversity, particularly in Bacteroidetes and SCFA-producing bacteria, with a positive correlation between opportunistic pathogen and C. difficile. Fatty acid metabolism, and amino acid biosynthesis were enriched in CDN, CDCp, and PRECDI, while bile secretion was enriched in ONCDI and POSTCDI. Microbiota and metabolic pathways interaction networks in CDN and CDCp were more complex, particularly pathways in fatty acid and bile acid metabolism. Increasing of Bacteroidetes and SCFA-producing bacteria, affecting amino acid and fatty acid metabolism, is associated with colonization resistance to C. difficile and inhibiting the development of CDI.