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Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.

Resequencing of 302 soybean accessions and GWAS provide a comprehensive resource for soybean geneticists and breeders. Understanding soybean ( Glycine max ) domestication and improvement at a genetic level is important to inform future efforts to further improve a crop that provides the world's main source of oilseed. We detect 230 selective sweeps and 162 selected copy number variants by analysis of 302 resequenced wild, landrace and improved soybean accessions at >11× depth. A genome-wide association study using these new sequences reveals associations between 10 selected regions and 9 domestication or improvement traits, and identifies 13 previously uncharacterized loci for agronomic traits including oil content, plant height and pubescence form. Combined with previous quantitative trait loci (QTL) information, we find that, of the 230 selected regions, 96 correlate with reported oil QTLs and 21 contain fatty acid biosynthesis genes. Moreover, we observe that some traits and loci are associated with geographical regions, which shows that soybean populations are structured geographically. This study provides resources for genomics-enabled improvements in soybean breeding.

Schizophrenia is a chronic neuropsychiatric disorder that causes distinct structural alterations within the brain. We hypothesize that deep learning applied to a structural neuroimaging dataset could detect disease-related alteration and improve classification and diagnostic accuracy. We tested this hypothesis using a single, widely available, and conventional T1-weighted MRI scan, from which we extracted the 3D whole-brain structure using standard post-processing methods. A deep learning model was then developed, optimized, and evaluated on three open datasets with T1-weighted MRI scans of patients with schizophrenia. Our proposed model outperformed the benchmark model, which was also trained with structural MR images using a 3D CNN architecture. Our model is capable of almost perfectly (area under the ROC curve = 0.987) distinguishing schizophrenia patients from healthy controls on unseen structural MRI scans. Regional analysis localized subcortical regions and ventricles as the most predictive brain regions. Subcortical structures serve a pivotal role in cognitive, affective, and social functions in humans, and structural abnormalities of these regions have been associated with schizophrenia. Our finding corroborates that schizophrenia is associated with widespread alterations in subcortical brain structure and the subcortical structural information provides prominent features in diagnostic classification. Together, these results further demonstrate the potential of deep learning to improve schizophrenia diagnosis and identify its structural neuroimaging signatures from a single, standard T1-weighted brain MRI.

Osteoporotic vertebral compression fractures (OVCFs) significantly increase morbidity and mortality, presenting a formidable challenge in healthcare. Traditional interventions such as vertebroplasty and kyphoplasty, despite their widespread use, are limited in addressing the secondary effects of vertebral fractures in adjacent areas and do not facilitate bone regeneration. This review paper explores the emerging domain of regenerative therapies, spotlighting stem cell therapy’s transformative potential in OVCF treatment. It thoroughly describes the therapeutic possibilities and mechanisms of action of mesenchymal stem cells against OVCFs, relying on recent clinical trials and preclinical studies for efficacy assessment. Our findings reveal that stem cell therapy, particularly in combination with scaffolding materials, holds substantial promise for bone regeneration, spinal stability improvement, and pain mitigation. This integration of stem cell-based methods with conventional treatments may herald a new era in OVCF management, potentially improving patient outcomes. This review advocates for accelerated research and collaborative efforts to translate laboratory breakthroughs into clinical practice, emphasizing the revolutionary impact of regenerative therapies on OVCF management. In summary, this paper positions stem cell therapy at the forefront of innovation for OVCF treatment, stressing the importance of ongoing research and cross-disciplinary collaboration to unlock its full clinical potential.

Study design A randomized controlled trial. Objective The aim of this study is to compare the efficacy of allografts and bioactive glass-ceramic (BG) cages for anterior cervical discectomy and fusion (ACDF) in treating cervical degenerative disc disease. Methods We conducted a single-center, randomized controlled trial between August 2017 and August 2022. Participants were randomized into two groups, and consecutive patients requiring ACDF were randomly assigned to receive either the allograft cage or the BG cage. The surgical outcomes measured included pain levels, neck disability, surgical details, and radiological assessments. Results Of the 45 assessed, 40 participants were included, with 18 in the allograft cage group and 22 in the BG cage group. By the 12-month follow-up, both groups exhibited significant improvements in pain levels and disability scores, with no notable intergroup differences. Over 85% of patients in both groups were satisfied with their outcomes. Radiological assessments revealed stability in the cervical spine with both cage types post intervention. Although both materials showed a trend toward increased subsidence over time, the difference between them was not statistically significant. Fusion rates were comparable between the groups at 12 months, with BG cage showing a slightly higher early fusion rate at 6 months. No significant differences were observed between the two groups in terms of complications. Conclusions Both allograft and BG cages are effective in ACDF surgeries for cervical degenerative disc disease, with both contributing to substantial postoperative improvements. Differences in disc height, interspinous motion, and subsidence were not significant in the last follow-up, indicating both materials' suitability for clinical use. Future research with a larger cohort and longer follow-up is needed to confirm these preliminary findings.

Background: Trastuzumab (Herceptin) can be administered intravenously (IV Herceptin) and subcutaneously, with similar efficacy and safety, but with differences in dosage and costs. Previous studies have evaluated the costs of both treatment approaches in the outpatient settings, but no study has compared the costs of IV Herceptin administered in outpatients with subcutaneous Herceptin administered at patients’ homes (Homecare SC Herceptin). Objectives: This study aimed to compare the per-patient costs of Homecare SC Herceptin versus IV Herceptin administered in a healthcare institution’s outpatient setting in Singapore. Designs: We performed a model-based cost-minimization analysis to estimate and compare the per-patient annual costs associated with each treatment modality from a societal perspective. Methods: Direct cost comprised healthcare resources utilization: drug, consumables, manpower, facility and cardiac assessment. Indirect cost was valued using a human capital approach to account for productivity lost by patients. Monte Carlo simulations with 1000 iterations were performed to account for parameter uncertainties. Costs were reported in 2023 Singapore dollars. Results: The annual societal cost per patient receiving IV Herceptin ranged from S$64,194 to S$65,135, while for Homecare SC Herceptin, it ranged from S$25,865 to S$26,807. Homecare SC Herceptin reduced the annual cost burden by 58.8% and 59.7%, per non-metastatic and metastatic breast cancer patient, respectively. The primary cost contributor was drug therapy, comprising more than 90% of the total cost. Even when excluding the cost of drugs, Homecare SC Herceptin remained cheaper by S$1912 annually. The cost reduction is approximately 60% compared to IV Herceptin regardless of disease status, with a 100% probability that the decision to adopt Homecare SC Herceptin leads to cost savings in Singapore. Conclusion: Treatment of breast cancer with Homecare SC Herceptin is a cost-saving option compared to IV Herceptin.

The particle phase state is crucial for reactive gas uptake, heterogeneous, and multiphase chemical reactions, thereby impacting secondary aerosol formation. This study provides valuable insights into the significance of particle-phase transition and aerosol liquid water (ALW) in particle mass growth during winter. Our findings reveal that particles predominantly exist in a semi-solid or solid state during clean winter days with ambient relative humidity (RH) below 30 %. However, a non-liquid to liquid phase transition occurs when the ALW mass fraction exceeds 15 % (dry mass) at transition RH thresholds of 40 %–60 %. During haze episodes, the transformation rates of sulfate and nitrate aerosols rapidly increase through phase transition and increased ALW by 48 % and 11 %, respectively, resulting in noticeable increases in secondary inorganic aerosols (SIA). The presence of abundant ALW, favored by elevated RH and higher proportion of SIA, facilitates the partitioning of water-soluble compounds from the gas to the particle phase, as well as heterogeneous and aqueous processes in liquid particles. This leads to a substantial increase in the formation of secondary organic aerosols and elevated aerosol oxidation. Consequently, the overall hygroscopicity parameters exhibit a substantial enhancement, with a mean value of 23 %. These results highlight phase transition as a key factor initiating the positive feedback loops between ALW and secondary aerosol formation during haze episodes over the North China Plain. Accurate predictions of secondary aerosol formation necessitate explicit consideration of the particle phase state in chemical transport models.

Spinal cord injury (SCI) is a devastating neurological condition that has limited therapeutic options; thus, developing innovative regenerative strategies to treat SCI is necessary. This study presents a multifunctional scaffold system that synergistically combines poly(lactic-co-glycolic acid) and multiple bioactive components such as magnesium hydroxide nanoparticles, decellularized brain extracellular matrix, two-dimensional MXene nanosheets, berberine, sertoli cell–derived extracellular vesicles, and neural progenitor cells. This synergistic design provides a bioactive microenvironment that mitigates inflammation and promotes antioxidative responses while delivering sustained bioactive signals for neural repair. In particular, the conductive property of the scaffold resulting from MXene incorporation facilitates intercellular electrical signaling to provide axonal regeneration. In vitro, the scaffold modulates macrophage polarization toward an anti-inflammatory M2 phenotype, promotes neural differentiation, and reduces oxidative stress. In a complete transection rat model, the scaffold enhances motor function recovery and reduces neuropathic pain. Histological analyses show reduced glial scar formation, enhanced remyelination, and robust axonal regeneration. Molecular studies further confirm the upregulation of anti-inflammatory cytokines and neurotrophic factors, thereby demonstrating the ability of the scaffold to reprogram the injury microenvironment for regeneration. These findings indicate the application potential of this multifunctional scaffold as a transformative therapy for SCI. Graphical Abstract

Spinal cord injury (SCI) disrupts neural architecture through a cascade of inflammatory, vascular, and glial responses that collectively create a regenerative deadlock. Overcoming this complex, temporally evolving pathology requires the coordinated delivery of structural, cellular, and biochemical cues. Here, we present a 3D bioprinted multifunctional scaffold composed of gelatin methacryloyl (GelMA), tetramethylpyrazine (TMP), neural progenitor cells (NPCs), and neural stem cell-derived extracellular vesicles (NSC-EVs). This combinatorial construct mimics essential features of the neural niche and orchestrates reparative processes across multiple levels. Compared to adipose-derived EVs, NSC-EVs demonstrated a superior cytokine and neurotrophic profile that enhanced angiogenesis and neuronal differentiation. In vitro, the integrated scaffold promoted NPC survival, neurogenesis, angiogenesis and immunomodulation. In a complete transection rat SCI model, the scaffold supported locomotor recovery by reducing cystic cavitation, facilitating axonal regeneration and remyelination, preserving parenchymal integrity, and attenuating neuroinflammation. Our findings suggest that integrated, multimodal interventions can modulate the hostile post-injury microenvironment and stimulate endogenous repair mechanisms, offering a clinically translatable paradigm for SCI regeneration.

High-density lipoprotein (HDL) cholesterol is inversely associated with the risk of cardiovascular disease (CVD). However, whether the protective effect of HDL becomes impaired by elevated high-sensitivity C-reactive protein (hs-CRP) is not well-established. We evaluated 13,572 United States adults aged ≥18 years who participated in the cross-sectional National Health and Nutrition Examination Survey 1999–2008. The subjects were classified according to the recognized cutpoints of HDL cholesterol elevations of ≥60 mg/dl, hs-CRP of >3 mg/L, and by a history of self-reported coronary heart disease (CHD) or CVD. Multivariate logistic regression analysis was used to assess the odds of prevalent CHD and CVD according to HDL cholesterol/hs-CRP group, after adjusting for known risk factors. Those with HDL cholesterol of ≥60 mg/dl and CRP >3 mg/L versus HDL cholesterol <60 mg/dl and CRP ≤3 mg/L had as high or a greater prevalence of CHD (5.5% and 5.3%, respectively) and CVD (8.6% and 6.9%, respectively). Compared to those with HDL cholesterol of ≥60 mg/dl and CRP ≤3 mg/L, those with HDL cholesterol ≥60 mg/dl and hs-CRP >3 mg/L had a 1.38 (95% confidence interval 0.94 to 2.02) adjusted odds of CHD and 1.38 (95% confidence interval 1.00 to 1.90) adjusted odds of CVD. Those with an HDL cholesterol <60 mg/dl and CRP >3 mg/L had the greatest adjusted odds of both CHD (1.75, 95% confidence interval 1.28 to 2.38) and CVD (1.74, 95% confidence interval 1.33 to 2.28). In conclusion, an hs-CRP >3 mg/L in the presence of HDL cholesterol of ≥60 mg/dl is associated with an attenuation in the protective association of HDL cholesterol ≥60 mg/dl and CRP of ≤3 mg/L with CHD and CVD.