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Activity shapes large herbivores' ecological influences.

The ecological effects of large herbivores are shaped by their spatial and temporal patterns of activity (i.e. where, when and how intensely they use specific locations). When large herbivores' ecological influences are perceived to be undesirable, the traditional approach has been to reduce their population size. This numbers-first logic assumes that ecological effects scale primarily with abundance. We argue that this framing provides an incomplete understanding of large herbivores' ecological impacts. Using African elephants (Loxodonta africana) as a well-documented case study, we show that ecological effects on plants, animals and ecosystem processes correlate more with spatio-temporal patterns of activity than with population size. In large, open systems characterized by strong gradients of water availability, forage quality, shade and risk, elephants concentrate into predictable hotspots while relaxing activity elsewhere, generating localized impacts and opportunities for recovery. By contrast, in small, fenced or fragmented landscapes, where movements are constrained, and gradients are weak, spatial self-regulation breaks down, producing homogenized use and widespread ecological effects. We contend that understanding where, when and under what constraints herbivores use space provides a more general and mechanistic basis for interpreting ecological influence than abundance alone, with implications that extend beyond elephants to large herbivores globally.

Animals

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12&#x202f;cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B)&#x202f;&#x2248;&#x202f;9, coefficient of variance (CV)&#x202f;<&#x202f;10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus

Mechanisms of high-humidity hot air impingement blanching (HHAIB) on microbial counts, functional properties, phenolic profile transformation, and volatile compounds in celery stalks (Apium graveolens L.).

In this study, celery stalks were pretreated with different durations (0-150&#xa0;s) of high-humidity hot air impingement blanching (HHAIB), followed by far-infrared radiation assisted pulsed vacuum freeze-drying (FIR-PVFD) at 60, 65, and 70&#xa0;&#xb0;C. The effects of HHAIB on the physicochemical properties, composition and transformation of phenolic compounds, volatile components, and antioxidant capacity of FIR-PVFD-dried celery stalks were systematically investigated. The results showed that HHAIB not only effectively reduced the counts of total mesophilic aerobic bacteria (TMAB) and total yeast and mold (TYM), but also decreased the relative activities of polyphenol oxidase (PPO) and lipoxygenase (LOX) by more than 91% after 90&#xa0;s of treatment. HHAIB altered the cellular structure of celery stalks, shortened the drying time by 29.33-41.43%, and improved their hydration properties. HHAIB pretreatment promoted the conversion of bound phenolics to free phenolics in celery stalks, with significant increases in the contents of p-coumaric acid, apigenin, graveobioside A, and other components. The total free phenolic content increased by 56.99%, thus HHAIB enhanced the antioxidant activity. An electronic nose and sensory evaluation revealed that HHAIB-pretreated celery stalks better retained the characteristic herbal and pungent notes. GC-MS results indicated that HHAIB treatment optimized the aroma profile by regulating the contents and composition of terpenes, aldehydes, ketones, alcohols, and aromatic compounds.

Apium

Intersphincteric resection versus abdominoperineal resection for lower rectal cancer: A systematic review and meta-analysis.

BACKGROUND: The optimal surgical approach for lower rectal cancer (LRC) remains debated, particularly between intersphincteric resection (ISR) and abdominoperineal resection (APR). While ISR offers potential sphincter preservation, its oncological efficacy compared to APR is unclear. METHODS: A systematic review was conducted to compare clinical and oncological outcomes of ISR versus APR in LRC patients. On December 8, 2024, a comprehensive search of Medline, Embase, Cochrane Library, Scopus, and Web of Science identified 24 retrospective studies involving 4502 patients. Key outcomes analyzed included positive circumferential resection margin (CRM), number of harvested lymph nodes (LNs), local recurrence (LR), length of hospital stay (LOS), early postoperative complications, and survival. RESULTS: Twenty-four retrospective studies involving 4502 patients (ISR: 2266 (50.3%) and APR: 1558 (34.6%)) met the eligibility criteria. ISR was associated with significantly lower rates of positive CRM (risk ratio (RR): 0.41, p&#x202f;<&#x202f;0.001), decreased early postoperative complications (RR: 0.76, p&#x202f;<&#x202f;0.001), lower LR (RR: 0.63, p&#x202f;=&#x202f;0.0038), and improvement in five-year overall survival (5YOS) (hazard ratio (HR)&#x202f;=&#x202f;0.42, p&#x202f;<&#x202f;0.001) and five-year disease-free survival (5YDFS) (HR&#x202f;=&#x202f;0.59, p&#x202f;<&#x202f;0.001). CONCLUSIONS: ISR demonstrates several advantages over APR in selected LRC patients, including lower rates of positive CRM, fewer early postoperative complications, reduced LR, greater LN harvest, shorter LOS, and improved long-term survival outcomes (5YOS and 5YDFS). Therefore, ISR can be considered a safe and effective alternative to APR in appropriately chosen patients, with careful patient selection and surgical expertise remaining essential.

Humans

Epigenetic drift and LINE-1 activation in aging brain: Implications for neurodegenerative disease.

Brain aging and age-associated neurological diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are largely attributed to epigenetic drift which is characterized by the gradual accumulation of alterations in neural cell methylation patterns over time. These methylation changes are particularly evident in transposable element (TE)-derived sequences such as Long interspersed element-1 (LINE-1) which comprises approximately 17% of the human genome. During aging, LINE-1 elements gradually lose their methylation, as well as the regulatory safeguard mechanisms that usually keep them inactive. This repression loss can lead to LINE-1 reactivation, contributing to harmful effects including genomic instability, neuroinflammation, and more. Together these findings indicate that impaired epigenetic maintenance, especially in repetitive genome regions, plays a key role in biological aging of neurons and glial cells. In this narrative review, we discuss the methylation dynamics and regulatory mechanisms of LINE-1 retrotransposons, their activation processes during aging, and contribution to age-associated neurological diseases. We also highlight the potential of targeting LINE-1 methylation to restore methylation homeostasis, epigenetic stability and delay brain aging.

Humans

Molecular adaptation of caspase genes to salinity stress in the tropical sea cucumber Stichopus monotuberculatus: A comparative analysis across echinoderms.

Apoptosis is an essential physiological process that plays a critical role in development and tissue homeostasis. Caspases, as central regulators of apoptosis, are crucial in controlling inflammation and cell death. In this study, we investigated the caspase gene family in Stichopus monotuberculatus to explore their potential roles in salinity stress adaptation. Five caspase genes were identified from the genome of S. monotuberculatus, including Smcaspase3, Smcaspase6, Smcaspase8a, Smcaspase8b, and Smcaspase8c. Phylogenetic analysis revealed that these Smcaspase genes clustered into distinct caspase subfamilies and showed high conservation with homologs from other echinoderms and representative vertebrates. Conserved motif and gene structure analyses showed relatively similar structural patterns within each clade, whereas divergence was observed among different subfamilies. Promoter analysis identified numerous cis-acting elements related to gene regulation, immune response, and growth and development. Expression profiling under salinity stress showed that Smcaspase8a was significantly upregulated, particularly under prolonged stress, whereas the other genes exhibited limited transcriptional responses. Our findings highlight caspase function in salinity stress and provide the foundation of molecular salinity adaptation mechanisms in S. monotuberculatus.

Animals

Gloeotrichia echinulata genomes from the United States are nontoxigenic and likely geosmin producers.

Six Gloeotrichia echinulata genomes derived from planktonic harmful algal blooms (HABs) with similar colonial morphology have been sequenced from lakes in the west and northeast regions of USA, four of them to completion. The c. 7 Mbp genomes exhibit a high level of conservation, with 98-99% pairwise genome-wide average nucleotide identity and high levels of synteny, representing a single species cluster. We observed strong conservation of gene clusters responsible for the synthesis of the secondary metabolites and bioactive peptides that are characteristic of HAB-forming cyanobacteria. All six G. echinulata genomes lack genes for the synthesis of classic cyanotoxins, including microcystin, but possess genes responsible for the synthesis of the taste and odor compound geosmin. Interestingly, the geoA geosmin synthase gene in three genomes is homologous to other cyanobacterial geoA genes, while the other three geoA genes are related to actinomyces geoA. Phylogenomic analysis places the G. echinulata genomes within a clade of benthic Nostocales, reflecting an ecological niche featuring extensive growth on the sediment surface before colonies disperse into the epilimnion for planktonic growth. We identify genes conserved in all six genomes that could represent physiological adaptations supporting active growth on sediments and pelagic recruitment independent of wind-driven mixing: phycoerythrin light harvesting complexes for optimal photosynthesis at depth; gliding motility to access patchy nutrient distributions; and gas vesicles with relatively small GvpC proteins that predict resistance to higher hydrostatic pressure. The strong genomic similarity across geographically distant populations suggests that G. echinulata in the United States is a tightly related non-toxigenic species group with predictable properties relevant to public health and drinking water management.

Cyanobacteria

A smartphone-integrated Pt@Cu-HCF nanozyme-based paper sensor for on-site determination of total antioxidant capacity in marine oils.

Total antioxidant capacity (TAC) serves as a key indicator for evaluating the nutritional quality of foods. In this study, we designed a platinum-embedded copper hexacyanoferrate (denoted as Pt@Cu-HCF) nanozyme that exhibits high oxidase-like activity, efficiently catalyzing the oxidation of chromogenic substrates to generate robust colorimetric signals. Antioxidants quench hydroxyl radicals (&#x2219;OH) produced during the catalytic process, leading to a concentration-dependent suppression of the color signal. Leveraging this mechanism, a smartphone-integrated, colorimetric paper sensor for on-site TAC quantification was developed, using vitamin E as the calibration standard. The sensor was applied to determine TAC in fish oil, algal oil, and krill oil, demonstrating a linear response range of 9.78-312.5&#xa0;&#x3bc;M and a limit of detection (LOD) of 6.41&#xa0;&#x3bc;M. Validation using real-world marine oil samples showed excellent agreement with a commercial assay kit, confirming the reliability and practical applicability of this portable sensor for TAC measurement in complex biological matrices.

Antioxidants

Integration of single-cell transcriptomics and genomic mutation analysis identifies an immunotherapy-resistant tumor subcluster and validates ARNTL2 as a malignant driver in lung adenocarcinoma.

BACKGROUND: Immunotherapy resistance in lung adenocarcinoma (LUAD) remains a critical clinical challenge, and the mechanisms underlying resistance-associated intratumoral heterogeneity are poorly characterized. METHODS: We performed single-cell RNA sequencing of LUAD patients receiving neoadjuvant immunotherapy (responders vs. non-responders), integrating inferCNV, GSVA, and differential expression analyses. Cluster-specific genes were validated across seven independent cohorts (TCGA-LUAD, GSE13213, GSE26939, GSE29016, GSE30219, GSE31210, GSE42127). A multi-algorithm machine learning framework was used to construct a prognostic model, and the immune microenvironment was characterized using TCIA scoring, seven infiltration algorithms, and ESTIMATE. ARNTL2 function was assessed by CCK-8 and Transwell assays in A549 and H1299 cells. RESULTS: Non-responders showed significant enrichment of epithelial cells, depletion of cytotoxic T/NK cells, and elevated copy number variation burden versus responders (p < 0.0001). A resistance-enriched malignant subcluster (Cluster 2) exhibited hyperproliferative and metabolic reprogramming signatures with upregulated KRT17, S100A2, and CST6, which showed tumor-specific overexpression, adverse prognostic value, and genomic amplification across cohorts. CoxBoost combined with survivalSVM achieved optimal predictive performance (C-index = 0.686), yielding robust risk stratification (HR: 2.54-10.51, all p < 0.05). Low-risk patients showed greater immune infiltration and higher TCIA immunophenoscores. ARNTL2 was an independent prognostic factor (HR: 2.07-4.64) strongly correlated with risk score (r = 0.69), and its knockdown suppressed proliferation and invasion in both LUAD cell lines (all p < 0.05). CONCLUSION: This study identifies a resistance-associated malignant subcluster in LUAD, constructs a validated CoxBoost + survivalSVM prognostic model with robust immune stratification, and establishes ARNTL2 as a core oncogenic driver and therapeutic target.

ARNTL2

Screening for neurofibromatosis type 1-related optic pathway gliomas: a systematic review.

BACKGROUND: Neurofibromatosis-type 1 (NF1) is a genetic disorder characterized by developing optic pathway gliomas (OPGs) in 15%-20% of patients with higher estimates where consanguinity is prevalent. Clinically, NF1-OPG might be unpredictable with the risk of OPG progression and visual impairment. The optimal time for screening is controversial. We aim to identify the mean/median age at diagnosis of NF1-OPG and its clinical spectrum. METHODS: A systematic review of PubMed, Web of Science, and Embase databases was conducted for English-language publications from January 1993 to October 2025, exploring the visual screening of OPGs in NF1 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews (PROSPERO ID: CRD420251036244). Inclusion criteria focused on studies reporting the age at OPG diagnosis and visual manifestations in NF1 patients. Data were extracted on demographics, age at NF1 and OPG diagnosis, tumour location (using the Dodge classification), and presenting symptoms. Sixteen studies met the inclusion criteria. RESULTS: Among 4 739 NF1 patients, 818 had OPGs, with prevalence ranging from 4.2% to 46.7%. The age at NF1 diagnosis ranged from 0 to 132 months (mean: 18-38 months), and at OPG diagnosis from 0-240 months (median: 29-58 months). Approximately 58.4% of OPGs were asymptomatic, and 25% were above the age of 5 years. Among symptomatic patients, the most frequent presentations included decreased visual acuity (62%), abnormal optic disc (45%), proptosis (20%), strabismus (12%), and visual field defects (7%). CONCLUSIONS: NF1-related OPGs typically present early within 6 years of age. Early ophthalmologic and/or radiologic screening at the time of NF1 diagnosis enhances the detection of silent OPGs.

Humans

Medication safety in older adults in India: an integrative PhD synthesis of direct evidence and contextual implementation evidence.

BACKGROUND: Unsafe medication practices among older adults are an important global health concern, particularly in low- and middle-income countries where multimorbidity, fragmented care, self-medication, and informal healthcare provision intersect. OBJECTIVE(S): To synthesize direct evidence on medication safety among older adults in India and contextual evidence on deprescribing and community-level provider interventions relevant to safer medication use. METHODS: This PhD synthesis integrates four studies: a record-based cross-sectional study on polypharmacy and cardiovascular autonomic function in Kolkata; a six-city community study of 600 Indian older adults; a systematic review and meta-analysis on deprescribing preventive medications in frail or end-of-life older adults; and a systematic review of informal healthcare provider interventions in low- and middle-income countries. Studies I-II provided direct Indian older-adult evidence, while Studies III-IV provided indirect contextual evidence for their optimization and implementation. RESULTS: Polypharmacy was associated with higher anticholinergic burden and numerically higher cardiac autonomic neuropathy although residual confounding limits causal interpretation. In the multicity study, one-third had polypharmacy, while potentially inappropriate medications, prescribing omissions, and self-medication were common. Risks were higher with multimorbidity, recent hospitalization, care transitions, or living alone. Deprescribing showed no statistically significant increase in mortality, hospitalization, or major cardiovascular events, but heterogeneity was high and certainty low to very low. Informal-provider interventions showed the potential to improve knowledge, referral, case management, and medication-related practices. CONCLUSIONS: Medication safety among older adults in India requires an integrated continuum approach, but direct evidence supports only some components and implementation strategies that need prospective evaluation.

Humans

Association of Age at Menarche With Depression in Adulthood in NHANES 2015-2023: A Cross-Sectional Study.

PURPOSE: The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association. METHODS: We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (&#x2265;15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics. RESULTS: The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions. DISCUSSION: Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.

Humans

Boosting domestic wastewater treatment with quorum signal-augmented heterotrophic nitrification-aerobic denitrification bacterial-algal aerobic granular sludge.

The aerobic bacterial-algal granular sludge (ABGS) enhanced with heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria, as a novel symbiotic technology, exhibits fluctuating treatment efficiency and unstable performance primarily due to the unstable symbiotic relationship. This study proposes an innovative approach to strengthening the bacteria-algae symbiosis by introducing exogenous signaling molecules. Concurrently, high-throughput, correlation analysis of environmental factors and metagenomic sequencing techniques are employed to elucidate the enhancement mechanisms of the signaling molecules. The results demonstrate that signaling molecule enhancement boosted total nitrogen (TN) removal efficiency by 24.51 % in the bacteria-algae symbiotic system (X1). Scanning electron microscopy (SEM) characterization revealed that the addition of signaling molecules resulted in more compact aerobic granular sludge (AGS) and markedly improved stability. High-throughput sequencing showed signaling molecules enriched denitrifying bacteria (Hydrogenophaga, Pseudoxanthomonas, Thauera, Zoogloea) and organic-degrading Desulfomicrobium, optimizing microbial diversity and enhancing nitrogen/organic removal. Correlation analysis of environmental factors indicate that the addition of C8-HSL facilitates the enrichment and functional activation of specific genera. Metagenomic analysis revealed that signaling molecules enhanced the system's denitrification performance by modulating gene expression and associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) analysis further confirmed that the signaling molecules upregulated the expression of the napA, nirK, and nirS genes. An increased abundance of the napA gene facilitated aerobic denitrification (NO&#x2083;&#x207b;-N&#x2192;NO&#x2082;&#x207b;-N), while upregulated abundance of the nirK and nirS genes accelerated nitrite reduction (NO&#x2082;&#x207b;-N&#x2192;N&#x2082;). This study aims to provide theoretical and practical foundations for implementing advanced bacteria-algae symbiotic technologies.

Denitrification

Perceptions of Pharmacogenomic Testing Among People With Treatment Resistant Depression: Legitimization as a Facilitator of Acceptance.

Pharmacogenomic testing for psychiatric medications has been proposed as both an early intervention to optimize treatment response, and for use among patients who have tried multiple medications without symptom remission. Therefore, this testing may be particularly salient to the subset of individuals with major depressive disorder for whom depression has been labeled as "treatment resistant". Understanding the impact of this diagnostic label on illness identity and attitudes towards new therapies is important as genomic technology expands and rates of depression increase. We sought to explore perceptions and attitudes towards pharmacogenomic testing among individuals who had received a diagnosis of treatment resistant depression. We conducted a qualitative study with a constructivist orientation. Participants were recruited from a larger genomic research study and interviewed by phone or video call. We took an inductive approach to coding guided by reflexive thematic analysis. Themes were then organized into a relational framework following principles of interpretive description. Twelve individuals were interviewed. Key themes included internalized acceptance/hopelessness, and external validation/frustration, which were cyclically interconnected. These themes were situated within a larger framework illustrating the ways that illness identity and modifying factors such as relief of guilt, social support, pharmacogenomic testing and depressive symptoms can either facilitate acceptance and validation or contribute to feelings of hopelessness and frustration. Though participants expressed some skepticism around its effectiveness, pharmacogenomic testing may contribute to the shift towards acceptance and validation by legitimizing individuals' experiences with lack of treatment response. Genetic counselors and other healthcare providers should be aware of the complex balance between hope and frustration underlying conversations around pharmacogenomic testing, and factors that are more likely to foster self-acceptance.

Humans

Evaluation of one-step amplicon-based targeted enrichment for SARS-CoV-2 whole-genome sequencing using the Midnight amplicon scheme.

Genomic surveillance proved invaluable during the COVID-19 pandemic for tracking SARS-CoV-2 variants and guiding outbreak responses, underscoring the ongoing need to reduce whole-genome sequencing (WGS) costs and improve workflow efficiency to ensure accessibility in resource limited settings. Here, we evaluated a one-step reverse transcription polymerase chain reaction (RT-PCR) approach using the Midnight V2 primer scheme for targeted amplification of the SARS-CoV-2 genome, assessed its compatibility with Illumina sequencing, and compared its performance to a well-established two-step method. Initially, we determined optimal RT-PCR reaction conditions using the Midnight V2 primer panel for the one-step RT-PCR kit and scaled reaction volumes for both RT-PCR and library preparation. Clinical specimens (n&#x202f;=&#x202f;53) that had undergone routine WGS for surveillance purposes using the established two-step RT-PCR method were compared using the one-step RT-PCR assay. For samples with genome completeness greater than 70%, both methods gave comparable results with similar sequence coverage and 100% concordance for lineage assignment. Further investigation revealed a higher percentage of reads aligning to the SARS-CoV-2 genome with a greater depth of coverage using the one-step method compared to the two-step method. Finally, analysis of scaled one-step and library reaction volumes revealed significant cost savings for samples undergoing WGS. Overall, the results presented here verify the accuracy and reproducibility of one-step targeted amplification and offer an efficient and cost-effective workflow for routine SARS-CoV-2 genomic surveillance.

Humans

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using &#x3c7;2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6&#x2009;months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p&#x2009;<&#x2009;0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p&#x2009;>&#x2009;0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans

The hidden threat from food-derived carbon dots: Formation, biodistribution, and potential health risks.

Food-derived carbon dots (CDs) are a new class of carbon-based nanoparticles generated during the thermal processing of food matrices. These nanomaterials have been extensively studied for their unique fluorescence, good biocompatibility, and tunable surface chemistry in food detection, intelligent packaging, and biomedical applications. However, their nanoscale size and high surface activity have raised safety concerns regarding biological interactions, in vivo biodistribution, and potential long-term health hazards. Although CDs have traditionally been regarded as low-toxicity materials due to their favorable biocompatibility, the potential hidden risks of CDs have not received sufficient attention. CDs exhibit dose-dependent toxicity, not only accumulating in various tissues and organs but also potentially inducing oxidative stress and interfering with cellular metabolic functions. Therefore, this review summarizes the advances in sources, synthetic strategies, and core properties of CDs, with a special focus on in vivo biological interactions, fates, and potential safety challenges. In addition, it is proposed that the standardized detection and risk assessment system should be established to further explore the long-term health effects of CDs under real dietary exposure, thereby ensuring their safety and sustainable application.

Carbon Quantum Dots

Effects of Sacubitril Valsartan Combined With Vericiguat on NT-proBNP and CK-MB Levels in Patients With Chronic Heart Failure.

This study aims to probe the influence of sacubitril valsartan sodium tablets combined with vericiguat on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) levels in patients with chronic heart failure (CHF). One hundred and twenty CHF patients were enrolled and stratified into a control group (sacubitril valsartan sodium tablets) and a combination group (sacubitril valsartan sodium tablets&#x2009;+&#x2009;vericiguat). Outcome measures included New York Heart Association (NYHA) functional class shifts, echocardiographic indices, cardiac injury markers, 6-min walk distance (6MWD), endothelial function parameters, inflammatory mediator levels, and adverse clinical events. Following a 6-month treatment period, patients in the combination group exhibited superior functional improvement, as reflected by greater advancement in NYHA class. Echocardiographic evaluation revealed more favorable ventricular remodeling in this group, with reduced left ventricular end-diastolic and end-systolic diameters and an elevated ejection fraction. The combination group had a higher 6MWD. Biomarker analysis showed lower NT-proBNP and CK-MB levels in the combination group. Furthermore, improvements in endothelial function were noted, with decreased endothelin and elevated NO, NOS, and CGRP levels in the combination group. Markers of systemic inflammation, including CRP and IL-6, were also attenuated in the combination group. The incidence of adverse reactions and cardiovascular events did not differ significantly between the groups. Co-administration of sacubitril/valsartan and vericiguat enhances cardiac performance, optimizes vascular endothelial responsiveness, modulates heart failure-related biomarkers, and mitigates inflammatory activity in patients with CHF without increasing the risk of adverse events.

Humans