A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management.

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Epidermal secretion-purified biosensing patch with hydrogel sebum filtering membrane and unidirectional flow microfluidic channels.

The development of biosensing electronics for real-time sweat analysis has attracted increasing research interest due to their promising applications for non-invasive health monitoring. However, one of the critical challenges lies in the sebum interference that largely limits the sensing reliability in practical scenarios. Herein, we report a flexible epidermal secretion-purified biosensing patch with a hydrogel filtering membrane that can effectively eliminate the impact of sebum and sebum-soluble substances. The as-prepared sebum filtering membranes feature a dual-layer sebum-resistant structure based on the poly(hydroxyethyl methacrylate) hydrogel functionalized with nano-brush structured poly(sulfobetaine) to eliminate interferences and provide self-cleaning capability. Furthermore, the unidirectional flow microfluidic channels design based on the Tesla valve was incorporated into the biosensing patch to prevent external sebum contamination and allow effective sweat refreshing for reliable sensing. By seamlessly combining these components, the epidermal secretion-purified biosensing patch enables continuous monitoring of sweat uric acid, pH, and sodium ions with significantly improved accuracy of up to 12 %. The proposed strategy for enhanced sweat sensing reliability without sebum interference shows desirable compatibility for different types of biosensors and would inspire the advances of flexible and wearable devices for non-invasive healthcare.

A recyclable dispersant based on carbomer utilizing controllable viscosity for high-efficiency dispersion of carbon fibers.

Good dispersion of carbon fibers is important for the carbon paper production, which is usually achieved using low carbon fiber concentrations and disposable dispersants. In this study, we developed carbomer as a recyclable and high-efficiency dispersant for carbon fibers. When the carbon fiber concentration was 0.1 wt%, carbon fiber suspension showed improved dispersion performance as increasing the carbomer dosage. It exhibited low Turbiscan Stability Index (TSI) of 0.41 and small change of delta backscattering between -0.5 to 0.8 % when using 0.5 wt% carbomer. However, the good dispersibility fade away when increasing the concentration of carbon fibers. Subsequently, the pH of the carbon fiber suspension was adjusted to 7.0 to improve the dispersibility by increasing the viscosity, but causing a worse flowability. Then the pH was further adjusted to 13.0 to ensure good flowability in the wet-forming process and good dispersibility at carbon fiber concentration of 0.5 wt%. More importantly, the dispersant was successfully recycled and still exhibited excellent dispersion effects for carbon fibers after 5 cycles. Notably, the high-efficiency dispersion of carbon fibers and the recyclability of dispersant were achieved simultaneously for the first time, which is suitable for the eco-friendly and sustainable production of carbon paper.

Predicting the Impact of Climate Change on the Selection of Reintroduction Sites for the South China Tiger (Panthera tigris amoyensis) in China.

The South China tiger (Panthera tigris amoyensis) is a tiger subspecies unique to China and one of the top ten endangered species in the world. It used to play an important role in the overall function of the ecosystem. This study rationally screened out key prey species of the South China tiger-the Chinese serow, Chinese goral, tufted deer, water deer, Chinese muntjac, red muntjac, sambar deer, and wild boar. Candidate sites for the rewilding and reintroduction of the South China tiger were derived by exploring changes in suitable habitats for the prey using the MaxEnt model. The results show that: (1) by 2070, except for the high-suitability areas of water deer and Chinese muntjac, the areas of suitable habitats for the other six prey species would all have decreased significantly; (2) the location of the high-suitability area of the South China tiger obtained by superimposing the suitable areas of the eight prey species would be almost stable in 2050 and 2070, but the habitat index of some high- and medium-suitability areas would decrease and turn into low-suitability areas; (3) the core candidate sites were 83,415 km2 in total, of which 25,630 km2 overlapped with existing protected areas, accounting for 30.7% of the core candidate sites, and the remaining 69.3% of the core candidate sites were mostly distributed around the protected areas; (4) the maximum core candidate site area was projected to be 10,000 km2 by 2070, which could support a small population of 23 male tigers and 66 female tigers to survive and reproduce in the wild. This study revealed the core candidate sites for the rewilding of South China tigers and estimated the number of tigers that could be reintroduced to these areas, providing a preliminary research basis for promoting the rewilding of South China tigers in China.

Modest survival benefits of autologous stem cell transplantation in multiple myeloma with renal impairment: a critical appraisal of the pre-antibody era.

The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.

Strengthening China's National Essential Public Health Services Package for hypertension and diabetes care: protocol for an interrupted time series study with mixed-methods process evaluation and health economic evaluation.

BACKGROUND: Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. "EMERALD" is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions. METHODS: The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and  (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions. DISCUSSION: This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector's contribution to addressing the growing burden of non-communicable diseases in China. TRIAL REGISTRATION: The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024).

Clinical and laboratory features between anti-TIF1γ dermatomyositis with and without malignancy: 37 case series and a review.

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti-transcriptional intermediary factor 1 antibody (anti-TIF1γ-Ab). A comparison was made between clinical information of anti-TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti-TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis-associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti-TIF1γ DM patients.

Targeting ferroptosis opens new avenues in gliomas.

Gliomas are one of the most challenging tumors to treat due to their malignant phenotype, brain parenchymal infiltration, intratumoral heterogeneity, and immunosuppressive microenvironment, resulting in a high recurrence rate and dismal five-year survival rate. The current standard therapies, including maximum tumor resection, chemotherapy with temozolomide, and radiotherapy, have exhibited limited efficacy, which is caused partially by the resistance of tumor cell death. Recent studies have revealed that ferroptosis, a newly defined programmed cell death (PCD), plays a crucial role in the occurrence and progression of gliomas and significantly affects the efficacy of various treatments, representing a promising therapeutic strategy. In this review, we provide a comprehensive overview of the latest progress in ferroptosis, its involvement and regulation in the pathophysiological process of gliomas, various treatment hotspots, the existing obstacles, and future directions worth investigating. Our review sheds light on providing novel insights into manipulating ferroptosis to provide potential targets and strategies of glioma treatment.

Fabrication of a novel macrophage-targeted biomimetic delivery composite hydrogel with multiple-sensitive properties for tri-modal combination therapy of rheumatoid arthritis.

In this study, a porous polydopamine (PDA) nanoparticle-decorated ß-glucan microcapsules (GMs) nanoplatform (PDA/GMs) were developed with macrophage-targeted biomimetic features and a carriers-within-carriers structure. Indocyanine green (ICG) and catalase (CAT) were subsequently co-encapsulated within the PDA/GMs to create a multifunctional nanotherapeutic agent, termed CIPGs. Furthermore, CIPGs and sinomenine (SIN) were co-loaded within a thermo-sensitive hydrogel to design an injectable delivery system, termed CIPG/SH, with potential for multi-modal therapy of rheumatoid arthritis (RA). Photothermal studies indicated that the CIPGs hold excellent photothermal conversion ability and thermal stability, as they combined the photothermal performance of both PDA and ICG. Meanwhile, the CIPGs displayed favorable oxygen self-supplying and photodynamic performance. The CIPGs showed near-infrared (NIR)-induced phototoxicity, effectively inhibiting macrophage proliferation and displaying remarkable antibacterial activity. In vitro drug release from the prepared CIPG/SH showed a controlled release pattern. Animal experiments conducted on an RA mice model confirmed that the formulated CIPG/SH exhibited significant therapeutic effects. By integrating the biological advantages, photothermal/photodynamic performance of the CIPGs, and controlled drug release performance of the thermo-sensitive hydrogels in a single delivery system, the prepared injectable CIPG/SH represents a novel versatile delivery system with great potential for multi-modal combination targeting therapy in RA.

Corrigendum: Anticancer applications of phytochemicals in gastric cancer: effects and molecular mechanism.

[This corrects the article DOI: 10.3389/fphar.2022.1078090.].

The impact of family climate on problematic internet use: Findings from one nationwide study in China.

BACKGROUND: With the growing attention paid to problematic internet use (PIU), this study aims to i) explore the prevalence of PIU based on a nationally representative sample and ii) propose and validate the theoretical model that correlates family climate with PIU. METHODS: One national cross-sectional study was conducted with probability sampling and stratified sampling. Overall, 21,854 sample were included and analyzed. Validated measures of family climate, loneliness, and PIU was distributed and collected from June 2022 to August 2022. RESULTS: The overall prevalence of PIU in the sample population is approximately 30.86 %. The model findings showed that family communication and family health had indirect effects of -0.12 and - 0.05 on PIU by the mediating effects of loneliness. The indirect effect explained 80.0 % of the total effect of family communication on PIU and 38.5 % of family health on PIU, highlighting the dominance effects of path family communication and PIU via loneliness. Extended family type (-0.047, p = 0.050), low family income (income≤3000 group, -0.127, p < 0.001) were identified as protective factors against PIU, while not living with family members (0.034, p = 0.021) was identified as risk factors of PIU. LIMITATIONS: The nature of cross-sectional data have the limitation of preventing examining the casual relationships of PIU and the loneliness and family climate, in which future longitudinal study design is needed. CONCLUSIONS: The high prevalence of PIU should be given adequate attention. Optimizing the family climate or family atmosphere by improving positive communication skills, providing family support and family health external resources can be served as effective strategies for controlling PIU.

Astrocytic RARγ mediates hippocampal astrocytosis and neurogenesis deficits in chronic retinoic acid-induced depression.

Accumulating clinical evidence indicates that chronic exposure to retinoic acid (RA) may lead to depressive symptoms and even increase the risk of suicidal behavior, which severely limits the clinical long-term application of RA. The exact mechanisms through which RA contributes to the onset of depression remain largely unclear. Here, we administered intraperitoneal injections of all-trans RA to male C57BL/6 J mice over a period of 21 days. Mice subjected to chronic RA exposure displayed depressive-like behaviors, accompanied by impaired hippocampal neurogenesis and heightened RA receptor gamma (RARγ) levels in the ventral hippocampus (vHip). The administration of an RARγ antagonist effectively mitigated these RA-induced neurogenesis impairments and depressive-like behaviors. Chronic exposure to RA was also observed to promote hippocampal astrocytosis and increase astrocytic Rarγ expression in the ventral dentate gyrus (vDG) of hippocampus. Notably, astrocytic RARγ in the vDG was found to be a key factor in the observed hippocampal astrocytosis and neurogenesis impairments, and depressive-like behaviors. Chronic exposure to RA resulted in increased extracellular glutamate levels in neural stem cells (NSCs), accompanied by a decrease in glutamate transporter 1 (GLT-1) expression. Enhancing astrocytic GLT-1 expression was found to alleviate both hippocampal astrocytosis and depressive-like behaviors caused by RA. These findings underscore the critical role of astrocytic RARγ-GLT-1 axis in the development of hippocampal astrocytosis, neurogenesis impairments, and depressive symptoms, suggesting that targeting RARγ-GLT-1 could potentially offer an effective therapeutic approach for depression.

Advances in microbial production of geraniol: from metabolic engineering to potential industrial applications.

Geraniol, an acyclic monoterpene alcohol, has significant potential applications in various fields, including: food, cosmetics, biofuels, and pharmaceuticals. However, the current sources of geraniol mainly include plant tissue extraction or chemical synthesis, which are unsustainable and suffer severely from high energy consumption and severe environmental problems. The process of microbial production of geraniol has recently undergone vigorous development. Particularly, the sustainable construction of recombinant Escherichia coli (13.2 g/L) and Saccharomyces cerevisiae (5.5 g/L) laid a solid foundation for the microbial production of geraniol. In this review, recent advances in the development of geraniol-producing strains, including: metabolic pathway construction, key enzyme improvement, genetic modification strategies, and cytotoxicity alleviation, are critically summarized. Furthermore, the key challenges in scaling up geraniol production and future perspectives for the development of robust geraniol-producing strains are suggested. This review provides theoretical guidance for the industrial production of geraniol using microbial cell factories.

Corrigendum: Effect of dexmedetomidine on somatosensory- and motor evoked potentials in patients receiving craniotomy under propofol-sevoflurane combined anesthesia.

[This corrects the article DOI: 10.3389/fsurg.2024.1386049.].

Population structure and breed identification of Chinese indigenous sheep breeds using whole genome SNPs and InDels.

BACKGROUND: Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. RESULTS: Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. CONCLUSIONS: Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.

Clathrin-associated carriers enable recycling through a kiss-and-run mechanism.

Endocytosis and recycling control the uptake and retrieval of various materials, including membrane proteins and lipids, in all eukaryotic cells. These processes are crucial for cell growth, organization, function and environmental communication. However, the mechanisms underlying efficient, fast endocytic recycling remain poorly understood. Here, by utilizing a biosensor and imaging-based screening, we uncover a recycling mechanism that couples endocytosis and fast recycling, which we name the clathrin-associated fast endosomal recycling pathway (CARP). Clathrin-associated tubulovesicular carriers containing clathrin, AP1, Arf1, Rab1 and Rab11, while lacking the multimeric retrieval complexes, are generated at subdomains of early endosomes and then transported along actin to cell surfaces. Unexpectedly, the clathrin-associated recycling carriers undergo partial fusion with the plasma membrane. Subsequently, they are released from the membrane by dynamin and re-enter cells. Multiple receptors utilize and modulate CARP for fast recycling following endocytosis. Thus, CARP represents a previously unrecognized endocytic recycling mechanism with kiss-and-run membrane fusion.

Early death incidence and prediction in stage IV large cell neuroendocrine carcinoma of the lung.

Nearly half of lung large cell neuroendocrine carcinoma (LCNEC) patients are diagnosed at an advanced stage and face a high early death risk. Our objective was to develop models for assessing early death risk in stage IV LCNEC patients. We used surveillance, epidemiology, and end results (SEER) databases to gather data on patients with stage IV LCNEC to construct models and conduct internal validation. Additionally, we collected a dataset from the Second Affiliated Hospital of Nanchang University for external validation. We used the Pearson correlation coefficient and variance inflation factor to identify collinearity among variables. Logistic regression analysis and least absolute shrinkage and selection operator analysis were employed to identify important independent prognostic factors. Prediction nomograms and network-based probability calculators were developed. The accuracy of the nomograms was evaluated using receiver operating characteristic curves. The goodness of fit of the nomograms was evaluated using the Hosmer-Lemeshow test and calibration curves. The clinical value of the models was assessed through decision curve analysis. We enrolled 816 patients from the surveillance, epidemiology, and end results database and randomly assigned them to a training group and a validation group at a 7:3 ratio. In the training group, we identified 9 factors closely associated with early death and included them in the prediction nomograms. The overall early death model achieved an area under the curve of 0.850 for the training group and 0.780 for the validation group. Regarding the cancer-specific early death model, the area under the curve was 0.853 for the training group and 0.769 for the validation group. The calibration curve and Hosmer-Lemeshow test both demonstrated a high level of consistency for the constructed nomograms. Additionally, decision curve analysis further confirmed the substantial clinical utility of the nomograms. We developed a reliable nomogram to predict the early mortality risk in stage IV LCNEC patients that can be a helpful tool for health care professionals to identify high-risk patients and create personalized treatment plans.

ROS-sensitive PD-L1 siRNA cationic selenide nanogels for self-inhibition of autophagy and prevention of immune escape.

In the field of cancer therapy, inhibiting autophagy has emerged as a promising strategy. However, pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1 (PD-L1), enabling tumor immune evasion. To address this issue, we developed innovative ROS-responsive cationic poly(ethylene imine) (PEI) nanogels using selenol chemistry-mediated multicomponent reaction (MCR) technology. This procedure involved simple mixing of low-molecular-weight PEI (LMW PEI), γ-selenobutylacetone (γ-SBL), and poly(ethylene glycol) methacrylate (PEGMA). Through high-throughput screening, we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels, which exhibited a size of approximately 200 nm, excellent colloidal stability, and the most effective PD-L1 silencing efficacy. These nanogels demonstrated enhanced uptake by tumor cells, excellent oxidative degradation ability, and inhibited autophagy by alkalinizing lysosomes. The A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I (MHC-I), resulting in robust proliferation of specific CD8+ T cells and a decrease in MC38 tumor growth. As a result, the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy, upregulation of MHC-I, and downregulation of PD-L1. Designed with dynamic diselenide bonds, the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.

Efficient Perovskite Solar Cells by Employing Triphenylamine-Functionalized Azadipyrromethene Dyes as Dopant-Free Hole-Transporting Materials and Bidentate Surface Passivating Agents.

In this study, a series of dopant-free, low-cost hole-transporting materials (HTMs) based on triphenylamine-functionalized azadipyrromethene dyes 1-3 (TPA-ADPs 1-3) were designed and synthesized. The properties of these new HTMs were investigated by optical spectroscopy, cyclic voltammetry, thermogravimetric analysis, differential scanning calorimetric, atomic force microscopy, and X-ray diffraction, as well as theoretical calculations. The results indicated that the TPA-ADPs 1-3 presented well-matched energy levels with perovskite, higher hole mobility, as well as more effective defect passivation at the perovskite/HTM interface by the coordination interaction between the ADP moiety and the undercoordinated Pb2+. The n-i-p perovskite solar cells (PSCs) employing HTMs 1-3 as well as doped Spiro-OMeTAD were fabricated and characterized. The TPA-ADP 1-based PSCs exhibited the best performance with a champion power conversion efficiency (PCE) of 22.13% and an fill factor of 0.81, which was superior to that of the devices based on the doped Spiro-OMeTAD. Long-term device performance studies indicated that the TPA-ADP 1-based PSCs maintained 80% of the initial PCE after 1800 h of storage in the ambient condition of 40-60% RH, which was also higher than the stability of doped Spiro-OMeTAD-based devices under the same conditions.

Associations of plasma arginine, homoarginine, and ADMA/SDMA levels with risk of ischemic stroke: A nested case-control study.

BACKGROUND AND AIMS: Previous studies have linked aberrant nitric oxide (NO) metabolism with vascular diseases. Although arginine, homoarginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) are involved in NO metabolic pathways, their associations with ischemic stroke (IS) remain unclear. METHODS AND RESULTS: We conducted a case-control study nested within the Prospective Follow-up Study on Cardiovascular Morbidity and Mortality in China (PFS-CMMC) (2013-2018, n = 16,457; median follow-up time: 5.3 y), which included 321 incident cases of IS and 321 controls matched by age and sex. Plasma arginine, homoarginine, ADMA/SDMA were measured by ultrahigh performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for the association between the plasma metabolites and IS risk. After adjustment for body mass index, educational attainment, smoking, hypertension, hyperlipidemia, diabetes, and family history of stroke, the OR of IS risk for the highest versus the lowest quartile was 2.46 (95% CI: 1.39-4.35, P trend = 0.004) for homoarginine and 2.22 (95% CI: 1.24-3.97, P trend = 0.003) for ADMA/SDMA. Spline regression analyses indicated positive dose-response relationships of homoarginine and ADMA/SDMA with the IS risk (both P for linearity <0.05). No significant association was observed between plasma arginine and IS risk. CONCLUSIONS: Elevated plasma levels of homoarginine and ADMA/SDMA were associated with a higher risk of IS. Our novel findings suggest a role of NO metabolism in the pathogenesis of IS.