miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

The fusiform skin paddle in fibula free flap: a fusiform-designed skin paddle for maxillofacial soft defect reconstruction and reducing leg wound tension.

Objective: To investigate the feasibility of leg wound closure and reconstruction of maxillofacial soft defect by a fusiform-designed skin paddle in fibula free flap (FFF). Methods: Fifty patients who underwent FFF for reconstruction of maxillofacial soft defect were divided into two groups. The fusiform group (20 patients) was treated using a fusiform-designed skin paddle in FFF (skin paddle width less than 2 cm), and leg wound was closed using primary suturing. Reconstruction of the maxillofacial soft defect or filling of dead space was achieved by folding the fusiform skin paddle. The conventional group (30 patients) was treated using the conventional-designed skin paddle (skin paddle width no less than 2.5 cm). The leg wound was closed using mattress suturing or skin graft, while reconstruction of the maxillofacial soft defect or filling of dead space by conventional way. The average postoperative length of hospital stay, healing time of leg wound, and post-surgical complications were recorded at least 6 months after the surgery. Results: Compared with traditional method, the fusiform-designed skin paddle reduced the average healing time of the leg wound (fusiform group: 11.05 days, conventional group: 14.77 days, P < 0.05). The average length-to-width ratio in fusiform group was significantly greater than that of in conventional group (fusiform group: 5.85, conventional group: 2.93, P < 0.05), and no difference was observed on the graft size of skin paddle between two groups (fusiform group: 23.13, conventional group: 27.13, P > 0.05). The post-surgical early complications of the leg wound in the conventional group were higher than that of in the fusiform group (fusiform group: 0%, conventional group: 6.67%), while the post-surgical late complication of the donor site between the two groups showed no case. Healing disorders of maxillofacial soft reconstruction in the conventional group were higher than that of in the fusiform group (fusiform group: 5.26%, conventional group: 20.69%). Conclusions: Fusiform-designed skin paddle for closure of the leg wound and maxillofacial soft defect is a feasible alternative to the conventional- designed skin paddle. The fusiform- designed skin paddle resulted in the less postoperative length of hospital stay, shorter healing time of leg wound and less complication.

Identification of novel biomarker hsa_circ_0003914 for rheumatoid arthritis from plasma exosomes.

Rheumatoid arthritis (RA) is a complex autoimmune disease featuring invasive and infiltrative fibroblast-like synoviocytes (FLS) that lead to joint damage. While current RA pathological mechanisms remain incompletely defined, exosomes have been implicated as having the potential to drive disease progression due to their ability to deliver different types of biomolecules to tissues effected by RA. One potentially disease exacerbating molecule type found in exosomes are Circular RNAs (circRNAs), which are highly stable and have been previously implicated in RA pathogenesis. Here, we examine hsa_circ_0003914, a circRNA found in exosomes located in blood plasma, for a role in RA. Plasma exosomes were isolated and injected into collagen-induced arthritis (CIA) mice, followed by functional experiments to analyze the influence of exosomes on FLS formation. Sequencing revealed the presence of hsa_circ_0003914 in exosomes, so we examined its association with clinical markers in RA. Finally, the role for hsa_circ_0003914 in RA was directly confirmed through in vivo and in vitro experiments. We found that plasma exosomes isolated from RA patients could aggravate the disease of CIA mice, compared to exosomes isolated from healthy control patients. Hsa_circ_0003914 was highly enriched in the exosomes of RA patients. Mechanistically, Hsa_circ_0003914 promoted abnormal cell proliferation, migration, invasion and stimulated the secretion of inflammatory cytokines in FLSs through targeting NF-κB/p65 signaling pathway. Interestingly, knockdown of hsa_circ_0003914 rescued disease phenotypes in CIA mice. Taken together, these data implicate hsa_circ_0003914 as a potential therapeutic target for the prevention and management of RA.

Evolutionary divergence of subgenomes in common carp provides insights into speciation and allopolyploid success.

Hybridization and polyploidization have made great contributions to speciation, heterosis, and agricultural production within plants, but there is still limited understanding and utilization in animals. Subgenome structure and expression reorganization and cooperation post hybridization and polyploidization are essential for speciation and allopolyploid success. However, the mechanisms have not yet been comprehensively assessed in animals. Here, we produced a high-fidelity reference genome sequence for common carp, a typical allotetraploid fish species cultured worldwide. This genome enabled in-depth analysis of the evolution of subgenome architecture and expression responses. Most genes were expressed with subgenome biases, with a trend of transition from the expression of subgenome A during the early stages to that of subgenome B during the late stages of embryonic development. While subgenome A evolved more rapidly, subgenome B contributed to a greater level of expression during development and under stressful conditions. Stable dominant patterns for homoeologous gene pairs both during development and under thermal stress suggest a potential fixed heterosis in the allotetraploid genome. Preferentially expressing either copy of a homoeologous gene at higher levels to confer development and response to stress indicates the dominant effect of heterosis. The plasticity of subgenomes and their shifting of dominant expression during early development, and in response to stressful conditions, provide novel insights into the molecular basis of the successful speciation, evolution, and heterosis of the allotetraploid common carp.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

RATIONALE: Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. PATIENT CONCERNS: A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. DIAGNOSES: The patient was diagnosed with a central nervous system infection. INTERVENTIONS: Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. OUTCOMES: Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. CONCLUSIONS: The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. LESSION: Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

The Investigation of Neuromimetic Dynamics in Ferroelectrics via In Situ TEM.

The core task of neuromorphic devices is to effectively simulate the behavior of neurons and synapses. Based on the functionality of ferroelectric domains with the advantages of low power consumption and high-speed response, great progress has been made in realizing neuromimetic behaviors such as ferroelectric synaptic devices. However, the correlation between the ferroelectric domain dynamics and neuromimetic behavior remains unclear. Here, we reveal the correlation between domain/domain wall dynamics and neuromimetic behaviors from a microscopic perspective in real-time by using high temporal and spatial resolution in situ transmission electron microscopy. Furthermore, we propose utilizing ferroelectric microstructures for the simultaneous simulation of neuronal and synaptic plasticity, which is expected to improve the integration and performance of ferroelectric neuromorphic devices. We believe that this work to study neuromimetic behavior from the perspective of domain dynamics is instructive for the development of ferroelectric neuromorphic devices.

The UF-5000 Atyp.C parameter is an independent risk factor for bladder cancer.

Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The "Atyp.C" parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case-control study identified clinical primary or newly recurrent BC (study period, 2022-2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman's rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P < 0.001). Urinary Atyp.C values were positively correlated with BC pathological grade and invasion (r = 0.360, P < 0.001; r = 0.367, P < 0.001). Urinary Atyp.C was an independent risk factor for BC and closely related with BC pathological grade and invasion. Elevated urinary Atyp.C values was an independent risk factor for BC. Our findings support the use of Atyp.C as a marker that will potentially aid in the early diagnosis and long-term surveillance of new and recurrent BC cases.

Alkali cation-induced cathodic corrosion in Cu electrocatalysts.

The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., -0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

On-mask detection of SARS-CoV-2 related substances by surface enhanced Raman scattering.

We have developed a convenient surface-enhanced Raman scattering (SERS) platform based on vertical standing gold nanowires (v-AuNWs) which enabled the on-mask detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related substances such as the Spike-1 protein and the corresponding pseudo-virus. The Spike-1 protein was clearly distinguished from BSA protein with an accuracy above 99 %, and the detection limit could be achieved down to 0.01 µg/mL. Notably, a similar accuracy was achieved for the pseudo-SARS-CoV-2 (pSARS-2) virus as compared to the pseudo-influenza H7N9 (pH7N9) virus. The sensing strategy and setups could be easily adapted to the real SARS-CoV-2 virus and other highly contagious viruses. It provided a promising way to screen the virus carriers by a fast evaluation of their wearing v-AuNWs integrated face-mask which was mandatory during the pandemic.

Revealing the structural evolution of CuAg composites during electrochemical carbon monoxide reduction.

Comprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.

Survival Analysis and Immune Differences of HIV Long-Term Non-progressors in Xinjiang China: A 12-Year Prospective Cohort Observation.

This 12-year cohort study of 80 long-term non-progressors (LTNPs) observed a cumulative follow-up duration of 628.5 person-years. Among them, 60 received antiretroviral therapy (ART) for a total of 418.6 person-years. Twenty-four deaths occurred during the follow-up period, with an average age of 42.36 years and a lowest 8-year survival rate of 0.90. Cox model analysis revealed that the risk of AIDS-related death was 1.47 times higher for non-marital, non-commercial heterosexual transmission than for injection drug use. Treatment initiation at ages 31-40 was correlated with an elevated risk of mortality, while treatment for 3-10 years reduced mortality risks in untreated LTNPs. Flow cytometry observed significant differences in the proportion of NK cells. Long-term ART (> 2 years) before LTNPs developed AIDS symptoms could lower mortality risk and potentially extend lifespan, especially when it was initiated at a younger age without affecting NK cell balance. Epidemiological and immunological studies on ART-treated LTNPs are vital for advancing HIV treatment and achieving functional cures for AIDS individuals.

RESUMEN: Este estudio de cohorte de 12 años con 80 no progresores a largo plazo (LTNPs) observó un total acumulado de 628.5 personas-año. De ellos, 60 recibieron terapia antirretroviral (TAR) durante un total de 418.6 personas-año. Se produjeron veinticuatro muertes durante el período del estudio, con una edad promedio de 42.36 años y una tasa de supervivencia más baja de 0.90 a los 8 años. El análisis del modelo de Cox identificó que la transmisión heterosexual no marital ni comercial presentaba un riesgo 1.47 veces mayor de muerte relacionada con el SIDA en comparación con el uso de drogas inyectables. Comenzar el tratamiento entre los 31-40 años mostró incrementos en los riesgos de mortalidad, mientras que 3-10 años de tratamiento redujeron los riesgos de mortalidad en LTNPs no tratados. Se observaron diferencias significativas en las proporciones de células NK desde el punto de vista inmunológico. La TAR a largo plazo (> 2 años) antes de la aparición de síntomas del SIDA en LTNPs podría disminuir el riesgo de mortalidad y potencialmente prolongar la vida, especialmente si se inicia a una edad más temprana sin afectar el equilibrio de las células NK. Los estudios epidemiológicos e inmunológicos sobre LTNPs tratados con TAR son fundamentales para el progreso del tratamiento del VIH y la cura funcional del SIDA.

Research progress on the quality control of mRNA vaccines.

INTRODUCTION: The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and development and clinical trials underway for many vaccines. Application of the quality by design (QbD) framework to mRNA vaccine development and establishing standardized quality control protocols for mRNA vaccines are essential for the continued development of high-quality mRNA vaccines. AREAS COVERED: mRNA vaccines include linear mRNA, self-amplifying mRNA, and circular RNA vaccines. This article summarizes the progress of research on quality control of these three types of vaccines and presents associated challenges and considerations. EXPERT OPINION: Although there has been rapid progress in research on linear mRNA vaccines, their degradation patterns remain unclear. In addition, standardized assays for key impurities, such as residual dsRNA and T7 RNA polymerase, are still lacking. For self-amplifying mRNA vaccines, a key focus should be control of stability in vivo and in vitro. For circular RNA vaccines, standardized assays, and reference standards for determining degree of circularization should be established and optimized.

The predictive accuracy of machine learning for the risk of death in HIV patients: a systematic review and meta-analysis.

BACKGROUND: Early prediction of mortality in individuals with HIV (PWH) has perpetually posed a formidable challenge. With the widespread integration of machine learning into clinical practice, some researchers endeavor to formulate models predicting the mortality risk for PWH. Nevertheless, the diverse timeframes of mortality among PWH and the potential multitude of modeling variables have cast doubt on the efficacy of the current predictive model for HIV-related deaths. To address this, we undertook a systematic review and meta-analysis, aiming to comprehensively assess the utilization of machine learning in the early prediction of HIV-related deaths and furnish evidence-based support for the advancement of artificial intelligence in this domain. METHODS: We systematically combed through the PubMed, Cochrane, Embase, and Web of Science databases on November 25, 2023. To evaluate the bias risk in the original studies included, we employed the Predictive Model Bias Risk Assessment Tool (PROBAST). During the meta-analysis, we conducted subgroup analysis based on survival and non-survival models. Additionally, we utilized meta-regression to explore the influence of death time on the predictive value of the model for HIV-related deaths. RESULTS: After our comprehensive review, we analyzed a total of 24 pieces of literature, encompassing data from 401,389 individuals diagnosed with HIV. Within this dataset, 23 articles specifically delved into deaths during long-term follow-ups outside hospital settings. The machine learning models applied for predicting these deaths comprised survival models (COX regression) and other non-survival models. The outcomes of the meta-analysis unveiled that within the training set, the c-index for predicting deaths among people with HIV (PWH) using predictive models stands at 0.83 (95% CI: 0.75-0.91). In the validation set, the c-index is slightly lower at 0.81 (95% CI: 0.78-0.85). Notably, the meta-regression analysis demonstrated that neither follow-up time nor the occurrence of death events significantly impacted the performance of the machine learning models. CONCLUSIONS: The study suggests that machine learning is a viable approach for developing non-time-based predictions regarding HIV deaths. Nevertheless, the limited inclusion of original studies necessitates additional multicenter studies for thorough validation.

Chemokines and lymphocyte homing in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that typically presents with lymphocyte, dendritic cell, and macrophage infiltration of exocrine gland ducts and the formation of ectopic germinal centers. The interactions of lymphocyte homing receptors and addressins and chemokines and their receptors, such as α4ß7/MAdCAM-1, LFA-1/ICAM-1, CXCL13/CXCR5, CCL25/CCR9, CX3CL1/CX3CR1, play important roles in the migration of inflammatory cells to the focal glands and the promotion of ectopic germinal center formation in SS. A variety of molecules have been shown to be involved in lymphocyte homing, including tumor necrosis factor-α, interferon (IFN)-α, IFN-ß, and B cell activating factor. This process mainly involves the Janus kinase-signal transducer and activator of transcription signaling pathway, lymphotoxin-ß receptor pathway, and nuclear factor-κB signaling pathway. These findings have led to the development of antibodies to cell adhesion molecules, antagonists of chemokines and their receptors, compounds interfering with chemokine receptor signaling, and gene therapies targeting chemokines and their receptors, providing new targets for the treatment of SS in humans. The aim of this study was to explore the relationship between lymphocyte homing and the pathogenesis of SS, and to provide a review of recent studies addressing lymphocyte homing in targeted therapy for SS.

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Mechanisms of ligand recognition and activation of melanin-concentrating hormone receptors.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, Gi/o, and MCHR2 can only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Gi and MCH-activated MCHR2 with Gq at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

Effectiveness of the acute stroke care map program in reducing in-hospital delay for acute ischemic stroke in a Chinese urban area: an interrupted time series analysis.

Background: Timely intravenous thrombolysis (IVT) is crucial for improving outcomes in acute ischemic stroke (AIS) patients. This study evaluates the effectiveness of the Acute Stroke Care Map (ASCaM) initiative in Shenyang, aimed at reducing door-to-needle times (DNT) and thus improving the timeliness of care for AIS patients. Methods: An retrospective cohort study was conducted from April 2019 to December 2021 in 30 hospitals participating in the ASCaM initiative in Shenyang. The ASCaM bundle included strategies such as EMS prenotification, rapid stroke triage, on-call stroke neurologists, immediate neuroimaging interpretation, and the innovative Pre-hospital Emergency Call and Location Identification feature. An interrupted time series analysis (ITSA) was used to assess the impact of ASCaM on DNT, comparing 9 months pre-intervention with 24 months post-intervention. Results: Data from 9,680 IVT-treated ischemic stroke patients were analyzed, including 2,401 in the pre-intervention phase and 7,279 post-intervention. The ITSA revealed a significant reduction in monthly DNT by -1.12 min and a level change of -5.727 min post-ASCaM implementation. Conclusion: The ASCaM initiative significantly reduced in-hospital delays for AIS patients, demonstrating its effectiveness as a comprehensive stroke care improvement strategy in urban settings. These findings highlight the potential of coordinated care interventions to enhance timely access to reperfusion therapies and overall stroke prognosis.

Leisure-time physical activity is associated with depressive symptoms in cancer patients: Data from the NHANES 2007-2018.

BACKGROUND: Cancer patients have a higher risk of depression and are associated with severe adverse prognosis. The relationship between leisure-time physical activity (LTPA) and depressive symptoms in cancer patients is currently unclear. Therefore, our study mainly explores the potential association between LTPA and the weekly cumulative time of LTPA with depressive symptoms in cancer patients. METHODS: We included and analyzed 3368 cancer patients (aged >20 years) from the National Health and Nutrition Examination Survey (NHANES) of the United States from 1999 to 2018. The LTPA score was evaluated through a self-report questionnaire, while depressive symptoms were evaluated through the Health Questionnaire-9 (PHQ-9). Multiple logistic regression analysis was used to explore the relationship between LTPA duration and the occurrence of cancer-related depressiive symptoms. Linear correlation was studied using the restricted cubic spline method. RESULTS: According to a fully adjusted multivariate logistic regression model with confounding variables, the odds ratio (OR) between LTPA and depressive symptoms in cancer patients in this study was 0.59 (95 % confidence interval = 0.39, 0.92; P = 0.02). When the LTPA level was ≥300 min/week, the incidence of depressive symptoms was reduced by 59 % (OR = 0.41, 95 % CI = 0.21, 0.83). In addition, the cubic spline method was used to obtain a linear negative correlation between LTPA duration and tumor depressive symptoms. CONCLUSION: LTPA was negatively correlated with cancer-related depressive symptoms, and the cumulative time of LTPA/week was linearly correlated with depressive symptoms. The slope of the benefit curve changed significantly when the cumulative time of LTPA reached 600 min per week, suggesting that appropriately increasing LTPA had significant benefits on mental health of cancer patients.

Cultivating High-Performance Flexible All-in-One Supercapacitors With 3D Network Through Continuous Biosynthesis.

Flexible supercapacitors can potentially power next-generation flexible electronics. However, the mechanical and electrochemical stability of flexible supercapacitors under different flexible conditions is limited by the weak bonding between adjacent layers, posing a significant hindrance to their practical applicability. Herein, based on the uninterrupted 3D network during the growth of bacterial cellulose (BC), a flexible all-in-one supercapacitor is cultivated through a continuous biosynthesis process. This strategy ensures the continuity of the 3D network of BC throughout the material, thereby forming a continuous electrode-separator-electrode structure. Benefitting from this bioinspired structure, the all-in-one supercapacitor not only achieves a high areal capacitance (3.79 F cm-2) of electrodes but also demonstrates the integration of high tensile strength (2.15 MPa), high shear strength (more than 54.6 kPa), and high bending resistance, indicating a novel pathway toward high-performance flexible power sources.

Prognostic factors and predictive models for patients with lung large cell neuroendocrine carcinoma: Based on SEER database.

BACKGROUND: Lung Large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive, high-grade neuroendocrine carcinoma with a poor prognosis, mainly seen in elderly men. To date, we have found no studies on predictive models for LCNEC. METHODS: We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database of confirmed LCNEC from 2010 to 2018. Univariate and multivariate Cox proportional risk regression analyses were used to identify independent risk factors, and then we constructed a novel nomogram and assessed the predictive effectiveness by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: A total of 2546 patients with LCNEC were included, excluding those diagnosed with autopsy or death certificate, tumor, lymph node, metastasis (TNM) stage, tumor grade deficiency, etc., and finally, a total of 743 cases were included in the study. After univariate and multivariate analyses, we concluded that the independent risk factors were N stage, intrapulmonary metastasis, bone metastasis, brain metastasis, and surgical intervention. The results of ROC curves, calibration curves, and DCA in the training and validation groups confirmed that the nomogram could accurately predict the prognosis. CONCLUSIONS: The nomogram obtained from our study is expected to be a useful tool for personalized prognostic prediction of LCNEC patients, which may help in clinical decision-making.