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The flexible pressure sensors with a broad pressure range and unsaturated sensitivity are highly desired in practical applications. However, pressure sensors by piezoresistive effect are always limited by the compressibility of sensing layers, resulting in a theoretically decreasing sensitivity of less than 100%. Here, a unique strategy is proposed that utilizes the strain effect, simultaneously achieving a trade-off between a wider pressure detection range and unsaturated sensitivity. Ascribed to the strain effect of sensing layers induced by interlaced microdomes, the sensors possess an increased sensitivity (5.22-70 MPa-1) over an ultrawide pressure range (45 Pa-4.1 MPa), a high-pressure resolution (5 Pa), fast response/recovery time (30/45 ms), and a robust response under a high-pressure loading of 3.5 MPa for more than 5000 cycles. These superior sensing performances allow the sensor to monitor large pressure. The flexible pressure sensor array can assist doctors in restoring the neutral mechanical axis, tracking knee flexion angles, and extracting gait features. Moreover, the flexible sensing array can be integrated into the joint motion surveillance system to map the balance medial-lateral contact forces on the metal compartments in real time, demonstrating the potential for further development into precise medical human-machine interfaces during total knee replacement surgery.
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The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.
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Envejecimiento , Aneurisma de la Aorta , Disección Aórtica , Senescencia Celular , MicroARNs , Músculo Liso Vascular , Quinasa de Cadena Ligera de Miosina , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Envejecimiento/genética , Envejecimiento/metabolismo , Angiotensina II/metabolismo , Aneurisma de la Aorta/metabolismo , Aneurisma de la Aorta/genética , Aneurisma de la Aorta/patología , Disección Aórtica/metabolismo , Disección Aórtica/genética , Disección Aórtica/patología , Proteínas de Unión al Calcio , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Quinasa de Cadena Ligera de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Aortic dissection is usually managed with interventional therapy, conservative therapy, and surgery to inhibit disease progression and improve prognoses. Nevertheless, the absence of meticulous and effective nursing during the treatment greatly increases the complication rates, which is detrimental to the recovery of patients. OBJECTIVE: This study aimed to explore the efficacy of predictive pain intervention in the nursing process of patients with aortic dissection. METHODS: Sixty patients with aortic dissection who were admitted to our hospital from December 2018 to December 2020 were observed in this study. Specifically, these patients were randomly and equally classified into Group A (patients who were given conventional nursing intervention) and Group B (patients who were given predictive pain intervention). Subsequently, the pain score, complication rates, and nursing satisfaction in the two groups were compared and analyzed. RESULTS: Compared with patients in Group A, patients in Group B had significantly lower pain scores (P< 0.05); complication rates were significantly lower in Group B than in Group A (6.67% vs. 23.33%, P< 0.05); patient satisfaction with care was significantly better in Group B compared to Group A (96.67% vs. 73.33%, P< 0.05). CONCLUSION: Predictive pain intervention is widely recognized as useful in the treatment of patients with aortic dissection. It has significant clinical application value as it can largely alleviate pain and is relatively safe for patients.
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Heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) are hazardous substances produced when food is heated. In this study, the ability of plasma-activated water (PAW) to simultaneously mitigate production of HAAs and AGEs in roasted beef patties was investigated. Assays of free radicals, lipid peroxidation, and active carbonyls were used to analyze the mechanisms. PAW treatment decreased the contents of free HAAs, free AGEs, bound HAAs, and bound AGEs to 12.65 ng/g, 0.10 µg/g, 297.74 ng/g, and 4.32 µg/g, with the inhibition rates of 23.88%, 23.08%, 11.02%, and 8.47%, respectively. PAW treatment decreased HAAs and AGEs and mitigated their increase during storage. The decrease of HAAs and AGEs in PAW-treated samples was correlated with the enhancement of antioxidant capacity. The increase of free radical scavenging ability by PAW treatment led to the decrease of lipid peroxidation and the decrease of active carbonyls, HAAs, and AGEs in meat products.
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Aminas , Productos Finales de Glicación Avanzada , Productos de la Carne , Productos Finales de Glicación Avanzada/metabolismo , Animales , Bovinos , Productos de la Carne/análisis , Aminas/metabolismo , Agua/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Calor , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/química , Culinaria , Antioxidantes/metabolismo , Antioxidantes/química , Antioxidantes/farmacologíaRESUMEN
Recreating the natural heart's mechanical and electrical environment is crucial for engineering functional cardiac tissue and repairing infarcted myocardium in vivo. In this study, multimaterial-printed serpentine microarchitectures are presented with synergistic mechanical/piezoelectric stimulation, incorporating polycaprolactone (PCL) microfibers for mechanical support, polyvinylidene fluoride (PVDF) microfibers for piezoelectric stimulation, and magnetic PCL/Fe3O4 for controlled deformation via an external magnet. Rat cardiomyocytes in piezoelectric constructs, subjected to dynamic mechanical stimulation, exhibit advanced maturation, featuring superior sarcomeric structures, improved calcium transients, and upregulated maturation genes compared to non-piezoelectric constructs. Furthermore, these engineered piezoelectric cardiac constructs demonstrate significant structural and functional repair of infarcted myocardium, as evidenced by enhanced ejection and shortening fraction, reduced fibrosis and inflammation, and increased angiogenesis. The findings underscore the therapeutic potential of piezoelectric cardiac constructs for myocardial infarction therapy.
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Additive manufacturing (3D printing) technology aligns with the direction of precision and customization in future medicine, presenting a significant opportunity for innovative development in high-end medical devices. Currently, research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants. Primary areas including metallic orthopaedic implants, polyether-ether-ketone (PEEK) bone implants, and biodegradable implants have been developed for clinical and industrial application. Recent research achievements in these areas are reviewed, with a discussion on the additive manufacturing technologies and applications for customized implants. Challenges faced by different types of implants are analyzed from technological, application, and regulatory perspectives. Furthermore, prospects and suggestions for future development are outlined.
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Impresión Tridimensional , Prótesis e Implantes , Benzofenonas , Polímeros , Humanos , Cetonas , Diseño de Prótesis , Materiales Biocompatibles , Polietilenglicoles , Implantes AbsorbiblesRESUMEN
Ultrasmall copper nanoclusters have recently emerged as promising photocatalysts for organic synthesis, owing to their exceptional light absorption ability and large surface areas for efficient interactions with substrates. Despite significant advances in cluster-based visible-light photocatalysis, the types of organic transformations that copper nanoclusters can catalyze remain limited to date. Herein, we report a structurally well-defined anionic Cu40 nanocluster that emits in the second near-infrared region (NIR-II, 1000-1700 nm) after photoexcitation and can conduct single-electron transfer with fluoroalkyl iodides without the need for external ligand activation. This photoredox-active copper nanocluster efficiently catalyzes the three-component radical couplings of alkenes, fluoroalkyl iodides, and trimethylsilyl cyanide under blue-LED irradiation at room temperature. A variety of fluorine-containing electrophiles and a cyanide nucleophile can be added onto an array of alkenes, including styrenes and aliphatic olefins. Our current work demonstrates the viability of using readily accessible metal nanoclusters to establish photocatalytic systems with a high degree of practicality and reaction complexity.
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The periocular mesenchyme (POM) is a transient migratory embryonic tissue derived from neural crest cells (NCCs) and paraxial mesoderm that gives rise to most of the structures in front of the eye. Morphogenetic defects of these structures can impair aqueous humor outflow, leading to elevated intraocular pressure and glaucoma. Mutations in collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) cause Gould syndrome - a multisystem disorder often characterized by variable cerebrovascular, ocular, renal, and neuromuscular manifestations. Approximately one-third of individuals with COL4A1 and COL4A2 mutations have ocular anterior segment dysgenesis (ASD), including congenital glaucoma resulting from abnormalities of POM-derived structures. POM differentiation has been a major focus of ASD research, but the underlying cellular mechanisms are still unclear. Moreover, earlier events including NCC migration and survival defects have been implicated in ASD; however, their roles are not as well understood. Vascular defects are among the most common consequences of COL4A1 and COL4A2 mutations and can influence NCC survival and migration. We therefore hypothesized that NCC migration might be impaired by COL4A1 and COL4A2 mutations. In this study, we used 3D confocal microscopy, gross morphology, and quantitative analyses to test NCC migration in Col4a1 mutant mice. We show that homozygous Col4a1 mutant embryos have severe embryonic growth retardation and lethality, and we identified a potential maternal effect on embryo development. Cerebrovascular defects in heterozygous Col4a1 mutant embryos were present as early as E9.0, showing abnormal cerebral vasculature plexus remodeling compared to controls. We detected abnormal NCC migration within the diencephalic stream and the POM in heterozygous Col4a1 mutants whereby mutant NCCs formed smaller diencephalic migratory streams and POMs. In these settings, migratory NCCs within the diencephalic stream and POM localize farther away from the developing vasculature. Our results show for the first time that Col4a1 mutations lead to cranial NCCs migratory defects in the context of early onset defective angiogenesis without affecting cell numbers, possibly impacting the relation between NCCs and the blood vessels during ASD development.
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Purpose: Mutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta (TGFß) signaling was elevated in developing anterior segments from Col4a1 mutant mice and that reducing TGFß signaling ameliorated ASD, supporting a role for the TGFß pathway in disease pathogenesis. Here, we tested whether altered TGFß signaling also contributes to glaucoma-related phenotypes in Col4a1 mutant mice. Methods: To test the role of TGFß signaling in glaucoma-relevant phenotypes, we genetically reduced TGFß signaling using mice with mutated Tgfbr2, which encodes the common receptor for all TGFß ligands in Col4a1+/G1344D mice. We performed slit-lamp biomicroscopy and optical coherence tomography for qualitative and quantitative analyses of anterior and posterior ocular segments, histological analyses of ocular tissues and optic nerves, and intraocular pressure assessments using rebound tonometry. Results: Col4a1+/G1344D mice showed defects of the ocular drainage structures, including iridocorneal adhesions, and phenotypes consistent with glaucomatous neurodegeneration, including thinning of the nerve fiber layer, retinal ganglion cell loss, optic nerve head excavation, and optic nerve degeneration. We found that reducing TGFß receptor 2 (TGFBR2) was protective for ASD, ameliorated ocular drainage structure defects, and protected against glaucomatous neurodegeneration in Col4a1+/G1344D mice. Conclusions: Our results suggest that elevated TGFß signaling contributes to glaucomatous neurodegeneration in Col4a1 mutant mice.
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Colágeno Tipo IV , Glaucoma , Receptor Tipo II de Factor de Crecimiento Transformador beta , Transducción de Señal , Factor de Crecimiento Transformador beta , Animales , Ratones , Segmento Anterior del Ojo/metabolismo , Segmento Anterior del Ojo/patología , Colágeno Tipo IV/metabolismo , Colágeno Tipo IV/genética , Modelos Animales de Enfermedad , Glaucoma/metabolismo , Glaucoma/genética , Glaucoma/patología , Presión Intraocular/fisiología , Ratones Endogámicos C57BL , Mutación , Nervio Óptico/patología , Nervio Óptico/metabolismo , Enfermedades del Nervio Óptico/metabolismo , Enfermedades del Nervio Óptico/genética , Fenotipo , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta/metabolismo , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/metabolismo , Transducción de Señal/fisiología , Microscopía con Lámpara de Hendidura , Tomografía de Coherencia Óptica , Tonometría Ocular , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Nature-inspired microfluidic networks are revolutionizing microphysiological systems, allowing for the precise emulation of human physiology. This article delves into the fabrication techniques of leaf-venation-inspired (LVI) microfluidic networks and explores their transformative applications in organ-on-a-chip and tissue engineering, showcasing their pivotal role in advancing biomedical research.
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Color-tunable organic light-emitting diodes (CT-OLEDs) have a large color-tuning range, high efficiency and operational stability at practical luminance, making them ideal for human-machine interactive terminals of wearable biomedical devices. However, the device operational lifetime of CT-OLEDs is currently far from reaching practical requirements. To address this problem, a tetradentate Pt(II) complex named tetra-Pt-dbf, which can emit efficiently in both monomer and aggregation states, is designed. This emitter has high Td of 508 °C and large intermolecular bonding energy of -52.0 kcal molâ»1, which improve its thermal/chemical stability. This unique single-emitter CT-OLED essentially avoids the "color-aging issue" and achieves a large color-tuning span (red to yellowish green) and a high external quantum efficiency ï¼EQEï¼ of ≈30% at 1000 cd m-2 as well as an EQE of above 25% at 10000 cd m-2. A superior LT90 operational lifetime of 520,536 h at a functional luminance of 100 cd m-2, which is over 20 times longer than the state-of-the-art CT-OLEDs, is estimated. To demonstrate the potential application of such OLEDs in wearable biomedical devices, a simple electromyography (EMG)-visualization system is fabricated using the CT-OLEDs.
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Lung cancer is the leading cause of cancer death, and its effective treatment is a difficult medical problem. Lung cancer belongs to the traditional Chinese medicine(TCM) disease categories of lung accumulation, lung amassment, and overstrain cough. Rich theoretical basis and practical experience have been accumulated in the TCM treatment of lung cancer. Astragali Radix is one of the representatives of Qi-tonifying drugs. It mainly treat the lung cancer with the syndrome of Qi deficiency and pathogen stagnation, following the principle of reinforcing healthy Qi and eliminating patgogenic Qi. Astragali Radix exerts a variety of pharmacological activities in the treatment of lung cancer, including inhibiting tumor cell proliferation and promoting tumor cell apoptosis, inhibiting tumor invasion and migration, regulating the tumor microenvironment, suppressing tumor angiogenesis, modulating autophagy, inducing macrophage polarization, enhancing immunity, inhibiting immune escape, and reversing cisplatin resistance. The active ingredients of Astragali Radix in treating lung cancer include polysaccharides, saponins, and flavonoids. This study reviewed the pharmacological activities and active ingredients of Astragali Radix in the treatment of lung cancer, providing a basis for the development and utilization of Astragali Radix resources and active ingredients and the research and development of anti-tumor drugs.
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Planta del Astrágalo , Medicamentos Herbarios Chinos , Neoplasias Pulmonares , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Medicina Tradicional China , Raíces de Plantas , Microambiente TumoralRESUMEN
Background: According to GLOBOCAN 2020, lymphoma ranked as the 9th most common cancer and the 12th leading cause of cancer-related deaths worldwide. Traditional diagnostic methods rely on the invasive excisional lymph node biopsy, which is an invasive approach with some limitations. Most lymphoma patients are diagnosed at an advanced stage since they are asymptomatic at the beginning, which has significantly impacted treatment efficacy and prognosis of the disease. Method: This study assessed the performance and utility of a newly developed blood-based assay (SeekInCare) for lymphoma early detection. SeekInCare utilized protein tumor markers and a comprehensive set of cancer-associated genomic features, including copy number aberration (CNA), fragment size (FS), end motif, and lymphoma-related virus, which were profiled by shallow WGS of cfDNA. Results: Protein marker CA125 could be used for lymphoma detection independent of gender, and the sensitivity was 27.8% at specificity of 98.0%. After integrating these multi-dimensional features, 77.8% sensitivity was achieved at specificity of 98.0%, while its NPV and PPV were both more than 92% for lymphoma detection. The sensitivity of early-stage (I-II) lymphoma was up to 51.3% (47.4% and 55.0% for stage I and II respectively). After 2 cycles of treatment, the molecular response of SeekInCare was correlated with the clinical outcome. Conclusion: In summary, a blood-based assay can be an alternative to detect lymphoma with adequate performance. This approach becomes particularly valuable in cases where obtaining tissue biopsy is difficult to obtain or inconclusive.
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To estimate the prevalence of dynapenia and examine potential risk factors for dynapenia using a sample of rural middle-aged and elderly Chinese. A cross-sectional study of 253 Chinese adults aged 50 years and older was conducted from June to August in 2022 in Nanjing. A questionnaire was used to collect data on all socioeconomic variables. Body weight, height, body fat percentage, grip strength, waist circumference, calf circumference, and gait speed were measured. The prevalence of dynapenia was 69.6 %, 62.3 % in men and 72.7 % in women respectively. Binary logistic regressions indicated significant associations between dynapenia and age (odds ratio [OR] = 2.59; 95 % confidence interval [CI] 1.63, 4.12; p < 0.001), educational level (OR = 0.55; 95 % CI 0.38, 0.80; p = 0.002). Dynapenia was prevalent among rural middle-aged and elderly people in southern China. Age and lower education level were both associated with dynapenia. Nutrition and physical activity should be strongly recommended as important strategies to maintain and improve muscle strength.
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Recent advances in heart-on-a-chip systems hold great promise to facilitate cardiac physiological, pathological, and pharmacological studies. This review focuses on the development of heart-on-a-chip systems with tissue-specific functionalities. For one thing, the strategies for developing cardiac microtissues on heart-on-a-chip systems that closely mimic the structures and behaviors of the native heart are analyzed, including the imitation of cardiac structural and functional characteristics. For another, the development of techniques for real-time monitoring of biophysical and biochemical signals from cardiac microtissues on heart-on-a-chip systems is introduced, incorporating cardiac electrophysiological signals, contractile activity, and biomarkers. Furthermore, the applications of heart-on-a-chip systems in intelligent cardiac studies are discussed regarding physiological/pathological research and pharmacological assessment. Finally, the future development of heart-on-a-chip toward a higher level of systematization, integration, and maturation is proposed.
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BACKGROUND: The significant clinical benefits of PD-1/PD-L1 immune checkpoint inhibitors (ICIP) in non-small cell lung cancer (NSCLC) have been widely recognized, emphasizing the urgent need for a reliable biomarker. In this study, we find the remarkable capacity of tumor mutational burden (TMB) to serve as an accessible and streamlined indicator. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 600 NSCLC patients treated with ICIP. Association between TMB and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) has been explored. RESULTS: A strong positive correlation between TMB levels and OS, PFS rates, clinical benefit has been found when TMB > = 16(TMB > = 16 mutations/megabase (mut/Mb)). However, when TMB < 16, increasing TMB values did not exhibit a gradual stepwise increase in OS and PFS rates. The median months of OS in the TMB > = 16 and < 16 are 35.58, and 10.71 months respectively with average 12.39 months (p < 0.0001). The median months of PFS in the TMB > = 16 and < 16 are not-obtained, and 2.79 months respectively with an average of 3.32 months (p < 0.0001). The DCR in the TMB > = 16 and < 16 are 71.4% and 44.2% respectively with an average of 47.7% (p < 0.0001). The ORR in the TMB > = 16 and < 16 are 49.4% and 20.8% respectively with an average of 24.5% (p < 0.0001). CONCLUSION: The TMB > = 16 shows significantly associated with optimal ICIP treatment outcomes, including higher patient survival rates, delayed disease progression, and significant clinical benefits. These results present the potential of TMB as a promising biomarker candidate for NSCLC patients undergoing ICIP treatment.
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Antígeno B7-H1 , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Mutación , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/genética , Antígeno B7-H1/antagonistas & inhibidores , Adulto , Anciano de 80 o más Años , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Supervivencia sin Progresión , Tasa de SupervivenciaRESUMEN
Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1st, 2019 to December 31st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.
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Lactante , Masculino , Recién Nacido , Humanos , Femenino , Estudios Prospectivos , Hipotiroidismo Congénito/epidemiología , Factores de Riesgo , Recién Nacido de muy Bajo Peso , Peso al Nacer , Edad Gestacional , Retinopatía de la Prematuridad/epidemiología , Enfermedades del Recién Nacido , HospitalesRESUMEN
The heat shock cognate 71 kDa protein (Hsc70) is a stressinducible ATPase that can protect cells against harmful stimuli. Transient receptor potential vanilloid 1 (TRPV1) is a welldocumented nociceptor. Notably, Hsc70 can inhibit TRPV1 expression and function, suggesting that Hsc70 may have pain regulation potential. However, the role of Hsc70 in stressinduced hyperalgesia remains unclear. In the present study, the participation of Hsc70 and its regulator microRNA (miR)3120 were investigated in forced swim (FS) stressinduced mechanical hyperalgesia in rats in an inflammatory state. Complete Freund's adjuvant (CFA) hind paw injection was performed to induce inflammatory pain in rats (CFA rats). Furthermore, in FS + CFA rats, FS stress was performed for 3 days before CFA injection. The levels of Hsc70, miR3120 and their downstream molecule TRPV1 were measured in the dorsal root ganglion (DRG) with western blotting, immunofluorescence, reverse transcriptionquantitative polymerase chain reaction and fluorescence in situ hybridization. The results revealed that FS stress significantly exacerbated CFAinduced mechanical pain. Furthermore, CFA upregulated Hsc70 and TRPV1 expression, which was partially inhibited or further enhanced by FS stress, respectively. In FS + CFA rats, intrathecal injection of a lentiviral vector overexpressing Hsc70 (LVHsc70) could decrease TRPV1 expression and improve the mechanical pain. Additionally, the expression levels of miR3120, a regulator of Hsc70, were markedly upregulated on day 3 following FS stress. Finally, miR3120 was identified to be colocalized with Hsc70 and expressed in all sizes of DRG neurons. In CFA rats, DRG injection of miR3120 agomir to induce overexpression of miR3120 resulted in similar TRPV1 expression and behavioral changes as those caused by FS stress, which were abolished in the presence of LVHsc70. These findings suggested that miR3120/Hsc70 may participate in FS stressinduced mechanical hyperalgesia in rats in an inflammatory state, possibly via disinhibiting TRPV1 expression in the DRG neurons.
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Hiperalgesia , MicroARNs , Animales , Ratas , Adyuvante de Freund/efectos adversos , Ganglios Espinales/metabolismo , Hiperalgesia/genética , Hiperalgesia/inducido químicamente , Hibridación Fluorescente in Situ , Inflamación/inducido químicamente , MicroARNs/genética , MicroARNs/metabolismo , Dolor/genética , Dolor/metabolismo , Ratas Sprague-Dawley , Canales Catiónicos TRPV/metabolismoRESUMEN
The ongoing coronavirus disease 2019 (COVID-19) pandemic, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the critical role of genomic surveillance in tracking rapidly spreading viruses and their evolving lineages. The emergence of the SARS-CoV-2 tiling array, a comprehensive tool capable of capturing the entire viral genome, has presented a promising avenue for variants. This study introduces the SARS-CoV-2 tiling array as a novel method for port inspection. Using next-generation sequencing as a benchmark, 35 positive samples underwent sequencing through both methodologies, including the Alpha variant (B.1.1.7), Delta variants (AY.120, AY.122, AY.23.1), and Omicron variants (BA.1, BA.2, BA.2.75, BA.4, BA.5, BE.1, BF.7, BN.1, BQ.1, XBB.1) within the sample set. The whole-genome tiling array demonstrated successful identification of various sublineages of SARS-CoV-2. The average sequencing coverage rates were 99.22% (96.82%-99.92%) for the whole-genome tiling array and 98.56% (92.81%-99.59%) for Illumina sequencing, respectively. The match rates of these two methods ranged from 92.81%-99.59%, with an average rate of 98.56%. Among the benefits of the whole-genome tiling array are its cost-effectiveness and equipment simplification, making it particularly suitable for identifying SARS-CoV-2 variants in the front-line inspection department. The aforementioned findings provide valuable insights into the surveillance of COVID-19 and present a pragmatic solution for improving quarantine measures at entry points.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiología , China/epidemiología , Genoma ViralRESUMEN
BACKGROUND: Circulating cell-free DNA (cfDNA) is a pool of short DNA fragments mainly released from apoptotic hematopoietic cells. Nevertheless, the precise physiological process governing the DNA fragmentation and molecular profile of cfDNA remains obscure. To dissect the DNA fragmentation process, we use a human leukemia cell line HL60 undergoing apoptosis to analyze the size distribution of DNA fragments by shallow whole-genome sequencing (sWGS). Meanwhile, we also scrutinize the size profile of plasma cfDNA in 901 healthy human subjects and 38 dogs, as well as 438 patients with six common cancer types by sWGS. RESULTS: Distinct size distribution profiles were observed in the HL60 cell pellet and supernatant, suggesting fragmentation is a stepwise process. Meanwhile, C-end preference was seen in both intracellular and extracellular cfDNA fragments. Moreover, the cfDNA profiles are characteristic and conserved across mammals. Compared with healthy subjects, distinct cfDNA profiles with a higher proportion of short fragments and lower C-end preference were found in cancer patients. CONCLUSIONS: Our study provides new insight into fragmentomics of circulating cfDNA processing, which will be useful for early diagnosis of cancer and surveillance during cancer progression.