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Purpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. Conclusion: A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Clinical Trial Registration: ChiCTR2400080363.
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Dexmedetomidina , Hipnóticos y Sedantes , Ketamina , Remifentanilo , Remifentanilo/administración & dosificación , Remifentanilo/farmacología , Humanos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/farmacología , Ketamina/administración & dosificación , Ketamina/farmacología , Método Doble Ciego , Femenino , Estudios Prospectivos , Masculino , Adulto , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/farmacología , Lipectomía , Persona de Mediana Edad , Analgésicos/administración & dosificación , Analgésicos/farmacología , Anestesia , Relación Dosis-Respuesta a Droga , Adulto JovenRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. METHODS: We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. RESULTS: Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. CONCLUSION: The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets.
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The rotating Ring Disk Electrode (RRDE), since its introduction in 1959 by Frumkin and Nekrasov, has become indispensable with diverse applications in electrochemistry, catalysis, and material science. The collection efficiency (N) is an important parameter extracted from the ring and disk currents of the RRDE, providing valuable information about reaction mechanism, kinetics, and pathways. The theoretical prediction of N is a challenging task: requiring solution of the complete convective diffusion mass transport equation with complex velocity profiles. Previous efforts, including by Albery and Bruckenstein who developed the most widely used analytical equations, heavily relied on approximations by removing radial diffusion and using approximate velocity profiles. 65 years after the introduction of RRDE, we employ a physics-informed neural network to solve the complete convective diffusion mass transport equation, to reveal the formerly neglected edge effects and velocity corrections on N, and to provide a guideline where conventional approximation is applicable.
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Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disease. Nusinersen sodium (NS) is the world's first antisense oligonucleotide (ASO) drug for SMA precise targeted therapy. However, the limited half-life of oligonucleotides and their tendency to accumulate in hepatic and renal tissues presented significant challenges for clinical investigation and therapeutic drug monitoring. In this study, we proposed an analytical strategy based on the specific capture of oligonucleotide functionalized fluorescent probes by single stranded binding proteins (SSB) for ultra-sensitive and high-throughput detection of nusinersen sodium in human serum. The magnetic nanoparticles modified with single-strand binding protein (MNPs-SSB) selectively bonded to the red fluorescent quantum dots functionalized with oligonucleotides (RQDs-ssDNA) that were complementary to nusinersen sodium. Upon interaction with nusinersen sodium, RQDs-ssDNA formed a double-stranded complex (RQDs-ssDNA-NS), resulting in enhanced red fluorescence after magnetic separation as it was no longer captured by MNPs-SSB but remained in the supernatant. A quantitative analysis of nusinersen sodium in biological samples was successfully achieved by establishing a relationship between fluorescence intensity and its concentration. The detection signal F/F0 exhibited a linear correlation (R2 = 0.9871) over a wide range from 0.1 nM to 200 nM, with a limit of detection (LOD) of 0.03 nM, demonstrating the high specificity and rapid analysis time (only 30 min). This method provided a novel approach for sensitive, high-throughput, and specific analysis of nusinersen sodium and similar ASO drugs.
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Colorantes Fluorescentes , Oligonucleótidos , Humanos , Oligonucleótidos/química , Colorantes Fluorescentes/química , Límite de Detección , Puntos Cuánticos/química , Espectrometría de Fluorescencia/métodos , Nanopartículas de Magnetita/químicaRESUMEN
INTRODUCTION: Exercise has been used to reverse dysglycaemic states in patients with pre-diabetes. Systematic reviews show that exercise is an effective way to reduce the incidence of diabetes, but there is conflicting evidence for reducing the occurrence of cardiovascular events. Therefore, we present a systematic review and network meta-analysis protocol designed to compare the effectiveness of different forms of exercise in reducing cardiovascular events and their tolerability in different populations. METHODS AND ANALYSIS: We will include all randomised controlled trials and compare one exercise intervention to another. We will compare the following exercise patterns: standard endurance training, strength training, high-intensity interval training, mind-body exercise, and mixed strength and aerobic training. The primary outcomes are the occurrence of major cardiovascular events and the rate of patient attrition during the intervention. We will search major English and Chinese databases as well as trial registry websites for published and unpublished studies. All reference selection and data extraction will be conducted by at least two independent reviewers. We will conduct a random effects model to combine effect sizes and use the surface under the cumulative ranking curve and the mean ranks to rank the effectiveness of interventions. All data will be fitted at WinBUGS in a Bayesian framework and correlation graphs will be plotted using StataSE 14. We will also use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to evaluate the quality of evidence for the study results. ETHICS AND DISSEMINATION: This study does not involve a population-based intervention, and therefore, does not require ethical approval. We will publish the findings of this systematic review in a peer-reviewed scientific journal, and the dataset will be made available free of charge. The completed review will be disseminated electronically in print and on social media, where appropriate. PROSPERO REGISTRATION NUMBER: CRD42023422737.
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Enfermedades Cardiovasculares , Metaanálisis en Red , Estado Prediabético , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Humanos , Enfermedades Cardiovasculares/prevención & control , Estado Prediabético/terapia , Proyectos de Investigación , Terapia por Ejercicio/métodos , Ejercicio Físico , Entrenamiento de Fuerza/métodosRESUMEN
Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.
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Biomarcadores de Tumor , Vesículas Extracelulares , Histonas , Neoplasias de la Próstata , Proteómica , Humanos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Masculino , Proteómica/métodos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/orina , Vesículas Extracelulares/metabolismo , Histonas/metabolismo , Medición de Riesgo/métodos , Persona de Mediana Edad , Anciano , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , LamininaRESUMEN
Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.
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Antidepresivos , Péptidos de Penetración Celular , Prolactina , Sulpirida , Animales , Prolactina/sangre , Sulpirida/farmacología , Antidepresivos/farmacología , Ratones , Masculino , Péptidos de Penetración Celular/farmacología , Depresión/tratamiento farmacológico , Depresión/sangre , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Disponibilidad BiológicaRESUMEN
OBJECTIVE: This review evaluates the efficacy and safety of dysphagia interventions for patients with prolonged endotracheal intubation (⩾48 h) in critical care units. DATA SOURCES: We systematically searched PubMed, Cochrane Library, Medline, Embase, OVID, CINAHL, Wanfang (China), CNKI (China), and ProQuest Dissertations for studies published up to December 31, 2023. STUDY SELECTION: Inclusion criteria encompassed randomized controlled trials (RCTs), quasi-randomized trials, and cohort studies comparing dysphagia rehabilitation - such as swallowing stimulation, swallowing and respiratory muscle exercise, and neuromuscular electrical stimulation - with standard care or no treatment. The primary outcomes assessed were dysphagia severity, time to resume oral intake, and incidence of aspiration and aspiration pneumonia. DATA EXTRACTION: Detailed information on study design, setting, participant demographics, interventions, and outcomes was systematically extracted. DATA SYNTHESIS: Our analysis included ten studies with a total of 1031 participants. The findings demonstrate a significant reduction in dysphagia severity, time to oral intake and the risk of aspiration pneumonia, and an improvement in quality of life among patients receiving swallowing therapy. However, no substantial difference was found in nutritional status. Limited data availability necessitated a descriptive presentation of outcomes like the risk of aspiration, ICU/hospital stay duration, pharyngeal/oral residue severity, and intervention-related adverse events. CONCLUSION: The current evidence for the effectiveness of dysphagia interventions in critically ill patients with prolonged endotracheal intubation is limited. There is a pressing need for future research, particularly high-quality RCTs employing standardized outcome measures, to substantiate these findings.
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Circular RNAs (circRNAs) play crucial biological functions in various tumors, including bladder cancer (BCa). However, the roles and underlying molecular mechanisms of circRNAs in the malignant proliferation of BCa are yet unknown. CircKDM1A was observed to be downregulated in BCa tissues and cells. Knockdown of circKDM1A promoted the proliferation of BCa cells and bladder xenograft growth, while the overexpression of circKDM1A exerts the opposite effect. The dual-luciferase reporter assay revealed that circKDM1A was directly bound to miR-889-3p, acting as its molecular sponge to downregulate CPEB3. In turn, the CPEB3 was bound to the CPE signal in p53 mRNA 3'UTR to stabilize its expression. Thus, circKDM1A-mediated CPEB3 downregulation inhibits the stability of p53 mRNA and promotes BCa malignant progression. In conclusion, circKDM1A functions as a tumor suppressor in the malignant proliferation of BCa via the miR-889-3p/CPEB3/p53 axis. CircKDM1A may be a potential prognostic biomarker and therapeutic target of BCa.
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Electron donor (D)-electron acceptor (A) type conjugated polymers present bright prospects as dopant-free hole-transporting materials (HTMs) for perovskite solar cells (PVSCs). Most of the reported D-A polymeric HTMs contain equivalent amounts of D and A units, while the appropriate excess proportion of D units could optimize the aggregation state of polymer chains and improve the hole transport properties of the polymers. Herein, a non-equivalent D-A copolymerization strategy was utilized to develop three indacenodithiophene-benzotriazole-based polymeric HTMs for PVSCs, named as F-10, F-15, and F-20, and the equivalent D-A polymer F-00 was studied in parallel. Effects of D : A ratio on the hole transport properties of these D-A type polymeric HTMs, including energy level, molecular stacking, hole mobility, and surface morphology, were investigated by theoretical simulation and test analysis. F-15 performed best due to the appropriate D : A ratio, endowing the PVSCs a champion power conversion efficiency of 20.37 % with high stability, which confirms the fine-tuning D : A ratio via non-equivalent D-A copolymerization strategy is very helpful to construct D-A type polymeric HTMs for high-performance PVSCs.
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This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF's mechanisms of action.
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Glucósidos , Hipoxia , Monoterpenos , Infarto del Miocardio , Estrés Oxidativo , Ratas Sprague-Dawley , Remodelación Ventricular , Animales , Glucósidos/farmacología , Glucósidos/uso terapéutico , Remodelación Ventricular/efectos de los fármacos , Masculino , Ratas , Monoterpenos/farmacología , Monoterpenos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Hipoxia/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Background: Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is widely used for maintenance immunosuppression in transplantation. The gastrointestinal toxicity of MMF has been widely uncovered. However, the comprehensive metabolic analysis of MMF-induced toxicity is lacking. This study is aimed to ascertain the metabolic changes after MMF administration in mice. Methods: A total of 700 mg MMF was dissolved in 7 mL dimethyl sulfoxide (DMSO), and then 0.5 mL of mixture was diluted with 4.5 mL of saline (100 mg/kg). Mice in the treatment group (n = 9) were given MMF (0.1 mL/10 g) each day via intraperitoneal injection lasting for 2 weeks, while those in the control group (n = 9) received the same amount of blank solvent (DMSO: saline = 1:9). Gas chromatography-mass spectrometry was utilized to identify the metabolic profiling in serum samples and multiple organ tissues of mice. The potential metabolites were identified using orthogonal partial least squares discrimination analysis. Meanwhile, we used the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (http://www.kegg.jp) to depict the metabolic pathways. The percentages of lymphocytes in spleens were assessed by multiparameter flow cytometry analysis. Results: Compared to the control group, we observed that MMF treatment induced differential expression of metabolites in the intestine, hippocampus, lung, liver, kidney, heart, serum, and cortex tissues. Subsequently, we demonstrated that multiple amino acids metabolism and fatty acids biosynthesis were disrupted following MMF treatment. Additionally, MMF challenge dramatically increased CD4+ T cell percentages but had no significant influences on other types of lymphocytes. Conclusion: MMF can affect the metabolism in various organs and serum in mice. These data may provide preliminary judgement for MMF-induced toxicity and understand the metabolic mechanism of MMF more comprehensively.
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In order to develop candidate materials for more metal ion battery anodes, a three-dimensional (3D) porous structure 3D-PGY was designed based on graphyne, and a sandwich structure graphene/PGY/graphene (G/PGY/G) was constructed by adjusting the distance between two layers of graphene with 3D-PGY as the middle layer. Systematic calculations have shown that 3D-PGY is thermally and mechanically stable even at temperatures up to 1000 K. Li can migrate in multiple diffusion directions in two structures because of its smaller radius while Na and K ions can only migrate through the larger pores. The energy barriers of Li, Na and K ions in 3D-PGY are 0.18, 0.43 and 0.27 eV respectively. After forming the sandwich structure with graphene, the minimum energy barriers of Li, Na and K ions are decreased to 0.12, 0.37 and 0.24 eV, respectively. As the anode for Li, Na, and K ion batteries, the theoretical specific capacities of 3D-PGY are about 558 mA h g-1, and the average open circuit voltages of 3D-PGY and G/PGY/G are about 0.48/0.52/0.29 and 1.08/1.04/1.39 V, respectively. Finally, using ab initio molecular dynamics simulations, the diffusion coefficients for 3D-PGY at different temperatures, as well as for G/PGY/G at 400 K were obtained. The Li, Na and K ions in both structures can diffuse rapidly and have good rate capabilities. These excellent performances show that the graphyne-based 3D porous structure and its sandwich-type graphene structure are very promising for the development of new battery materials.
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The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.
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Colecistitis , Colesterol/análogos & derivados , Cálculos Biliares , Fitosteroles , Humanos , Lipoproteínas/genética , Análisis de la Aleatorización Mendeliana , Transportador de Casete de Unión a ATP, Subfamilia G, Miembro 8/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 5/genética , Colecistitis/epidemiología , Colecistitis/genética , Cálculos Biliares/epidemiología , Cálculos Biliares/genética , Cálculos Biliares/metabolismoRESUMEN
The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 µm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m/z 400.7 â 285.1 for FR-6 and m/z 406.1 â 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61-6.85% and 1.76-11.75%; the inter-day and intra-day accuracy were -7.28-0.13% and -7.20-2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.
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Background: Non-suicidal self-injury (NSSI) and depression often co-occur among adolescents with more severe clinical symptoms. This study examined the network structures of NSSI and depressive symptoms in adolescents. Methods: Participants were recruited in the psychiatric outpatient clinics of three tertiary hospitals between April 10 and July 10, 2023. All participants been already found with self-injury behaviors in outpatient when enrolled. NSSI diagnostic criteria and Patient Health Questionnaire-9 (PHQ-9) were utilized to collect NSSI and depressive symptoms separately. We performed a network analysis to visualize the correlation between each symptom and to identify core and bridging symptoms in comorbidities. Results: A total of 248 patients were enrolled in the study, with a mean age of 15.48 (SD = 1.62). Based on the PHQ-9 scores and grades, our results showed that the incidence of depression in adolescents with non-suicidal self-injury behavior was relatively high (N=235, 94.76%), with the majority having severe depression. The network analysis revealed that nodes D-6 "feeling bad, failing or letting yourself or your family down", D-1 "little interest or pleasure" and D-4 "feeling tired" were the most vital and most central symptoms. The most crucial bridging symptom is the node NSSI-8 "frequent thinking about self-injury", which connects the NSSI to the depression comorbid network. Conclusion: This study offers a significant symptom-level conceptualization of the association between NSSI and depressive symptoms in a clinical sample of adolescents, which not only enhances our understanding of the comorbid but also identifies potential treatment targets to prevent and treat comorbidity between adolescent NSSI and depression.
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Machine learning is increasingly integrated into chemistry research by guiding experimental procedures, correlating structure and function, interpreting large experimental datasets, to distill scientific insights that might be challenging with traditional methods. Such applications, however, largely focus on gaining insights via big data and/or big computation, while neglecting the valuable chemical prior knowledge dwelling in chemists' minds. In this paper, we introduce an Electrochemistry-Informed Neural Network (ECINN) by explicitly embedding electrochemistry priors including the Butler-Volmer (BV), Nernst and diffusion equations on the backbone of neural networks for multi-task discovery of electrochemistry parameters. We applied the ECINN to voltammetry experiments of F e 2 + / F e 3 + ${{\rm F}{{\rm e}}^{2+}/{\rm F}{{\rm e}}^{3+}}$ and R u N H 3 6 2 + / R u N H 3 6 3 + ${{\rm R}{\rm u}{\left({\rm N}{{\rm H}}_{3}\right)}_{6}^{2+{\rm \ }}/{\rm R}{\rm u}{\left({\rm N}{{\rm H}}_{3}\right)}_{6}^{3+{\rm \ }}}$ redox couples to discover electrode kinetics and mass transport parameters. Notably, ECINN seamlessly integrated mass transport with BV to analyze the entire voltammogram to infer transfer coefficients directly, so offering a new approach to Tafel analysis by outdating various mass transport correction methods. In addition, ECINN can help discover the nature of electron transfer and is shown to refute incorrect physics if imposed. This work encourages chemists to embed their domain knowledge into machine learning models to start a new paradigm of chemistry-informed machine learning for better accountability, interpretability, and generalization.
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Using mechanical cues for cancer cells can realize precise control and efficient therapeutic effects. However, the cell cycle-specific response for dynamic mechanical manipulation is barely investigated. Here, RGD-modified iron oxide nanomanipulators were utilized as the intracellular magneto-mechanical transducers to investigate the mechanical impacts on the cell cycle under a dynamic magnetic field for cancer treatment. The G2/M phase was identified to be sensitive to the intracellular magneto-mechanical modulation with a synergistic treatment effect between the pretreatment of cell cycle-specific drugs and the magneto-mechanical destruction, and thus could be an important mechanical-targeted phase for regulation of cancer cell death. Finally, combining the cell cycle-specific drugs with magneto-mechanical manipulation could significantly inhibit glioma and breast cancer growth in vivo. This intracellular mechanical stimulus showed cell cycle-dependent cytotoxicity and could be developed as a spatiotemporal therapeutic modality in combination with chemotherapy drugs for treating deep-seated tumors.
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Glioma , Humanos , División Celular , Ciclo Celular , Muerte Celular , Campos MagnéticosRESUMEN
Few studies have investigated the association between PM2.5 and hypertension among floating populations. We therefore examined the relationship using binary logistic regression. Each grade of increment in the annual average PM2.5 (grade one: ≤15 µg/m3; grade two: 15-25 µg/m3; grade three: 25-35 µg/m3 [Excluding 25]; grade four: ≥35 µg/m3) was associated with an increased risk of hypertension (odds ratio [OR] = 1.081, 95% confidence interval (CI): 1.034-1.129). Among the female floating population (OR = 1.114, 95% CI: 1.030-1.204), those with education level of primary school and below (OR = 1.140, 95% CI: 1.058-1.229), construction workers (OR = 1.228, 95% CI: 1.058-1.426), and those living in the eastern region of China (OR = 1.241, 95% CI: 1.145-1.346) were more vulnerable to PM2.5. These results indicate that PM2.5 is positively associated with hypertension in floating populations. Floating populations who are female, less educated, construction workers, and living in the eastern region of China are more vulnerable to the adverse impacts of PM2.5.
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Contaminantes Atmosféricos , Contaminación del Aire , Hipertensión , Humanos , Femenino , Masculino , Material Particulado/toxicidad , Material Particulado/análisis , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Estudios Transversales , Hipertensión/epidemiología , Hipertensión/etiología , China/epidemiología , Exposición a Riesgos AmbientalesRESUMEN
There are limited studies investigating the association between short-term exposure to PM2.5 and incident cardiovascular disease (CVD) cases in China. This study aims to examine the short-term effects of PM2.5 on the incidence of cardiovascular diseases. A combination of Poisson-distribution generalized linear model and distributed lag non-linear model was used to examine the association between short-term exposure to PM2.5 and incident cases of CVD. The results revealed that per 10 µg/m3 increment of PM2.5 would increase the incident CVD cases by 0.147% (Relative Risk: 1.00147, 95% Confidence Interval: 1.00008-1.00286) at a lag of 2 days. The stratified analyses showed higher effects risk in females, older residents (aged 60-75 years), and acute myocardial infarction group (p-value for difference <0.05). This study indicates that short-term exposure to PM2.5 may increase the risk of CVD and highlights the necessity for a higher air quality standard in Yantai, China.