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Histone deacetylase 6 (HDAC6) belongs to the class IIb group of the histone deacetylase family, which participates in remodelling of various tissues. Herein, we sought to examine the potential regulation of HDAC6 in cardiac remodelling post-infarction. Experimental myocardial infarction (MI) was created in HDAC6-deficient (HDAC6-/-) mice and wild-type (HADC6+/+) by left coronary artery ligation. At days 0 and 14 post-MI, we evaluated cardiac function, morphology and molecular endpoints of repair and remodelling. At day 14 after surgery, the ischemic myocardium had increased levels of HADC6 gene and protein of post-MI mice compared to the non-ischemic myocardium of control mice. As compared with HDAC6-/--MI mice, HADC6 deletion markedly improved infarct size and cardiac fibrosis as well as impaired left ventricular ejection fraction and left ventricular fraction shortening. At the molecular levels, HDAC6-/- resulted in a significant reduction in the levels of the transforming growth factor-beta 1 (TGF-ß1), phosphor-Smad-2/3, collagen I and collagen III proteins and/or in the ischemic cardiac tissues. All of these beneficial effects were reproduced by a pharmacological inhibition of HADC6 in vivo. In vitro, hypoxic stress increased the expressions of HADC6 and collagen I and III gene; these alterations were significantly prevented by the HADC6 silencing and TubA loading. These findings indicated that HADC6 deficiency resists ischemic injury by a reduction of TGF-ß1/Smad2/3 signalling activation, leading to decreased extracellular matrix production, which reduces cardiac fibrosis and dysfunction, providing a potential molecular target in the treatment of patients with MI.

Asunto(s)

Fibrosis , Histona Desacetilasa 6 , Infarto del Miocardio , Transducción de Señal , Proteína Smad2 , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Remodelación Ventricular , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/genética , Factor de Crecimiento Transformador beta1/metabolismo , Proteína Smad2/metabolismo , Ratones , Histona Desacetilasa 6/metabolismo , Histona Desacetilasa 6/genética , Proteína smad3/metabolismo , Proteína smad3/genética , Miocardio/metabolismo , Miocardio/patología , Ratones Noqueados , Masculino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad

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BACKGROUND: To compare the difference of postoperative anastomotic leakage (AL) rate between neoadjuvant chemoradiotherapy (NCRT) with pembrolizumab and NCRT group, and investigate the risk factors of developing AL for locally advanced esophageal squamous cell cancer (ESCC). MATERIALS AND METHODS: The GF was contoured on the pretreatment planning computed tomography and dosimetric parameters were retrospectively calculated. Univariate and multivariate logistic regression analysis was performed to determine the independent risk predictors for the entire cohort. A nomogram risk prediction model for postoperative AL was established. RESULTS: A total of 160 ESCC patients were included for analysis. Of them, 112 were treated with NCRT with pembrolizumab and 44 patients with NCRT. Seventeen (10.6%) patients experienced postoperative AL with a rate of 10.7% (12/112) in NCRT with pembrolizumab and 11.4% (5/44) in NCRT group. For the entire cohort, mean, D50, Dmax, V5, V10 and V20 GF dose were statistically higher in those with AL (all p < 0.05). Multivariate logistic regression analysis indicated that tumor length (p = 0.012), volume of GF (p = 0.003) and mean dose of GF (p = 0.007) were independently predictors for postoperative AL. Using receiver operating characteristics analysis, the mean dose limit on the GF was defined as 14 Gy. CONCLUSION: Based on our prospective database, no significant difference of developing AL were observed between NCRT with pembrolizumab and NCRT group. We established an individualized nomograms based on mean GF dose combined with clinical indicators to predict AL in the early postoperative period.

Asunto(s)

Fuga Anastomótica , Anticuerpos Monoclonales Humanizados , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Fuga Anastomótica/etiología , Fuga Anastomótica/epidemiología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Estudios Prospectivos , Anciano , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Nomogramas , Factores de Riesgo , Estudios Retrospectivos , Adulto , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología

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Background: A combination of standard biomedical treatment and traditional Chinese medicine (TCM) has been suggested as a therapeutic approach for rosacea that may significantly lower the recurrence rate and clinical symptom scores. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of this combination treatment on clinical symptom and TCM syndrome scores, as well as on the scores of the Dermatology Life Quality Index (DLQI), erythema index (EI), and interleukin 37 (IL-37) levels in patients with rosacea. Methods: The PROSPERO registration number for the study is CRD42023472737. We systematically searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure Wanfang Database, China Biomedical Medicine database (CBM), and the VIP information resource integration service platform (cqvip) databases for RCTs (published from the beginning to September 2023, regardless of the language used) that compared the traditional Chinese medicine and standard biomedical treatment combination treatment to conventional anti-rosacea treatments. Our primary outcomes comprised the clinical symptom and TCM syndrome scores, and the scores of Dermatology Life Quality Index, erythema index, and IL-37 levels. We used a random-effects model to evaluate the pooled data. Results: We identified 260 studies. Of these, 13 eligible studies were employed for analysis (N = 1,348 participants). Compared with other anti-rosacea treatments, the TCM and standard biomedical treatment combination treatment yielded an improved mean reduction in the clinical symptom score -2.24% [95% CI (-3.02 to -1.46), p < 0.00001], TCM syndrome score -4.42 [95% CI (-5.33 to -3.50), p < 0.00001], and the score of DLQI of -2.55 [95% CI (-3.73 to -1.36), p < 0.00001], EI of -151.97 [95% CI (-276.59 to -27.36), p < 0.00001], and IL-37 level -4.23 [95% CI (-4.95 to -3.51), p = 0.854], as well as in the overall effective rate risk ratio (RR) = 1.25 [95%CI (1.18, 1.32), p = 0.994] and the recurrence rate = 0.27 [95%CI (0.15, 0.46), p = 0.297]. Conclusion: The TCM and standard biomedical treatment combination treatment can provide a better outcome, including a reduction in the TCM syndrome and clinical symptom scores, and in the scores of DLQI, EI, and IL-37. Hence, this combination is a viable and more effective therapeutic approach for rosacea. However, these results should be considered cautiously because of uncertain evidence and the low quality of the study reports considered in this meta-analysis. Systematic Review Registration: website, identifier CRD42023472737.

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Objectives: While electrical stimulation has been demonstrated to improve medical research council (MRC) scores in critically ill patients, its effectiveness remains a subject of debate. This meta-analysis aimed to discuss recent insights into the effectiveness of electrical stimulation in improving muscle strength and its effects on different clinical outcomes in critically ill adults. Methods: A comprehensive search of major electronic databases, including PubMed, Cochrane Library, and Embase, was conducted from inception to June 15, 2024, to identify randomized controlled trials (RCTs) that evaluated the effects of electrical stimulation in critically ill patients. The analysis focused on comparing electrical stimulation to standard care, sham interventions, or placebo. Outcomes of interest included MRC scores, duration of mechanical ventilation (MV), mortality rate, and intensive care unit (ICU) and hospital length of stay (LOS). Results: A total of 23 RCTs, including 1798 patients, met the inclusion criteria. The findings demonstrated a significant benefit of electrical stimulation over usual care in enhancing global muscle strength, as measured by MRC scores (MD =3.62, 95% CI 0.94 to 6.30, p = 0.0008, I2 = 87%). While subgroup analysis of electrical muscle stimulation (EMS) demonstrated no significant effect on ICU LOS, sensitivity analysis indicated a potential reduction in ICU LOS for both EMS (MD = -11.0, 95% CI -21.12 to -0.88, p = 0.03) and electrical stimulation overall (MD = -1.02, 95% CI -1.96 to -0.08, p = 0.03) compared to the control group. In addition, sensitivity analysis suggested that both electrical stimulation (MD = -2.38, 95% CI -3.81 to -0.94, p = 0.001) and neuromuscular electrical stimulation (NMES) specifically (MD = -2.36, 95% CI -3.85 to -0.88, p = 0.002) may contribute to a decrease in hospital LOS. No statistically significant differences were observed in mortality or duration of MV. Conclusion: Electrical stimulation appears to be an effective intervention for improving MRC scores in critically ill patients. However, further research is warranted to explain the potential effects of electrical stimulation on hospital LOS and ICU LOS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

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Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

Asunto(s)

Anticuerpos Antivirales , Formación de Anticuerpos , Linfocitos B , Vacunas contra la COVID-19 , COVID-19 , Centro Germinal , Inmunización Secundaria , SARS-CoV-2 , Células T Auxiliares Foliculares , Animales , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Linfocitos B/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Ratones , COVID-19/inmunología , COVID-19/prevención & control , Células T Auxiliares Foliculares/inmunología , Centro Germinal/inmunología , Formación de Anticuerpos/inmunología , Femenino , Hipermutación Somática de Inmunoglobulina , Vacunación , Ratones Endogámicos BALB C , Humanos , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética

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Artemisia argyi, a perennial herb of the genus Artemisia in the family Asteraceae, holds significant importance in Chinese traditional medicine, referred to as "Aicao". Here, we report a high-quality reference genome of Artemisia argyi L. cv. beiai, with a genome size up to 4.15 Gb and a contig N50 of 508.96 Kb, produced with third-generation Nanopore sequencing technology. We predicted 147,248 protein-coding genes, with approximately 68.86% of the assembled sequences comprising repetitive elements, primarily long terminal repeat retrotransposons(LTRs). Comparative genomics analysis shows that A. argyi has the highest number of specific gene families with 5121, and much more families with four or more members than the other 6 plant species, which is consistent with its more expanded gene families and fewer contracted gene families. Furthermore, through transcriptome sequencing of A. argyi in response to exogenous MeJA treatment, we have elucidated acquired regulatory insights into MeJA's impact on the phenylpropanoid, flavonoid, and terpenoid biosynthesis pathways of A. argyi. The whole-genome information obtained in this study serves as a valuable resource for delving deeper into the cultivation and molecular breeding of A. argyi. Moreover, it holds promise for enhancing genome assemblies across other members of the Asteraceae family. The identification of key genes establishes a solid groundwork for developing new varieties of Artemisia with elevated concentrations of active compounds.

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The genomic landscape of esophageal squamous cell cancer (ESCC), as well as its impact on the regulation of immune microenvironment, is not well understood. Thus, tumor samples from 92 patients were collected from two centers and subjected to targeted-gene sequencing. We identified frequently mutated genes, including TP53, KMT2C, KMT2D, LRP1B, and FAT1. The most frequent mutation sites were ALOX12B (c.1565C > T), SLX4 (c.2786C > T), LRIG1 (c.746A > G), and SPEN (c.6915_6917del) (6.5%). Pathway analysis revealed dysregulation of cell cycle regulation, epigenetic regulation, PI3K/AKT signaling, and NOTCH signaling. A 17-mutated gene-related risk model was constructed using random survival forest analysis and showed significant prognostic value in both our cohort and the validation cohort. Based on the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE) algorithm, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm, and the MCPcounter algorithm, we found that the risk score calculated by the risk model was significantly correlated with stimulatory immune checkpoints (TNFSF4, ITGB2, CXCL10, CXCL9, and BTN3A1; p < 0.05). Additionally, it was significantly associated with markers that are important in predicting response to immunotherapy (CD274, IFNG, and TAMM2; p < 0.05). Furthermore, the results of immunofluorescence double staining showed that patients with high risk scores had a significantly higher level of M2 macrophage than those with low risk scores (p < 0.05). In conclusion, our study provides insights into the genomic landscape of ESCC and highlights the prognostic value of a genomic mutation signature associated with the immune microenvironment in southern Chinese patients with ESCC.

Asunto(s)

Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Mutación , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Pronóstico , Masculino , Femenino , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Persona de Mediana Edad , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/mortalidad , Biomarcadores de Tumor/genética , Anciano , China , Adulto , Genómica/métodos , Pueblo Asiatico/genética , Pueblos del Este de Asia

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Mucosal immunity plays a crucial role in combating and controlling the spread of highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recombinant subunit vaccines have shown safety and efficacy in clinical trials, but further investigation is necessary to evaluate their feasibility as mucosal vaccines. This study developed a SARS-CoV-2 mucosal vaccine using spike (S) proteins from a prototype strain and the omicron variant, along with a cationic chitosan adjuvant, and systematically evaluated its immunogenicity after both primary and booster immunization in mice. Primary immunization through intraperitoneal and intranasal administration of the S protein elicited cross-reactive antibodies against prototype strains, as well as delta and omicron variants, with particularly strong effects observed after mucosal vaccination. In the context of booster immunization following primary immunization with inactivated vaccines, the omicron-based S protein mucosal vaccine resulted in a broader and more robust neutralizing antibody response in both serum and respiratory mucosa compared to the prototype vaccine, enhancing protection against different variants. These findings indicate that mucosal vaccination with the S protein has the potential to trigger a broader and stronger antibody response during primary and booster immunization, making it a promising strategy against respiratory pathogens.

Asunto(s)

Administración Intranasal , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Ratones Endogámicos BALB C , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Glicoproteína de la Espiga del Coronavirus/inmunología , Ratones , Inmunización Secundaria/métodos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Femenino , Inmunidad Mucosa , Inmunogenicidad Vacunal , Reacciones Cruzadas/inmunología , Quitosano/inmunología , Quitosano/administración & dosificación , Adyuvantes de Vacunas/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación

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Background: Falls pose a serious health risk for the elderly, particular for those who are living alone. The utilization of WiFi-based fall detection, employing Channel State Information (CSI), emerges as a promising solution due to its non-intrusive nature and privacy preservation. Despite these advantages, the challenge lies in optimizing cross-individual performance for CSI-based methods. Objective: This study aimed to develop a resilient real-time fall detection system across individuals utilizing CSI, named TCS-Fall. This method was designed to offer continuous monitoring of activities over an extended timeframe, ensuring accurate and prompt detection of falls. Methods: Extensive CSI data on 1800 falls and 2400 daily activities was collected from 20 volunteers. The grouped coefficient of variation of CSI amplitudes were utilized as input features. These features capture signal fluctuations and are input to a convolutional neural network classifier. Cross-individual performance was extensively evaluated using various train/test participant splits. Additionally, a user-friendly CSI data collection and detection tool was developed using PyQT. To achieve real-time performance, data parsing and pre-processing computations were optimized using Numba's just-in-time compilation. Results: The proposed TCS-Fall method achieved excellent performance in cross-individual fall detection. On the test set, AUC reached 0.999, no error warning ratio score reached 0. 955 and correct warning ratio score reached of 0.975 when trained with data from only two volunteers. Performance can be further improved to 1.00 when 10 volunteers were included in training data. The optimized data parsing/pre-processing achieved over 20× speedup compared to previous method. The PyQT tool parsed and detected the fall within 100 ms. Conclusions: TCS-Fall method enables excellent real-time cross-individual fall detection utilizing WiFi CSI, promising swift alerts and timely assistance to elderly. Additionally, the optimized data processing led to a significant speedup. These results highlight the potential of our approach in enhancing real-time fall detection systems.

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While immersive shopping has injected new vitality into China's e-commerce, it has also resulted in consumers' over-reliance on online shopping. Psychological studies have linked online shopping addiction with depression, but business practices challenge this conclusion. This study, grounded in addiction theory, developed a theoretical model, and conducted an online survey with 214 live-streaming shoppers using structural equation modeling for validation. The primary focus was on determining whether consumers truly become addicted to online shopping in the four stages of the addiction model. The study unveils the process of consumers becoming addicted to online shopping. It explores the moderating role of perceived risk in the relationship between utilitarian and hedonic purchases and online shopping addiction. The findings suggest that through tactics such as traffic promotion, traffic trapping, anchor feature utilization, and incorporation of consumer aesthetics, merchants may induce utilitarian and hedonic purchases, leading to addiction to live-streaming shopping among consumers. Furthermore, perceived risk significantly and negatively moderates the relationship between utilitarian purchases and online shopping addiction. Our research indicates that merchants intentionally create external stimuli, enticing consumers to indulge in online shopping, suggesting that online shopping addiction is not merely a simple psychological state but may be influenced by external factors. This study provides novel insights into the phenomenon of online shopping addiction while offering valuable recommendations for consumers seeking to avoid succumbing to its allure.

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BACKGROUND: Early diagnosis of acute gallstone pancreatitis severity (GSP) is challenging in clinical practice. We aimed to investigate the efficacy of CT features and radiomics for the early prediction of acute GSP severity. METHODS: We retrospectively recruited GSP patients who underwent CT imaging within 48 h of admission from tertiary referral centre. Radiomics and CT features were extracted from CT scans. The clinical and CT features were selected by the random forest algorithm to develop the ML GSP model for the identification of severity of GSP (mild or severe), and its predictive efficacy was compared with radiomics model. The predictive performance was assessed by the area under operating characteristic curve. Calibration curve and decision curve analysis were performed to demonstrate the classification performance and clinical efficacy. Furthermore, we built a web-based open access GSP severity calculator. The study was registered with ClinicalTrials.gov (NCT05498961). RESULTS: A total of 301 patients were enrolled. They were randomly assigned into the training (n = 210) and validation (n = 91) cohorts at a ratio of 7:3. The random forest algorithm identified the level of calcium ions, WBC count, urea level, combined cholecystitis, gallbladder wall thickening, gallstones, and hydrothorax as the seven predictive factors for severity of GSP. In the validation cohort, the areas under the curve for the radiomics model and ML GSP model were 0.841 (0.757-0.926) and 0.914 (0.851-0.978), respectively. The calibration plot shows that the ML GSP model has good consistency between the prediction probability and the observation probability. Decision curve analysis showed that the ML GSP model had high clinical utility. CONCLUSIONS: We built the ML GSP model based on clinical and CT image features and distributed it as a free web-based calculator. Our results indicated that the ML GSP model is useful for predicting the severity of GSP.

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ML GSP model based on machine learning has good severity discrimination in both training and validation cohorts (0.916 (0.872­0.958), 0.914 (0.851­0.978), respectively).We built an online user-friendly platform for the ML GSP model to help clinicians better identify the severity of GSP.

Asunto(s)

Cálculos Biliares , Aprendizaje Automático , Pancreatitis , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Humanos , Pancreatitis/diagnóstico por imagen , Pancreatitis/diagnóstico , Femenino , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/complicaciones , Masculino , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Enfermedad Aguda , Valor Predictivo de las Pruebas , Diagnóstico Precoz , Algoritmos , Curva ROC

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In this study, the whole HD-Zip family members of G. hirsutum were identified, and GhHDZ76 was classified into the HD-Zip IV subgroup. GhHDZ76 was predominantly expressed in the 0-5 DPA of fiber development stage and localized in the nucleus. Overexpression of GhHDZ76 significantly increased the length and density of trichomes in Arabidopsis thaliana. The fiber length of GhHDZ76 knockout lines by CRISPR/Cas9 was significantly shorter than WT at the early elongation and mature stage, indicating that GhHDZ76 positively regulate the fiber elongation. Scanning electron microscopy showed that the number of ovule surface protrusion of 0 DPA of GhHDZ76 knockout lines was significantly lower than WT, suggesting that GhHDZ76 can also promote the initiation of fiber development. The transcript level of GhWRKY16, GhRDL1, GhEXPA1 and GhMYB25 genes related to fiber initiation and elongation in GhHDZ76 knockout lines were significantly decreased. Yeast two-hybrid and Luciferase complementation imaging (LCI) assays showed that GhHDZ76 can interact with GhWRKY16 directly. As a transcription factor, GhHDZ76 has transcriptional activation activity, which could bind to L1-box elements of the promoters of GhRDL1 and GhEXPA1. Double luciferase reporter assay showed that the GhWRKY16 could enhance the transcriptional activity of GhHDZ76 to pGhRDL1, but it did not promote the transcriptional activity of GhHDZ76 to pGhEXPA1. GhHDZ76 protein may also promote the transcriptional activity of GhWRKY16 to the downstream target gene GhMYB25. Our results provided a new gene resource for fiber development and a theoretical basis for the genetic improvement of cotton fiber quality.

Asunto(s)

Fibra de Algodón , Regulación de la Expresión Génica de las Plantas , Gossypium , Proteínas de Plantas , Factores de Transcripción , Gossypium/genética , Gossypium/crecimiento & desarrollo , Gossypium/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Sistemas CRISPR-Cas

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Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.

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Macrófagos , Fagocitosis , Ratones , Animales , Inflamación/metabolismo , Interferones/metabolismo , Análisis de Secuencia de ARN

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OBJECTIVE: The preoperative prediction of the overall survival (OS) status of patients with head and neck cancer (HNC) is significant value for their individualized treatment and prognosis. This study aims to evaluate the impact of adding 3D deep learning features to radiomics models for predicting 5-year OS status. METHODS: Two hundred twenty cases from The Cancer Imaging Archive public dataset were included in this study; 2212 radiomics features and 304 deep features were extracted from each case. The features were selected by univariate analysis and the least absolute shrinkage and selection operator, and then grouped into a radiomics model containing Positron Emission Tomography /Computed Tomography (PET/CT) radiomics features score, a deep model containing deep features score, and a combined model containing PET/CT radiomics features score +3D deep features score. TumorStage model was also constructed using initial patient tumor node metastasis stage to compare the performance of the combined model. A nomogram was constructed to analyze the influence of deep features on the performance of the model. The 10-fold cross-validation of the average area under the receiver operating characteristic curve and calibration curve were used to evaluate performance, and Shapley Additive exPlanations (SHAP) was developed for interpretation. RESULTS: The TumorStage model, radiomics model, deep model, and the combined model achieved areas under the receiver operating characteristic curve of 0.604, 0.851, 0.840, and 0.895 on the train set and 0.571, 0.849, 0.832, and 0.900 on the test set. The combined model showed better performance of predicting the 5-year OS status of HNC patients than the radiomics model and deep model. The combined model was shown to provide a favorable fit in calibration curves and be clinically useful in decision curve analysis. SHAP summary plot and SHAP The SHAP summary plot and SHAP force plot visually interpreted the influence of deep features and radiomics features on the model results. CONCLUSIONS: In predicting 5-year OS status in patients with HNC, 3D deep features could provide richer features for combined model, which showed outperformance compared with the radiomics model and deep model.

Asunto(s)

Aprendizaje Profundo , Neoplasias de Cabeza y Cuello , Nomogramas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Anciano , Imagenología Tridimensional/métodos , Adulto , Estudios Retrospectivos , Radiómica

RESUMEN

The effects of isochlorogenic acid (ICGA) on ewes rumen environment, microbial diversity, and immunity at different physiological stages (estrus, pregnancy and lactation) were studied in this experiment. Twenty healthy female Hu lambs of 1.5 months with similar body weight (17.82 ± 0.98 kg) and body condition were selected and randomly divided into two groups: the control group (CON) and the ICGA group (ICGA). The lambs of CON were fed a basal diet, while the lambs of ICGA were supplemented with 0.1% ICGA based on the basal diet. Lambs rumen fermentation characteristics, microbial diversity and immunity at estrus, pregnancy, and lactation stages were determined and analyzed, respectively. The results showed that the rumen pH in CON increased first and then decreased as lambs grew (p < 0.05). However, it showed the opposite change in ICGA. The content of ammonia nitrogen (NH3-N) showed the highest at estrus stage in both groups, but it was significantly higher in ICGA than that in CON (p < 0.05). The Acetic acid/propionic acid (A/P) ratio at estrus stage and the volatile fatty acids (VFAs) at pregnancy stage in ICGA were significantly higher than those of the CON (p < 0.05). The 16S rDNA sequencing analysis showed that the Shannon, Chao 1 and ACE indexes of the ICGA were significantly higher than those of the CON both at estrus and lactation stages (p < 0.05), while they showed higher at the pregnancy stage in CON (p > 0.05). Principal component analysis (PCA) showed that there were significant differences in rumen microorganism structure between CON and ICGA at all physiological stages (p < 0.01). At the phylum level, compared with the CON, Firmicutes relative abundance of three physiological stages decreased (p > 0.05) while Bacteroidota increased (p > 0.05). The relative abundance of Synergistota at estrus stage and Patescibacteria at the lactation stage increased significantly too (p < 0.05). At the genus level, compared with the CON, the relative abundance of Prevotella at three stages showed the highest (p > 0.05), while the relative abundance of Succiniclasticum, unclassified_Selenomonadaceae and Rikenellaceae_RC9_gut_group showed different abundances at different physiological stages in ICGA. Compared with the CON, the lambs of the ICGA showed higher blood IgG, IgM, and TNF- α contents at three physiological stages and higher IL-6 contents at pregnancy stage (p < 0.05). Conclusion: Adding ICGA could regulate ewes rumen fermentation mode at different physiological stages by increasing rumen NH3-N at estrus, VFAs at pregnancy, and the ratio of A/P at lactation. It optimizes rumen microbial flora of different physiological stages by increasing Bacteroidota relative abundance while reducing Firmicutes relative abundance, maintaining rumen microbial homeostasis at pregnant stage, increasing the number of beneficial bacteria in later lactating and ewes blood immunoglobulins content at three physiological stages.

RESUMEN

Objective: The objective of this study was to evaluate the effects of comfort care on perioperative outcomes and postoperative recovery of breast cancer patients. Evaluating comfort care is important in the context of breast cancer surgery because it can potentially alleviate pain, improve patient comfort, enhance postoperative recovery, and reduce complications, ultimately leading to better patient outcomes. Methods: Between March 2020 and December 2021, 78 patients undergoing breast cancer surgery at our hospital were randomly assigned to receive either routine nursing (routine group) or comfort care (experimental group). The comfort care intervention included various components such as health education, preoperative care, intraoperative care, postoperative care, pain care, and psychological care. The routine group received standard nursing care following medical advice. Results: The patient characteristics between the two groups were comparable. Comfort care resulted in significantly higher visual analog scale (VAS) scores, indicating reduced pain, and better improvement in functional recovery of the upper limb compared to routine nursing. Comfort care was also associated with better postoperative recovery, as evidenced by lower self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores. The experimental group had a significantly lower incidence of complications compared to the routine group. Additionally, the experimental group reported better 24-hour comfort and higher nursing satisfaction. Conclusion: In conclusion, comfort care effectively reduces postoperative pain, promotes postoperative recovery, improves patient emotions, lowers the incidence of complications, and enhances comfort and care satisfaction in breast cancer patients undergoing radical surgery. These findings highlight the importance of incorporating comfort care interventions in the perioperative management of breast cancer patients. Further research and implementation of comfort care strategies may have implications for improving clinical practice and patient outcomes in the future.

RESUMEN

Background: We aim to evaluate the value of an integrated multimodal radiomics with machine learning model to predict the pathological complete response (pCR) of primary tumor in a prospective cohort of esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT) and anti-PD-1 inhibitors. Materials and methods: Clinical information of 126 ESCC patients were included for analysis. Radiomics features were extracted from 18F-FDG PET and enhanced plan CT images. Four machine learning algorithms, including SVM (Support Vector Machine), Random Forest (RF), and eXtreme Gradient Boosting (XGB) and logistic regression (LR), were applied using k-fold cross-validation to predict pCR after nCRT. The predictive ability of the models was assessed using receiver operating characteristics (ROC) curve analysis. Results: A total of 842 features were extracted. Among the four machine learning algorithms, SVM achieved the most promising performance on the test set for PET(AUC:0.775), CT (AUC:0.710) and clinical model (AUC:0.722). For all combinations of various modalities-based models, the combination model of 18 F-FDG PET, CT and clinical features with SVM machine learning had the highest AUC of 0.852 in the test set when compared to single-modality models in various algorithms. The other combined models had AUC ranged 0.716 to 0.775. Conclusion: Machine learning models utilizing radiomics features from 18F-FDG PET and enhanced plan CT exhibit promising performance in predicting pCR in ESCC after nCRT and anti-PD-1 inhibitors. The fusion of features from multiple modalities radiomics and clinical features enhances the better predictive performance compared to using a single modality alone.

Asunto(s)

Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Terapia Neoadyuvante , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/terapia , Fluorodesoxiglucosa F18 , Estudios Prospectivos , Radiómica , Inhibidores de Puntos de Control Inmunológico , Aprendizaje Automático

RESUMEN

BACKGROUND: Among all of the assisted reproductive technology (ART) methods, in vitro fertilization-embryo transfer (IVF-ET) holds a prominent position as a key solution for overcoming infertility. However, its success rate hovers at a modest 30% to 70%. Adding to the challenge is the absence of effective models and clinical tools capable of predicting the outcome of IVF-ET before embryo formation. Our study is dedicated to filling this critical gap by aiming to predict IVF-ET outcomes and ultimately enhance the success rate of this transformative procedure. METHODS: In this retrospective study, infertile patients who received artificial assisted pregnancy treatment at Gansu Provincial Maternity and Child-care Hospital in China were enrolled from 2016 to 2020. Individual's clinical information were studied by cascade XGBoost method to build an intelligent assisted system for predicting the outcome of IVF-ET, called IAS-FET. The cascade XGBoost model was trained using clinical information from 2292 couples and externally tested using clinical information from 573 couples. In addition, several schemes which will be of help for patients to adjust their physical condition to improve their success rate on ART were suggested by IAS-FET. RESULTS: The outcome of IVF-ET can be predicted by the built IAS-FET method with the area under curve (AUC) value of 0.8759 on the external test set. Besides, this IAS-FET method can provide several schemes to improve the successful rate of IVF-ET outcomes. The built tool for IAS-FET is addressed as a free platform online at http://www.cppdd.cn/ART for the convenient usage of users. CONCLUSIONS: It suggested the significant influence of personal clinical features for the success of ART. The proposed system IAS-FET based on the top 27 factors could be a promising tool to predict the outcome of ART and propose a plan for the patient's physical adjustment. With the help of IAS-FET, patients can take informed steps towards increasing their chances of a successful outcome on their journey to parenthood.

Asunto(s)

Transferencia de Embrión , Fertilización In Vitro , Embarazo , Humanos , Femenino , Fertilización In Vitro/métodos , Estudios Retrospectivos , Transferencia de Embrión/métodos , Índice de Embarazo , Fertilización

RESUMEN

Feline chaphamaparvovirus (FeChPV) is a new viral strain detected in Chinese Mainland in recent years. The symptoms mainly include diarrhea and bloody stool in young cats, which can lead to death in severe cases. In this study, a TaqMan-based real-time quantitative PCR (qPCR) with specific primers and TaqMan probes based on the VP1 gene sequence of FeChPV was performed to detect the virus. The established qPCR indicated that there is no cross-reaction of FeChPV with other common feline viruses. The minimum detection limit of the established qPCR method is 3.75 × 10 copies/µL, while conventional PCR is 3.75 × 103 copies/µL. The result that the proposed qPCR protocol was shown to be 100 times more sensitive than conventional PCR. The correlation coefficients exceeded 0.995, and the amplification efficiency was 98%. The difference within and between groups is less than 5%, indicating that the established method has good repeatability. The results of clinical sample detection shown that 16 positive samples were detected from 45 stool samples by the established qPCR method. The conventional PCR method only detected 3 positive samples. In conclusion, the established qPCR method is fast and effective in identifying FeChPV, with higher specificity and sensitivity. It could be used as a diagnostic tool to quantitatively detect the virus content, which is conducive to disease monitoring and epidemiological investigation.