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BACKGROUND: Several HER2-targeting antibody-drug conjugates (ADC) have gained market approval for the treatment of HER2-expressing metastasis. Promising responses have been reported with the new generation of ADCs in patients who do not respond well to other HER2-targeting therapeutics. However, these ADCs still face challenges of resistance and/or severe adverse effects associated with their particular payload toxins. Eribulin, a therapeutic agent for the treatment of metastatic breast cancer and liposarcoma, is a new choice of ADC payload with a distinct mechanism of action and safety profile. METHODS: We've generated a novel HER2-tageting eribulin-containing ADC, BB-1701. The potency of BB-1701 was tested in vitro and in vivo against cancer cells where HER2-expressing levels vary in a large range. Bystander killing effect and toxin-induced immunogenic cell death (ICD) of BB-1701 were also tested. RESULTS: In comparison with HER2-targeting ADCs with DM1 and Dxd payload, eribulin-containing ADC demonstrated higher in vitro cytotoxicity in HER2-low cancer cell lines. BB-1701 also effectively suppressed tumors in models resistant to DM1 or Dxd containing ADCs. Mode of action studies showed that BB-1701 had a significant bystander effect on HER2-null cells adjacent to HER2-high cells. In addition, BB-1701 treatment induced ICD. Repeated doses of BB-1701 in nonhuman primates showed favorable pharmacokinetics and safety profiles at the intended clinical dosage, route of administration, and schedule. CONCLUSIONS: The preclinical data support the test of BB-1701 in patients with various HER2-expressing cancers, including those resistant to other HER2-targeting ADCs. A phase I clinical trial of BB-1701 (NCT04257110) in patients is currently underway.
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The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from â¼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.
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Bone morphogenetic protein 6 (BMP-6) is a constituent of the TGF-ß superfamily, known for its ability to stimulate bone and cartilage formation. The investigation of bmp6's involvement in the formation of intermuscular bones in fish has garnered significant attention in recent years. The rib cage is an important skeletal structure that plays a protective function for internal organs in fish. However, there has been limited research conducted on the effects of the bmp6 gene on rib development. Silver carp is one of four major fish in China, favoured for its affordability and tender muscle. Nevertheless, the presence of numerous intermuscular bones in silver carp significantly hinders the advancement of its palatability and suitability for processing. This study showcases the effective utilisation of CRISPR/Cas9 technology for the purpose of disrupting the bmp6 gene in silver carp, leading to the creation of chimeras in the P0 generation, marking the first instance of such an achievement. The chimeras exhibited complete viability, normal appearance, and partial intermuscular bones loss, with approximately 30% of them displaying rib bifurcation or bending. Subsequently, a transcriptome analysis on ribs of P0 chimeras and wild-type silver carp was conducted, leading to the identification of 934 genes exhibiting differential expression, of which 483 were found to be up-regulated and 451 were found to be down-regulated. The results of the KEGG analysis revealed that the "NF-kappa B signalling pathway", "Hippo signalling pathway", "osteoclast differentiation", and "haematopoietic cell lineage" exhibited enrichment and displayed a significant correlation with bone development. The up-regulated genes such as tnfα, fos, and ctgf in pathways may facilitate the proliferation and differentiation of osteoclasts, whereas the down-regulation of genes such as tgfb2 and tgfbr1 in pathways may hinder the formation and specialisation of osteoblasts, ultimately resulting in rib abnormalities. This study presents novel findings on the impact of bmp6 gene deletion on the rib development of silver carp, while simultaneously investigating the previously unexplored molecular mechanisms underlying rib defects in fish.
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PURPOSE: To compare the image quality of multiplexed sensitivity-encoding diffusion-weighted imaging (MUSE-DWI) and single-shot echo-planar imaging (SS-EPI-DWI) techniques in uterine MRI. METHODS: Eighty-eight eligible patients underwent MUSE-DWI and SS-EPI-DWI examinations simultaneously using a 3.0 T MRI system. Two radiologists independently performed quantitative and qualitative analysis of the two groups of images using a double-blind method. The weighted Kappa test was used to evaluate the interobserver agreement. Wilcoxon's rank sum test was used for qualitative parameters, and paired t-test was used for quantitative parameters. Spearman rank correlation analysis was used to obtained correlation between pathological results and mean apparent diffusion coefficient (ADC) value. RESULTS: The qualitative and quantitative analysis of the images by the two radiologists were in good or excellent agreement, with weighted kappa value ranging from 0.636 to 0.981. The scores of total subjective image quality (15.4 ± 0.99) and signal-to-noise ratio (158.99 ± 60.71) of MUSE-DWI were significantly higher than those of SS-EPI-DWI (12.93 ± 1.62 P < 0.001; 130.23 ± 48.29 P < 0.05). It effectively reduced image distortion and artifact, and had better lesion conspicuity. There was no significant difference in contrast-to-noise ratio score and average ADC values between the two DWI sequences. The average ADC values of the two DWI sequences were highest in the normal uterus group and lowest in the endometrial cancer group, with statistically significant differences among groups (P < 0.01). In addition, the average ADC values of the two DWI sequences were negatively correlated with the type of lesions, decreasing with the malignancy of the lesions (r = -0.805 P < 0.01, r = -0.815 P < 0.01). CONCLUSION: Compared to SS-EPI-DWI, MUSE-DWI can significantly reduce distortion, artifacts, and fuzziness in MRI of uterine lesions, which is more conducive to lesion detection.
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Imagen de Difusión por Resonancia Magnética , Imagen Eco-Planar , Relación Señal-Ruido , Neoplasias Uterinas , Útero , Humanos , Femenino , Imagen de Difusión por Resonancia Magnética/métodos , Persona de Mediana Edad , Adulto , Neoplasias Uterinas/diagnóstico por imagen , Imagen Eco-Planar/métodos , Útero/diagnóstico por imagen , Útero/patología , Variaciones Dependientes del Observador , Anciano , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Interpretación de Imagen Asistida por Computador/métodos , Método Doble Ciego , Procesamiento de Imagen Asistido por Computador/métodos , Aumento de la Imagen/métodosRESUMEN
A comprehensive understanding of the terrestrial carbon sink is essential for proficient regional carbon management. However, previous studies predominantly relied on net ecosystem productivity (NEP) as an indicator of regional carbon sink, overlooking the impacts of carbon emissions from physical processes and carbon leakage associated with anthropogenic activities. In this study, net region productivity (NRP), a vital metric representing carbon sink dynamics in regional multi-landscape ecosystems, was employed to systematically analyze the patterns, trends, and causes of carbon sink in Ordos. The results revealed that spatially averaged NRP in Ordos was 70.334 g·m-2·a-1, indicating a carbon sink effect. The coefficient of variation of NRP was 68.035%, with a higher NRP in the southern region. Normalized difference vegetation index (NDVI) predominantly controlled the spatial heterogeneity of NRP in Ordos, while precipitation emerged as the primary climatic factor influencing spatial differences in NRP. Regional variations in the impact of environmental factors on NRP were evident. In most areas, NRP showed a notable increasing trend influenced by various factors. Specifically, the simultaneous rise in NDVI and improvements in hydrothermal conditions contributed to the gradual elevation of NRP, each with varying degrees of influence across Ordos and its sub-regions.
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Secuestro de Carbono , Ecosistema , China , Carbono/análisis , CausalidadRESUMEN
Magnetic resonance imaging (MRI) has been proven to be an indispensable imaging method in bladder cancer, and it can accurately identify muscular invasion of bladder cancer. Multiparameter MRI is a promising tool widely used for preoperative staging evaluation of bladder cancer. Vesical Imaging-Reporting and Data System (VI-RADS) scoring has proven to be a reliable tool for local staging of bladder cancer with high accuracy in preoperative staging, but VI-RADS still faces challenges and needs further improvement. Artificial intelligence (AI) holds great promise in improving the accuracy of diagnosis and predicting the prognosis of bladder cancer. Automated machine learning techniques based on radiomics features derived from MRI have been utilized in bladder cancer diagnosis and have demonstrated promising potential for practical implementation. Future work should focus on conducting more prospective, multicenter studies to validate the additional value of quantitative studies and optimize prediction models by combining other biomarkers, such as urine and serum biomarkers. This review assesses the value of multiparameter MRI in the accurate evaluation of muscular invasion of bladder cancer, as well as the current status and progress of its application in the evaluation of efficacy and prognosis.
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OBJECTIVE: To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential (CHIP) related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events (CCEs) in patients with myeloproliferative neoplasms (MPNs). METHODS: The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed. Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients. RESULTS: Fifty-five cases of MPN (75.3%) showed positive in CHIP-related genes. There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia (ET) and polycythemia vera (PV). CHIP-related gene mutations were mainly single gene mutations, with mutation rate from high to low as JAK2V617F (63.0%, 46/73), ASXL1 (16.4%, 12/73), TET2 (11.0%, 8/73), DNMT3A (9.6%, 7/73), SRSF2 (6.9%, 5/73), SF3B1 (4.1%, 3/73), TP53(1.4%, 1/73) and PPM1D (1.4%, 1/73). The mutation rate of CHIP-related genes in MPN patients >60 years old was significantly higher than that in the patients ≤60 years old ï¼»91.7%(33/36) vs 59.5%(22/37)ï¼½. CCEs occurred in 27 MPNs patients (37.0%, MPNs/CCEs), and 5 had recurrent CCEs, all of which were arterial events. Age (62.8±12.8 years vs 53.9±15.8 years, P =0.015), IL-1ß level (17.7±26.0 vs 4.3±8.6, P =0.012), IL-8 level (360.7±598.6 vs 108.3±317.0, P =0.045), the proportion of the patients with thrombosis history (29.6% vs 2.2%, P =0.020), and the detection rate of CHIP-related mutations (88.9% vs 67.4%, P =0.040) in the group with CCEs were higher than those in the group without CCEs. Multivariate Logistic regression analysis showed that ageï¼OR =0.917ï¼ 95%CI ï¼0.843-0.999, P =0.047ï¼, thrombosis history (OR =34.148ï¼ 95%CI ï¼2.392-487.535, P =0.009), any CHIP-related mutations(OR =16.065ï¼ 95%CI ï¼1.217-212.024ï¼ P =0.035), and elevated level of IL-1ß (OR =0.929ï¼ 95%CI ï¼0.870-0.992ï¼ P =0.027) were independent risk factors for MPNs/CCEs. CHIP-related gene mutations were not associated with CCEs in MPN patients, but DNMT3A (OR =88.717ï¼ 95%CI ï¼2.690-292.482ï¼ P =0.012) and ASXL1 (OR =7.941ï¼ 95%CI ï¼1.045-60.353ï¼ P =0.045) were independent risk factors for CCEs in PV. CONCLUSION: There is a higher mutation rate of CHIP-related genes in MPN patients, especially those over 60 years old. Older age, thrombosis history, CHIP-related mutations and IL-1ß elevated levels are independent risk factors for CCEs in MPN. DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients. CHIP-related gene mutations and inflammatory cytokine IL-1 ß elevated levels may be the novel risk factors for CCEs in MPN.
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Trastornos Mieloproliferativos , Policitemia Vera , Trombosis , Humanos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Hematopoyesis Clonal , Janus Quinasa 2/genética , Trastornos Mieloproliferativos/genética , Policitemia Vera/genética , MutaciónRESUMEN
Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.
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Secuenciación de Inmunoprecipitación de Cromatina , Cromatina , Bases de Datos Genéticas , Análisis de la Célula Individual , Cromatina/genética , Epigénesis Genética , Humanos , AnimalesRESUMEN
The electrochemical reduction of carbon dioxide (CO2) to ethylene creates a carbon-neutral approach to converting carbon dioxide into intermittent renewable electricity. Exploring efficient electrocatalysts with potentially high ethylene selectivity is extremely desirable, but still challenging. In this report, a laboratory-designed catalyst HKUST-1@Cu2O/PTFE-1 is prepared, in which the high specific surface area of the composites with improved CO2 adsorption and the abundance of active sites contribute to the increased electrocatalytic activity. Furthermore, the hydrophobic interface constructed by the hydrophobic material polytetrafluoroethylene (PTFE) effectively inhibits the occurrence of hydrogen evolution reactions, providing a significant improvement in the efficiency of CO2 electroreduction. The distinctive structures result in the remarkable hydrocarbon fuels generation with high Faraday efficiency (FE) of 67.41%, particularly for ethylene with FE of 46.08% (-1.0 V vs RHE). The superior performance of the catalyst is verified by DFT calculation with lower Gibbs free energy of the intermediate interactions with improved proton migration and selectivity to emerge the polycarbonï¼C2+ï¼ product. In this work, a promising and effective strategy is presented to configure MOF-based materials with tailored hydrophobic interface, high adsorption selectivity and more exposed active sites for enhancing the efficiency of the electroreduction of CO2 to C2+ products with high added value.
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BACKGROUND: Stroke, which is the main element of cerebrovascular disease (CVD), has become the foremost reason for death and disability on a global scale. The systemic inflammation response index (SIRI), a newly developed and comprehensive indicator, has demonstrated promise in forecasting clinical results for diverse ailments. Nevertheless, the uncertainty surrounding the assessment and prediction of clinical outcomes for stroke patients by SIRI persists, and the conflicting findings from the limited studies conducted on this matter further complicate the situation. Consequently, we performed a thorough systematic review and meta-analysis to explore the correlation between SIRI and the clinical results in individuals suffering from stroke. METHODS: This research was registered in PROSPERO and carried out following the PRISMA guidelines. A thorough investigation was carried out on PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. Furthermore, we conducted a manual search in Chinese databases, such as China national Knowledge Infrastructure (CNKI), WanFang, VIP, and China Biology Medicine (CBM). We assessed the potential for bias in the studies included by utilizing the Newcastle-Ottawa Scale (NOS) tool. Adverse clinical outcomes were the main focus of the study, with secondary endpoints including mortality, the predictive value of SIRI, SIRI values across various endpoints, and clinical parameters associated with subarachnoid hemorrhage (SAH) in relation to low and high SIRI group. RESULTS: Following rigorous evaluation, a grand total of 22 investigations, encompassing a populace of 12,737 individuals, were considered suitable for incorporation in the final analysis. The findings from our meta-analysis indicate a strong and consistent correlation between elevated SIRI levels and adverse functional outcomes, irrespective of the method used to evaluate unfavorable outcomes. Furthermore, increased SIRI values have a strong correlation with mortality rates in both the short and long term. Besides, SIRI is a useful indicator of the severity of SAH. SIRI demonstrates strong predictive ability in identifying unfavorable outcomes and stroke-related pneumonia (SAP), as higher SIRI values are typically linked to negative endpoints. Nevertheless, the meta-analysis indicated that there was no significant increase in the risk of early neurological deterioration (END) and acute hydrocephalus (AHC) in high SIRI group when comparing to low SIRI. CONCLUSION: This study could potentially pave the way for groundbreaking insights into the relationship between SIRI and stroke patient outcomes, as it appears to be the first meta-analysis to explore this association. Given the critical role of the inflammatory response in stroke recovery, closely monitoring patients with high SIRI levels could represent a promising strategy for mitigating brain damage post-stroke. Thus, further investigation into SIRI and its impact on clinical outcomes is essential. While our initial findings offer valuable insights into this area, continued research is necessary to fully elucidate the potential of SIRI, ideally through dynamic monitoring and large-scale, multi-center studies. Ultimately, this research has the potential to inform clinical decision-making and improve patient outcomes following stroke. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ ; Identifier CRD42023405221.
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Inflamación , Accidente Cerebrovascular , Humanos , Pronóstico , Accidente Cerebrovascular/diagnósticoRESUMEN
Purpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD. Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3-4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT). Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: -0.35; 95% CI: -0.61, -0.10; P = 0.006) and AE-related hospitalizations (-0.18; 95% CI: -0.36, -0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P < 0.001), mMRC (-0.57; 95% CI: -0.76, -0.37; P < 0.001), total symptoms (-2.18; 95% CI: -2.84, -1.53; P < 0.001), SF-36 (11.60; 95% CI: 8.23, 14.97; P < 0.001), and mCOPD-PRO (-0.45; 95% CI: -0.57, -0.33; P < 0.001) after treatment. However, there were no significant differences in mortality, pulmonary function, and mESQ-PRO scores (P > 0.05). No obvious adverse events were observed. Conclusion: BYG, as compared to a placebo, could significantly reduce the frequencies of AEs and AE-related hospitalizations for GOLD 3-4 COPD patients. Clinical symptoms, treatment satisfaction, quality of life, and exercise capacity improved. There was no significant improvement in mortality and pulmonary function.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Calidad de Vida , Pulmón , Disnea , CaminataRESUMEN
Indium antimonide nanowires (InSb NWs) are attractive building-block candidates for bottom-up construction of high-efficiency electronics and optoelectronics due to their narrow direct band gap, fast room temperature carrier mobilities and small exciton binding energy. However, InSb NWs synthesized by the vapor-liquid-solution (VLS) mechanism generally suffer from an increased carrier and phonon scattering rate, which is thought to be caused by randomly distributed crystal defects along the NW growth direction. In this study, by utilizing the recently developed low-temperature, solution-processed technique, these crystal defects were successfully suppressed by periodically distributed twin planes to form twinned InSb nanowires. Importantly, measurements of the electrical transport properties of field effect transistors (FETs) reveal that the InSb NWs exhibit a hole-dominated conductivity with room temperature mobilities of up to 50.71 cm2 V-1 s-1, which is distinctly contrary to the intrinsic n-type InSb NWs. This observation of n-p switching behavior is probably attributed to the surface band bending effect with regard to the Fermi energy level, which is caused by surface oxide trap states arising from the native-oxide layer at the surface of the InSb NWs. All these results illustrate that the as-prepared colloidal InSb NWs can potentially be used as p-type materials for integration with next-generation nanoscale electronics and optoelectronics via surface engineering.
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Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochloride, a drug known for its antiviral properties, shows promise as it accumulates in the small intestine and modulates the intestinal microbiota. Therefore, we formulated a hypothesis that metformin hydrochloride could inhibit rotavirus replication in the intestine. To validate the anti-rotavirus effect of metformin hydrochloride, we conducted infection experiments using different models, ranging from in vitro cells and organoids to small intestines in vivo. The findings indicate that a concentration of 0.5 mM metformin hydrochloride significantly inhibits the expression of rotavirus mRNA and protein in Caco-2 cells, small intestinal organoids, and suckling mice models. Rotavirus infections lead to noticeable pathological changes, but treatment with metformin has been observed to mitigate the lesions caused by rotavirus infection in the treated group. Our study establishes that metformin hydrochloride can inhibit rotavirus replication, while also affirming the reliability of organoids as a virus model for in vitro research.
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BACKGROUND: to evaluate the feasibility of texture analysis (TA) based on diffusion kurtosis imaging (DKI) in staging and grading bladder cancer (BC) and to compare it with apparent diffusion coefficient (ADC) and biparametric vesical imaging reporting and data system (VI-RADS). MATERIALS AND METHODS: In this retrospective study, 101 patients with pathologically confirmed BC underwent MRI with multiple-b values ranging from 0 to 2000 s/mm2. ADC- and DKI-derived parameters, including mean kurtosis (MK) and mean diffusivity (MD), were obtained. First-order texture histogram parameters of MK and MD, including the mean; 5th, 25th, 50th, 75th, and 90th percentiles; inhomogeneity; skewness: kurtosis; and entropy; were extracted. The VI-RADS score was evaluated based on the T2WI and DWI. The Mann-Whitney U-test was used to compare the texture parameters and ADC values between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), as well as between low and high grades. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of each significant parameter and their combinations. RESULTS: The NMIBC and low-grade group had higher MDmean, MD5th, MD25th, MD50th, MD75th, MD90th, and ADC values than those of the MIBC and the high-grade group. The NMIBC and low-grade group yielded lower MKmean, MK25th, MK50th, MK75th, and MK90th than the MIBC and high-grade group. Among all histogram parameters, MD75th and MD90th yielded the highest AUC in differentiating MIBC from NMIBC (both AUCs were 0.87), while the AUC for ADC was 0.86. The MK75th and MK90th had the highest AUC (both 0.79) in differentiating low- from high-grade BC, while ADC had an AUC of 0.68. The AUC (0.92) of the combination of DKI histogram parameters (MD75th, MD90th, and MK90th) with biparametric VI-RADS in staging BC was higher than that of the biparametric VI-RADS (0.89). CONCLUSIONS: Texture-analysis-derived DKI is useful in evaluating both the staging and grading of bladder cancer; in addition, the histogram parameters of the DKI (MD75th, MD90th, and MK90th) can provide additional value to VI-RADS.
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Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanalysis 2.0 (http://licpathway.net/SEanalysis), an updated version of the SEanalysis web server for the comprehensive analyses of transcriptional regulatory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, documenting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly improved the ability of original SE-related network analyses ('pathway downstream analysis', 'upstream regulatory analysis' and 'genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis models, 'TF regulatory analysis' and 'Sample comparative analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE regions to provide potential SE-related disease/trait information. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capabilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs.
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Elementos de Facilitación Genéticos , Redes Reguladoras de Genes , Programas Informáticos , Factores de Transcripción , Animales , Humanos , Ratones , Regulación de la Expresión Génica , Genómica , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Lentinula edodes has high nutritional value and abundant protein. In order to develop and utilize edible mushroom protein, this study was designed to investigate the effects of TGase-catalyzed glycosylation and cross-linking on the physicochemical and functional properties of Lentinus edodes protein fraction. The results showed that within a certain time, glycosylation and TGase-catalyzed glycosylation decreased the total sulfydryl, free sulfydryl, disulfide bond, surface hydrophobicity, ß-fold and α-helix, but increased the fluorescence intensity, random coil, ß-turn, particle size and thermal stability. The apparent viscosity and the shear stress of the protein with an increase in shear rate were increased, indicating that TGase-catalyzed glycosylation promoted the generation of cross-linked polymers. In addition, the TGase-catalyzed glycosylated proteins showed a compact texture structure similar to the glycosylated proteins at the beginning, indicating that they formed a stable three-dimensional network structure. The flaky structure of proteins became more and more obvious with time. Moreover, the solubility, emulsification, stability and oil-holding capacity of enzymatic glycosylated Lentinus edodes protein fraction were significantly improved because of the proper TGase effects of glycosylation grafting and cross-linking. These results showed that glycosylation and TGase-catalyzed glycosylation could improve the processing characteristics of the Lentinula edodes protein fraction to varying degrees.
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With an ageing population, healthy longevity is becoming an important scientific concern. The longevity phenomenon is closely related to the intestinal microflora and is highly complicated; it is challenging to identify and define the core gut microbiota associated with longevity. Therefore, in this study, 16S rRNA sequencing data were obtained from a total of 135 faecal samples collected as part of the latest sampling and pre-collection initiative in the Guangxi longevity area, and weighted gene co-expression network analysis (WGCNA) was used to find a mediumpurple3 network module significantly associated with the Guangxi longevity phenomenon. Five core genera, namely, Alistipes, Bacteroides, Blautia, Lachnospiraceae NK4A136 group, and Lactobacillus, were identified via network analysis and random forest (RF) in this module. Two potential probiotic strains, Lactobacillus fermentum and Bacteroides fragilis, were further isolated and screened from the above five core genera, and then combined and used as an intervention in naturally ageing mice. The results show a change in the key longevity gut microbiota in mice toward a healthy longevity state after the intervention. In addition, the results show that the probiotic combination effectively ameliorated anxiety and necrosis of hippocampal neuronal cells in senescent mice, improving their antioxidant capacity and reducing their inflammation levels. In conclusion, this longer-term study provides a new approach to the search for longevity hub microbiota. These results may also provide an important theoretical reference for the healthification of the intestinal microflora in the general population, and even the remodelling of the structure of the longevity-state intestinal microflora.
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Microbioma Gastrointestinal , Probióticos , Humanos , Ratones , Animales , Microbioma Gastrointestinal/fisiología , ARN Ribosómico 16S/genética , China , Envejecimiento/fisiologíaRESUMEN
We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.
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Adenocarcinoma del Pulmón , Fritillaria , Neoplasias Pulmonares , Trichosanthes , Humanos , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Adenocarcinoma del Pulmón/tratamiento farmacológico , Bases de Datos Genéticas , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Simulación del Acoplamiento MolecularRESUMEN
BACKGROUND: The aim of this study is to investigate the feasibility of amide proton transfer-weighted (APTw) imaging combined with ZOOMit diffusion kurtosis imaging (DKI) in predicting lymph node metastasis (LNM) in cervical cancer (CC). MATERIALS AND METHODS: Sixty-one participants with pathologically confirmed CC were included in this retrospective study. The APTw MRI and ZOOMit diffusion-weighted imaging (DWI) were acquired. The mean values of APTw and DKI parameters including mean kurtosis (MK) and mean diffusivity (MD) of the primary tumors were calculated. The parameters were compared between the LNM and non-LNM groups using the Student's t-test or Mann-Whitney U test. Binary logistic regression analysis was performed to determine the association between the LNM status and the risk factors. The diagnostic performance of these quantitative parameters and their combinations for predicting the LNM was assessed with receiver operating characteristic (ROC) curve analysis. RESULTS: Patients were divided into the LNM group (n = 17) and the non-LNM group (n = 44). The LNM group presented significantly higher APTw (3.7 ± 1.1% vs. 2.4 ± 1.0%, p < 0.001), MK (1.065 ± 0.185 vs. 0.909 ± 0.189, p = 0.005) and lower MD (0.989 ± 0.195 × 10-3 mm2/s vs. 1.193 ± 0.337 ×10-3 mm2/s, p = 0.035) than the non-LNM group. APTw was an independent predictor (OR = 3.115, p = 0.039) for evaluating the lymph node status through multivariate analysis. The area under the curve (AUC) of APTw (0.807) was higher than those of MK (AUC, 0.715) and MD (AUC, 0.675) for discriminating LNM from non-LNM, but the differences were not significant (all p > 0.05). Moreover, the combination of APTw, MK, and MD yielded the highest AUC (0.864), with the corresponding sensitivity of 76.5% and specificity of 88.6%. CONCLUSION: APTw and ZOOMit DKI parameters may serve as potential noninvasive biomarkers in predicting LNM of CC.
RESUMEN
BACKGROUND: Pretreatment prediction of stage in patients with cervical cancer (CC) is vital for tailoring treatment strategy. This study aimed to explore the feasibility of a model combining reduced field-of-view (rFOV) diffusion-weighted imaging (DWI)-derived radiomics with clinical features in staging CC. METHODS: Patients with pathologically proven CC were enrolled in this retrospective study. The rFOV DWI with b values of 0 and 800 s/mm2 was acquired and the clinical characteristics of each patient were collected. Radiomics features were extracted from the apparent diffusion coefficient maps and key features were selected subsequently. A clinical-radiomics model combining radiomics with clinical features was constructed. The receiver operating characteristic curve was introduced to evaluate the predictive efficacy of the model, followed by comparisons with the MR-based subjective stage assessment (radiological model). RESULTS: Ninety-four patients were analyzed and divided into training (n = 61) and testing (n = 33) cohorts. In the training cohort, the area under the curve (AUC) of clinical-radiomics model (AUC = 0.877) for staging CC was similar to that of radiomics model (AUC = 0.867), but significantly higher than that of clinical model (AUC = 0.673). In the testing cohort, the clinical-radiomics model yielded the highest predictive performance (AUC = 0.887) of staging CC, even without a statistically significant difference when compared with the clinical model (AUC = 0.793), radiomics model (AUC = 0.846), or radiological model (AUC = 0.823). CONCLUSIONS: The rFOV DWI-derived clinical-radiomics model has the potential for staging CC, thereby facilitating clinical decision-making.