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Tubocapsicum anomalum, a Chinese medicinal plant rich in anti-tumor withanolides, requires efficient extraction methods. In this paper, an HPLC method was first established for the detection of withanolides, and gradient elution was carried out using a methanol-water solvent system. It was found that the content of withanolides was the highest in the leaves of T. anomalum, followed by the stems and fruits, and almost none in the roots. During the actual picking process, the quantity of leaves collected was relatively small, while the number of stems was the highest. Therefore, the Box-Behnken response surface method was used to optimize the ultrasonic-assisted extraction process of withanolides from the stems of T. anomalum. The optimal extraction conditions were determined as follows: the liquid-solid ratio was 20:1, the extraction solvent was 70 % ethanol, the ultrasonic power was 250 W, the ultrasonic time was 40 min, and the ultrasonic temperature was 50 °C. Under these conditions, the average yields of tubocapsenolide A (Te-A) and tubocapsanolide A (Ta-A) can reach 2.87 ± 0.12 mg/g and 1.18 ± 0.05 mg/g, respectively. We further compared extraction rates of two withanolides from different parts of T. anomalum using ultrasonic and traditional extraction methods. Ultrasonic extraction significantly increased rates, with the highest yields from leaves, followed by stems and fruits. The results show that ultrasonic optimization can improve extraction rate, reduce time, lower costs, enhance quality, and increase yield. Therefore, the optimized ultrasonic-assisted extraction process was adopted to extract the aerial parts of T. anomalum and separate the components. After optimization, the extract underwent several chromatographic separations to isolate eight previously undescribed withanolides (1-8) and two artificial withanolides (9-10), in addition to fifteen known compounds (11-25). Their structures were established through extensive spectroscopic data analysis. The compounds were evaluated for their antiproliferative effects against multiple cancer cell lines, including human hepatocellular carcinoma cells (HepG2, Hep3B, and MHCC97-H), human lung cancer cells (A549), human fibro-sarcoma cancer cells (HT1080), human chronic myeloid leukemia cells (K562), and human breast cancer cells (MDA-MB-231 and MCF7). Compounds 1-3, 5, 7, 11, 13, 15-16, and 22 displayed significant activity with IC50 values of 5.14-19.87 µM. The above results indicate that ultrasonic-assisted extraction technology can be used to obtain new withanolides more efficiently from T. anomalum, thereby enhancing the utilization rate of T. anomalum resources.

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Colorectal cancer (CRC) is one of the most common malignant tumors globally, with metastasis emerging as the leading cause of mortality in CRC patients. Transcription factors play pivotal roles in the metastatic process. Using bioinformatics tools, we analyzed the TCGA-COAD and GES146587 datasets and identified ZNF248 participating in tumor progression. By analyzing 100 CRC patient tissues, it is found that ZNF248 is highly expressed in cancer tissue as well as in CRC cell lines identified by qRT-PCR. Our study discovered that ZNF248 enhances CRC cell migratory and invasive capabilities. A positive correlation was found between ZNF248 and epithelial-mesenchymal transition (EMT)-related markers (ZEB1, snail1), while E-cadherin exhibited a negative correlation with ZNF248. In addition, the analysis of the TCGA dataset demonstrated a strong correlation between the mRNA level of ZNF248 and ZEB1 expressions. Furthermore, it is found that the overexpression of ZEB1 could reverse CRC cell invasion and migration, along with the inhibition on EMT marker expressions induced by the RNA interference with ZNF248. Immunohistochemical analysis indicated a substantial association of ZNF248 expression with the lymph node metastasis, and with the liver metastasis (P =0.01, P =0.01), and a positive correlation between ZNF248 and ZEB1 expression (P =0.021) was also identified. Using Chip-PCR assay, it is found that ZNF248 bound to the ZEB1 promoter region. These findings showed that ZNF248 promotes CRC metastasis in vivo, revealed its role as an oncogene in CRC by targeting ZEB1 and activating the EMT pathway, which provided novel and promising biomarkers for CRC therapy through targeting ZEB1.

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The arthroconidial yeast-like species currently classified in the asexual genera Geotrichum and Saprochaete and the sexual genera Dipodascus, Galactomyces and Magnusiomyces are frequently associated with dairy and cosmetics production, fruit rot and human infection. However, the taxonomic system of these fungi has not been updated to accommodate the new nomenclature code adopting the "one fungus, one name" principle. Here, we performed phylogenetic analyses of these yeast-like species based on the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit of the rRNA gene. Two monophyletic groups were recognised from these species. One group contained Dipodascus, Galactomyces, and Geotrichum species and the other Magnusiomyces and Saprochaete species. We thus assigned the species in each group into one genus and selected the genus name Geotrichum for the first group and Magnusiomyces for the second one based on the principle of priority of publication. Five new Geotrichum species were identified from arthroconidial yeast strains recently isolated from various sources in China. The new species are described as Ge. dehoogii sp. nov., Ge. fujianense sp. nov., Ge. maricola sp. nov., Ge. smithiae sp. nov., and Ge. sinensis sp. nov.

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OBJECTIVES: Disaster experiences have long-term effects on disaster preparedness. This study examined the long-term (10-y) effect of disaster severity of the 2008 Wenchuan earthquake on survivors' disaster preparedness and the moderating effects of household vulnerability. METHODS: The data were collected in January 2018 covering 30 counties in Wenchuan earthquake-stricken areas. The dependent variable was survivors' disaster preparedness (including overall, material, knowledge and awareness, and action preparedness) in 2018. Disaster severity included survivors' housing damage and county death rate caused by the earthquake in 2008. Household vulnerability is a set of conditions that negatively affects the ability of people to prepare for and withstand disaster, proxied by households' per-capita income and the highest years of schooling of household members. We performed multivariable linear regression models to answer the research questions. RESULTS: A higher county death rate was associated with better overall preparedness (ß = 0.043; P < 0.05) and knowledge and awareness preparedness (ß = 0.018; P < 0.05), but housing damage was not significantly associated with disaster preparedness. The positive association of county death rate with overall preparedness (ß = -0.065; P < 0.05) becomes weaker when a household has a higher per-capita income. Also, with the household per-capita income increasing, the associations of county death rate with material preparedness (ß = -0.037; P < 0.05) and action preparedness (ß = -0.034; P < 0.01) become weaker. CONCLUSIONS: Disaster severity has positive and long-term effects on survivors' disaster preparedness. Also, the positive and long-term effects are affected by household vulnerability. Specifically, the positive and long-term effects of disaster severity on disaster preparedness are more substantial when a household is more vulnerable.

Asunto(s)

Terremotos , Sobrevivientes , Humanos , China/epidemiología , Sobrevivientes/estadística & datos numéricos , Sobrevivientes/psicología , Terremotos/estadística & datos numéricos , Encuestas y Cuestionarios , Masculino , Femenino , Persona de Mediana Edad , Adulto , Defensa Civil/estadística & datos numéricos , Defensa Civil/métodos , Defensa Civil/normas , Planificación en Desastres/métodos , Planificación en Desastres/estadística & datos numéricos

RESUMEN

As a kind of tonic Chinese medicine with dual use in medicine and food, there is a large market demanding for Codonopsis pilosula. Taking one-year-old C. pilosula seedlings as materials, we conducted a field experiment to examine the effect of compound fertilizer (750 kg·hm-2), organic fertilizer (15 t·hm-2) and Streptomyces pactum Act12 agent (9 t·hm-2 Act12+10 t·hm-2 organic fertilizer) treatments on root morphology, secondary metabolite content and expression level of lobetyolin metabolic pathway gene of C. pilosula, to clarify the effects of three fertilizers on the root morphology and medicinal quality. Compared to the control (10 t·hm-2 organic fertilizer, conventional fertilization), three fertilization treatments could promote root growth and formation. All fertilization treatments promoted the accumulation of C. pilosula polysaccharides and secondary metabolites. Act12 agent significantly increased the content of lobetyolin, atractylenolideIII, and 5-hydroxymethylfurfural. The qRT-PCR analysis indicated that three fertilization treatments increased the expression level of lobetyolin metabolic pathway genes, with Act12 agent treatment showing the most significant effect. Pearson correlation analysis demonstrated that the expression level of CpHCT and CpFAD genes was significantly positively correlated with atractylenolide III content. In conclusion, three fertilization treatments could effectively improve the yield and quality of C. pilosula. Among the three treatments, Act12 agent performed better than that of compound fertilizer and organic fertilizer, which was an effective measure to increase the yield and quality of C. pilosula.

Asunto(s)

Codonopsis , Fertilizantes , Raíces de Plantas , Streptomyces , Codonopsis/crecimiento & desarrollo , Codonopsis/metabolismo , Streptomyces/crecimiento & desarrollo , Streptomyces/metabolismo , Streptomyces/genética , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Plantas Medicinales/crecimiento & desarrollo , Plantas Medicinales/metabolismo , Plantas Medicinales/química

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Marine heatwaves (MHWs) are increasing in frequency and intensity, threatening marine organisms and ecosystems they support. Yet, little is known about impacts of intensifying MHWs on ecologically and economically important bivalves cultured in the South China Sea. Here, we compared survival and physiological responses of five bivalve species, Pinctada fucata, Crassostrea angulata, Perna viridis, Argopecten irradians and Paphia undulata, to two consecutive MHWs events (3 days of thermal exposure to + 4 °C or + 8 °C, following 3 days of recovery under ambient conditions). While P. fucata, P. viridis, and P. undulata are native to the South China Sea region, C. angulata and A. irradians are not. Individuals of P. fucata, C. angulata and P. viridis had higher stress tolerance to MHWs than A. irradians and P. undulata, the latter already experiencing 100% mortality under +8 °C conditions during the first event. With increasing intensity of MHWs, standard metabolic rates of all five species increased significantly, in line with significant depressions of function-related energy-metabolizing enzymes (CMA, NKA, and T-ATP). Likewise, activities of antioxidant enzymes (SOD, CAT, and MDA) and shell mineralization-related enzymes (AKP and ACP) responded significantly to MHWs, despite species-specific performances observed. These findings demonstrate that some bivalve species can likely fail to accommodate intensifying MHWs events in the South China Sea, but some may persist. If this is the case, then one would expect substantial loss of fitness in bivalve aquaculture in the South China Sea under intensifying MHWs conditions.

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Cochlear hair cells (HCs) sense sound waves and allow us to hear. Loss of HCs will cause irreversible sensorineural hearing loss. It is well known that DNA damage repair plays a critical role in protecting cells in many organs. However, how HCs respond to DNA damage and how defective DNA damage repair contributes to hearing loss remain elusive.In this study, we showed that cisplatin induced DNA damage in outer hair cells (OHCs) and promoted OHC loss, leading to hearing loss in mice of either sex. Cisplatin induced the expression of Brca1, a DNA damage repair factor, in OHCs. Deficiency of Brca1 induced OHC and hearing loss, and further promoted cisplatin-induced DNA damage in OHCs, accelerating OHC loss. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in OHCs and that BRCA1 promotes repair of DNA damage in OHCs and prevents hearing loss. Our findings not only demonstrate that DNA-damage inducible agent generates DNA damage in postmitotic HCs, but also suggest that DNA repair factors, like BRCA1, protect postmitotic HCs from DNA-damage induced cell death and hearing loss.Significance statement Sensorineural hearing loss is the most severe hearing loss caused by irreversible loss of cochlear hair cells. Hair cells are vulnerable to aging and ototoxic drug. Though DNA damage repair plays a critical role in protecting cells in many organs, it is poorly understood how DNA damage is repaired in hair cells. This study provides the first in vivo evidence demonstrating that cisplatin mainly induces DNA damage in outer hair cells and that BRCA1 promotes repair of DNA damage in outer hair cells and prevents outer hair cell loss as well as hearing loss.

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Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m-2. In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.

RESUMEN

Background: The femoral artery is the standard route for transarterial chemoembolization (TACE); however, it is negatively associated with the quality of life of patients, and carries an increased risk of deep vein thrombosis in the lower limbs. We employed the distal radial approach to TACE to assess its feasibility and safety. Methods: We conducted a retrospective study at the First Hospital of Jilin University from August 1, 2020 to October 31, 2023. To be eligible for inclusion in the study, the patients had to meet the following main inclusion criteria: (I) have undergone a preoperative imaging (abdominal computed tomography enhancement or magnetic resonance dynamic enhancement) examination, or have a pathologically confirmed diagnosis of primary liver cancer, and a Child-Pugh score of A or B; and (II) have undergone distal radial artery puncture. The primary endpoint of this study was the success rate of distal radial artery puncture. The secondary endpoints were complications and the duration of the puncture. Results: Among the 343 patients with primary liver cancer (of whom 236 were male and 107 were female), a total of 1,315 distal radial artery punctures were attempted. The success rate was remarkably high at 95.13% (1,251/1,315), with only 64 cases requiring an alternative approach due to failed puncture. The average puncture duration was 20±7.43 minutes. No bleeding and hematoma, no arterial dissection and pseudoaneurysm formation were observed on ultrasound, and the radial pulse was palpable in all patients, highlighting the safety of the procedure. Further, no adverse events of vascular occlusion were observed among the 12 patients who received 6 or more punctures, indicating the sustainability of the distal radial artery access under the premise of adequate vascular protection. The development of this technique requires a learning curve of at least 50 cases to break through the learning baseline and be proficient in distal radial artery blind puncture. This may be the reason why many interventional physicians are reluctant to perform this procedure, adapting to the femoral approach with a shorter learning curve. Conclusions: The distal radial artery approach is feasible and safe in hepatic arterial chemoembolization, and should be widely promoted in TACE.

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Sepsis is a systemic inflammatory reaction syndrome caused by infections. Acute lung injury (ALI) occurs first and most frequently in patients with sepsis. Gentiopicroside (GPS), which originates mostly from Gentiana, is classified as a secoiridoid glycosides. Terpenoid glycosides have various biological effects, including liver protection, blood glucose and cholesterol level management, and anti-inflammatory and antitumor effects. However, presently, the biochemical foundation and mechanism of the anti-inflammatory effects of GPS in sepsis-induced ALI have not been explained. In the present study, we established a rat model of sepsis ALI induced by cecal ligation and puncture. This enables us to observe the effects of GPS therapy, which significantly reduced the inflammatory response (TNF-α, IL-1ß, and IL-6), nitrogen stress, oxidative stress, and severity of ALI at both the whole animal and molecular levels. In addition, GPS ameliorates LPS-induced ALI via regulation of inflammatory response and cell proptosis in BEAS-2B. This study provides a theoretical basis for treating sepsis-induced ALI with GPS.

Asunto(s)

Lesión Pulmonar Aguda , Glucósidos Iridoides , Sepsis , Animales , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Glucósidos Iridoides/farmacología , Glucósidos Iridoides/uso terapéutico , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/tratamiento farmacológico , Ratas , Masculino , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Estrés Oxidativo/efectos de los fármacos , Inflamación/tratamiento farmacológico

RESUMEN

BACKGROUND: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. RESULTS: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan-Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05). CONCLUSIONS: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.

Asunto(s)

Neoplasias de la Mama , Carcinoma Ductal de Mama , Terapia Neoadyuvante , Receptor ErbB-2 , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/mortalidad , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/metabolismo , Persona de Mediana Edad , Tasa de Supervivencia , Pronóstico , Receptor ErbB-2/metabolismo , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Receptores de Progesterona/metabolismo , Programa de VERF , Receptores de Estrógenos/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Quimioterapia Adyuvante/métodos , Estudios Retrospectivos

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Noncoding RNA plays a pivotal role as novel regulators of endothelial cell function. Type 2 diabetes, acknowledged as a primary contributor to cardiovascular diseases, plays a vital role in vascular endothelial cell dysfunction due to induced abnormalities of glucolipid metabolism and oxidative stress. In this study, aberrant expression levels of circHMGCS1 and MIR4521 were observed in diabetes-induced human umbilical vein endothelial cell dysfunction. Persistent inhibition of MIR4521 accelerated development and exacerbated vascular endothelial dysfunction in diabetic mice. Mechanistically, circHMGCS1 upregulated arginase 1 by sponging MIR4521, leading to decrease in vascular nitric oxide secretion and inhibition of endothelial nitric oxide synthase activity, and an increase in the expression of adhesion molecules and generation of cellular reactive oxygen species, reduced vasodilation and accelerated the impairment of vascular endothelial function. Collectively, these findings illuminate the physiological role and interacting mechanisms of circHMGCS1 and MIR4521 in diabetes-induced cardiovascular diseases, suggesting that modulating the expression of circHMGCS1 and MIR4521 could serve as a potential strategy to prevent diabetes-associated cardiovascular diseases. Furthermore, our findings provide a novel technical avenue for unraveling ncRNAs regulatory roles of ncRNAs in diabetes and its associated complications.

Asunto(s)

Diabetes Mellitus Tipo 2 , Endotelio Vascular , Hidroximetilglutaril-CoA Sintasa , MicroARNs , ARN Circular , Animales , Humanos , Masculino , Ratones , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Ratones Endogámicos C57BL , MicroARNs/metabolismo , MicroARNs/genética , ARN Circular/genética , ARN Circular/metabolismo , Hidroximetilglutaril-CoA Sintasa/genética

RESUMEN

KEY MESSAGES: Sixty-nine quantitative trait nucleotides conferring maize resistance to Gibberella ear rot were detected, including eighteen novel loci. Four candidate genes were predicted, and four kompetitive allele-specific PCR markers were developed. Maize Gibberella ear rot (GER), caused by Fusarium graminearum, is one of the most devastating diseases in maize-growing regions worldwide. Enhancing maize cultivar resistance to this disease requires a comprehensive understanding of the genetic basis of resistance to GER. In this study, 334 maize inbred lines were phenotyped for GER resistance in five environments and genotyped using the Affymetrix CGMB56K SNP Array, and a genome-wide association study of resistance to GER was performed using a 3V multi-locus random-SNP-effect mixed linear model. A total of 69 quantitative trait nucleotides (QTNs) conferring resistance to GER were detected, and all of them explained individually less than 10% of the phenotypic variation, suggesting that resistance to GER is controlled by multiple minor-effect genetic loci. A total of 348 genes located around the 200-kb genomic region of these 69 QTNs were identified, and four of them (Zm00001d029648, Zm00001d031449, Zm00001d006397, and Zm00001d053145) were considered candidate genes conferring susceptibility to GER based on gene expression patterns. Moreover, four kompetitive allele-specific PCR markers were developed based on the non-synonymous variation of these four candidate genes and validated in two genetic populations. This study provides useful genetic resources for improving resistance to GER in maize.

Asunto(s)

Resistencia a la Enfermedad , Fusarium , Gibberella , Fenotipo , Enfermedades de las Plantas , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Zea mays , Zea mays/genética , Zea mays/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Marcadores Genéticos , Gibberella/genética , Fusarium/patogenicidad , Fusarium/fisiología , Genotipo , Mapeo Cromosómico , Estudio de Asociación del Genoma Completo , Estudios de Asociación Genética , Alelos , Genes de Plantas

RESUMEN

The accurate and efficient segmentation of the spine is important in the diagnosis and treatment of spine malfunctions and fractures. However, it is still challenging because of large inter-vertebra variations in shape and cross-image localization of the spine. In previous methods, convolutional neural networks (CNNs) have been widely applied as a vision backbone to tackle this task. However, these methods are challenged in utilizing the global contextual information across the whole image for accurate spine segmentation because of the inherent locality of the convolution operation. Compared with CNNs, the Vision Transformer (ViT) has been proposed as another vision backbone with a high capacity to capture global contextual information. However, when the ViT is employed for spine segmentation, it treats all input tokens equally, including vertebrae-related tokens and non-vertebrae-related tokens. Additionally, it lacks the capability to locate regions of interest, thus lowering the accuracy of spine segmentation. To address this limitation, we propose a novel Vertebrae-aware Vision Transformer (VerFormer) for automatic spine segmentation from CT images. Our VerFormer is designed by incorporating a novel Vertebrae-aware Global (VG) block into the ViT backbone. In the VG block, the vertebrae-related global contextual information is extracted by a Vertebrae-aware Global Query (VGQ) module. Then, this information is incorporated into query tokens to highlight vertebrae-related tokens in the multi-head self-attention module. Thus, this VG block can leverage global contextual information to effectively and efficiently locate spines across the whole input, thus improving the segmentation accuracy of VerFormer. Driven by this design, the VerFormer demonstrates a solid capacity to capture more discriminative dependencies and vertebrae-related context in automatic spine segmentation. The experimental results on two spine CT segmentation tasks demonstrate the effectiveness of our VG block and the superiority of our VerFormer in spine segmentation. Compared with other popular CNN- or ViT-based segmentation models, our VerFormer shows superior segmentation accuracy and generalization.

RESUMEN

Tyrosinase, a key enzyme in melanin synthesis, represents a crucial therapeutic target for hyperpigmentation disorders due to excessive melanin production. This study aimed to design and evaluate a series of indole-thiourea derivatives by conjugating thiosemicarbazones with strong tyrosinase inhibitory activity to indole. Among these derivatives, compound 4b demonstrated tyrosinase inhibitory activity with an IC50 of 5.9 ± 2.47 µM, outperforming kojic acid (IC50 = 16.4 ± 3.53 µM). Kinetic studies using Lineweaver-Burk plots confirmed competitive inhibition by compound 4b. Its favorable ADMET and drug-likeness properties make compound 4b a promising therapeutic candidate with a reduced risk of toxicity. Molecular docking revealed that the compounds bind strongly to mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (TYRP1), with compound 4b showing superior binding energies of -7.0 kcal/mol (mTYR) and -6.5 kcal/mol (TYRP1), surpassing both kojic acid and tropolone. Molecular dynamics simulations demonstrated the stability of the mTYR-4b complex with low RMSD and RMSF and consistent Rg and SASA values. Persistent strong hydrogen bonds with mTYR, along with favorable Gibbs free energy and MM/PBSA calculations (-19.37 kcal/mol), further support stable protein-ligand interactions. Overall, compound 4b demonstrated strong tyrosinase inhibition and favorable pharmacokinetics, highlighting its potential for treating pigmentary disorders.

Asunto(s)

Inhibidores Enzimáticos , Indoles , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Tiourea , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/química , Monofenol Monooxigenasa/metabolismo , Indoles/química , Indoles/farmacología , Indoles/síntesis química , Tiourea/química , Tiourea/farmacología , Tiourea/análogos & derivados , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Cinética , Humanos , Simulación de Dinámica Molecular , Agaricales/enzimología , Relación Estructura-Actividad

RESUMEN

Extended exposure to seawater results in the erosion of the structural high-strength steels utilized in marine equipment, primarily due to the infiltration of hydrogen. Consequently, this erosion leads to a decrease in the mechanical properties of the material. In this investigation, the mechanical responses of Q690 structural high-strength steel specimens were investigated by considering various hydrogen charging parameters, such as the current density, charging duration, and solution concentration values. The findings highlighted the significant impacts of electrochemical hydrogen charging parameters on the mechanical behaviors of Q690 steel samples. Specifically, a linear relationship was observed between the mechanical properties and the hydrogen charging current densities, while the associations with the charging duration and solution concentration were nonlinear. Additionally, the fracture morphology under various hydrogen charging parameters was analyzed and discussed. The results demonstrate that the mechanical properties of the material degrade with increasing hydrogen charging parameters, with tensile strength and yield stress decreasing by approximately 2-4%, and elongation after fracture reducing by about 20%. The findings also reveal that macroscopic fractures exhibit significant necking in uncharged conditions. As hydrogen charging parameters increase, macroscopic necking gradually diminishes, the number of microscopic dimples decreases, and the material ultimately transitions to a fully brittle fracture.

RESUMEN

The non-trivial magnetic and electronic phases occurring in topological magnets are often entangled, thus leading to a variety of exotic physical properties. Recently, the BaAl4-type compounds have been extensively investigated to elucidate the topological features appearing in their real- and momentum spaces. In particular, the topological Hall effect and the spin textures, typical of the centrosymmetric Eu(Al,Ga)4family, have stimulated extensive experimental and theoretical research. In this topical review, we discuss the latest findings regarding the Eu(Al,Ga)4topological antiferromagnets and related materials, arising from a vast array of experimental techniques. We show that Eu(Al,Ga)4represents a suitable platform to explore the interplay between lattice-, charge-, and spin degrees of freedom, and associated emergent phenomena. Finally, we address some key questions open to future investigation.