RESUMEN
The migration of breast cancer cells is the main cause of death and significantly regulated by physical factors of the extracellular matrix (ECM). To be specific, the curvature and stiffness of the ECM were discovered to effectively guide cell migration in velocity and direction. However, it is not clear what the extent of effect is when these dual-physical factors regulate cell migration. Moreover, the mechanobiology mechanism of breast cancer cell migration in the molecular level and analysis of cell traction force (CTF) are also important, but there is a lack of systematic investigation. Therefore, we employed a microfluidic platform to construct hydrogel microspheres with an independently adjustable curvature and stiffness as a three-dimensional substrate for breast cancer cell migration. We found that the cell migration velocity was negatively correlated to curvature and positively correlated to stiffness. In addition, curvature was investigated to influence the focal adhesion expression as well as the assignment of F-actin at the molecular level. Further, with the help of a motor-clutch mathematical model and hydrogel microsphere stress sensors, it was concluded that cells perceived physical factors (curvature and stiffness) to cause changes in CTF, which ultimately regulated cell motility. In summary, we employed a theoretical model (motor-clutch) and experimental strategy (stress sensors) to understand the mechanism of curvature and stiffness regulating breast cancer cell motility. These results provide evidence of force driven cancer cell migration by ECM physical factors and explain the mechanism from the perspective of mechanobiology.
RESUMEN
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.
Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Epítopos , Phlebovirus , Síndrome de Trombocitopenia Febril Grave , Animales , Phlebovirus/inmunología , Ratones , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Síndrome de Trombocitopenia Febril Grave/inmunología , Síndrome de Trombocitopenia Febril Grave/virología , Síndrome de Trombocitopenia Febril Grave/prevención & control , Humanos , Epítopos/inmunología , Femenino , Ratones Endogámicos BALB C , Proteínas del Envoltorio Viral/inmunología , Cristalografía por Rayos X , Chlorocebus aethiops , Glicoproteínas/inmunología , Células VeroRESUMEN
Phosphate deficiency and drought are significant environmental constraints that impact both the productivity and quality of wheat. The interaction between phosphorus and water facilitates their mutual absorption processes in plants. Under conditions of both phosphorus deficiency and drought stress, we observed a significant upregulation in the expression of wheat MYB-CC transcription factors through the transcriptome analysis. 52 TaMYB-CC genes in wheat were identified and analyzed their evolutionary relationships, structures, and expression patterns. The TaMYB-CC5 gene exhibited specific expression in roots and demonstrated significant upregulation under phosphorus deficiency and drought stress compared to other TaMYB-CC genes. The overexpression of TaMYB-CC5A in Arabidopsis resulted in a significant increase of root length under stress conditions, thereby enhancing tolerance to phosphate starvation and drought stress. The wheat lines with silenced TaMYB-CC5 genes exhibited reduced root length under stress conditions and increased sensitivity to phosphate deficiency and drought stress. In addition, silencing the TaMYB-CC5 genes resulted in altered phosphorus content in leaves but did not lead to a reduction in phosphorus content in roots. Enrichment analysis the co-expression genes of TaMYB-CC5 transcription factors, we found the zinc-induced facilitator-like (ZIFL) genes were prominent associated with TaMYB-CC5 gene. The TaZIFL1, TaZIFL2, and TaZIFL5 genes were verified specifically expressed in roots and regulated by TaMYB-CC5 transcript factor. Our study reveals the pivotal role of the TaMYB-CC5 gene in regulating TaZIFL genes, which is crucial for maintaining normal root growth under phosphorus deficiency and drought stress, thereby enhanced resistance to these abiotic stresses in wheat.
RESUMEN
This study aims to explore the relationship between the Systemic Immune-Inflammation Index (SII) and Cardiovascular-Kidney-Metabolic (CKM) Syndrome and its components. Data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018 were analyzed. CKM Syndrome is defined as the coexistence of Cardiometabolic Syndrome (CMS) and Chronic Kidney Disease (CKD). The SII is calculated using the formula: SII = (Platelet count × Neutrophil count)/Lymphocyte count. Weighted logistic regression models were used to examine the associations between SII and CKM, as well as its specific components. Restricted cubic splines explored non-linear relationships, and piecewise linear regression models assessed threshold effects. A consistent positive correlation was observed between elevated SII levels and the likelihood of CKM and its related diseases. In the fully adjusted Model 3, an increase of 1000 units in SII was associated with a 1.48-fold increase in the odds of CKM (95% CI 1.20-1.81, p < 0.001). Quartile analysis revealed a dose-response relationship, with the highest quartile of SII (Q4) showing the strongest association with CKM and its components. Nonlinear analyses revealed inflection points for waist circumference, triglycerides, low HDL-C, and cardiometabolic syndrome at specific SII levels, indicating a change in the direction or strength of associations beyond these points. Conversely, a linear relationship was observed between SII and chronic kidney disease. The SII is positively correlated with the risk of CKM Syndrome and its individual components, with evidence of non-linear relationships and threshold effects for some components.
Asunto(s)
Inflamación , Síndrome Metabólico , Insuficiencia Renal Crónica , Humanos , Síndrome Metabólico/inmunología , Síndrome Metabólico/sangre , Masculino , Femenino , Persona de Mediana Edad , Inflamación/sangre , Inflamación/inmunología , Insuficiencia Renal Crónica/inmunología , Insuficiencia Renal Crónica/sangre , Adulto , Encuestas Nutricionales , Síndrome Cardiorrenal/sangre , Síndrome Cardiorrenal/inmunología , Anciano , Factores de Riesgo , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/sangreRESUMEN
The identification and analysis of network motifs has been widely used in the functional analysis of signaling components, disease discovery and other fields. The positive feedback loop (PFL) is a simple but important network motif. The formation of a PFL is regulated by mechanical cues such as substrate stiffness, fiber stretching and cell compression in the cell microenvironment. Here, we propose a new term, 'mechanical PFL', and analyze the mechanisms of mechanical PFLs at molecular, subcellular and cellular scales. More and more therapies are being targeted against mechanosignaling pathways at the experimental and preclinical stages, and exploring mechanical PFLs as potential mechanomedicine targets could be a new direction for disease treatment.
RESUMEN
OBJECTIVE: Lennox-Gastaut Syndrome (LGS) is characterized by the presence of multiple seizure types and encompasses a heterogenous group of etiologies. The aim of our study was to evaluate the etiological profile of LGS and investigate seizure outcomes based on different clinical variables. METHODS: The clinical features, neuroimaging findings, genetic testing and other testing results of LGS patients were systematically reviewed. The identifiable etiology was categorized as either acquired or nonacquired. Univariate and multivariate regression analyses were performed to explore the association between clinical variables and seizure outcome at the last follow-up. RESULTS: We enrolled 156 patients diagnosed with LGS, of whom 66% were male. The mean age of patients was 34.2 months and the median follow-up duration was 29.5 months (interquartile range = 14-56.25 months). The initial seizure type was epileptic spasm in 61 patients, among which 33 of them met the criteria for infantile epileptic spasm syndrome. All patients underwent neuroimaging test, with 25% falling into the acquired structural category. Etiology could be identified in 84 individuals, including pathogenetic variants found in 34 out of 117 patients with nonacquired etiology. CHD2 mutations were most frequently observed among these pathogenetic variants. At the last follow-up, favorable outcomes were observed in 27 patients. The identification of etiology emerged as a significant determinant influencing LGS outcome; specifically, patients with unknown etiology had a higher likelihood of experiencing favorable outcomes compared to those with known cause (p = 0.041). Early onset age and longer epilepsy duration significantly increased the odds of an unfavorable outcome (p = 0.006 and 0.024). SIGNIFICANCE: We present novel data on the clinical and etiological spectrum of LGS, with determined etiology observed in over half of the patients. Epileptic spasms were found to be more prevalent than tonic seizures as seizure onset types in LGS. The presence of a known etiology, earlier age at onset, and longer duration of epilepsy were associated with a poorer long-term epileptological outcome.
Asunto(s)
Síndrome de Lennox-Gastaut , Humanos , Masculino , Síndrome de Lennox-Gastaut/fisiopatología , Femenino , Preescolar , Lactante , Niño , Estudios de Seguimiento , Estudios Retrospectivos , Espasmos Infantiles/etiología , Espasmos Infantiles/fisiopatología , ElectroencefalografíaRESUMEN
Purpose: Acute ischemic stroke (AIS) has seriously threatened people's health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS. Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4. Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients. Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.
RESUMEN
In this work, we propose elastic metamaterials with phase discontinuities to steer the propagation of near-source bulk waves in a semi-infinite elastic medium. Our design exploits an array of embedded subwavelength resonators with tailored masses to attain a complete phase shift spanning [Formula: see text]. This phase control allows for diverse wave functionalities, such as directional refraction and energy focusing. Through the use of dispersion diagrams and the generalized Snell's law, along with a multiple scattering formulation, we analytically demonstrate the effectiveness of our design in achieving the desired wavefront manipulation. The proposed design has the potential to advance the field of guiding elastic waves using metamaterials and find practical applications in areas such as isolating ground-borne vibrations in densely urbanized regions and energy harvesting. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'.
RESUMEN
BACKGROUND: Recent studies show that malnutrition increases all-cause mortality by 1.11 times and cardiovascular mortality by 2.60 times. Similarly, metabolic syndrome raises overall mortality by 40% and cardiovascular mortality by 37%. This research assesses the Nutritional Metabolic Risk Index (NMRI) for predicting these mortality risks. METHODS: We analyzed data from 14,209 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, where the NMRI was calculated based on the ratio of GNRI to TyG-WHtR. The relationship between NMRI and mortality was investigated using Kaplan-Meier methods and Cox regression models, with restricted cubic splines (RCS) employed to examine non-linear associations. The predictive capabilities of NMRI, GNRI, and TyG-WHtR for mortality were assessed using receiver operating characteristic curve (ROC) curve analysis. RESULTS: Over a median follow-up period of 89 months, there were 1358 all-cause deaths and 345 cardiovascular deaths recorded. Cox regression analysis indicated that each unit increase in NMRI was associated with an 8% reduction in all-cause mortality risk and a 15% reduction in cardiovascular mortality risk. RCS analysis found a nonlinear negative correlation between NMRI and both all-cause and cardiovascular mortality. NMRI demonstrated superior predictive accuracy for all-cause mortality (AUC: 0.696, 95% CI: 0.682-0.710) and cardiovascular mortality (AUC: 0.713, 95% CI: 0.689-0.737) compared to GNRI and TyG-WHtR (P < 0.05). CONCLUSIONS: The NMRI is inversely associated with the risk of all-cause and cardiovascular mortality in American adults.
RESUMEN
Objective: Colorectal cancer (CRC) incidence has been increasing worldwide over time. This study investigated whether drinking was associated with CRC risk. Methods: We designed a case-control study nested in a mass CRC screening program in Quzhou, China. Cases were newly diagnosed CRC in 2020-2022. Controls were randomly sampled using frequency match. Drinking variables included drinking status, frequency, duration, and others. Logistic regressions were used to estimate odds ratio (OR) and 95 % confidence interval (CI). Results: The crude OR (cOR) (95 % CI) of drinking between 153 cases and 650 controls was 1.46 (0.99, 2.16) in current drinkers, 3.31 (1.44, 7.60) in former drinkers, 1.82 (1.21, 2.74) in drinking 6-7 days/week, and 3.48 (1.29, 9.37) in drinking 1-19 years. Stratifying by sex, all drinking variables in women but not all in men were consistently associated with CRC risk. The adjusted OR (aOR) (95 % CI) was 1.01 (0.59, 1.74) in current drinking men, 2.27 (0.78, 6.64) in former drinking men, and 4.24 (1.61, 11.13) in current drinking women. The aOR (95 % CI) of drinking whisky was 0.19 (0.04, 0.83), 1.89 (0.86, 4.17), 2.25 (1.05, 4.83), and 1.82 (0.85, 3.92) in men drinking ≤0.5, >0.5-≤1.0, >1.0-≤1.5, and >1.5 Liter/week (P trend = 0.011), and 3.80 (1.03, 14.00) and 9.92 (2.01, 49.00) in women drinking ≤0.5 and >0.5 Liter/week (P trend = 0.001), respectively. Conclusions: There was sex difference in drinking associated with increased risk of CRC which association was stronger in women than that in men. Men's association between drinking whisky and CRC risk was J-shaped.
RESUMEN
AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.
RESUMEN
Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively explore the mechanisms underlying this age-related disparity, we conducted the integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, and elucidated six functionally and spatially distinctive macrophage groups and lymphocytes surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we characterized the dysfunction of Spp1+ macrophages in aged mice impeded the activation of the type â ¡ immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies.
Asunto(s)
Matriz Extracelular , Macrófagos , Andamios del Tejido , Cicatrización de Heridas , Animales , Matriz Extracelular/metabolismo , Andamios del Tejido/química , Ratones , Macrófagos/metabolismo , Envejecimiento , Ratones Endogámicos C57BL , Fibroblastos/metabolismo , Masculino , Humanos , Materiales Biocompatibles/químicaRESUMEN
Cancer remains a leading cause of mortality and poses a substantial threat to public health. Studies have revealed that Long noncoding RNA DANCR is a cytoplasmic lncRNA whose aberrant expression plays a pivotal role in various cancer types. Within tumour biology, DANCR exerts regulatory control over crucial processes such as proliferation, invasion, metastasis, angiogenesis, inflammatory responses, cellular energy metabolism reprogramming, and apoptosis. By acting as a competitive endogenous RNA for miRNAs and by interacting with proteins and mRNAs at the molecular level, DANCR contributes significantly to cancer progression. Elevated DANCR levels have also been linked to heightened resistance to anticancer drugs. Moreover, the detection of circulating DANCR holds promise as a valuable biomarker for aiding in the clinical differentiation of different cancer types. This article offers a comprehensive review and elucidation of the primary functions and molecular mechanisms through which DANCR influences tumours.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , AnimalesRESUMEN
BACKGROUND AND PURPOSE: To test the hypothesis that myoclonic seizures can evolve to tonic seizures, we documented the electroclinical features of this under-recognized seizure type. METHODS: We observed a distinct seizure pattern starting with myoclonus without returning to an interictal state, which subsequently evolved into generalized tonic seizures. The detailed symptomatic and electroencephalographic characteristics of this seizure were extracted, and the clinical manifestations, drug curative responses in patients with this seizure were reviewed and analyzed. RESULTS: The onset of all seizures was characterized by a preceding period of myoclonus and bursts of generalized spike or poly-spike slow wave discharges with high amplitude. This was closely followed by the occurrence of tonic seizures, which were distinguished by bursts of generalized fast activity at 10 Hz or higher frequency. This under-recognized seizure type has been designated as myoclonic-to-tonic (MT) seizure. The number of patients identified with MT seizures in this study was 34. The prevalence rate of MT seizures was found to be higher in males. While MT seizures typically included a tonic component, it should be noted that some patients experiencing this seizure type never presented with isolated tonic seizures. Generalized Epilepsy not further defined (GE) accounted for approximately one-third of the diagnosed cases, followed by Lennox-Gastaut syndrome and Epilepsy with Myoclonic-Atonic seizures. In comparison to other types of epilepsy, GE with MT seizures demonstrated a more favorable prognosis. CONCLUSIONS: The classification of myoclonic-to-tonic seizure represents a novel approach in comprehending the ictogenesis of generalized seizures and can provide valuable assistance to clinicians in epilepsy diagnosis.
Asunto(s)
Electroencefalografía , Epilepsias Mioclónicas , Convulsiones , Humanos , Masculino , Femenino , Electroencefalografía/métodos , Adulto , Adolescente , Convulsiones/fisiopatología , Convulsiones/diagnóstico , Niño , Adulto Joven , Epilepsias Mioclónicas/fisiopatología , Epilepsias Mioclónicas/diagnóstico , Epilepsia Generalizada/fisiopatología , Epilepsia Generalizada/diagnóstico , Preescolar , Persona de Mediana Edad , Mioclonía/fisiopatología , Mioclonía/diagnóstico , LactanteRESUMEN
To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.
Asunto(s)
Neoplasias Colorrectales , Enterotoxinas , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Mapas de Interacción de ProteínasRESUMEN
BACKGROUND: Rectal mucinous adenocarcinoma (MAC) is a rare pathological type of rectal cancer with unique pathological features and a poor prognosis. It is difficult to diagnose and treat early because of the lack of specific manifestations in some aspects of the disease. The common metastatic organs of rectal cancer are the liver and lung; however, rectal carcinoma with metastasis to subcutaneous soft tissue is a rare finding. CASE SUMMARY: In this report, the clinical data, diagnosis and treatment process, and postoperative pathological features of a patient with left waist subcutaneous soft tissue masses were retrospectively analyzed. The patient underwent surgical treatment after admission and recovered well after surgery. The final pathological diagnosis was rectal MAC with left waist subcutaneous soft tissue metastasis. CONCLUSION: Subcutaneous soft tissue metastasis of rectal MAC is rare, and it can suggest that the tumor is disseminated, and it can appear even earlier than the primary malignant tumor, which is occult and leads to a missed diagnosis and misdiagnosis clinically. When a subcutaneous soft tissue mass of unknown origin appears in a patient with rectal cancer, a malignant tumor should be considered.
RESUMEN
Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.
RESUMEN
Tropical Cyclones (TCs) are devastating natural disasters. Analyzing four decades of global TC data, here we find that among all global TC-active basins, the South China Sea (SCS) stands out as particularly difficult ocean for TCs to intensify, despite favorable atmosphere and ocean conditions. Over the SCS, TC intensification rate and its probability for a rapid intensification (intensification by ≥ 15.4 m s-1 day-1) are only 1/2 and 1/3, respectively, of those for the rest of the world ocean. Originating from complex interplays between astronomic tides and the SCS topography, gigantic ocean internal tides interact with TC-generated oceanic near-inertial waves and induce a strong ocean cooling effect, suppressing the TC intensification. Inclusion of this interaction between internal tides and TC in operational weather prediction systems is expected to improve forecast of TC intensity in the SCS and in other regions where strong internal tides are present.
RESUMEN
Omics, bioinformatics, molecular docking, and experimental validation were used to elucidate the hepatoprotective effects, mechanisms, and active compounds of Shandougen (SDG) based on the biolabel-led research pattern. Integrated omics were used to explore the biolabels of SDG intervention in liver tissue. Subsequently, bioinformatics and molecular docking were applied to topologically analyze its therapeutic effects, mechanisms, and active compounds based on biolabels. Finally, an animal model was used to verify the biolabel analysis results. Omics, bioinformatics, and molecular docking revealed that SDG may exert therapeutic effects on liver diseases in the multicompound and multitarget synergistic modes, especially liver cirrhosis. In the validation experiment, SDG and its active compounds (betulinic acid and gallic acid) significantly improved the liver histopathological damage in the CCl4-induced liver cirrhosis model. Meanwhile, they also produced significant inhibitory effects on the focal adhesion pathway (integrin alpha-1, myosin regulatory light chain 2, laminin subunit gamma-1, etc.) and alleviated the associated pathological processes: focal adhesion (focal adhesion kinase 1)-extracellular matrix (collagen alpha-1(IV) chain, collagen alpha-1(VI) chain, and collagen alpha-2(VI) chain) dysfunction, carcinogenesis (alpha-fetoprotein, NH3, and acetylcholinesterase), inflammation (tumor necrosis factor alpha, interleukin-1 [IL-1], IL-6, and IL-10), and oxidative stress (reactive oxygen species, malonaldehyde, and superoxide dismutase). This study provides new evidence and insights for the hepatoprotective effects, mechanisms, and active compounds of SDG.
Asunto(s)
Biología Computacional , Simulación del Acoplamiento Molecular , Animales , Hígado/efectos de los fármacos , Hígado/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Masculino , Ratas , Tetracloruro de Carbono , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Ácido Gálico/química , Ácido Gálico/farmacología , Triterpenos/química , Triterpenos/farmacología , Proteómica/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/químicaRESUMEN
Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.