RESUMEN
Edwardsiella piscicida is a severe fish pathogen with wide host range, causing the huge economic losses in the aquaculture industry. Cyclic adenosine monophosphate (cAMP) as an important second messenger regulates the physiological and behavioral responses to environmental cues in eukaryotic and prokaryotic. The intracellular level of cAMP for effective activity is tightly controlled by the synthesis of adenylate cyclase, excretion and degradation of phosphodiesterase. In this study, we identified and characterized a class III cAMP phosphodiesterase, named as CpdA, in the E. piscicida. To investigate the role of CpdA in the physiology and pathogenicity, we constructed the in-frame deletion mutant of cpdA of E. piscicida, TX01ΔcpdA. The results showed that TX01ΔcpdA accumulated the higher intracellular cAMP concentration than TX01, indicating that CpdA exerted the hydrolysis of cAMP. In addition, compared to the TX01, the TX01ΔcpdA slowed growth rate, diminished biofilm formation and lost motility. More importantly, pathogenicity analysis confirmed that TX01ΔcpdA significantly impaired the ability of invading the epithelial cells, reproduction in macrophages, tissues dissemination and lethality for healthy tilapias. The most of lost properties of TX01ΔcpdA were restored partially or fully by the introduction of cpdA gene. These results suggest that cpdA is required for regulation of the physiology and virulence of E. piscicida.
Asunto(s)
Edwardsiella , Infecciones por Enterobacteriaceae , Enfermedades de los Peces , Animales , Virulencia , Hidrolasas Diéster Fosfóricas/genética , AMP Cíclico/metabolismo , Biopelículas , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
α-Aryl substituted nitroalkanes are valuable synthetic building blocks that can be easily converted into α-aryl substituted aldehydes, ketones, carboxylic acids, as well as amines. Herein, an efficient Cu/oxalamide-catalyzed coupling between nitroalkanes and (hetero)aryl halides (Br, I) was developed to direct access highly diverse α-aryl substituted nitroalkanes. Compared with the current state of art, this protocol is more environmentally friendly and practical for synthetic chemists. This approach is characterized by a broad substrate scope on both nitroalkane part (primary nitroalkanes and nitromethane) and sp2 halide part ((hetero)aryl bromides/iodides and alkenyl bromides/iodides). The excellent functional group tolerance was observed, which would enable real world synthetic applications. More importantly, TON of current transformation reached to 3640, when some aryl iodides were used as coupling partners. This represents currently the highest catalyst turnover for transition-metal catalyzed α-arylation of nitroalkanes. Furthermore, the successful application in late-stage modification of complex molecules and synthesis of a known retinoid X receptor (RXR) antagonist exemplified its synthetic potential.
RESUMEN
BACKGROUND: With the increasing number of studies on osteoporosis and muscle adipose tissue, existing studies have shown that skeletal muscle tissue and adipose tissue are closely related to osteoporosis by dual-energy x-ray absorptiometry (DXA) measurement. However, few studies have explored whether the skeletal muscle and adipose tissue index measured at the lumbar spine 3 (L3) level are closely related to bone mineral density (BMD) and can even predict osteoporosis. Therefore, this study aimed to prove whether skeletal muscle and adipose tissue index measured by computed tomography (CT) images based on a single layer are closely related to BMD. METHODS: A total of 180 participants were enrolled in this study to obtain skeletal muscle index (SMI), psoas muscle index (PMI), subcutaneous fat index (SFI), visceral fat index (VFI), and the visceral-to-subcutaneous ratio of the fat area (VSR) at L3 levels and divide them into osteoporotic and normal groups based on the T-score of DXA. Spearman rank correlation was used to analyze the correlation between SMI, PMI, SFI, VFI, VSR, and BMD. Similarly, spearman rank correlation was also used to analyze the correlation between SMI, PMI, SFI, VFI, VSR, and the fracture risk assessment tool (FRAX). Receiver operating characteristic (ROC) was used to analyze the efficacy of SMI, PMI, SFI, VFI, and VSR in predicting osteoporosis. RESULTS: BMD of L1-4 was closely correlated with SMI, PMI, VFI and VSR (r = 0.199 p = 0.008, r = 0.422 p < 0.001, r = 0.253 p = 0.001, r = 0.310 p < 0.001). BMD of the femoral neck was only correlated with PMI and SFI (r = 0.268 p < 0.001, r = - 0.164 p-0.028). FRAX (major osteoporotic fracture) was only closely related to PMI (r = - 0.397 p < 0.001). FRAX (hip fracture) was closely related to SMI and PMI (r = - 0.183 p = 0.014, r = - 0.353 p < 0.001). Besides, FRAX (major osteoporotic fracture and hip fracture) did not correlate with VFI, SFI, and VSR. SMI and PMI were statistically significant, with the area under the curve (AUC) of 0.400 (95% confidence interval 0.312-0.488 p = 0.024) and 0.327 (95% confidence interval 0.244-0.410 p < 0.001), respectively. VFI, SFI, and VSR were not statistically significant in predicting osteoporosis. CONCLUSIONS: This study demonstrated that L3-based muscle index could assist clinicians in the diagnosis of osteoporosis to a certain extent, and PMI is superior to SMI in the diagnosis of osteoporosis. In addition, VFI, SFI, and VSR do not help clinicians to diagnose osteoporosis well.
Asunto(s)
Fracturas de Cadera , Osteoporosis , Fracturas Osteoporóticas , Humanos , Fracturas Osteoporóticas/diagnóstico , Músculos Psoas/diagnóstico por imagen , Factores de Riesgo , Medición de Riesgo/métodos , Osteoporosis/diagnóstico por imagen , Absorciometría de Fotón/métodos , Densidad Ósea/fisiología , Fracturas de Cadera/diagnóstico , Vértebras Lumbares/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Photonic jets (PJs) formed on the shadow side of micro-sized dielectric spheres excited by focused Gaussian beams are investigated within the framework of the generalized Lorenz-Mie theory (GLMT). The intrinsic advantages of rapidity and high accuracy of the GLMT in calculations enable us to conduct a systematic study of PJs at a low cost and a high reliability. To reveal the influence of beam parameters on the properties of PJs, numerical results concerning variations of key parameters of PJs, including the maximal intensity, the focal distance, which is linked to the position of maximal intensity, and longitudinal and transversal dimensions are presented with the change of the beam waist radius and the focal center location of the Gaussian beam. The results show that as the beam waist radius approaches the radius of the particle, the energy stream of the Gaussian beam contributes more efficiently to the formation of PJs. By properly tuning the location of the beam focal center, the PJ pattern can be efficiently engineered to a large extent.
RESUMEN
Cross-dimerization of a methylenecyclopropane (1) and an unactivated alkene (2) with typical hydroalkenylation reactivity was observed for the first time by using a [NHC-Ni(allyl)]BArF catalyst (NHC=N-heterocyclic carbene). Results show that the C-C cleavage of 1 did not involve a Ni0 oxidative addition, which was crucial in former systems. Thus the method reported here emerges as a complementary method for attaining highly chemo- and regioselective synthesis of methylenecyclopentanes (3) with broad scope. An efficient NHC/NiII -catalyzed rearrangement of 1 leads to the convergent synthesis of 3 in the presence of 2.
RESUMEN
A cross-hydroalkenylation/rearrangement cascade (HARC), using a cyclopropene and alkyne as substrate pairs, was achieved for the first time by using new [(NHC)Ni(allyl)]BArF catalysts (NHC=N-heterocyclic carbenes). By controlling the (NHC)NiII H relative insertion reactivity with cyclopropene and alkyne, a broad scope of cyclopentadienes was obtained with highly selectively. The structural features of the new (NHC)NiII catalyst were important for the success of the reaction. The mild reaction conditions employed may serve as an entry for exploring (NHC)NiII -assisted vinylcyclopropane rearrangement reactivity.
RESUMEN
PURPOSE: To investigate the pain relief effect and safety of percutaneous radiofrequency ablation (RFA) with a multitined electrode combined with cement injection in patients with painful metastatic bone tumors. MATERIALS AND METHODS: Sixteen patients with 34 osteolytic metastatic lesions were treated with RFA including 4 males and 12 females (age range 54-84). Thirteen patients with spinal metastases received additional cement injection. Medical imaging, a visual analog scale (VAS) and the EORTC QLQ-C30 were performed to evaluate the metastatic lesion, pain and quality of life, respectively, before and after RFA and at follow-ups. RESULTS: The RFA and/or vertebroplasty with cement injection were successful in all patients (100%). Except for one patient who had cement leakage, no intraprocedural complications occurred. After RFA, severe refractory pain was greatly relieved in all patients, with pretreatment VAS score of 8.1 ± 1.4 significantly reduced to 5.5 ± 1.1 at 24 h, 2.8 ± 0.6 at 1 week and 1.4 ± 0.8 at 6 months (P < 0.01). The EORTC QLQ-C30 scale at 1 month demonstrated significant improvement (P < 0.05) in the physical (P = 0.03) and emotion function (P = 0.003), global health status (P = 0.002), pain (P = 0.001) and insomnia (P = 0.002). The analgesics were reduced after the procedure and stopped 2 months later in all patients, with greatly improved quality of life and no apparent pain. Followed up for 6-12 months, all patients remained alive with no recurrence of pain. Palliative pain relief and safety of percutaneous radiofrequency ablation combined with cement injection for bone metastasis. CONCLUSION: RFA with or without bone cement is safe and effective in the palliative treatment of pain caused by metastatic bone tumors.
Asunto(s)
Cementos para Huesos/uso terapéutico , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Ablación por Catéter/efectos adversos , Manejo del Dolor , Cuidados Paliativos , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Dimensión del Dolor , Calidad de Vida , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To investigate factors affecting effects of ultrasound guided high intensity focused ultrasound (USgHIFU) in the treatment of single uterine fibroids (UFs) with different magnetic resonance imaging (MRI) features. METHODS: A total of 207 patients with single symptomatic UFs who were treated with HIFU were retrospectively analyzed. All UFs were grouped according to MRI features, and factors affecting HIFU ablation were set as independent variables. Non-perfusion volume ratio (NPVR) and energy efficiency factor (EEF) were set as dependent variables to establish multiple linear regression models with a stepwise method. RESULTS: All patients had successful HIFU treatment, with the mean NPVR of 74.7 ± 15.1% and the mean EEF of 7.4 ± 5.2 j/mm3. The NPVR was negatively correlated with transmural type of UFs, hyperintense on T2 weighted image (T2WI), enhancement type on T1 weighted image (T1WI), distance from UFs ventral side to skin and posterior location of UFs, but positively correlated with anterior location of UFs, hypointense on T2WI and anteverted uterus (uterine location). The EEF was negatively correlated with size, anterior location of UFs and hypointense on T2WI, but positively correlated with distance from UFs ventral side to skin, enhancement type on T1WI and transmural type of UFs. The UFs size and enhancement type on T1WI were the greatest factors affecting the ablation effect. CONCLUSIONS: The effect of HIFU treatment for single UFs is affected by multiple factors, and the UFs of hypointense on T2WI, large size, mild enhancement on T1WI and anteverted uterus can be easily ablated with high ablation efficiency.
Asunto(s)
Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Leiomioma/cirugía , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
AIM: The aims of the study are to investigate the changes in platelet indexes, including platelet count, platelet distribution width (PDW), and mean platelet volume (MPV), in patients with pulmonary embolism (PE) and to evaluate their diagnostic values in relation to this disease. METHODS: The study included 70 patients with PE as the observation group and 75 patients without PE as the control group. The differences in platelet count, PDW, MPV, d-dimer, and other indicators between the 2 groups were retrospectively analyzed. RESULTS: Platelet distribution width and MPV were significantly higher in patients with PE than in the controls (16.40% [13.70%-16.85%] vs 16.00% [11.28%-16.60%], P = .023; 9.91 ± 1.40 fL. vs 8.84 ± 1.68 fL, P < .001, respectively). Multivariate logistic regression analysis showed that MPV and d-dimer were independent influencing factors for the diagnosis of PE. Receiver operating characteristic curve analysis showed that MPV (with the cut-off value set at 8.45 fL) had a sensitivity of 88.7%, negative predictive value of 78.7%, specificity of 50.0%, and positive predictive value of 61.9%. d-Dimer (with the cut-off value set at 835.5 µg/L) had a sensitivity of 80.6%, negative predictive value of 77.8%, specificity of 62.1%, and positive predictive value of 66.7%. The combination of d-dimer and MPV resulted in an increase in the area under the curve (0.799; 95% confidence interval, 0.724-0.874; P < .001). CONCLUSION: Higher PDW and MPV levels are noticed in patients with PE. The combined application of MPV can improve the diagnostic value of d-dimer for PE.
Asunto(s)
Pruebas de Función Plaquetaria , Embolia Pulmonar/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Embolia Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
By consideration of the mechanism of Pd-catalyzed cyclopropanation and allylation, NHC-pyridine compounds were adopted as the ligand in Pd-catalyzed cyclopropanation of esters and monosubstituted allylic reagents. The corresponding cyclopropanes were afforded as major products in moderate to good yields with high cyclopropane/allylation selectivity.
Asunto(s)
Carbonatos/química , Ciclopropanos/química , Piridinas/química , Catálisis , Ésteres , Indicadores y Reactivos/química , Ligandos , Estructura Molecular , PaladioRESUMEN
A deformation coordination method is proposed in this study to account for the distortion effects on a box girder. The differential equation for distortion in vertical web box girders is derived based on the deformation coordination condition of the distortion angle, considering both external loads and internal forces. Subsequently, a comparative analysis is conducted to explore the similarities and differences between the differential equations derived from the proposed deformation coordination method, the plate element analysis method and the total potential energy variation method. The accuracy of the proposed approach is verified through bench-scale tests and numerical simulations. The findings indicate that the derived governing distortion differential equation and distortion attenuation coefficients in the proposed method align with those obtained from the plate element analysis method and the total potential energy variational method, which enhances the applicability to allow for the distortion equations to be obtained simply by calculating the distortion displacements. The analytical findings regarding the distortion warping normal stresses on the cross-sections of the box girders demonstrate favorable correspondence with the experimental results, displaying an acceptable error ranging from - 0.3% to 5.4%. Moreover, the peak of distortion warping normal stresses on the mid-span cross-section increases with higher span-to-depth ratios and height-to-thickness ratios of the web. Consequently, augmenting the thickness of the box wall proves to be an effective means of reducing the distortion effect in box girders.
RESUMEN
Fungi from the Pyricularia genus cause blast disease in many economically important crops and grasses, such as wheat, rice, and Cenchrus grass JUJUNCAO. Structure variation associated with the gain and loss of effectors contributes largely to the adaptive evolution of this fungus towards diverse host plants. A telomere-to-telomere genome assembly would facilitate the identification of genome-wide structural variations through comparative genomics. Here, we report a telomere-to-telomere, near-complete genome assembly of a Pyricularia penniseti isolate JC-1 infecting JUJUNCAO. The assembly consists of eight core chromosomes and two supernumerary chromosomes, named mini1 and mini2, spanning 42.1 Mb. We annotated 12,156 protein-coding genes and identified 4.54% of the genome as repetitive sequences. The two supernumerary chromosomes contained fewer genes and more repetitive sequences than the core chromosomes. Our genome and results provide valuable resources for the future study in genome evolution, structure variation and host adaptation of the Pyricularia fungus.
Asunto(s)
Ascomicetos , Cenchrus , Cromosomas Fúngicos , Genoma Fúngico , Ascomicetos/genética , Cenchrus/microbiología , Cromosomas Fúngicos/genética , Enfermedades de las Plantas/microbiología , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
Background: Preoperative nutritional support studies for patients undergoing gastrointestinal (GI) surgery mostly focused on enteral nutrition (EN) or long-term (≥7 days) parenteral nutrition (PN). Some studies also found that preoperative short-term PN could improve the postoperative short-term nutritional status of tumor patients. But whether short-term PN support (1-6 days) before surgery can improve the prognosis of patients undergoing surgery for gastric cancer (GC) remains unclear. Therefore, we focused on assessing the effect of preoperative short-term PN on the outcomes of patients undergoing radical surgery for GC. Methods: A retrospective analysis of 1,155 patients who underwent radical gastrectomy for GC between July 2014 and February 2019 was conducted. According to whether patients received short-term (1-6 days) PN support before surgery, patients were divided into non-PN group and PN group. After 1:1 propensity score matching (PSM), two groups of patients with similar baseline clinical characteristics were obtained. The incidence of various complications and overall survival (OS) rate were compared between the two groups, and logistic regression analysis for complications, Cox regression analysis for OS, and subgroup analysis were performed. Results: Each group had 478 patients after PSM, and the clinical characteristics were balanced. There were no significant differences in overall postoperative complications (pre-PSM: P=0.495; post-PSM: P>0.99), postoperative length of stay (LOS; pre-PSM: P=0.092; post-PSM: P=0.460), or readmission rate within 30 days (pre-PSM: P=0.496; post-PSM: P=0.793) between the two groups before and after PSM. The OS of PN group before matching was lower than that of non-PN group (P=0.023), but this difference was not significant after matching (P=0.950), but the PN group's hospitalization expenses were substantially greater than those of the control group (post-PSM: P<0.001). Preoperative short-term PN support was not an independent factor in the incidence of postoperative complications (P>0.99) and OS (P=0.949). Subgroup analyses failed to identify those patients who might benefit from preoperative short-term PN support. Conclusions: Preoperative short-term PN support may have no significant benefit on short-term postoperative complications or the long-term OS of patients with GC but increase hospitalization costs. It thus should not be the first choice of treatment for these patients.
RESUMEN
With the intensification of global change, forests are subjected to varying degrees of drought or high-temperature stress, which has an indelible impact on the growth of trees. However, knowledge on the response of sap flow to environmental changes in different types of forests is still rare, especially in China's subtropical forest ecosystem. Consequently, studying how different tree species regulate their sap flow in response to shifting environmental conditions is essential for understanding forest transpiration, water use efficiency, and drought stress resilience. Therefore, this study aimed to investigate the sap flow dynamics of seven tree species in five forest plots, i.e., pine forest (PF), two types of mixed conifer-broadleaf forests (MF1+MF2), monsoon evergreen broadleaved forest (MEBF), and montane monsoonal evergreen broad-leaf forest (MOBF) at Dinghushan National Reserve in Southern China, using the heat dissipation probe technique and synchronous environmental factor recordings. Results demonstrated a significant influence of photosynthetic active radiation (PAR) on sap flow across all tree species, with mean PAR values ranging from over 1200 to 425 µmol m-2 s-1, establishing it as the principal driving factor. This observation underscores the heightened responsiveness or sensitivity of tree species to variations in PAR as the forest undergoes development and maturation. The correlation between vapor pressure deficit (VPD) and tree sap flow decreased as succession progressed. Moreover, the influence of soil water content (SWC) on sap flow stability against environmental changes increased. Similar patterns were also found between the two MF, with MF-2 displaying ecological characteristics and environmental conditions more closely aligned with those of the late-successional MEBF. The study reveals the intricate relationship between environmental factors and sap flow regulation in tree species within a subtropical forest ecosystem. Addressing a comparative gap in sap flow correlation among dominant tree species at Dinghushan, it establishes a hydro-physiological foundation for understanding tree species substitution during forest succession. The results provide key insights for forest management and climate-related research. Future studies should delve into the long-term implications of observed sap flow dynamics, exploring their impact on tree species adaptability amid ongoing environmental changes.
RESUMEN
Introduction: Arteriovenous fistula (AVF) is the first choice of vascular access for hemodialysis treatment, and its surgical maturity rate is not high, and its postoperative complications (mostly stenosis) significantly shorten its life. At present, there are few studies on treatment methods to improve the maturity and survival of AVF. In this study, the effect of far infrared therapy (FIR) on the maturity and longevity of arteriovenous fistula in hemodialysis patients was discussed, and the protective mechanism of AVF induced by FIR therapy was explored, aiming at exploring a new treatment method. Methods: The hemodialysis patients admitted to the 900th Hospital of the Chinese Joint Logistics Support Force of the People's Liberation Army from January 2021 to April 2023 were randomly divided into control group and intervention group, with 40 cases in each group. Among them, the control group was coated with mucopolysaccharide polysulfonate cream; Intervention group: The patients were treated with mucopolysaccharide polysulfonate cream and far infrared radiation at the same time. After 3 months' intervention, the arteriovenous fistula (vein diameter, mature time of arteriovenous fistula, blood flow controlled by pump during dialysis, blood flow of brachial artery during dialysis and the occurrence of complications of internal fistula (oozing, occlusion and infection) and the pain score (numerical rating scale, NRS) of the two groups were compared, and the curative effects were compared. Results: There was no significant difference in general data between the two groups (P > 0.05), which indicated that the study was comparable. After 3 months' intervention, the vein diameter, pump-controlled blood flow and brachial artery blood flow in the intervention group were significantly higher than those in the control group (P < 0.05). And the maturity time, NRS score and complication rate of arteriovenous fistula were significantly lower than those of the control group (P < 0.05). The primary patency rate of AVF in the intervention group was higher than that in the control group, and the overall patency rate between the two groups was statistically significant (P < 0.05). Conclusions: As a promising new treatment method, far infrared therapy can effectively promote the maturity of AVF, increase venous diameter, pump controlled blood flow during dialysis, brachial artery blood flow during dialysis, and prolong the service life of AVF.
RESUMEN
Haemophilus parasuis is a commensal organism of the upper respiratory tract of pigs, but virulent strains can cause Glässer's disease, resulting in significant economic losses to the swine industry. OmpP2 is an outer membrane protein of this organism that shows considerable heterogeneity between virulent and non-virulent strains, with classification into genotypes I and II. It also acts as a dominant antigen and is involved in the inflammatory response. In this study, 32 monoclonal antibodies (mAbs) against recombinant OmpP2 (rOmpP2) of different genotypes were tested for reactivity to a panel of OmpP2 peptides. Nine linear B cell epitopes were screened, including five common genotype epitopes (Pt1a, Pt7/Pt7a, Pt9a, Pt17, and Pt19/Pt19a) and two groups of genotype-specific epitopes (Pt5 and Pt5-II, Pt11/Pt11a, and Pt11a-II). In addition, we used positive sera from mice and pigs to screen for five linear B-cell epitopes (Pt4, Pt14, Pt15, Pt21, and Pt22). After porcine alveolar macrophages (PAMs) were stimulated with overlapping OmpP2 peptides, we found that the epitope peptides Pt1 and Pt9, and the loop peptide Pt20 which was adjacent epitopes could all significantly upregulated the mRNA expression levels of IL-1α, IL-1ß, IL-6, IL-8, and TNF-α. Additionally, we identified epitope peptides Pt7, Pt11/Pt11a, Pt17, Pt19, and Pt21 and loop peptides Pt13 and Pt18 which adjacent epitopes could also upregulate the mRNA expression levels of most proinflammatory cytokines. This suggested that these peptides may be the virulence-related sites of the OmpP2 protein, with proinflammatory activity. Further study revealed differences in the mRNA expression levels of proinflammatory cytokines, including IL-1ß and IL-6, between genotype-specific epitopes, which may be responsible for pathogenic differences between different genotype strains. Here, we profiled a linear B-cell epitope map of the OmpP2 protein and preliminarily analyzed the proinflammatory activities and effects of these epitopes on bacterial virulence, providing a reliable theoretical basis for establishing a method to distinguish strain pathogenicity and to screen candidate peptides for subunit vaccines.
Asunto(s)
Infecciones por Haemophilus , Haemophilus parasuis , Enfermedades de los Porcinos , Porcinos , Animales , Ratones , Epítopos de Linfocito B/genética , Interleucina-6/metabolismo , Citocinas/metabolismo , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/metabolismo , Infecciones por Haemophilus/microbiología , Enfermedades de los Porcinos/microbiología , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Propranolol is the first choice for treating infantile hemangioma (IH). How propranolol works in IH remains unclear. Infantile hemangioma endothelial cells (HemECs) express Notch1, Jagged, Hey1, and other molecules in the Notch pathway, suggesting that Notch pathway-related molecules play an important role in affecting vascular endothelial cell proliferation. Whether propranolol can affect the Notch signaling pathway in IH treatment is unclear. METHODS: We performed this study to observe the effect of propranolol on the expression of Notch signaling pathway molecules in human umbilical vein endothelial cells (HUVECs) and to explore the therapeutic mechanism of propranolol on IH. HUVECs cultured in vitro were exposed to 60, 120, 240, 360, or 480 µM propranolol. The morphological changes of the HUVECs were observed under an inverted microscope. HUVECs proliferation was detected with Cell Counting Kit-8 (CCK-8). The effects of propranolol on HUVECs apoptosis were detected by flow cytometry. The role of Notch in propranolol inhibition of HUVEC proliferation was analyzed with real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Propranolol reduced HUVECs numbers and altered their morphology. The inhibitory effect of propranolol on cell proliferation was dependent on the reaction time and drug concentration. Propranolol upregulated Jagged1, Notch1, and Hey1 expression and downregulated delta-like ligand4 (DLL4) expression. CONCLUSIONS: Propranolol may play a role in IH treatment by increasing Jagged1 expression in endothelial cells, activating the Notch pathway and inducing the upregulation of the downstream target gene HEY1.
Asunto(s)
Hemangioma , Propranolol , Humanos , Células Endoteliales de la Vena Umbilical Humana , Propranolol/farmacología , Propranolol/uso terapéutico , Transducción de Señal/genética , Hemangioma/tratamiento farmacológico , Hemangioma/genética , Biología , Proliferación CelularRESUMEN
Laryngeal cancer poses a significant global health burden, with late-stage diagnoses contributing to reduced survival rates. This study explores the application of deep convolutional neural networks (DCNNs), specifically the Densenet201 architecture, in the computer-aided diagnosis of laryngeal cancer using laryngoscopic images. Our dataset comprised images from two medical centers, including benign and malignant cases, and was divided into training, internal validation, and external validation groups. We compared the performance of Densenet201 with other commonly used DCNN models and clinical assessments by experienced clinicians. Densenet201 exhibited outstanding performance, with an accuracy of 98.5% in the training cohort, 92.0% in the internal validation cohort, and 86.3% in the external validation cohort. The area under the curve (AUC) values consistently exceeded 92%, signifying robust discriminatory ability. Remarkably, Densenet201 achieved high sensitivity (98.9%) and specificity (98.2%) in the training cohort, ensuring accurate detection of both positive and negative cases. In contrast, other DCNN models displayed varying degrees of performance degradation in the external validation cohort, indicating the superiority of Densenet201. Moreover, Densenet201's performance was comparable to that of an experienced clinician (Clinician A) and outperformed another clinician (Clinician B), particularly in the external validation cohort. Statistical analysis, including the DeLong test, confirmed the significance of these performance differences. Our study demonstrates that Densenet201 is a highly accurate and reliable tool for the computer-aided diagnosis of laryngeal cancer based on laryngoscopic images. The findings underscore the potential of deep learning as a complementary tool for clinicians and the importance of incorporating advanced technology in improving diagnostic accuracy and patient care in laryngeal cancer diagnosis. Future work will involve expanding the dataset and further optimizing the deep learning model.
RESUMEN
The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane with monosubstituted allyl substrates was realized for the first time to provide corresponding products in high yields with excellent regio- and enantioselectivities. The protocol was applied to the enantioselective synthesis of (R)-baclofen and (R)-rolipram.