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Stroke is the second leading cause of death worldwide, and China has the highest stroke incidence in the world. The systemic inflammatory response index (SIRI), systemic inflammatory response index (SIRI), systemic immune-inflammatory index (SII), neutrophil-to-high-density lipoprotein ratio (NHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) have clinical in predicting the prognosis of acute ischaemic stroke (AIS) patients. No studies have compared the predictive value of these six composite inflammatory markers. This study included 516 AIS patients with AIS symptoms for < 24 h. The short-term prognosis of AIS patients at 30 days was assessed using the modified Rankin scale (mRS), an mRS score > 2 defining poor prognosis. The results of the univariate analysis showed that all six composite inflammatory indices, SIRI, SII, NHR, NLR, PLR and MLR, were associated with a poor prognosis in patients with AIS. All six composite inflammatory indicators correlated with the short-term prognosis of AIS patients. The six composite inflammation indicators were included in the binary logistic regression, and the results showed that SIRI, NLR and PLR were found to be independent risk factors for poor short-term prognosis in AIS patients. Among the six inflammatory markers, SIRI, NLR and PLR were the most clinically valuable for predicting the short-term prognosis of patients with AIS. Peripheral blood indices are easy to obtain clinically and can provide important clinical value for early prognosis and treatment adjustment.
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Biomarcadores , Inflamación , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Pronóstico , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Inflamación/sangre , Neutrófilos , Plaquetas/metabolismo , Plaquetas/patología , Linfocitos/metabolismo , Factores de Riesgo , Monocitos/metabolismoRESUMEN
A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis, which can lead to poor quality of sexual life. Here, the association between foreskin length and sexual dysfunction was evaluated. A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China (Hefei, China). Clinical characteristics, including foreskin length, were collected, and sexual function was assessed by the International Index of Erectile Function-5 (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) questionnaires. Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction. Among the 2721 erectile dysfunction (ED) patients and 1064 premature ejaculation (PE) patients, 301 (11.1%) ED patients and 135 (12.7%) PE patients had redundant foreskin, respectively. Men in the PE group were more likely to have redundant foreskin than men in the non-PE group (P = 0.004). Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED (adjusted odds ratio [aOR] = 1.31, adjusted P = 0.04), moderate PE (aOR = 1.38, adjusted P = 0.02), and probable PE (aOR = 1.37, adjusted P = 0.03) after adjusting for confounding variables. Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction, especially in PE patients. Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.
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Objectives: To avoid postoperatively acquired cholesteatoma, whether there was any squamous epithelial tissues residue around the tip of the malleus handle, and the need to remove these tissues were explored. Methods: This prospective study enrolled 197 patients who underwent endoscopic tympanoplasty. A postoperative pathological evaluation of the tissue around the tip of the malleus handle was performed to determine the presence of squamous epithelium. Analyzed correlation of epithelial remnants with exposure of malleus handle and microbial infection of middle ear. Results: The detection rate of squamous epithelial retention around the tip of the malleus handle differed significantly among patients with adhesive otitis media (AdOM), acquired cholesteatoma, and chronic suppurative otitis media (CSOM). The detection rate was significantly higher in the acquired cholesteatoma group than in the AdOM and CSOM groups (P < .001). The rate of squamous epithelial retention around the tip of the malleus handle was not significantly associated with microbial infection of the middle ear, the surgical side (P = .672), dry or wet ear status (P = .702), or exposure of the malleus handle (P = .06). Conclusions: In patients with acquired cholesteatoma, AdOM, or COM with severe tympanic sclerosis, the tissue around the tip of the malleus handle should be removed completely. For patients with simple COM, that is, without tympanic sclerosis or keratinizing stratified squamous epithelium at the edge of the perforation, the tissue can be retained.
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BACKGROUND: The manipulation of ferroptosis in cancer cells is a possible therapeutic technique that has been investigated for use in the treatment of cancer. Consequently, ferroptosis-inducing medications have recently received increased interest in cancer therapy. In this research, we assessed the anticancer efficacy of 14ß-hydroxy- 3ß-(ß-D-Glucopyranosyloxy)-5α-bufa-20,22-dienolide (HTB50-2), a natural product derived from the plant Helleborus thibetanus Franch, in Triple-Negative Breast Cancer (TNBC). Moreover, we also studied its potential mechanisms. METHODS: The biological effects of HTB50-2 in a series of breast cancer cell lines were analyzed using sulforhodamine B (SRB) and other methods. The migration ability was analyzed using three methods: wound healing assay, transwell assay, and Western blot. Meanwhile, the potential therapeutic value of HTB50-2 was evaluated in BALB/c mice by orthotopic transplantation. Transcriptome sequencing was conducted to explore the FOS-like antigen 2 (FOSL2) gene, and its role in ferroptosis was verified by Western blot and immunohistochemistry. The association of FOSL2 and ferroptosis-related genes was analyzed using NetworkAnalyst databases, and a TF-Gene interaction network was constructed. RESULTS: Ferroptosis was found to be induced in TNBC cells by HTB50-2. Furthermore, HTB50-2 inhibited tumor development by inducing ferroptosis in TNBC in vivo. Mechanistically, we demonstrated that a transcription factor FOSL2 mediated ferroptosis by HTB50-2. Additionally, it was found that Forkhead box C1 (FOXC1) was regulated by FOSL2 and correlated with ferroptosis. CONCLUSION: Our data suggest that HTB50-2 exerts its anti-cancer properties by ferroptosis via FOSL2/FOXC1 signaling pathway. Hence, HTB50-2 has an important application potential in the treatment of TNBC.
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AIMS: To investigate the relationship between medical narrative ability and humanistic care ability among Chinese clinical nurses, examining the potential mediating role of empathy. BACKGROUND: In the context of the bio-psychosocial medical model and humanistic nursing care, understanding the core competencies of medical narrative ability, empathy and humanistic care in nursing is crucial. This study explored the mediating role of empathy between medical narrative ability and humanistic care ability. DESIGN: A cross-sectional study. METHODS: The study employed a descriptive, cross-sectional survey design, involving 741 nurses from Wuxi People's Hospital. It assessed nurses' demographic characteristics, medical narrative ability, empathy, and humanistic care ability using an online questionnaire from December 2022 to February 2023. Pearson correlation analysis evaluated variable correlations, and PROCESS v3.3 model 4 was utilised for mediation analysis. The STROBE statement was chosen as the EQUATOR checklist. RESULTS: A positive correlation was found between nurses' medical narrative ability, humanistic care ability and empathy. Empathy partially mediated the relationship between medical narrative ability and humanistic care ability. CONCLUSION: Nurses' medical narrative ability directly and indirectly (via empathy) influences their humanistic care ability. Enhancing nurses' narrative and empathic skills can improve humanistic care, nursing quality and nurse-patient relationships. RELEVANCE TO CLINICAL PRACTICE: Managers should prioritise programmes to improve nurses' storytelling and empathy skills to enhance humanistic care, improving nursing quality and patient relationships. PUBLIC CONTRIBUTION: This study involves clinical nurses as participants and does not involve patients. This study collected data from clinical nurses using an online questionnaire platform in China. The questionnaire consisted of four sections, including demographic information and scales such as Narrative Competence Scale, Caring Ability Inventory and the Jefferson Scale of Empathy-Health Professional. Clear instructions were given to participants on how to complete each scale, and measures were taken to prevent missing or duplicate responses.
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In this study, we explore the mass transfer and separation mechanism of Li+ and Mg2+ confined within the flexible nanoporous zeolite imidazolate framework ZIF-8 under the influence of an electric field, employing molecular dynamics simulation. Our results highlight that the electric field accelerates the dehydration process of ions and underscore the critical importance of ZIF-8 framework flexibility in determining the separation selectivity of the ZIF-8 membrane. The electric field is shown to diminish ion hydration in the confined space of ZIF-8, notably disrupting the orientation of water molecules in the first hydration shells of ions, leading to an asymmetrical ionic hydration structure characterized by the uniform alignment of water dipoles. Furthermore, despite the geometrical constraints imposed by the ZIF-8 framework, the electric field significantly enhances ionic mobility. Notably, the less stable hydration shell of Li+ facilitates its rapid, dehydration-induced transit through ZIF-8 nanopores, unlike Mg2+, whose stable hydration shell impedes dehydration. Further investigation into the structural characteristics of the six-ring windows traversed by Li+ and Mg2+ ions reveals distinct mechanisms of passage: for Mg2+ ions, significant window expansion is necessary, while for Li+ ions, the mechanism involves both window expansion and partial dehydration. These findings reveal the profound impact of the electric field and framework flexibility on the separation of Li+ and Mg2+, offering critical insights for the potential application of flexible nanoporous materials in the selective extraction of Li+ from salt-lake brine.
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This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.
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BACKGROUND: Despite the known association between chronic inflammation and reduced muscle mass, there is a gap in research regarding the association between the systemic immune-inflammation index (SII) and sarcopenic obesity (SO). This study aims to assess the relationship between SII and SO in middle-aged and elderly adults and the mediating role of triglyceride-glucose index (TyG). METHODS: This cross-sectional study involved 2,719 participants aged 45-90 years who underwent health check-ups. SO was evaluated by combining sarcopenia [assessed by handgrip strength and appendicular skeletal muscle index (ASMI)] with obesity (determined by body fat percentage). Association between SII and SO, sarcopenia, and obesity in middle-aged and elderly individuals was examined using multivariable logistic regression, restricted cubic spline analysis, and subgroup analysis. Bidirectional mediation analysis was conducted to determine the direct and indirect effects through SII and TyG. RESULTS: The study included 2,719 participants, of which 228 had SO (8.4%). SO prevalence increased as the SII quartiles rose (Pfor trend <0.001). SII (per SD increase) had a significantly positive association with SO in both middle-aged individuals (OR = 1.69, 95% CI: 1.43 ~ 1.99) and older adults (OR = 2.52, 95% CI: 1.68 ~ 3.77). The relationship between SII and SO was found to be non-linear (Pnonlinear<0.05). In addition, SII showed a strong negative relationship with both handgrip strength and ASMI across all participants. In subgroup analysis, SII was still shown to significantly increase the risk of SO in all subgroups by gender, body mass index, waist circumference, smoking, drinking, hypertension, diabetes, dyslipidemia. TyG was found to mediate 21.36%, 11.78%, and 9.94% of the associations between SII and SO, sarcopenia, and obesity, respectively. SII had no mediation effect on the association between TyG and SO, sarcopenia, and obesity (P>0.05). CONCLUSIONS: Elevated levels of SII were associated with an increased risk of SO in middle-aged and elderly adults, especially in the elderly population, and elevated TyG levels played a role in this relationship.
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Fuerza de la Mano , Inflamación , Obesidad , Sarcopenia , Humanos , Sarcopenia/sangre , Sarcopenia/epidemiología , Sarcopenia/inmunología , Anciano , Masculino , Femenino , Obesidad/sangre , Obesidad/complicaciones , Obesidad/inmunología , Obesidad/epidemiología , Persona de Mediana Edad , Estudios Transversales , Inflamación/sangre , Anciano de 80 o más Años , Triglicéridos/sangre , Análisis de Mediación , China/epidemiología , Índice de Masa Corporal , Músculo Esquelético/patología , Glucemia , Factores de Riesgo , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Imbalanced intestinal microbiota and damage to the intestinal barrier contribute to the development of necrotizing enterocolitis (NEC). Autoinducer-2 (AI-2) plays a crucial role in repairing intestinal damage and reducing inflammation. OBJECTIVE: This study aimed to investigate the impact of AI-2 on the expression of intestinal zonula occludens-1 (ZO-1) and occludin proteins in NEC. We evaluated its effects in vivo using NEC mice and in vitro using lipopolysaccharide (LPS)-stimulated intestinal cells. METHODS: Pathological changes in the intestines of neonatal mice were assessed using histological staining and scoring. Cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to determine the optimal conditions for LPS and AI-2 interventions. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the mRNA levels of matrix metalloproteinase-3 (MMP3), protease activated receptor-2 (PAR2), interleukin-1ß (IL-1ß), and IL-6. Protein levels of MMP3, PAR2, ZO-1, and occludin were evaluated using western blot, immunohistochemistry, or immunofluorescence. RESULTS: AI-2 alleviated NEC-induced intestinal damage (P < 0.05) and enhanced the proliferation of damaged IEC-6 cells (P < 0.05). AI-2 intervention reduced the mRNA and protein expressions of MMP3 and PAR2 in intestinal tissue and cells (P < 0.05). Additionally, it increased the protein levels of ZO-1 and occludin (P < 0.05), while reducing IL-1ß and IL-6 mRNA expression (P < 0.05). CONCLUSION: AI-2 intervention enhances the expression of tight junction proteins (ZO-1 and occludin), mitigates intestinal damage in NEC neonatal mice and IEC-6 cells, potentially by modulating PAR2 and MMP3 signaling. AI-2 holds promise as a protective intervention for NEC. AI-2 plays a crucial role in repairing intestinal damage and reducing inflammation.
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Enterocolitis Necrotizante , Metaloproteinasa 3 de la Matriz , Receptor PAR-2 , Transducción de Señal , Animales , Humanos , Ratones , Animales Recién Nacidos , Línea Celular , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/patología , Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/metabolismo , Homoserina/análogos & derivados , Homoserina/farmacología , Mucosa Intestinal/patología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/inmunología , Intestinos/patología , Intestinos/efectos de los fármacos , Lactonas/farmacología , Lipopolisacáridos , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/genética , Ratones Endogámicos C57BL , Ocludina/metabolismo , Ocludina/genética , Receptor PAR-2/metabolismo , Receptor PAR-2/genética , Transducción de Señal/efectos de los fármacos , Proteína de la Zonula Occludens-1/metabolismo , Proteína de la Zonula Occludens-1/genéticaRESUMEN
Background: Extramammary Paget's disease (EMPD) is a rare epithelial malignancy, and approximately 30%-40% of EMPD patients overexpress human epidermal growth factor receptor 2 (Her-2). Currently, there are no established standard treatments for advanced EMPD while anti-Her-2 therapy is recommended for Her-2-positive cases. Case presentation: Here, we report a 51-year-old male diagnosed with advanced Her-2-positive EMPD, presenting with numerous lymph node metastases. This patient received disitamab vedotin (an antibody-drug conjugate, targeting Her-2) combined with serplulimab as first-line treatment. After seven cycles of combination therapy, the patient tolerated the treatment well and the lymph node lesions continued to shrink. However, the patient developed immunotherapy-related pneumonia following the eighth treatment. Hormone therapy was administered while all the anti-tumor therapies were halted. After the pneumonia improved, the patient underwent positron emission tomography-computed tomography, revealing a complete response to his tumor. To consolidate the effect, he received another five cycles of disitamab vedotin monotherapy as maintenance therapy, without experiencing any adverse events. To date, the patient has remained in good health without any recurrence 10 months after drug discontinuance. Conclusion: Disitamab vedotin combined with immunotherapy demonstrated a long-term clinical benefit in advanced Her-2-positive EMPD. For rare solid tumors with Her-2 overexpression, disitamab vedotin combined with immunotherapy might offer a viable therapeutic choice.
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Enfermedad de Paget Extramamaria , Receptor ErbB-2 , Humanos , Masculino , Persona de Mediana Edad , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Enfermedad de Paget Extramamaria/terapia , Escroto/patología , Resultado del Tratamiento , Inmunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Inmunoconjugados/uso terapéuticoRESUMEN
Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Inmunoterapia , Aprendizaje Automático , Terapia Neoadyuvante , Tomografía Computarizada por Rayos X , Humanos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Masculino , Femenino , Terapia Neoadyuvante/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Inmunoterapia/métodos , Nomogramas , Resultado del Tratamiento , Adulto , RadiómicaRESUMEN
BACKGROUND: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness. METHODS: PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1-deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity. RESULTS: PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1-deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content. CONCLUSIONS: PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.
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Five new sesquiterpenoids, (4S, 5S, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (1), (4S, 5 R, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (2), 6-O-propionyl-britannilactone (3), 1ß-hydroxy-3α-acetoxyeudesma-11(13)-en-12,8ß-olide (4) and 1ß,5ß-dihydroxyeudesma-11(13)-en-12,8ß-olide (5), along with twelve known ones were isolated from the flowers of Pentanema britannicum (L.) D.Gut.Larr. Among them, compounds 1 and 2 were stereoisomers which belong to 1,10-seco-eudesmane sesquiterpenoid with rare double bond between C-10 and C-14. The structures of the isolated compounds were elucidated by various spectroscopic methods, including 1D and 2D NMR experiments.
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BACKGROUND: Leaf morphology plays a crucial role in photosynthetic efficiency and yield potential in crops. Cigar tobacco plants, which are derived from common tobacco (Nicotiana tabacum L.), possess special leaf characteristics including thin and delicate leaves with few visible veins, making it a good system for studying the genetic basis of leaf morphological characters. RESULTS: In this study, GWAS and QTL mapping were simultaneously performed using a natural population containing 185 accessions collected worldwide and an F2 population consisting of 240 individuals, respectively. A total of 26 QTLs related to leaf morphological traits were mapped in the F2 population at three different developmental stages, and some QTL intervals were repeatedly detected for different traits and at different developmental stages. Among the 206 significant SNPs identified in the natural population using GWAS, several associated with the leaf thickness phenotype were co-mapped via QTL mapping. By analyzing linkage disequilibrium and transcriptome data from different tissues combined with gene functional annotations, 7 candidate genes from the co-mapped region were identified as the potential causative genes associated with leaf thickness. CONCLUSIONS: These results presented a valuable cigar tobacco resource showing the genetic diversity regarding its leaf morphological traits at different developmental stages. It also provides valuable information for novel genes and molecular markers that will be useful for further functional verification and for molecular breeding of leaf morphological traits in crops in the future.
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Mapeo Cromosómico , Estudio de Asociación del Genoma Completo , Nicotiana , Hojas de la Planta , Sitios de Carácter Cuantitativo , Nicotiana/genética , Nicotiana/anatomía & histología , Nicotiana/crecimiento & desarrollo , Hojas de la Planta/anatomía & histología , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Fenotipo , Polimorfismo de Nucleótido Simple , Desequilibrio de LigamientoRESUMEN
Being a major obstacle, Ag2Te has always been restricted in p-type AgSbTe2-based materials to improve their thermoelectric performance. This work reveals a stabilized AgSbTe2 through Sn/Ge alloying as synthesized by melting, annealing, and hot press. Interestingly, addition of Sn/Ge in AgSbTe2 extended the solubility limit up to â¼30% and hence suppressed Ag2Te in Ag(1-x)SnxSb(1-y)GeyTe2 compounds and led to enhanced electrical transport. Moreover, electrical and thermal transport properties of AgSbTe2 have been greatly affected by the phase transition of Ag2Te near 425 K. However, high-entropy Ag0.85Sn0.15Sb0.85Ge0.15Te2 compound results in a stabilized rock-salt structure and presents a high power factor of â¼10.8 µW cm-1 K-2 at 757 K. Besides, density functional theory reveals that available multivalence bands in Sn/Ge-doped AgSbTe2 lead to reduction in energy offsets. Meanwhile, a variety of defects appear in the Ag0.85Sn0.15Sb0.85Ge0.15Te2 sample due to entropy change, and thus lattice thermal conductivity decreases. Ultimately, a high figure of merit of â¼1.5 is attained at 757 K. This work demonstrates a roadmap for other group IV-VI materials so that the high-entropy approach may inhibit the impurity phases with extended solubility limit and result in high thermoelectric performance.
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OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.
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Purpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris. Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo. Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy. Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.
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Acné Vulgar , Antibacterianos , Ácidos Dicarboxílicos , Folículo Piloso , Nanopartículas , Acné Vulgar/tratamiento farmacológico , Animales , Ratones , Ácidos Dicarboxílicos/química , Ácidos Dicarboxílicos/farmacología , Folículo Piloso/efectos de los fármacos , Células RAW 264.7 , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Tamaño de la Partícula , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Piel/efectos de los fármacos , Piel/metabolismoRESUMEN
Inspired by adaptive natural organisms and living matter, soft actuators appeal to a variety of innovative applications such as soft grippers, artificial muscles, wearable electronics, and biomedical devices. However, their fabrication is typically limited in laboratories or a few enterprises since specific instruments, strong stimuli, or specialized operation skills are inevitably involved. Here a straightforward "cloth-to-clothes-like" method to prepare soft actuators with a low threshold by combining the hysteretic behavior of liquid crystal elastomers (LCEs) with the exchange reaction of dynamic covalent bonds, is proposed. Due to the hysteretic behavior, the LCEs (resemble "cloth") effectively retain predefined shapes after stretching and releasing for extended periods. Subsequently, the samples naturally become soft actuators (resemble "clothes") via the exchange reaction at ambient temperatures. As a post-synthesis method, this strategy effectively separates the production of LCEs and soft actuators. LCEs can be mass-produced in bulk by factories or producers and stored as prepared, much like rolls of cloth. When required, these LCEs can be customized into soft actuators as needed. This strategy provides a robust, flexible, and scalable solution to engineer soft actuators, holding great promise for mass production and universal applications.
RESUMEN
OBJECTIVES: To summarize the clinical characteristics and genetic variations in children with cystic fibrosis (CF) primarily presenting with pseudo-Bartter syndrome (CF-PBS), with the aim to enhance understanding of this disorder. METHODS: A retrospective analysis was performed on the clinical data of three children who were diagnosed with CF-PBS in Hunan Children's Hospital from January 2018 to August 2023, and a literature review was performed. RESULTS: All three children had the onset of the disease in infancy. Tests after admission showed hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis, and genetic testing showed the presence of compound heterozygous mutation in the CFTR gene. All three children were diagnosed with CF. Literature review obtained 33 Chinese children with CF-PBS, with an age of onset of 1-36 months and an age of diagnosis of 3-144 months. Among these children, there were 29 children with recurrent respiratory infection or persistent pneumonia (88%), 26 with malnutrition (79%), 23 with developmental retardation (70%), and 18 with pancreatitis or extrapancreatic insufficiency (55%). Genetic testing showed that c.2909G>A was the most common mutation site of the CFTR gene, with a frequency of allelic variation of 23% (15/66). CONCLUSIONS: CF may have no typical respiratory symptoms in the early stage. The possibility of CF-PBS should be considered for infants with recurrent hyponatremia, hypokalemia, hypochloremia, and metabolic alkalosis, especially those with malnutrition and developmental retardation. CFTR genetic testing should be performed as soon as possible to help with the diagnosis of CF.
Asunto(s)
Síndrome de Bartter , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Mutación , Humanos , Fibrosis Quística/genética , Fibrosis Quística/complicaciones , Masculino , Femenino , Lactante , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Síndrome de Bartter/genética , Síndrome de Bartter/diagnóstico , Síndrome de Bartter/complicaciones , Preescolar , Niño , Estudios RetrospectivosRESUMEN
BACKGROUND: The parents of children with autism spectrum disorder (ASD) are under great pressure and experience discrimination in their daily lives, which affects their family quality of life (FQOL). OBJECTIVE: METHODS: A total of 237 parents of children with ASD were recruited in a university-affiliated hospital in Guangzhou, China, from October 2020 to April 2021 by convenience sampling. The Affiliate Stigma Scale, Parenting Sense of Competence Scale and Beach Center Family Quality of Life Scale were employed for data collection. RESULTS: The results showed that affiliate stigma negatively predicts total FQOL and the dimensions of FQOL through both a direct effect and an indirect effect through parenting self-efficacy. CONCLUSIONS: The findings suggest that affiliate stigma is an important predictor of FQOL, and interventions to reduce affiliate stigma and strengthen parenting self-efficacy might be effective in improving FQOL in the parents of children with ASD.