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The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHPplus, which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa. Furthermore, dHTSN1@pHPplus was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHPplus exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa-infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHPplus in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa.
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Antibacterianos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Factores de Virulencia , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/patogenicidad , Animales , Antibacterianos/farmacología , Antibacterianos/química , Ratones , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/microbiología , Inmunidad Adaptativa/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Humanos , Farmacorresistencia Bacteriana/efectos de los fármacos , Ratones Endogámicos BALB C , FemeninoRESUMEN
BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve the survival of patients with Epidermal growth factor receptor (EGFR) sensitive mutations in non-small cell lung cancer (NSCLC). CASE SUMMARY: A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment. Secondary pathological tissue biopsy confirmed squamous cell carcinoma (SCC) transformation. Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time, while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC. Notably, EGFR-TKIs resistance includes primary and acquired. Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs, with SCC transformation being relatively rare. Our results provide more detailed results of the patient's diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma. CONCLUSION: Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.
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BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. METHODS: One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. RESULTS: The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: - 15.03 ± 2.52% vs. - 13.39 ± 2.48% vs. - 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (ß = - 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (ß = 0.283 and - 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (ß = - 0.266, p = 0.007). CONCLUSIONS: There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.
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Enfermedades Asintomáticas , Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , Neuropatías Diabéticas , Imagen por Resonancia Cinemagnética , Valor Predictivo de las Pruebas , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Persona de Mediana Edad , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico por imagen , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/epidemiología , Anciano , Estudios de Casos y Controles , Cardiomiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/etiología , Factores de Riesgo , Prevalencia , Estudios Transversales , Volumen Sistólico , Contracción MiocárdicaRESUMEN
BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. PURPOSE: To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. STUDY TYPE: Cross-sectional, retrospective study. POPULATION: 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). FIELD STRENGTH/SEQUENCE: 2D balanced steady-state free precession cine sequence at 3.0 T. ASSESSMENT: LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. STATISTICAL TESTS: Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. RESULTS: Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (ß = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (ß = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (ß = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (ß = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (ß = 1.07). DATA CONCLUSION: In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.
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Paclitaxel (PTX) serves as a primary chemotherapy agent against diverse solid tumors including breast cancer, lung cancer, head and neck cancer and ovarian cancer, having severe adverse effects including PTX-induced peripheral neuropathy (PIPN) and hypersensitivity reactions (HSR). A recommended anti-allergic agent diphenhydramine (DIP) has been used to alleviate PTX-induced HSR. Desloratadine (DLT) is a third generation of histamine H1 receptor antagonist, but also acted as a selective antagonist of 5HTR2A. In this study we investigated whether DLT ameliorated PIPN-like symptoms in mice and the underlying mechanisms. PIPN was induced in male mice by injection of PTX (4 mg/kg, i.p.) every other day for 4 times. The mice exhibited 50% reduction in mechanical threshold, paw thermal response latency and paw cold response latency compared with control mice. PIPN mice were treated with DLT (10, 20 mg/kg, i.p.) 30 min before each PTX administration in the phase of establishing PIPN mice model and then administered daily for 4 weeks after the model was established. We showed that DLT administration dose-dependently elevated the mechanical, thermal and cold pain thresholds in PIPN mice, whereas administration of DIP (10 mg/kg, i.p.) had no ameliorative effects on PIPN-like symptoms. We found that the expression of 5HTR2A was selectively elevated in the activated spinal astrocytes of PIPN mice. Spinal cord-specific 5HTR2A knockdown by intrathecal injection of AAV9-5Htr2a-shRNA significantly alleviated the mechanical hyperalgesia, thermal and cold hypersensitivity in PIPN mice, while administration of DLT (20 mg/kg) did not further ameliorate PIPN-like symptoms. We demonstrated that DLT administration alleviated dorsal root ganglion neuronal damage and suppressed sciatic nerve destruction, spinal neuron apoptosis and neuroinflammation in the spinal cord of PIPN mice. Furthermore, we revealed that DLT administration suppressed astrocytic neuroinflammation via the 5HTR2A/c-Fos/NLRP3 pathway and blocked astrocyte-neuron crosstalk by targeting 5HTR2A. We conclude that spinal 5HTR2A inhibition holds promise as a therapeutic approach for PIPN and we emphasize the potential of DLT as a dual-functional agent in ameliorating PTX-induced both PIPN and HSR in chemotherapy. In summary, we determined that spinal 5HTR2A was selectively activated in PIPN mice and DLT could ameliorate the PTX-induced both PIPN- and HSR-like pathologies in mice. DLT alleviated the damages of DRG neurons and sciatic nerves, while restrained spinal neuronal apoptosis and CGRP release in PIPN mice. The underlying mechanisms were intensively investigated by assay against the PIPN mice with 5HTR2A-specific knockdown in the spinal cord by injection of adeno-associated virus 9 (AAV9)-5Htr2a-shRNA. DLT inhibited astrocytic NLRP3 inflammasome activation-mediated spinal neuronal damage through 5HTR2A/c-FOS pathway. Our findings have supported that spinal 5HTR2A inhibition shows promise as a therapeutic strategy for PIPN and highlighted the potential advantage of DLT as a dual-functional agent in preventing against PTX-induced both PIPN and HSR effects in anticancer chemotherapy.
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BACKGROUND: Atrial fibrillation (AF) has been linked to an increased risk of cardiovascular death, overall mortality and heart failure in patients with type 2 diabetes mellitus (T2DM). The present study investigated the additive effects of paroxysmal AF on left ventricular (LV) function and deformation in T2DM patients with or without AF using the cardiovascular magnetic resonance feature tracking (CMR-FT) technique. METHODS: The present study encompassed 225 T2DM patients differentiated by the presence or absence of paroxysmal AF [T2DM(AF+) and T2DM(AF-), respectively], along with 75 age and sex matched controls, all of whom underwent CMR examination. LV function and global strains, including radial, circumferential and longitudinal peak strain (PS), as well as peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were measured and compared among the groups. Multivariable linear regression analysis was used to examine the factors associated with LV global strains in patients with T2DM. RESULTS: The T2DM(AF+) group was the oldest, had the highest LV endsystolic volume index, lowest LV ejection fraction and estimated glomerular filtration rate compared to the control and T2DM(AF-) groups, and presented a shorter diabetes duration and lower HbA1c than the T2DM(AF-) group. LV PS-radial, PS-longitudinal and PDSR-radial declined successively from controls through the T2DM(AF-) group to the T2DM(AF+) group (all p < 0.001). Compared to the control group, LV PS-circumferential, PSSR-radial and PDSR-circumferential were decreased in the T2DM(AF+) group (all p < 0.001) but preserved in the T2DM(AF-) group. Among all clinical indices, AF was independently associated with worsening LV PS-longitudinal (ß = 2.218, p < 0.001), PS-circumferential (ß = 3.948, p < 0.001), PS-radial (ß = - 8.40, p < 0.001), PSSR-radial and -circumferential (ß = - 0.345 and 0.101, p = 0.002 and 0.014, respectively), PDSR-radial and -circumferential (ß = 0.359 and - 0.14, p = 0.022 and 0.003, respectively). CONCLUSIONS: In patients with T2DM, the presence of paroxysmal AF further exacerbates LV function and deformation. Proactive prevention, regular detection and early intervention of AF could potentially benefit T2DM patients.
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Fibrilación Atrial , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Humanos , Fibrilación Atrial/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Función Ventricular Izquierda , Espectroscopía de Resonancia MagnéticaRESUMEN
Effectively harnessing solar energy for the conversion of CO2 into valuable chemical energy presents a viable solution to address energy scarcity and climate change concerns. Nonetheless, the limited light absorption and sluggish charge kinetics significantly hinder the photoreduction of CO2. In this study, we employed a facile sol-gel method combined with wetness impregnation to synthesize Cu-doped TiO2 coated with NiOx nanoparticles. Various characterizations verified the successful incorporation of Cu ions into the TiO2 crystal lattice and the formation of NiOx co-catalysts within the composites. The optimal performance attained with CTN-0.5 demonstrates an output of 11.85 µmol h-1 g-1 for CO and 9.51 µmol h-1 g-1 for CH4, which represent a 4.4-fold and 15.6-fold increase, respectively, compared to those achieved with pure TiO2. The induced Cu defect band broadens the light absorption by decreasing the conduction band edge of TiO2, while NiOx upshifts the valence band of TiO2 because of the interaction of valence orbitals. Light irradiation EPR and FTIR tests suggest that the collaboration of CuOx and NiOx promotes the formation of oxygen vacancies/defects and a rapid charge transfer pathway, thereby provides numerous active sites and electrons to enhance CO2 photoreduction performance.
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In this work, a fluorescent probe, TPABF-HS, was developed for detecting hydrogen sulfide (H2S) using a human serum albumin (HSA)-binding-based approach for amplifying the fluorescence signal and extending the linear correlation range. Compared to the most recent probes for H2S, the most interesting feature of the detection system developed herein was the especially wide linear range (0-1000 µM (0-100 eq.)), which covered the physiological and pathological levels of H2S. TPABF-HS could be used in applications high sensitivity and selectivity with an LOD value of 0.42 µM. Further, site-competition experiments and molecular docking simulation experiments indicated that signal amplification was realized by the binding of the TPABF fluorophore to the naproxen-binding site of HSA. Moreover, the extension of the measurement span could allow for applications in living cells and Caenorhabditis elegans for imaging both exogenous and endogenous H2S. This work brings new information to the strategy of signal processing by exploiting fluorescent probes.
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Colorantes Fluorescentes , Sulfuro de Hidrógeno , Humanos , Colorantes Fluorescentes/toxicidad , Colorantes Fluorescentes/química , Sulfuro de Hidrógeno/química , Simulación del Acoplamiento Molecular , Células HeLa , Microscopía FluorescenteRESUMEN
In this work, we reported a fluorescent probe Fur-SH, a derivative of benzofuranone, which was used to detect H2S in living cells and zebrafish. Based on the three structural characteristics of the probe, the effects of different structural modifications on the optical properties of the fluorophore were compared. Then, the fluorophore Fur-OH was synthesized by modifying diethylamino group with benzofuranone as the main skeleton. With 2,4-dinitrofluorobenzene as the recognition group and diethylamino as the electron donor, the push-pull electron effect occurred with nitro group, which led to fluorescence quenching, and an openable fluorescent probe Fur-SH was formed. The probe Fur-SH (λex = 510 nm; λem = 570 nm) had the advantages of smaller full width at half maxima, rapid response (5 min) and wide pH window. The quantitative properties of the probe were excellent, reaching saturation at 50 equivalents of substrate. The probe Fur-SH showed high sensitivity to H2S, with LOD of 48.9 nM and LOQ of 50 nM. At present, the probe Fur-SH had been applied to fluorescence imaging of MCF-7 cells and zebrafish. By comparing the effects of different structures on the optical properties of fluorophores, this work was expected to be helpful to the development of fluorescent probes in the future.
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Colorantes Fluorescentes , Sulfuro de Hidrógeno , Humanos , Animales , Colorantes Fluorescentes/química , Pez Cebra , Sulfuro de Hidrógeno/análisis , Mitocondrias/química , Imagen Óptica , Células HeLaRESUMEN
OBJECTIVES: To compare the effects of 2 Hz continuous wave and 2 Hz/100 Hz dilatational wave setting in electroacupuncture(EA) on ovulation frequency, hormone levels, body fat parameters, quality of life and depression-anxiety level in polycystic ovary syndrome (PCOS) patients with abdominal obesity. METHODS: PCOS patients with abdominal obesity were randomly divided into low-frequency group (n=29) and dilatational wave group (n=29). Patients in both groups were treated with "Tongtiaodaimai" (regulating Dai Meridian) acupuncture therapy, and EA was applied to bilateral Daimai (GB26), Tianshu (ST25), Shenshu (BL23) and Ciliao (BL32). The low-frequency group received EA using a continuous wave at a frequency of 2 Hz, while the dilatational wave group received dilatational wave at a frequency of 2 Hz/100 Hz. Both groups received treatment for 30 min each time, 3 times per week for 12 consecutive weeks. Ovulation frequency was calculated according to the ovulation cycle. The contents of serum anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG) were detected with electrochemiluminescence method. Body weight (BW) and waist circumference (WC) were measured, and body mass index (BMI) and waist-height ratio (WHtR) were calculated. PCOS questionnaire (Chi-PCOSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. RESULTS: Compared with before treatment, both the low-frequency group and the dilatational wave group showed an increase in ovulation frequency (P<0.01, P<0.05), and a decrease in BW, BMI, WC, WHtR, and SDS score (P<0.01, P<0.05)ï¼the dilatational wave group showed decreased serum AMH contents (P<0.05) and increased serum SHBG contents (P<0.05), the scores related to acne, fatigue, and dysmenorrhea in the Chi-PCOSQ increased (P<0.01, P<0.05). Compared with the low-frequency group, the dilatational wave group showed a reduction (P<0.05) in WC after treatment. CONCLUSIONS: 2 Hz/100 Hz dilatational wave EA is equally effective as 2 Hz low-frequency EA in improving ovulation frequency. In terms of reducing WC in abdominal obesity type PCOS patients, 2 Hz/100 Hz dilatational wave EA is superior to 2 Hz low-frequency EA. 2 Hz/100 Hz dilatational wave EA can decrease serum AMH, increase serum SHBG, and improve symptoms of acne, fatigue, and dysmenorrhea.
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Acné Vulgar , Electroacupuntura , Síndrome del Ovario Poliquístico , Femenino , Humanos , Obesidad Abdominal/terapia , Calidad de Vida , Síndrome del Ovario Poliquístico/terapia , Dismenorrea , Puntos de Acupuntura , Obesidad/terapiaRESUMEN
BACKGROUND: Diabetic peripheral neuropathy (DPN) has been shown to be independently associated with cardiovascular events and mortality. This study aimed to evaluate changes in left ventricular (LV) microvascular perfusion and myocardial deformation in type 2 diabetes mellitus (T2DM) patients with and without DPN, as well as to investigate the association between myocardial perfusion and LV deformation. METHODS: Between October 2015 and July 2022, one hundred and twenty-three T2DM patients without DPN, fifty-four patients with DPN and sixty age and sexmatched controls who underwent cardiovascular magnetic resonance imaging were retrospectively analyzed. LV myocardial perfusion parameters at rest, including upslope, time to maximum signal intensity (TTM), max signal intensity (max SI), and myocardial strains, including global radial, circumferential and longitudinal strain (GRS, GCS and GLS, respectively), were calculated and compared among the groups with Oneway analysis of variance. Univariable and multivariable linear regression analyses were performed to explore the independent factors influencing LV myocardial perfusion indices and LV strains in diabetes. RESULTS: The LV GLS, upslope and max SI were significantly deteriorated from controls, through patients without DPN, to patients with DPN (all P < 0.001). Compared with controls, TTM was increased and LV GRS and GCS were decreased in both patient groups (all P < 0.05). Multivariable regression analyses considering covariates showed that DPN was independently associated with reduced upslope, max SI and LV GLS (ß = - 0.360, - 2.503 and 1.113, p = 0.021, 0.031 and 0.010, respectively). When the perfusion indices upslope and max SI were included in the multivariable analysis for LV deformation, DPN and upslope (ß = 1.057 and - 0.870, p = 0.020 and 0.018, respectively) were significantly associated with LV GLS. CONCLUSION: In patients with T2DM, there was more severe LV microvascular and myocardial dysfunction in patients with complicated DPN, and deteriorated subclinical LV systolic dysfunction was associated with impaired myocardial circulation.
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Diabetes Mellitus Tipo 2 , Enfermedades del Sistema Nervioso Periférico , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Estudios Retrospectivos , Corazón , Imagen por Resonancia MagnéticaRESUMEN
OBJECTIVES: NLR family CARD domain containing 5 (NLRC5) could promote major histocompatibility complex class I (MHC-I)-dependent CD8+ T cell-mediated anticancer immunity. In this study, the immunosurveillance role and underlying mechanisms of NLRC5 in endometrial cancer (EC) were characterized. METHODS: CD8+ T cells were separated from healthy women's peripheral blood by using magnetic beads. The effect of NLRC5 and interferon-ß (IFN-ß) on immunosurveillance of EC were examined through a mouse tumor model and a CD8+ T cell-EC cell coculture system after NLRC5 overexpression and IFN-ß overexpression or depletion. The effect of NLRC5 on IFN-ß expression was examined with gain- and loss-of-function experiments. RESULTS: NLRC5 overexpression in the EC cell and CD8+ T cell coculture system inhibited EC cell proliferation and migration and promoted EC cell apoptosis and CD8+ T cell proliferation. In vivo, NLRC5 overexpression increased the proportion of CD8+ T cells and inhibited EC progression. Furthermore, IFN-ß overexpression in the EC cell and CD8+ T cell coculture system activated CD8+ T cell proliferation; however, genetic depletion of IFN-ß exerted the opposite effects. In addition, NLRC5 could negatively regulate IFN-ß expression in EC cells. Mechanistically, NLRC5 potentiated the antitumor responses of CD8+ T cells to EC by activating IFN-ß. CONCLUSIONS: Taken together, our findings demonstrated that NLRC5 potentiates anti-tumor CD8+ T cells responses by activating interferon-ß in EC, suggesting that genetically escalated NLRC5 and IFN-ß may act as potential candidates for the clinical translation of adjuvant immunotherapies to patients with EC.
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RATIONALE: In 1865, Trousseau first discovered pulmonary embolism caused by multiple venous thrombosis in patients with gastric cancer, and later all clinical manifestations of malignant patients during pathogenesis due to abnormal coagulation and fibrinolysis were referred to collectively as Trousseau syndrome. Trousseau syndrome is not a benign thrombophlebitis, and when diagnosed it requires immediate treatment. The survival rate over 1 year is only 12%. Stroke in cancer patients has distinct characteristics different from conventional stroke and has higher mortality. PATIENT CONCERNS: A 54-year-old female presented to the Department of Otolaryngology with recurrent right nasal bleeding for 4 days. After surgery, the patient experienced 7 different cerebral infarction courses. Finally died of brain herniation. DIAGNOSIS: The specific abnormal laboratory index is the increase of D-dimer, suggesting the hypercoagulation state. The patient developed multiple cerebral infarction, myocardial injury, renal infarction, splenic infarction, and lower extremity arterial thrombosis, and finally was diagnosed Trousseau syndrome. INTERVENTIONS: In the treatment, aspirin and atorvastatin were selected, but it did not work very well. D-dimer were high, we used low molecular weight heparin, and D-dimer decreased significantly. OUTCOMES: Finally the patient died of brain herniation. CONCLUSION: The raise of D-dimer and typical magnetic resonance imaging manifestation which provides a greater basis for diagnosis. The specific abnormal laboratory index is the increase of D-dimer, which provides direction for treatment and helps to evaluate treatment effect.
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Accidente Cerebrovascular , Trombosis , Femenino , Humanos , Persona de Mediana Edad , Infarto Cerebral/etiología , Infarto Cerebral/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Síndrome , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
BACKGROUND: Microvascular submandibular gland transplantation (SMGT) for severe dry eye disease (DED) has rarely been reported in the literature. The aim of this study was to report a case series of SMGT with the special focus on monitoring and management of postoperative vascular compromise. METHODS: Using a retrospective single-cohort study design, the investigators enrolled a sample of DED patients undergoing SMGT in a Chinese university hospital during 1999 and 2021. The main outcomes were baseline and surgical data, post-operative manifestations, and surgical results. Descriptive, uni- and bivariate statistics were computed with the significant P < 0.05. RESULTS: During the study period, 220 DED patients (55.9% female) with a mean age of 32.66±14.47 years underwent SMGT. Vascular compromises occurred in 27 grafted glands (12.3%; 22 venous compromises and 5 arterial compromises) at a median of 27 h(range, 3.3 to 288 h) after surgery. Harden texture and swelling of the covering skin flap of the donor indicated venous compromises, while some specific sign was absent for arterial compromise. The accompanying vein of the facial artery (FAV) as a donor's vein was associated with less vascular compromise compared to the anterior facial vein (AFV). Timely reexploration was performed in 25 glands (92.6%), with a salvaged rate of 48%, and more venous compromises were salvaged compared to artery compromises (54.6% vs. 0%, P = 0.047). Temporary hypersecretion on postoperative 2-5 days was noticed in the grafted glands with no or salvaged vascular compromise (Schirmer's test, 35 mm/5 min and 37 mm/5 min, respectively, P = 0.749), while they were absent for the 15 surgically failed grands (Schirmer's test 0 mm/5 min, P<0.001). CONCLUSIONS: Vascular compromise appears to be a common complication of SMGT. Postoperative hypersecretion of the grafted glands may indicate good circulation, and the use of FAV as the donor's vein could help to decrease the risk of vascular compromise.
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Trasplante de Órganos , Glándula Submandibular , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , Trasplante Autólogo , Glándula Submandibular/irrigación sanguínea , Glándula Submandibular/trasplante , Estudios Retrospectivos , Estudios de CohortesRESUMEN
Resonant Auger scattering (RAS) provides information on the core-valence electronic transition and impresses a rich fingerprint of the electronic structure and nuclear configuration at the time-initiating RAS process. Here, we suggest using a femtosecond X-ray pulse to trigger RAS in a distorted molecule, which is generated from the nuclear evolution on a valence excited state pumped by a femtosecond ultraviolet pulse. With the time delay varied, the amount of molecular distortion can be controlled and the RAS measurements imprint both their electronic structures and changing geometries. This strategy is showcased in H2O prepared in an O-H dissociative valence state, where molecular and fragment lines appear in RAS spectra as signatures of ultrafast dissociation. Given the generality of this approach for a broad class of molecules, this work opens a new alternative pump-probe technique for mapping the core and valence dynamics with ultrashort X-ray probe pulses.
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BACKGROUND: Hepatic fibrosis is a serious condition, and the development of hepatic fibrosis can lead to a series of complications. However, the pathogenesis of hepatic fibrosis remains unclear, and effective therapy options are still lacking. Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1 (NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis, but its role in diseases including hepatic fibrosis remains undefined. Therefore, additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment. AIM: To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1. METHODS: Twenty-four male C57BL/6 mice were randomized and separated into three groups, comprising the normal, fibrosis, and calcitriol treatment groups, and liver fibrosis was modeled by carbon tetrachloride (CCl4). To evaluate the level of hepatic fibrosis in every group, serological and pathological examinations of the liver were conducted. TGF-ß1 was administered to boost the in vitro cultivation of LX-2 cells. NS3TP1, α-smooth muscle actin (α-SMA), collagen I, and collagen III in every group were examined using a Western blot and real-time quantitative polymerase chain reaction. The activity of the transforming growth factor beta 1 (TGFß1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected. The statistical analysis of the data was performed using the Student's t test. RESULTS: NS3TP1 promoted the activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhanced hepatic fibrosis via the TGFß1/Smad3 and NF-κB signaling pathways, as evidenced by the presence of α-SMA, collagen I, collagen III, p-smad3, and p-p65 in LX-2 cells, which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference. The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression, as shown by the luciferase assay. NS3TP1 inhibited the apoptosis of HSCs. Moreover, both Smad3 and p65 could bind to NS3TP1, and p65 increased the promoter activity of NS3TP1, while NS3TP1 increased the promoter activity of TGFß1 receptor I, as indicated by coimmunoprecipitation and luciferase assay results. Both in vivo and in vitro, treatment with calcitriol dramatically reduced the expression of NS3TP1. Calcitriol therapy-controlled HSCs activation, proliferation, and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice. Furthermore, calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1. CONCLUSION: Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique, prospective therapeutic target in hepatic fibrosis.
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Calcitriol , FN-kappa B , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Proteínas no Estructurales Virales , Animales , Masculino , Ratones , Calcitriol/farmacología , Calcitriol/uso terapéutico , Tetracloruro de Carbono/toxicidad , Colágeno Tipo I/metabolismo , Hepacivirus/metabolismo , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/prevención & control , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas no Estructurales Virales/metabolismo , Proteína smad3/metabolismoRESUMEN
Funiu Mountains are located in a transition region between warm temperate zone and northern subtropical region, where a variety of plant species are distributed with sensitive response to climate change. Their response characteristics to climate change are still unclear. We developed the basal area increment (BAI) index chronologies of Pinus tabuliformis, P. armandii, and P. massoniana in the Funiu Mountains to examine their growth trend and their sensitivity to climatic change. The results showed that the BAI chronologies gave a clue that the three conife-rous species had similar radial growth rate. The large Gleichlufigkeit (GLK) indices among the three BAI chronologies also indicated that the three species had a similar growth trend. Results of correlation analysis showed that the three species also had similar response to climatic change to a certain extent. Radial growth of all the three species was significantly positively correlated with the total monthly precipitation in December of previous year and June of the current year, but negatively correlated with the precipitation in September and the mean monthly temperature in June of the current year. There were some differences in the responses of the three coniferous to climate change. P. massoniana had a significant negative correlation with the mean temperature in March, and a significant positive correlation with the precipitation in March, while P. armandii and P. massoniana were affected negatively by the maximum temperature in August. Results of the moving correlation analysis showed that the three coniferous species had some similar sensitivity to climate change. Their positive responses to precipitation in previous December consistently increased, as well as the negative correlation with precipitation in current September. As to P. masso-niana, they had a relatively stronger climatic sensitivity and higher stability than the other two species. It would be more suitable for P. massoniana trees on the southern slope of the Funiu Mountains under global warming.
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Pinus , Tracheophyta , Cambio Climático , Árboles , China , Calentamiento GlobalRESUMEN
Endometriosis is closely associated with ectopic focal inflammation and immunosuppressive microenvironment. Multiple types of pattern recognition receptors (PRRs) are present in the innate immune system, which are able to detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in both intracellular and external environments. However, the exact role of PRRs in endometriosis and the underlying molecular mechanism are unclear. PRRs are necessary for the innate immune system to identify and destroy invasive foreign infectious agents. Mammals mainly have two types of microbial recognition systems. The first one consists of the membrane-bound receptors, such as toll-like receptors (TLRs), which recognize extracellular microorganisms and activate intracellular signals to stimulate immune responses. The second one consists of the intracellular PRRs, including nod-like receptors (NLRs) and antiviral proteins retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) with helix enzyme domain. In this review, we mainly focus on the key role of PRRs in the pathological processes associated with endometriosis. PRRs recognize PAMPs and can distinguish pathogenic microorganisms from self, triggering receptor ligand reaction followed by the stimulation of host immune response. Activated immune response promotes the transmission of microbial infection signals to the cells. As endometriosis is characterized by dysregulated inflammation and immune response, PRRs may potentially be involved in the activation of endometriosis-associated inflammation and immune disorders. Toll-like receptor 2 (TLR2), toll-like receptor 3 (TLR3), toll-like receptor 4 (TLR4), nod-like receptor family caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5), nod-like receptor family pyrin domain containing 3 (NLRP3), and c-type lectin receptors (CLRs) play essential roles in endometriosis development by regulating immune and inflammatory responses. Absent in melanoma 2 (AIM2)-like receptors (ALRs) and retinoic acid-inducible gene I-like receptors (RLRs) may be involved in the activation of endometriosis-associated immune and inflammation disorders. PRRs, especially TLRs, may serve as potential therapeutic targets for alleviating pain in endometriosis patients. PRRs and their ligands interact with the innate immune system to enhance inflammation in the stromal cells during endometriosis. Thus, targeting PRRs and their new synthetic ligands may provide new therapeutic options for treating endometriosis.
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Endometriosis , Melanoma , Animales , Femenino , Humanos , Inmunidad Innata/fisiología , Transducción de Señal , Ligandos , Moléculas de Patrón Molecular Asociado a Patógenos , Receptores de Reconocimiento de Patrones/metabolismo , Receptores Toll-Like/metabolismo , Inflamación , Proteínas NLR/metabolismo , Proteínas Portadoras/metabolismo , Tretinoina/metabolismo , Mamíferos/metabolismo , Microambiente TumoralRESUMEN
On-chip light sources are an essential component of scalable photonic integrated circuits (PICs), and coupling between light sources and waveguides has attracted a great deal of attention. Photonic waveguides based on bound states in the continuum (BICs) allow optical confinement in a low-refractive-index waveguide on a high-refractive-index substrate and thus can be employed for constructing PICs. In this work, we experimentally demonstrated that the photoluminescence (PL) from a monolayer of tungsten sulfide (WS2) could be coupled into a BIC waveguide on a lithium-niobate-on-insulator (LNOI) substrate. Using finite-difference time-domain simulations, we numerically obtained a coupling efficiency of â¼2.3% for an in-plane-oriented dipole and a near-zero loss at a wavelength of 620 nm. By breaking through the limits of 2D-material integration with conventional photonic architectures, our work offers a new perspective for light-matter coupling in monolithic PICs.
RESUMEN
Vibronic coupling is a critical mechanism in chemical reactions. However, its quantitative evaluation is challenging due to mathematical complexity and programming difficulty, and its experimental proof is often elusive due to overlap among neighboring states. Here, after exciting a vibrational level (ν = 0, 1, 2) of the intermediate N 1sâπg* core-excited state in N2 molecules, we separate the resonant Auger decay channels that lead to the lowest dissociation limit in the two-dimensional energy correlation maps. From three kinetic energy release spectra of these channels at different vibrational quantum numbers, we give the first experimental proof of the vibronic coupling between two resonant Auger final states 12Πg and 22Πg.