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1.
Adv Sci (Weinh) ; : e2400741, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992961

RESUMEN

Myocardial infarction (MI) triggers a poor ventricular remodeling response, but the underlying mechanisms remain unclear. Here, the authors show that sentrin-specific protease 1 (SENP1) is downregulated in post-MI mice and in patients with severe heart failure. By generating cardiomyocyte-specific SENP1 knockout and overexpression mice to assess cardiac function and ventricular remodeling responses under physiological and pathological conditions. Increased cardiac fibrosis in the cardiomyocyte-specific SENP1 deletion mice, associated with increased fibronectin (Fn) expression and secretion in cardiomyocytes, promotes fibroblast activation in response to myocardial injury. Mechanistically, SENP1 deletion in mouse cardiomyocytes increases heat shock protein 90 alpha family class B member 1 (HSP90ab1) SUMOylation with (STAT3) activation and Fn secretion after ventricular remodeling initiated. Overexpression of SENP1 or mutation of the HSP90ab1 Lys72 ameliorates adverse ventricular remodeling and dysfunction after MI. Taken together, this study identifies SENP1 as a positive regulator of cardiac repair and a potential drug target for the treatment of MI. Inhibition of HSP90ab1 SUMOylation stabilizes STAT3 to inhibit the adverse ventricular remodeling response.

2.
Front Endocrinol (Lausanne) ; 15: 1399517, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38982990

RESUMEN

Background: Thyroid hormones (THs) have been found that it is closely associated with the onset and progression of non-alcoholic fatty liver disease (NAFLD). However, the current study could not verify the intrinsic relationship between thyroid hormones and NAFLD, which requires further research. Methods: The searches of studies reported both TH level in serum and NAFLD were performed in PubMed, Web of Science, Cochrane Library, and Embase databases. We combined an overall meta-analysis with a dose-response meta-analysis to assess the correlation and dose-response relationship between thyroid function levels and the risk of NAFLD. Results: Overall, 10 studies were included with a total of 38,425 individuals. We found that the non-linear dose-response model showed that for every 1 ng/dL increase in FT4, the risk of NAFLD was reduced by 10.56% (p=0.003). The odds ratios (ORs) for NAFLD with high free triiodothyronine (FT3) exposure compared to those with low FT3 were 1.580 (95% CI 1.370 to 1.830, I2 = 0.0%, p<0.001) in the overall meta-analysis. The continuous variable meta-analysis indicated that individuals with high levels of TSH (SMD=1.32, 95% CI 0.660 to 1.970, p<0.001) had significantly higher levels of liver fibrosis than those with low levels. Conclusions: Our findings only validate that there is a correlation between the occurrence of NAFLD and abnormal levels of THs, and it is expected that more observational studies will still be conducted in the future to further demonstrate the relationship between thyroid hormones and NAFLD. Trial registration: Registered number in PROSPERO: CRD42023405052.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Glándula Tiroides , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Pruebas de Función de la Tiroides , Glándula Tiroides/fisiopatología , Hormonas Tiroideas/sangre , Triyodotironina/sangre
4.
World J Hepatol ; 16(6): 966-972, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38948434

RESUMEN

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations, which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes, skin, bone marrow and liver. Although porphyria-related severe liver damage is rare, its consequences can be severe with limited treatment options. CASE SUMMARY: This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment, employing a combination of red blood cell (RBC) exchange and therapeutic plasma exchange (TPE). The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange. CONCLUSION: The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.

5.
CNS Neurosci Ther ; 30(6): e14782, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828651

RESUMEN

BACKGROUND: The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially the arousal stage of general anesthesia (GA). But the function of thalamus in GA-induced loss of consciousness (LOC) is little known. The thalamic reticular nucleus (TRN) is the only GABAergic neurons-composed nucleus in the thalamus, which is composed of parvalbumin (PV) and somatostatin (SST)-expressing GABAergic neurons. The anterior sector of TRN (aTRN) is indicated to participate in the induction of anesthesia, but the roles remain unclear. This study aimed to reveal the role of the aTRN in propofol and isoflurane anesthesia. METHODS: We first set up c-Fos straining to monitor the activity variation of aTRNPV and aTRNSST neurons during propofol and isoflurane anesthesia. Subsequently, optogenetic tools were utilized to activate aTRNPV and aTRNSST neurons to elucidate the roles of aTRNPV and aTRNSST neurons in propofol and isoflurane anesthesia. Electroencephalogram (EEG) recordings and behavioral tests were recorded and analyzed. Lastly, chemogenetic activation of the aTRNPV neurons was applied to confirm the function of the aTRN neurons in propofol and isoflurane anesthesia. RESULTS: c-Fos straining showed that both aTRNPV and aTRNSST neurons are activated during the LOC period of propofol and isoflurane anesthesia. Optogenetic activation of aTRNPV and aTRNSST neurons promoted isoflurane induction and delayed the recovery of consciousness (ROC) after propofol and isoflurane anesthesia, meanwhile chemogenetic activation of the aTRNPV neurons displayed the similar effects. Moreover, optogenetic and chemogenetic activation of the aTRN neurons resulted in the accumulated burst suppression ratio (BSR) during propofol and isoflurane GA, although they represented different effects on the power distribution of EEG frequency. CONCLUSION: Our findings reveal that the aTRN GABAergic neurons play a critical role in promoting the induction of propofol- and isoflurane-mediated GA.


Asunto(s)
Anestesia General , Estado de Conciencia , Neuronas GABAérgicas , Isoflurano , Propofol , Propofol/farmacología , Isoflurano/farmacología , Animales , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/fisiología , Ratones , Estado de Conciencia/efectos de los fármacos , Estado de Conciencia/fisiología , Masculino , Electroencefalografía , Anestésicos por Inhalación/farmacología , Núcleos Talámicos Anteriores/efectos de los fármacos , Núcleos Talámicos Anteriores/fisiología , Ratones Endogámicos C57BL , Ratones Transgénicos , Anestésicos Intravenosos/farmacología , Proteínas Proto-Oncogénicas c-fos/metabolismo , Optogenética
6.
Front Public Health ; 12: 1390643, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873287

RESUMEN

Objective: This study aimed to analyze the relationship between the sleep quality of healthcare professionals and the incidence of overweight and obesity, exploring the potential impact of sleep quality on the onset of overweight and obesity in order to provide a scientific basis for formulating effective health intervention measures. Methods: A convenience sampling method was used to conduct a survey on the sleep characteristics and obesity status among healthcare professionals at Peking Union Medical College Hospital and Tianjin Dongli District Traditional Chinese Medicine Hospital. The survey was conducted via online questionnaires, which included demographic data, the Pittsburgh Sleep Quality Index (PSQI), height, weight, and related sleep, exercise, and dietary habits. Univariate and multivariate logistic regression analyses were applied to study the relationship between sleep quality and overweight/obesity among healthcare professionals. Results: A total of 402 questionnaires were distributed, with a 100% retrieval rate, yielding 402 valid questionnaires. The average body mass index of the 402 participants was 23.22 ± 3.87 kg/m^2. Among them, 144 cases were overweight or obese, accounting for 35.8% (144/402) of the total. The prevalence of poor sleep quality among healthcare professionals was 27.4% (110/402), with an average PSQI score of 8.37 ± 3.624. The rate of poor sleep quality was significantly higher in the overweight and obese group compared to the normal weight group (36.1% vs. 22.5%, p = 0.003). The multivariate analysis indicated that gender, marital status, lower education level, sleep duration (odds ratio [OR] =1.411, 95% confidence interval [CI] 1.043-1.910, p = 0.026), and sleep disturbances (OR = 1.574, 95%CI 1.123-2.206, p = 0.008) were significant risk factors for overweight and obesity among healthcare professionals. Conclusion: Overweight or obese healthcare professionals had poorer sleep quality compared to those with a normal weight. Sleep duration and sleep disorders were identified as independent risk factors for overweight or obesity in healthcare professionals. Increasing sleep duration and improving sleep disorders may play a positive role in controlling overweight and obesity among healthcare professionals.


Asunto(s)
Personal de Salud , Obesidad , Sobrepeso , Calidad del Sueño , Humanos , Masculino , Femenino , Estudios Transversales , Adulto , Personal de Salud/estadística & datos numéricos , Obesidad/epidemiología , Encuestas y Cuestionarios , Sobrepeso/epidemiología , Persona de Mediana Edad , China/epidemiología , Índice de Masa Corporal , Trastornos del Sueño-Vigilia/epidemiología , Prevalencia
7.
Anal Chem ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38912660

RESUMEN

Development of an accurate, rapid, and cost-effective portable device is in high demand for point-of-care molecular diagnosis toward disease screening. Here we report a one-pot homogeneous isothermal assay that leverages nicking endonuclease and minimum secondary structured rolling circle amplification (N-MSSRCA) for fast and sensitive quantification of nucleic acids on distance microfluidic paper-based analytical devices (dµPAD) by a portable custom-made fluorescence detector. Human papillomavirus (HPV) oncogenic E7 mRNA as the biomarker for cervical cancer was used as the model analyte. N-MSSRCA integrates ligase for target recognition, the nicking enzyme for primer generation, and the dual function of the Phi29 DNA polymerase for both on- and off-loop amplification. The proposed method was capable of detecting 1 and 10 fM of the analyte using the microplate reader and portable detector with dµPAD, respectively, with ∼1 h assay time. A cohort study of 40 cervical swab samples shows N-MSSRCA reached positive and negative predictive values of 87.5% and 93.5% using the portable detector with dµPAD, compared to 91.67% and 100% using the microplate reader. N-MSSRCA demonstrates potential in early screening of high-risk HPV infection as a generic strategy to detect various nucleic acids in point-of-care scenarios.

8.
Sci Rep ; 14(1): 12621, 2024 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824201

RESUMEN

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause anaplasmoses and ehrlichioses in humans and animals. In this study, we examined the prevalence of Anaplasma and Ehrlichia species in ticks and domesticated animals in Suizhou County, Hubei Province in the central China. We used PCR amplification and DNA sequencing of the 16S rRNA, groEL, and gltA genes to analyze. We collected 1900 ticks, including 1981 Haemaphysalis longicornis and 9 Rhipicephalus microplus, 159 blood samples of goats (n = 152), cattle (n = 4), and dogs (n = 3) from May to August of 2023. PCR products demonstrated that Anaplasma bovis, Anaplasma capra, and an Ehrlichia species were detected in the H. longicornis with the minimum infection rates (MIR) of 1.11%, 1.32%, and 0.05%, respectively; A. bovis, A. capra, and unnamed Anaplasma sp. were detected in goats with an infection rate of 26.31%, 1.31% and 1.97%, respectively. Anaplasma and Ehrlichia species were not detected from cattle, dogs and R. microplus ticks. The genetic differences in the groEL gene sequences of the Anaplasma in the current study were large, whereas the 16S rRNA and gltA gene sequences were less disparate. This study shows that ticks and goats in Suizhou County, Hubei Province carry multiple Anaplasma species and an Ehrlichia species, with relatively higher infection rate of A. bovis in goats. Our study indicates that multiple Anaplasma and Ehrlichia species exist in ticks and goats in the central China with potential to cause human infection.


Asunto(s)
Anaplasma , Anaplasmosis , Animales Domésticos , Ehrlichia , Variación Genética , Cabras , ARN Ribosómico 16S , Animales , Anaplasma/genética , Anaplasma/aislamiento & purificación , China/epidemiología , Ehrlichia/genética , Ehrlichia/aislamiento & purificación , Cabras/microbiología , Perros , Bovinos , Anaplasmosis/epidemiología , Anaplasmosis/microbiología , Prevalencia , Animales Domésticos/microbiología , ARN Ribosómico 16S/genética , Garrapatas/microbiología , Ehrlichiosis/epidemiología , Ehrlichiosis/veterinaria , Ehrlichiosis/microbiología , Filogenia
9.
Zhongguo Gu Shang ; 37(5): 445-50, 2024 May 25.
Artículo en Chino | MEDLINE | ID: mdl-38778526

RESUMEN

OBJECTIVE: To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture. METHODS: From October 2019 to May 2021, 14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame, including 9 males and 5 females. The age ranged from 33 to 69 years. All the 14 patients had fresh closed fractures without femur, tibia and fibula fracture. Surgery was completed from 4 to 7 d after hospital admission. During the operation, the X-ray carbon bed was used, the pelvic ring was reduced by Starr pelvis reduction frame, and pelvic ring fracture was treated by orthopedic robot. Operation time, bleeding volume, fluoroscopy times of single screw placement, fracture reduction quality, affected limb function and complications were observed. Radiological reduction was evaluated using Matta scoring standard, and clinical efficacy was evaluated by Majeed pelvic function scoring system at the final follow-up. RESULTS: All of 14 patients successfully completed the operation, the operation time was 84 to 141 min, the bleeding volume was 20 to 50 ml, and the fluoroscopy times of single screw insertion was 4 to 9 times. All of 14 patients were followed up for 12 to 24 months. The healing time was 3 to 7 months. No complications such as fracture of internal fixation, screw loosening, infection and nerve injury were found. According to the evaluation criteria of Matta imaging reduction, 9 cases were excellent, 4 cases were good, and 1 case was fair. At the final follow-up, Majeed pelvic function scoring system was used:10 cases were excellent, 4 cases were good. CONCLUSION: The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple, time-saving, less trauma, less complications and effective.


Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Anciano , Fracturas Óseas/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Fijación Interna de Fracturas/métodos
10.
Autophagy ; : 1-13, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38762760

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) nonstructural protein (NSs) is an important viral virulence factor that sequesters multiple antiviral proteins into inclusion bodies to escape the antiviral innate immune response. However, the mechanism of the NSs restricting host innate immunity remains largely elusive. Here, we found that the NSs induced complete macroautophagy/autophagy by interacting with the CCD domain of BECN1, thereby promoting the formation of a BECN1-dependent autophagy initiation complex. Importantly, our data showed that the NSs sequestered antiviral proteins such as TBK1 into autophagic vesicles, and therefore promoted the degradation of TBK1 and other antiviral proteins. In addition, the 8A mutant of NSs reduced the induction of BECN1-dependent autophagy flux and degradation of antiviral immune proteins. In conclusion, our results indicated that SFTSV NSs sequesters antiviral proteins into autophagic vesicles for degradation and to escape antiviral immune responses.

11.
Ecol Evol ; 14(5): e11323, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38694750

RESUMEN

Meconopsis biluoensis, a new species of Papaveraceae in an alpine meadow from Yunnan, Southwest China, is described and illustrated. Morphologically, it resembles Meconopsis georgei, while it is distinct in acaulescent and hispid with clearly expanded bases on the leaves. A genus-level molecular phylogenetic analysis supported the closest relationship between M. biluoensis and M. georgei. In a finer population-level molecular phylogenetic analysis using ribosomal DNA (rDNA) and the chloroplast genome, individuals from M. biluoensis and M. georgei were clearly separated, and the extremely short branch length indicated that the two species had a very short differentiation time. The species has currently been assessed as "endangered" (EN) due to its small-sized population and narrow distribution following the IUCN categories and criteria.

12.
Heliyon ; 10(8): e30123, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38699735

RESUMEN

Background: Tumor genetic anomalies and immune dysregulation are pivotal in the progression of multiple myeloma (MM). Accurate patient stratification is essential for effective MM management, yet current models fail to comprehensively incorporate both molecular and immune profiles. Methods: We examined 776 samples from the MMRF CoMMpass database, employing univariate regression with LASSO and CIBERSORT algorithms to identify 15 p53-related genes and six immune cells with prognostic significance in MM. A p53-TIC (tumor-infiltrating immune cells) classifier was constructed by calculating scores using the bootstrap-multicox method, which was further validated externally (GSE136337) and through ten-fold internal cross-validation for its predictive reliability and robustness. Results: The p53-TIC classifier demonstrated excellent performance in predicting the prognosis in MM. Specifically, patients in the p53low/TIChigh subgroup had the most favorable prognosis and the lowest tumor mutational burden (TMB). Conversely, those in the p53high/TIClow subgroup, with the least favorable prognosis and the highest TMB, were predicted to have the best anti-PD1 and anti-CTLA4 response rate (40 %), which can be explained by their higher expression of PD1 and CTLA4. The three-year area under the curve (AUC) was 0.80 in the total sample. Conclusions: Our study highlights the potential of an integrated analysis of p53-associated genes and TIC in predicting prognosis and aiding clinical decision-making in MM patients. This finding underscores the significance of comprehending the intricate interplay between genetic abnormalities and immune dysfunction in MM. Further research into this area may lead to the development of more effective treatment strategies.

13.
J Agric Food Chem ; 72(21): 12057-12071, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38753758

RESUMEN

Plant growth-promoting endophytes (PGPE) can effectively regulate plant growth and metabolism. The regulation is modulated by metabolic signals, and the resulting metabolites can have considerable effects on the plant yield and quality. Here, tissue culture Houttuynia cordata Thunb., was inoculated with Rhizobium sp. (BH46) to determine the effect of BH46 on H. cordata growth and metabolism, and elucidate associated regulatory mechanisms. The results revealed that BH46 metabolized indole-3-acetic acid and induced 1-aminocyclopropane-1-carboxylate deaminase to decrease ethylene metabolism. Host peroxidase synthesis MPK3/MPK6 genes were significantly downregulated, whereas eight genes associated with auxins, cytokinins, abscisic acid, jasmonic acid, and antioxidant enzymes were significantly upregulated. Eight genes associated with flavonoid biosynthesis were significantly upregulated, with the CPY75B1 gene regulating the production of rutin and quercitrin and the HCT gene directly regulating the production of chlorogenic acid. Therefore, BH46 influences metabolic signals in H. cordata to modulate its growth and metabolism, in turn, enhancing yield and quality of H. cordata.


Asunto(s)
Endófitos , Houttuynia , Proteínas de Plantas , Houttuynia/microbiología , Houttuynia/metabolismo , Houttuynia/genética , Endófitos/metabolismo , Endófitos/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Ácidos Indolacéticos/metabolismo , Rhizobium/genética , Rhizobium/metabolismo , Flavonoides/metabolismo , Ácido Abscísico/metabolismo , Etilenos/metabolismo , Liasas de Carbono-Carbono/metabolismo , Liasas de Carbono-Carbono/genética
14.
Phytochemistry ; 223: 114120, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38705265

RESUMEN

Eleven previously undescribed sesquiterpenoids (8-18), one undescribed jasmonic acid derivative (35) and 28 known compounds were isolated from the leaves of Artemisia stolonifera. Undescribed compounds with their absolute configurations were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction and ECD calculation. Compound 8 was identified as a rare sesquiterpenoid featuring a rearranged 5/8 bicyclic ring system, whereas compound 17 was found to be an unprecedented monocyclic sesquiterpenoid with methyl rearrangement. Evaluation of biological activity showed that compounds 1-5 and 7 displayed cytotoxicity against six tumor cells. In the meantime, compounds 11, 12, 18 and 35 exhibited inhibitory effects against LPS-stimulated NO production in RAW 264.7 macrophage cells and reduced the transcription of IL-6 and IL-1ß in a dose-dependent manner at 25, 50 and 100 µM. Moreover, the anti-inflammatory-based network pharmacology and molecular docking analyses revealed potential target proteins of 11, 12, 18 and 35.


Asunto(s)
Antiinflamatorios , Artemisia , Ciclopentanos , Óxido Nítrico , Oxilipinas , Sesquiterpenos , Artemisia/química , Ratones , Oxilipinas/farmacología , Oxilipinas/química , Oxilipinas/aislamiento & purificación , Animales , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Ciclopentanos/química , Ciclopentanos/farmacología , Ciclopentanos/aislamiento & purificación , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Estructura Molecular , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Humanos , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Hojas de la Planta/química , Ensayos de Selección de Medicamentos Antitumorales
15.
Asian J Androl ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38722110

RESUMEN

ABSTRACT: Ejaculation is regulated by the central nervous system. However, the central pathophysiology of primary intravaginal anejaculation (PIAJ) is unclear. The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ. A total of 20 PIAJ patients and 16 healthy controls (HCs) were enrolled from September 2020 to September 2022 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Magnetic resonance imaging data were acquired from all participants and then were preprocessed. The measures of fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) were calculated and compared between the groups. PIAJ patients showed increased fALFF values in the left precuneus compared with HCs. Additionally, PIAJ patients showed increased ReHo values in the left precuneus, left postcentral gyrus, left superior occipital gyrus, left calcarine fissure, right precuneus, and right middle temporal gyrus, and decreased ReHo values in the left inferior parietal gyrus, compared with HCs. Finally, brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions, which included the frontal, parietal, temporal, and occipital regions, compared with HCs. In conclusion, increased regional brain activity in the parietal, temporal, and occipital regions, and increased FC between these brain regions, may be associated with PIAJ occurrence.

16.
IEEE Trans Cybern ; PP2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713577

RESUMEN

State responses for several classes of linear systems are investigated in this article. The involved systems include state-delayed linear systems, and high-order linear systems. At first, the single-fundamental-matrix-based approach is extended to these systems, and their state responses are expressed by their fundamental matrices (FMs). In addition, the multiple-FMs-based approach is presented for these systems. Based on a group of FMs, the state responses for the considered time-invariant systems are derived. For the considered time-variant systems, their state responses are explicitly expressed by their transition matrices. As an application of the fundamental-matrix-based approach, a stabilizing control law is designed for a class of high-order fully actuated continuous-time linear systems with a single input-delay.

17.
Nat Genet ; 56(5): 925-937, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38658794

RESUMEN

CRISPR base editing screens enable analysis of disease-associated variants at scale; however, variable efficiency and precision confounds the assessment of variant-induced phenotypes. Here, we provide an integrated experimental and computational pipeline that improves estimation of variant effects in base editing screens. We use a reporter construct to measure guide RNA (gRNA) editing outcomes alongside their phenotypic consequences and introduce base editor screen analysis with activity normalization (BEAN), a Bayesian network that uses per-guide editing outcomes provided by the reporter and target site chromatin accessibility to estimate variant impacts. BEAN outperforms existing tools in variant effect quantification. We use BEAN to pinpoint common regulatory variants that alter low-density lipoprotein (LDL) uptake, implicating previously unreported genes. Additionally, through saturation base editing of LDLR, we accurately quantify missense variant pathogenicity that is consistent with measurements in UK Biobank patients and identify underlying structural mechanisms. This work provides a widely applicable approach to improve the power of base editing screens for disease-associated variant characterization.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Genotipo , Fenotipo , ARN Guía de Sistemas CRISPR-Cas , Humanos , Edición Génica/métodos , ARN Guía de Sistemas CRISPR-Cas/genética , Teorema de Bayes , Receptores de LDL/genética , Células HEK293
18.
Cancer Med ; 13(8): e7215, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38659392

RESUMEN

OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Cisplatino , Etopósido , Neoplasias Pulmonares , Puntaje de Propensión , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/terapia , Carcinoma Pulmonar de Células Pequeñas/patología , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Anciano , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Quimioradioterapia/métodos , Estudios Retrospectivos , Estudios Prospectivos , Estadificación de Neoplasias , Adulto , Supervivencia sin Progresión , Esquema de Medicación
19.
Talanta ; 275: 126132, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38669959

RESUMEN

Given the levels of pollution in the aquatic environment and the development of antimicrobial resistance, it is essential to develop sensors, with sensitivity, selectivity, stability, and cost-effectiveness, for the determination of antibiotics. The present article highlights the fabrication of an ultra-sensitive graphene and copper sensor, Gr/Cu, supported on glassy carbon (GCE/Gr/Cu) for the electroanalysis of levofloxacin through a cost-effective electrodeposition method. The sequential electrodeposition of graphene and Cu was optimised to give GCE/Gr/Cu, with the Cu particles well dispersed on the graphene sheets. The composite exhibited very good conducting properties as evidenced from electrochemical impedance studies. Using cyclic voltammetry, an impressive sensitivity of 19.7 µA µM-1 cm-2 was achieved with a detection limit of 11.86 nM, providing a promising electrocatalytic material for the determination of this antibiotic. Moreover, good selectivity was observed in the presence of various ions typically found in water and other drug molecules, while very good stability exceeding a 21-day period was achieved, and recovery values between 97.7 and 103.8 % were obtained in tap water.

20.
Medicine (Baltimore) ; 103(17): e37851, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669413

RESUMEN

RATIONALE: Eosinophilic pulmonary disease (EPD) is a general term for a large group of diseases with complex etiology. Ulcerative colitis is an inflammatory bowel disease (IBD). Patients with IBD may have pulmonary involvement. We herein present a case of ulcerative colitis complicated with EPD. PATIENT CONCERNS: A 34-year-old woman with ulcerative colitis presented with dry cough. She had peripheral eosinophilia and apical ground glass opacities on CT (computed tomography) of her chest. Antibiotic treatment was ineffective. DIAGNOSES: Lung biopsy revealed eosinophil infiltration in the alveolar space and interstitial space, so EPD was considered. INTERVENTIONS: After oral administration of prednisone, the lung shadow on CT disappeared when the cough symptoms resolved. However, the symptoms recurred after drug withdrawal, and the lung shadow reappeared on imaging. The cough symptoms and lung shadow disappeared after oral prednisone was given again. Prednisone was slowly discontinued after 6 months of treatment. OUTCOMES: The patient stopped prednisone for half a year. No recurrence or abnormal CT findings were detected during the half-year follow-up. LESSONS: The clinical manifestations of EPD are atypical, laboratory and imaging findings are not specific, and it is difficult to make a definite diagnosis before lung biopsy. The diagnosis depends on pathological examination. Glucocorticoid treatment is effective, but some patients may relapse after drug withdrawal. Active follow-up after glucocorticoid treatment is very important for identifying disease recurrence. Patients with IBD are relatively prone to developing EPD. The etiology of EPD is complex. In clinical practice, we need to make a diagnosis and differential diagnosis to clarify its etiology.


Asunto(s)
Colitis Ulcerosa , Prednisona , Eosinofilia Pulmonar , Humanos , Femenino , Adulto , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/tratamiento farmacológico , Eosinofilia Pulmonar/etiología , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Tomografía Computarizada por Rayos X , Glucocorticoides/uso terapéutico , Glucocorticoides/administración & dosificación , Diagnóstico Diferencial
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