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1.
Quant Imaging Med Surg ; 14(9): 6285-6293, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39281172

RESUMO

Background: In recent years, several functional imaging studies have shown that the hypothalamus is closely associated with migraine and have suggested that the hypothalamus may be a potential site of migraine generation. Studying the characteristics of the functional network of the hypothalamus in persons with migraines may help to understand the neural mechanisms of migraine. We thus used resting-state functional magnetic resonance imaging (rsfMRI) and Granger causal analysis to investigate the effective connectivity (EC) of the hypothalamus in persons with migraines. Methods: The study included 17 healthy volunteers and 39 persons with migraines. The EC calculation was based on rsfMRI data from a 3-T magnetic resonance imaging scanner. The brain networks of the hypothalamus were compared using a general linear model to determine if there were any differences between the two groups. We used Pearson correlation analysis to examine the correlation between EC values in abnormal brain regions and clinical variables. Results: Compared with healthy controls, those with migraines showed decreased EC from the hypothalamus to the left fusiform and increased EC from the hypothalamus to the medial frontal gyrus/orbital part, right lingual gyrus, left superior frontal gyrus, and right middle frontal gyrus (P<0.05). Meanwhile, persons with migraines also showed decreased EC from the left middle frontal gyrus and right medial frontal gyrus/orbital part to the hypothalamus (P<0.05). EC from the hypothalamus to the left superior frontal gyrus correlated significantly and positively with the visual analogue scale in those with migraines (r=-0.3820; P=0.0164). Conclusions: Disturbances in the EC between the hypothalamus and the prefrontal gyrus and visual cortex may play a key role in the neuropathological features of persons with migraines. The current study adds to our understanding of the complexity of migraine mechanisms.

2.
Heliyon ; 10(17): e37201, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39286187

RESUMO

Background: Although studies in China have found that school bullying is prevalent among adolescents, most relevant research has focused on southern China, while research in northern China is limited. This study aimed to explore ethnic disparities in the socio-demographic determinants of school bullying in Inner Mongolia, a northern region of China. Methods: A cross-sectional study was conducted among 2891 adolescents in Inner Mongolia, China, from September to December 2022. Data on participants' sociodemographic characteristics and school bullying experiences were collected through questionnaires. Multivariate logistic regression analyses, stratified by ethnicity, were employed to examine factors associated with school bullying. Furthermore, subgroup analyses and interaction tests were conducted to explore potential effect modifiers of the relationship between ethnicity and bullying. Results: The prevalence of school bullying was 18.99 % (549/2891) overall, with 17.96 % (420/2339) among Han and 23.37 % (129/552) among ethnic minorities. Minority adolescents faced a higher risk of bullying compared to Han (OR = 1.35, 95 % CI: 1.08-1.69, P < 0.05). Middle school students were more vulnerable to bullying than high school students (OR = 1.25, 95%CI:1.03-1.52, P < 0.05). Among Han adolescents, having a mother with high school education was protective against bullying (OR = 0.71, 95 % CI: 0.54-0.93, P < 0.05), while it was an associated factor for minorities (OR = 2.06, 95%CI:1.23-3.46, P < 0.05). Good family economic status was an associated factor for bullying among Han (OR = 1.62, 95%CI: 1.11-2.36, P < 0.05), but not among minorities. Belonging to other family structures (remarriage/foster family, intergenerational families, live with relatives and elders) was an associated factor for minorities (OR = 2.60, 95 % CI: 1.37-4.92, P < 0.05), but not for Han. Subgroup analyses revealed significant ethnic disparities in bullying experiences among middle school students, those from nuclear family, other family, and fair economic backgrounds (all P < 0.05). Interaction effects between ethnicity and these variables were not significant (all P > 0.05). Limitations: This cross-sectional study has limitations in establishing causal relationships between identified associated factors and school bullying. Conclusions: Ethnic minority adolescents in Inner Mongolia, China, especially middle school students, face a higher risk of school bullying than their Han peers. The differential impact of maternal education, family economic status, and family structure on bullying risk between Han and minority adolescents underscores the need for culturally sensitive, targeted interventions that consider the unique challenges faced by ethnic minority students.

3.
Appl Microbiol Biotechnol ; 108(1): 467, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292268

RESUMO

Epigenetic regulation plays a central role in the regulation of a number of cellular processes such as proliferation, differentiation, cell cycle, and apoptosis. In particular, small molecule epigenetic modulators are key elements that can effectively influence gene expression by precisely regulating the epigenetic state of cells. To identify useful small-molecule regulators that enhance the expression of recombinant proteins in Chinese hamster ovary (CHO) cells, we examined a novel dual-HDAC/LSD1 inhibitor I-4 as a supplement for recombinant CHO cells. Treatment with 2 µM I-4 was most effective in increasing monoclonal antibody production. Despite cell cycle arrest at the G1/G0 phase, which inhibits cell growth, the addition of the inhibitor at 2 µM to monoclonal antibody-expressing CHO cell cultures resulted in a 1.94-fold increase in the maximal monoclonal antibody titer and a 2.43-fold increase in specific monoclonal antibody production. In addition, I-4 significantly increased the messenger RNA levels of the monoclonal antibody and histone H3 acetylation and methylation levels. We also investigated the effect on HDAC-related isoforms and found that interference with the HDAC5 gene increased the monoclonal antibody titer by 1.64-fold. The results of this work provide an effective method of using epigenetic regulatory strategies to enhance the expression of recombinant proteins in CHO cells. KEY POINTS: • HDAC/LSD1 dual-target small molecule inhibitor can increase the expression level of recombinant monoclonal antibodies in CHO cells. • By affecting the acetylation and methylation levels of histones in CHO cells and downregulating HDAC5, the production of recombinant monoclonal antibodies increased. • It provides an effective pathway for applying epigenetic regulation strategies to enhance the expression of recombinant proteins.


Assuntos
Anticorpos Monoclonais , Cricetulus , Epigênese Genética , Proteínas Recombinantes , Células CHO , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/farmacologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Epigênese Genética/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histonas/metabolismo , Histonas/genética , Acetilação , Cricetinae , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Metilação
4.
Dig Liver Dis ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39261265

RESUMO

BACKGROUND: The safety of extracorporeal shock wave lithotripsy for pancreatic stones (P-ESWL) and adverse events were not evaluated and classified within large sample population. This study aimed to evaluate the safety and classify the adverse events of P-ESWL based on a large sample cohort. METHODS: This is an observational study based on the large prospective chronic pancreatitis (CP) cohort. Patients with painful pancreatic stones over 5 mm who underwent P-ESWL between March 2011 and June 2018 at Shanghai Changhai Hospital were included. Adverse events after P-ESWL including complications and transient adverse events (TAEs) were recorded. Risk factors of adverse events were analyzed through univariable and multivariable logistics regression analysis. Sensitivity analysis was conducted to test the stability of the study. RESULTS: Totally 2,071 patients underwent 5,002 sessions of P-ESWL were included. The overall complication rate and TAEs rate after all P-ESWL procedures were 5.2% and 20.9%. The complications and TAEs rate decreased obviously within the first 6 sessions. Several independent risk factors for adverse events after P-ESWL were identified. Sensitivity analysis suggested the stability of the results. CONCLUSIONS: P-ESWL is a safe treatment for pancreatic stones. Multiple P-ESWL sessions did not increase the complications and TAEs rate. ClincialTrials.gov number, NCT05916547.

5.
Int J Biol Macromol ; 279(Pt 4): 135286, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245100

RESUMO

Benefiting from the good electromechanical performance, ionic conductive hydrogel can easily convert the deformation into electrical signals, showing great potential in wearable electronic devices. However, due to the high water content, icing and water evaporation problems seriously limit their development. Although additives can ease these disadvantages, the accompanying performance degradation and complex preparation processes couldn't meet application needs. In this work, a convenient method was provided to prepare ionic conductive hydrogels with sensitive electromechanical performance, harsh environmental tolerance, and long-term stability without additives. Based on the hydratability between metal ions and water molecules resulting in spatial condensation of the hydrogel framework, the hydrogel exhibits good flexibility and ionic conductivity (70.3 mS/cm). Furthermore, the metal salt can bind with water molecules to reduce the vapor pressure, thus endowing the hydrogel with good freezing resistance (-40 °C) and long-term stability over a wide temperature range (-20 °C-50 °C). Based on these unique advantages, the hydrogel shows good sensitivity. Even in a harsh environment, it still maintained excellent stability (-20 °C-50 °C, GF = 2.2, R2 > 0.99). Assembled with a Wi-Fi device, the hydrogel sensor demonstrates good health activity and physiological state detection performance, demonstrating great potential for wearable medical devices.

6.
Cytokine ; 184: 156759, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39293182

RESUMO

Granulocyte colony-stimulating factor (G-CSF), also known as colony-stimulating factor 3 (CSF3), is a proinflammatory cytokine that primarily stimulates the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils. Over the past years, G-CSF has mainly been used to cure patients with neutropenia and as a part of chemotherapy to induct the remission for refractory/relapse leukemia. Recent studies showed that C-CSF can been used as condition regimens and as a part of preventive methods after allogeneic transplantation to improve the survival of patients and also has immunoregulation, and has promote or inhibit the proliferation of solid tumors. Therefore, in this review, we firstly describe the structure for G-CSF. Then its functions and mechanism were reviewed including the neutrophil mobilization, differentiation, migration, and inhibiting apoptosis of neutrophils, and its immunoregulation. Finally, the clinical applications were further discussed.

7.
Eur J Med Chem ; 279: 116807, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39243453

RESUMO

Natural product evodiamine (Evo) and its synthetic derivatives represent an attractive dual Topo 1/2 inhibitors with broad-spectrum antitumor efficacy. However, the clinical applications of these compounds have been impeded by their poor aqueous solubility. Herein, a series of water-soluble 10-substituted-N(14)-phenylevodiamine derivatives were designed and synthesized. The most potent compound 45 featuring a quaternary ammonium salt fragment achieved robust aqueous solubility and nanomolar potency against a panel of human hepatoma cell lines Huh7, HepG2, SK-Hep-1, SMMC-7721, and SMMC-7721/DOX (doxorubicin-resistant cell). Further studies revealed that 45 could inhibit Topo 1 and Topo 2, induce apoptosis, arrest the cell cycle at the G2/M stage and inhibit the migration and invasion. Compound 45 exhibited potent antitumor activity (TGI = 51.1 %, 10 mg/kg) in the Huh7 xenograft model with acceptable safety profile. In addition, a 21-day long-term dose toxicity study confirmed that the maximum tolerated dose of compound 45 was 20 mg/kg. Overall, this study presented a promising Evo-derived candidate for the treatment of hepatocellular carcinoma.

8.
J Musculoskelet Neuronal Interact ; 24(3): 291-300, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39219327

RESUMO

OBJECTIVES: To investigate the therapeutic effect and mechanism of Danggui Buxue Tang in the treatment of biceps longus tendon lesions, and to preliminarily explore the relevant factors affecting this injury. METHODS: Using network pharmacology analysis methods, the potential mechanism of Danggui Buxue Tang in treating key lesions of the long head of the biceps brachii muscle was studied. RESULTS: Model analysis revealed 44 protein-protein interactions associated with long head binding. The distribution of 19 strongly correlated targets is Pharmaper>SEA>Stitch>Swiss. Further discovery revealed 17 immune system and inflammation related KEGG pathways with P values less than 0.01. The TNF and sphingolipid signaling pathways are associated with inflammation, while the MAPK signaling pathway is associated with immunity. Finally, it was found that the FoxO and HIF-1 signaling pathways are directly associated with long head restraint injury in the biceps brachii muscle. CONCLUSION: Danggui Buxue Tang inhibits related pathways, regulates the immune system, reduces inflammation, and alleviates disease progression. Danggui Buxue Tang can be an effective choice for treating combined lesions of the long head of the biceps brachii muscle.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Tendinopatia , Farmacologia em Rede/métodos , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Tendinopatia/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculos Isquiossurais/efeitos dos fármacos
9.
Int J Biol Macromol ; 279(Pt 2): 135259, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233175

RESUMO

Consumer perception and market demand have driven the replacement of synthetic colorants with naturally derived alternatives in the cosmetic industry. This study describes a facile way to prepare durable inorganic-organic hybrid pigment with advanced biocompatibility, antibacterial and hydrophobic properties tailored for color cosmetics by initial modification of palygorskite with chitosan to anchor sappanwood dye extract and subsequently coating with amino-modified silicone oil (ASO). The hybrid pigments were characterized by transmittance electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and the Brunauer-Emmett-Teller method. The results indicated that the sappanwood dye was loaded on chitosan-modified palygorskite via hydrogen bonding and electrostatic interaction. Furthermore, the chitosan-palygorskite/sappanwood hybrid pigment exhibited enhanced biocompatibility and color stability on exposure to different heating temperatures and UVA radiation after subsequent hydrophobic modification with amino-modified silicone oil. Moreover, facial foundation cosmetics based on the chitosan-palygorskite/sappanwood@ASO composites exhibited excellent brightening and skin color corrective effect on human volunteers without any adverse response. And no significant difference was observed in 12 out of 14 sensory evaluation indexes in the comparison of this hybrid pigment-based makeup with two commercially available products. This study provides a new route to stabilize natural botanical colorant for cosmetic use by chitosan-modified clay minerals.

10.
Diagn Microbiol Infect Dis ; 110(4): 116534, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39276718

RESUMO

This study investigated the diagnostic potential of targeted next-generation sequencing (tNGS) for pulmonary infections. The positivity rate of tNGS was significantly higher than that of traditional microbial culture (92.6 % vs 25.2 %, χ2 = 378.272, P < 0.001). The proportion of two or more species of pathogens detected using tNGS exceeded that detected using microbial culture (χ2 = 337.283, P < 0.001). There were inconsistencies between the results of the tNGS antibiotic resistance gene and the drug susceptibility test resistance phenotype. The tNGS technique demonstrates rapid and effective capabilities in identifying bacteria, fungi, viruses, and specific pathogens, with a detection sensitivity that surpasses that of conventional culture methodologies. Microbial drug resistance genotypes detected by tNGS cannot accurately predict drug resistance phenotypes and require further improvement or integration with traditional microbial culture to establish a foundation for effective clinical treatment.

11.
Nanoscale ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292163

RESUMO

Emergent ferromagnetism in ß-Ga2O3 with an ultra-wide bandwidth and high electrical breakdown strength offers exciting opportunities for fabricating robust spintronic devices. One pertinent obstacle in the material has been the low saturation magnetization, which precludes its practical application in magnetic devices. In this work, large-scale Fe-doped ß-Ga2O3 diluted magnetic semiconductor (DMS) films are synthesized using a polymer-assisted deposition method, and the effect of Fe doping on their structural and magnetic properties is investigated. Remarkably, the optimal sample exhibits a high saturation magnetization (70 emu cm-3 at 300 K), much larger than those in previously reported stable oxide DMS films, as well as a low coercivity (12 Oe at 300 K). Further analysis shows that our samples manifest a typical bound magnetic polaron (BMP) model and the high saturation magnetization originates from the strong ferromagnetic coupling between the BMPs which is enhanced by Ga vacancies. The Fe-doped ß-Ga2O3 thin films with high saturation magnetization and low coercivity may provide a promising platform for related semiconductor spintronics.

12.
Neurosurg Rev ; 47(1): 633, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292301

RESUMO

Chronic subdural hematoma (CSDH) is a common condition in neurosurgery. With an aging population, there is increasing attention on the prognosis of patients following surgical intervention. We developed a postoperative short-term prognostic prediction model using preoperative clinical indicators, aiming to assist in perioperative medical decision-making and management. The dataset was randomly divided into training and validation cohorts. An mRS score greater than 2 one month after discharge was considered indicative of a poor prognosis. In the training cohort, the least absolute shrinkage and selection operator (LASSO) regression analysis was used for multivariate analysis to identify independent risk factors and construct a prediction nomogram for poor prognosis one month after discharge. The performance of the nomogram was assessed using the Receiver Operating Characteristic (ROC) curve and calibration curve. A Decision Curve Analysis (DCA) was also conducted to determine the net benefit threshold of the prediction model. Among the 505 participants, 18.8% (95/505) had a poor prognosis one month after discharge. The baseline characteristics did not significantly differ between the training cohort and the validation cohort. LASSO regression analysis in the training cohort reduced the predictors to four potential factors. Further multivariate logistic analyses in the training cohort identified four independent predictors: age, admission Glasgow Coma Scale (GCS) score, hemiparesis, and hemoglobin count. These predictors were incorporated into the nomogram prediction model. Internal validation using ROC analysis, calibration curves, and other methods demonstrated a strong correlation between the observed and predicted likelihood of poor prognosis one month after discharge. The visualized nomogram prediction model we developed for short-term postoperative prognosis of chronic subdural hematoma after burr hole drainage aids in predicting short-term outcomes and guiding clinical treatment decisions. Further external validation is needed in the future to confirm its effectiveness.


Assuntos
Drenagem , Hematoma Subdural Crônico , Humanos , Hematoma Subdural Crônico/cirurgia , Masculino , Feminino , Idoso , Prognóstico , Pessoa de Meia-Idade , Drenagem/métodos , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Nomogramas , Trepanação , Adulto , Estudos de Coortes , Fatores de Risco , Escala de Coma de Glasgow
13.
BMJ Open Gastroenterol ; 11(1)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39266020

RESUMO

OBJECTIVE: Serum amyloid A (SAA) was found to be positively correlated with the activity of Crohn's disease (CD); however, its prognostic value remains uncertain. Here, we examined its predictive ability in newly diagnosed CD and explored genetic association. METHODS: This retrospective cohort study included patients newly diagnosed as CD at the First Affiliated Hospital of Sun Yat-sen University between June 2010 and March 2022. We employed receiver operating characteristic curve, Cox proportional hazard regression models and restricted cubic splines to investigate the prognostic performance of SAA for surgery and disease progression. To assess possible causality, a two-sample Mendelian randomisation (MR) of published genome-wide association study data was conducted. RESULTS: During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease progression events were documented. A 100-unit increment in SAA level generated 14% higher risk for surgery (adjusted HR (95% CI): 1.14 (1.05-1.23), p=0.001) and 12% for disease progression (1.12 (1.05-1.19), p<0.001). Baseline SAA level ≥89.2 mg/L led to significantly elevated risks for surgery (2.08 (1.31-3.28), p=0.002) and disease progression (1.72 (1.22-2.41), p=0.002). Such associations were assessed as linear. Adding SAA into a scheduled model significantly improved its predictive performances for surgery and disease progression (p for net reclassification indexes and integrated discrimination indexes <0.001). Unfortunately, no genetic causality between SAA and CD was observed in MR analysis. Sensitivity analyses showed robust results. CONCLUSION: Although causality was not found, baseline SAA level was an independent predictor of surgery and disease progression in newly diagnosed CD, and had additive benefit to existing prediction models.


Assuntos
Doença de Crohn , Progressão da Doença , Proteína Amiloide A Sérica , Humanos , Doença de Crohn/genética , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Proteína Amiloide A Sérica/análise , Proteína Amiloide A Sérica/metabolismo , Masculino , Feminino , Adulto , Estudos Retrospectivos , Prognóstico , Curva ROC , Estudo de Associação Genômica Ampla , Biomarcadores/sangue , Análise da Randomização Mendeliana/métodos , Valor Preditivo dos Testes , Adulto Jovem , Modelos de Riscos Proporcionais
14.
Plant Cell ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283506

RESUMO

The geometric shape and arrangement of individual cells play a role in shaping organ functions. However, analyzing multicellular features and exploring their connectomes in centimeter-scale plant organs remain challenging. Here, we established a set of frameworks named Large-Volume Fully Automated Cell Reconstruction (LVACR), enabling the exploration of three-dimensional (3D) cytological features and cellular connectivity in plant tissues. Through benchmark testing, our framework demonstrated superior efficiency in cell segmentation and aggregation, successfully addressing the inherent challenges posed by light sheet fluorescence microscopy (LSFM) imaging. Using LVACR, we successfully established a cell atlas of different plant tissues. Cellular morphology analysis revealed differences of cell clusters and shapes in between different poplar (P. simonii Carr. and P. canadensis Moench.) seeds, whereas topological analysis revealed that they maintained conserved cellular connectivity. Furthermore, LVACR spatiotemporally demonstrated an initial burst of cell proliferation, accompanied by morphological transformations at an early stage in developing the shoot apical meristem. During subsequent development, cell differentiation produced anisotropic features, thereby resulting in various cell shapes. Overall, our findings provided valuable insights into the precise spatial arrangement and cellular behavior of multicellular organisms, thus enhancing our understanding of the complex processes underlying plant growth and differentiation.

15.
Angew Chem Int Ed Engl ; : e202414892, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258945

RESUMO

Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (PZI) and trioxytriphenylamine (TOT) ligands, was synthesized. PZI-Au-TOT displays decent thermally activated delayed fluorescence (TADF) with a quantum yield of 93% in doped film. The crystals of PZI-Au-TOT show simultaneous TADF, polymorphism, and linearly polarized luminescence (LPL). The polymorph-dependent emission properties with widely varied peaks from 560 to 655 nm are attributed to different packing modes in terms of isolated monomers, discrete π-π stacked dimers or dimer PLUS. Two well-defined microcrystals of PZI-Au-TOT exhibit linearly polarized thermally activated delayed fluorescence with a degree of polarization up to 0.64. This work demonstrates that the molecular rotational flexibility of D-M-A type complexes endows an integration of multiple functions into one complex through manipulation of supramolecular aggregation. This type of complexes is expected to serve as a versatile platform for the fabrication of crystal materialsfor advanced photonic applications.

16.
J Inflamm Res ; 17: 5977-5983, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247838

RESUMO

Hereditary spherocytosis (HS) is the most common hereditary hemolytic disease with defects in red blood cells (RBC) membrane proteins caused by mutations in membrane protein genes, like SPTB, SPTA1 and ANK1. Gilbert syndrome (GS) is a disease characterized by a mild deficiency of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity and unconjugated hyperbilirubinemia, largely caused by UGT1A1 mutations. The two inherited diseases HS and GS are rarely occurred in the same patient and are easy to be misdiagnosed, resulting in excessive diagnosis and treatment. Here, we report a rare case of HS combined with GS due to mutations in the SPTB and UGT1A1 genes. A 50-year-old man who had an over 40-year history of jaundice was admitted to our hospital owing to fatigue and fever. His blood analysis showed low hemoglobin (74 g/L), high reticulocyte (23.5%) and high serum bilirubin (65 µmol/L); abdominal ultrasound revealed calculous cholecystitis and splenomegaly. Considering a possible diagnosis of hemolytic anemia, further examinations showed 42% spherocytes in blood smears and high erythroid lineage hyperplasia in bone marrow. Subsequently, 151 jaundice-related genes panel sequencing was done and results showed SPTB p.N1260fs and UGT1A1 p.G71R mutations. Then the patient was diagnosed with HS complicated with GS. Anti-infection and supportive treatments were providing to the patient, while infection removed, the hemoglobin recovered to normal, and no additional treatment was given. These findings of this report indicate that patients who are considered hemolytic anemia presenting with jaundice and anemia, genetic testing is a crucial method for the final diagnosis and bilirubin metabolic disease should also be concerned.

17.
Sci Rep ; 14(1): 20856, 2024 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242806

RESUMO

At present, biopharmaceuticals have received extensive attention from the society, among which recombinant proteins have a good growth trend and a large market share. Chinese hamster ovary (CHO) cells are the preferred mammalian system to produce glycosylated recombinant protein drugs. A highly efficient and stable cell screening method needs to be developed to obtain more and useful recombinant proteins. Limited dilution method, cell sorting, and semi-solid medium screening are currently the commonly used cell cloning methods. These methods are time-consuming and labor-intensive, and they have the disadvantage of low clone survival rate. Here, a method based on semi-solid medium was developed to screen out high-yielding and stable cell line within 3 weeks to improve the screening efficiency. The semi-solid medium was combined with an expression vector containing red fluorescent protein (RFP) for early cell line development. In accordance with the fluorescence intensity of RFP, the expression of upstream target gene could be indicated, and the fluorescence intensity was in direct proportion to the expression of upstream target gene. In conclusion, semi-solid medium combined with bicistronic expression vector provides an efficient method for screening stable and highly expressed cell lines.


Assuntos
Cricetulus , Proteínas Recombinantes , Células CHO , Animais , Proteínas Recombinantes/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Vetores Genéticos/genética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Cricetinae , Proteína Vermelha Fluorescente , Meios de Cultura/química
18.
J Hypertens ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39248099

RESUMO

OBJECTIVE: Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. In this study, we aimed to investigate the associations of ultra long-term blood pressure (BP) variability from childhood to midlife with vascular aging in midlife. METHODS: Using data from the longitudinal cohort of Hanzhong Adolescent Hypertension Study, 2065 participants aged 6-18 years were enrolled and followed up with seven visits over 30 years. Ultra long-term BP variability (BPV) was defined as the standard deviation (SD) and average real variability (ARV) of BP over 30 years (seven visits). Vascular aging included arterial stiffness, carotid hypertrophy, and carotid plaque. RESULTS: After adjusting for demographic variables, clinical characteristics and mean BP over 30 years, higher SD SBP , ARV SBP , SD DBP and ARV DBP since childhood were significantly associated with arterial stiffness in midlife. Additionally, higher SD DBP and ARV DBP were significantly associated with carotid hypertrophy and the presence of carotid plaque in midlife. When we used cumulative exposure to BP from childhood to midlife instead of mean BP as adjustment factors, results were similar. Furthermore, we found a significant association between long-term BPV from childhood to adolescence and the presence of carotid plaque, whereas long-term BPV from youth to adulthood is associated with arterial stiffness. CONCLUSION: Higher BPV from childhood to adulthood was associated with vascular aging in midlife independently of mean BP or cumulative BP exposure. Therefore, long-term BPV from an early age may serve as a predictor of cardiovascular diseases (CVDs) in later life.

19.
Adv Sci (Weinh) ; : e2405926, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264302

RESUMO

Herein, the study reports the first electrochemical nickel-catalyzed enantioselective hydro-arylation/alkenylation of enones in an undivided cell with low-cost electrodes in the absence of external reductants and supporting electrolytes. Aryl bromides/iodides/triflates or alkenyl bromides are employed as electrophiles for the efficient preparation of more than 56 valuable ß-arylated/alkenylated ketones in a simple manner (up to 97% yield, 97% ee). With the advantages of electrochemistry, excellent functional group tolerance and late-stage modification of complex natural products and pharmaceuticals made the established protocol greener and more economic. Mechanism investigation suggests that a NiI/NiIII cycle may be involved in this electro-reductive reaction rather than metal reductant driven Ni0/NiII cycle. Overall, the efficient electrochemical activation and turnover of the nickel catalyst avoid the drawbacks posed by the employment of stoichiometric amount of sensitive metal powder reductants.

20.
Sci Rep ; 14(1): 21072, 2024 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-39256543

RESUMO

Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan-Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan-Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P < 0.05), but the groups had similar secondary patency. Cox proportional hazard analysis indicated that none of the analyzed clinical and biochemical indexes had clinically meaningful effects on primary patency, assisted primary patency, or secondary patency in either group. The patency and safety after PTA for inflow arterial stenosis were satisfactory, and none of the examined risk factors had a major clinical impact on patency. We recommend PTA as treatment for inflow stenosis of an AVF.


Assuntos
Angioplastia , Diálise Renal , Grau de Desobstrução Vascular , Humanos , Masculino , Feminino , Estudos Retrospectivos , Angioplastia/métodos , Angioplastia/efeitos adversos , Pessoa de Meia-Idade , Idoso , Constrição Patológica , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Fatores de Risco , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Resultado do Tratamento , Artéria Radial , Arteriopatias Oclusivas/terapia , Arteriopatias Oclusivas/etiologia
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