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1.
Lab Chip ; 24(13): 3284-3293, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38847194

ABSTRACT

The prostate-specific antigen (PSA) test is considered an important way for preoperative diagnosis and accurate screening of prostate cancer. Current antigen detection methods, including radioimmunoassay, enzyme-linked immunosorbent assay and microfluidic electrochemical detection, feature expensive equipment, long testing time and poor stability. Here, we propose a portable biosensor composed of electrolyte-gated amorphous indium gallium zinc oxide (a-IGZO) transistors with an extended gate, which can achieve real-time, instant PSA detection at a low operating voltage (<2 V) owing to the liquid-free ionic conductive elastomer (ICE) serving as the gate dielectric. The electric double layer (EDL) capacitance in ICE enhances the accumulation of carriers in the IGZO channel, leading to strong gate modulation, which enables the IGZO transistor to have a small subthreshold swing (<0.5 V dec-1) and a high on-state current (∼4 × 10-4 A). The separate, biodegradable, and pluggable sensing pad, serving as an extended gate connected to the IGZO transistor, prevents contamination and depletion arising from direct contact with biomolecular buffers, enabling the IGZO transistor to maintain superior electronic performance for at least six months. The threshold voltage and channel current of the transistor exhibit excellent linear response to PSA molecule concentrations across five orders of magnitude ranging from 1 fg mL-1 to 10 pg mL-1, with a detection limit of 400 ag mL-1 and a detection time of ∼5.1 s. The fabricated biosensors offer a point-of-care system for antigen detection, attesting the feasibility of the electrolyte-gated transistors in clinical screening, healthcare diagnostics and biological management.


Subject(s)
Biosensing Techniques , Electrolytes , Gallium , Prostate-Specific Antigen , Transistors, Electronic , Zinc Oxide , Prostate-Specific Antigen/analysis , Humans , Electrolytes/chemistry , Zinc Oxide/chemistry , Biosensing Techniques/instrumentation , Gallium/chemistry , Male , Indium/chemistry , Equipment Design
2.
Poult Sci ; 103(8): 103873, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38833747

ABSTRACT

Dietary energy density influences feed intake (FI) and development of layer-type pullets. A total of 384 nine-wk-old Hy-Line Brown pullets were randomly assigned to one of 3 dietary treatments: fed a diet with 2,600, 2,750, and 2,900 Kcal metabolizable energy/kg (ME/kg) from 10 to 21 wk of age. The results showed that the 2,900 and 2,600 ME groups had lower feed and ME intake (P < 0.01) from 10 to 21 wk of age. The 2,600 ME pullets had heavier body weight (BW) and longer shank length (P < 0.05) at 21 wk of age than the 2,750 ME group. The eggshell percentage was increased by the 2,600 and 2,900 kcal/kg treatments (P = 0.002). Serum concentration of 17-ß-estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) decreased at 70 wk of age (P < 0.05). Pullet diet and its interaction with age had a significant influence (P < 0.001) on the expression of gonadotropin-releasing hormone 1 (GnRH-1) and gonadotropin-inhibitory hormone (GnIH) in the hypothalamus and of gonadotropin releasing hormone 1 receptor (GnRH-1R) and gonadotropin-inhibitory hormone receptor (GnIHR) in the pituitary. In the hypothalamus, GnRH-1 expression increased from 9 to 40 wk of age and then decreased; however, GnIH expression was highest at 70 wk of age. Follicle-stimulating hormone receptor (FSHR) expression increased (P < 0.001) at wk 40 and decreased at wk 70 compared to wk 21 at various follicular stages. In conclusion, the energy level of pullet diet had no unfavorable influence on feed intake, laying rate, egg mass, and FCR, whereas change egg weight and mortality during the laying period from 21 to 70 wk of age. during the laying period. These results suggest that pullet dietary energy can activate the expression of genes related to reproduction in the hypothalamus, whereas it plays a minor role in the regulation of genes in the pituitary and ovary. Age-induced gene expression in the hypothalamus-pituitary-gonadal (HPG) axis is associated with laying performance in hens.

3.
Sci Total Environ ; 940: 173689, 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-38825203

ABSTRACT

Atmospheric particulate matter (PM) pollution is one of the world's most serious environmental challenges, and it poses a significant threat to environmental quality and human health. Biomagnetic monitoring of PM has great potential to improve spatial resolution and provide alternative indicators for large area measurements, with respect and complementary to standard air quality monitoring stations. In this study, 160 samples of evergreen plant leaves were collected from park green spaces within five different functional areas of Shanghai. Magnetic properties were investigated to understand the extent and nature of particulate pollution and the possible sources, and to assess the suitability of various plant leaves for urban particulate pollution monitoring. The results showed that magnetic particles of the plant leaf-adherent PM were predominantly composed of pseudo-single domain (PSD) and multi-domain (MD) ferrimagnetic particles. Magnolia grandiflora, as a large evergreen arbor with robust PM retention capabilities, proved to be a more suitable candidate for monitoring urban particulate pollution compared to Osmanthus fragrans, a small evergreen arbor, and Aucuba japonica Thunb. var. variegata and Photinia serratifolia, evergreen shrubs. Meanwhile, there were significant differences in the spatial distribution of the magnetic particle content and heavy metal enrichment of the samples, mainly showing regional variations of industrial area > traffic area > commercial area > residential area > clean area. Additionally, the combination with the results of scanning electron microscopy, shows that industrial production (metal smelting, coal burning), transport and other activities are the main sources of particulate pollution. Plant leaves can be used as an effective tool for urban particulate pollution monitoring and assessment of atmospheric particulate pollution characteristics, and the technique provided useful information on particle size, mineralogy and possible sources.


Subject(s)
Air Pollutants , Environmental Monitoring , Particulate Matter , Particulate Matter/analysis , Environmental Monitoring/methods , China , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Air Pollution/analysis , Plant Leaves/chemistry
4.
J Clin Med ; 13(12)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38930036

ABSTRACT

Objectives: Gait speed indicates the individual's functional status and predicts overall health. This study aims to determine (1) the intra- and inter-rater and test-retest reliability of the dynamic 4 m gait speed test protocol; (2) establish the normative reference values of habitual and fast gait speeds in community-dwelling healthy Singaporean adults aged 21 to 80; and (3) explore the association of age, gender, height, weight, and body mass index (BMI) on gait speed. Methods: This prospective cross-sectional study recruited healthy ambulatory community-dwelling Singaporeans aged 21 to 80 who could ambulate independently without aid. Participants were excluded if they required walking aids; were pregnant; or had physical, medical, or cognitive conditions that may affect gait. Each participant completed at least two habitual and fast gait speed test trials via a 4 m walkway with a dynamic start. The data were analysed by descriptive statistics, the Mann-Whitney test, the Spearman coefficient, and the interclass correlation coefficient (ICC). Results: In total, 178 males and 201 females were included in the data analysis. The median age was 45.0 years [interquartile range (IQR) 26.2-59.0], and the median height was 1.64 metres (m) (IQR 1.58-1.70). The median habitual gait speed was 1.08 metre/second (m/s) (IQR 0.97-1.22), and the fast gait speed was 1.55 m/s (IQR 1.40-1.70). The ICC for reliability ranged from 0.84 to 0.99, indicating that the 4 m gait speed test had good-to-excellent reliability. Conclusions: Gait speeds were not influenced by gender but declined with age advancement. Age and height and age and BMI were weakly correlated to habitual and fast gait speed, respectively. We established the norm values for the 4 m gait speeds in Singapore and proved it to be a reliable gait speed assessment ready for immediate community applications.

5.
Colloids Surf B Biointerfaces ; 240: 113968, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38788472

ABSTRACT

Due to the unique structure, carbon nanomaterials could convert near-infrared (NIR) light into heat efficiently in tumor ablation using photothermal therapy (PTT). However, none of them has been applied in clinical treatment, because they have not been approved for clinical evaluations and the precise temperature control facility is scarce. In this study, we designed a temperature-responsive controller for PTT and used carbon nanoparticles-Fe(II) complex (CNSI-Fe) as photothermal conversion agent (PTA) for PTT of tumor in vitro and in vivo. CNSI-Fe was an innovative drug under the evaluations in clinical trials. CNSI-Fe showed excellent photothermal conversion ability in water to increase the water temperature by 40 °C within 5 min under irradiation of 808 nm laser at 0.5 W/cm2. The temperature was precisely controlled at 52 °C for both in vitro and in vivo tumor inhibition. CNSI-Fe with NIR irradiation showed higher tumor cell inhibition than CNSI. In tumor bearing mice, CNSI-Fe with NIR irradiation achieved an inhibition rate of 84.7 % and 71.4 % of them were completely cured. Mechanistically, CNSI-Fe under NIR irradiation induced the radical generation, oxidative damage and ferroptosis to kill tumor. In addition, CNSI-Fe showed good biosafety during PTT according to hematological, serum biological and histopathological examinations. These results indicated that the combination of chemotherapy and PTT provided higher antitumor efficiency using CNSI-Fe as PTA.


Subject(s)
Carbon , Nanoparticles , Photothermal Therapy , Animals , Carbon/chemistry , Mice , Nanoparticles/chemistry , Humans , Mice, Nude , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Mice, Inbred BALB C , Infrared Rays , Ferrous Compounds/chemistry , Ferrous Compounds/pharmacology , Cell Survival/drug effects , Cell Proliferation/drug effects , Cell Line, Tumor , Particle Size , Drug Screening Assays, Antitumor
6.
Heliyon ; 10(9): e30586, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38765177

ABSTRACT

Employing the Complex Adaptive System (CAS) framework, we analyzed the evolution of digitally transformed financial networks, underscoring the pivotal role of adaptation and learning among network participants. Government funds supporting banks and platforms in digital transformation prove more effective than direct subsidies to SMEs. Achieving sustainable development requires an optimal balance between investment and efficiency due to the impact of digitalization costs on constructing digital financial networks. The study advocates for a long-term microcredit financing mode tailored to SMEs, aiding them in maintaining financial stability. Additionally, intermediary nodes within the network, such as credit rating companies, can facilitate information sharing, thereby fostering the growth of digital financial networks. This heightened information sharing enhances the payoff for each subject and reduces financing constraints. Furthermore, the study establishes that digital financial networks can alleviate the repercussions of unforeseen events, such as the COVID-19 pandemic. Finally, empirical analysis of the Beijing University Inclusive Finance Index data and financial records of Chinese SMEs listed on the New Third Board from 2016 to 2018 confirms that digital finance can alleviate the financing constraints of SMEs. In summary, the progression of digital financial networks is intricate, necessitating a thorough comprehension of diverse factors. The government is encouraged to guide the enhancement of relevant systems and regulations, bolstering supervision, and facilitating the high-quality development of digital finance networks.

7.
Org Biomol Chem ; 22(19): 3904-3909, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38656504

ABSTRACT

A method for the α-oxidation and sulfonation of benzyl secondary amines was developed utilizing Ir(III) or Eosin Y as the photocatalyst in the presence of O2 as a green oxidant. Using commercial substrates, 37 products from cyclic and acyclic benzylamines were achieved with good functional group compatibility in 48-87% yields. Furthermore, tetrahydroisoquinoline protected by an Ac or a Boc group was oxidized under standard conditions.

8.
Nanotechnology ; 35(15)2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38198735

ABSTRACT

Electronical properties of top gate amorphous InGaZnO4thin film transistors (TFTs) could be controlled by post-annealing treatment, which has a great impact on the Al2O3insulator. To investigate the effect of post-annealing on Al2O3, Al/Al2O3/p-Si MOS capacitoras with Al2O3films treated under various post-deposition annealing (PDA) temperature were employed to analysis the change of electrical properties, surface morphology, and chemical components by electrical voltage scanning, atomic force microscope (AFM), and x-ray photoelectron spectroscopy (XPS) technologies. After PDA treatment, the top gate TFTs had a mobility about 7 cm2V-1s-1and the minimum subthreshold swing (SS) about 0.11 V/dec, and the threshold voltage (Vth) shifted from positive direction to negative direction as the post-annealing temperature increased. Electrical properties of MOS capacitors revealed the existence of positive fixed charges and the variation of trap state density with increasing PDA temperature, and further explained the change of negative bias stress (NBS) stability in TFT. AFM results clarified the increased leakage current, degraded SS, and NBS stability in MOS capacitors and TFTs, respectively. XPS results not only illuminated the origin of fixed charges and the trap density variation with PDA temperatures of Al2O3films, but also showed the O and H diffusion from Al2O3into IGZO during post-annealing process, which led to the deviation ofVth, the change of current density, and the negativeVthshift after positive bias stress in TFTs.

9.
Neuropsychiatr Dis Treat ; 19: 2573-2583, 2023.
Article in English | MEDLINE | ID: mdl-38046832

ABSTRACT

Purpose: We aimed to explore whether anxiety is a risk factor for acute mountain sickness [AMS] in a young Chinese male population. Patients and Methods: A total of 143 young Chinese men with a median age of 23 years (IQR, 21-25) were employed in the present study, and they were divided into the AMS+ and AMS- groups according to the Lake Louise AMS score [AMS-S] after exposure at 3800 m for two days. Participants' pulse oximeter saturation [SpO2] and heart rate [HR] were measured. AMS was evaluated using the AMS-S. The anxiety and sleep quality of the subjects were assessed using the Zung Self-Rating Anxiety Scale [SAS] and the Athens Insomnia Scale [AIS], respectively. Outcomes were analysed using Spearman's partial correlation and logistic regression analysis. Results: After two days of exposure at 3800 m, the overall prevalence of AMS was 54% in the whole group. The HR was significantly higher in the AMS+ group than in the AMS- group, as well as the SAS score and AIS score. A converse pattern was observed for SpO2. A significant difference was observed for the change in SAS and AIS score between the AMS+ and AMS- groups. Correlation analysis showed that AMS-S was positively correlated with SAS score, AIS score, HR, ΔSAS score, ΔAIS score, and ΔHR but negatively correlated with SpO2. AIS score was positively correlated with SAS score. After logistic regression analysis was adjusted for HR, SpO2, ΔAIS and ΔHR, SAS score (OR=1.446, 95% CI 1.200-1.744, p<0.001), AIS score (OR=1.216, 95% CI 1.033-1.432) and ΔSAS score (OR=1.158, 95% CI 1.012-1.327) were identified as independent risk factors for AMS. Conclusion: The present study suggests that anxiety is a risk factor for AMS among young Chinese men, and poor sleep quality may partially mediate the association.

10.
Ying Yong Sheng Tai Xue Bao ; 34(9): 2436-2444, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37899110

ABSTRACT

Rapid urbanization would have significant impacts on vegetation phenology. However, the factors influencing the spatiotemporal changes in urban vegetation phenology are still unclear. We used five fitting methods to construct normalized difference vegetation index (NDVI) curves in the Beijing-Tianjin-Hebei urban agglomeration, and obtained the phenology characteristics of urban vegetation in this area from 2001 to 2019 by the threshold method. We compared the spring and autumn phenology in urban built-up areas and hilly areas, and analyzed the effects of precipitation, air temperature, and land surface temperature (LST) on vegetation phenology. The results showed that from 2001 to 2019, the start of the growing season (SOS) in urban built-up areas in the Beijing-Tianjin-Hebei agglomeration was on average 16.88 days earlier than that in hilly areas, and that the end of the growing season (EOS) in urban built-up areas was 12.22 days later than that in hilly areas. During the study period, the SOS of vegetation in urban built-up areas of the Beijing-Tianjin-Hebei region had been gradually delayed, while that in hilly areas was gradually advanced, and the rate of change of phenology in the urban built-up areas was faster than that in the hilly areas. The difference between the SOS of the two areas decreased significantly over time (-0.58 d·a-1). As for the EOS, the urban built-up areas and hilly areas both showed a trend of delayed, but the differences between them was not significant with time (-0.10 d·a-1). The contribution of LST in the urban built-up areas to SOS was close to that of air temperature, while the contribution of LST in hilly areas to SOS was only 1/2 of that of air temperature, indicating that the heat island effect and air temperature within the city jointly influenced urban vegetation phenology, and their contributions were almost equal. The results could help understand the role of urbanization in the variations of vegetation phenology and provide a reference for further assessment of carbon sink potential of urban vegetation.


Subject(s)
Hot Temperature , Urbanization , Cities , Seasons , Temperature
11.
J Obstet Gynaecol ; 43(2): 2259982, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37743728

ABSTRACT

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication, resulting in potentially life-threatening conditions for both mother and foetus. It is worth noting that early-onset PE has become a great challenge for clinicians due to its complex manifestation, rapid progression and serious complications. This study aims to investigate differential serum proteome profiles in patients with early-onset PE. METHODS: Each serum sample was separated using a nanoliter flow rate Easy-nLC chromatography system. Then the samples were analysed by mass spectrometry. Bioinformatics analyses were conducted to analyse the functional categories or signal transduction pathways for differentially abundant proteins. Key proteins identified by mass spectrometry were verified by ELISA. RESULTS: We found 30 and 34 proteins were upregulated and downregulated in early-onset PE patients (n = 3) vs controls (n = 3), respectively. Functional enrichment analysis revealed differentially expressed proteins related to the immune response and regulation of peptidase activity. ELISA confirmed that there were lower CSH1 levels and higher LPA concentrations in the serum samples of early-onset PE patients (n = 22) than in healthy controls (n = 19) (p < 0.05 for CSH1 and p < 0.001 for LPA). CONCLUSIONS: This study revealed the critical features of serum proteins in early-onset PE patients. LPA and CSH1 may serve as biomarkers for early-onset PE diagnosis and therapy.


Early-onset preeclampsia (PE) is still lacking definitive diagnostic or therapeutic strategies. Thus, we tried to identify effective and specific biomarkers for early-onset PE. In this study, we explored the serum protein profiles through the approach of label-free quantitation proteomics between early-onset PE patients and healthy controls. We identified 64 differentially expressed proteins in early-onset PE patients' serum samples. These differentially expressed proteins are associated with the immune response and regulation of peptidase activity. In addition, our findings suggest that LPA and CSH1 may serve as candidate biomarkers for early-onset PE diagnosis and therapy. These results may help physicians to diagnose early-onset PE clinically. What's more, our findings provide new insights into the onset and progression of early-onset PE disease.


Subject(s)
Pre-Eclampsia , Pregnancy , Female , Humans , Pre-Eclampsia/diagnosis , Proteomics/methods , Mass Spectrometry , Biomarkers , Blood Proteins
12.
J Anim Sci ; 1012023 Jan 03.
Article in English | MEDLINE | ID: mdl-37773415

ABSTRACT

Bile acids (BA), a series of hydroxylated steroids secreted by the liver, are involved in the digestion and absorption of dietary fats. In the present study, the effect of exogenous BAs on the performance and liver lipid metabolism of laying hens was investigated. Three hundred and sixty 50-wk-old Hy-line Brown hens were randomly allocated into three groups and subjected to one of the following treatments: fed with the basal diet (control, Con), the basal diet supplemented with 0.1 g/kg (0.1 g/kg BAs), or 0.2 g/kg (0.2 g/kg BAs) porcine BAs. Laying performance, egg quality, and blood parameters were measured during the 8-wk experimental period. The expression of genes related to hepatic lipid metabolism was determined at the end of experiment. The results showed that BAs treatments had no influence (P > 0.05) on laying rate, egg weight, and feed efficiency. BAs treatment, however, significantly decreased mortality of hens (P = 0.006). BAs treatment showed a transient negative influence on eggshell quality at week 4 but not at week 8. The yolk color on week 8 was increased by BAs treatments (P < 0.0001) compared to control. The duodenum index showed a tendency to be increased (P = 0.053) and jejunum index were increased (P = 0.007) by BAs treatment. Compared to control, BAs treatments decreased lipid droplet content (P < 0.0001) and TG content (P = 0.002) of liver. Fatty acid synthase activity was also decreased as an effect of BAs dietary supplementation. Compared to the control group, 0.1 g/kg BAs treatment increased (P < 0.05) the mRNA expression of genes Farnesoid X receptor (FXR) (P = 0.042), cytochrome P450 family 7 subfamily A member 1 (CYP7A1) (P = 0.002), and cytochrome P450 family 8 subfamily B member 1 (CYP8B1) (P = 0.017), fatty acid synthase (FAS) (P = 0.020), acetyl-CoA carboxylase (ACC) (P = 0.032), sterol regulatory element binding protein-1c (SREBP-1c) (P = 0.037), proliferator-activated receptor gamma (PPARγ) (P = 0.002), apolipoprotein B (APO-B) (P = 0.020), and very low density lipoprotein receptor (VLDLR) (P = 0.024). In conclusion, the addition of exogenous BAs reduces lipid accumulation in liver. BA supplementation reduces the mortality of hens and improves egg yolk color, with no unfavorable effect on laying performance. The result suggests that suppressed FAS activity is involved in the reduced hepatic lipid accumulation by BAs treatment.


Fatty liver hemorrhagic syndrome is one of the most common diseases in laying hens and is a metabolic disease characterized by disorders of lipid metabolism in the liver, manifested by fatty liver degeneration and varying degrees of hemorrhage, which often occurs in caged hens in good condition and with high egg production rates. Bile acids (BA), a group of hydroxylated steroids synthesized from cholesterol in the liver, play an important role in lipid metabolism. This study aimed to examine the effects of dietary addition of different levels of BAs on the production performance and liver fat metabolism of 50-wk-old Hy-line Brown hens. The result indicates that the addition of exogenous BAs reduces lipid accumulation in liver. BAs supplementation reduces the mortality of hens and improves egg yolk color, with no other unfavorable side effects on laying performance. The results of the present study suggest that suppressed fatty acid synthase activity is involved in the reduced hepatic lipid accumulation as an effect of BAs dietary supplementation.


Subject(s)
Bile Acids and Salts , Lipid Metabolism , Animals , Female , Swine , Bile Acids and Salts/metabolism , Chickens/metabolism , Ovum/metabolism , Dietary Supplements , Diet/veterinary , Liver/metabolism , Dietary Fats/pharmacology , Fatty Acid Synthases , Animal Feed/analysis
13.
Immun Inflamm Dis ; 11(6): e903, 2023 06.
Article in English | MEDLINE | ID: mdl-37382269

ABSTRACT

BACKGROUND: The aryl hydrocarbon receptor (AhR) is a critical regulator of the pathogenesis of autoimmune disorders. We aimed to investigate the therapeutic effect of the AhR agonist tapinarof during the development of systemic lupus erythematosus (SLE). METHODS: MRL/lpr mice were intraperitoneally injected with 1 or 5 mg/kg tapinarof for 6 weeks. Kidney histopathology was evaluated using hematoxylin and eosin (H&E) and Periodic-Acid-Schiff (PAS) staining. Immunofluorescence microscopy was performed to detect immune complex renal depositions. Flow cytometry (FCM) analysis was carried out to determine the proportions of T and B cell subsets. Realtime qPCR was used to quantify the expression of Tfh cell-associated genes. We conducted an in vitro polarization experiment to observe the effect of tapinarof on Tfh differentiation. Western blotting was used to detect the expression of target proteins. RESULTS: We found that tapinarof treatment ameliorated lupus phenotypes, including splenomegaly, lymph node enlargement, kidney damages, immune complex deposition, and excessive secretion of antibodies. Additionally, we showed that Treg subpopulation frequencies significantly increased in MRL/lpr mice treated with tapinarof, while the proportion of Th1/Th2 cells was reduced after tapinarof administration. Moreover, tapinarof suppressed Tfh cell differentiation and germinal center (GC) reaction in vivo. The inhibitory effect of tapinarof on Tfh cells was further verified in the in vitro Tfh cell polarization experiment. Realtime qPCR revealed that tapinarof repressed the expression of Tfh signature genes. Mechanistically, tapinarof significantly inhibited the phosphorylation levels of JAK2 and STAT3. The capacity for Tfh differentiation was partially rescued by the STAT3 activator Colivelin TFA. Furthermore, our in vitro Tfh polarization experiments indicated that tapinarof suppressed Tfh cell development in SLE. CONCLUSIONS: Our data demonstrated that tapinarof modulated the JAK2-STAT3 pathway to suppress Tfh cell differentiation for the treatment of lupus symptoms in MRL/lpr mice.


Subject(s)
Lupus Erythematosus, Systemic , T Follicular Helper Cells , Animals , Mice , Antigen-Antibody Complex , Autoimmunity , Lupus Erythematosus, Systemic/drug therapy , Mice, Inbred MRL lpr , Receptors, Aryl Hydrocarbon/agonists
14.
J Comp Eff Res ; 12(7): CER, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37338181

ABSTRACT

Aim: This study assessed the cost-utility of mogamulizumab, a novel monoclonal antibody, versus established clinical management (ECM) in UK patients in previously treated advanced mycosis fungoides (MF)/Sézary syndrome (SS). Materials & methods: Lifetime partitioned survival model based on overall survival, next treatment-free survival and the use of allogeneic stem cell transplant was developed. Inputs were from the pivotal MAVORIC trial, real-world evidence and published literature. Extensive sensitivity analyses were conducted. Results: Discounted incremental quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratio were 3.08, £86,998 and £28,233. Results were most sensitive to the survival extrapolations, utilities and costs after loss of disease control. Conclusion: Mogamulizumab is a cost-effective alternative to ECM in UK patients with previously treated advanced MF/SS.


Subject(s)
Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Sezary Syndrome , Skin Neoplasms , Humans , Sezary Syndrome/drug therapy , Sezary Syndrome/pathology , Cost-Benefit Analysis , Skin Neoplasms/drug therapy , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Lymphoma, T-Cell, Cutaneous/drug therapy , Lymphoma, T-Cell, Cutaneous/pathology
15.
J Org Chem ; 88(13): 9293-9305, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37284734

ABSTRACT

A visible-light-induced three-component reaction of 2-aryl indoles/benzimidazoles, Hantzsch esters, and sodium pyrosulfite through a radical cascade cyclization process with the insertion of sulfur dioxide is described. It provides a novel and powerful way for the synthesis of alkylsulfonated isoquinolinones. Hantzsch esters and Na2S2O5 are employed as alkyl radical precursors and SO2 surrogate, respectively. This transformation exhibits good functional group tolerance and substrate applicability under mild conditions.


Subject(s)
Benzimidazoles , Sulfur Dioxide , Cyclization , Esters , Indoles
16.
J Colloid Interface Sci ; 648: 169-180, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37301142

ABSTRACT

Porous alumina has been widely used as catalytic support for industrial processes. Under carbon emission constraints, developing a low-carbon porous aluminum oxide synthesis method is a long-standing challenge for low-carbon technology. Herein, we report a method involving the only use of elements of the aluminum-containing reactants (e.g. sodium aluminate and aluminum chloride), sodium chloride was introduced as the coagulation electrolyte to adjust the precipitation process. Noticeably, the adjustment of the dosages of NaCl would allow us to tailor the textural properties and surface acidity with a volcanic-type change of the assembled alumina coiled plates. As a result, porous alumina with a specific surface area of 412 m2/g, large pore volume of 1.96 cm3/g, and concentrated pore size distribution at 30 nm was obtained. The function of salt on boehmite colloidal nanoparticles was proven by colloid model calculation, dynamic light scattering, and scanning/transmission electron microscopy. Afterward, the synthesized alumina was loaded with PtSn to prepare catalysts for the propane dehydrogenation reaction. The obtained catalysts were active but showed different deactivation behavior that was related to the coke resistance capability of the support. We figure out the correlation between pore structure and the activity of the PtSn catalysts associated with the maximum conversion of 53 % and minimum deactivation constant occurring at the pore diameter around 30 nm of the porous alumina. This work offers new insight into the synthesis of porous alumina.

17.
ACS Appl Mater Interfaces ; 15(27): 32561-32568, 2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37368844

ABSTRACT

In this work, square nanopore arrays were developed on the surface of ß-Ga2O3 microflakes using focused ion beam (FIB) etching, and solar-blind photodetectors (PDs) were fabricated based on the ß-Ga2O3 microflakes with square nanopore arrays. The ß-Ga2O3 microflake-based device was transformed from a gate voltage depletion mode to an oxygen depletion mode by FIB etching. The developed device exhibited excellent solar-blind PD performance with extremely high responsivity (1.8 × 105 at 10 V), detectivity (3.4 × 1018 Jones at 10 V), and light-to-dark ratio (9.3 × 108 at 5 V) as well as good repeatability and excellent stability. The intrinsic mechanism responsible for this performance was then systematically discussed. This work opens up a new avenue for the fabrication of high-performance ß-Ga2O3-based low-dimensional PDs with high reproducibility by employing the FIB etching process.

18.
J Clin Endocrinol Metab ; 108(11): 2981-2989, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37084400

ABSTRACT

CONTEXT: Longitudinal patterns of resting heart rate (RHR) in patients with diabetes mellitus and their association with health outcomes are not well-characterized. OBJECTIVE: We sought to explore the RHR trajectories in patients with diabetes mellitus and their association with cardiovascular disease (CVD) and all-cause mortality. DESIGN: The Kailuan Study is a prospective cohort study. Participants underwent health examinations biennially starting in 2006 and were followed until December 31, 2020. SETTING: General community. PARTICIPANTS: A total of 8218 diabetic participants who attended at least 3 of the examinations conducted in 2006, 2008, 2010, and 2012 were included. MAIN OUTCOME MEASURES: CVD and all-cause mortality. RESULTS: We identified 4 RHR trajectories in participants with diabetes mellitus between 2006 and 2012: low-stable (range, 66.83-64.91 beats/min; n = 1705), moderate-stable (range, 76.30-76.95 beats/min; n = 5437), high-decreasing (mean decreased from 92.14 to 85.60 beats/min; n = 862), and high-increasing (mean increased from 84.03 to 111.62 beats/min; n = 214). During an average follow-up of 7.25 years, 977 cases of CVD and 1162 deaths were identified. Compared with the low-stable trajectory, adjusted hazard ratios (HRs) for CVD were 1.48 (95% CI, 1.02-2.14; P = .04) for the high-increasing trajectory, adjusted HRs for all-cause mortality were 1.34 (95% CI, 1.14-1.58; P < .01) for the moderate-stable trajectory, 1.68 (95% CI, 1.35-2.10; P < .01) for the high-decreasing trajectory, and 2.47 (95% CI, 1.85-3.31; P < .01) for the high-increasing trajectory. CONCLUSIONS: RHR trajectories were associated with the subsequent risks of CVD and all-cause mortality in patients with diabetes mellitus.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Humans , Risk Factors , Prospective Studies , Heart Rate , Diabetes Mellitus/epidemiology
19.
Chin Med J (Engl) ; 136(5): 588-595, 2023 Mar 05.
Article in English | MEDLINE | ID: mdl-36914935

ABSTRACT

BACKGROUND: The clinical characteristics of patients with the comorbidities of hypertension and coronary artery disease (HT-CAD) and atrial fibrillation (AF) are largely unknown. This study aimed to investigate the prevalence of AF in patients with HT-CAD and clinical characteristics of patients with both HT-CAD and AF. METHODS: This cross-sectional study was conducted in Chinese People's Liberation Army General Hospital in Beijing, China, and included 20,747 inpatients with HT-CAD with or without AF from August 2008 to July 2018. We examined the overall prevalence, clinical characteristics, comorbidity profiles, treatment patterns, and blood pressure (BP) control of patients with both HT-CAD and AF. Multivariate logistic regression was used to investigate the associations of cardiovascular risk factors with AF in patients with HT-CAD. RESULTS: The overall prevalence of AF in patients with HT-CAD was 4.87% (1011/20,747), and this increased with age; to be specific, the prevalence in women and men increased from 0.78% (2/255) and 1.02% (26/2561) at the age of <50 years to 8.73% (193/2210) and 10.28% (298/2900) at the age of ≥70 years, respectively. HT-CAD patients who had AF had a higher prevalence of cardiovascular-related comorbidities than those without AF. Multivariate logistic regression showed that age, gender (male), body mass index, heart failure, and chronic kidney disease were independently associated with the risk of AF in patients with HT-CAD. For those with both HT-CAD and AF, 73.49% (743/1011) had a CHA 2 DS 2 -VASc score of ≥4, and only about half of them had the BP controlled at <140/90 mmHg, which indicated a high risk of thromboembolism and stroke. The use of oral anticoagulation increased during the study period (10.00% [20/200] in 2008 to 2011 vs. 30.06% [159/529] in 2015 to 2018, P  < 0.01), but remained at a relatively low level. CONCLUSIONS: AF is highly prevalent among patients with HT-CAD. Patients with both HT-CAD and AF have a higher prevalence of cardiovascular-related comorbidities, lower BP control rate, and lower use of oral anticoagulation.


Subject(s)
Atrial Fibrillation , Coronary Artery Disease , Hypertension , Humans , Male , Female , Middle Aged , Aged , Coronary Artery Disease/complications , Atrial Fibrillation/drug therapy , Cross-Sectional Studies , Prevalence , Risk Factors , Hypertension/complications , Anticoagulants/therapeutic use
20.
J Kidney Cancer VHL ; 10(1): 1-8, 2023.
Article in English | MEDLINE | ID: mdl-36713028

ABSTRACT

Ligustrazine is a Chinese herb (Chuanxiong) approved for use as a medical drug in China. Recent evidence suggests that ligustrazine has promising antitumor properties. Our preliminary results showed that ligustrazine could inhibit the growth of human renal cell carcinoma (RCC) cell lines. However, the complicated molecular mechanism has not been fully revealed. Therefore, the purpose of this study to investigate the mechanism of ligustrazine resistance in human RCC cells. Cell proliferation, migration, invasion, and colony-formation ability of RCC cells A498 were detected by MTT assay, clonal formation rates, and transwell chamber assay in vitro. The expression of epithelial-mesenchymal transition (EMT)-related proteins were analyzed using western blot test. The effect of ligustrazine on the growth of A498 cells in nude mice was investigated in vivo. Our results showed that ligustrazine could significantly inhibit the proliferation, migration, and invasion of A498 both in vivo and vitro. Western blot analysis showed that the expressions of EMT-related, N-cadherin, snail, and slug proteins were significantly decreased in A498 in the ligustrazine treatment group. This study indicated that ligustrazine could significantly inhibit the malignant biological behaviors of RCC cell lines, possibly by inhibiting the EMT process.

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