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1.
Nature ; 618(7963): 80-86, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36990110

ABSTRACT

All-perovskite tandem solar cells provide high power conversion efficiency at a low cost1-4. Rapid efficiency improvement in small-area (<0.1 cm2) tandem solar cells has been primarily driven by advances in low-bandgap (approximately 1.25 eV) perovskite bottom subcells5-7. However, unsolved issues remain for wide-bandgap (> 1.75 eV) perovskite top subcells8, which at present have large voltage and fill factor losses, particularly for large-area (>1 cm2) tandem solar cells. Here we develop a self-assembled monolayer of (4-(7H-dibenzo[c,g]carbazol-7-yl)butyl)phosphonic acid as a hole-selective layer for wide-bandgap perovskite solar cells, which facilitates subsequent growth of high-quality wide-bandgap perovskite over a large area with suppressed interfacial non-radiative recombination, enabling efficient hole extraction. By integrating (4-(7H-dibenzo[c,g]carbazol-7-yl)butyl)phosphonic acid in devices, we demonstrate a high open-circuit voltage (VOC) of 1.31 V in a 1.77-eV perovskite solar cell, corresponding to a very low VOC deficit of 0.46 V (with respect to the bandgap). With these wide-bandgap perovskite subcells, we report 27.0% (26.4% certified stabilized) monolithic all-perovskite tandem solar cells with an aperture area of 1.044 cm2. The certified tandem cell shows an outstanding combination of a high VOC of 2.12 V and a fill factor of 82.6%. Our demonstration of the large-area tandem solar cells with high certified efficiency is a key step towards scaling up all-perovskite tandem photovoltaic technology.

2.
Int J Obes (Lond) ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237758

ABSTRACT

BACKGROUND/AIMS: Elevated systemic inflammation, common in obesity, increases cardiovascular disease risk. Obesity is linked to a pro-inflammatory gut microbiota that releases uremic toxins like p-cresylsulfate (PCS) and indoxyl sulfate (IS), which are implicated in coronary atherosclerosis, insulin resistance, and chronic kidney disease. This study examines the relationship between total PCS and IS levels and central obesity in patients with stable coronary artery disease (CAD). METHODS: A cross-sectional study was conducted on 373 consecutive patients with stable CAD from a single center. Serum levels of total PCS and IS were measured using an Ultra Performance LC System. Central obesity was evaluated using a body shape index (ABSI) and conicity index (CI). Six obesity-related proteins were also analyzed. Structural equation modeling (SEM) assessed direct and indirect effects of total PCS, IS, and the six obesity-related proteins on central obesity. RESULTS: Significant positive correlations were found between total PCS and IS with waist-to-hip ratio (WHR) (r = 0.174, p = 0.005 for total PCS; r = 0.144, p = 0.021 for IS), CI (r = 0.273, p < 0.0001 for total PCS; r = 0.260, p < 0.0001 for IS), and ABSI (r = 0.297, p < 0.0001 for total PCS; r = 0.285, p < 0.0001 for IS) in male patients, but not in female patients. Multivariate analysis showed higher odds ratios (ORs) for elevated CI (OR = 3.18, 95% CI: 1.54-6.75, p = 0.002) and ABSI (OR = 3.28, 95% CI: 1.54-7.24, p = 0.002) in patients with high PCS levels, and elevated CI (OR = 2.30, 95% CI: 1.15-4.66, p = 0.018) and ABSI (OR = 2.22, 95% CI: 1.07-4.72, p = 0.033) in those with high IS levels, compared to those with low toxin levels. SEM analysis indicated that total PCS and IS directly impacted central obesity indices and indirectly influenced central adiposity measures like WHR through high sensitivity C-reactive protein (hs-CRP) (ß = 0.252, p < 0.001). CONCLUSIONS: Circulating total PCS and IS contribute to central obesity in male patients with stable CAD, partially mediated by hs-CRP.

3.
Int J Med Sci ; 21(3): 483-491, 2024.
Article in English | MEDLINE | ID: mdl-38250610

ABSTRACT

Background: Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether TCF21 gene (12190287G/C) variants affect coronary artery disease risk. Methods: We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the TCF21 gene was performed. Results: Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the TCF21 gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore, TCF21 CC genotypes showed positive correlations with both stable angina and STEMI, whereas TCF21 GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with TCF21 gene polymorphisms (p for trend < 0.05). Conclusion: TCF21 gene polymorphisms may increase susceptibility to stable angina and STEMI.


Subject(s)
Angina, Stable , Diabetes Mellitus, Type 2 , Hyperlipidemias , Hypertension , ST Elevation Myocardial Infarction , Humans , Angina, Stable/genetics , ST Elevation Myocardial Infarction/genetics , China , Basic Helix-Loop-Helix Transcription Factors/genetics
4.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Article in English | MEDLINE | ID: mdl-33723062

ABSTRACT

Xylem patterning in the root is established through the creation of opposing gradients of miRNAs and their targets, transcripts of the HD-ZIP III family of transcriptions factors, enabled by the cell-to-cell spread of the former. The miRNAs regulating xylem patterning, miR165/6, move through plasmodesmata, but how their trafficking is regulated remains elusive. Here, we describe that simultaneous mutation of the plasma membrane- and plasmodesmata-localized receptor-like kinases (RLKs) BARELY ANY MERISTEM (BAM) 1 and 2 or expression of the geminivirus-encoded BAM1/2-interactor C4 results in higher accumulation and broader distribution of the HD-ZIP III transcripts despite normal total accumulation of miR165/6, and ultimately causes defects in xylem patterning, which depend on the function of the aforementioned miRNA targets. Taken together, our results show that BAM1 and BAM2 are redundantly required for proper xylem patterning in the Arabidopsis root, by ensuring the proper distribution and accumulation of miR165/6-targeted transcripts.


Subject(s)
Genes, Plant , Plant Development/genetics , Plant Roots/cytology , Plant Roots/genetics , Protein Serine-Threonine Kinases/genetics , Xylem/cytology , Xylem/genetics , Arabidopsis/physiology , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , MicroRNAs/genetics , Protein Serine-Threonine Kinases/metabolism
5.
Opt Lett ; 48(24): 6384-6387, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38099754

ABSTRACT

In this work, a solar-blind UV metal-semiconductor Schottky photodiode array is constructed by using metalorganic chemical vapor deposition grown ε-Ga2O3 thin film, possessing high-performance and self-powered characteristics, toward dual-mode (self-powered and biased modes) binary light communication. For the array unit, the responsivity, specific detectivity, and external quantum efficiency are 30.8 A/W/6.3 × 10-2 A/W, 1.51 × 104%/30.9%, 1.28 × 1014/5.4 × 1012 Jones for biased (-10 V)/self-powered operation. The rise and decay time are 0.19 and 7.96 ms at biased modes, respectively, suggesting an ability to trace fast light signal. As an array, the deviation of photocurrent is only 4.3%, highlighting the importance of accurate information communication. Through certain definition of "1/0" binary digital information, the "NY" and "IC" characters are communicated to illustrate the self-powered and biased modes by right of ASCII codes, based on the prepared ε-Ga2O3 solar-blind UV Schottky photodiode array. This work made dual-mode binary deep-UV light communication come true and may well guide the development of UV optoelectronics.

6.
Protein Expr Purif ; 208-209: 106293, 2023 08.
Article in English | MEDLINE | ID: mdl-37137401

ABSTRACT

Porcine circovirus type-2 capsid protein contains a major immunodominant epitope used as a subunit vaccine. Transient expression in mammalian cells is an efficient process for producing recombinant proteins. However, there is still a lack of research on the efficient production of virus capsid proteins in mammalian cells. Here we present a comprehensive study to investigate and optimize the production process of a model "difficult-to-express" virus capsid protein, PCV2 capsid protein in HEK293F transient expression system. The study evaluated the transient expression of PCV2 capsid protein in the mammalian cell line HEK293F and investigated the subcellular distribution by confocal microscopy. In addition, the RNA sequencing (RNA-seq) was used to detect the differential expression of genes after cells transfected with pEGFP-N1-Capsid or empty vectors. The analysis revealed that the PCV2 capsid gene affected a panel of differential genes of HEK293F cells involved in protein folding, stress response, and translation process, such as SHP90ß, GRP78, HSP47, and eIF4A. An integrated strategy of protein engineering combined with VPA addition was applied to promote the expression of PCV2 capsid protein in HEK293F. Moreover, this study significantly increased the production of the engineered PCV2 capsid protein in HEK293F cells, reaching a yield of 8.7 mg/L. Conclusively, this study may provide deep insight for other "difficult-to-express" virus capsid proteins in the mammalian cell system.


Subject(s)
Capsid Proteins , Circovirus , Swine , Animals , Humans , Circovirus/genetics , HEK293 Cells , Capsid/metabolism , Recombinant Proteins/genetics , Antibodies, Viral , Mammals
7.
Nanotechnology ; 35(5)2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37890476

ABSTRACT

With the continuous advancement of deep-ultraviolet (DUV) communication and optoelectronic detection, research in this field has become a significant focal point in the scientific community. For more accurate information collection and transport, the photodetector array of many pixels is the key of the UV imaging and commnication systems, and its photoelectric performance seriously depends on semiconductor material and array layout. Gallium oxide (Ga2O3) is an emerging wide bandgap semicondutor material which has been widely used in DUV dectection. Therefore, this paper mainly focuses on Ga2O3semiconductor detector array which has gained widespread attention in the field of DUV technique, from the perspective of individual device to array and its optoelectonic integration, for reviewing and discussing the research progress in design, fabrication, and application of Ga2O3arrays in recent years. It includes the structure design and material selection of array units, units growth and array layout, response to solar blind light, the method of imaging and image recognition. Morever, the future development trend of the photodetector array has been analyzed and reflected, aiming to provide some useful suggestions for the optimizing array structure, improving patterned growth technology and material growth quality. As well as Ga2O3optoelectronic devices and their applications are discussed in view of device physics and photophysics in detector.

8.
Nanotechnology ; 35(9)2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38029450

ABSTRACT

As an ultra-wide bandgap semiconductor, gallium oxide (Ga2O3) has been extensively applied in solar-blind photodetectors (PDs) owing to the absorbance cut-off wavelength of shorter than 280 nm, and the optimized technologies of detection performance is seriously essential for its further usages. Herein, a feasible thermal reorder engineering method was performed through annealing Ga2O3films in vacuum, O2and oxygen plasma atmospheres, realizing to tune solar-blind photosensing performance of Ga2O3PDs. Thermal treatment, in fact a crystal reorder process, significantly suppressed the noise in Ga2O3-based PDs and enhanced the photo-sensitivity, with the dark current decreasing from 154.63 pA to 269 fA and photo-to-dark current ratio magically raising from 288 to 2.85 × 104. This achievement is dependent of energy-band modulation in Ga2O3semiconductor, that is certified by first-principles calculation. Additionally, annealing in oxygen atmospheres notably reduces the concentration of oxygen vacancies in the surface of films, thereby improving the performance of the PDs; the oxygen vacancy is extremely concerned in oxide semiconductors in the view of physics of surface defects. In all, this work could display a promising guidance for modulating the performance of PDs based on wide bandgap oxide semiconductor, especially for hot Ga2O3issue.

9.
Int J Med Sci ; 20(8): 1091-1096, 2023.
Article in English | MEDLINE | ID: mdl-37484802

ABSTRACT

Background: Ficolin-3 (FCN3) is a well-known circulating pattern recognition molecule which plays a role in host immune responses to cancer via activation of the lectin complement pathway. Nevertheless, the clinical significance of FCN3 in patients with hepatocellular carcinoma (HCC) is unclear. Methods: Eighty-seven HCC patients who received hepatectomy at our hospital were included. Immunohistochemical staining was used to assess the FCN3 expression in both tumorous and non-tumorous tissues from the patients, who were classified into high and low expression groups. Differences in clinicopathological characteristics between the two groups were then analyzed. Results: Survival was significantly associated with FCN3 immunohistochemical score (p for trend = 0.048). Kaplan-Meier analysis revealed a higher overall survival rate in the patients with a high FCN3 expression than in those with a low FCN3 expression (p=0.031). A high FCN3 expression in tumor tissue was independently associated with better overall survival (p=0.042). However, multivariate analysis showed that FCN3 expression was not an independent risk factor for overall survival. Conclusion: Our findings suggest that FCN3 is significantly related to the prognosis of HCC. FCN3 may be a prognostic marker in patients with HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/metabolism , Kaplan-Meier Estimate , Lectins/genetics , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Liver Neoplasms/metabolism , Prognosis , Ficolins
10.
J Clin Lab Anal ; 37(19-20): e24974, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37840358

ABSTRACT

BACKGROUND: Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). METHODS: A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. RESULTS: The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. CONCLUSIONS: In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.


Subject(s)
Hypertension , Leptin , Humans , Female , Renal Dialysis/adverse effects , Biomarkers , Hypertension/complications , Inflammation/complications , Body Mass Index
11.
Molecules ; 28(22)2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38005202

ABSTRACT

The design of well-defined hierarchical free-standing electrodes for robust high-performance energy storage is challenging. We report herein that azo-linkage redox metal-organic frameworks (MOFs) incorporate single-walled carbon nanotubes (CNTs) as flexible electrodes. The in situ-guided growth, crystallinity and morphology of UiO-66-NO2 MOFs were finely controlled in the presence of CNTs. The MOFs' covalent anchoring to CNTs and solvothermal grafting anthraquinone (AQ) pendants endow the hybrid (denoted as CNT@UiO-66-AQ) with greatly improved conductivity, charge storage pathways and electrochemical dynamics. The flexible CNT@UiO-66-AQ displays a highest areal specific capacitance of 302.3 mF cm-2 (at 1 mA cm-2) in -0.4~0.9 V potential window, together with 100% capacitance retention over 5000 cycles at 5 mA cm-2. Its assembled symmetrical supercapacitor (SSC) achieves a maximum energy density of 0.037 mWh cm-2 and a maximum power density of 10.4 mW cm-2, outperforming many MOFs-hybrids-based SSCs in the literature. Our work may open a new avenue for preparing azo-coupled redox MOFs hybrids with carbaneous substrates for high-performance robust aqueous energy storage.

12.
Small ; 18(25): e2201209, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35607794

ABSTRACT

Emerging unfused-ring acceptors (UFAs) have been explored in pursuit of low-cost high-efficient organic solar cells (OSCs). Assembling unfused building blocks into proper frameworks are challenging for the molecular design of UFAs. The authors report herein four UFAs adopting either dithiophene cyclopentadiene (DTC) or dithieno[3,2-b:2',3'-d]pyrrole (DTP) as π-bridge units with different molecular frameworks for high-efficient as-cast OSCs. All these acceptors exhibit strong near-infrared absorption and narrow optical band gap (Eg opt  < 1.50 eV). DTC-bridged symmetric and DTP-bridged asymmetric UFAs exhibit higher planar conformation as well as suitable miscibility and homogeneous phase separation when blending with polymer donor PBDB-T to promote efficient charge transport in the blends. Their blends with PBDB-T contribute optimal PCE of 12.17% and 11.92% in as-cast OSCs, among the highest values for UFAs based as-cast devices in the literature. Experimental and theoretical simulations systematically reveal the impact of manipulating the molecular framework of UFAs on their conformation, optoelectronic, and photovoltaic performance. The results indicate the matching π-bridge units with molecular frameworks as an attractive approach to design UFAs for high-performance as-cast OSCs.

13.
Blood ; 136(26): 2994-3003, 2020 12 24.
Article in English | MEDLINE | ID: mdl-32870250

ABSTRACT

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene. We report the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mavorixafor from a phase 2 open-label dose-escalation and extension study in 8 adult patients with genetically confirmed WHIM syndrome. Mavorixafor is an oral small molecule selective antagonist of the CXCR4 receptor that increases mobilization and trafficking of white blood cells from the bone marrow. Patients received escalating doses of mavorixafor, up to 400 mg once daily. Five patients continued on the extension study for up to 28.6 months. Mavorixafor was well tolerated with no treatment-related serious adverse events. At a median follow-up of 16.5 months, we observed dose-dependent increases in absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). At doses ≥300 mg/d, ANC was maintained at >500 cells per microliter for a median of 12.6 hours, and ALC was maintained at >1000 cells per microliter for up to 16.9 hours. Continued follow-up on the extension study resulted in a yearly infection rate that decreased from 4.63 events (95% confidence interval, 3.3-6.3) in the 12 months prior to the trial to 2.27 events (95% confidence interval, 1.4-3.5) for patients on effective doses. We observed an average 75% reduction in the number of cutaneous warts. This study demonstrates that mavorixafor, 400 mg once daily, mobilizes neutrophil and lymphocytes in adult patients with WHIM syndrome and provides preliminary evidence of clinical benefit for patients on long-term therapy. The trial was registered at www.clinicaltrials.gov as #NCT03005327.


Subject(s)
Aminoquinolines/administration & dosage , Benzimidazoles/administration & dosage , Butylamines/administration & dosage , Primary Immunodeficiency Diseases/drug therapy , Receptors, CXCR4/antagonists & inhibitors , Warts/drug therapy , Administration, Oral , Adolescent , Adult , Aminoquinolines/adverse effects , Benzimidazoles/adverse effects , Butylamines/adverse effects , Female , Humans , Leukocyte Count , Male , Middle Aged , Neutrophils , Primary Immunodeficiency Diseases/blood , Primary Immunodeficiency Diseases/genetics , Prospective Studies , Receptors, CXCR4/genetics , Warts/blood , Warts/genetics
14.
Phys Chem Chem Phys ; 24(35): 21270-21282, 2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36043262

ABSTRACT

The acceptor-donor-acceptor structured fused-ring electron acceptors (FREAs) have piqued interest for organic solar cells. We herein employ time-dependent density functional theory to evaluate the effect of Hartree-Fock exact exchange (HFX) on the performance of 16 global hybrid functionals for computing the maximum absorption wavelengths (λver-theo) and the vertical excitation energies (Ever-theo) of 34 molecules. We customize the HFX ratio in the functionals used to perform an in-depth analysis of its impact on the Ever-theo values. The computed λver-theo values strictly follow an inverse proportionality to the HFX percentage. The performance of the methods with the same ratio of HFX is almost identical, such as B3LYP, B3PW91, and mPW3PBE containing 20% HFX. The performance enhances with a relatively higher HFX ratio of 21% in X3LYP, B971, B972, and 22% in B98 giving smaller deviations. APF and APFD containing 23% HFX provide the smallest deviations for all compounds, with a mean signed error limited to 0.02 eV and a mean absolute error (MAE) of 0.06 eV. The performance drops using M06 and M05 with comparatively higher HFX ratios providing MAE values of 0.07 eV and 0.1 eV, respectively. M06-2X with 54% HFX provides the largest MAE value of 0.35 eV. The lowest obtained MAE is 0.06 eV at 23 to 25% HFX in most of the functionals considered in this study, suggesting that these are the optimal values for the prediction of excitation energies of FREAs. It has also been found that global hybrids seem to be more efficient for larger-sized molecules with a smaller bandgap.

15.
BMC Cardiovasc Disord ; 22(1): 432, 2022 09 30.
Article in English | MEDLINE | ID: mdl-36180826

ABSTRACT

BACKGROUND: Fibroblast growth factor 21 (FGF21) is produced by cardiac cells, may acts in an autocrine manner, and was suggested to has a cardioprotective role in atherosclerosis. Wide QRS complex and heart rate-corrected QT interval (QTc interval) prolongation are associated to dangerous ventricular arrhythmias and cardiovascular disease mortality. Yet, the role of FGF21 in cardiac arrhythmia has never been studied. The aim of the study was to investigate the relationship between plasma FGF21 and the QRS duration and QTc interval in patients with stable angina. METHODS: Three hundred twenty-one consecutive stable angina patients were investigated. Plasma FGF21 was measured through ELISA, and each subject underwent 12-lead electrocardiography. RESULTS: FGF21 plasma levels were positively associated with the QRS duration (ß = 0.190, P = 0.001) and QTc interval (ß = 0.277, P < 0.0001). With increasing FGF21 tertiles, the patients had higher frequencies of wide QRS complex and prolonged QTc interval. After adjusting for patients' anthropometric parameters, the corresponding odd ratios (ORs) for wide QRS complex of the medium and high of FGF21 versus the low of FGF21 were 1.39 (95% CI 0.51-3.90) and 4.41 (95% CI 1.84-11.59), respectively, and p for trend was 0.001. Furthermore, multiple logistic regression analysis also showed the corresponding odd ratios (ORs) for prolonged QTc interval of the medium and high of FGF21 versus the low of FGF21 were 1.02 (95% CI 0.53-1.78) and 1.93 (95% CI 1.04-3.60) respectively with the p for trend of 0.037. In addition, age- and sex-adjusted FGF21 levels were positively associated with fasting glucose, HbA1c, creatinine, and adiponectin, but negatively associated with albumin, and the estimated glomerular filtration rate. CONCLUSIONS: This study indicates that plasma FGF21 is associated with wide QRS complex and prolonged corrected QT interval in stable angina patients, further study is required to investigate the role of plasma FGF21 for the underlying pathogenesis.


Subject(s)
Angina, Stable , Fibroblast Growth Factors , Long QT Syndrome , Humans , Adiponectin , Albumins , Arrhythmias, Cardiac , Creatinine , Electrocardiography , Electrolytes , Fibroblast Growth Factors/metabolism , Glucose , Glycated Hemoglobin
16.
Int J Med Sci ; 19(11): 1660-1671, 2022.
Article in English | MEDLINE | ID: mdl-36237991

ABSTRACT

Background: Obesity and cognitive function decline are independent risk factors for chronic kidney disease (CKD). However, few studies have examined the combined effects of obesity status and cognitive function on change in CKD risk. We aimed to evaluate the association between obesity status, cognitive function and CKD risk change in patients with type 2 diabetes mellitus (T2DM). Methods: Data on 3399 T2DM patients were extracted from a diabetes disease management program between 2006 and 2018. Univariate and multivariate analyses were used to assess the association between obesity, cognitive decline, and CKD risk change. Three indexes, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze interactions. CKD risk was classified according to the KDIGO 2012 CKD definition. Results: In multivariate analysis, the hazard ratio (HR, 95%Cis) for CKD risk progression was 1.34 (1.12-1.61) times higher in the moderate and severely obese patients compared with the normal weight patients, and 1.34 (1.06-1.67) times higher in the patients with a Mini-Mental State Examination (MMSE) score ≤18 compared to those with an MMSE score ≥24. There was a synergistic interaction between moderate and severe obesity and MMSE score ≤18 on CKD risk progression (SI=4.461; 95% CI: 1.998-9.962), and the proportion of CKD risk progression caused by this interaction was 52.7% (API=0.527; 95% CI: 0.295-0.759). However, normal weight and MMSE score ≥24 were not beneficial on CKD risk improvement in the patients with a moderate risk and very high-risk stage of CKD. Conclusion: There may be a synergistic interaction between obesity and cognitive function decline, and the synergistic interaction may increase the risk of CKD progression.


Subject(s)
Cognitive Dysfunction , Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Cognition , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Cohort Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Glomerular Filtration Rate , Humans , Obesity/complications , Obesity/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Risk Factors
17.
J Clin Lab Anal ; 36(11): e24745, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36268984

ABSTRACT

BACKGROUND: Growth differentiation factor 1 (GDF1) is a member of the transforming growth factor-ß (TGF-ß) superfamily and a protective mediator against the development of post-infarction cardiac remodeling by negatively regulating MEK-ERK1/2 and Smad signaling pathways in the heart. The TGF-ß/SMAD pathway has been shown to play a key role in the development of hepatic fibrosis. In addition, fatty liver disease has been associated with reduced MEK/ERK1/2 signaling. However, no previous study has investigated the association between GDF1 and liver fibrosis. Therefore, the aim of this study was to investigate the association between plasma GDF1 and liver fibrosis in patients with stable angina. METHODS: We included 327 consecutive patients with stable angina. ELISA was used to measure circulating levels of GDF1, and the fibrosis-4 index was used to assess liver fibrosis. RESULTS: The advanced liver fibrosis group had lower median plasma GDF1 levels than those with minimal liver fibrosis. There was a significant negative association between GDF1 plasma level and fibrosis-4 index (r = -0.135, p = 0.019). A lower concentration of GDF1 was significantly and independently associated with an increased risk of liver fibrosis when concentration was analyzed as a continuous variable and by tertile. In addition, fibrosis-4 index, aspartate aminotransferase (AST)-to-platelet ratio index, and AST/alanine aminotransferase ratio were significantly associated with GDF1 concentration. CONCLUSIONS: Our results indicated an association between low plasma GDF1 and liver fibrosis in the enrolled patients. Further investigations into the role of plasma GDF1 in the pathogenesis of liver fibrosis are warranted.


Subject(s)
Angina, Stable , Growth Differentiation Factor 1 , Liver Cirrhosis , Humans , Growth Differentiation Factor 1/blood , Liver/metabolism , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Mitogen-Activated Protein Kinase Kinases/metabolism , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolism
18.
Drug Dev Res ; 83(1): 88-96, 2022 02.
Article in English | MEDLINE | ID: mdl-34196024

ABSTRACT

Sodium Danshensu, extracted from the root of the Salvia miltiorrhiza, has pleiotropic effects including anti-oxidation, anti-inflammation and anti-tumor. However, whether Sodium Danshensu has an anti-cancer effect in lung cancer remains to be elucidated. The present study aimed to illustrate the effects of Sodium Danshensu on lung cancer cells and the potential molecular mechanisms. BEAS-2B, A549, and NCI-H1299 cells were stimulated with 25, 50, and 100 µM Sodium Danshensu for 24, 48, and 72 h, and then cell viability, apoptosis, migration and invasion were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry and Transwell assays, respectively. Moreover, the levels of Proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP9), B-cell lymphoma-2 (Bcl-2) associated X (Bax), Bcl-2, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), and p-Protein kinase B (AKT) in lung cancer cells were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blot assays. We observed that Sodium Danshensu suppressed cells viability, migration, and invasion, as well as promoted cells apoptosis in A549 and NCI-H1299 cells in a dose-dependent manner, while Sodium Danshensu had no cytotoxic effect on the proliferation activity of BEAS-2B cells. Moreover, the expression of PCNA, MMP9, Bcl-2 were decreased, but Bax was up-regulated in Sodium Danshensu-treated A549 and NCI-H1299 cells. Our findings also revealed that Sodium Danshensu inhibited PI3K/AKT pathway in A549 and NCI-H1299 cells. In conclusion, our study provided the first evidence that Sodium Danshensu suppressed the malignant biological behaviors of lung cancer cells, indicating that Sodium Danshensu might be a latent candidate for lung cancer therapy.


Subject(s)
Lung Neoplasms , Phosphatidylinositol 3-Kinases , A549 Cells , Apoptosis , Cell Movement , Cell Proliferation , Humans , Lactates , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Sodium/pharmacology
19.
J Am Chem Soc ; 143(47): 19719-19730, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34784713

ABSTRACT

Fusarium graminearum is a pathogenic fungus causing huge economic losses worldwide via crop infection leading to yield reduction and grain contamination. The process through which the fungal invasion occurs remains poorly understood. We recently characterized fusaoctaxin A in F. graminearum, where this octapeptide virulence factor results from an assembly line encoded in fg3_54, a gene cluster proved to be involved in fungal pathogenicity and host adaptation. Focusing on genes in this cluster that are related to fungal invasiveness but not to the biosynthesis of fusaoctaxin A, we here report the identification and characterization of fusaoctaxin B, a new octapeptide virulence factor with comparable activity in wheat infection. Fusaoctaxin B differs from fusaoctaxin A at the N-terminus by possessing a guanidinoacetic acid (GAA) unit, formation of which depends on the combined activities of the protein products of fgm1-3. Fgm1 is a cytochrome P450 protein that oxygenates l-Arg to 4(R)-hydroxyl-l-Arg in a regio- and stereoselective manner. Then, Cß-Cγ bond cleavage proceeds in the presence of Fgm3, a pyridoxal-5'-phosphate-dependent lyase, giving guanidinoacetaldehyde and l-Ala. Rather than being directly oxidized to GAA, the guanidine-containing aldehyde undergoes spontaneous cyclization and subsequent enzymatic dehydrogenation to provide glycociamidine, which is linearized by Fgm2, a metallo-dependent amidohydrolase. The GAA path in F. graminearum is distinct from that previously known to involve l-Arg:l-Gly aminidotransferase activity. To provide this nonproteinogenic starter unit that primes nonribosomal octapeptidyl assembly, F. graminearum employs new chemistry to process l-Arg through inert C-H bond activation, selective C-C bond cleavage, cyclization-based alcohol dehydrogenation, and amidohydrolysis-associated linearization.


Subject(s)
Fungal Proteins/biosynthesis , Fusarium/metabolism , Oligopeptides/biosynthesis , Virulence Factors/biosynthesis , Amidohydrolases/metabolism , Carbon-Carbon Lyases/metabolism , Cytochrome P-450 Enzyme System/metabolism , Fungal Proteins/genetics , Fusarium/genetics , Multigene Family , Oligopeptides/genetics , Virulence Factors/genetics
20.
Small ; 17(18): e2007746, 2021 May.
Article in English | MEDLINE | ID: mdl-33738971

ABSTRACT

Organic solar cells (OSCs) can achieve greatly improved power conversion efficiency (PCE) by incorporating suitable additives in active layers. Their structure design often faces the challenge of operation generality for more binary blends. Herein, a simple dithieno[3,2-b:2',3'-d]pyrrole-rhodanine molecule (DR8) featuring high compatibility with polymer donor PM6 is developed as a cost-effective third component. By employing classic ITIC-like ITC6-4Cl and Y6 as model nonfullerene acceptors (NFAs) in PM6-based binary blends, DR8 added PM6:ITC6-4Cl blends exhibit significantly promoted energy transfer and exciton dissociation. The PM6:ITC6-4Cl:DR8 (1:1:0.1, weight ratio) OSCs contribute an exciting PCE of 14.94% in comparison to host binary devices (13.52%), while PM6:Y6:DR8 (1:1.2:0.1) blends enable 16.73% PCE with all simultaneously improved photovoltaic parameters. To the best of the knowledge, this performance is among the best for ternary OSCs with simple small molecular third components in the literature. More importantly, DR8-added ternary OSCs exhibit much improved device stability against thermal aging and light soaking over binary ones. This work provides new insight on the design of efficient third components for OSCs.

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