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1.
Environ Sci Technol ; 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724064

RESUMO

Adding conductive materials to the cathode of a microbial electrochemical system (MES) can alter the route of interspecies electron transfer and the kinetics of reduction reactions. We tested reductive dechlorination of γ-hexachlorocyclohexane (γ-HCH), along with CH4 production, in MES systems whose cathodes were coated with conductive magnetite nanoparticles (NaFe), biochar (BC), magnetic biochar (FeBC), or anti-conductive silica biochar (SiBC). Coating with NaFe enriched electroactive microorganisms, boosted electro-bioreduction, and accelerated γ-HCH dechlorination and CH4 production. In contrast, BC only accelerated dechlorination, while FeBC only accelerated methanogenesis, because of their assemblies of functional taxa that selectively transferred electrons to those electron sinks. SiBC, which decreased electro-bioreduction, yielded the highest CH4 production and increased methanogens and the mcrA gene. This study provides a strategy to selectively control the distribution of electrons between reductive dechlorination and methanogenesis by adding conductive or anti-conductive materials to the MES's cathode. If the goal is to maximize dechlorination and minimize methane generation, then BC is the optimal conductive material. If the goal is to accelerate electro-bioreduction, then the best addition is NaFe. If the goal is to increase the rate of methanogenesis, adding anti-conductive SiBC is the best.

2.
Adv Mater ; : e2209239, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688343

RESUMO

Chelate phosphine oxide ligand (9,9-dimethyl-9H-xanthene-4,5-diyl) bis (diphenylphosphineoxide) (XPO) is prepared as a neutral ligand to synthesize complex Nd (TTA)3 (XPO) (TTA = 2-thenoyltrifluoroacetone). An appropriate energy gap between the XPO and TTA ligands, which can support two additional energy transfer routines from the first excited triplet state (T1 ) energy level of the XPO to that of the TTA, improves energy transfer in the Nd complex. Based on intramolecular energy transfer mechanism, optical gains at 1.06 and 1.31 µm are demonstrated in Nd (TTA)3 (XPO)-doped polymer waveguides with the excitation of low-power light-emitting diodes (LEDs) instead of semiconductor lasers as pump sources. Using the vertical top-pumping mode of a 365 nm LED, relative gains of 22.5 and 8.4 dB cm-1 are obtained at 1.06 and 1.31 µm, respectively, in a 0.2-cm long embedded waveguide with a cross-section of 8 × 5 µm2 . The active core layer is Nd (TTA)3 (XPO)-doped SU-8 polymer. Moreover, relative gains are achieved in evanescent-field waveguide with a cross-section of 6 × 4 µm2 . The 21.0 and 5.6 dB cm-1 relative gains are achieved at 1.06 and 1.31 µm, respectively, with a net gain of 13.8 ± 0.3 dB cm-1 obtained at 1.06 µm in a 0.9-cm long SU-8 waveguide with Nd (TTA)3 (XPO)-doped polymethylmethacrylate as upper cladding. This article is protected by copyright. All rights reserved.

3.
Chem Sci ; 14(2): 338-344, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36687340

RESUMO

Carbyne with one-dimensional sp-hybridized carbon atoms is the third form of carbon following diamond and graphite. Although carbyne nanocrystals have been synthesized, little is known about its structural details. Here, we report experimental evidence of the kinked structure of carbon chains and interchain van der Waals interaction of carbyne nanocrystals by near edge X-ray absorption fine structure (NEXAFS) spectroscopy. We measure the resonance and the feature peaks of the kinked configuration of carbon chains and the van der Waals interaction between chains of carbyne nanocrystals using NEXAFS spectroscopy. We also perform theoretical calculations of density functional theory and simulations based on the super-cell core-hole method for carbon K-edge NEXAFS. The theoretical results are in good agreement with the experimental measurements, which demonstrates that carbyne nanocrystals are van der Waals crystals with kinked chains as structural units. Note that the peak at 288.5 eV in the simulated NEXAFS spectrum implies the possible presence of hydrogen-terminated kinks or hydrogen-terminated chains in carbyne nanocrystals, which clarifies the understanding of the C-H bond in carbyne nanocrystals. These findings are enlightening and significant for pursuing physics and potential applications of carbyne.

4.
Chemosphere ; 314: 137729, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36603676

RESUMO

The role of biochar as the redox catalyst in the removal of reductive pollutants from soil and water system has been extensively studied recently, but there is still a lack of qualitative description of its specific mechanisms in redox processes. In this study, the mechanism of biochar in the transformation process of γ-HCH under anoxic condition was revealed by the compound-specific isotope analysis. The concentration and carbon isotopic composition (δ13C) of γ-HCH were detected in the treatments with different initial concentrations of γ-HCH and biochar materials with different redox properties and varied doses. The surface functional groups and electrochemical properties of biochar before and after the reaction were also characterized. The addition amount of biochar could affect the reduction of γ-HCH concentration, which were 59.1%, 34.6% and 22.4% in treatments with the addition of 5%, 1% and 0.2% biochar, respectively. Meanwhile, the δ13C value of γ-HCH also increased from -26.6 ± 0.2‰ to -23.8 ± 0.2‰ with the addition amount of biochar, especially in the treatment with 5% biochar. As evidenced by X-ray diffraction analysis and electrochemical analysis, biochar promoted the adsorption and transformation of γ-HCH simultaneously, and the oxygen-containing functional groups on the surface of biochar played an important role in the redox process. The isotopic fractionation value (εC) of γ-HCH transformation by biochar was first reported as -3.4 ± 0.4‰. The results will enable the quantitative description of the transformation degree of organic pollutants induced by biochar, and provide a new approach for evaluating the in-situ remediation effects of biochar in a complex environment.


Assuntos
Poluentes Ambientais , Hexaclorocicloexano , Hexaclorocicloexano/análise , Biodegradação Ambiental , Isótopos de Carbono/análise , Poluentes Ambientais/análise
5.
Signal Transduct Target Ther ; 8(1): 14, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36617552

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Identification of the underlying mechanism of HCC progression and exploration of new therapeutic drugs are urgently needed. Here, a compound library consisting of 419 FDA-approved drugs was taken to screen potential anticancer drugs. A series of functional assays showed that desloratadine, an antiallergic drug, can repress proliferation in HCC cell lines, cell-derived xenograft (CDX), patient-derived organoid (PDO) and patient-derived xenograft (PDX) models. N-myristoyl transferase 1 (NMT1) was identified as a target protein of desloratadine by drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) assays. Upregulation of NMT1 expression enhanced but NMT1 knockdown suppressed tumor growth in vitro and in vivo. Metabolic labeling and mass spectrometry analyses revealed that Visinin-like protein 3 (VILIP3) was a new substrate of NMT1 in protein N-myristoylation modification, and high NMT1 or VILIP3 expression was associated with advanced stages and poor survival in HCC. Mechanistically, desloratadine binds to Asn-246 in NMT1 and inhibits its enzymatic activity, disrupting the NMT1-mediated myristoylation of the VILIP3 protein and subsequent NFκB/Bcl-2 signaling. Conclusively, this study demonstrates that desloratadine may be a novel anticancer drug and that NMT1-mediated myristoylation contributes to HCC progression and is a potential biomarker and therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Ácido Mirístico/metabolismo , Processamento de Proteína Pós-Traducional
6.
Phytomedicine ; 109: 154548, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610154

RESUMO

BACKGROUND: Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins. OBJECTIVE: In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models. METHODS: The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans (C. elegans) DA2123 strain. The neuroprotective effects of the identified autophagy enhancers were evaluated in multiple C. elegans ND models by measuring Aß-, Tau-, α-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 × Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo. Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway. RESULTS: The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited Aß, α-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans, while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans. Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 × Tg-AD mice. CONCLUSION: FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy. These findings offer a new and reliable strategy for screening autophagy inducers, as well as providing evidence that FHME may serve as a possible therapeutic agent for NDs.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Camundongos , alfa-Sinucleína/metabolismo , Caenorhabditis elegans , Doenças Neurodegenerativas/tratamento farmacológico , Animais Geneticamente Modificados , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Autofagia , Doença de Alzheimer/tratamento farmacológico
7.
Bioact Mater ; 24: 535-550, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36714332

RESUMO

Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites. Among these, the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones, and thus are highly desired. The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature. In this review, we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine. We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts. As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites, the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites. The inorganic particles that are covered in this review are categorised into two broad types (1) solid (e.g., calcium phosphate, hydroxyapatite, etc.) and (2) porous particles (e.g., mesoporous silica, porous silicon etc.), which are elaborated in detail with recent examples. The review also covers other new types of inorganic material (e.g., 2D inorganic materials, clays, etc.) based polymer composites for tissue engineering applications. Lastly, we provide our expert analysis and opinion of the field focusing on the limitations of the currently used inorganic/organic combination composites and the immense potential of new generation of composites that are in development.

8.
Bioorg Chem ; 132: 106349, 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36716644

RESUMO

Photosensitizers play a key role in bioimaging and photodynamic therapy (PDT) of cancer. However, conventional photosensitizers usually do not achieve the desired efficacy in PDT due to their poor photostability, targeting ability, and responsiveness. Herein, we designed a series of photosensitizers with aggregation-induced emission (AIE) effect using benzothiazole- triphenylamine (BZT-triphenylamine) as the parent nucleus. The synthesized compound SIN ((E)-2-(4-(diphenylamino)styryl)-3-(4-iodobutyl)benzo[d]thiazol-3-ium) exhibits good biocompatibility, photostability, and bright emission in the near-infrared range (600-800 nm). The fluorescence emission intensity is responsive to viscosity, with significant fluorescence enhancement (48 times) and high fluorescence quantum yield (4.45 %) at high viscosity. Moreover, SIN has particular lysosome targeting properties with a Pearson correlation coefficient (PCC) of 0.97 and has good 1O2 generation ability under white light irradiation, especially in a weak acidic environment. Thus, SIN can realize good bioimaging ability and photodynamic therapeutic efficacy under the highly viscous and weakly acidic environment of lysosomes in the tumor cells. This study indicates that SIN has potential as a multifunctional organic photosensitizer for bioimaging and PDT of tumor.

9.
Anal Biochem ; 665: 115051, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36681139

RESUMO

Home-acquired pneumonia is a common infection in nursing at the emergency department and the incidence increased in recent years as population ages. Pseudomonas aeruginosa (P. aeruginosa) is common in nursing home residents and in hospital infections, remaining a huge threaten to human health. Therefore, it is essential to develop a novel and portable P. aeruginosa analysis method for the early diagnosis and nursing of home-acquired pneumonia. Few of the established approach enables isolation and synchronous quantification of P. aeruginosa. Herein, we propose a novel platform by integrating aptamer recognition-based aggregation of target bacteria and personal glucose meters (PGMs) based readout of results. Based on this, the method enables low-speed centrifugation (5000 rpm) based isolation and personal glucose meter assisted synchronous quantification of P. aeruginosa. In addition, the chain displacement process is included for signal amplification that endows the method a wide detection range of six orders of magnitudes and a low limit of detection of 36 cfu/mL. Besides the sensitivity, the approach also shows a good selectivity to P. aeruginosa detection, making it a promising tool to report P. aeruginosa based home-acquired pneumonia and guiding the early-nursing of P. aeruginosa infections at the emergency department.

10.
J Colloid Interface Sci ; 636: 42-54, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36621128

RESUMO

A method for simultaneous labeling and multicolor fluorescence imaging of different hepatic immune cells below freezing point is established based on quantum dots. In the experiment, carbon quantum dots with emission wavelength of 435 nm, CdTe@CdS quantum dots at 542 nm and CdSe@ZnS quantum dots at 604 nm are synthesized respectively, it is found that when the mass fractions of KCl (as antifreeze) are 12 %, 14 %, and 12 %, respectively, the three quantum dot dispersion systems remain liquid state at -20 °C. After they are conjugated with the corresponding secondary antibodies, agarose gel electrophoresis, circular dichroism and capillary electrophoresis confirm the effectiveness of conjugation. By indirect immunofluorescence method, the above three quantum dot fluorescent probes are used to simultaneously and specifically target a variety of liver immune cells, and the multi-color simultaneous imaging of different liver immune cells is realized under the same excitation wavelength, it is found that hepatic macrophages are arranged radially in the liver, hepatic stellate cells present punctate distribution, and hepatic sinusoidal endothelial cells present circular distribution, which is consistent with the results of H&E staining and ultrathin section TEM. This study provides an important technical means for elucidating the structure and function of the liver.

11.
NPJ Biofilms Microbiomes ; 9(1): 1, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596826

RESUMO

Tibial dyschondroplasia (TD) with multiple incentives is a metabolic skeletal disease that occurs in fast-growing broilers. Perturbations in the gut microbiota (GM) have been shown to affect bone homoeostasis, but the mechanisms by which GM modulates bone metabolism in TD broilers remain unknown. Here, using a broiler model of TD, we noted elevated blood glucose (GLU) levels in TD broilers, accompanied by alterations in the pancreatic structure and secretory function and damaged intestinal barrier function. Importantly, faecal microbiota transplantation (FMT) of gut microbes from normal donors rehabilitated the GM and decreased the elevated GLU levels in TD broilers. A high GLU level is a predisposing factor to bone disease, suggesting that GM dysbiosis-mediated hyperglycaemia might be involved in bone regulation. 16S rRNA gene sequencing and short-chain fatty acid analysis revealed that the significantly increased level of the metabolite butyric acid derived from the genera Blautia and Coprococcus regulated GLU levels in TD broilers by binding to GPR109A in the pancreas. Tibial studies showed reduced expression of vascular regulatory factors (including PI3K, AKT and VEFGA) based on transcriptomics analysis and reduced vascular distribution, contributing to nonvascularization of cartilage in the proximal tibial growth plate of TD broilers with elevated GLU levels. Additionally, treatment with the total flavonoids from Rhizoma drynariae further validated the improvement in bone homoeostasis in TD broilers by regulating GLU levels through the regulation of GM to subsequently improve intestinal and pancreatic function. These findings clarify the critical role of GM-mediated changes in GLU levels via the gut-pancreas axis in bone homoeostasis in TD chickens.


Assuntos
Microbioma Gastrointestinal , Osteocondrodisplasias , Animais , Osteocondrodisplasias/terapia , Osteocondrodisplasias/veterinária , Osteocondrodisplasias/metabolismo , Tiram , Galinhas , RNA Ribossômico 16S , Homeostase , Glucose
12.
Small ; : e2207615, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36605013

RESUMO

Next-generation imaging systems require photodetectors with high sensitivity, polarization sensitivity, miniaturization, and integration. By virtue of their intriguing attributes, emerging 2D materials offer innovative avenues to meet these requirements. However, the current performance of 2D photodetectors is still below the requirements for practical application owing to the severe interfacial recombination, the lack of photoconductive gain, and insufficient photocarrier collection. Here, a tunneling dominant imaging photodetector based on WS2 /Te heterostructure is reported. This device demonstrates competitive performance, including a remarkable responsivity of 402 A W-1 , an outstanding detectivity of 9.28 × 1013 Jones, a fast rise/decay time of 1.7/3.2 ms, and a high photocurrent anisotropic ratio of 2.5. These outstanding performances can be attributed to the type-I band alignment with carrier transmission barriers and photoinduced tunneling mechanism, allowing reduced interfacial trapping effect, effective photoconductive gains, and anisotropic collection of photocarriers. Significantly, the constructed photodetector is successfully integrated into a polarized light imaging system and an ultra-weak light imaging system to illustrate the imaging capability. These results suggest the promising application prospect of the device in future imaging systems.

13.
Curr Res Food Sci ; 6: 100421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36605465

RESUMO

Kojic acid-aromatic aldehydes 6a-6m were synthesized and screened for their anti-tyrosinase activities. These compounds showed potently anti-tyrosinase activity with IC50 values in the range of 5.32 ± 0.23 to 77.89 ± 3.36 µM compared with kojic acid (IC50 = 48.05 ± 3.28 µM). Thereinto, compound 6j with 3-fluorine and 4-aldehyde substitutions showed the most potent anti-tyrosinase activity (IC50 = 5.32 ± 0.23 µM). Enzyme kinetic study revealed that 6j is a noncompetitive tyrosinase inhibitor (Ki = 2.73 µM). The action mechanism of 6j was evaluated by fluorescence spectrum quenching, molecular docking, 1H NMR titration, etc. The anti-browning assay showed that 6j could delay the enzymatic browning of fresh-cut apples. Besides, the cell viability assay proved that 6j had a good safety profile as an anti-browning agent. Hence, these results identify a new class of anti-tyrosinase and anti-browning agents for further investigation in the food industry.

14.
ACS Appl Mater Interfaces ; 15(1): 1891-1902, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36591955

RESUMO

Metal oxides, as promising electrode materials for sodium-ion batteries, usually need to be formed by exposure to oxygen, which usually thermally corrodes the carbon material with which they are compounded, reducing their flexibility and electrical conductivity. Herein, we present for the first time a preoxidation-assisted mechanism to prepare bismuth oxide and carbon nanofibers (Bi2O3@C-NFs) by electrospinning, using Bi2S3 nanorods as multifunctional templates. The bismuth could be oxidized by C═O bonds formed through the cyclization reaction in the high-temperature calcination process, effectively avoiding thermal corrosion of carbon in oxygen atmosphere at high temperature. More importantly, the uniformly distributed Bi2O3 nanodots and longitudinal tunnels are formed inside the S- and N-doped carbon nanofibers with the continuous diffusion of Bi generated from the decomposition of Bi2S3 nanorods and the conversion to Bi─O bonds with C═O bonds being broken. Benefiting from the structural and composition merits arising from preoxidation, Bi2O3@C-NFs self-supporting anodes show high specific capacity (439 mAh g-1 at 0.05 A g-1), superior rate performance (243 mAh g-1 at a current density of 20 A g-1), and outstanding cycling stability (211 mAh g-1 after 2000 cycles at 5 A g-1). The effective combination of the well-established electrospinning technology and the preoxidation assisted mechanism provides a new way for the preparation of metal oxide and carbon composites.

15.
FASEB J ; 37(2): e22753, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36624683

RESUMO

Fibroblasts are stromal cells abundant throughout tissues, including the lungs. Fibroblasts are integral coordinators of immune cell recruitment through chemokine secretion. Circadian rhythms direct the recruitment of immune cells to the lung, which in turn impacts response to infection and survival. Although fibroblasts display robust circadian rhythms, the contribution of the fibroblast molecular clock to lung-specific migration of immune cells and recruitment remains to be established. Mice challenged intranasally with lipopolysaccharide (LPS) at dusk showed increased expression of the pro-inflammatory cytokine IL-1ß and chemokine CXCL5 in the lung, which was accompanied by increased neutrophil recruitment. Primary lung fibroblasts with knockdown of the core clock gene Bmal1 and immortalized Bmal1-/- lung fibroblasts also displayed increased Cxcl5 expression under IL-1ß stimulation. Conditioned media obtained from IL-1ß-stimulated Bmal1-/- immortalized fibroblasts-induced greater neutrophil migration compared with Bmal1+/+ lung fibroblast controls. Phosphorylation of the NF-κB subunit, p65, was enhanced in IL-1ß-stimulated Bmal1-/- lung fibroblasts, and pharmacological inhibition of NF-κB attenuated the enhanced CXCL5 production and neutrophil recruitment observed in these cells. Collectively, these results demonstrate that Bmal1 represses NF-κB activity in lung fibroblasts to control chemokine expression and immune cell recruitment during an inflammatory response.


Assuntos
Fatores de Transcrição ARNTL , NF-kappa B , Animais , Camundongos , Infiltração de Neutrófilos , Fatores de Transcrição ARNTL/genética , Fibroblastos , Movimento Celular , Ritmo Circadiano
16.
Forensic Sci Int ; 343: 111563, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36630768

RESUMO

Sudden cardiac death (SCD) is the leading cause of natural death worldwide which is responsible for almost half of all heart disease deaths, making it a substantial public health problem. Previous epidemiological studies from different countries have demonstrated the significant SCD incident difference rate between males and females. Besides environmental and social effects, differential genetic architecture also underlines the SCD incidence discrepancy. To this end, the functional (CAG)n repeat polymorphism within Androgen Receptor (AR) gene was analyzed to evaluate its associations with SCD originated from coronary artery disease (SCD-CAD) susceptibility in Chinese populations using 182 SCD-CAD cases and 564 healthy controls. At allelic level, the (CAG)26 allele conferred a lower SCD-CAD risk in males (adjusted odds ratio [OR] = 0.428; 95% confidence interval [CI] = 0.254, 0.915; P = 0.023). On the contrary, the (CAG)26 allele was reversely associated with a higher SCD-CAD risk in females (OR = 2.581; 95% CI = 0.944, 7.056; P = 0.057). Further cutoff strategy analysis revealed that those male subjects carrying shorter allele (≤26 repeats) had significantly lower SCD-CAD risk (OR = 0.343; 95% CI = 0.221, 0.531; P = 8.1653e-7). Additionally, an allele-dependent SCD risk tendency was observed in male subjects. Specifically, compared with males carrying allele longer than 26 repeats, the SCD-CAD risk (OR value) for male subjects carrying shorter alleles (from 25 to 21) gradually increased from 0.437 to 0.533, indicating the (CAG)26 allele of the repeat polymorphism may be the watershed in male SCD etiology. Lastly, the length variations associated with multiple phenotypes were also summarized. Collectively, our results revealed for the first time that the (CAG)n repeat polymorphism within the AR gene was associated with SCD-CAD risk in Chinese populations with sex discrepancy, proposing a new candidate genetic marker for molecular diagnosis of SCD-CAD. Furthermore, a sex-dependent SCD-CAD risk stratification and prevention approach was encouraged. Further studies with more female samples were warranted to validate our findings.

17.
Biomed Res Int ; 2023: 2763320, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36647546

RESUMO

Objective: Ischemia reperfusion injury greatly damages liver function and deteriorates the prognosis of patients undergoing partial hepatectomy. This study is to compare the protective efficiency of direct and remote ischemic preconditioning (DIPC and RIPC) on ischemia reperfusion injury of the liver in patients undergoing partial hepatectomy. Methods: 90 patients scheduled for partial hepatectomy were enrolled and randomly divided into control (n = 30), DIPC (n = 30), and RIPC (n = 30) groups. Baseline and surgery characteristics were collected, and ischemic preconditioning methods were carried out. Intraoperative hemodynamics, liver function and liver reserve capacity, oxidative stress, and inflammatory responses were measured, and the incidence of postoperative adverse reactions was calculated finally. Results: 10 patients were excluded from the study, and finally, the eligible patients in three groups were 27, 28, and 25, separately. No significant differences were observed in baseline and surgery characteristics among the three groups. SBP and DBP were significantly higher after hepatic portal vein occlusion while they were significantly lower after surgery in the DIPC and RIPC groups compared with that in the control group, SBP and DBP were of great fluctuation at different time points in the control group while they showed much more stabilization in the DIPC and RIPC groups. ALT, AST, and TBIL were significantly decreased on days 1, 3, and 5 after surgery, and ICG R15 was significantly decreased while ICG K value and EHBF were significantly increased on day 1 after surgery in the DIPC and RIPC groups compared with that in the control group. Moreover, antioxidant enzyme SOD was increased, and inflammatory factors TNF-α and IL-1ß were decreased 24 hours after surgery in the DIPC and RIPC groups compared with that in the control group. DIPC and RIPC also decreased hospital stays and the incidence of nausea, vomiting, and hypertension. Conclusion: DIPC and RIPC both alleviated ischemia reperfusion injury of the liver and reduced perioperative complications with similar protective efficiency in patients undergoing partial hepatectomy.


Assuntos
Precondicionamento Isquêmico , Hepatopatias , Traumatismo por Reperfusão , Humanos , Hepatectomia/efeitos adversos , Precondicionamento Isquêmico/métodos , Traumatismo por Reperfusão/prevenção & controle
18.
Int Immunopharmacol ; 115: 109681, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36634416

RESUMO

BACKGROUND: Prostaglandins (PGs) are bioactive lipid mediators derived from the nuclear and plasma membranes via the cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism. PGs bridge the interactions between various immunomodulatory cells in allergic rhinitis (AR) and are considered key players in regulating pro-inflammatory and anti-inflammatory responses. AA conversion to PGs involves rate-limiting enzymes that may be blocked by statins. The mechanisms by which statins regulate these enzymes in AR remain unclear. We investigated the effects of oral atorvastatin on PGs production in AR. METHODS: An ovalbumin-induced AR rat model was constructed and the changes in nasal symptom score and nasal mucosa histopathological characteristics of AR rats under different atorvastatin doses were assessed. qRT-PCR, western blotting, and immunofluorescence were used to detect the mRNA and protein expression levels of rate-limiting enzymes and downstream molecules of AA metabolism in the nasal mucosa and liver. RESULTS: Oral atorvastatin significantly alleviated symptoms and eosinophil infiltration in the nasal mucosa, inhibited goblet cell hyperplasia and mast cell recruitment, and decreased mucus secretion in AR rats. Increasing atorvastatin dose increased the anti-inflammatory effects. High-dose atorvastatin inhibited upregulation of the inflammatory mediator PGD2 in the nasal mucosa of AR rats. Compared to the control group, the mRNA and protein expression of the rate-limiting enzymes COX-2, PGDS, and PGES in AA metabolism in the AR group were upregulated but downregulated after the oral administration of high-dose atorvastatin. Atorvastatin also showed dose-dependent inhibition of ERK1/2 and downstream NF-κB phosphorylation in the nasal mucosa and liver of AR rats. CONCLUSIONS: Atorvastatin inhibited allergic inflammation and attenuated AR nasal symptoms by downregulating PGD2 and rate-limiting enzyme expression in PGD2 biosynthesis, possibly by blocking the RAS/ERK/NF-κB signaling pathway.

19.
EBioMedicine ; 88: 104438, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36681000

RESUMO

BACKGROUND: Fungal keratitis (FK) is a leading cause of corneal blindness in developing countries due to poor clinical recognition and laboratory identification. Here, we aimed to identify the distinct clinical signature of FK and develop a diagnostic model to differentiate FK from other types of infectious keratitis. METHODS: We reviewed the electronic health records (EHRs) of all patients with suspected infectious keratitis in Beijing Tongren Hospital from January 2011 to December 2021. Twelve clinical signs of slit-lamp images were assessed by Lasso regression analysis and collinear variables were excluded. Three models based on binary logistic regression, random forest classification, and decision tree classification were trained for FK diagnosis and employed for internal validation. Independent external validation of the models was performed in a cohort of 420 patients from seven different ophthalmic centers to evaluate the accuracy, specificity, and sensitivity in real world. FINDINGS: Three diagnostic models of FK based on binary logistic regression, random forest classification, and decision tree classification were established and internal validation were achieved with the mean AUC of 0.916, 0.920, and 0.859, respectively. The models were well-calibrated by external validation using a prospective cohort including 210 FK and 210 non-FK patients from seven eye centers across China. The diagnostic model with the binary logistic regression algorithm classified the external validation dataset with a sensitivity of 0.907 (0.774, 1.000), specificity 0.899 (0.750, 1.000), accuracy 0.905 (0.805, 1.000), and AUC 0.903 (0.808, 0.998). INTERPRETATION: Our model enables rapid identification of FK, which will help ophthalmologists to establish a preliminary diagnosis and to improve the diagnostic accuracy in clinic. FUNDING: The Open Research Fund from the National Key Research and Development Program of China (2021YFC2301000) and the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing Tongren Hospital, Beihang University &Capital Medical University (BHTR-KFJJ-202001) supported this study.

20.
J Org Chem ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693384

RESUMO

We report visible light-induced cross-dehydrocoupling of 3-cyanocoumarins with unactivated aliphatic aldehydes for the direct synthesis of 4-acylated coumarins. Inexpensive and readily available (n-Bu)4NBr was used as a precursor of the hydrogen atom transfer (HAT) catalyst and [Ir(ppy)2(dtbbpy)PF6] as a photocatalyst. A variety of aldehydes including linear, branched, cyclic, and α,ß-unsaturated aliphatic aldehydes were suitable for this reaction yielding the desired acylated coumarin derivatives in 41-98% yields. This method provides a mild, atom-economical, and environmentally friendly synthetic route for the direct acylation of 3-cyanocoumarins. This is the first example so far of C-4 aliphatic acylation of coumarins.

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