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1.
J Biomater Sci Polym Ed ; : 1-15, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082937

RESUMO

Anticoagulation treatment for patients with high bleeding risk during hemodialysis is challenging. Contact between the dialysis membrane and the blood leads to protein adsorption and activation of the coagulation cascade reaction. Activated coagulation Factor X (FXa) plays a central role in thrombogenesis, but anticoagulant modification of the dialysis membrane is rarely targeted at FXa. In this study, we constructed an anticoagulant membrane using the polydopamine coating method to graft FXa inhibitors (apixaban and rivaroxaban) on the membrane surface. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) were used to characterize the membranes. The apixaban- and rivaroxaban-modified membranes showed lower water contact angles, decreased albumin protein adsorption, and suppressed platelet adhesion and activation compared to the unmodified PES membranes. Moreover, the modified membranes prolonged the blood clotting times in both the intrinsic and extrinsic coagulation pathways and inhibited FXa generation and complement activation, which suggested that the modified membrane enhanced biocompatibility and antithrombotic properties through the inhibition of FXa. Targeting FXa to design antithrombotic HD membranes or other blood contact materials might have great application potential.

2.
Front Endocrinol (Lausanne) ; 15: 1365283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988998

RESUMO

Background: Research has shown that gonadal hormones are involved in metabolic pathways relevant to metabolic syndrome (MetS). Nevertheless, no longitudinal study has been conducted on the association between SHBG and MetS in Chinese. The objective of our study was to determine whether there is any association between middle-aged and elderly males in China. Methods: A total of 531 eligible male subjects, aged above 40 years or older, without MetS at baseline, were recruited. Sex hormone binding globulin (SHBG), total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. A harmonized definition and recommended thresholds for the Chinese population were used to determine metabolic syndrome. Results: During 3.2 years of follow-up, 20.7% of subjects had developed MetS. Compared with the non-MetS group, subjects in the new-onset MetS group had significantly lower SHBG (43.5 nmol/L [28.8, 74.9] vs 53.7nmol/L [33.8, 115.0], P=0.0018), TT (18.1nmol/L [13.6-21.7] vs 19.5nmol/L[15.0-23.6], P=0.0204), and LH (5.13mIU/L [3.63-7.29] vs 5.87mIU/L [4.05-8.36]) at baseline. The incidence of MetS was decreased according to elevated SHBG quartiles (Q1:26.9%, Q2:22.7%, Q3:21.1%, Q4:12.1%, P for trend =0.0035), TT (Q1: 25.2%, Q2:23.7%, Q3: 17.3%, Q4: 16.7%, P for trend=0.0425), and LH (Q1:25.0%, Q2:21.8%, Q3: 21.8%, Q4: 14.3%, P for trend=0.0411). Compared with those in quartile 4, the OR[CI] of incident MetS for participants in Quartile 1 was 2.33[1.13-4.79] after multiple adjustments. But associations between incident MetS and different quartiles of LH, TT, and FSH were not observed after multiple adjustments. In the subgroup analyses, the significant association between SHBG level and Mets was detected in subjects over 60 years or older, with normal BMI, without insulin resistance, and with eGFR ≥90 mL/min per 1.73m2. Conclusion: Compared with TT, LH, and FSH, a lower level of SHBG is significantly related to the incidence of MetS among middle-aged and elderly males in China.


Assuntos
Hormônio Luteinizante , Síndrome Metabólica , Globulina de Ligação a Hormônio Sexual , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , China/epidemiologia , Estudos Prospectivos , Idoso , Globulina de Ligação a Hormônio Sexual/metabolismo , Globulina de Ligação a Hormônio Sexual/análise , Hormônio Luteinizante/sangue , Testosterona/sangue , Hormônio Foliculoestimulante/sangue , Hormônios Gonadais/sangue , Adulto , Seguimentos , Estudos Longitudinais , Estudos de Coortes
3.
Eur J Sport Sci ; 24(6): 834-845, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38874991

RESUMO

This study investigates whether exercise as a strategy for improving physical fitness at sea level also offers comparable benefits in the unique context of high altitudes (HA), considering the physiological challenges of hypoxic conditions. Overall, 121 lowlanders who had lived on the Tibetan Plateau for >2 years and were still living at HA during the measurements were randomly classified into four groups. Each individual of the low-intensity (LI), moderate-intensity (MI), and high-intensity (HI) groups performed 20 sessions of aerobic exercise at HA (3680 m) over 4 weeks, while the control group (CG) did not undergo any intervention. Physiological responses before and after the intervention were observed. The LI and MI groups experienced significant improvement in cardiopulmonary fitness (0.27 and 0.35 L/min increases in peak oxygen uptake [ V ˙ $\dot{\mathrm{V}}$ O2peak], both p < 0.05) after exercise intervention, while the hematocrit (HCT) remained unchanged (p > 0.05). However, HI exercise was less efficient for cardiopulmonary fitness of lowlanders (0.02 L/min decrease in V ˙ $\dot{\mathrm{V}}$ O2peak, p > 0.05), whereas both the HCT (1.74 %, p < 0.001) and glomerular filtration rate (18.41 mL/min, p < 0.001) increased with HI intervention. Therefore, LI and MI aerobic exercise, rather than HI, can help lowlanders in Tibet become more acclimated to the HA by increasing cardiopulmonary function and counteracting erythrocytosis.


Assuntos
Aclimatação , Altitude , Aptidão Cardiorrespiratória , Exercício Físico , Consumo de Oxigênio , Humanos , Tibet , Exercício Físico/fisiologia , Masculino , Adulto , Aclimatação/fisiologia , Consumo de Oxigênio/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Feminino , Hematócrito , Adulto Jovem , Taxa de Filtração Glomerular/fisiologia , Aptidão Física/fisiologia , Frequência Cardíaca/fisiologia
4.
Br J Nutr ; : 1-10, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634368

RESUMO

Malnutrition significantly hampers wound healing processes. This study aimed to compare the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) and Subjective Global Assessment (SGA) in diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers (DFU). GLIM criteria were evaluated for sensitivity (SE), specificity (SP), positive predictive value, negative predictive value and kappa (κ) against SGA as the reference. Modified Poisson regression model and the DeLong test investigated the association between malnutrition and non-healing ulcers over 6 months. This retrospective cohort study included 398 patients with DFU, with a mean age of 66·3 ± 11·9 years. According to SGA and GLIM criteria, malnutrition rates were 50·8 % and 42·7 %, respectively. GLIM criteria showed a SE of 67·3 % (95 % CI 60·4 %, 73·7 %) and SP of 82·7 % (95 % CI 76·6 %, 87·7 %) in identifying malnutrition, with a positive predictive value of 80·0 % and a negative predictive value of 71·1 % (κ = 0·50) compared with SGA. Multivariate analysis demonstrated that malnutrition, as assessed by SGA, was an independent risk factor for non-healing (relative risk (RR) 1·84, 95 % CI 1·45, 2·34), whereas GLIM criteria were associated with poorer ulcer healing in patients with estimated glomerular filtration rate ≥ 60 ml/min/1·73m2 (RR: 1·46, 95 % CI 1·10, 1·94). SGA demonstrated a superior area under the receiver's operating characteristic curve for predicting non-healing compared with GLIM criteria (0·70 (0·65-0·75) v. 0·63 (0·58-0·65), P < 0·01). These findings suggest that both nutritional assessment tools effectively identify patients with DFU at increased risk, with SGA showing superior performance in predicting non-healing ulcers.

5.
Am J Chin Med ; 52(2): 541-563, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38490807

RESUMO

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.


Assuntos
Melanoma , Humanos , Melanoma/tratamento farmacológico , Quercetina/farmacologia , Quercetina/uso terapêutico , Evasão Tumoral , Antígeno CD47/genética , RNA Mensageiro , Microambiente Tumoral
6.
Foods ; 13(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38540887

RESUMO

Deoxynivalenol (DON) is a harmful fungal toxin, and its contamination in wheat flour poses a food safety concern globally. This study proposes the combination of fluorescence hyperspectral imaging (FHSI) and qualitative discrimination methods for the detection of excessive DON content in wheat flour. Wheat flour samples were prepared with varying DON concentrations through the addition of trace amounts of DON using the wet mixing method for fluorescence hyperspectral image collection. SG smoothing and normalization algorithms were applied for original spectra preprocessing. Feature band selection was carried out by applying the successive projection algorithm (SPA), uninformative variable elimination (UVE), competitive adaptive reweighted sampling (CARS), and the random frog algorithm on the fluorescence spectrum. Random forest (RF) and support vector machine (SVM) classification models were utilized to identify wheat flour samples with DON concentrations higher than 1 mg/kg. The results indicate that the SG-CARS-RF and SG-CARS-SVM models showed better performance than other models, achieving the highest recall rate of 98.95% and the highest accuracy of 97.78%, respectively. Additionally, the ROC curves demonstrated higher robustness on the RF algorithm. Deep learning algorithms were also applied to identify the samples that exceeded safety standards, and the convolutional neural network (CNN) model achieved a recognition accuracy rate of 97.78% for the test set. In conclusion, this study demonstrates the feasibility and potential of the FHSI technique in detecting DON infection in wheat flour.

7.
Sci Total Environ ; 920: 171006, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38369137

RESUMO

Understanding the patterns and controls regulating nitrogen (N) transformation and its response to N enrichment is critical to re-evaluating soil N limitation or availability and its environmental consequences. Nevertheless, how climatic conditions affect nitrate dynamics and the response of gross N cycling rates to N enrichment in forest soils is still only rudimentarily known. Through collecting and analyzing 4426-single and 769-paired observations from 231 15N labeling studies, we found that nitrification capacity [the ratio of gross autotrophic nitrification (GAN) to gross N mineralization (GNM)] was significantly lower in tropical/subtropical (19%) than in temperate (68%) forest soils, mainly due to the higher GNM and lower GAN in tropical/subtropical regions resulting from low C/N ratio and high precipitation, respectively. However, nitrate retention capacity [the ratio of dissimilatory nitrate reduction to ammonium (DNRA) plus gross nitrate immobilization (INO3) to gross nitrification] was significantly higher in tropical/subtropical (86%) than in temperate (54%) forest soils, mainly due to the higher precipitation and GNM of tropical/subtropical regions, which stimulated DNRA and INO3. As a result, the ratio of GAN to ammonium immobilization (INH4) was significantly higher in temperate than in tropical/subtropical soils. Climatic rather than edaphic factors control heterotrophic nitrification rate (GHN) in forest soils. GHN significantly increased with increasing temperature in temperate regions and with decreasing precipitation in tropical/subtropical regions. In temperate forest soils, gross N transformation rates were insensitive to N enrichment. In tropical/subtropical forests, however, N enrichment significantly stimulated GNM, GAN and GAN to INH4 ratio, but inhibited INH4 and INO3 due to reduced microbial biomass and pH. We propose that temperate forest soils have higher nitrification capacity and lower nitrate retention capacity, implying a higher potential risk of N losses. However, tropical/subtropical forest systems shift from a conservative to a leaky N-cycling system in response to N enrichment.


Assuntos
Compostos de Amônio , Nitrogênio , Nitrogênio/análise , Nitratos/análise , Solo , Florestas
8.
Eur J Cancer Prev ; 33(3): 232-240, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37997905

RESUMO

OBJECTIVE: This study employed time series data to assess long-term changes in the burden of lung cancer (LC) caused by residential radon exposure, an important environmental risk factor, so as to develop evidence-based strategies for future public health management. METHODS: Based on the open data from the Global Burden of Disease (GBD 2019) database, we conducted an analysis of the residential radon exposure-caused LC mortality, disability-adjusted life years (DALYs), and corresponding crude rates and age-standardized rates (ASRs) for various age groups. We employed the employed age-period-cohort (APC) model to investigate the age, period, and cohort effects of the data, allowing us to discern the trends in LC disease burden attributable to radon exposure in residential settings over time. RESULTS: From 1990 to 2019, age-standardized mortality rates (ASMR) and age-standardized DALYs rates of LC caused by residential radon exposure in China demonstrated an overall increasing trend, with males higher than females. The CMR and crude DALYs rate for males were higher than those for females across all age groups. The APC analysis revealed that the local drift of LC death and DALYs rates in males and females showed a decreasing trend before 60 and an increasing trend after 60. CONCLUSION: The persistent presence of residential radon exposure as a crucial risk factor for LC underscores the need for public health authorities and policymakers to take more proactive measures to reduce radon exposure. Particularly, attention should be paid on the elderly population and male patients.


Assuntos
Neoplasias Pulmonares , Radônio , Feminino , Humanos , Masculino , Idoso , Neoplasias Pulmonares/epidemiologia , China , Saúde Pública , Anos de Vida Ajustados por Qualidade de Vida
9.
ACS Appl Mater Interfaces ; 16(1): 860-868, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38151338

RESUMO

Due to the strong Coulomb interaction, in most polymer photocatalysts, electron-hole pairs exist in the form of excitons rather than free charge carriers. The giant excitonic effect is a key obstacle to generating free charge carriers. Therefore, effectively regulating the exciton effect is the first step to achieving optimized carrier separation. Here, we used C-ring/g-C3N4 as the prototypical model system to design a photocatalyst with a Na-coordination-induced trap state. We demonstrate that the excitons can be effectively dissociated into charge carriers by combining with the trap state formed by Na doping sites. Encouragingly, signals from the dissociation of excitons into carriers were observed by ultrafast transient spectroscopy. Benefiting from the enhanced exciton dissociation, Na-C/CN displayed a H2O2 production rate of 17.4 mmol·L-1·h-1 with an apparent quantum efficiency up to 26.9% at 380 nm, which is much higher than many other g-C3N4-based photocatalysts. This work explains the effect of cation doping on the exciton-carrier behavior in polymers. Also, it provides a new way to regulate the exciton effect.

10.
Adv Mater ; 36(14): e2309298, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38146682

RESUMO

Solid-state sodium (Na) batteries (SSNBs) hold great promise but suffer from several major issues, such as high interfacial resistance at the solid electrolyte/electrode interface and Na metal dendrite growth. To address these issues, a piezoelectric interlayer design for an Na3Zr2Si2PO12 (NZSP) solid electrolyte is proposed herein. Two typical piezoelectric films, AlN and ZnO, coated onto NZSP function as interlayers designed to generate a local stress-induced field for alleviating interfacial charge aggregation coupling stress concentration and promoting uniform Na plating. The results reveal that the interlayer (ZnO) with matched modulus, high Na-adhesion, and sufficient piezoelectricity can provide a favorable interphase. Low interfacial resistances of 91 and 239 Ω cm2 are achieved for the ZnO layer at 30 and 0 °C, respectively, which are notably lower than those for bare NZSP. Moreover, steady Na plating/stripping cycles are rendered over 850 and 4900 h at 0 and 30 °C, respectively. The superior anodic performance is further manifested in an Na2MnFe(CN)6-based full cell which delivers discharge capacities of 125 mA h g-1 over 1600 cycles at 30 °C and 90 mA h g-1 over 500 cycles at 0 °C. A new interlayer-design insight is clearly demonstrated for SSNBs breaking low-temperature limits.

11.
Environ Pollut ; 335: 122370, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37586684

RESUMO

Converting natural forests to managed ecosystems generally increases soil nitrous oxide (N2O) emission. However, the pattern and underlying mechanisms of N2O emissions after converting tropical forests to managed plantations remain elusive. Hence, a laboratory incubation study was investigated to determine soil N2O emissions of four land uses including forest, eucalyptus, rubber, and paddy field plantations in a tropical region of China. The effect of soil carbon (C) and nitrogen (N) fractions on soil N2O emissions and related functional genes was also estimated. We found that the conversion of natural forests to managed forests significantly decreased soil N2O emissions, but the conversion to paddy field had no effect. Soil N2O emissions were controlled by both nitrifying and denitrifying genes in tropical natural forest, but only by nitrifying genes in managed forests and by denitrifying genes in paddy field. Soil total N, extractable nitrate, particulate organic C (POC), and hydrolyzable ammonium N showed positive relationship with soil N2O emission. The easily oxidizable organic C (EOC), POC, and light fraction organic C (LFOC) had positive linear correlation with the abundance of AOA-amoA, AOB-amoA, nirK, and nirS genes. The ratios of dissolved organic C, EOC, POC, and LFOC to total N rather than soil C/N ratio control soil N2O emissions with a quadratic function relationship, and the local maximum values were 0.16, 0.22, 1.5, and 0.55, respectively. Our results provided a new evidence of the role of soil C and N fractions and their ratios in controlling soil N2O emissions and nitrifying and denitrifying genes in tropical soils.


Assuntos
Carbono , Solo , Nitrogênio , Ecossistema , Microbiologia do Solo , Óxido Nitroso/análise
12.
MedComm (2020) ; 4(4): e317, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37457661

RESUMO

Although great advances have been made over the past decades, therapeutics for osteosarcoma are quite limited. We performed long-read RNA sequencing and tandem mass tag (TMT)-based quantitative proteome on osteosarcoma and the adjacent normal tissues, next-generation sequencing (NGS) on paired osteosarcoma samples before and after neoadjuvant chemotherapy (NACT), and high-throughput drug combination screen on osteosarcoma cell lines. Single-cell RNA sequencing data were analyzed to reveal the heterogeneity of potential therapeutic target genes. Additionally, we clarified the synergistic mechanisms of doxorubicin (DOX) and HDACs inhibitors for osteosarcoma treatment. Consequently, we identified 2535 osteosarcoma-specific genes and several alternative splicing (AS) events with osteosarcoma specificity and/or patient heterogeneity. Hundreds of potential therapeutic targets were identified among them, which showed the core regulatory roles in osteosarcoma. We also identified 215 inhibitory drugs and 236 synergistic drug combinations for osteosarcoma treatment. More interestingly, the multiomic analysis pointed out the pivotal role of HDAC1 and TOP2A in osteosarcoma. HDAC inhibitors synergized with DOX to suppress osteosarcoma both in vitro and in vivo. Mechanistically, HDAC inhibitors synergized with DOX by downregulating SP1 to transcriptionally modulate TOP2A expression. This study provided a comprehensive view of molecular features, therapeutic targets, and synergistic drug combinations for osteosarcoma.

13.
Adv Sci (Weinh) ; 10(27): e2302774, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37485585

RESUMO

Achieving satisfactory performance for a solid-state Na-metal battery (SSNMB) with an inorganic solid electrolyte (SE), especially under freezing temperatures, poses a challenge for stabilizing a Na-metal anode. Herein, this challenge is addressed by utilizing a Natrium super ionic conductor (NASICON) NASICON-type solid electrolyte, enabling the operation of a rechargeable SSNMB over a wide temperature range from -20 to 45 °C. The interfacial resistance at the Na metal/SE interface is only 0.4 Ω cm2 at 45 °C and remains below 110 Ω cm2 even at -20 °C. Remarkably, long-term Na-metal plating/stripping cycles lasting over 2000 h at -20 °C are achieved with minimal polarization voltages at 0.1 mA cm-2 . Further analysis reveals the formation of a uniform Na3- x Cax PO4 interphase layer at the interface, which significantly contributes to the exceptional interfacial performance observed. By employing a Na3 V1.5 Al0.5 (PO4 )3 cathode, the full battery system demonstrates excellent adaptability to low temperatures, exhibiting a capacity of 80 mA h g-1 at -20 °C over 50 cycles and retaining a capacity of 108 mAh g-1 (88.5% of the capacity at 45 °C) at 0 °C over 275 cycles. This research significantly reduces the temperature threshold for SSNMB operation and paves the way toward solid-state batteries suitable for all-season applications.

14.
Proteomics ; 23(18): e2200330, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37271885

RESUMO

Cardiovascular diseases (CVDs) are among the most morbid and deadly types of diseases worldwide, while the existing therapeutic approaches all have their limitations. Mouse heart undergoes a very complex postnatal developmental process, including the 1-week window in which cardiomyocytes (CMs) maintain relatively high cell activity. The underlying mechanism provides an attractive direction for CVDs treatment. Herein, we collected ventricular tissues from mice of different ages from E18.5D to P8W and performed iTRAQ-based quantitative proteomics to characterize the atlas of cardiac development. A total of 3422 proteins were quantified at all selected time points, revealing critical proteomic changes related to cardiac developmental events such as the metabolic transition from glycolysis to beta-oxidation. A cluster of significantly dysregulated proteins containing proteins that have already been reported to be associated with cardiac regeneration (Erbb2, Agrin, and Hmgb) was identified. Meanwhile, the peroxisome proliferator-activated receptor (PPAR) signaling pathway (Cpt1α, Hmgcs2, Plin2, and Fabp4) was also found specifically enriched. We further revealed that bezafibrate, a pan-activator of PPAR signaling pathway markedly enhanced H9C2 cardiomyocyte activity via enhancing Cpt1α expression. This work provides new hint that activation of PPAR signaling pathway could potentially be a therapeutic strategy for the treatment of CVDs.


Assuntos
Doenças Cardiovasculares , Miócitos Cardíacos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Animais Recém-Nascidos , Proteômica , Transdução de Sinais , Doenças Cardiovasculares/metabolismo
15.
Mol Ther Nucleic Acids ; 32: 879-895, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37273781

RESUMO

MicroRNAs (miRNAs) regulate various cellular functions, but their specific roles in the regulation of Leydig cells (LCs) have yet to be fully understood. Here, we found that the expression of miR-300-3p varied significantly during the differentiation from progenitor LCs (PLCs) to adult LCs (ALCs). High expression of miR-300-3p in PLCs inhibited testosterone production and promoted PLC proliferation by targeting the steroidogenic factor-1 (Sf-1) and transcription factor forkhead box O1 (FoxO1) genes, respectively. As PLCs differentiated into ALCs, the miR-300-3p expression level significantly decreased, which promoted testosterone biosynthesis and suppressed proliferation of ALCs by upregulating SF-1 and FoxO1 expression. The LH/METTL3/SMURF2/SMAD2 cascade pathway controlled miR-300-3p expression, in which luteinizing hormone (LH) upregulated SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) expression through methyltransferase like 3 (METTL3)-mediated Smurf2 N6-methyladenosine modification. The Smurf2 then suppressed miR-300 transcription by inhibiting SMAD family member 2 (SMAD2) binding to the promoter of miR-300. Notably, miR-300-3p was associated with an obesity-related testosterone deficiency in men and the inhibition of miR-300-3p effectively rescued testosterone deficiency in obese mice. These findings suggested that miR-300-3p plays a pivotal role in LC differentiation and function, and could be a promising diagnostic or therapeutic target for obesity-related testosterone deficiency.

16.
Int J Biol Macromol ; 239: 124326, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37011757

RESUMO

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in reproductive regulation in vertebrates. However, GnRH was rarely isolated and its function remains poorly characterized in invertebrates. The existence of GnRH in ecdysozoa has been controversial for a long. Here, we isolated and identified two GnRH-like peptides from brain tissues in Eriocheir sinensis. Immunolocalization showed that the presence of EsGnRH-like peptide in brain, ovary and hepatopancreas. Synthetic EsGnRH-like peptides can induce germinal vesicle breakdown (GVBD) of oocyte. Similar to vertebrates, ovarian transcriptomic analysis revealed a GnRH signaling pathway in the crab, in which most genes exhibited dramatically high expression at GVBD. RNAi knockdown of EsGnRHR suppressed the expression of most genes in the pathway. Co-transfection of the expression plasmid for EsGnRHR with reporter plasmid bearing CRE-luc or SRE-luc response element into 293T cells showed that EsGnRHR transduces its signal via cAMP and Ca2+ signaling transduction pathways. In vitro incubation of the crab oocyte with EsGnRH-like peptide confirmed the cAMP-PKA cascade and Ca2+ mobilization signaling cascade but lack of a PKC cascade. Our data present the first direct evidence of the existence of GnRH-like peptides in the crab and demonstrated its conserved role in the oocyte meiotic maturation as a primitive neurohormone.


Assuntos
Braquiúros , Hormônio Liberador de Gonadotropina , Animais , Feminino , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Oócitos/metabolismo , Ovário/metabolismo , Perfilação da Expressão Gênica , Transdução de Sinais , Braquiúros/genética
17.
ACS Appl Mater Interfaces ; 15(9): 11731-11740, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36821726

RESUMO

The Z-scheme heterojunction shows great potential in photocatalysis due to its superior carrier separation efficiency and strong photoredox properties. However, how to regulate the charge separation at the nanometric interface of heterostructures still remains a challenge. Here, we take g-C3N4 and MoS2 as models and design the Mo-N chemical bond, which connects exactly the CB of MoS2 and VB of g-C3N4. Thus, the Mo-N bond could act as an atomic-level interfacial "bridge" that provides a direct migration path of charge carriers between g-C3N4 and MoS2. Experiments confirmed that the Mo-N bond and the internal electric field promote greatly the photogenerated carrier separation. The optimized photocatalyst exhibits a high hydrogen evolution rate that is about 19.6 times that of the pristine bulk C3N4. This study demonstrates the key role of an atomic-level interfacial chemical bond design in heterojunctions and provides a new idea for the design of efficient catalytic heterojunctions.

18.
Small ; 18(45): e2204487, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36161766

RESUMO

Solid-state alkaline metal batteries are highly sought out for their improved energy density and security over the current lithium-ion batteries. However, their practical application is heavily hindered by the interfacial issues originating from the solid electrolyte/electrode mismatch. This work demonstrates that a CuO coating layer as an active interphase can thoroughly promote the intimate contact between a Na3 Zr2 Si2 PO12 solid electrolyte and a Na metal anode through an in situ conversion reaction. The resultant Cu/Na2 O matrix forms a mixed electron/ion conducting scaffold, which facilitates stable and homogeneous Na metal plating without dendrite formation. Moreover, the symmetric Na metal cell realizes impressively steady plating/stripping cycles for 5000 h even under a high current density of 0.3 mA cm-2 . The novelty is further manifested as a room-temperature solid-state Na metal full battery of Na3 V1.5 Al0.5 (PO4 )3 |CuO@NZSPO|Na is assembled and exhibits a highly reversible cyclability (99.85% coulombic efficiency and 99.0% capacity retention) under a charge/discharge rate of 5 C for 2250 cycles. This work effectively solves the interfacial issues at the Na metal/solid electrolyte interface and provides a convenient way toward high-performance solid-state Na metal batteries operated at room temperature.

19.
J Proteome Res ; 21(10): 2504-2514, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36066509

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) is a lethal hepatobiliary malignancy that arises from the epithelial cells of the intrahepatic bile ducts, accounting for approximately 10% of cholangiocarcinoma (CCA). According to the 2019 World Health Organization (WHO) classification of tumors of the digestive system, iCCA is divided into small-duct type (SD-type) and large-duct type (LD-type). However, it remains unknown which molecular events contribute to the disparity. To explore the proteomic characteristics of iCCA, we used an isobaric tag for relative and absolute quantitation (iTRAQ) based quantitative proteomics strategy to investigate stably dysregulated proteins in the SD-type and LD-type of iCCA tissues. Importantly, we found three glycolysis/gluconeogenesis-related enzymes, triosephosphate isomerize 1 (TPI1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and phosphoglycerate kinase 1 (PGK1), were significantly down-regulated in the LD-type iCCA, which were further confirmed by immunohistochemistry using tissue microarray. Moreover, we demonstrated that the knockdown of these three candidate proteins by siRNAs notably increased the ability of proliferation in two CCA cell lines (HuH28 and RBE), suggesting that effective down-regulation of the glycolysis/gluconeogenesis pathway might be an underlying novel mechanism contributing to the LD-type iCCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Gluconeogênese , Glicólise/genética , Humanos , Fosfoglicerato Quinase , Proteômica
20.
Phys Chem Chem Phys ; 24(31): 18722-18728, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35899833

RESUMO

We perform a theoretical exploration of quantum coherent control of enantio-selective state transfer (ESST) of chiral molecules with three rotational states connected by the a-type, b-type, and c-type components of the transition dipole moments. A pulse-area theorem based on a closed-loop three-level system is derived without applying the rotating-wave approximation and used to analytically design three linearly polarized microwave pulses with optimal amplitudes and phases. By utilizing two optimized microwaves to mix two excited rotational states into the maximal coherence, we find that the discrimination of enantiomers via ESST for chiral molecules can be achieved by controlling the delay time of the third optimized microwave pulse. We examine the robustness of such control schemes against the Rabi frequency and detuning errors and the environment effect through pure dephasing processes for practical applications. This work provides an alternative approach to analytically designing optimal control fields for quantum control of ESST by using complex pulse areas.

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