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1.
J Cell Mol Med ; 28(3): e18099, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38164021

RESUMO

Our previous study found that miR-26a alleviates aldosterone-induced tubulointerstitial fibrosis (TIF). However, the effect of miR-26a on TIF in diabetic kidney disease (DKD) remains unclear. This study clarifies the role and possible mechanism of exogenous miR-26a in controlling the progression of TIF in DKD models. Firstly, we showed that miR-26a was markedly decreased in type 2 diabetic db/db mice and mouse tubular epithelial cells (mTECs) treated with high glucose (HG, 30 mM) using RT-qPCR. We then used adeno-associated virus carrying miR-26a and adenovirus miR-26a to enhance the expression of miR-26a in vivo and in vitro. Overexpressing miR-26a alleviated the TIF in db/db mice and the extracellular matrix (ECM) deposition in HG-stimulated mTECs. These protective effects were caused by reducing expression of protease-activated receptor 4 (PAR4), which involved in multiple pro-fibrotic pathways. The rescue of PAR4 expression reversed the anti-fibrosis activity of miR-26a. We conclude that miR-26a alleviates TIF in DKD models by directly targeting PAR4, which may provide a novel molecular strategy for DKD therapy.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , Animais , Camundongos , Nefropatias Diabéticas/metabolismo , Fibrose , MicroRNAs/metabolismo , Receptores de Trombina
2.
Plant Cell Physiol ; 65(1): 95-106, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-37874689

RESUMO

The spatial separation of photosystems I and II (PSI and PSII) is thought to be essential for efficient photosynthesis by maintaining a balanced flow of excitation energy between them. Unlike the thylakoid membranes of plant chloroplasts, cyanobacterial thylakoids do not form tightly appressed grana stacks that enforce strict lateral separation. The coexistence of the two photosystems provides a ground for spillover-excitation energy transfer from PSII to PSI. Spillover has been considered as a pathway of energy transfer from the phycobilisomes to PSI and may also play a role in state transitions as means to avoid overexcitation of PSII. Here, we demonstrate a significant degree of energy spillover from PSII to PSI in reconstituted membranes and isolated thylakoid membranes of Thermosynechococcus (Thermostichus) vulcanus and Synechocystis sp. PCC 6803 by steady-state and time-resolved fluorescence spectroscopy. The quantum yield of spillover in these systems was determined to be up to 40%. Spillover was also found in intact cells but to a considerably lower degree (20%) than in isolated thylakoid membranes. The findings support a model of coexistence of laterally separated microdomains of PSI and PSII in the cyanobacterial cells as well as domains where the two photosystems are energetically connected. The methodology presented here can be applied to probe spillover in other photosynthetic organisms.


Assuntos
Synechocystis , Tilacoides , Tilacoides/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Fotossíntese , Complexo de Proteína do Fotossistema I/metabolismo , Synechocystis/metabolismo
3.
Anal Chem ; 96(1): 317-324, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38154037

RESUMO

Arc-induced electrospray ionization mass spectrometry (AESI-MS) was developed during which alternating current electrospray is simply achieved through the arc plasma. The AESI source exploits the arc's temperature and charge properties to generate aerosols consisting of charged microdroplets. The electrospray region, in which organic molecules are contained within microdroplets, partially overlaps with the arc plasma region. Guided by the electric field, these molecules undergo ionization, yielding ionic target analytes. AESI represents a soft ionization method that combines the mechanisms of atmospheric pressure chemical ionization and electrospray ionization, facilitating the ionization of analytes with wide ranging polarities. The precisely targeted spraying area enhances ion entry into the mass analyzer, thereby enabling excellent ionization efficiency. The AESI source exhibits several notable advantages over the electrospray ionization source, including an elevated but comparable level of active species concentrations and types, simplified mass spectra for direct amino acid analysis, high salt tolerance, versatile analysis of compounds with varying polarities, and reliable quantitative analysis of amino acids in complex matrices. Overall, AESI broadens the methodologies employed to generate microdroplets, providing a technological and scientific framework for creating distinctive electrospray ionization techniques.

4.
Acta Pharmacol Sin ; 45(5): 1032-1043, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38286833

RESUMO

It is well established that the synthesis of extracellular matrix (ECM) in mesangial cells is a major determinant of diabetic kidney disease (DKD). Elucidating the major players in ECM synthesis may be helpful to provide promising candidates for protecting against DKD progression. tRF3-IleAAT is a tRNA-derived fragment (tRF) produced by nucleases at tRNA-specific sites, which is differentially expressed in the sera of patients with diabetes mellitus and DKD. In this study we investigated the potential roles of tRFs in DKD. Db/db mice at 12 weeks were adapted as a DKD model. The mice displayed marked renal dysfunction accompanied by significantly reduced expression of tRF3-IleAAT and increased ferroptosis and ECM synthesis in the kidney tissues. The reduced expression of tRF3-IleAAT was also observed in high glucose-treated mouse glomerular mesangial cells. We administered ferrostatin-1 (1 mg/kg, once every two days, i.p.) to the mice from the age of 12 weeks for 8 weeks, and found that inhibition of the onset of ferroptosis significantly improved renal function, attenuated renal fibrosis and reduced collagen deposition. Overexpression of tRF3-IleAAT by a single injection of AAV carrying tRF3-IleAAT via caudal vein significantly inhibited ferroptosis and ECM synthesis in DKD model mice. Furthermore, we found that the expression of zinc finger protein 281 (ZNF281), a downstream target gene of tRF3-IleAAT, was significantly elevated in DKD models but negatively regulated by tRF3-IleAAT. In high glucose-treated mesangial cells, knockdown of ZNF281 exerted an inhibitory effect on ferroptosis and ECM synthesis. We demonstrated the targeted binding of tRF3-IleAAT to the 3'UTR of ZNF281. In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.


Assuntos
Nefropatias Diabéticas , Matriz Extracelular , Ferroptose , Animais , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Nefropatias Diabéticas/metabolismo , Matriz Extracelular/metabolismo , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Humanos , Células Mesangiais/metabolismo
5.
J Invertebr Pathol ; 203: 108067, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38278342

RESUMO

Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs.


Assuntos
Monoterpenos Cicloexânicos , Insetos , Rabditídios , Animais , Rabditídios/fisiologia
6.
Environ Geochem Health ; 46(4): 116, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478189

RESUMO

Ecological pollution caused by heavy metals released from sediments is a worldwide concern. However, the effect of changes in sediment speciation on their release of heavy metals has not been adequately reported. In this study, the research focused on Pb and Cr in the ice period of Wuliangsuhai. This study analyzed changes in the sediment speciation of Pb and Cr before and after a release experiment using four risk assessment methods while varying the temperature, pH, and salinity of the water column. The results indicated that the total concentration of Pb ranged from 11.17 to 24.25 mg/kg, while for Cr it ranged from 42.26 to 69.68 mg/kg. Both elements exhibited mild contamination. The release of Pb and Cr from sediments increases with increasing water temperature, mainly due to the conversion of the residual fraction of Pb to the Fe-Mn oxide fraction and Cr converting more residual fraction to the organic matter and sulfide fraction. The release of sediment Pb and Cr decreased with increasing pH, with Pb converting more acid extractable fraction to the residual fraction and Cr converting more organic matter and sulfide fraction to the residual fraction. In contrast, the release of Pb and Cr increased and then decreased with increasing salinity. For Pb, the acid extractable fraction was more susceptible to conversion to the residual fraction by environmental influences, whereas for Cr, the organic matter and sulfide fraction were susceptible to conversion to the residual fraction.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Lagos , Gelo , Chumbo , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Água , Medição de Risco , Sulfetos , China
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 662-670, 2024 May 20.
Artigo em Zh | MEDLINE | ID: mdl-38948267

RESUMO

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Modelos Logísticos , Feminino , Masculino , China/epidemiologia , Estudos de Coortes , Saúde Pública , Incidência
8.
Mol Med ; 29(1): 164, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049750

RESUMO

BACKGROUND: Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-ß-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. METHODS: To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. RESULTS: We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. CONCLUSIONS: Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.


L-BAIBA upregulates the expression of GPX4 and SLC7A11 by activating the AMPK/Nrf-2/GPX4/SLC7A11 signaling pathway, thereby protecting against I/R-induced increase in ROS and ferroptosis in the lung.


Assuntos
Ferroptose , Traumatismo por Reperfusão , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Camundongos Endogâmicos C57BL , Pulmão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
9.
Breast Cancer Res Treat ; 202(1): 117-127, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37541965

RESUMO

BACKGROUND: Inflammatory adipokines and cytokines play a pivotal role in linking obesity and breast cancer (BC) risk in women. We investigated the longitudinal associations between BMI change and trajectories of inflammatory biomarkers related to BC risk. METHODS: A longitudinal study was conducted among 442 Chinese women with 3-year repeated measures from 2019 to 2021. Plasma circulating inflammatory biomarkers related to BC risk, including adiponectin (ADP), resistin (RETN), soluble leptin receptor (sOB-R), insulin-like growth factor-binding protein-3 (IGFBP-3), and C-reactive protein (CRP), were examined annually. Linear mixed-effect models (LMM) were applied to investigate associations of time-varying BMI with trajectories of biomarkers. We additionally examined the modification effect of baseline BMI groups, menopausal status, and metabolic syndrome. RESULTS: BMI was associated with increased levels of RETN, CRP, sOB-R, and decreased levels of ADP at baseline. An increasing BMI rate was significantly associated with an average 3-year increase in RETN (ß = 0.019, 95% CI 0.004 to 0.034) and sOB-R (ß = 0.022, 95% CI 0.009 to 0.035), as well as a decrease in ADP (ß = - 0.006, 95% CI - 0.012 to 0.001). These associations persisted across different baseline BMI groups. An increasing BMI rate was significantly associated with an average 3-year increase in CRP levels among normal weight (ß = 0.045, 95% CI 0.001 to 0.088) and overweight (ß = 0.060, 95% CI 0.014 to 0.107) women. As BMI increased over time, a more remarkable decrease in ADP was observed among women with metabolic syndrome (ß = - 0.016, 95% CI - 0.029 to - 0.004) than those without metabolic syndrome at baseline. CONCLUSIONS: A higher increase rate of BMI was associated with poorer trajectories of inflammatory biomarkers related to BC risk. Recommendations for BMI reduction may benefit BC prevention in women, particularly for those with metabolic syndrome.


Assuntos
Neoplasias da Mama , Síndrome Metabólica , Feminino , Humanos , Leptina/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos Longitudinais , Índice de Massa Corporal , Biomarcadores , Proteína C-Reativa/metabolismo , Adiponectina
10.
Opt Express ; 31(14): 23693-23701, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37475448

RESUMO

The Brewster effect has been previously reported as an essential mechanism for terahertz (THz) wave sensing application. However, generally in a sensing application, a complex rotation apparatus is required for detecting the slight change in Brewster angle. Here, we propose a graphene-based Brewster angle device operating at a specific terahertz frequency capable of sensing the refractive index at a fixed incident angle. In other words, our sensing device could avoid the impact of Brewster angle shift and eliminate the need for high-precision rotating equipment, which is usually required in traditional sensing applications. The conversion from the refractive index to a Volt-level detectable voltage roots from the tunability of graphene's Fermi level in the external electrical field. A linear correlation between the output voltage and the background refractive index is observed and theocratically analyzed. Furthermore, we present the improvement of our device in terms of sensing range and sensitivity by adjusting the permittivity of the dielectric substrate. As a demonstration of our proposed device, a detection range of 1.1-2.4 and a sensitivity of 20.06 V/RIU for refractive index is achieved on a high-resistance silicon substrate operating at 0.3 THz.

11.
Theor Appl Genet ; 136(9): 206, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37672067

RESUMO

KEY MESSAGE: Two recessive powdery mildew resistance loci pmAeCIae8_2DS and pmAeCIae8_7DS from Aegilops tauschii were mapped and two synthesized hexaploid wheat lines were developed by distant hybridization. Wheat powdery mildew (Pm), one of the worldwide destructive fungal diseases, causes significant yield loss up to 30%. The identification of new Pm resistance genes will enrich the genetic diversity of wheat breeding for Pm resistance. Aegilops tauschii is the ancestor donor of sub-genome D of hexaploid wheat. It provides beneficial genes that can be easily transferred into wheat by producing synthetic hexaploid wheat followed by genetic recombination. We assessed the Pm resistance level of 35 Ae. tauschii accessions from different origins. Accession CIae8 exhibited high Pm resistance. Inheritance analysis and gene mapping were performed using F2 and F2:3 populations derived from the cross between CIae8 and a Pm susceptible accession PI574467. The Pm resistance of CIae8 was controlled by two independent recessive genes. Bulked segregate analysis using a 55 K SNP array revealed the SNPs were mainly enriched into genome regions, i.e. 2DS (13.5-20 Mb) and 7DS (4.0-15.5 Mb). The Pm resistance loci were named as pmAeCIae8_2DS and pmAeCIae8_7DS, respectively. By recombinant screening, we narrowed the pmAeCIae8_2DS into a 370-kb interval flanked by markers CINAU-AE7800 (14.89 Mb) and CINAU-AE20 (15.26 Mb), and narrowed the pmAeCIae8_7DS into a 260-kb interval flanked by markers CINAU-AE58 (4.72 Mb) and CINAU-AE25 (4.98 Mb). The molecular markers closely linked with the resistance loci were developed, and two synthesized hexaploid wheat (SHW) lines were produced. These laid the foundation for cloning of the two resistance loci and for transferring the resistance into common wheat.


Assuntos
Aegilops , Genes Recessivos , Melhoramento Vegetal , Triticum , Mapeamento Cromossômico , Poaceae
12.
J Org Chem ; 88(4): 2214-2220, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36655882

RESUMO

This paper describes the synthesis and stereochemical determination of Novo29 (clovibactin), a new peptide antibiotic that is related to teixobactin and is active against Gram-positive bacteria. Novo29 is an eight-residue depsipeptide that contains the noncanonical amino acid hydroxyasparagine of hitherto undetermined stereochemistry in a macrolactone ring. The amino acid building blocks Fmoc-(2R,3R)-hydroxyasparagine-OH and Fmoc-(2R,3S)-hydroxyasparagine-OH were synthesized from (R,R)- and (S,S)-diethyl tartrate. Novo29 and epi-Novo29 were then prepared by solid-phase peptide synthesis using these building blocks. Correlation with an authentic sample of Novo29 through 1H NMR spectroscopy, LC-MS, and in vitro antibiotic activity established that Novo29 contains (2R,3R)-hydroxyasparagine. X-ray crystallography reveals that epi-Novo29 adopts an amphiphilic conformation, with a hydrophobic surface and a hydrophilic surface. Four sets of epi-Novo29 molecules pack in the crystal lattice to form a hydrophobic core. The macrolactone ring adopts a conformation in which the main-chain amide NH groups converge to create a cavity, which binds ordered water and acetate anion. The amphiphilic conformation of epi-Novo29 is reminiscent of the amphiphilic conformation adopted by the related antibiotic teixobactin and its derivatives, which contains a hydrophobic surface that interacts with the lipids of the bacterial cell membrane and a hydrophilic surface that interacts with the aqueous environment. Molecular modeling suggests that Novo29 can adopt an amphiphilic conformation similar to teixobactin, suggesting that Novo29 may interact with bacteria in a similar fashion to teixobactin.


Assuntos
Aminoácidos , Antibacterianos , Antibacterianos/farmacologia , Antibacterianos/química , Modelos Moleculares , Conformação Molecular , Aminoácidos/química , Espectroscopia de Ressonância Magnética
13.
Acta Pharmacol Sin ; 44(12): 2455-2468, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37596398

RESUMO

Renal tubulointerstitial fibrosis (TIF) is considered as the final convergent pathway of diabetic nephropathy (DN) without effective therapies currently. MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases, while miRNA clusters, formed by the cluster arrangement of miRNAs on chromosomes, can regulate diverse biological functions alone or synergistically. In this study, we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells-derived exosomes (Exos) engineered with RVG peptide, and investigated their therapeutic efficacy in a murine model of DN. Firstly, we showed that miR-23a-3p, miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing. Meanwhile, we confirmed that miR-23a-3p, miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/db mice at 20 weeks of age. We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells, which not only enhanced the stability of miR-23a/27a/26a cluster, but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney. More importantly, administration of RVG-miR-23a/27a/26a-Exos (100 µg, i.v., once a week for 8 weeks) significantly ameliorated tubular injury and TIF in db/db mice at 20 weeks of age. We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously, as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42, respectively. Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice. Taken together, we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN, thus providing a promising therapeutic strategy for DN.


Assuntos
Nefropatias Diabéticas , Exossomos , MicroRNAs , Células Satélites de Músculo Esquelético , Animais , Humanos , Camundongos , Diabetes Mellitus/terapia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/terapia , Exossomos/metabolismo , Fibrose , MicroRNAs/metabolismo , MicroRNAs/farmacologia , MicroRNAs/uso terapêutico , Células Satélites de Músculo Esquelético/metabolismo , Complicações do Diabetes/terapia
14.
Appl Opt ; 62(5): 1167-1174, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36821214

RESUMO

A quantitative analysis method for corrosion products based on terahertz spectroscopy is proposed in this paper. Mixture samples consisting of three major corrosion products (magnetite, hematite, and goethite) were prepared in 51 different concentrations. The refractive index spectra measured by terahertz time-domain spectroscopy were projected to the 2D score diagram by performing principal component analysis. The Euclidean distances between the mixtures and pure analyte on the diagram were used to build a concentration prediction model. The results indicate that the established model can precisely predict the concentration of magnetite, which is essential for a stability evaluation of the corrosion system.

15.
Plant Dis ; 107(4): 1027-1034, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36096101

RESUMO

On a global basis, potato cyst nematodes (Globodera spp. Skarbilovich 1959 [Behrens 1975]) are one of the most serious soilborne pathogens in potato (Solanum tuberosum L.) production. In 2019 to 2020, 188 soil samples were taken from rhizosphere soil associated with the roots of stunted and chlorotic potato plants in the main potato-growing areas of Yunnan and Sichuan Provinces of China. Globodera rostochiensis Wollenweber 1923 (Skarbilovich 1959) was recovered from 112 of the samples. Nematode identification was as confirmed by morphometric, light microscopy, electron microscopy, and molecular methodologies. Population densities of G. rostochiensis ranged from 47.0 to 69.0 eggs/g of soil. A BLASTn homology search program was used to compare the sequences of populations of G. rostrochienses from Yunnan and Sichuan Provinces with populations of other Heteroderinae spp. and populations of G. rostochiensis from other nations. Although potato has been grown in China for at least 400 years and the nation produces more potato than any other country, potato cyst nematodes were not reported in China until 2022.


Assuntos
Nematoides , Solanum tuberosum , Animais , China , Solo
16.
J Sports Sci ; 41(10): 937-946, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37598352

RESUMO

While a higher level of physical activity (PA) is inversely associated with a higher breast cancer (BC) risk, the health benefits of daily steps on obesity-related BC biomarkers remain unclear. We aimed to understand the associations of changes in step counts with levels of five obesity-related BC biomarkers during a two-year follow-up. In total, 144 non-cancer women (47.96 ± 5.72) were observed on both 2019 and 2021. A structured questionnaire, daily steps and fasting blood samples were collected before (t0, 2019) and after (t1, 2021). Levels of biomarkers (IGF-binding proteins 3, adiponectin, soluble leptin receptor, C-reactive protein, and resistin) were assayed by ELISA. Participants were divided into persistent low steps, decreasing steps, increasing steps, and persistent high steps. Associations of categories on proposed biomarkers were estimated using linear regression models, with persistent low steps as reference. Associations between time-varying step counts with biomarkers were quantified using mixed linear models. Compared with persistent low steps, increasing steps is associated with a reduction in C-reactive protein level (ß=-0.74, 95%CI=-1.23--0.26, P-value = 2.98 × 10-3). An inverse association between time-varying step counts with C-reactive protein level was identified, consistent across different obesity types and baseline step level categories. No association with daily step counts was observed for other proteins.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Humanos , Feminino , Actigrafia , Smartphone , Proteína C-Reativa , Obesidade , Biomarcadores
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 386-392, 2023 Mar.
Artigo em Zh | MEDLINE | ID: mdl-36949703

RESUMO

Objective: To explore the impact of socioeconomic status and productive aging on the frailty index of urban elderly population in China, and to provide reference for improving their health level. Methods: We obtained data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) and included 1890 urban elderly people aged 60 and over in the study. Multiple linear regression model was used to analyze the influencing factors of the productive aging and the frailty index of the urban elderly population in China. A structural equation model was constructed to explore the relationship between socioeconomic status, productive aging, and frailty index. Results: Elderly people with high socioeconomic status ( ß=0.082, P<0.001) had higher level of productive aging. Elderly people with high socioeconomic status ( ß=-0.091, P<0.001) and high level of productive aging ( ß=-0.330, P<0.001) had lower frailty index. Productive aging played an intermediary role ( ß=-0.259, 95% CI: -0.380--0.181) between socioeconomic status and frailty index. Conclusion: The socioeconomic status and productive aging of the elderly people are important predictors of their frailty index. The government should exert its leadership functions to encourage the elderly, especially those with low education and income levels, to actively learn knowledge and skills, and to provide support for the elderly to participate in productive activities.


Assuntos
Fragilidade , Humanos , Idoso , Pessoa de Meia-Idade , Envelhecimento , Classe Social , Nível de Saúde , China/epidemiologia , Fatores Socioeconômicos
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(5): 978-984, 2023 Sep.
Artigo em Zh | MEDLINE | ID: mdl-37866956

RESUMO

Objective: To investigate the associatiojn of body mass index (BMI) at different stages of life and weight gain in adulthood with obesity-related breast cancer risk biomarkers and to provide evidence for formulating policies concerning the prevention and control of breast cancer. Methods: A cross-sectional study was designed based on the follow-up cohort of southwest China community-based breast cancer screening of women. Using sequential sampling, eligible participants were enrolled from the cohort as the subjects of the study. Information on the basic risk factors was collected and the height, weight, and plasma biomarker levels were measured. Multiple linear regression model was applied to analyze the associations of early adulthood BMI (defined as the BMI of the participant at age 20), adulthood BMI (defined as the BMI measured at the time of enrollment), and weight gain in adulthood with the biomarkers. The concentrations of the biomarkers were incorporated in the model after log transformation. Results: The average age of the 442 participants was 49 (45, 54) years old, the average early adulthood BMI and adulthood BMI were 21.47 (19.56, 23.11) and 24.10 (22.59, 25.97) kg/m 2, respectively, and the average weight gain in adulthood was 6.60 (2.00, 11.00) kg. Adulthood BMI was negatively associated with adiponectin level ( ß=-0.026, 95% CI: -0.045--0.008, P=0.006), and positively associated with C-reactive protein level ( ß=0.095, 95% CI: 0.054-0.137, P<0.001) and leptin receptor level ( ß=0.090, 95% CI: 0.063-0.117, P<0.001). No association was found between adulthood BMI and resistin levels or between adulthood BMI and insulin-like growth factor-binding protein-3 levels. BMI in early adulthood was found to be negatively associated with only insulin-like growth factor-binding protein-3 levels ( ß=-0.039, 95% CI: -0.068--0.010, P=0.009). Further analysis of adulthood weight gain after the age of 20 revealed that average annual weight gain in adulthood was negatively associated with adiponectin levels and positively associated with 4 other biomarkers. Furthermore, compared with those of women whose weight remained stable, the adiponectin level of women whose weight gain in adulthood exceeded 5.00 kg was much lower ( ß=-0.185, 95% CI: -0.320--0.049, P=0.008), while their insulin-like growth factor-binding protein-3 ( ß=0.389, 95% CI: 0.183-0.594, P<0.001) and leptin receptor ( ß=0.245, 95% CI: 0.048-0.442, P=0.015) levels were higher. Conclusion: Weight gain in adulthood is strongly associated with the changes in obesity-related breast cancer risk biomarkers. Women should maintain a stable weight throughout adulthood and it is preferred that their weight gain should not exceed 5.00 kg.


Assuntos
Neoplasias da Mama , Somatomedinas , Humanos , Adulto , Feminino , Adulto Jovem , Índice de Massa Corporal , Neoplasias da Mama/etiologia , Adiponectina , Estudos Transversais , População do Leste Asiático , Receptores para Leptina , Obesidade/complicações , Aumento de Peso , Fatores de Risco , Biomarcadores , Peso Corporal
19.
BMC Plant Biol ; 22(1): 476, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36203126

RESUMO

BACKGROUND: Strawberries are an important economic fruit crop world-wide. In strawberry cultivation, continuous cropping (CC) can seriously threaten yield and quality. However, our understanding of the gene expression changes in response to CC and during subsequent defense processes is limited. In this study, we analyzed the impact of CC on the transcriptome of strawberry roots using RNA-Seq technology to elucidate the effect of CC and the subsequent molecular changes. RESULTS: We found that CC significantly affects the growth of strawberry plants. The transcriptome analysis identified 136 differentially expressed genes (DEGs), including 49 up-regulated and 87 down-regulated DEGs. A Gene Ontology (GO) analysis indicated that the up-regulated DEGs were mainly assigned to defense-related GO terms, and most down-regulated DEGs were assigned to nutrient-related GO terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the responsive DEGs were classified in a large number of important biological pathways, such as phenylalanine metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism and plant-pathogen interaction. We also found that four WRKY transcription factors and three peroxidase genes involved in plant defense pathways were up-regulated in the roots of strawberry plants subjected to CC. CONCLUSION: Several unigenes involved in plant defense processes, such as CNGCs, WRKY transcription factors, PR1, and peroxidase genes with highly variable expression levels between non-CC and CC treatments may be involved in the regulation of CC in strawberry. These results indicate that strawberry roots reallocate development resources to defense mechanisms in response to CC. This study will further deepen our understanding of the fundamental regulatory mechanisms of strawberry resource reallocation in response to CC.


Assuntos
Fragaria , Fragaria/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Glutationa/metabolismo , Peroxidases/metabolismo , Fenilalanina/genética , Fenilalanina/metabolismo , Amido/metabolismo , Sacarose , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma
20.
Photosynth Res ; 152(2): 193-206, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35503495

RESUMO

Photosystem II (PSII) has a number of hydrogen-bonding networks connecting the manganese cluster with the lumenal bulk solution. The structure of PSII from Thermosynechococcus vulcanus (T. vulcanus) showed that D1-R323, D1-N322, D1-D319 and D1-H304 are involved in one of these hydrogen-bonding networks located in the interfaces between the D1, CP43 and PsbV subunits. In order to investigate the functions of these residues in PSII, we generated seven site-directed mutants D1-R323A, D1-R323E, D1-N322R, D1-D319L, D1-D319R, D1-D319Y and D1-H304D of T. vulcanus and examined the effects of these mutations on the growth and functions of the oxygen-evolving complex. The photoautotrophic growth rates of these mutants were similar to that of the wild type, whereas the oxygen-evolving activities of the mutant cells were decreased differently to 63-91% of that of the wild type at pH 6.5. The mutant cells showed a higher relative activity at higher pH region than the wild type cells, suggesting that higher pH facilitated proton egress in the mutants. In addition, oxygen evolution of thylakoid membranes isolated from these mutants showed an apparent decrease compared to that of the cells. This is due to the loss of PsbU during purification of the thylakoid membranes. Moreover, PsbV was also lost in the PSII core complexes purified from the mutants. Taken together, D1-R323, D1-N322, D1-D319 and D1-H304 are vital for the optimal function of oxygen evolution and functional binding of extrinsic proteins to PSII core, and may be involved in the proton egress pathway mediated by YZ.


Assuntos
Cianobactérias , Complexo de Proteína do Fotossistema II , Mutação , Oxigênio , Prótons , Thermosynechococcus
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