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1.
Am J Physiol Renal Physiol ; 326(6): F1004-F1015, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38634129

RESUMO

Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents. There were two aims of the study in polycystic kidney disease (PKD): 1) to determine whether increasing serum uric acid with the uricase inhibitor, oxonic acid, resulted in faster cyst growth and 2) to determine whether treatment with the xanthine oxidase inhibitor, oxypurinol, reduced the cyst growth caused by oxonic acid. Orthologous models of human PKD were used: PCK rats, a polycystic kidney and hepatic disease 1 (Pkhd1) gene model of autosomal recessive PKD (ARPKD) and Pkd1RC/RC mice, a hypomorphic Pkd1 gene model. In PCK rats and Pkd1RC/RC mice, oxonic acid resulted in a significant increase in serum uric acid, kidney weight, and cyst index. Mechanisms of increased cyst growth that were investigated were proinflammatory cytokines, the inflammasome, and crystal deposition in the kidney. Oxonic acid resulted in an increase in proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice. Oxonic acid did not cause activation of the inflammasome or uric acid crystal deposition in the kidney. In Pkd1RC/RC male and female mice analyzed together, oxypurinol decreased the oxonic acid-induced increase in cyst index. In summary, increasing serum uric acid by inhibiting uricase with oxonic acid results in an increase in kidney weight and cyst index in PCK rats and Pkd1RC/RC mice. The effect is independent of inflammasome activation or crystal deposition in the kidney.NEW & NOTEWORTHY This is the first reported study of uric acid measurements and xanthine oxidase inhibition in polycystic kidney disease (PKD) rodents. Raising serum uric acid with a uricase inhibitor resulted in increased kidney weight and cyst index in Pkd1RC/RC mice and PCK rats, elevated levels of proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice, and no uric acid crystal deposition or activation of the caspase-1 inflammasome in the kidney.


Assuntos
Modelos Animais de Doenças , Rim , Doenças Renais Policísticas , Urato Oxidase , Ácido Úrico , Animais , Ácido Úrico/sangue , Doenças Renais Policísticas/patologia , Doenças Renais Policísticas/metabolismo , Doenças Renais Policísticas/tratamento farmacológico , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Oxipurinol/farmacologia , Ácido Oxônico/farmacologia , Inibidores Enzimáticos/farmacologia , Ratos , Feminino , Inflamassomos/metabolismo , Citocinas/metabolismo , Citocinas/sangue , Camundongos , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , Ratos Sprague-Dawley , Camundongos Endogâmicos C57BL
2.
Dev Sci ; 27(4): e13485, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38351606

RESUMO

Disparities in socioeconomic status (SES) may affect individuals' risk preferences, which have important developmental consequences across the lifespan. Yet, previous research has shown inconsistent associations between SES and risky decision-making, and little is known about how this link develops from a young age. The current research is among the first to examine how SES influences preschoolers' risky decisions in both gain and loss frames. Across two studies, children aged 5 to 6 years (total N = 309, 154 boys) were asked to choose between certain and risky options. The risky option was more advantageous, equal to, or less advantageous than the certain option. Study 1 revealed that in the loss frame, high-SES children (n = 84, 44 boys) chose more risky options and were more sensitive to the expected value compared to low-SES children (n = 78, 42 boys), especially when the risk was more advantageous. However, this SES difference was not significant in the gain frame. Supporting the potential causal link between SES and risky decision-making, Study 2 further found that experimentally increasing low-SES children's (n = 68, 30 boys) status by providing additional resources increased their risk-seeking behavior in the loss frame. Overall, our findings suggest an interaction between environmental cues (gain vs. loss) and early life circumstances (SES) in shaping children's risk preferences. RESEARCH HIGHLIGHTS: This research is among the first to examine how school backgrounds and experimentally manipulated SES influence preschoolers' risk preferences in gain and loss frames. Children were more risk-seeking for losses than for gains; this framing effect was stronger in higher-SES than lower-SES children. Lower-SES children exhibited fewer risk-seeking behaviors and decreased sensitivity to the expected value of options for losses, but not for gains. A temporary boost in SES increased children's risk-seeking behavior, but not sensitivity to expected values.


Assuntos
Tomada de Decisões , Assunção de Riscos , Classe Social , Humanos , Pré-Escolar , Masculino , Feminino , Criança
3.
Cereb Cortex ; 33(4): 933-947, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35332916

RESUMO

Recently, the functional roles of the human cortical folding patterns have attracted increasing interest in the neuroimaging community. However, most existing studies have focused on the gyro-sulcal functional relationship on a whole-brain scale but possibly overlooked the localized and subtle functional differences of brain networks. Actually, accumulating evidences suggest that functional brain networks are the basic unit to realize the brain function; thus, the functional relationships between gyri and sulci still need to be further explored within different functional brain networks. Inspired by these evidences, we proposed a novel intrinsic connectivity network (ICN)-guided pooling-trimmed convolutional neural network (I-ptFCN) to revisit the functional difference between gyri and sulci. By testing the proposed model on the task functional magnetic resonance imaging (fMRI) datasets of the Human Connectome Project, we found that the classification accuracy of gyral and sulcal fMRI signals varied significantly for different ICNs, indicating functional heterogeneity of cortical folding patterns in different brain networks. The heterogeneity may be contributed by sulci, as only sulcal signals show heterogeneous frequency features across different ICNs, whereas the frequency features of gyri are homogeneous. These results offer novel insights into the functional difference between gyri and sulci and enlighten the functional roles of cortical folding patterns.


Assuntos
Córtex Cerebral , Conectoma , Humanos , Córtex Cerebral/diagnóstico por imagem , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Redes Neurais de Computação
4.
Cereb Cortex ; 33(11): 6708-6722, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-36646465

RESUMO

Cortical folding patterns are related to brain function, cognition, and behavior. Since the relationship has not been fully explained on a coarse scale, many efforts have been devoted to the identification of finer grained cortical landmarks, such as sulcal pits and gyral peaks, which were found to remain invariant across subjects and ages and the invariance may be related to gene mediated proto-map. However, gyral peaks were only investigated on macaque monkey brains, but not on human brains where the investigation is challenged due to high inter-individual variabilities. To this end, in this work, we successfully identified 96 gyral peaks both on the left and right hemispheres of human brains, respectively. These peaks are spatially consistent across individuals. Higher or sharper peaks are more consistent across subjects. Both structural and functional graph metrics of peaks are significantly different from other cortical regions, and more importantly, these nodal graph metrics are anti-correlated with the spatial consistency metrics within peaks. In addition, the distribution of peaks and various cortical anatomical, structural/functional connective features show hemispheric symmetry. These findings provide new clues to understanding the cortical landmarks, as well as their relationship with brain functions, cognition, behavior in both healthy and aberrant brains.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Animais , Humanos , Membrana Celular , Córtex Cerebral , Macaca
5.
Am J Physiol Renal Physiol ; 325(3): F328-F344, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471421

RESUMO

Prerenal azotemia (PRA) is a major cause of acute kidney injury and uncommonly studied in preclinical models. We sought to develop and characterize a novel model of PRA that meets the clinical definition: acute loss of glomerular filtration rate (GFR) that returns to baseline with resuscitation. Adult male C57BL/6J wild-type (WT) and IL-6-/- mice were studied. Intraperitoneal furosemide (4 mg) or vehicle was administered at time = 0 and 3 h to induce PRA from volume loss. Resuscitation began at 6 h with 1 mL intraperitoneal saline for four times for 36 h. Six hours after furosemide administration, measured glomerular filtration rate was 25% of baseline and returned to baseline after saline resuscitation at 48 h. After 6 h of PRA, plasma interleukin (IL)-6 was significantly increased, kidney and liver histology were normal, kidney and liver lactate were normal, and kidney injury molecule-1 immunofluorescence was negative. There were 327 differentially regulated genes upregulated in the liver, and the acute phase response was the most significantly upregulated pathway; 84 of the upregulated genes (25%) were suppressed in IL-6-/- mice, and the acute phase response was the most significantly suppressed pathway. Significantly upregulated genes and their proteins were also investigated and included serum amyloid A2, serum amyloid A1, lipocalin 2, chemokine (C-X-C motif) ligand 1, and haptoglobin; hepatic gene expression and plasma protein levels were all increased in wild-type PRA and were all reduced in IL-6-/- PRA. This work demonstrates previously unknown systemic effects of PRA that includes IL-6-mediated upregulation of the hepatic acute phase response.NEW & NOTEWORTHY Prerenal azotemia (PRA) accounts for a third of acute kidney injury (AKI) cases yet is rarely studied in preclinical models. We developed a clinically defined murine model of prerenal azotemia characterized by a 75% decrease in measured glomerular filtration rate (GFR), return of measured glomerular filtration rate to baseline with resuscitation, and absent tubular injury. Numerous systemic effects were observed, such as increased plasma interleukin-6 (IL-6) and upregulation of the hepatic acute phase response.


Assuntos
Injúria Renal Aguda , Azotemia , Animais , Masculino , Camundongos , Injúria Renal Aguda/metabolismo , Reação de Fase Aguda/complicações , Azotemia/complicações , Biomarcadores , Modelos Animais de Doenças , Furosemida , Taxa de Filtração Glomerular/fisiologia , Interleucina-6/genética , Interleucina-6/metabolismo , Lipocalina-2/genética , Fígado/metabolismo , Camundongos Endogâmicos C57BL
6.
Cereb Cortex ; 32(16): 3359-3376, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34875041

RESUMO

Prior studies reported the global structure of brain networks exhibits the "small-world" and "rich-world" attributes. However, the underlying structural and functional architecture highlighted by these graph theory findings hasn't been explicitly related to the morphology of the cortex. This could be attributed to the lower resolution of used folding patterns, such as gyro-sulcal patterns. By defining a novel gyral folding pattern, termed gyral hinge (GH), which is the conjunction of ordinary gyri from multiple directions, we found GHs possess the highest length and cost in the white matter fiber connective network, and the shortest paths in the network tend to travel through GHs in their middle part. Based on these findings, we would hypothesize GHs could reside in the centers of a network core, thereby accounting for the highest cost and the highest communication capacity in a corticocortical network. The following results further support our hypothesis: 1) GHs possess stronger functional network integration capacity. 2) Higher cost is found on the connection with GHs to hinges and GHs to GHs. 3) Moving GHs introduces higher extra network cost. Our findings and hypotheses could reveal a profound relationship among the cortical folding patterns, axonal wiring architectures, and brain functions.


Assuntos
Encéfalo , Córtex Cerebral , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Imageamento por Ressonância Magnética/métodos
7.
Brain Inj ; 37(8): 706-713, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-36527380

RESUMO

OBJECTIVE: Cerebral ischemic reperfusion injury (CIRI) is a common cerebrovascular disorder with high disability and morbidity that threatens human health. Former investigations found that dexmedetomidine (DEX) has a protective effect against CIRI, but regulatory mechanism is unclear. METHODS: The current study utilized C57BL/6 mice to establish a focal cerebral ischemic reperfusion model. Cerebral infarct volume was defined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. BV2 cells and primary neurons were utilized for molecular mechanism studies after treatment with DEX or autophagy inhibitor 3-Methyladenine (3-Ma). RESULTS: Data revealed that DEX pretreatment protected nerves against CIRI. In vitro studies also found that DEX pretreatment enhanced microglial M2 polarization and protected against neuronal apoptosis by autophagy activation. Downregulation of hypoxia inducible factor (HIF)-1α or Beclin-1 inhibited the promotional effects of DEX on microglial M2 polarization and inhibited the protective effects of DEX against neuronal apoptosis. CONCLUSION: The present study found that DEX treatment protects against CIRI by modulating microglial polarization via HIF-1α/Beclin1-mediated autophagy.


Assuntos
Isquemia Encefálica , Dexmedetomidina , Traumatismo por Reperfusão , Ratos , Camundongos , Animais , Humanos , Proteína Beclina-1/farmacologia , Ratos Sprague-Dawley , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Camundongos Endogâmicos C57BL , Apoptose , Autofagia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Isquemia Encefálica/tratamento farmacológico
8.
Opt Express ; 30(7): 10414-10427, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473009

RESUMO

Rare-earth-doped ZBLAN (ZrF4-BaF2-LaF3-AlF3-NaF) fibers have evolved to become promising candidates for efficient UV-visible emission because of their low phonon energy and low optical losses, as well as their well-defined absorption bands. We investigate the efficient emission of UV-visible light in a low-concentration (0.1 mol%) Ho3+-doped ZBLAN fiber excited by a 532 nm CW laser. In addition to the direct populating of the thermalized 5F4+5S2 levels by ground-state absorption, the upconversion processes responsible for UV-visible emission from the higher emitting levels, 3P1+3D3, 3K7+5G4, 5G5, and 5F3, of the Ho3+ ions are examined using excited-state absorption. The dependence of UV-visible fluorescence intensity on launched green pump power is experimentally determined, confirming the one-photon and two-photon characters of the observed processes. We theoretically investigate the excitation power dependence of the population density for nine Ho3+ levels based on a rate equation model. This qualitative model has shown a good agreement with the measured power dependence of UV-visible emission. Moreover, the emission cross-sections for blue, green, red, and deep-red light in the visible region are measured using the Füchtbauer-Ladenburg method and corroborated by McCumber theory, and the corresponding gain coefficients are derived. We propose an alternative approach to achieve efficient UV-visible emission in an Ho3+-doped ZBLAN fiber using a cost-effective, high-brightness 532 nm laser.

9.
Ann Vasc Surg ; 81: 316-323, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34762999

RESUMO

OBJECTIVES: To compare drug-coated balloon (DCB) and bare metal stent (BMS) for primary lesions in femoropopliteal artery disease in Chinese population and to make subgroup analysis between the groups. METHODS: Patients with primary lesions who underwent BMS or DCB treatment of a single tertiary vascular center were included and followed up for 24 months. Clinical and anatomic status were reported using the criteria recommended by the Society for Vascular Surgery. The primary endpoint included primary patency, clinically target limb revascularization, composite safety endpoint and all-cause death over 24 months assessed by Kaplan-Meier. Secondary endpoints included technical success rate and stent-related complications. RESULTS: A total of 284 patients with 324 limbs were pooled into analysis and most of the baseline characteristics did not show significant difference. A total of 74 in BMS group and 71 in DCB group were claudicants while 83 in BMS group and 56 in DCB group suffered from chronic limb threatening ischemia (CLTI). The mean cumulative lesion length was 18.7 ± 9.8cm in BMS group while 17.2 ± 10.3cm in DCB group. Kaplan-Meier estimates of primary patency were 75.3% and 80.9% for BMS and DCB groups at 12 months while decreased to 63.9% and 70.2% at 24 months (log-rank P = 0.167), respectively. Freedom from clinically driven target limb revascularization was 86.8% and 92.7% for BMS and DCB groups at 12 months while dropped to 82.5% and 85.9% at 24 months (log-rank P = 0.342). Estimates of primary patency between BMS and DCB group did not show significant difference on lesions with poor runoff (58.8% vs. 67.3%, log-rank P = 0.127), severe calcification (64.5% vs. 69.4%, log-rank P = 0.525) and popliteal artery involvement (59.3% vs. 60.3%, log-rank P = 0.695) at 24 months. The overall survival (92.6% for BMS, 90.3% for DCB, log-rank P = 0.391) and freedom from composite safety endpoint (79.3% for BMS, 79.2% for DCB, log-rank P = 0.941) showed no significant difference at 24 months. CONCLUSIONS: Over the 24 month follow-up, BMS and DCB showed equivalent efficacy and safety outcomes for primary femoropopliteal artery disease, which indicated the reduction of permanent metallic implant insertion might be possible.


Assuntos
Angioplastia com Balão , Doença Arterial Periférica , Ligas , Angioplastia com Balão/efeitos adversos , Materiais Revestidos Biocompatíveis , Artéria Femoral/cirurgia , Humanos , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Artéria Poplítea , Stents , Resultado do Tratamento , Grau de Desobstrução Vascular
10.
Int J Biometeorol ; 66(4): 741-751, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35230530

RESUMO

In montane systems, there are normally significant spatial differences in vegetation community structure and ecological processes due to the complex topography. The study of such topographic effect can provide scientific basis for the prediction of vegetation dynamics. In this work, the effects of altitude and slope aspect on species richness and flowering phenology of herbaceous communities were investigated in Qilian Mountains, a typical mountainous region in arid climate zones of China. Our monitoring of 102 plots in 34 sites revealed that there were significant topographic effects on species richness and flowering phenology. Specifically, the results showed a spatial pattern that the average number of species in plots was slightly higher at middle altitudes, and was higher on shady than sunny slopes. In flowering phenology, the flowering onsets of low-altitude and sunny-slope communities are generally earlier than that of high-altitude and shady-slope communities, respectively, while the ending dates of flowering between slope aspects and between altitudes are relatively small. This topographic effect revealed the influences of temperature and soil moisture on community structure and flowering phenology, which is reflected in the inverse responses of species richness to temperature and soil water content, and the high sensitivity of flowering phenology to temperature. It can be inferred that under the conditions of climate warming and wetting in the future, the species diversity of herbaceous community may increase at high altitudes, and the flowering duration is likely to be further prolonged in Qilian Mountains.


Assuntos
Mudança Climática , Solo , Altitude , China , Ecossistema , Plantas
11.
Biomacromolecules ; 22(11): 4479-4488, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34605629

RESUMO

The fabrication of biomimetic photonic materials with environmental stimuli-responsive functions from entirely biobased materials is becoming increasingly challenging with the growing demand for biodegradable materials. Herein, the effect of glucan with different molecular weights on the mechanical performance and tunable structural color of iridescent CNC composite films was investigated. The existence of glucan did not influence the self-assembly performance of CNCs, but rather led to an improvement in the mechanical performance, enabling cholesteric CNC composite films with an adjustable structural color. Simultaneously, the iridescent films showed a conspicuous redshift and enlarged initial pitch without obstruction of the chiral structure. In response to environmental humidity, the structural colors of the iridescent composite films can be changed by regulating their chiral nematic structure. In particular, the films demonstrate a reversible structural color change between blue and red at RH between 50 and 98%. The resulting biobased iridescent composite films have potential applications in decorative coating, optical and humidity sensing, and anticounterfeiting.


Assuntos
Celulose , Nanopartículas , Glucanos , Umidade , Iridescência
12.
Int J Biometeorol ; 65(11): 1849-1858, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33974125

RESUMO

There is growing evidence that mountains are experiencing some of the highest rates of climate warming, but assessment of the ecological impacts of climate change is often limited due to a lack of long-term monitoring data for comparative study in many ecosystems. In this study, we present an empirical work for assessing ecological responses with botanical legacy data in the Qilian Mountains of China. Plot-scale and transect-wide survey was conducted for alpine shrub communities along an elevational gradient 20 years ago. Recently, we resampled the permanent plots to investigate how the community changes may be linked to climatic variability. We found no significant temporal shifts in species richness; but the community structure underwent substantial changes, as indicated by visible shifts in the relative density of dominant shrub species and the frequency of occurrence of understory herbaceous species. This reshuffling of plant community composition reflected a series of complex responses to climate change. Specifically, wet-demanding species have become more frequent due to the recently enhanced precipitation, while the replacement of some low-statured plants with different requirements for light was indirectly regulated by climate warming via reshaping the altitudinal patterns of dominant shrubs. Climate-mediated shifts in shrub species distribution altered the expected evolutional trajectory of alpine community, which increased the complexity and nonlinearity of the responses of the communities at different altitudes to climatic variability. Our results suggested that in-depth knowledge of indirect effects can facilitate to lessen the uncertainty in predicting future community dynamics in a changing climate.


Assuntos
Mudança Climática , Ecossistema , Altitude , China , Plantas
13.
Cellulose (Lond) ; 28(13): 8641-8651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305338

RESUMO

Lateral flow assay (LFA) is an important point-of-care (POC) test platform due to the associated portability, on-site testing, and low cost for diagnosis of pathogen infections and disease biomarkers. However, compared to high-end analyzers in hospitals, LFA devices, in particular, paper- based LFA tests, fall short in accuracy. This study focuses on two ways to improve LFAs: (1) using cellulose fibers, rather than glass fibers for a sample pad, and (2) incorporating a one-step simple, facile, and low cost PVA dam into the LFA. Both strategies (cellulose fiber as a sample pad and water dissolvable PVA dam) contributed to delaying the controlled biomolecule's flow through the nitrocellulose membrane's capillary channels resulting in increased bio-recognition time, thus contributing to the enhancement of LFA sensitivity. PVA modified cellulose fiber-based LFA demonstrated 10 times higher sensitivity than the cellulose fiber-based unmodified LFA, whereas 2 times enhancement was obtained in the cellulose fiber-based sample pad LFA compared to the glass fiber-based sample pad LFA. Ultimately, 20 times increase in sensitivity was achieved in the modified LFA device. This study shows that PVA and eco-friendly cellulose fibers could be incorporated into other paper based POC testing devices for future development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10570-021-04083-3.

14.
Ann Vasc Surg ; 57: 274.e1-274.e3, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30500636

RESUMO

A case with an extremely rare intravenous cystic lesion in the suprahepatic inferior vena cava was reported, which originated from the lymphatic system and had induced Budd-Chiari syndrome. To the best of our knowledge, this is the first report of a benign cystic lesion originating from the wall of a suprahepatic inferior vena cava which results in Budd-Chiari syndrome.


Assuntos
Síndrome de Budd-Chiari/etiologia , Linfocele/complicações , Veia Cava Inferior , Biópsia , Síndrome de Budd-Chiari/diagnóstico por imagem , Síndrome de Budd-Chiari/patologia , Síndrome de Budd-Chiari/cirurgia , Angiografia por Tomografia Computadorizada , Humanos , Linfocele/diagnóstico por imagem , Linfocele/patologia , Linfocele/cirurgia , Masculino , Pessoa de Meia-Idade , Flebografia/métodos , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia
15.
Hum Mol Genet ; 23(18): 4919-31, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-24847003

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the USA. In human ADPKD studies, sirolimus, a mammalian target of rapamycin complex 1 (mTORC1) inhibitor, had little therapeutic effect. While sirolimus robustly inhibits mTORC1, it has a minimal effect on mTOR complex 2 (mTORC2). Polycystic kidneys of Pkd2WS25/- mice, an orthologous model of human ADPKD caused by a mutation in the Pkd2 gene, had an early increase in pS6 (marker of mTORC1) and pAktSer(473) (marker of mTORC2). To investigate the effect of combined mTORC1 and 2 inhibition, Pkd2WS25/- mice were treated with an mTOR anti-sense oligonucleotide (ASO) that blocks mTOR expression thus inhibiting both mTORC1 and 2. The mTOR ASO resulted in a significant decrease in mTOR protein, pS6 and pAktSer(473). Pkd2WS25/- mice treated with the ASO had a normalization of kidney weights and kidney function and a marked decrease in cyst volume. The mTOR ASO resulted in a significant decrease in proliferation and apoptosis of tubular epithelial cells. To demonstrate the role of mTORC2 on cyst growth, Rictor, the functional component of mTORC2, was silenced in Madin-Darby canine kidney cell cysts grown in 3D cultures. Silencing Rictor significantly decreased cyst volume and expression of pAktSer(473). The decreased cyst size in the Rictor silenced cells was reversed by introduction of a constitutively active Akt1. In vitro, combined mTORC1 and 2 inhibition reduced cyst growth more than inhibition of mTORC1 or 2 alone. In conclusion, combined mTORC1 and 2 inhibition has therapeutic potential in ADPKD.


Assuntos
Oligonucleotídeos Antissenso/administração & dosagem , Doenças Renais Policísticas/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Canais de Cátion TRPP/genética , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Cães , Regulação da Expressão Gênica/efeitos dos fármacos , Terapia Genética/métodos , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Renais Policísticas/genética , Proteína Companheira de mTOR Insensível à Rapamicina , Sirolimo/farmacologia , Canais de Cátion TRPP/metabolismo
16.
J Plant Res ; 129(5): 841-851, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27262588

RESUMO

A better understanding of the sap flow characteristics of maize plants is critical for improving irrigation water-use efficiency, especially for regions facing water resource shortages. In this study, sap flow rates, related soil-physics and plant-growth parameters, and meteorological factors, were simultaneously monitored in a maize field in two consecutive years, 2011 and 2012, and the sap flow rates of the maize plants were extensively analyzed based on the monitored data. Seasonal and daily variational characteristics were identified at different growth stages and under different weather conditions, respectively. The analyses on the relationships between sap flow rate and reference evapotranspiration (ET0), as well as several plant-growth parameters, indicate that the irrigation schedule can exert an influence on sap flow, and can consequently affect crop yield. The ranking of the main meteorological factors affecting the sap flow rate was: net radiation > air temperature > vapor pressure deficit > wind speed. For a quick estimation of sap flow rates, an empirical formula based on the two top influencing factors was put forward and verified to be reliable. The sap flow rate appeared to show little response to irrigation when the water content was relatively high, implying that some of the irrigation in recent years may have been wasted. These results may help to reveal the bio-physical processes of maize plants related to plant transpiration, which could be beneficial for establishing an efficient irrigation management system in this region and also for providing a reference for other maize-planting regions.


Assuntos
Exsudatos de Plantas/fisiologia , Rios , Zea mays/fisiologia , Irrigação Agrícola , China , Clima , Luz , Folhas de Planta/anatomia & histologia , Caules de Planta/anatomia & histologia , Transpiração Vegetal/fisiologia , Estações do Ano , Solo/química , Temperatura , Água , Zea mays/anatomia & histologia , Zea mays/crescimento & desenvolvimento
17.
J Pharmacol Exp Ther ; 349(3): 518-25, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24727856

RESUMO

Triptolide, a traditional Chinese medicine, has anti-inflammatory, antiproliferative, and proapoptotic properties. As interstitial inflammation and tubular apoptosis are features of cisplatin-induced acute kidney injury (AKI), we determined the effect of the water-soluble triptolide derivative 14-succinyl triptolide sodium salt (PG490-88) in a mouse model of cisplatin-induced AKI. PG490-88 resulted in a significant decrease in blood urea nitrogen (BUN), serum creatinine, and acute tubular necrosis (ATN) score, and a nonsignificant increase in tubular apoptosis score in AKI. The mitogen-activated protein kinase (MAPK) pathway is activated in AKI. On immunoblot analysis, phosphoextracellular signal-regulated kinase (p-ERK) was increased 3.6-fold in AKI and 2.0-fold inhibited by PG490-88. Phospho-c-Jun N-terminal kinase (p-JNK) was increased in AKI. PG490-88 resulted in a nonsignificant decrease in p-JNK. Phospho-p38 was not affected by cisplatin or PG490-88. MAPK phosphatase-1 (MKP-1) that negatively regulates MAPK signaling has not previously been studied in AKI. MKP-1 activity was not affected by cisplatin or PG490-88. Changes in p-ERK, p-JNK, and MKP-1 were confirmed on reverse protein phase analysis. The ERK inhibitor U0126 resulted in lower BUN and serum creatinine, suggesting a mechanistic role of ERK in AKI. The increase in interleukin-1α (IL-1α), IL-1ß, IL-6, CXCL1, and IL-33 in the kidney in AKI was unaffected by PG490-88. In summary, PG490-88 protects against AKI and ATN despite no decrease in tubular apoptosis. The protection of PG490-88 against AKI was associated with a decrease in p-ERK and was independent of MKP-1 and proinflammatory cytokines. In conclusion, PG490-88 protects against cisplatin-induced AKI possibly by decreasing p-ERK.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Diterpenos/química , Diterpenos/uso terapêutico , Fenantrenos/química , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/enzimologia , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Citocinas/imunologia , Diterpenos/administração & dosagem , Diterpenos/farmacologia , Compostos de Epóxi/química , Testes de Função Renal , MAP Quinase Quinase 4/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
18.
Nanomaterials (Basel) ; 14(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38869538

RESUMO

Magnetoresistance, the change in resistance with applied magnetic fields, is crucial to the magnetic sensor technology. Linear magnetoresistance has been intensively studied in semimetals and semiconductors. However, the air-stable oxides with a large linear magnetoresistance are highly desirable but remain to be fully explored. In this paper, we report the direct observation of linear magnetoresistance in polycrystalline MoO2 without any sign of saturation up to 7 T under 50 K. Interestingly, the linear magnetoresistance reaches as large as 1500% under 7 T at 2 K. The linear field dependence is in great contrast to the parabolic behavior observed in single-crystal MoO2, probably due to phonon scattering near the grain boundaries. Our results pave the way to comprehending magneto-transport behavior in oxides and their potential applications in magnetic sensors.

19.
Adv Mater ; 36(9): e2307582, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37781979

RESUMO

Learning about the strain/stress distribution in a material is essential to achieve its mechanical stability and proper functionality. Conventional techniques such as universal testing machines only apply to static samples with standardized geometry in laboratory environment. Soft mechanical sensors based on stretchable conductors, carbon-filled composites, or conductive gels possess better adaptability, but still face challenges from complicated fabrication process, dependence on extra readout device, and limited strain/stress mapping ability. Inspired by the camouflage mechanism of cuttlefish and chameleons, here an innovative responsive hydrogel containing light-scattering "mechano-iridophores" is developed. Force induced reversible phase separation manipulates the dynamic generation of mechano-iridophores, serving as optical indicators of local deformation. Patch-shaped mechanical sensors made from the responsive hydrogel feature fast response time (<0.4 s), high spatial resolution (≈100 µm), and wide dynamic ranges (e.g., 10-150% strain). The intrinsic adhesiveness and self-healing material capability of sensing patches also ensure their excellent applicability and robustness. This combination of chemical and optical properties allows strain/stress distributions in target samples to be directly identified by naked eyes or smartphone apps, which is not yet achieved. The great advantages above are ideal for developing the next-generation mechanical sensors toward material studies, damage diagnosis, risk prediction, and smart devices.

20.
Sci Total Environ ; 915: 170093, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38224885

RESUMO

Tree stem radial growth could be used to estimate forest productivity, which plays a dominant role in the carbon sink of terrestrial ecosystems. However, it is still obscure how intra-annual stem radial growth is regulated by environmental variables. Here, we monitored Qinghai spruce stem radial growth over seven years and analyzed the environmental drivers of the intra-annual stem radial changes in the Qilian Mountains at low (2700 m) and high altitudes (3200 m). We found that stem radial growth initiated when the daily mean minimum air temperature reached 1.6oC, while the cessation of stem growth was unrelated to temperatures and water conditions. Initiations of stem growth at 2700 m were significantly earlier than that at 3200 m. Maximum growth rates were observed before the summer solstice at low altitude, whereas at high altitude, the majority of them occurred after the summer solstice. Most variability in annual stem increment (AI) can be explained by the rate (Rm) than by the duration of stem growth (∆t), and 78.9 % and 69.6 % of the variability in AI were attributable to Rm for the lower and upper site, respectively. Structural equation modeling revealed that precipitation (P) could both directly positively influence stem radial increment (SRI) and indirectly positively influence SRI through influencing relative humidity (RH), but the positive effect of P on SRI was higher at low altitude than at high altitude. Daily minimum air temperature (Tmin) was also the main direct diver of SRI, and the positive effect of Tmin on SRI was higher at high altitude than at low altitude. Considering the trends in climate warming and humidification over the past decades, climate changes would result in earlier initiation of Qinghai spruce stem growth and promote the growth through positive response to increased precipitation in low altitude and through elevated temperature in high altitude, respectively.

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