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1.
Brain Sci ; 12(9)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36138942

RESUMO

Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson's disease (PD), and a noble cause of disability in advanced PD patients. Circular RNA (circRNA) is a novel type of non-coding RNA with a covalently closed-loop structure, which can regulate gene expression and participate in many biological processes. However, the biological roles of circRNAs in LID are not completely known. In the present study, we established typical LID rat models by unilateral lesions of the medial forebrain bundle and repeated levodopa therapy. High-throughput next-generation sequencing was used to screen circRNAs differentially expressed in the brain of LID and non-LID (NLID) rats, and key circRNAs were selected according to bioinformatics analyses. Regarding fold change ≥2 and p < 0.05 as the cutoff value, there were a total of 99 differential circRNAs, including 39 up-regulated and 60 down-regulated circRNAs between the NLID and LID groups. The expression of rno-Rsf1_0012 was significantly increased in the striatum of LID rats and competitively bound rno-mir-298-5p. The high expression of target genes PCP and TBP in LID rats also supports the conclusion that rno-Rsf1_0012 may be related to the occurrence of LID.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36121575

RESUMO

B cells play a role in the progression of multiple sclerosis (MS) and are closely related to Fc-receptor like-3 (FCRL3), but little is known about FCRL3 in B cells and MS. Activation of TLR9 in B cells with CpG found that CpG promoted FCRL3 expression in a dose- and time-dependent manner. CpG significantly activated ERK1/2, p38, and STAT3 pathways, and FCRL3 overexpression further promoted the activation of these pathways, while FCRL3 siRNA significantly inhibited the activation of these pathways by CpG. CpG stimulation significantly promoted the viability of B cells, inhibited cell apoptosis, and enhanced the production of antibodies and secretion of IL-10 by B cells. FCRL3 siRNA blocked most of the above regulatory effects of CpG, but promoted the further production of antibodies by B cells. FCRL3 overexpression enhanced the pro-survival, anti-apoptotic, and IL-10-inducing effects of CpG, but inhibited the effect of CpG on promoting antibody production. After adding inhibitors of ERK1/2, p38, and STAT3 pathways, respectively, the effects of CpG on promoting cell viability, antibody production, and IL-10 secretion were significantly reduced, but the anti-apoptotic effect of CpG was only affected by the blockade of STAT3 pathway. In addition, FCRL3 regulated B cell antibody and IL-10 secretion mainly through its ITIMs. These results indicate that TLR9 activation affects B cell proliferation, apoptosis, antibody production, and IL-10 secretion by upregulating FCRL3 expression, and is associated with ERK1/2, p38, and STAT3 pathways. Therefore, FCRL3 may be an important target for the diagnosis and treatment of B cell-related diseases.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36141538

RESUMO

Heavy metals have the potential to influence the transmission of antimicrobial resistance (AMR). However, the effect on AMR caused by heavy metals has not been clearly revealed. In this study, we used a microcosm experiment and metagenomics to examine whether common levels of Cu and Zn in pig manure influence AMR transmission in manured soil. We found that the abundance of 204 ARGs significantly increased after manure application, even though the manure did not contain antibiotic residuals. However, the combined addition of low Cu and Zn (500 and 1000 mg/kg, respectively) only caused 14 ARGs to significantly increase, and high Cu and Zn (1000 and 3000 mg/kg, respectively) caused 27 ARGs to significantly increase. The disparity of these numbers suggested that factors within the manure were the primary driving reasons for AMR transmission, rather than metal amendments. A similar trend was found for biocide and metal resistance genes (BMRGs) and mobile genetic elements (MGEs). This study offers deeper insights into AMR transmission in relation to the effects of manure application and heavy metals at commonly reported levels. Our findings recommend that more comprehensive measures in controlling AMR in the pig industry are needed apart from restricting heavy metal additions.

4.
Environ Int ; 169: 107511, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36095929

RESUMO

BACKGROUND: Metals in the human body represent both environmental exposure and nutritional status. Little is known about the miRNA signature in relation to circulating metals in humans. OBJECTIVES: To characterize metal-associated miRNAs in leukocytes, individually and collectively as networks. METHODS: In a panel of 160 Chinese adults, we measured 23 metals/metalloids in plasma, and sequenced miRNAs and mRNAs in leukocytes. We used linear regression to model the associations between ln-transformed metal concentrations and normalized miRNA levels adjusting for potential confounders. We inferred the enriched leukocyte subtypes for the identified miRNAs using an association approach. We utilized mRNA sequencing data to explore miRNA functions. We also constructed modules to identify metal-associated miRNA networks. RESULTS: We identified 55 metal-associated miRNAs at false discovery rate-adjusted P < 0.05. In particular, we found that lead, nickel, and vanadium were positively associated with potentially lymphocyte-enriched miR-142-3p, miR-150-3p, miR-28-5p, miR-361-3p, and miR-769-5p, and were inversely associated with potentially granulocyte-enriched let-7a/c/d-5p and miR-1294. Interestingly, the five lymphocyte-enriched miRNAs inhibited, whereas miR-1294 activated, ROS and DNA repair pathways. We further confirmed the findings using oxidative damage biomarkers. Next, we clustered co-expressed miRNAs into modules, and identified four miRNA modules that were associated with different metals. The identified modules represented miRNAs enriched in different leukocyte subtypes, and were involved in biological processes including hematopoiesis and immune response, mitochondrial functions, and response to the stimulus. CONCLUSIONS: At commonly exposed low levels, circulating metals were associated with distinct miRNA signatures in leukocytes. The identified miRNAs, individually or as regulatory networks, may provide a mechanistic link between metal exposure and pathophysiological changes in the immune system.

5.
Aging (Albany NY) ; 14(17): 7126-7136, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36098743

RESUMO

Zbtb34 is a novel zinc finger protein, which is revealed by biological software analysis to have 3 zinc fingers, but its functions remain unknown. In this study, mouse Zbtb34 cDNA was amplified by PCR and inserted into the plasmid pEGFP-N1 to generate Zbtb34-EGFP fusion protein. The upregulation of Zbtb34 in mouse embryonic stem cells promoted telomere elongation and increased cell proliferation. In order to understand the above phenomena, the telomere co-immunoprecipitation technique was employed to investigate the relationship between Zbtb34 and telomeres. The results indicated that Zbtb34 could bind to the DNA sequences of the telomeres. Alanine substitution of the third zinc finger abolished such binding. Since Pot1 is the only protein binding to the single-stranded DNA at the end of the telomeres, we further investigated the relationship between Zbtb34 and Pot1. The results revealed that the upregulation of Zbtb34 decreased the binding of Pot1b to the telomeres. Through the upregulation of Pot1b, the binding of Zbtb34 to the telomeres was also reduced. In conclusion, we showed that the main biological function of Zbtb34 was to bind telomere DNA via its third ZnF, competing with Pot1b for the binding sites, resulting in telomere elongation and cell proliferation.


Assuntos
DNA de Cadeia Simples , Proteínas de Ligação a Telômeros , Alanina/genética , Animais , Proliferação de Células , DNA , DNA Complementar , Proteínas de Ligação a DNA/genética , Células-Tronco Embrionárias/metabolismo , Camundongos , Complexo Shelterina , Telômero/genética , Telômero/metabolismo , Proteínas de Ligação a Telômeros/genética , Proteínas de Ligação a Telômeros/metabolismo
6.
Light Sci Appl ; 11(1): 261, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36055999

RESUMO

Lidar techniques present a distinctive ability to resolve vertical structure of optical properties within the upper water column at both day- and night-time. However, accuracy challenges remain for existing lidar instruments due to the ill-posed nature of elastic backscatter lidar retrievals and multiple scattering. Here we demonstrate the high performance of, to the best of our knowledge, the first shipborne oceanic high-spectral-resolution lidar (HSRL) and illustrate a multiple scattering correction algorithm to rigorously address the above challenges in estimating the depth-resolved diffuse attenuation coefficient Kd and the particulate backscattering coefficient bbp at 532 nm. HSRL data were collected during day- and night-time within the coastal areas of East China Sea and South China Sea, which are connected by the Taiwan Strait. Results include vertical profiles from open ocean waters to moderate turbid waters and first lidar continuous observation of diel vertical distribution of thin layers at a fixed station. The root-mean-square relative differences between the HSRL and coincident in situ measurements are 5.6% and 9.1% for Kd and bbp, respectively, corresponding to an improvement of 2.7-13.5 and 4.9-44.1 times, respectively, with respect to elastic backscatter lidar methods. Shipborne oceanic HSRLs with high performance are expected to be of paramount importance for the construction of 3D map of ocean ecosystem.

7.
Medicine (Baltimore) ; 101(36): e30192, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086752

RESUMO

INTRODUCTION: Prognostic biomarkers for osteosarcoma (OS) are still very few, and this study aims to examine 2 novel prognostic biomarkers for OS through combined bioinformatics and experimental approach. MATERIALS AND METHODS: Expression profile data of OS and paraneoplastic tissues were downloaded from several online databases, and prognostic genes were screened by differential expression analysis, Univariate Cox analysis, least absolute shrinkage and selection operator regression analysis, and multivariate Cox regression analysis to construct prognostic models. The accuracy of the model was validated using principal component analysis, constructing calibration plots, and column line plots. We also analyzed the relationship between genes and drug sensitivity. Gene expression profiles were analyzed by immunocytotyping. Also, protein expressions of the constructed biomarkers in OS and paraneoplastic tissues were verified by immunohistochemistry. RESULTS: Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) and Syndecan 3 (SDC3, met all our requirements after screening. The constructed prognostic model indicated that patients in the high-risk group had a much lower patient survival rate than in the low-risk group. Moreover, these genes were closely related to immune cells (P < .05). Drug sensitivity analysis showed that the 2 genes modeled were strongly correlated with multiple drugs. Immunohistochemical analysis showed significantly higher protein expression of both genes in OS than in paraneoplastic tissues. CONCLUSIONS: HS2ST1 and SDC3 are significantly dysregulated in OS, and the prognostic models constructed based on these 2 genes have much lower survival rates in the high-risk group than in the low-risk group. HS2ST1 and SDC3 can be used as glycolytic and immune-related prognostic biomarkers in OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Osteossarcoma/genética , Sindecana-3/genética , Sindecana-3/metabolismo
8.
Orthop Surg ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098492

RESUMO

OBJECTIVE: A stable animal model was needed to study bone non-union caused by insufficient blood supply, the main object of this paper is to develop a medial malleolar fracture model with controllable arterial vascular injuries in rats for revealing the biochemical mechanism of non-union by insufficient blood supply. METHODS: A total of 18 rats were randomly divided into three equal groups: the Sham group, the Fracture group, and the Fracture + Vascular group. The animals were subjected to unilateral medial malleolar bone fracture and vascular injury using customized molding equipment. The fracture site was scanned by micro-CT, and vascular injury was evaluated by laser Doppler flowmetry (LDF) 24 h after modeling. Histological examination (HE), alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry and immunofluorescence were conducted on the medial malleolar fracture tissues of three rats randomly selected from each group 24 h after modeling. Subsequently, to further confirm the success of fracture modeling, the fracture sites of three other rats in each group underwent micro-CT scanning again 6 weeks after surgery. RESULTS: The results of a 24 h micro-CT showed that all rats used to create the fracture models showed controlled injury of the medial malleolus. The model was stable, and the satisfaction of the homemade equipment agreed with the expectation. LDF showed that the blood flow of rats in the Fracture + Vascular group decreased significantly 24 h after fracture injury, while collateral blood flow perfusion increased by 50% on average. The results of HE, ALP and TRAP staining in the medial malleolus showed that the number of osteoblasts (OBs) and osteoclasts (OCs) in the Fracture group increased significantly, but the number of OBs and OCs in the Fracture + Vascular group decreased sharply relative to the number in the Sham group 24 h later. Furthermore, immunohistochemistry and immunofluorescence results showed that the number of neovessels in the Fracture group was significantly increased, while the number of neovessels in the Fracture + Vascular group was significantly decreased, which was consistent with the above results. After 6 weeks of modeling, the micro-CT results showed that the fractures in the Fracture group had healed substantially, while those in the Fracture + Vascular group had not. CONCLUSION: This study provided a reproducible and stable experimental animal model for medial malleolar fractures with arterial injury.

9.
Foods ; 11(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36076770

RESUMO

Lactic acid bacteria have been considered to be a very important species during sourdough fermentation. In order to explore the effects of bifidobacteria fermentation on thermal, physico-chemical and structural properties of wheat starch during dough fermentation, starch granules were separated from the fermented dough at different fermentation times, including 0 h, 2 h, 6 h, 9 h and 12 h. The results showed that the morphology of starch granules was destroyed gradually as the fermentation time increased, which appeared as erosion and rupture. With the increase in fermentation time, the solubility showed a significant increase, which changed from 8.51% (0 h) to 9.80% (12 h), and the swelling power was also increased from 9.31% (0 h) to 10.54% (12 h). As for the gelatinization property, the enthalpy was increased from 6.77 J/g (0 h) to 7.56 J/g (12 h), indicating a more stable thermal property of fermented starch, especially for the longer fermentation. The setback value was decreased with short fermentation time, indicating that the starch with a longer fermentation time was difficult to retrograde. The hardness of the gel texture was decreased significantly from 50.11 g to 38.66 g after fermentation for 12 h. The results show that bifidobacteria fermentation is an effective biological modification method of wheat starch for further applications.

10.
Proc Natl Acad Sci U S A ; 119(32): e2206321119, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35914135

RESUMO

A fundamental understanding of extracellular microenvironments of O2 and reactive oxygen species (ROS) such as H2O2, ubiquitous in microbiology, demands high-throughput methods of mimicking, controlling, and perturbing gradients of O2 and H2O2 at microscopic scale with high spatiotemporal precision. However, there is a paucity of high-throughput strategies of microenvironment design, and it remains challenging to achieve O2 and H2O2 heterogeneities with microbiologically desirable spatiotemporal resolutions. Here, we report the inverse design, based on machine learning (ML), of electrochemically generated microscopic O2 and H2O2 profiles relevant for microbiology. Microwire arrays with suitably designed electrochemical catalysts enable the independent control of O2 and H2O2 profiles with spatial resolution of ∼101 µm and temporal resolution of ∼10° s. Neural networks aided by data augmentation inversely design the experimental conditions needed for targeted O2 and H2O2 microenvironments while being two orders of magnitude faster than experimental explorations. Interfacing ML-based inverse design with electrochemically controlled concentration heterogeneity creates a viable fast-response platform toward better understanding the extracellular space with desirable spatiotemporal control.


Assuntos
Microambiente Celular , Eletroquímica , Peróxido de Hidrogênio , Aprendizado de Máquina , Oxigênio , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/metabolismo , Oxigênio/análise , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Angew Chem Int Ed Engl ; : e202210658, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913045

RESUMO

Part of tetrahedral framework aluminum in a protonic mordenite (HMOR) will convert geometry to distorted tetrahedral and octahedral coordination. High-field 27 Al NMR data show that more framework Al atoms at T3 and T4 sites change geometry to nonframework structures than others. These nonframework Al species preferentially reside in the side pockets, which will decrease the accessibility of acid sites in the 8-membered ring (MR) channel, impairing the dimethyl ether (DME) carbonylation reaction. The arisen octahedrally coordinated Al species are framework-associated, which can be reverted into the zeolite framework. Herein, we find that a facile treatment with pyridine could force the octahedral coordination Al back into a tetrahedral environment, which could increase the number of available active sites and enhance the diffusion of DME, thus improving the reactivity (4 times) of the DME carbonylation reaction and prolonging the lifetime of catalysts.

12.
Front Surg ; 9: 935656, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959114

RESUMO

Background: Anterior cervical decompression and fusion can effectively treat cervical spondylotic myelopathy (CSM). Accurately classifying patients with CSM who have undergone anterior cervical decompression and fusion is the premise of precision medicine. In this study, we used machine learning algorithms to classify patients and compare the postoperative efficacy of each classification. Methods: A total of 616 patients with cervical spondylotic myelopathy who underwent anterior cervical decompression and fusion were enrolled. Unsupervised machine learning algorithms (UMLAs) were used to cluster subjects according to similar clinical characteristics. Then, the results of clustering were visualized. The surgical outcomes were used to verify the accuracy of machine learning clustering. Results: We identified two clusters in these patients who had significantly different baseline clinical characteristics, preoperative complications, the severity of neurological symptoms, and the range of decompression required for surgery. UMLA divided the CSM patients into two clusters according to the severity of their illness. The repose to surgical treatment between the clusters was significantly different. Conclusions: Our results showed that UMLA could be used to rationally classify a heterogeneous cohort of CSM patients effectively, and thus, it might be used as the basis for a data-driven platform for identifying the cluster of patients who can respond to a particular treatment method.

13.
Biofabrication ; 14(4)2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35973411

RESUMO

Most ofin vivotissue cells reside in 3D extracellular matrix (ECM) with fluid flow. To better study cell physiology and pathophysiology, there has been an increasing need in the development of methods for culturing cells inin vivolike microenvironments with a number of strategies currently being investigated including hydrogels, spheroids, tissue scaffolds and very promising microfluidic systems. In this paper, a 'sandwich' structure-liked microfluidic device integrated with a 3D printing scaffold is proposed for three-dimensional and dynamic cell culture. The device consists of three layers, i.e. upper layer, scaffold layer and bottom layer. The upper layer is used for introducing cells and fixing scaffold, the scaffold layer mimicking ECM is used for providing 3D attachment areas, and the bottom layer mimicking blood vessels is used for supplying dynamic medium for cells. Thermally assisted electrohydrodynamic jet (TAEJ) printing technology and microfabrication technology are combined to fabricate the device. The flow field in the chamber of device is evaluated by numerical simulation and particle tracking technology to investigate the effects of scaffold on fluid microenvironment. The cell culturing processes are presented by the flow behaviors of inks with different colors. The densities and viabilities of HeLa cells are evaluated and compared after 72 h of culturing in the microfluidic devices and 48-well plate. The dose-dependent cell responses to doxorubicin hydrochloride (DOX) are observed after 24 h treatment at different concentrations. These experimental results, including the evaluation of cell proliferation andin vitrocytotoxicity assessment of DOX in the devices and plate, demonstrate that the presented microfluidic device has good biocompatibility and feasibility, which have great potential in providing native microenvironments forin vitrocell studies, tissue engineering and drug screening for tumor therapy.


Assuntos
Dispositivos Lab-On-A-Chip , Impressão Tridimensional , Células HeLa , Humanos , Engenharia Tecidual/métodos , Tecidos Suporte
14.
Environ Int ; 167: 107446, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35940031

RESUMO

BACKGROUND: Bisphenol A (BPA) as an endocrine disrupting chemical has been shown to alter reproductive endocrine function, but little is known on its analogues such as bisphenol F (BPF) and bisphenol S (BPS) with increasing usage and exposure. OBJECTIVE: To explore the associations between exposures to BPA, BPF and BPS and serum reproductive hormones among reproductive-aged Chinese men. METHODS: We measured BPA, BPF and BPS concentrations in repeated urine samples and multiple reproductive hormones in the serum samples collected from 462 men attending an infertility clinic in Wuhan, China. Linear regression models were applied to assess the associations between averaged urinary BPA, BPF and BPS levels and serum hormone concentrations, and restricted cubic spline (RCS) models were further utilized to explore potential non-linear associations. We also examined potential modifying effects by age and body mass index (BMI). RESULTS: There was little evidence of associations between BPA exposure and altered reproductive hormones. However, we found that elevated BPF and BPS exposures were in negative associations with estrogen (E2) levels and E2/T (total testosterone) ratio (all P for trends < 0.05), and that elevated BPS exposure was negatively associated with SHBG levels (P for trend = 0.09). Based on the RCS models, these linear negative associations except that between BPS exposure and E2/T ratio were further confirmed. In stratified analyses, BPF and BPS exposures in relation to reduced E2 and E2/T ratio were more pronounced among men aged > 30 years, whereas their associations with reduced SHBG levels were more pronounced among men aged ≤ 30. Also, BPS exposure in negative association with FSH only emerged among men with BMI ≥ 24 kg/m2 (P for interaction = 0.03). CONCLUSION: BPF and BPS exposures were negatively associated with male serum E2, E2/T ratio and SHBG levels, and these associations varied by age and BMI.


Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Adulto , Compostos Benzidrílicos/urina , China , Disruptores Endócrinos/efeitos adversos , Humanos , Masculino , Fenóis , Reprodução , Testosterona
15.
Genes (Basel) ; 13(8)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-36011261

RESUMO

Although salinity stress is one of the principal abiotic stresses affecting crop yield, a suitable concentration of NaCl has proven to be useful for increasing crop quality. This study used low salinity (34 mmol/L NaCl) and high salinity (85 mmol/L) to cultivate purple sweetpotato. Using transcriptomics and metabolomics to profile the pathway indicated that glycometabolism, secondary metabolite biosynthesis and the starch catabolic process were the significant pathways under the salinity stress. Further research showed that purple sweetpotato could regulate genes related to the regulation of the cellular Na+, K+, and other ions concentration in response to the low salinity tolerance, but loses this ability under high salinity. Meanwhile, under low salinity, the activity of antioxidant enzymes and their related gene expression are maintained at a high level. The low salinity influences the monosaccharide composition as well as the content and regulation of genes related to starch synthesis. Quality analysis showed that the low salinity could increase the starch content and influence the amylopectin biosynthesis. It suggested that low salinity promotes substance accumulation. High salinity could increase the anthocyanins biosynthesis and low salinity had a significant impact on phenolic acid and flavonol. Finally, the gene expression levels also prove the low salinity could change the composition and content level of the purple sweetpotato. This study showed that an appropriate concentration of NaCl can be used as an elicitor for application in purple sweetpotato planting.


Assuntos
Ipomoea batatas , Adaptação Psicológica , Antocianinas/genética , Antocianinas/metabolismo , Ipomoea batatas/genética , Salinidade , Cloreto de Sódio/metabolismo , Cloreto de Sódio/farmacologia , Amido/metabolismo
16.
Nat Commun ; 13(1): 4579, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931691

RESUMO

Electrochemical intercalation can enable lithium extraction from dilute water sources. However, during extraction, co-intercalation of lithium and sodium ions occurs, and the response of host materials to this process is not fully understood. This aspect limits the rational materials designs for improving lithium extraction. Here, to address this knowledge gap, we report one-dimensional (1D) olivine iron phosphate (FePO4) as a model host to investigate the co-intercalation behavior and demonstrate the control of lithium selectivity through intercalation kinetic manipulations. Via computational and experimental investigations, we show that lithium and sodium tend to phase separate in the host. Exploiting this mechanism, we increase the sodium-ion intercalation energy barrier by using partially filled 1D lithium channels via non-equilibrium solid-solution lithium seeding or remnant lithium in the solid-solution phases. The lithium selectivity enhancement after seeding shows a strong correlation with the fractions of solid-solution phases with high lithium content (i.e., LixFePO4 with 0.5 ≤ x < 1). Finally, we also demonstrate that the solid-solution formation pathway depends on the host material's particle morphology, size and defect content.

17.
Front Pharmacol ; 13: 870553, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935862

RESUMO

Osteoporosis is among the major contributors of pathologic fracture in postmenopausal women, which is caused by the bone metabolic disorder owing to the over-activation of osteoclasts. Inhibition of osteoclast differentiation and maturation has become a mainstream research interest in the prevention of osteoporosis. Isoliensinine (Iso) is a dibenzyl isoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-cancer activities. However, whether it can be used as a potential treatment for osteoporosis remains undiscovered. Here, we investigated whether Iso might suppress the differentiation of osteoclasts in vitro and in vivo to play an anti-osteoporosis role. Our results showed that Iso inhibits the formation of mature multinuclear osteoclasts induced by RANKL, the bone resorption, and the osteoclast-specific genes expression by blocking the nuclear translocation of NF-κB p65, and the effect was in a dosage-dependent way. Furthermore, we investigated the therapeutic effect of Iso on osteoporosis in ovariectomized (OVX) mice. We found that Iso attenuated bone loss in the OVX mice and significantly promoted BS, Conn. DN, Tb.Th, TB.N, and BV/TV Index. All in all, Iso showed a prominent effect of osteoclast inhibition, with great promise for treating osteoporosis.

18.
Theranostics ; 12(12): 5418-5433, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910800

RESUMO

Rational: The complex vascular architecture and diverse immune cells of the liver are critical for maintaining liver homeostasis. However, quantification of the network of liver vasculature and immunocytes at different scales from a single hepatic lobule to an intact liver lobe remains challenging. Methods: Here, we developed a fast and fluorescence-preserving transparency method, denoted liver-CUBIC, for systematic and integrated analysis of the microcirculation and the three-dimensional distribution of dendritic cells (DCs)/macrophages in intact liver lobes. Results: Whole-mount imaging at mesoscale revealed that the hepatic classical lobule preferred the oblate ellipsoid morphology in the mouse liver and exhibited hepatic sinusoids with heterogeneous arrangement and intricate loop structure. Liver fibrosis not only induces sinusoidal density increase but also promotes sinusoidal arrangement with increased sinusoidal branch and loop structure. Meanwhile, we found that CD11c+ DCs followed a lognormal distribution in the hepatic lobules, skewing toward lobular boundary in steady state. CCl4-induced chronic liver injury promoted CD11c+ DC rearrangement at the lobular border before the formation of liver fibrosis. Furthermore, through whole-mount imaging of tumor-immune cell-vascular crosstalk in intact lobes based on liver-CUBIC, we characterized an accumulation of CX3CR1+CCR2+F4/80+ macrophages at metastatic foci in early colorectal liver metastases. Importantly, colorectal cells secrete CCL2 to mobilize CX3CR1+CCR2+F4/80+ macrophages to accumulate at liver micrometastases, and the interruption of CCL2-induced macrophage accumulation inhibits early colonization of metastasis in the liver. Conclusions: Our investigation of the sinusoidal network and DC/macrophage arrangements through the liver-CUBIC approach and whole-mount imaging provide a powerful platform for understanding hepatic circulatory properties and immune surveillance in the liver.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Animais , Neoplasias Colorretais/patologia , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Macrófagos/patologia , Camundongos
19.
Artigo em Inglês | MEDLINE | ID: mdl-35801670

RESUMO

Separation of Cs/Sr is one of many coordination-chemistry-centered processes in the grand scheme of spent nuclear fuel reprocessing, a critical link for a sustainable nuclear energy industry. To deploy a crystallizing Cs/Sr separation technology, we planned to systematically screen and identify candidate ligands that can efficiently and selectively bind to Sr2+ and form coordination polymers. Therefore, we mined the Cambridge Structural Database for characteristic structural information and developed a machine-learning-guided methodology for ligand evaluation. The optimized machine-learning model, correlating the molecular structures of the ligands with the predicted coordinative properties, generated a ranking list of potential compounds for Cs/Sr selective crystallization. The Sr2+ sequestration capability and selectivity over Cs+ of the promising ligands identified (squaric acid and chloranilic acid) were subsequently confirmed experimentally, with commendable performances, corroborating the artificial-intelligence-guided strategy.

20.
Nat Commun ; 13(1): 3835, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35788583

RESUMO

Global obesity epidemics impacts human health and causes obesity-related illnesses, including the obesity-related kidney and liver diseases. UTX, a histone H3K27 demethylase, plays important roles in development and differentiation. Here we show that kidney-specific knockout Utx inhibits high-fat diet induced lipid accumulation in the kidney and liver via upregulating circulating serine levels. Mechanistically, UTX recruits E3 ligase RNF114 to ubiquitinate phosphoglycerate dehydrogenase, the rate limiting enzyme for de novo serine synthesis, at Lys310 and Lys330, which leads to its degradation, and thus suppresses renal and circulating serine levels. Consistently, phosphoglycerate dehydrogenase and serine levels are markedly downregulated in human subjects with diabetic kidney disease or obesity-related renal dysfunction. Notably, oral administration of serine ameliorates high-fat diet induced fatty liver and renal dysfunction, suggesting a potential approach against obesity related metabolic disorders. Together, our results reveal a metabolic homeostasis regulation mediated by a renal UTX-PHGDH-serine axis.


Assuntos
Nefropatias Diabéticas , Doenças Metabólicas , Histona Desmetilases , Humanos , Rim , Fígado , Obesidade/complicações , Fosfoglicerato Desidrogenase/genética , Serina
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