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1.
Sci Rep ; 11(1): 6969, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772055

RESUMO

Treatment of ventilated patients with gram-negative pneumonia (GNP) is often unsuccessful. We aimed to assess the efficacy and safety of nebulized amikacin (NA) as adjunctive therapy to systemic antibiotics in this patient population. PubMed, Embase, China national knowledge infrastructure, Wanfang, and the Cochrane database were searched for randomized controlled trials (RCTs) investigating the effect of NA as adjunctive therapy in ventilated adult patients with GNP. Heterogeneity was explored using subgroup analysis and sensitivity analysis. The Grading of recommendations assessment, development, and evaluation approach was used to assess the certainty of the evidence. Thirteen RCTs with 1733 adults were included. The pooled results showed NA had better microbiologic eradication (RR = 1.51, 95% CI 1.35 to 1.69, P < 0.0001) and improved clinical response (RR = 1.23; 95% CI 1.13 to 1.34; P < 0.0001) when compared with control. Meanwhile, overall mortality, pneumonia associated mortality, duration of mechanical ventilation, length of stay in ICU and change of clinical pneumonia infection scores were similar between NA and control groups. Additionally, NA did not add significant nephrotoxicity while could cause more bronchospasm. The use of NA adjunctive to systemic antibiotics therapy showed better benefits in ventilated patients with GNP. More well-designed RCTs are still needed to confirm our results.

2.
Orthop Surg ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686801

RESUMO

OBJECTIVE: To evaluate whether it is safe and effective for orthopaedic medical staff to provide support to the work against COVID-19. METHODS: One hundred and twenty-two orthopaedic medical staff from the orthopaedic center of Zhongnan Hospital of Wuhan University were included in this retrospective investigation. A total of 43 surgeons and 69 nurses provided medical support in the treatment of COVID-19 patients from 1 January 2020 to 8 April 2020 in four different hospitals in Wuhan. We collected data on the age, gender, and body temperature of orthopaedic medical staff, as well as the results for their chest CT scans, SARS-CoV-2 RNA, SARS-CoV-2 IgM and SARS-CoV-2 IgG tests, and training and examinations on COVID-19 knowledge. We also collected data on the time span of work, the number of infected staff during the support period, the number of COVID-19 patients the surgeons treated and the cure rate, the performance of the surgeons as assessed by the specialists and patients, and the number of infected staff during the pandemic. RESULTS: Among the 49 surgeons and 73 nurses, 43 surgeons and 69 nurses provided support against COVID-19. A total of 12 surgeons and 11 nurses provided support in the fields of respiration, intensive care, and emergency. A total of 34 surgeons and 58 nurses worked in the designated wards restructured for COVID-19 in the orthopaedic building. The average time span of work for the surgeons and nurses was 14.78 ± 3.64 days and 24.77 ± 7.58 days, respectively. No staff were infected during the support period. Over 1000 patients were received in the fever clinic by orthopaedic surgeons. The overall number of the treated hospitalized patients was 622. Among these patients, 226 cases were mild, 318 were mild to moderate, and 58 were severe or critical. The cure rate was 96.01%, 99.37%, and 52.00% respectively. The performance of the surgeons was scored 87.02 ± 3.17 and 90.69 ± 3.58 by the specialists and the patients, respectively. During the whole pandemic, 3 surgeons and 3 nurses who did not participate in the support work were infected in the early stages. The morbidity of all the orthopaedic staff was 4.92% during the whole pandemic, while no one was infected during the support work. CONCLUSION: Our investigation indicated that although they worked outside their specialty, it was safe and effective for the orthopaedic staff to provide medical support in the work against COVID-19 with adequate precautions and proper training.

3.
PLoS Biol ; 19(2): e3001122, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33630828

RESUMO

The Hippo-YAP pathway responds to diverse environmental cues to manage tissue homeostasis, organ regeneration, tumorigenesis, and immunity. However, how phosphatase(s) directly target Yes-associated protein (YAP) and determine its physiological activity are still inconclusive. Here, we utilized an unbiased phosphatome screening and identified protein phosphatase magnesium-dependent 1A (PPM1A/PP2Cα) as the bona fide and physiological YAP phosphatase. We found that PPM1A was associated with YAP/TAZ in both the cytoplasm and the nucleus to directly eliminate phospho-S127 on YAP, which conferring YAP the nuclear distribution and transcription potency. Accordingly, genetic ablation or depletion of PPM1A in cells, organoids, and mice elicited an enhanced YAP/TAZ cytoplasmic retention and resulted in the diminished cell proliferation, severe gut regeneration defects in colitis, and impeded liver regeneration upon injury. These regeneration defects in murine model were largely rescued via a genetic large tumor suppressor kinase 1 (LATS1) deficiency or the pharmacological inhibition of Hippo-YAP signaling. Therefore, we identify a physiological phosphatase of YAP/TAZ, describe its critical effects in YAP/TAZ cellular distribution, and demonstrate its physiological roles in mammalian organ regeneration.

5.
Artif Cells Nanomed Biotechnol ; 49(1): 71-82, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33423558

RESUMO

Hydrogel serve as bone tissue engineering have lately received great attention for their good biocompatibility and structures similar to natural extracellular matrices. However, a single component polymer hydrogel is generally detrimental to cell adhesion due to the weaker mechanical properties, which limits their application considerably. In an effort to overcome this disadvantage, we adopt an unconventional dual network hydrogels consisting of the polyethylene glycol diacrylate (PEGDA) covalent network, a thiolated chitosan (TCS) ion crosslinking network and thiolated halloysites (T-HNTs) as reinforcing filler. In addition, bone morphogenetic protein-2 (BMP-2) was loaded into the prepared dual network (DN) hydrogel to improve the bone regeneration function of the DN hydrogel. The resulting PEGDA/TCS/T-HNTs hydrogels showed favourable mechanical property, higher crosslinking density, the lower swelling degree, excellent biocompatibility and cell adhesion ability. The histomorphometric and immunohistochemical analyses revealed the excellent bone regeneration ability for composite hydrogel after implant into rat skull defect. Thus, our results indicated that composite scaffold can be applied as a new bone regeneration biomaterial to be applied as a local drug delivery system with good bone induction performance.

6.
Cell Death Differ ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504946

RESUMO

Protein Preferentially Expressed Antigen in Melanoma (Prame), a tumor-associated antigen, has been found to frequently overexpress in various cancers, which indicates advanced cancer stages and poor clinical prognosis. Moreover, previous reports noted that Prame functions as a substrate recognizing receptor protein of Cullin RING E3 ligases (CRLs) to mediate potential substrates degradation through Ubiquitin Proteasome System (UPS). However, none of the Prame specific substrate has been identified so far. In this study, proteomic analysis of RBX1-interacting proteins revealed p14/ARF, a well-known tumor suppressor, as a novel ubiquitin target of RBX1. Subsequently, immunoprecipitation and in vivo ubiquitination assay determined Cullin2-RBX1-Transcription Elongation Factor B Subunit 2 (EloB) assembled CRL2 E3 ligase complex to regulate the ubiquitination and subsequent degradation of p14/ARF. Finally, through siRNA screening, Prame was identified as the specific receptor protein responsible for recognizing p14/ARF to be degraded. Additionally, via bioinformatics analysis of TCGA database and clinical samples, Prame was determined to overexpress in tumor tissues vs. paired adjacent tissues and associated with poor prognosis of cancer patients. As such, downregulation of Prame expression significantly restrained cancer cell growth by inducing G2/M phase cell cycle arrest, which could be rescued by simultaneously knocking down of p14/ARF. Altogether, targeting overexpressed Prame in cancer cells inactivated RBX1-Cullin2-EloB-Prame E3 ligase (CRL2Prame) and halted p14/ARF degradation to restrain tumor growth by inducing G2/M phase cell cycle arrest.

7.
Genes Genomics ; 43(2): 141-150, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33481227

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are a crucial class of regulatory RNAs in cancer procession, including papillary thyroid cancer (PTC). Circ-Pumilio 1 (circPUM1) is a novel circRNA with the oncogenic function in ovarian cancer and lung cancer. However, the role of circPUM1 in PTC is undiscovered. OBJECTIVE: This study was performed to investigate the biological function and molecular mechanism of circPUM1 in PTC. METHODS: CircPUM1 and microRNA-21-5p (miR-21-5p) levels were analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular viability and metastasis were measured using Cell Counting Kit 8 (CCK-8) and transwell migration/invasion assay. Glycolysis was evaluated by glucose uptake and lactate production. Associated proteins were examined applying with western blot. Dual-luciferase reporter assay and RNA pull-down assay were used to analyze the interaction between circPUM1 or mitogen-activated protein kinase 1 (MAPK1) and miR-21-5p. Moreover, the role of circPUM1 in vivo was explored by xenograft tumor experiment. RESULTS: Significantly, circPUM1 was upregulated in PTC tissue samples and cells. Cell growth, metastasis and glycolytic process of PTC cells were all inhibited after downregulation of circPUM1. Besides, circPUM1 could sponge miR-21-5p and MAPK1 was a target gene of miR-21-5p. Furthermore, we found that the anti-cancer effect of circPUM1 knockdown on PTC was partly ascribed to MAPK1 downregulation by upregulating miR-21-5p. Silencing circPUM1 also impeded tumorigenesis of PTC in vivo via miR-21-5p/MAPK1 axis. CONCLUSION: These findings suggested that circPUM1 knockdown inhibited MAPK1 expression by targeting miR-21-5p, consequently leading to the repressive effect on PTC progression. CircPUM1 might be a promising target to improve the diagnosis and treatment of PTC.

8.
Protein Sci ; 30(3): 531-542, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33336515

RESUMO

Focal adhesions (FAs) are integrin-containing protein complexes regulated by a network of hundreds of protein-protein interactions. They are formed in a spatiotemporal manner upon the activation of integrin transmembrane receptors, which is crucial to trigger cell adhesion and many other cellular processes including cell migration, spreading and proliferation. Despite decades of studies, a detailed molecular level understanding on how FAs are organized and function is lacking due to their highly complex and dynamic nature. However, advances have been made on studying key integrin activators, talin and kindlin, and their associated proteins, which are major components of nascent FAs critical for initiating the assembly of mature FAs. This review will discuss the structural and functional findings of talin and kindlin and their immediate interaction network, which will shed light upon the architecture of nascent FAs and how they act as seeds for FA assembly to dynamically regulate diverse adhesion-dependent physiological and pathological responses.

9.
Mol Cell ; 80(6): 1013-1024.e6, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33338401

RESUMO

Impaired DNA crosslink repair leads to Fanconi anemia (FA), characterized by a unique manifestation of bone marrow failure and pancytopenia among diseases caused by DNA damage response defects. As a germline disorder, why the hematopoietic hierarchy is specifically affected is not fully understood. We find that reprogramming transcription during hematopoietic differentiation results in an overload of genotoxic stress, which causes aborted differentiation and depletion of FA mutant progenitor cells. DNA damage onset most likely arises from formaldehyde, an obligate by-product of oxidative protein demethylation during transcription regulation. Our results demonstrate that rapid and extensive transcription reprogramming associated with hematopoietic differentiation poses a major threat to genome stability and cell viability in the absence of the FA pathway. The connection between differentiation and DNA damage accumulation reveals a novel mechanism of genome scarring and is critical to exploring therapies to counteract the aplastic anemia for the treatment of FA patients.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Reprogramação Celular/genética , Anemia de Fanconi/genética , Formaldeído/toxicidade , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/genética , Anemia de Fanconi/sangue , Anemia de Fanconi/patologia , Formaldeído/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Instabilidade Genômica/genética , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Células K562 , Transcrição Genética
10.
Mol Cell ; 80(5): 810-827.e7, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33171123

RESUMO

Mitochondrial morphology shifts rapidly to manage cellular metabolism, organelle integrity, and cell fate. It remains unknown whether innate nucleic acid sensing, the central and general mechanisms of monitoring both microbial invasion and cellular damage, can reprogram and govern mitochondrial dynamics and function. Here, we unexpectedly observed that upon activation of RIG-I-like receptor (RLR)-MAVS signaling, TBK1 directly phosphorylated DRP1/DNM1L, which disabled DRP1, preventing its high-order oligomerization and mitochondrial fragmentation function. The TBK1-DRP1 axis was essential for assembly of large MAVS aggregates and healthy antiviral immunity and underlay nutrient-triggered mitochondrial dynamics and cell fate determination. Knockin (KI) strategies mimicking TBK1-DRP1 signaling produced dominant-negative phenotypes reminiscent of human DRP1 inborn mutations, while interrupting the TBK1-DRP1 connection compromised antiviral responses. Thus, our findings establish an unrecognized function of innate immunity governing both morphology and physiology of a major organelle, identify a lacking loop during innate RNA sensing, and report an elegant mechanism of shaping mitochondrial dynamics.

11.
J Pathol ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009820

RESUMO

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient-derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

12.
Oncogene ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051597

RESUMO

Oxidative stress-responsive kinase 1 (OSR1) plays a critical role in multiple carcinogenic signal pathways, and its overexpression has been found in various types of cancer; however, the pathophysiological role of OSR1 in breast cancer has not been evaluated. This study aims to elaborate on the role of OSR1 in breast cancer metastasis and the specific regulatory mechanism. Our results showed that OSR1 mRNA and protein were upregulated in both human breast cancer samples and cell lines. Moreover, phosphorylated OSR1 (p-OSR1) was an independent poor prognostic indicator in patients with breast cancer. OSR1 upregulation induced epithelial-to-mesenchymal transition (EMT) in normal and malignant mammary epithelial cells with the increasing metastatic capacity. In contrast, deleting OSR1 in aggressive breast cancer cells inhibited these phenotypes. OSR1 is the critical activator for transcription factors of EMT. Mechanistically, we found that OSR1 can directly interact and phosphorylate the linker region of Smad2 at Thr220 and Smad3 at Thr179. Phosphorylated Smad2/3 translocated into the nucleus to enhance transforming growth factor-ß1 (TGF-ß1) autocrine signalling and increase the transcription of EMT regulators. Importantly, interruption of the OSR1-Smad2/3-TGF-ß1 signalling axis elicited a robust anti-EMT and anti-metastatic effect in vitro and in vivo. Taken together, we conclude that OSR1-mediated Smad2/3-TGF-ß1 signalling promotes EMT and metastasis representing a promising therapeutic target in breast cancer treatment.

14.
Sci Data ; 7(1): 311, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968064

RESUMO

Surface solar radiation is an indispensable parameter for numerical models, and the diffuse component contributes to the carbon uptake in ecosystems. We generated a 12-year (2007-2018) hourly dataset from Multi-functional Transport Satellite (MTSAT) satellite observations, including surface total solar radiation (Rs) and diffuse radiation (Rdif), with 5-km spatial resolution through deep learning techniques. The used deep network tacks the integration of spatial pattern and the simulation of complex radiation transfer by combining convolutional neural network and multi-layer perceptron. Validation against ground measurements shows the correlation coefficient, mean bias error and root mean square error are 0.94, 2.48 W/m2 and 89.75 W/m2 for hourly Rs and 0.85, 8.63 W/m2 and 66.14 W/m2 for hourly Rdif, respectively. The correlation coefficient of Rs and Rdif increases to 0.94 (0.96) and 0.89 (0.92) at daily (monthly) scales, respectively. The spatially continuous hourly maps accurately reflect regional differences and restore the diurnal cycles of solar radiation at fine resolution. This dataset can be valuable for studies on regional climate changes, terrestrial ecosystem simulations and photovoltaic applications.

15.
J Psychiatr Res ; 131: 108-113, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32950707

RESUMO

BACKGROUND: Neural cell adhesion molecule (NCAM) plays an important role in neurodevelopmental processes and regulates hippocampal plasticity. This study investigated the relationship between the serum NCAM concentrations and hippocampal volume and psychotic symptoms in first-episode drug naïve schizophrenia (FES) patients. METHODS: Forty-four FES patients and forty-four healthy controls (HC) were recruited in this study. Serum concentrations of NCAM were measured by ELISA. Psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). Brain structural images were obtained using a 3T MRI Scanner and obtained T1 images were processed in order to determine hippocampal grey matter volumes. RESULTS: Schizophrenia patients revealed significantly decreased serum NCAM concentrations (p = 0.017), which were positively correlated with the left (r = 0.523, p < 0.001) and right (r = 0.449, p = 0.041) hippocampal volumes, but negatively correlated with the PANSS positive symptom scores (r = -0.522 p = 0.001). However, no such correlations existed in the HC group. CONCLUSIONS: This is the first time to report that decreased serum NCAM concentrations were associated with hippocampal volumes and symptom severity in FES patients. Our data indicate that the low NCAM is possible neuropathology that is associated with the decreased hippocampus in FES patients.

16.
Biomed Pharmacother ; 131: 110707, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32905942

RESUMO

The antipsychotic effect of Quetiapine (Que) has been extensively studied and growing evidence suggests that Que has a beneficial effect, improving cognitive functions and promoting myelin repair. However, the effects of Que on the brain lipidome and the association between Que-associated cognitive improvement and changes in lipids remain elusive. In the present study, we assessed the cognitive protective effects of Que treatment and used a mass spectrometry-based lipidomic approach to evaluated changes in lipid composition in the hippocampus, prefrontal cortex (PFC), and striatum in a mouse model of cuprizone (CPZ)-induced demyelination. CPZ induces cognitive impairment and remarkable lipid changes in the brain, specifically in lipid species of glycerophospholipids and sphingolipids. Moreover, the changes in lipid classes of the PFC were more extensive than those observed in the hippocampus and striatum. Notably, Que treatment ameliorated cuprizone-induced cognitive impairment and partly normalized CPZ-induced lipid changes. Taken together, our data suggest that Que may rescue cognitive behavioral changes from CPZ-induced demyelination through modulation of the brain lipidome, providing new insights into the pharmacological mechanism of Que for schizophrenia.

17.
Life Sci ; 262: 118477, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971103

RESUMO

OBJECTIVE: To investigate how the interaction of CtBP2 with ZBTB18 affect glioblastoma (GBM). METHODS: Western blotting was performed to detect CtBP2 and ZBTB18 expression in GBM and normal brain tissues (NBT). U-87 MG cells were transfected with ZBTB18 CRISPR activation plasmid, CtBP2 shRNA with/without ZBTB18 shRNA. The biological characteristics were detected by EdU assay, MTT, Wound-healing, Transwell, TUNEL staining, and Flow cytometry. Furthermore, U-87 MG cells transfected with CtBP2 shRNA and/or ZBTB18 shRNA were injected into the flank region of mice and the tumor volume was measured. The mRNA and protein expression was quantified by qRT-PCR or Western blotting. RESULTS: GBM tissues exhibited increased CtBP2 expression and decreased ZBTB18 expression, which demonstrated a negative correlation in GBM tissues and showed the combined effect on prognosis. Based on immunoprecipitation and immunofluorescence, there was an interaction between CtBP2 and ZBTB18 in U-87 MG cells. CtBP2 shRNA counteracted the effect of ZBTB18 shRNA on inhibiting U-87 MG cell apoptosis, as well as promoting cell proliferation and viability with increased EMT, invasion and migration. Meanwhile, CtBP2 shRNA interact with ZBTB18 to block cells at phase G0/G1 and suppress SHH-GLI1 pathway. CtBP2 shRNA decreased tumor volume, increase ZBTB18 expression in tumor tissues, and inhibit SHH-GLI1 pathway in mice, which could be reversed by ZBTB18 shRNA. CONCLUSION: CtBP2 elevation and ZBTB18 down-regulation were found in GBM, both of which were associated with prognosis of GBM patients. CtBP2 interacted with ZBTB18 to affect biological characteristics of GBM cells, and the tumor growth, which may be related to the SHH-GLI1 pathway.

18.
Psychiatry Res ; 293: 113436, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889343

RESUMO

A marker for distinguishing patients with obsessive-compulsive disorder (OCD) spectrum has not yet been identified. Whole-brain resting-state effective and functional connectivity (rsEC and rsFC, respectively) networks were constructed for 50 unmedicated OCD (U-OCD) patients, 45 OCD patients in clinical remission (COCD), 47 treatment-resistant OCD (T-OCD) patients, 42 chronic schizophrenia patients who exhibit OCD symptoms (SCHOCD), and 50 healthy controls (HCs). Multivariate pattern analysis (MVPA) was performed to investigate the accuracy of using connectivity alterations to distinguished among the aforementioned groups. Compared to HCs, rsEC connections were significantly disrupted in the U-OCD (n = 15), COCD (n = 8), and T-OCD (n = 19) groups. Additionally, 21 rsEC connections were significantly disrupted in the T-OCD group compared to the SCHOCD group. The disrupted rsEC networks were associated mainly with the frontal-parietal cortex, basal ganglia, limbic regions, and the cerebellum. Classification accuracies for distinguishing OCD patients from HCs and SCHOCD patients ranged from 66.6% to 98.0%. In conclusion, disrupted communication from the frontal-parietal cortices to subcortical basal nuclei and the cerebellum may represent a functional pathological feature of the OCD spectrum. MVPA based on both abnormal rsEC and rsFC patterns may aid in early differential diagnosis of OCD.

19.
Adv Mater ; 32(44): e2004414, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32902012

RESUMO

Metal-organic frameworks (MOFs) based on group 3 and 4 metals are considered as the most promising MOFs for varying practical applications including water adsorption, carbon conversion, and biomedical applications. The relatively strong coordination bonds and versatile coordination modes within these MOFs endow the framework with high chemical stability, diverse structures and topologies, and interesting properties and functions. Herein, the significant progress made on this series of MOFs since 2018 is summarized and an update on the current status and future trends on the structural design of robust MOFs with high connectivity is provided. Cluster chemistry involving Y, lanthanides (Ln, from La to Lu), actinides (An, from Ac to Lr), Ti, and Zr is initially introduced. This is followed by a review of recently developed MOFs based on group 3 and 4 metals with their structures discussed based on the types of inorganic or organic building blocks. The novel properties and arising applications of these MOFs in catalysis, adsorption and separation, delivery, and sensing are highlighted. Overall, this review is expected to provide a timely summary on MOFs based on group 3 and 4 metals, which shall guide the future discovery and development of stable and functional MOFs for practical applications.

20.
Signal Transduct Target Ther ; 5(1): 177, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32873793

RESUMO

Cancer cells are usually characterized by hyperactive glucose metabolism, which can often lead to glucose scarcity; thus, alternative pathways to rewire cancer metabolism are required. Here, we demonstrated that GLUT3 was highly expressed in colorectal cancer (CRC) and negatively linked to CRC patient outcomes, whereas GLUT1 was not associated with CRC prognosis. Under glucose-limiting conditions, GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide synthesis. Notably, GLUT3 had a greater impact on cell growth than GLUT1 under glucose-limiting stress. Mechanistically, low-glucose stress dramatically upregulated GLUT3 via the AMPK/CREB1 pathway. Furthermore, high GLUT3 expression remarkably increased the sensitivity of CRC cells to treatment with vitamin C and vitamin C-containing regimens. Together, the results of this study highlight the importance of the AMPK/CREB1/GLUT3 pathway for CRC cells to withstand glucose-limiting stress and underscore the therapeutic potential of vitamin C in CRC with high GLUT3 expression.

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