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1.
ACS Omega ; 7(2): 2438-2443, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35071931

RESUMO

In this work, the expanded vermiculite/poly(ethylene glycol)-boron nitride (E/PB-X) shape-stabilized composite phase-change materials with the encapsulation capacity of ∼66.16 wt % were prepared by a typical vacuum impregnation method to overcome liquid leakage during phase transition and poor thermal conductivity during heat transfer of poly(ethylene glycol). It was found that the boron nitride showed a great influence on the heat transfer and heat storage of E/PB-X. The thermal conductivity of E/PB-X was 0.45-0.49 W/(m·K), indicating that the heat transfer of E/PB-X was significantly enhanced by the dispersed boron nitride fillers, which was mainly attributed to the reduction of interfacial thermal resistance and the formation of rapid thermally conductive channels. However, the latent heat (∼55.76 J/g) of E/PB-X decreased with the increase in the boron nitride content, revealing that the heat storage behavior of E/PB-X was strongly affected by the confinement of surface interactions of boron nitride and expanded vermiculite, which was consistent with the crystallization behavior determined by X-ray diffractometer (XRD) results. Moreover, the spectroscopy (FT-IR) and thermogravimetric analyzer (TGA) results confirmed that E/PB-X exhibited excellent chemical compatibility and thermal stability, respectively, which were conducive to practical heat storage applications.

2.
Biol Direct ; 17(1): 2, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996511

RESUMO

BACKGROUND: Hepatoblastoma (HB) is identified to be the most common liver malignancy which occurs in children. Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes and diseases, including HB. LncRNA MIR205 host gene (MIR205HG) has been investigated in multiple cancers, however, its role in HB remains to be elucidated. METHODS: MIR205HG expression was analyzed by RT-qPCR. EdU, colony formation and transwell assays were implemented to measure the biological function of MIR205HG on the progression of HB. Mechanism assays were carried out to probe into the underlying mechanism of MIR205HG in HB cells. RESULTS: MIR205HG was significantly overexpressed in HB. Moreover, MIR205HG inhibition suppressed the proliferative, migratory and invasive capacities of HB cells. Furthermore, MIR205HG competitively bound to microRNA-514a-5p (miR-514a-5p) and targeted mitogen-activated protein kinase 9 (MAPK9) to stimulate mitogen activated protein kinase (MAPK) signaling pathway. Besides, MIR205HG also served as a sponge for microRNA-205-5p (miR-205-5p) to activate the PI3K/AKT signaling pathway. CONCLUSION: MIR205HG drives the progression of HB which might provide an efficient marker and new therapeutic target for HB.

3.
Nat Commun ; 13(1): 202, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017484

RESUMO

The redox reactions occurring in the Li-S battery positive electrode conceal various and critical electrocatalytic processes, which strongly influence the performances of this electrochemical energy storage system. Here, we report the development of a single-dispersed molecular cluster catalyst composite comprising of a polyoxometalate framework ([Co4(PW9O34)2]10-) and multilayer reduced graphene oxide. Due to the interfacial charge transfer and exposure of unsaturated cobalt sites, the composite demonstrates efficient polysulfides adsorption and reduced activation energy for polysulfides conversion, thus serving as a bifunctional electrocatalyst. When tested in full Li-S coin cell configuration, the composite allows for a long-term Li-S battery cycling with a capacity fading of 0.015% per cycle after 1000 cycles at 2 C (i.e., 3.36 A g-1). An areal capacity of 4.55 mAh cm-2 is also achieved with a sulfur loading of 5.6 mg cm-2 and E/S ratio of 4.5 µL mg-1. Moreover, Li-S single-electrode pouch cells tested with the bifunctional electrocatalyst demonstrate a specific capacity of about 800 mAh g-1 at a sulfur loading of 3.6 mg cm-2 for 100 cycles at 0.2 C (i.e., 336 mA g-1) with E/S ratio of 5 µL mg-1.

4.
ACS Nano ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35044741

RESUMO

The successful treatment of osteomyelitis remains a great challenge in the field of orthopedics. The clinical method for treating refractory bone infection requires a combination therapy of long-term systemic antibiotics administration and surgical debridement. It is highly desirable to develop an antibiotic-free, noninvasive, rapid strategy to eradicate osteomyelitis. Herein, we fabricate a piezoelectric-enhanced sonosensitizer that consists of a porphyrin-based hollow metal-organic framework (HNTM), MoS2 nanosheets, and a red cell (RBC) membrane. We find that the ultrasound (US)-induced piezoelectric polarization of MoS2 can improve the charge transfer of HNTM at the heterointerface of HNTM-MoS2, increasing the production of reactive oxygen species (ROS). Besides, MoS2 increases the asymmetric shape of HNTM, leading to the strong US-propelling ability of HNTM-MoS2. The produced ROS and strong mechanical force can kill methicillin-resistant Staphylococcus aureus (MRSA) with an antibacterial efficiency of 98.5% under 15 min of US treatment, resulting in intracellular DNA damage and increased oxidative stress and disturbance of purine metabolism, tryptophan metabolism, and pantothenate and CoA biosynthesis of MRSA. Together with the toxin neutralization ability, the RBC-HNTM-MoS2 successfully eliminates the bone infection and suppresses inflammation and bone loss. This work provides another strategy for developing an efficient sonosensitizer through piezoelectric-assisted sonocatalysis and enhancing US-propelling ability.

5.
Adv Mater ; : e2107425, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34866255

RESUMO

A highly soluble and stable Li5 BW12 O40 cluster delivers 2 e- redox reaction with fast electron transfer rates (2.5 * 10-2  cm s-1 ) and high diffusion coefficients (∼2.08 * 10-6 cm2 s-1 ) at mild pH ranging from 3 to 8. In-operando aqueous-flowing Raman spectroscopy and DFT calculations reveals that Raman shift changing of {BW12} clusters should be due to the bond length changing between W-Ob -W and W-Oc -W at different redox states of clusters. All above structure changing and redox chemistry of Li5 BW12 O40 are highly reversible, which makes the Li5 BW12 O40 cluster versatile to construct all-anion aqueous redox flow batteries at different pH. The cation-exchange Nafion membrane will also repel the cross permeability of the anion redox couples. As a result, by coupling with Li3 K[Fe(CN)6 ] catholyte, the aqueous RFB can be operated at pH 8 with a capacity retention up to 95% and an average Coulombic efficiency (CE) more than 99.79% over 300 cycles within the voltage window ranging from 0 to 1.2 V. Meanwhile, Li5 BW12 O40 cluster can also be paired with LiI catholyte to form aqueous RFBs at pH 7 and pH 3, the capacity retention of 94% and 90% can be realized over 300 cycles within 0 to 1.3 V. This article is protected by copyright. All rights reserved.

6.
Small ; : e2105775, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34889522

RESUMO

Osteomyelitis is considered as the most serious bone infection, which can lead to the bone destruction or fatal sepsis. Clinical treatments through frequent antibiotics administration and surgical debridement bring inevitable side effects including drug-resistance and disfigurements. It is urgent to develop an antibiotics-free and rapid strategy to treat osteomyelitis. Herein, a bifunctional sonosensitizer that consists of porphyrin-like Zn single-atom catalysts (g-ZnN4 ) and MoS2 quantum dots is developed, which exhibits excellent sonodynamic antibacterial efficiency and osteogenic ability. It is found that the construction of heterogeneous interfaces of g-ZnN4 -MoS2 fully activates the adsorbed O2 due to the increased interface charge transfer, enhanced spin-flip, and reduced activation energy of O2 . The generated 1 O2 can kill methicillin-resistant Staphylococcus aureus (MRSA) with an antibacterial efficiency of 99.58% under 20 min of ultrasound (US) irradiation. The Zn single atoms immobilized in g-ZnN4 can be released steadily in the form of Zn2+ for 28 days within safe concentration, realizing the great osteoinductive ability of such a sonosensitizer. For the treatment of MRSA-infected osteomyelitis, the inflammation and bone loss can be significantly suppressed through sonodynamic ion therapy. This work provides another strategy for developing high efficiency sonosensitizer through ultrasound interfacial engineering.

7.
ACS Nano ; 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34935354

RESUMO

Engineered small extracellular vesicles (sEVs) are used as tools to enhance therapeutic efficacy. However, such application of sEVs is associated with several issues, including high costs and a high risk of tumorigenesis. Nanotopography has a greater influence on bone-related cell behaviors. However, whether nanotopography specifically mediate sEV content to perform particular biological functions remains unclear. Here, we demonstrate that selective nanotopography may be used to sequentially mediate human bone mesenchymal stem cell (hBMSC) sEVs to enhance the therapeutic efficacy of hBMSCs-EVs for osteogenesis. We subjected sEVs harvested from hBMSCs cultured on polished titanium plates (Ti) or nanotopographical titanium plates (Ti4) after 7, 14, and 21 d for RNA sequencing, and we found that there was no significant difference in sEV-miRNA expression after 7 d. Differentially expressed osteogenic-related microRNAs were founded after 14 days, and KEGG analysis indicated that the main microRNAs were associated with osteogenesis-related pathways, such as TGF-beta, AMPK, and FoxO. A significant difference was found in sEV-miRNAs expression after 21 d. We loaded sEV secreted from hBMSCs cultured on Ti4 after 21 d on 3D-printed porous PEEK scaffolds with poly dopamine (PDA) and found that such scaffolds showed superior osteogenic ability after 6- and 12-weeks. Here, we demonstrate the alkali- and heat-treated nanotopography with the ability of stimulating osteogenic differentiation of hBMSC can induce the secretion of pro-osteogenesis sEV, and we also found that sEVs meditate osteogenesis through miRNA. Thus, whether nanotopography has the ability to regulate other contents of sEVs such as proteins for enhancing osteogenesis needs further research. These findings may help us use nanotopography to extract sEVs for other biomedical applications, including cancer therapy.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34902629

RESUMO

BACKGROUND & AIMS: Gut microbiota and microbial factors regulate the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in patients with obesity and metabolic abnormalities, but little is known about their roles in nonobese NAFLD. Expansion of Escherichia is associated with NAFLD pathogenesis. We aimed to investigate the pathogenic role of Escherichia fergusonii and its products in the development of nonobese NAFLD. METHODS: We characterized the intestinal microbiome signature in a cohort of NAFLD patients and healthy controls by 16S ribosomal RNA sequencing. The role of E fergusonii was estimated in rats after 16 weeks of administration, and features of NAFLD were assessed. E fergusonii-derived microRNA-sized, small RNAs (msRNAs) were analyzed by deep sequencing. RESULTS: We detected an expansion of Escherichia_Shigella in NAFLD patients compared with healthy controls, and its increase was associated with disease severity independent of obesity. E fergusonii, a member of the genus Escherichia, induced the development of nonobese NAFLD characterized by hepatic steatosis and hepatocyte ballooning in rats without obesity. It disturbed host lipid metabolism by inhibiting hepatic lipid ß-oxidation and promoting de novo lipogenesis. We also showed that E fergusonii caused the development of hepatic inflammation and fibrosis in a sizable fraction of animals at an advanced stage of NAFLD. Mechanistically, E fergusonii-derived msRNA 23487 down-regulated host hepatic peroxisome proliferator-activated receptor α expression, which could contribute to lipid accumulation in the liver. CONCLUSIONS: These results suggest that E fergusonii promotes the pathogenesis of steatohepatitis and fibrosis in nonobese rats by secreting msRNA 23487, and it might be a potential biomarker for predicting steatohepatitis in nonobese NAFLD.

9.
Animals (Basel) ; 11(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34944139

RESUMO

As one of the pioneer bacterial sources of intestinal microbiota, the information of bacterial composition in colostrum might provide a reference for developing specific probiotics for newborn calves, especially calves fed with pasteurized milk. The present study aimed to detect the core bacteria at different taxonomic levels and the common beneficial ones in colostrum by analyzing the bacterial composition in 34 colostrum samples of healthy cows selected from two dairy farms. The results of the further analysis showed that the bacterial composition in the colostrum of the two dairy farms was different, but their four most dominant phyla were the same including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The microbiome of all colostrum samples shared ten core operational taxonomic units (OTUs), 21 core genera, and 34 core families, and most of them had no difference in relative abundance between the two farms. The ten core OTUs did not belong to the identified commensal bacteria and have not been detected by previous study. However, several core genera found in our study were also identified as core genus in a previous study. Some well-known beneficial and pathogenic bacteria including Lactobacillus plantarum, Bacillus subtilis, Acinetobacter lwoffii, and Streptococcus pneumoniae were present in the colostrum of healthy cows. However, none had a correlation with the number of somatic cell count (SCC), but the core genera Nubella and Brevundinimas and the core families Methylobacteriaceae and Caulobacteraceae positively correlated with the number of SCC. The genus Staphylococcus, Pseudomonas, and Chryseobacterium in colostrum had a positive correlation with each other, while the probiotics unidentified-Bacteroidales-S24-7-group had a negative correlation with Pseudomonas and Chryseobacterium. In addition, more than 50% bacterial OTUs in colostrum were detected in the rectal content including some strictly anaerobic bacteria that are generally present in the intestine and rumen. However, of the top 30 commonly shared bacterial genera in the colostrum and rectal feces, no genus in colostrum was positively correlated with that same genus in rectal feces. In conclusion, the bacterial composition of colostrum microbiota is greatly influenced by external factors and individuals. There were several core OTUs, and some core genus and families in the colostrum samples. Colostrum from healthy cows contained both beneficial and pathogenic bacteria and shared many common bacteria with rectal content including some gastrointestinal anaerobes.

10.
Int J Biol Sci ; 17(15): 4365-4376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803504

RESUMO

Given the heterogeneity of solid tumors, single-target CAR-T cell therapy often leads to recurrence, especially in ovarian cancer (OV). Here, we constructed a Tandem-CAR targeting two antigens with secretory activity (IL-12) to improve the effects of CAR-T cell therapy. Twenty coexpressed upregulated genes were identified from the GEO database, and we found FOLR1 (folate receptor 1) and MSLN (mesothelin) were specifically and highly expressed in cancer tissues and only 11.25% of samples were negative for both antigens. We observed an increased proliferation rate for these three CAR-T cells, and Tandem CAR-T cells could efficiently lyse antigen-positive OV cells in vitro and secrete higher levels of cytokines than single-target CAR-T cells. More importantly, in vivo experiments indicated that Tandem CAR-T cells markedly decreased tumor volume, exhibited enhanced antitumor activity, and prolonged mouse survival. Furthermore, the infiltration and persistence of T cells in the Tandem-CAR group were higher than those in the MSLN-CAR and Control-T groups but comparable to those in the FOLR1-CAR group. Collectively, this study demonstrated that Tandem CAR-T cells secreting IL-12 could enhance immunotherapeutic effects by reducing tumor antigen escape and increasing T cell functionality, which could be a promising therapeutic strategy for OV and other solid tumors.

11.
Mol Neurobiol ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34796463

RESUMO

A common phenomenon called social buffering (SB), communication within conspecific animals is a benefit for a stressed individual to better recover from aversive events, is crucial to all mammals. Although the dopamine reward system has been implicated in SB, it is not clear which neuronal populations are relevant and how they contribute. Here, we adopted a learned helplessness (LH) animal model of depression and found that LH subjects housed with a conspecific partner show better performance in the shuttle box test, showing that SB improves the stress-coping abilities to deal with stress. Bidirectional manipulation of ventral tegmental area (VTA) dopamine neurons by chemogenetic tools can mimic or block the SB effect in LH mice. To screen for SB-induced structure plasticity of VTA dopamine neurons, we employed viral genetic tools for mapping input and output architecture and found LH- and SB-triggered circuit-level changes in neuronal ensembles. Zona incerta (ZI), an overlapping brain region, was significantly changed in both anterograde and retrograde tracing during LH and SB. These results reveal a neural loop with structural plasticity between VTA dopamine neurons and ZI underlies the SB effects in LH and lays a foundation for studying how VTA dopamine neurons regulate SB-related neural circuits.

12.
IEEE Trans Cybern ; PP2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797771

RESUMO

In this article, we propose a novel filter pruning method for deep learning networks by calculating the learned representation median (RM) in frequency domain (LRMF). In contrast to the existing filter pruning methods that remove relatively unimportant filters in the spatial domain, our newly proposed approach emphasizes the removal of absolutely unimportant filters in the frequency domain. Through extensive experiments, we observed that the criterion for ``relative unimportance'' cannot be generalized well and that the discrete cosine transform (DCT) domain can eliminate redundancy and emphasize low-frequency representation, which is consistent with the human visual system. Based on these important observations, our LRMF calculates the learned RM in the frequency domain and removes its corresponding filter, since it is absolutely unimportant at each layer. Thanks to this, the time-consuming fine-tuning process is not required in LRMF. The results show that LRMF outperforms state-of-the-art pruning methods. For example, with ResNet110 on CIFAR-10, it achieves a 52.3% FLOPs reduction with an improvement of 0.04% in Top-1 accuracy. With VGG16 on CIFAR-100, it reduces FLOPs by 35.9% while increasing accuracy by 0.5%. On ImageNet, ResNet18 and ResNet50 are accelerated by 53.3% and 52.7% with only 1.76% and 0.8% accuracy loss, respectively. The code is based on PyTorch and is available at https://github.com/zhangxin-xd/LRMF.

13.
J Am Dent Assoc ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34756591

RESUMO

BACKGROUND: Studies have indicated the negative effects of temporomandibular disorders (TMDs) on oral health-related quality of life (OHRQoL). The authors investigated the OHRQoL of patients with acute and chronic TMD subtypes. METHODS: The authors recruited a total of 830 patients. They derived TMD diagnoses using the Diagnostic Criteria for TMDs protocol involving symptom history, physical examination, and diagnostic imaging as indicated. The authors categorized patients into acute (≤ 3 months) or chronic (> 3 months) pain-related TMD (PT), nonpainful intra-articular TMD (IT), and combined TMD (CT) groups. They also gathered sociodemographic information and assessed OHRQoL with the Oral Health Impact Profile (OHIP)-TMDs. The authors evaluated data using 2-way analysis of variance and Bonferroni test and multiple regression analysis. RESULTS: Patients in the chronic PT and CT subgroups had significantly higher mean global OHIP scores than their acute counterparts. The authors observed significant acute-chronic differences in OHIP-TMDs domain scores in 5 and 2 domains for the PT and CT groups, respectively. Patients in the acute IT group had significantly higher functional limitation scores than those in the chronic IT group. The ranking of mean global scores, in descending order was CT, PT, and IT for acute TMDs and PT, CT, and IT for chronic TMDs, with significant differences observed among the 3 TMD subtypes (P < .001). CONCLUSIONS: Both TMD chronicity and subtypes influenced OHRQoL. Painful TMDs (PT and CT) were associated with significantly poorer OHRQoL than nonpainful TMDs. TMD chronicity appeared to affect OHRQoL only for the painful TMD conditions. Future work on the impact of TMDs on OHRQoL should strive to stratify patients by TMD chronicity and subtypes. PRACTICAL IMPLICATIONS: TMD chronicity and subtypes influence the impact of TMDs on OHRQoL. Given that chronic painful TMDs impair quality of life, early biopsychosocial intervention of acute TMD pain is important for minimizing chronification and OHRQoL deterioration.

14.
Liver Int ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34619026

RESUMO

BACKGROUND: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. RESULTS: Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P < .0001) were positively correlated with prevalent NAFLD. CONCLUSIONS: In Asia, paediatric NAFLD is becoming prevalent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of paediatric NAFLD dimorphism need further investigation.

15.
Commun Biol ; 4(1): 1171, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620988

RESUMO

Grain size is a key component trait of grain weight and yield. Numbers of quantitative trait loci (QTLs) have been identified in various bioprocesses, but there is still little known about how metabolism-related QTLs influence grain size and yield. The current study report GS3.1, a QTL that regulates rice grain size via metabolic flux allocation between two branches of phenylpropanoid metabolism. GS3.1 encodes a MATE (multidrug and toxic compounds extrusion) transporter that regulates grain size by directing the transport of p-coumaric acid from the p-coumaric acid biosynthetic metabolon to the flavonoid biosynthetic metabolon. A natural allele of GS3.1 was identified from an African rice with enlarged grains, reduced flavonoid content and increased lignin content in the panicles. Notably, the natural allele of GS3.1 caused no alterations in other tissues and did not affect stress tolerance, revealing an ideal candidate for breeding efforts. This study uncovers insights into the regulation of grain size though metabolic-flux distribution. In this way, it supports a strategy of enhancing crop yield without introducing deleterious side effects on stress tolerance mechanisms.

16.
China CDC Wkly ; 3(30): 637-644, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34594958

RESUMO

What is already known about this topic? Though coronavirus disease 2019 (COVID-19) has largely been controlled in China, several outbreaks of COVID-19 have occurred from importation of cases or of suspected virus-contaminated products. Though several outbreaks have been traced to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated on the outer packaging of cold chain products, live virus has not been obtained. What is added by this report? In September 2020, two dock workers were detected as having asymptomatic SARS-CoV-2 infection using throat swabs during routine screening in Qingdao, China. Epidemiological information showed that the two dock workers were infected after contact with contaminated outer packaging, which was confirmed by genomic sequencing. Compared to the Wuhan reference strain, the sequences from the dock workers and the package materials differed by 12-14 nucleotides. Furthermore, infectious virus from the cold chain products was isolated by cell culture, and typical SARS-CoV-2 particles were observed under electron microscopy. What are the implications for public health practice? The international community should pay close attention to SARS-CoV-2 transmission mode through cold chain, build international cooperative efforts in response, share relevant data, and call on all countries to take effective prevention and control measures to prevent virus contamination in cold-chain food production, marine fishing and processing, transportation, and other operations.

17.
Plant Biotechnol J ; 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655511

RESUMO

Starch accounts for over 80% of the total dry weight in cereal endosperm and determines the kernel texture and nutritional quality. Amyloplasts, terminally differentiated plastids, are responsible for starch biosynthesis and storage. We screened a series of rice mutants with floury endosperm to clarify the mechanism underlying amyloplast development and starch synthesis. We identified the floury endosperm19 (flo19) mutant which shows opaque of the interior endosperm. Abnormal compound starch grains (SGs) were present in the endosperm cells of the mutant. Molecular cloning revealed that the FLO19 allele encodes a plastid-localized pyruvate dehydrogenase complex E1 component subunit α1 (ptPDC-E1-α1) that is expressed in all rice tissues. In vivo enzyme assays demonstrated that the flo19 mutant showed decreased activity of the plastidic pyruvate dehydrogenase complex. In addition, the amounts of monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) were much lower in the developing flo19 mutant endosperm, suggesting that FLO19 participates in fatty acid supply for galactolipid biosynthesis in amyloplasts. FLO19 overexpression significantly increased seed size and weight, but did not affect other important agronomic traits, such as panicle length, tiller number and seed setting rate. An analysis of single nucleotide polymorphism data from a panel of rice accessions identified that the pFLO19L haplotype was positively associated with grain length, implying a potential application in rice breeding. In summary, our study demonstrates that FLO19 is involved in galactolipid biosynthesis which is essential for amyloplast development and starch biosynthesis in rice.

18.
Nanoscale ; 13(42): 17912-17919, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34679146

RESUMO

Periodontitis is a common chronic inflammatory disease associated with biofilm formation, gingival recession, and supporting bone loss that can lead to the formation of periodontal pockets and, ultimately, tooth loss. Clinical treatment for periodontitis through scaling and antibiotics still faces the problems of unavoidable bleeding, injury to periodontal tissue, drug resistance, and insufficient treatment. Herein we prepared an injectable anti-periodontitis ointment with catalytic activity that consists of Pt nanocluster (PtNC) modified g-C3N4 (CN), and PEG400/PEG4000, which efficiently treated biofilm-infected periodontitis. PtNCs (<2 nm) with ultralow content (0.07%) were formed on the surface of CN using mild ultraviolet (UV) irradiation. Due to the strong O2 adsorption and activation ability of CN-PtNCs and their mutual electron transfer, they show both oxidase-like and peroxidase-like activities and produce reactive oxygen species (ROS) in the dark. CN-PtNCs showed strong biofilm elimination ability towards Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, benefiting from the good biocompatibility of CN-PtNCs and the injectable property of the PEG400/PEG4000 ointment, the CN-PtNC ointment with high bioavailability successfully treated periodontitis in rats, alleviating inflammation and reducing bone loss, and showed better performance than periocline. Therefore, this catalytic system is promising for an efficient, non-invasive, and antibiotic-free treatment of periodontitis.


Assuntos
Nanopartículas Metálicas/uso terapêutico , Periodontite , Platina/uso terapêutico , Animais , Biofilmes/efeitos dos fármacos , Catálise , Escherichia coli , Periodontite/tratamento farmacológico , Ratos , Staphylococcus aureus
19.
Cell Death Dis ; 12(10): 893, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593753

RESUMO

Uncontrolled mitosis is one of the most important features of cancer, and mitotic kinases are thought to be ideal targets for anticancer therapeutics. However, despite numerous clinical attempts spanning decades, clinical trials for mitotic kinase-targeting agents have generally stalled in the late stages due to limited therapeutic effectiveness. Alisertib (MLN8237) is a promising oral mitotic aurora kinase A (AURKA, Aurora-A) selective inhibitor, which is currently under several clinical evaluations but has failed in its first Phase III trial due to inadequate efficacy. In this study, we performed genome-wide CRISPR/Cas9-based screening to identify vulnerable biological processes associated with alisertib in breast cancer MDA-MB-231 cells. The result indicated that alisertib treated cancer cells are more sensitive to the genetic perturbation of oxidative phosphorylation (OXPHOS). Mechanistic investigation indicated that alisertib treatment, as well as other mitotic kinase inhibitors, rapidly reduces the intracellular ATP level to generate a status that is highly addictive to OXPHOS. Furthermore, the combinational inhibition of mitotic kinase and OXPHOS by alisertib, and metformin respectively, generates severe energy exhaustion in mitotic cells that consequently triggers cell death. The combination regimen also enhanced tumor regression significantly in vivo. This suggests that targeting OXPHOS by metformin is a potential strategy for promoting the therapeutic effects of mitotic kinase inhibitors through the joint targeting of mitosis and cellular energy homeostasis.

20.
ACS Nano ; 15(9): 14709-14724, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34476937

RESUMO

Extracellular vesicles (EVs) are potential alternatives for mesenchymal stem cells (MSCs) in the treatment of musculoskeletal degenerative diseases, including intervertebral disc degeneration (IDD). Usually, EVs are internalized and then deliver bioactive molecules that impart phenotypic changes in recipient cells. For effective utilization of EVs in the IDD therapy, understanding the mechanism of EV uptake is of vital importance. In this study, we found that EVs delivered antioxidant proteins to protect against pyroptosis of nucleus pulposus cells (NPCs). In particular, the therapeutic effect of EVs decreased in TNF-α-treated NPCs due to the impaired caveolae-mediated endocytosis pathway. Transcriptome sequencing and functional verification revealed that caveolae associated protein 2 (Cavin-2) played an important role in the uptake process of EVs. We then constructed the Cavin-2-modified engineering EVs via the gene-editing of parental MSCs. These kinds of modified EVs presented an improved uptake rate in TNF-α-treated NPCs, which effectively ameliorated the cell death of NPCs in a three-dimensional hydrogel culture model and retarded the progression of IDD in the ex vivo organ culture model. Collectively, these findings illustrate the mechanism of EV uptake in NPCs and explore the application of engineering EVs in the treatment of IDD.


Assuntos
Vesículas Extracelulares , Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , Transporte Biológico , Morte Celular , Humanos , Degeneração do Disco Intervertebral/terapia
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