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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 740-746, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622586

RESUMO

Nano hydroxyapatite (nHAp), a main component of the inorganic composition of human bones and teeth, is widely used in bone tissue engineering, bone defect repair and replacement, for example, for its biocompatibility, bioactivity, bioaffinity and the ability to induce bone regeneration. Nano hydroxyapatite contains calcium and phosphorus, elements that can be replaced through the normal metabolic channels of the human body. Therefore, after implantation, it can be partially or completely absorbed and replaced by human tissues and can effectively assist bone regeneration, which makes it an ideal material for bone repair. However, traditional nHAp material is brittle and hard to be degraded in human body. In addition, nHAp has poor stability due to its high surface energy and tendency for agglomeration, which causes rapid attenuation of its mechanical strength and limits its clinical application. At present, the mechanical properties and biocompatibility of nHAp can be effectively improved by loading the related growth factors, proteins, peptides and other bioactive molecules, so as to better meet the biological requirements of bone repair materials. However, the traditional physicochemical modification methods are complicated and may interfere with the bioactivity of nHAp. It is simple to biomimetically synthesize nanomaterials by direct utilization of the molecular recognition and self-assemble capabilities of biomolecules or living microorganisms. Furthermore, the properties of the synthesized nanomaterials are stable, and the method has been extensively studied in recent years. Due to the unique crystaline structure and physicochemical properties of nHAp, results of a large number of studies have shown that its affinity with biological molecules can be used to produce bioactive nHAp by biomimetic synthesis methods. Biomimetically synthesized nHAp is expected to become the mainstream bone tissue engineering scaffold material. Analyzing and summarizing the biomimetic synthetic process and the characteristics of different nHAp materials will facilitate further development of bone defect repair materials with better mechanical and biological properties. Herein we reviewed methods of biomimetic synthesis of nHAp based on different biomolecular templates. Furthermore, we also discussed applications of biomimetic synthesized nHAp in bone tissue engineering, which can used as reference information for further research and development of new-generation bone repair biomaterials.


Assuntos
Durapatita , Engenharia Tecidual , Biomimética , Osso e Ossos , Humanos , Tecidos Suporte
2.
Front Pharmacol ; 12: 668887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630073

RESUMO

Jujuboside B (JB) is one of the main biologically active ingredients extracted from Zizyphi Spinosi Semen (ZSS), a widely used traditional Chinese medicine for treating insomnia and anxiety. Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. The purpose of this study was to examine whether JB could prevent breast cancer and its underlying mechanism. First, we reported that JB induced apoptosis and autophagy in MDA-MB-231 and MCF-7 human breast cancer cell lines. Further mechanistic studies have revealed that JB-induced apoptosis was mediated by NOXA in both two cell lines. Moreover, the AMPK signaling pathway plays an important role in JB-induced autophagy in MCF-7. To confirm the anti-breast cancer effect of JB, the interaction of JB-induced apoptosis and autophagy was investigated by both pharmacological and genetic approaches. Results indicated that autophagy played a pro-survival role in attenuating apoptosis. Further in vivo study showed that JB significantly suppressed the growth of MDA-MB-231 and MCF-7 xenografts. In conclusion, our findings indicate that JB exerts its anti-breast cancer effect in association with the induction of apoptosis and autophagy.

3.
Inflamm Res ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633468

RESUMO

OBJECTIVE AND DESIGN: We aim to explore the molecular mechanism of myocardial ischemia-reperfusion injury (MIRI). METHODS: The H9C2 cells were cultured under hypoxia/reoxygenation (H/R) condition to induce myocardial injury in vitro. The expression of miR-451-3p and MAP1LC3B was detected by RT-qPCR. Dual-luciferase reporter assay and RNA pull-down assay were performed to examine the relationship between microRNA (miR)-451-3p and MAP1LC3B. CCK8 was used to test cell viability. The level of LDH and CK was evaluated via ELISA. Immunofluorescence assay and flow cytometry were applied to detect autophagy and apoptosis, respectively. Autophagy-related protein expressions were determined by western blotting. Furthermore, an in vivo rat model of MIRI was established by subjection to 30 min ischemia and subsequently 24 h reperfusion for validation of the role of miR-451-3p in regulating MIRI in vivo. RESULTS: miR-451-3p was down-regulated in MIRI, and miR-451-3p mimics transfection alleviated autophagy and apoptosis induced by MIRI. miR-451-3p could target MAP1LC3B directly. Co-transfection miR-451-3p mimics and pcDNA 3.1 MAP1LC3B curbed the protected effects of miR-451-3p mimics on MIRI. CONCLUSIONS: miR-451-3p played a protective role in MIRI via inhibiting MAP1LC3B-mediated autophagy, which may provide new molecular targets for the treatment of MIRI and further improves the clinical outcomes of heart diseases.

4.
Gene ; 808: 145991, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626723

RESUMO

Porcine circovirus 4 (PCV4) was identified as a novel porcine circovirus in China in 2019. To investigate the prevalence and genetic characteristics of PCV2 and PCV4, 133 clinical samples (103 tissue samples and 30 serum samples) were collected from 30 different pig farms in Henan province of China, and a SYBR Green I-based duplex quantitative real-time polymerase chain reaction assay was established to detect PCV2 and PCV4 genomes simultaneously. The complete genome sequences of 20 PCV2 and 6 PCV4 strains from 19 and 6 clinical samples respectively were sequenced and analyzed. The results showed the detection limits of this assay were 80.2 copies/µL for PCV2 and 58.6 copies/µL for PCV4. The detection results of clinical samples revealed the PCV2 positive rate was 63.16% (84/133), the PCV4 positive rate was 33.33% (45/133), and the PCV2 and PCV4 co-infection positive rate was 21.05% (28/133). Among 20 PCV2 strains, 6 belonged to PCV2a, 6 belonged to PCV2b and 8 belonged to PCV2d. Co-infection with JZ1 (PCV2b) and JZ2 (PCV2d) strains was identified in one sample (JZ-1). Eleven putative recombination events were found through the recombination analysis, suggesting that the new PCV2 variant strains had circulated in Henan province, which contributes to our understanding of evolutionary characteristics of PCV2 in China. The possible genotypes of PCV4 strains were determined based on genomic sequences of 6 PCV4 strains in this study and 29 PCV4 reference strains available at GenBank. According to three different phylogenetic trees (ORF1, ORF2 and complete genome), all 35 PCV4 strains were clustered into two major genotypes (PCV4a and PCV4b), and 6 PCV4 strains in this study belonged to PCV4a. Additionally, the functional regions of PCV4 strains were predicted by comparison with other circoviruses, which are conducive to the further study of the biological functions of PCV4 genome.

5.
Theranostics ; 11(19): 9397-9414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646377

RESUMO

Rationale: Most current cardiac regeneration approaches result in very limited cell division and little new cardiomyocyte (CM) mass. Positive feedback loops are vital for cell division, but their role in CM regeneration remains unclear. We aimed to determine whether the lncRNA small nucleolar RNA host gene 1 Snhg1 (Snhg1) could form a positive feedback loop with c-Myc to induce cardiac regeneration. Methods: Quantitative PCR and in situ hybridization experiments were performed to determine the Snhg1 expression patterns in fetal and myocardial infarction (MI) hearts. Gain- and Loss-of-function assays were conducted to explore the effect of Snhg1 on cardiomyocyte (CM) proliferation and cardiac repair following MI. We further constructed CM-specific Snhg1 knockout mice to confirm the proliferative effect exerted by Snhg1 using CRISPR/Cas9 technology. RNA sequencing and RNA pulldown were performed to explore how Snhg1 mediated cardiac regeneration. Chromatin immunoprecipitation and luciferase reporter assays were used to demonstrate the positive feedback loop between Snhg1 and c-Myc. Results: Snhg1 expression was increased in human and mouse fetal and myocardial infarction (MI) hearts, particularly in CMs. Overexpression of Snhg1 promoted CM proliferation, angiogenesis, and inhibited CM apoptosis after myocardial infarction, which further improved post-MI cardiac function. Antagonism of Snhg1 in early postnatal mice inhibited CM proliferation and impaired cardiac repair after MI. Mechanistically, Snhg1 directly bound to phosphatase and tensin homolog (PTEN) and induced PTEN degradation, activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway to promote CM proliferation. The c-Myc protein, one of downstream targets of PI3K/AKT signaling, functioned as a transcription factor by binding to the promoter regions of Snhg1. Perturbation of the positive feedback between Snhg1 and c-Myc by mutation of the binding sequence significantly affected Snhg1-induced CM proliferation. Conclusions: Snhg1 effectively elicited CM proliferation and improved cardiac function post-MI by forming a positive feedback loop with c-Myc to sustain PI3K/Akt signaling activation, and thus may be a promising cardiac regeneration strategy in treating heart failure post-MI.

6.
AMB Express ; 11(1): 142, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34693461

RESUMO

Microorganisms play an essential role in sulfide removal. Alkaline absorption solution facilitates the sulfide's dissolution and oxidative degradation, so haloalkaliphile is a prospective source for environmental-friendly and cost-effective biodesulfurization. In this research, 484 sulfide oxidation genes were identified from the metagenomes of the soda-saline lakes and a haloalkaliphilic heterotrophic bacterium Halomonas salifodinae IM328 (=CGMCC 22183) was isolated from the same habitat as the host for expression of a representative sequence. The genetic manipulation was successfully achieved through the conjugation transformation method, and sulfide: quinone oxidoreductase gene (sqr) was expressed via pBBR1MCS derivative plasmid. Furthermore, a whole-cell catalyst system was developed by using the engineered strain that exhibited a higher rate of sulfide oxidation under the optimal alkaline pH of 9.0. The whole-cell catalyst could be recycled six times to maintain the sulfide oxidation rates from 41.451 to 80.216 µmol·min-1·g-1 dry cell mass. To summarize, a whole-cell catalyst system based on the engineered haloalkaliphilic bacterium is potentiated to be applied in the sulfide treatment at a reduced cost.

7.
ACS Appl Mater Interfaces ; 13(41): 49254-49265, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34633173

RESUMO

Membrane biofouling has long been a major obstacle to highly efficient water treatment. The modification of the membrane surface with hydrophilic materials can effectively enhance biofouling resistance. However, the water flux of the membranes is often compromised for the improvement of antifouling properties. In this work, a composite membrane composed of a zwitterionic hydrogel and electrospinning fibers was prepared by a spin-coating and UV cross-linking process. At the optimum conditions, the composite membrane could effectively resist the biofouling contaminations, as well as purify polluted water containing bacteria or diatoms with a high flux (1349.2 ± 85.5 L m-2 h-1 for 106 CFU mL-1 of an Escherichia coli solution). Moreover, compared with the commercial poly(ether sulfone) (PES) membrane, the membrane displayed an outstanding long-term filtration performance with a lower water flux decline. Therefore, findings in this work provide an effective antifouling modification strategy for microfiltration membranes and hold great potential for developing antifouling membranes for water treatment.

8.
Ecotoxicol Environ Saf ; 227: 112903, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34673417

RESUMO

As a new pollutant, microplastics have increasingly drawn public attention to its toxic behavior in the environment. The aim was to investigate the effect of styrene-butadiene-rubber microplastics (mSBR) with different degrees of aging on petroleum hydrocarbon (PHC) degrading bacteria in an environment with simultaneously existing pollutants. A series of experiments were carried out to investigate the changes in the physical and chemical properties of mSBR with aging and to examine the influence of these changes on the inhibition of PHC-degrading bacteria by mSBR in the vicinity of coexisting pollutants. The results showed that in the early stage of ultraviolet aging (10d), the particle surface shows wrinkles, but the structure is intact. After reaching the late stage of aging (20d), nano-scale fragments were generated on the surface of mSBR, the average particle size decreased from 3.074 µm to 2.297 µm, and the zeta potential increased from - 25.1 mV to - 33.1 mV. The inhibitory effect of bacteria is greater. At the same time, these changes in the physicochemical properties increase the adsorption effect of Cd by 20%, and also improve the stability of mSBR in solution, whereby bacterial growth is inhibited by inhibiting the LPO activity and protein concentration of PHC degrading bacteria.

9.
J Health Popul Nutr ; 40(1): 41, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544498

RESUMO

BACKGROUND: The objective of this study was to develop a scale to assess eating behaviors of school-aged children (6-12 years old) in China. METHODS: To develop the scale, a literature review and qualitative interviews were conducted. The draft scale contained 115 items and went through three evaluations among three groups of caregivers (n = 140, 400, 700) selected from suburban and urban kindergartens in Xi'an, Hanzhong, and Yanan, China, from March 2017 to October 2018. The psychometric properties of the scale were assessed using exploratory, confirmatory factor analysis, and variability analysis. RESULTS: The final scale consisted of 46 items across eight dimensions including food fussiness, satiety responsiveness, food responsiveness, bad eating habits, susceptible diet, restrained eating, enjoyment of food, and junk food addiction. The total cumulative variance contribution rate was 52.16%. The scale and dimensions' Cronbach's α coefficients, Guttman split-half reliability, and test- retest reliability were all above 0.65. The fitting indices for the confirmatory factor analysis were all close to 1. The scores for education of caregiver, family structure, and the body mass index of children were different among dimensions and groups, thus suggesting good discriminative utility. CONCLUSIONS: All of the results indicated that the scale has good reliability and construct validity for evaluating the eating behaviors of school-aged children in China.

10.
Protein Pept Lett ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34551686

RESUMO

BACKGROUND: Sanghuangporus baumii is a traditional Chinese medicine with anti-cancer, anti-tumor, and anti-inflammatory effects. Triterpenoids are one of the main medicinal ingredients found in S. baumii. However, the dynamic changes of triterpenoids content and its molecular regulation mechanism are still unclear. OBJECTIVE: Some studies have shown that Lanosterol synthase (LS) is a key enzyme involved in the mevalonate pathway (MVA pathway) to produce lanosterol, which is a precursor for synthesizing S. baumii triterpenoids. Therefore, the study of LS gene and expression characteristics can provide clues for the further study of triterpenoids synthesis. METHODS: The PCR, RACE PCR, RT-PCR, seamless cloning and prokaryotic expression technology were used to research the gene characteristic and dynamic changes of LS transcription level. RESULTS: The S. baumii LS sequence included a 5'-untranslated region (129 bp), a 3'-untranslated region (87 bp), and an open reading frame (2,229 bp) encoding 734 amino acids. The S. baumii LS protein was expressed in E. coli BL21 (DE3). The transcription start site of the S. baumii LS promoter sequence ranged from 1 740 bp to 1790 bp. The LS promoter contained 12 CAAT-boxes, 5 ABREs, 6 G-Boxes, 6 CGTCA-motifs, and so on. The LS transcription levels were the highest on day 11 in mycelia (1.6-fold), and the triterpenoids content also gradually increased. The transcription levels began to decrease on day 13, but the triterpenoids content still increased. CONCLUSION: The S. baumii LS was cloned and characterized to help to understand the mechanism of triterpenoids synthesis. In addition, we studied the relationship between LS transcription level and triterpenoid dynamic accumulation, and we found that they had a certain correlation.

11.
Dalton Trans ; 50(37): 13096-13102, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581332

RESUMO

Herein, a novel 3-dimensional (3D) Cu(II) metal-organic framework (MOF), [Cu3(µ2-O)2(p-tr2Ph)2(HCOO)][NO3]·3DMF·3H2O (compound 1), which is constructed by directly interlocking regionalized hollow two-dimensional (2D) layers, has been conceived and solvothermally synthesized. Such a distinctive regionalized pore system effectively maintains the uniformity of the pore structure, isolates the counterions and bridging ligands in the partition layer, and endows compound 1 with high porosity. In consequence, compound 1 exhibits excellent adsorption ability of iodine in cyclohexane. The removal efficiency in cyclohexane solution (0.01 mol L-1) can reach up to 80% in 8 min, and the absorption ability towards iodine can reach about 1.15 g g-1. Moreover, iodine can also be controllably released in ethanol. The release rate was up to 4 × 10-5 mol L-1 min-1. Furthermore, compound 1 also showed prominent recyclability due to the high stability, and the maximum sorption amount could be retained after 3 cycles. This study paves a new way towards opening up MOFs' potential application in capturing radioactive iodine to protect the environment.

12.
Sci Total Environ ; : 150546, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34582862

RESUMO

The concentrations of 75 polychlorinated naphthalene (PCN) congeners in 95 human serum samples from the Fengjiang electronic waste dismantling area and Huangyan District in Taizhou City (Zhejiang Province, China) were determined. Thyroid hormone (FT3, FT4, TSH, and TRH) concentrations in the samples were also determined. The total PCN concentrations in the samples from Fengjiang and Huangyan were 1.29 × 104-4.28 × 105 and 8.29 × 102-6.45 × 105 pg/g lipid, respectively. The less-chlorinated (Cl1-3) PCN concentrations were relatively high in all of the samples, and the concentrations in the samples from the two areas were not significantly different. The sums of the combustion-related PCN congener concentrations were significantly higher in the samples from Fengjiang than in the samples from Huangyan, and the sums of the more-chlorinated (Cl4-8) PCNs were slightly higher in the samples from Fengjiang than in the samples from Huangyan. The relationship between the PCN concentration and age indicated that electronic waste controls have decreased human exposure to PCNs but that attention should still be paid to exposure to less-chlorinated PCNs. The main PCN congeners that contributed to the toxic equivalent concentrations were markedly different for the samples from Fengjiang and Huangyan. CN-66/67 was dominant for the Fengjiang samples and CN-10 was dominant for the Huangyan samples. Attention should be paid to the risks posed by less-chlorinated PCNs to human health. CN-1, CN-2, and CN-20 concentrations are related to human thyroid hormone levels, and the relationships between less-chlorinated PCN concentrations and thyroid hormone concentrations should be further studied.

13.
Planta Med ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521131

RESUMO

The dried stem bark of Berberis kansuensis is a commonly used Tibetan herbal medicine for the treatment of diabetes. Its main chemical components are alkaloids, such as berberine, magnoflorine and jatrorrhizine. However, the role of gut microbiota in the in vivo metabolism of these chemical components has not been fully elucidated. In this study, an ultra-high performance liquid chromatography method coupled with Orbitrap mass spectrometry (UHPLC-Orbitrap-MS) technology was applied to detect and identify prototype components and metabolites in rat intestinal contents and serum samples after oral administration of a B. kansuensis extract. A total of 16 prototype components and 40 metabolites were identified. The primary metabolic pathways of the chemical components from B. kansuensis extract were demethylation, desaturation, deglycosylation, reduction, hydroxylation, and other conjugation reactions including sulfation, glucuronidation, glycosidation, and methylation. By comparing the differences of metabolites between diabetic and pseudo-germ-free diabetic rats, we found that the metabolic transformation of some chemical components in B. kansuensis extract such as bufotenin, ferulic acid 4-O-ß-D-glucopyranoside, magnoflorine, and 8-oxyberberine, was affected by the gut microbiota. The results revealed that the gut microbiota can affect the metabolic transformation of chemical constituents in B. kansuensis extract. These findings can enhance our understanding of the active ingredients of B. kansuensis extract and the key role of the gut microbiota on them.

14.
Int J Oral Sci ; 13(1): 28, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34475379

RESUMO

Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite mechanisms remain elusive. Emerging evidence supports an association between mitochondrial dysfunction and AS. In our study, the impact of P. gingivalis on mitochondrial dysfunction and the potential mechanism were investigated. The mitochondrial morphology of EA.hy926 cells infected with P. gingivalis was assessed by transmission electron microscopy, mitochondrial staining, and quantitative analysis of the mitochondrial network. Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP) levels. Cellular ATP production was examined by a luminescence assay kit. The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence. Mdivi-1, a specific Drp1 inhibitor, was used to elucidate the role of Drp1 in mitochondrial dysfunction. Our findings showed that P. gingivalis infection induced mitochondrial fragmentation, increased the mtROS levels, and decreased the MMP and ATP concentration in vascular endothelial cells. We observed upregulation of Drp1 (Ser616) phosphorylation and translocation of Drp1 to mitochondria. Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P. gingivalis. Collectively, these results revealed that P. gingivalis infection promoted mitochondrial fragmentation and dysfunction, which was dependent on Drp1. Mitochondrial dysfunction may represent the mechanism by which P. gingivalis exacerbates atherosclerotic lesions.


Assuntos
Dinâmica Mitocondrial , Porphyromonas gingivalis , Células Endoteliais , Mitocôndrias
15.
Medicine (Baltimore) ; 100(36): e26220, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516486

RESUMO

BACKGROUND: Laminectomy with lateral mass screw fixation (LCS) is considered an effective surgical procedure for cervical spondylotic myelopathy. However, varying degrees of loss of the cervical curvature were noted in some patients postoperatively. The aim of this study was to observe the relationship between cervical curvature and spinal drift distance after LCS and to determine its effect on neurological function, axial symptoms, and C5 palsy. METHODS: A total of 117 consecutive cervical spondylotic myelopathy patients with normal cervical curvature underwent LCS from April 2015 to May 2017 in our institution. Of these patients, 90 patients who accepted to undergo an integrated follow-up were enrolled in this study. The patients were divided into 3 groups based on their postoperative cervical curvature. In group A (28 patients), the cervical curvature became straight postoperatively (0°≤cervical spine angle≤5°); in group B (36 patients), the cervical curvature decreased (5°16.5°). Spinal drift distance, neurological recovery, axial symptoms, and C5 palsy in the patients were recorded and analyzed. RESULTS: Postoperative measurements showed that there was no significant difference in laminectomy width between the groups (P > .05). The cervical spine angle was 2.7°â€Š±â€Š0.5° in group A, 11.2°â€Š±â€Š2.6° in group B, and 20.8°â€Š±â€Š4.1° in group C (P < .05), while the spinal drift distance was 1.2 ±â€Š0.2 mm, 1.8 ±â€Š0.4 mm, and 3.0 ±â€Š0.5 mm, respectively (P < .05). The postoperative Japanese Orthopedic Association score was significantly increased in all groups (P < .05), and there was no significant difference between the groups at different time points (P > .05). However, significant differences were noted between the groups in axial symptoms (P < .05), which were analyzed via the visual analog scale score. The occurrence of C5 palsy in groups A, B, and C was 7.1% (2/28), 8.3% (3/36), and 11.5% (3/26), respectively (P > .05). CONCLUSION: In LCS, the cervical curvature should be maintained at the normal angle to obtain a good spinal cord drift distance and a lower incidence of axial symptoms.


Assuntos
Parafusos Ósseos , Vértebras Cervicais/cirurgia , Medula Espinal/fisiopatologia , Espondilose/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/fisiopatologia , Feminino , Humanos , Laminectomia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Resultado do Tratamento
16.
Microb Biotechnol ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473895

RESUMO

Polyhydroxyalkanoates (PHA) are a promising and sustainable alternative to the petroleum-based synthetic plastics. Regulation of PHA synthesis is receiving considerable importance as engineering the regulatory factors might help developing strains with improved PHA-producing abilities. PHA synthesis is dedicatedly regulated by a number of regulatory networks. They tightly control the PHA content, granule size and their distribution in cells. Most PHA-accumulating microorganisms have multiple regulatory networks that impart a combined effect on PHA metabolism. Among them, several factors ranging from global to specific regulators, have been identified and characterized till now. This review is an attempt to categorically summarize the diverse regulatory circuits that operate in some important PHA-producing microorganisms. However, in several organisms, the detailed mechanisms involved in the regulation of PHA synthesis is not well-explored and hence further research is needed. The information presented in this review might help researcher to identify the prevailing research gaps in PHA regulation.

17.
Oral Dis ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479400

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC), a main type of squamous cell cancer, is associated with considerable morbidity and mortality. Recent reports suggested methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification to be an essential regulator in the fate determination of stem cells. However, the functional significance of METTL3 in OSCC remains largely unknown. METHODS: METTL3 expression was examined in OSCC patient samples, followed by correlation analysis against clinical tumor features. Functional assays, such as assessment of surface marker expression, colony forming, BrdU incorporation, tumor xenograft assay, and m6A dot blot, were conducted to study the impact of METTL3 knockdown (KD) in OSCC cells. RESULTS: High METTL3 expression was positively correlated with more severe clinical features of OSCC tumors. METTL3 KD caused impairment of stem-like capacities in OSCC cells, such as tumorigenicity in vivo and colony-forming ability in vitro. Furthermore, METTL3-KD and cycloleucine, a methylation inhibitor, decreased m6A levels and down-regulated p38 expression in OSCC cells. On the contrary, the impaired cell proliferation capacity of OSCC cells after METTL3-KD was restored by exogenous expression of p38. CONCLUSION: Our findings identified m6A methyltransferase METTL3 as a key element in the regulation of tumorigenesis in OSCC.

18.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445086

RESUMO

The introduction of herbaceous peony (Paeonia lactiflora Pall.) in low-latitude areas is of great significance to expand the landscape application of this world-famous ornamental. With the hazards of climate warming, warm winters occurs frequently, which makes many excellent northern herbaceous peony cultivars unable to meet their chilling requirements (CR) and leads to their poor growth and flowering in southern China. Exploring the endodormancy release mechanism of underground buds is crucial for improving low-CR cultivar screening and breeding. A systematic study was conducted on P. lactiflora 'Meiju', a screened cultivar with a typical low-CR trait introduced from northern China, at the morphological, physiological and molecular levels. The CR value of 'Meiju' was further verified as 677.5 CUs based on the UT model and morphological observation. As a kind of signal transducer, reactive oxygen species (ROS) released a signal to enter dormancy, which led to corresponding changes in carbohydrate and hormone metabolism in buds, thus promoting underground buds to acquire strong cold resistance and enter endodormancy. The expression of important genes related to ABA metabolism, such as NCED3, PP2C, CBF4 and ABF2, reached peaks at the critical stage of endodormancy release (9 January) and then decreased rapidly; the expression of the GA2ox8 gene related to GA synthesis increased significantly in the early stage of endodormancy release and decreased rapidly after the release of ecodormancy (23 January). Cytological observation showed that the period when the sugar and starch contents decreased and the ABA/GA ratio decreased was when 'Meiju' bud endodormancy was released. This study reveals the endodormancy regulation mechanism of 'Meiju' buds with the low-CR trait, which lays a theoretical foundation for breeding new herbaceous peony cultivars with the low-CR trait.


Assuntos
Paeonia/crescimento & desenvolvimento , Dormência de Plantas , Clima , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Paeonia/genética , Paeonia/fisiologia , Melhoramento Vegetal , Estações do Ano
19.
Commun Biol ; 4(1): 1007, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433872

RESUMO

The haloarchaeon Haloferax mediterranei is a potential strain for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production, yet the production yield and cost are the major obstacles hindering the use of this archaeal strain. Leveraging the endogenous type I-B CRISPR-Cas system in H. mediterranei, we develop a CRISPR-based interference (CRISPRi) approach that allows to regulate the metabolic pathways related to PHBV synthesis, thereby enhancing PHBV production. Our CRISPRi approach can downregulate the gene expression in a range of 25% to 98% depending upon the target region. Importantly, plasmid-mediated CRISPRi downregulation on the citrate synthase genes (citZ and gltA) improves the PHBV accumulation by 76.4% (from 1.78 to 3.14 g/L). When crRNA cassette integrated into chromosome, this further shortens the PHBV fermentation period and enhances PHA productivity by 165%. Our transcriptome analysis shows that repression of citrate synthase genes redirects metabolic flux from the central metabolic pathways to PHBV synthesis pathway. These findings demonstrate that the CRISPRi-based gene regulation is a transformative toolkit for fine-tuning the endogenous metabolic pathways in the archaeal system, which can be applied to not only the biopolymer production but also many other applications.

20.
IEEE Trans Image Process ; 30: 8454-8467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34464261

RESUMO

To train accurate deep object detectors under the extreme foreground-background imbalance, heuristic sampling methods are always necessary, which either re-sample a subset of all training samples (hard sampling methods, e.g. biased sampling, OHEM), or use all training samples but re-weight them discriminatively (soft sampling methods, e.g. Focal Loss, GHM). In this paper, we challenge the necessity of such hard/soft sampling methods for training accurate deep object detectors. While previous studies have shown that training detectors without heuristic sampling methods would significantly degrade accuracy, we reveal that this degradation comes from an unreasonable classification gradient magnitude caused by the imbalance, rather than a lack of re-sampling/re-weighting. Motivated by our discovery, we propose a simple yet effective Sampling-Free mechanism to achieve a reasonable classification gradient magnitude by initialization and loss scaling. Unlike heuristic sampling methods with multiple hyperparameters, our Sampling-Free mechanism is fully data diagnostic, without laborious hyperparameters searching. We verify the effectiveness of our method in training anchor-based and anchor-free object detectors, where our method always achieves higher detection accuracy than heuristic sampling methods on COCO and PASCAL VOC datasets. Our Sampling-Free mechanism provides a new perspective to address the foreground-background imbalance. Our code is released at https://github.com/ChenJoya/sampling-free.

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