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1.
Autoimmun Rev ; : 103161, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926770

RESUMO

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), which are pivotal sensors of RNA virus invasions, mediate the transcriptional induction of genes encoding type I interferons (IFNs) and proinflammatory cytokines, successfully establishing host antiviral immune response. A few excellent reviews have elaborated on the structural biology of RLRs and the antiviral mechanisms of RLR activation. In this review, we give a basic understanding of RLR biology and summarize recent findings of how RLR signaling cascade is strictly controlled by host regulatory mechanisms, which include RLR-interacting proteins, post-translational modifications and microRNAs (miRNAs). Furthermore, we pay particular attention to the relationship between RLRs and diseases, especially how RLRs participate in SARS-CoV-2, malaria or bacterial infections, how single-nucleotide polymorphisms (SNPs) or mutations in RLRs and antibodies against RLRs lead to autoinflammatory diseases and autoimmune diseases, and how RLRs are involved in anti-tumor immunity. These findings will provide insights and guidance for antiviral and immunomodulatory therapies targeting RLRs.

2.
Med Sci Monit ; 28: e936703, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35909265

RESUMO

BACKGROUND The aim of this study was to identify the diagnostic magnetic resonance imaging (MRI) findings in 47 shoulders with subcoracoid impingement syndrome by comparison with 100 normal shoulders. MATERIAL AND METHODS The subcoracoid impingement syndrome group consisted of 47 shoulders with subcoracoid impingement syndrome and the normal group consisted of 100 normal shoulders. The MRI parameters - coracoids-humeral distance (CHD), coracoid index (CI), height of the lesser tuberosity (HLT), coracoid obliquity (CO), coracoglenoid angle (CGA), coracohumeral angle (CHA), width of the subscapular tendon (WST), and contact distance between subscapular tendon and coracoid process (CD) - were compared between the subcoracoid impingement syndrome group and the normal group. The areas under the curves (AUCs) from the receiver operating characteristic (ROC) for single MRI parameters were recorded, in which the MRI parameters with AUC exceeding 0.70 were included in the analysis of combined parameters. Comparisons of ROC were made among single parameters and combined parameters. RESULTS For diagnosing subcoracoid impingement syndrome by using single MRI parameters (CHD, CI, HLT, CGA, CHA, WST, and CD), the AUCs were 0.963, 0.806, 0.745, 0.691, 0.613, 0.685, and 0.614, respectively, of which CHD had the largest AUC. CHD, CI, and HLT (AUC exceeding 0.70) were included in the study of the combined parameters. The AUC of combined CHD and HLT showed a significantly larger AUC than that of CHD (0.986 vs 0.963, P=0.036), and showed no significant difference compared with that of combined CHD, CI, and HLT (0.986 vs 0.987, P=0.882). CONCLUSIONS Measurement of the coracoid-humeral distance and height of the lesser tuberosity were key MRI diagnostic findings for subcoracoid impingement syndrome.


Assuntos
Lesões do Manguito Rotador , Síndrome de Colisão do Ombro , Articulação do Ombro , Humanos , Imageamento por Ressonância Magnética/métodos , Manguito Rotador , Ombro , Síndrome de Colisão do Ombro/diagnóstico por imagem
3.
Cell Prolif ; : e13318, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35932176

RESUMO

OBJECTIVES: Diabetes mellitus is associated with refractory wound healing, yet current therapies are insufficient to accelerate the process of healing. Recent studies have indicated chemically modified mRNA (modRNA) as a promising therapeutic intervention. The present study aimed to explore the efficacy of small skin engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) facilitating wound healing in a full-thickness skin defect rat model. This study, devised therapeutic strategies for diabetic wounds by pre-treating small skin with SDF-1α modRNA. MATERIALS AND METHODS: The in vitro transfection efficiency was evaluated using fluorescence microscopy and the content of SDF-1α in the medium was determined using ELISA after the transfection of SDF-1α into the small skin. To evaluate the effect of SDF-1α modRNA and transplantation of the small skin cells on wound healing, an in vivo full-thickness skin defect rat model was assessed. RESULTS: The results revealed that a modRNA carrying SDF-1α provided potent wound healing in the small skin lesions reducing reduced scar thickness and greater angiogenesis (CD31) in the subcutaneous layer. The SDF-1α cytokines were significantly secreted by the small skin after transfection in vitro. CONCLUSIONS: This study demonstrated the benefits of employing small skin combined with SDF-1α modRNA in enhancing wound healing in diabetic rats having full-thickness skin defects.

4.
Front Plant Sci ; 13: 959784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937355

RESUMO

Yields of wheat crops that succeed rice paddy crops are generally low. To date, it has been unclear whether such low yields were due to rice paddies altering soil physical or mineral characteristics, or both. To investigate this quandary, we conducted field experiments in the Jianghan Plain to analyze differences in the spatial distribution of wheat roots between rice-wheat rotation (RW) and dryland-wheat rotations (DW) using a range of nitrogen treatments. Dryland wheat crops were preceded by either dryland soybean or corn in the prior summer. Biomass of wheat crops in RW systems was significantly lower than that of DW for all N fertilizer treatments, although optimal nitrogen management resulted in comparable wheat yields in both DW and RW. Soil saturated water capacity and non-capillary porosity were higher in DW than RW, whereas soil bulk density was higher in RW. Soil available nitrogen and organic matter were higher in DW than RW irrespective of N application, while soil available P and K were higher under RW both at anthesis and post-harvest stages. At anthesis, root length percentage (RLP) was more concentrated in surface layers (0-20 cm) in RW, whereas at 20-40 cm and 40-60 cm, RLP was higher in DW than RW for all N treatments. At maturity, RLP were ranked 0-20 > 20-40 > 40-60 cm under both cropping systems irrespective of N fertilization. Root length percentage and soil chemical properties at 0-20 cm were positively correlated (r = 0.79 at anthesis, r = 0.68 at post-harvest) with soil available P, while available N (r = -0.59) and soil organic matter (r = -0.39) were negatively correlated with RLP at anthesis. Nitrogen applied at 180 kg ha-1 in three unform amounts of 60 kg N ha-1 at sowing, wintering and jointing resulted in higher yields than other treatments for both cropping systems. Overall, our results suggest that flooding of rice paddies increased bulk density and reduced available nitrogen, inhibiting the growth and yield of subsequent wheat crops relative to rainfed corn or soybean crops.

5.
Anal Methods ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943237

RESUMO

A novel qNMR method was developed for the simultaneous determination of the component ratio and moisture content in triethyleneglycol dinitrate (TEGDN) and nitroglycerin (NG) composites. Using the ERETIC module technique of NMR spectrometry, moisture in the solvent and internal standard were eliminated by the integral value subtraction method, and the component ratio and moisture content in TEGDN/NG composites could be accurately calculated. Method validation was carried out in terms of the precision, stability, linearity, recovery, robustness, limit of quantification (LOQ) and limit of detection (LOD). The results of the qNMR method show good accuracy compared with the HPLC and Karl Fischer methods. Statistical Student's t-test and F-test at the 95% confidence level proved that there was no significant difference between the qNMR method and the other two methods. For TEGDN/NG composites of high-energy and high-sensitivity explosives, the low dose and high efficiency of the qNMR method could effectively avoid the danger of explosion and burning.

6.
Int J Med Sci ; 19(8): 1307-1319, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928717

RESUMO

Tissue regeneration is the preferred treatment for dentin and bone tissue defects. Dental pulp stem cells (DPSCs) have been extensively studied for their use in tissue regeneration, including the regeneration of dentin and bone tissue. LIM mineralization protein-1 (LMP-1) is an intracellular non-secretory protein that plays a positive regulatory role in the mineralization process. In this study, an LMP-1-induced DPSCs model was used to explore the effect of LMP-1 on the proliferation and odonto/osteogenic differentiation of DPSCs, as well as the underlying mechanisms. As indicated by the cell counting kit-8 assay, the results showed that LMP-1 did not affect the proliferation of DPSCs. Overexpression of LMP-1 significantly promoted the committed differentiation of DPSCs and vice versa, as shown by alkaline phosphatase activity assay, alizarin red staining, western blot assay, quantitative real-time polymerase chain reaction assay, and in vivo mineralized tissue formation assay. Furthermore, inhibiting the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways using specific pathway inhibitors showed that the ERK1/2 and p38 MAPK pathways attenuated the differentiation of DPSCs. Besides, the expression of BMP signaling pathway components were also determined, which suggested that LMP-1 could activate BMP-2/Smad1/5 signaling pathway. Our results not only indicated the underlying mechanism of LMP-1 treated DPSCs but also provided valuable insight into therapeutic strategies in regenerative medicine.


Assuntos
Osteogênese , Proteínas Quinases p38 Ativadas por Mitógeno , Diferenciação Celular , Proliferação de Células/genética , Células Cultivadas , Polpa Dentária/metabolismo , Sistema de Sinalização das MAP Quinases , Proteína Quinase 3 Ativada por Mitógeno , Osteogênese/genética , Transdução de Sinais , Células-Tronco/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-35912639

RESUMO

Microbial fuel cells (MFCs) are promising ecofriendly techniques for harvesting bioenergy from organic and inorganic matter. Currently, it is challenging to design MFC anodes with favorable microorganism attachment and fast extracellular electron transfer (EET) rate for high MFC performance. Here we prepared N-doped carbon nanotubes (NCNTs) on carbon felt (CF) and used it as a support for growing hierarchical Co8FeS8-FeCo2O4/NCNTs core-shell nanostructures (FeCo/NCNTs@CF). We observed improved wettability, specific areal capacitance, and diffusion coefficient, as well as small charge transfer resistance compared with bare CF. MFCs equipped with FeCo/NCNTs@CF displayed a power density of 3.04 W/m2 and COD removal amount of 221.0 mg/L/d, about 47.6 and 290.1% improvements compared with that of CF. Biofilm morphology and 16s rRNA gene sequence analysis proved that our anode facilitated the enrichment growth of exoelectrogens. Flavin secretion was also promoted on our hierarchical elelctrode, effectively driving the EET process. This work disclosed that hierarchical nanomaterials modified electrode with tailored physicochemical properties is a promising platform to simultaneously enhance exoelectrogen attachment and EET efficiency for MFCs.

8.
J Parkinsons Dis ; 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35912751

RESUMO

BACKGROUND: Pathological changes in the brain can affect the gastrointestinal tract, whereas there is less evidence regarding the brain-gut axis. OBJECTIVE: To identify whether cerebral endogenous phosphorylated α-synuclein induces gastrointestinal dysfunction via the brain-gut axis, mediated by the vagus nerve. METHODS: α-syn N103/tau N368 preformed fibrils were injected into the dorsal lateral striatum of rodents, and the cerebral and colonic synucleinopathies and changes in the enteric nervous system were analyzed. Moreover, subdiaphragmatic vagotomy was conducted to confirm the role of the vagus nerve in brain-gut propagation. RESULTS: An anterograde propagation of phosphorylated α-synuclein from the brain to the proximal colon mainly via the vagus nerve was observed at one month. The accumulation of phosphorylated α-synuclein was detected in the proximal colon over time, accompanied by infiltration of macrophages and eosinophils in the mucosa and submucosa. Upon injection with lower doses of preformed fibrils, the accumulation of phosphorylated α-synuclein and dopaminergic neuron loss was reduced to levels consistent with control at six months, while the expression levels of GFAP, Iba-1, and IL-6 increased. Under high preformed fibrils dose conditions, fecal traits and gastrointestinal motility were significantly reduced at six months, and aggregations of phosphorylated α-synuclein and an increasing level of IL-1ß appeared. CONCLUSION: Induced endogenous α-synuclein can quickly propagate into the proximal colon mainly via the vagus nerve. Injections of low doses of preformed fibrils can elicit recovery of the enteric nervous system and degradation of α-synuclein aggregates whereas high doses cause accumulation of pathological α-synuclein, enteric inflammation, and prominent gastrointestinal dysfunction.

9.
Front Physiol ; 13: 913369, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910569

RESUMO

Objectives: The purpose of this study was to elucidate the relationship between sleep disorders and male reproductive health, and to explore the underlying mechanisms via a systematic review and meta-analysis. Methods: PubMed, Embase, The Cochrane library, Web of Science, Scopus databases were searched to collect clinical research on the effects of sleep disorders on male semen parameters from inception to February 24, 2022. RevMan 5.4 was used for meta-statistical analysis. Stata16 software was used to detect publication bias. Results: The results of meta-analysis showed that sleep disorders were associated with reduced total sperm count (mean difference (MD) = -27.91, 95% CI = (-37.82, -18.01), p < 0.001), reduced sperm concentration (MD = -5.16, 95% CI = (-9.67, -0.65), p = 0.02), reduced progressive motility (MD = -2.94, 95% CI = (-5.28, -0.59), p = 0.01), and reduced normal morphology (MD = -0.52, 95% CI = (-0.80, -0.24), p < 0.001). However, there is no significant association between sleep disorders and semen volume/reproductive hormones. Further bioinformatics mining revealed that related clock genes (PER1, PER2, CRY2, NR1D1 and NPAS2) were down-regulated in non-obstructive azoospermia patients. Conclusion: In conclusion, current evidence suggests that sleep disorders have a negative impact on male reproductive health, and its underlying mechanism may be related to circadian rhythm disorders. However, the relationship between sleep disorders and reproductive hormone levels has not been found. Due to the limited number and quality of included studies, the above findings need to be validated by more high-quality studies.

10.
Anal Chem ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921590

RESUMO

Reliable detection of airborne chemical warfare agents (CWAs) at the site and in real-time remains a challenge due to the rarity of miniaturized analytical tools. Herein, an o-carborane-functionalized benzothiazole derivative (PCBO) with excited-state intramolecular proton transfer (ESIPT) and AIE characteristics was synthesized. The PCBO-based film sensor showed a highly sensitive response to representative simulants of CWAs, and detection limits were found to be 1.0 mg·m-3 for triphosgene, 6.0 mg·m-3 for chloroethyl ethyl sulfide, and 0.2 mg·m-3 for diethyl chlorophosphite. Moreover, the sensor showed great reusability (>100 cycles) and unprecedented response speed (<0.5 s). The excellent sensing performance was ascribed to the microenvironmental sensitivity of the sensing fluorophore, the porous adlayer structure of the film, and the specific binding of the fluorophore to the analytes. Furthermore, discrimination and identification of the examined CWA simulants were realized via the introduction of another fluorophore (HCBO)-based film. Importantly, a portable fluorescent CWA detector was built with the sensor as the key component, and its applicability was demonstrated by the successful detection of a typical CWA sample (Sarin). The present study indicates that fluorescent film sensors could satisfy reliable onsite and real-time detection of harmful chemicals.

11.
J Neurosci Methods ; 379: 109674, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35842015

RESUMO

BACKGROUND: Steady-state visual evoked potential (SSVEP) is a prevalent paradigm of brain-computer interface (BCI). Recently, deep neural networks (DNNs) have been employed for SSVEP target recognition. However, current DNN models can not fully extract information from SSVEP harmonic components, and ignore the influence of non-target stimuli. NEW METHOD: To employ information of multiple sub-bands and non-target stimulus data, we propose a DNN model for SSVEP target detection, i.e., FB-EEGNet, which fuses features of multiple neural networks. Additionally, we design a multi-label for each sample and optimize the parameters of FB-EEGNet across multi-stimulus to incorporate the information from non-target stimuli. RESULTS: Under the subject-specific condition, FB-EEGNet achieves the average classification accuracies (information transfer rate (ITR)) of 76.75 % (50.70 bits/min) and 89.14 % (70.45 bits/min) in a time widow of 0.7 s under the public 12-target dataset and our experimental 9-target dataset, respectively. Under the cross-subject condition, FB-EEGNet achieved mean accuracies (ITRs) of 81.72 % (67.99 bits/min) and 92.15 % (76.12 bits/min) on the public and experimental datasets in a time window of 1 s, respectively. COMPARISON WITH EXISTING METHODS: FB-EEGNet shows superior performance than CCNN, EEGNet, CCA and FBCCA both for subject-dependent and subject-independent SSVEP target recognition. CONCLUSION: FB-EEGNet can effectively extract information from multiple sub-bands and cross-stimulus targets, providing a promising way for extracting deep features in SSVEP using neural networks.


Assuntos
Interfaces Cérebro-Computador , Potenciais Evocados Visuais , Algoritmos , Eletroencefalografia , Redes Neurais de Computação , Estimulação Luminosa
12.
ACS Infect Dis ; 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35830188

RESUMO

Bacterial biofilms are surface-attached communities of slow- or non-replicating cells embedded within a protective matrix of biomolecules. Unlike free-floating planktonic bacteria, biofilms are innately tolerant to conventional antibiotics and are prevalent in recurring and chronic infections. Nitroxoline, a broad-spectrum biofilm-eradicating agent, was used to probe biofilm viability. Transcript profiling (RNA-seq) showed that 452 of 2594 genes (17.4%) in methicillin-resistant Staphylococcus aureus (MRSA) biofilms were differentially expressed after a 2 h treatment of nitroxoline. WoPPER analysis and time-course validation (RT-qPCR) revealed that gene clusters involved in iron acquisition (sbn, isd, MW2101, MW0695, fhu, and feo) were rapidly up-regulated following nitroxoline treatment, which is indicative of iron starvation in MRSA biofilms. In addition, genes related to oligopeptide transporters and riboflavin biosynthesis were found to be up-regulated, while genes related to carotenoid biosynthesis and nitrate assimilation were down-regulated. RT-qPCR experiments revealed that iron uptake transcripts were also up-regulated in established Staphylococcus epidermidis and Acinetobacter baumannii biofilms following nitroxoline treatment. Overall, we show RNA-seq to be an ideal platform to define cellular pathways critical for biofilm survival, in addition to demonstrating the need these bacterial communities have for iron.

13.
Int J Biol Sci ; 18(10): 3981-3992, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844797

RESUMO

Intestinal ischemia/reperfusion (I/R) is a common pathophysiological process in clinical severe patients, and the effect of intestinal I/R injury on the patient's systemic pathophysiological state is far greater than that of primary intestinal injury. In recent years, more and more evidence has shown that intestinal microbiota and its metabolites play an important role in the occurrence, development, diagnosis and treatment of intestinal I/R injury. Intestinal microbiota is regulated by host genes, immune response, diet, drugs and other factors. The metabolism and immune potential of intestinal microbiota determine its important significance in host health and diseases. Therefore, targeting the intestinal microbiota and its metabolites may be an effective therapy for the treatment of intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury. This review focuses on the role of intestinal microbiota and its metabolites in intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury, and summarizes the latest progress in regulating intestinal microbiota to treat intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury.


Assuntos
Microbioma Gastrointestinal , Traumatismo por Reperfusão , Humanos , Intestinos , Traumatismo por Reperfusão/metabolismo
14.
Sci Rep ; 12(1): 11997, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35835850

RESUMO

Phosphorus (P) deficiency is the main hurdle in achieving sustainable crop production ps especially in calcareous soils. Using bio-fertilizers like phosphate solubilizing bacteria (PSB) could be a useful approach for sustainable P management as they improve P availability in soil via dissolution, desorption and mineralization reactions. In addition, application of organic amendments with PSB could further ameliorate soil conditions for sustainable management of immobilized nutrients in calcarious soils. Therefore, we performed pot experiment to study the role of PSB in nullifying antagonistic effects of liming (4.78, 10, 15 and 20%) on P availability from poultry manure (PM), farm yard manure (FYM), single super phosphate (SSP) and rock phosphate (RP) in alkaline soils. PSB inoculation improved wheat growth, P availability and stimulated soil acidification over control regardless of P sources and lime levels. Soil calcification adversely affected plant growth, P nutrition, induced soil salinity and alkalinity, however, PSB and manures application potentially nullified such harmful effects over mentioned traits. Individually, organic sources were superior than mineral sources however, the performance of mineral fertilizers with PSB was at par to sole application of manures. Furthermore, application of RP with PSB proved as effective as sole SSP. Therefore, using PSB as bio-fertilizer has huge potential for improving P availability in calcareous soils.


Assuntos
Fertilizantes , Solo , Bactérias , Fertilizantes/análise , Esterco , Fosfatos/análise , Fósforo , Triticum
15.
Zookeys ; 1095: 43-74, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836687

RESUMO

A list of 34 thomisid species belonging to 21 genera collected in Jangxi Province of China is provided. Five new species are described: Angaeusxieluae Liu, sp. nov. (♂♀), Lysitelessubspirellus Liu, sp. nov. (♀), Oxytatemucunica Liu, sp. nov. (♀), Phartalingxiufengica Liu, sp. nov. (♀), Stephanopisxiangzhouica Liu, sp. nov. (♀). A new combination is proposed: Ebelingiaforcipata (Song & Zhu, 1993) comb. nov. (ex. Ebrechtella Dahl, 1907). Previously unknown females of E.forcipata (Song & Zhu, 1993), Oxytatebicornis Liu, Liu & Xu, 2017, and Xysticuslesserti Schenkel, 1963 are described for the first time. Stephanopis O Pickard-Cambridge, 1869, a genus previously known from Australasia and South America, is recorded from the Asian mainland for the first time.

16.
Front Plant Sci ; 13: 947132, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837461

RESUMO

Contemporary wisdom suggests that inclusion of legumes into crop rotations benefit subsequent cereal crop yields. To investigate whether this maxim was generically scalable, we contrast summer soybean-winter wheat (SW) with summer maize-winter wheat (MW) rotation systems in an extensive field campaign in the North China Plain (NCP). We identify heretofore unseen interactions between crop rotation, synthetic N fertilizer application, and stored soil water. In the year with typical rainfall, inclusion of soybean within rotation had no effect on wheat ear number and yield, while N fertilization penalized wheat yields by 6-8%, mainly due to lower dry matter accumulation after anthesis. In contrast, in dry years prior crops of soybean reduced the rate and number of effective ears in wheat by 5-27 and 14-17%, respectively, leading to 7-23% reduction in wheat yield. Although N fertilization increased the stem number before anthesis in dry years, there was no corresponding increase in ear number and yield of wheat in such years, indicating compensating reduction in yield components. We also showed that N fertilization increased wheat yield in MW rather than SW as the former better facilitated higher dry matter accumulation after flowering in dry years. Taken together, our results suggest that soybean inclusion reduced soil available water for subsequent wheat growth, causing yield penalty of subsequent wheat under drought conditions. We call for more research into factors influencing crop soil water, including initial state, crop water requirement, and seasonal climate forecasts, when considering legumes into rotation systems. Graphical AbstractResponse of wheat population and yield to soybean inclusion under limited-irrigation.

17.
Synth Syst Biotechnol ; 7(3): 1002-1011, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35782483

RESUMO

Genomic integration of genes and pathway-sized DNA cassettes is often an indispensable way to construct robust and productive microbial cell factories. For some uncommon microbial hosts, such as Mycolicibacterium and Mycobacterium species, however, it is a challenge. Here, we present a multiplexed integrase-assisted site-specific recombination (miSSR) method to precisely and iteratively integrate genes/pathways with controllable copies in the chromosomes of Mycolicibacteria for the purpose of developing cell factories. First, a single-step multi-copy integration method was established in M. neoaurum by a combination application of mycobacteriophage L5 integrase and two-step allelic exchange strategy, the efficiencies of which were ∼100% for no more than three-copy integration events and decreased sharply to ∼20% for five-copy integration events. Second, the R4, Bxb1 and ΦC31 bacteriophage Att/Int systems were selected to extend the available integration toolbox for multiplexed gene integration events. Third, a reconstructed mycolicibacterial Xer recombinases (Xer-cise) system was employed to recycle the selection marker of gene recombination to facilitate the iterative gene manipulation. As a proof of concept, the biosynthetic pathway of ergothioneine (EGT) in Mycolicibacterium neoaurum ATCC 25795 was achieved by remodeling its metabolic pathway with a miSSR system. With six copies of the biosynthetic gene clusters (BGCs) of EGT and pentose phosphate isomerase (PRT), the titer of EGT in the resulting strain in a 30 mL shake flask within 5 days was enhanced to 66 mg/L, which was 3.77 times of that in the wild strain. The improvements indicated that the miSSR system was an effective, flexible, and convenient tool to engineer the genomes of Mycolicibacteria as well as other strains in the Mycobacteriaceae due to their proximate evolutionary relationships.

18.
iScience ; 25(7): 104533, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35784791

RESUMO

Ferroptosis is crucial to the pathology of many neurological diseases. Here, we found pre-treatment with myriocin, an inhibitor of de novo synthesis of sphingolipid, significantly decreased the erastin- or glutamate-induced ferroptosis of HT22 cells without requiring the recovery of intracellular glutathione. The transcriptome analysis of HT22 cells treated with or without myriocin identified the hypoxia-inducible factor 1 (HIF-1) pathway as a prime and novel drug target. Further study validated that HIF1α was required for the cytoprotective effects of myriocin. Myriocin treatment promoted the expression of HIF-1 pathway effectors including PDK1 and BNIP3 and altered the intracellular levels of glucose metabolites. Additionally, myriocin treatment stabilized HIF1α protein by decreasing its ubiquitination and proteasomal degradation. Similar effects of myriocin on HIF1α stabilization were also found in other mammalian cell lines indicating this is a common mechanism for the cytoprotective role of myriocin.

19.
J Environ Manage ; 319: 115655, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35839651

RESUMO

Digestate recirculation is often considered an important way to improve system stability (system acidification, ammonia inhibition, hydrolysis limitations, etc.) and gas production performance. However, it is not clear how the promotion of biohythane production works in anaerobic co-digestion with digestate recirculation of rice straw (RS) and pig manure (PM). Two sets of laboratory-scale two-stage continuous stirred tank reactors were operated continuously for 95 d to investigate the performance of biohythane production in the first/second phase under mesophilic (M)/thermophilic (T) and digestate recirculation conditions. Firstly, biohythane was not produced by PM with RS under digestate recirculation. The main reasons were: 1) Digestive recirculation promoted the growth of hydrogenotrophic methanogenic bacteria; and 2) limitations in hydrolysis. Secondly, digestate recirculation has positive effects on the removal rates (removal rates of TS, VS, polysaccharide, protein and TCOD increased by 30.4%, 22.3%, 9.9%, 31.4%, and 11.9%, respectively) and energy yield (up to 68.7%). Finally, there was a higher abundance of hydrogen-producing bacteria (Fervidobacterium [44.9%] and Coprothermobacter [18.8%]) in T2, accounting for >80% of the total, and of which the huge hydrogen production potential cannot be ignored. The results provide new ideas for alleviating the energy crisis and developing green energy in the future.

20.
Int J Oral Sci ; 14(1): 36, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35851058

RESUMO

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.


Assuntos
Carcinoma de Células Escamosas , Vesículas Extracelulares , MicroRNAs , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica , Regulação para Baixo , Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Humanos , MicroRNAs/metabolismo , Neoplasias Bucais/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteína Supressora de Tumor p53/metabolismo
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