MtTRC-1, a Novel Transcription Factor, Regulates Cellulase Production via Directly Modulating the Genes Expression of the Mthac-1 and Mtcbh-1 in Myceliophthora thermophila.

The thermophilic fungus Myceliophthora thermophila has been used to produce industrial enzymes and biobased chemicals. In saprotrophic fungi, the mechanisms regulating cellulase production have been studied, which revealed the involvement of multiple transcription factors. However, in M. thermophila, the transcription factors influencing cellulase gene expression and secretion remain largely unknown. In this study, we identified and characterized a novel cellulase regulator (MtTRC-1) in M. thermophila through a combination of functional genomics and genetic analyses. Deletion of Mttrc-1 resulted in significantly decreased cellulase production and activities. Transcriptome analysis revealed downregulation of not only the encoding genes of main cellulases but also the transcriptional regulator MtHAC-1 of UPR pathway after disruption of MtTRC-1 under cellulolytic induction conditions. Herein, we also characterized the ortholog of the yeast HAC1p in M. thermophila. We show that Mthac-1 mRNA undergoes an endoplasmic reticulum (ER) stress-induced splicing by removing a 23-nucleotide (nt) intron. Notably, the protein secretion on cellulose was dramatically impaired by the deletion of MtHAC-1. Moreover, the colonial growth on various carbon sources was defective in the absence of MtHAC-1. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays verified MtTRC-1 regulates the transcription of Mthac-1 and the major cellulase gene Mtcbh-1 by binding directly to the promoters in vitro and in vivo. Furthermore, DNase I footprinting assays identified the putative consensus binding site (5'-GNG/C-3'). These results revealed the importance of MtTRC-1 for positively regulating cellulase production. This finding has clarified the complex regulatory pathways involved in cellulolytic enzyme production. IMPORTANCE In the present study, we characterized a novel regulator MtTRC-1 in M. thermophila, which regulated cellulase production through direct transcriptional regulation of the Mthac-1 and Mtcbh-1 genes. Our data demonstrated that MtHAC-1 is a key factor for the cellulase secretion capacity of M. thermophila. Our data indicate that this thermophilic fungus regulates cellulase production through a multilevels network, in which the protein secretory pathway is modulated by MtHAC-1-dependent UPR pathway and the cellulase gene expression is directly regulated in parallel by transcription factors. The conservation of Mttrc1 in filamentous fungi suggests this mechanism may be exploited to engineer filamentous fungal cell factories capable of producing proteins on an industrial scale.

A Good Aesthetic Outcome After Gross Total Tumor Resection in Combination With the Skull Reconstruction on Giant Epidermal Cyst Involving Both Intracranial and Extracranial Tissues.

ABSTRACT: Epidermal or epidermoid cysts are 1 of the most frequent benign masses, they rarely grow to a huge size, and only a few cases have been reported. We report a rare case of a 52-year-old man with giant neoplasm growing invasively in the frontal region, including both intracranial and extracranial extensions, and caused extensive brain deformation and skull lesions. It is worth noting that the patient did not present any significant neurological symptoms and deficits for more than 40 years on admission. A combination of gross total tumor resection and cranioplasty was performed. The patient was satisfied with the results of the surgery, and no evidence of recurrence or complications were found in the 2 years follow-up. The authors reported the case not only to propose the first-stage aesthetic treatment option for this unusual mass on the scalp but also hinted at the vigilance and importance of systematic monitoring of the small skull mass for avoiding the potential risk of tumor progression, malignant transformation, operative trauma, and financial burden.

Hybrid Helical Polymer Nanochannels Constructed by Combining Aromatic Amide and Pyridine-Oxadiazole Structural Sequences.

An effective method is reported to synthesize aromatic helical polymer nanochannels by combining both the well-studied aromatic amide helical codons with pyridine-oxadiazole helical codons into helical structure sequences. With this strategy, a type of helical polymer nanochannel that shows structure-directed transmembrane transport functions is synthesized. Although such nanochannels show relatively weak selectivity for the transportation of alkali metal ions, accessible chemical mutation of helical structure sequences will provide a great chance for the design of desired channel property. The straightforward preparation of well-established pyridine-oxadiazole helical structure will significantly promote the synthesis of this kind of aromatic helical polymer nanochannels. With the development of aromatic amide foldamers, moreover, a number of "monomers" will be available for the preparation of helical polymer nanochannels.

2-hydroxy-3-phenylpropanoic acid suppressed the growth of Alternaria alternata through damaging cell membrane integrity and modulating reactive oxygen species metabolism.

Black spot rot caused by Alternaria alternata is one of the major postharvest disease of apple fruit during logistic. This study evaluated in vitro inhibitory effect of 2-hydroxy-3-phenylpropanoic acid (PLA) at various concentrations on A. alternata and the possible mechanisms involved in its action. Results showed that different concentrations of PLA inhibited conidia germination and mycelial growth of A. alternata in vitro, and 1.0 g L-1 was the lowest effective concentration to suppress A. alternata growth. Moreover, PLA significantly reduced relative conductivity and increased malondialdehyde and soluble protein contents. PLA also increased H2O2 and dehydroascorbic acid contents, but reduced ascorbic acid content. Additionally, PLA treatment inhibited catalase, ascorbate peroxidase, monodehydroascorbate acid reductase, dehydroascorbic acid reductase and glutathione reductase activities, whereas promoted superoxide dismutase activity. All these findings suggest that the possible mechanisms involved in the inhibitory effect of PLA on A. alternata included damaging the cell membrane integrity to cause electrolyte leakage and destroying reactive oxygen species balance.

Safety of paclitaxel-coated devices in the femoropopliteal arteries: A systematic review and meta-analysis.

BACKGROUND: Clinical benefit of paclitaxel-coated devices for patients with peripheral arterial disease has been confirmed in randomized controlled trials (RCTs). A meta-analysis published in 2018 identified late mortality risk over a long follow-up period due to use of paclitaxel-coated devices in the femoropopliteal arteries, which caused enormous controversy and debates globally. This study aims to further evaluate the safety of paclitaxel-coated devices by incorporating the most recently published data. METHODS: We searched for candidate studies in PubMed (MEDLINE), Scopus, EMBASE (Ovid) online databases, government web archives and international cardiovascular conferences. Safety endpoints of interest included all-cause mortality rates at one, two and five years and the risk ratio (RR) was used as the summary measure. The primary analysis was performed using random-effects models to account for potential clinical heterogeneity. FINDINGS: Thirty-nine RCTs including 9164 patients were identified. At one year, the random-effects model yielded a pooled RR of 1.06 (95% CI [0.87, 1.29]) indicating no difference in short-term all-cause deaths between the paclitaxel and control groups (crude mortality, 4.3%, 214/5025 versus 4.5%, 177/3965). Two-year mortality was reported in 26 RCTs with 382 deaths out of 3788 patients (10.1%) in the paclitaxel arm and 299 out of 2955 patients (10.1%) in the control arm and no association was found between increased risk of death and usage of paclitaxel-coated devices (RR 1.08, 95% CI [0.93, 1.25]). Eight RCTs recorded all-cause deaths up to five years and a pooled RR of 1.18 (95% CI [0.92, 1.51]) demonstrated no late mortality risk due to use of paclitaxel-coated devices (crude mortality, paclitaxel 18.2%, 247/1360 versus control 15.2%, 122/805). CONCLUSIONS: We found no significant difference in either short- or long-term all-cause mortalities between patients receiving paclitaxel-coated and uncoated devices. Further research on the longer-term safety of paclitaxel usage (e.g., 8- or 10-year) is warranted. REGISTRATION: PROSPERO, CRD42021246291.

Correlation Analysis of Gut Microbiota and Serum Metabolome With Porphyromonas gingivalis-Induced Metabolic Disorders.

Periodontitis has been demonstrated to increase the risk of metabolic syndrome (MetS), but the underlying mechanism remains unclear. Recent studies have indicated periodontopathic bacteria such as Porphyromonas gingivalis could induce gut microbiota (GM) dysbiosis and aggravate metabolic disorders. However, the effects of microbial metabolites have barely been evaluated. Here, we investigated the alteration of serum metabolome with P. gingivalis-induced metabolic disorders, and explored the correlations of GM and serum metabolites. In this study, we orally administered P. gingivalis ATCC33277 to C57BL/6 mice and performed metagenomic sequencing and untargeted metabolomics with fecal samples and serum collection. In vivo experiments showed a higher proportion of fat mass and worse glucose tolerance in P. gingivalis-administered mice, accompanied with an increase of adipose inflammation and gut permeability, which was similar to HFD-induced obese mice. Metagenomic sequencing indicated a compositional and functional alteration of GM. Untargeted metabolomics revealed an alteration of metabolites in P. gingivalis-administered mice, and most of them were engaged in metabolic pathways, such as tryptophan metabolism and choline metabolism. Correlation analysis between GM and serum metabolome indicated strong relativity with P. gingivalis administration. These results demonstrated some specific microbiota-derived metabolites in the pathogenesis of P. gingivalis-induced metabolic disorders, providing promising targets for the development of novel treatment strategies for MetS.

[Evaluation of domestically made recalled nitinol alloy stent implantation for severe airway stenosis].

OBJECTIVE: it is more difficult and carries more risks to place airway stent under local anaesthesia for the patient with severe airway stenosis. The technique and method of domestically made recalled nitinol alloy stent implantation for severe airway stenosis was explored and evaluated. METHODS: by using bronchoscopy via larynx mask, trachea intubation, or rigid bronchoscope under general anaesthesia and mechanical ventilation, stents are placed in the airway of patients with severe airway stenosis for which had been difficult to performed under local anaesthesia. RESULTS: according to the various tracheobronchial lesions of patients, 42 stents were successfully placed in 40 patients, via larynx mask 23 cases, trachea intubation 11 cases, and rigid bronchoscope 6 cases under general anaesthesia and mechanical ventilation. No complications happened. The recalled nitinol alloy stents were placed in trachea 27 cases (membrane covered stent 9 cases), left primary bronchus 8 cases, right primary bronchus to medial segment 2 cases, trachea to left primary bronchus (wedge shaped stent) 5 cases respectively. The airway pressure decreased to normal level and other ventilator parameters also recovered after stents were placed. In most patients, the dyspnea index was improved immediately and the scores decreased from grades IV-V to grades 0-II, with higher scores indicating worse dyspnea. CONCLUSION: for patients with severe airway stenosis, it is safer, effective and more comfortable to place the stent via larynx mask, trachea intubation, or rigid bronchoscope under general anaesthesia and mechanical ventilation compared to local anaesthesia and is worth spread and popularization in the future.

Glycosylation of Dentin Matrix Protein 1 is critical for osteogenesis.

Proteoglycans play important roles in regulating osteogenesis. Dentin matrix protein 1 (DMP1) is a highly expressed bone extracellular matrix protein that regulates both bone development and phosphate metabolism. After glycosylation, an N-terminal fragment of DMP1 protein was identified as a new proteoglycan (DMP1-PG) in bone matrix. In vitro investigations showed that Ser(89) is the key glycosylation site in mouse DMP1. However, the specific role of DMP1 glycosylation is still not understood. In this study, a mutant DMP1 mouse model was developed in which the glycosylation site S(89) was substituted with G(89) (S89G-DMP1). The glycosylation level of DMP1 was down-regulated in the bone matrix of S89G-DMP1 mice. Compared with wild type mice, the long bones of S89G-DMP1 mice showed developmental changes, including the speed of bone remodeling and mineralization, the morphology and activities of osteocytes, and activities of both osteoblasts and osteoclasts. These findings indicate that glycosylation of DMP1 is a key posttranslational modification process during development and that DMP1-PG functions as an indispensable proteoglycan in osteogenesis.