Synergistic detoxification efficiency and mechanism of triclocarban degradation by a bacterial consortium in the liver-gut-microbiota axis of zebrafish (Danio rerio).

Triclocarban (TCC), an emerging organic contaminant, poses a potential threat to human health with long-term exposure. Here, Rhodococcus rhodochrous BX2 and Pseudomonas sp. LY-1 were utilized to degrade TCC at environmental related concentrations for enhancing TCC biodegradation and investigating whether the toxicity of intermediate metabolites is lower than that of the parent compound. The results demonstrated that the bacterial consortium could degrade TCC by 82.0% within 7 days. The calculated 96 h LC50 for TCC, as well as its main degradation product 3,4-Dichloroaniline (DCA) were 0.134 mg/L and 1.318 mg/L respectively. Biodegradation also alleviated histopathological lesions induced by TCC in zebrafish liver and gut tissues. Liver transcriptome analysis revealed that biodegradation weakened differential expression of genes involved in disrupted immune regulation and lipid metabolism caused by TCC, verified through RT-qPCR analysis and measurement of related enzyme activities and protein contents. 16 S rRNA sequencing indicated that exposure to TCC led to gut microbial dysbiosis, which was efficiently improved through TCC biodegradation, resulting in decreased relative abundances of major pathogens. Overall, this study evaluated potential environmental risks associated with biodegradation of TCC and explored possible biodetoxification mechanisms, providing a theoretical foundation for efficient and harmless bioremediation of environmental pollutants.

Universal and divergent P-stereogenic building with camphor-derived 2,3-diols.

The access to P-stereogenic motifs has always been considered a very challenging and high attractive mission in modern organic synthesis. While several chiral auxiliaries employed by the practical Jugé-Stephan-like methodology have been developed, new type of readily accessible bifunctional ligands toward P-stereogenic building still remain much desirable. Herein, we present a powerful chiral template, camphor-derived 2,3-diols named CAMDOL, which were designed and synthesized from the commercially cheap camphorquinone in high yields at 50 grams scale with a column-free purification. Diverse P(III)-chiral compounds and their borane forms including phosphinous acids, phosphinites, and phosphines, as well as the corresponding P(V)-chiral compounds including phosphinates, phosphine oxides, phosphinothioates, phosphine sulfides, and secondary phosphine oxides were afforded in high yields and ee values through the optimal 2,3-diphenyl CAMDOL platform. An unusual C3-OP bond cleavage following the first P-OC2 bond breaking was observed during the ring-opening process when quenching by NH4Cl solution, which generates a unique but valuable camphor-epoxide scaffold as by-product.

Biological saccharification coupled with anaerobic digestion using corn straw for sustainable methane production.

In this study, accumulated fermentable sugars from biosaccharified corn straw were used to generate methane through anaerobic digestion (AD). The results showed that reducing sugars from biosaccharification expanded corn straw (BECS) treated with Clostridium thermocellum XF811 accumulated with yields of 94.9 mg/g. The BECS used for AD was converted into a high methane yield (7436 mL), which was 49.3 % higher than that of expanded corn straw (ECS). High-throughput microbial analysis suggested that Methanoculleus and Methanobacterium greatly contributed to the high methane yield. Industrial experiments demonstrated that the methane production from BECS by AD was 72,955 m3, which increased by 13.2 % compared to that from ECS. Biosaccharification pretreatment accelerated ECS destruction and accumulated sugars, thereby increasing methane yields. This study provides a strategy for producing clean energy from lignocellulose biomass.

Copper-catalyzed stereo- and regioselective hydrophosphorylation of terminal alkynes: scope and mechanistic study.

Herein, a protocol for copper-catalyzed highly stereo- and regioselective hydrophosphorylation of terminal alkynes to E-alkenylphosphorus compounds was well developed. It represents a general and practical hydrophosphorylation method, of which diarylphosphine oxide, dialkylphosphine oxide and dialkyl phosphite all had effective P(O)H parts to react with different types of terminal alkynes. Contrary to previous air-sensitive reports, all the reactions proceeded well under air. This methodology is quite attractive owing to the high stereo- and regioselectivity, good functional group tolerance, scalability and facile late-stage derivatization of some natural product derivatives and commercially available herbicides. What's more, investigations on the reaction mechanism with deuterium-labeling experiments and DFT studies firstly disclosed the deprotonation-protonation equilibrium of terminal alkynes and P(O)H part during the catalytic hydrophosphorylation process.

Efficient conversion of hemicellulose into 2, 3-butanediol by engineered psychrotrophic Raoultella terrigena: mechanism and efficiency.

Low-temperature biorefineries inhibit the multiplication of undesired microorganisms, improve product purity and reduce economic costs. Herein, to improve the 2,3-butanediol (2,3-BD) bioconversion efficiency from hemicellulose, a psychrotrophic hemicellulose-degrading strain Raoultella terrigena HC6 with high ß-xylosidase activity 1520 U/mL was isolated and genetically modified. Xylan (hemicellulose replacement) was depolymerized into xylooligosaccharides (XOS) and xylose by HC6, which were further converted into 2,3-BD. Transcriptomic analysis revealed that ß-xylosidase gene (xynB) and xylose isomerase gene (xylA), which are beneficial for increasing the carbon flux from xylan to 2,3-BD, were significantly upregulated 56.9-fold and 234-fold, respectively. A recombinant strain was constructed by overexpressing xynB in HC6, which obtained 0.389 g/g yield of 2,3-BD from hemicellulose extracted from corn straw at 15 °C. This study proposed a promised strategy for the bioconversion of agricultural waste into 2,3-BD at low temperatures and provides a basis for future efforts in the achievement of carbon neutrality.

Organobase-catalyzed 1,1-diborylation of terminal alkynes under metal-free conditions.

An organobase-catalyzed 1,1-diborylation of terminal alkynes from propargylic derivatives with bis(2,4-dimethylpentane-2,4-glycolato)diboron (B2oct2) is first reported, regioselectively providing 1,1-diborylalkene products with high efficiency. The catalytic pathway is well postulated on the basis of DFT calculations.

Synthesis of enol phosphates directly from ketones via a modified one-pot Perkow reaction.

A modified Perkow reaction, named Perkow-Shi reaction, was developed based on the one-pot α-tosyloxylation of ketones following by addition of P(iii)-reagents and 4 Å molecular sieves. Diversity of enol phosphates, as well as enol phosphonates, enol phosphinates, and enol phosphoramidates were synthesized in high yields directly from the ubiquitously available ketones instead of the unfavourable α-chloroketones under a mild and environmental friendly condition.

Near infrared light fluorescence imaging-guided biomimetic nanoparticles of extracellular vesicles deliver indocyanine green and paclitaxel for hyperthermia combined with chemotherapy against glioma.

BACKGROUND: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma. METHODS: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo. RESULTS: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group. CONCLUSION: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia.

Improvement in the Palladium-Catalyzed Miyaura Borylation Reaction by Optimization of the Base: Scope and Mechanistic Study.

Aryl boronic acids and esters are important building blocks in API synthesis. The palladium-catalyzed Suzuki-Miyaura borylation is the most common method for their preparation. This paper describes an improvement of the current reaction conditions. By using lipophilic bases such as potassium 2-ethyl hexanoate, the borylation reaction could be achieved at 35 °C in less than 2 h with very low palladium loading (0.5 mol %). A preliminary mechanistic study shows a hitherto unrecognized inhibitory effect by the carboxylate anion on the catalytic cycle, whereas 2-ethyl hexanoate minimizes this inhibitory effect. This improved methodology enables borylation of a wide range of substrates under mild conditions.

Glioma exosomal microRNA-148a-3p promotes tumor angiogenesis through activating the EGFR/MAPK signaling pathway via inhibiting ERRFI1.

BACKGROUND: Glioma is the most frequent and lethal primary brain malignancy. Amounting evidence has highlighted the importance of exosomal microRNAs (miRNAs or miRs) in this malignancy. This study aimed to investigate the regulatory role of exosomal miR-148a-3p in glioma. METHODS: Bioinformatics analysis was firstly used to predict the target genes of miR-148a-3p. Exosomes were then extracted from normal human astrocytes and glioma cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine the expression patterns of miR-148a-3p and ERBB receptor feedback inhibitor 1 (ERRFI1). Dual-luciferase reporter gene assay was applied to verify the direct binding between miR-148a-3p and ERRFI1. Cell counting kit-8 and tube formation assays were further conducted to assess the proliferation and angiogenic properties of human umbilical vein endothelial cells (HUVECs) in the co-culture system with exosomes. Lastly, glioma tumor models were established in BALB/c nude mice to study the role of exosomal miR-148a-3p in vivo. RESULTS: miR-148a-3p was highly expressed, while ERRFI1 was poorly expressed in glioma. miR-148a-3p was found to be enriched in glioma cells-derived exosomes and could be transferred to HUVECs via exosomes to promote their proliferation and angiogenesis. ERRFI1 was identified as a target gene of miR-148a-3p. In addition, miR-148a-3p activated the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting ERRFI1. In the co-culture system, our data demonstrated that glioma cells-derived exosomal miR-148a-3p down-regulated ERRFI1 and activated the EGFR/MAPK signaling pathway, so as to promote cell proliferation and angiogenesis. In vivo experimentation further demonstrated that this mechanism was responsible for the promotive role of exosomal miR-148a-3p in tumorigenesis and angiogenesis. CONCLUSION: Taken together, glioma-derived exosomal miR-148a-3p promoted tumor angiogenesis through activation of the EGFR/MAPK signaling pathway by ERRFI1 inhibition.

A positive feedback loop of miR-30a-5p-WWP1-NF-κB in the regulation of glioma development.

Previous studies demonstrated that miR-30a-5p promotes glioma cell growth and invasion. Furthermore, WWP1 (WW domain containing E3 ubiquitin protein ligase 1) inhibits NF-κB activation that is strongly correlated with gliomagenesis. Using the GEO database and bioinformatics analyses, we identified WWP1 was downregulated in glioma tissues and might be a putative target for miR-30a-5p. Hence, this study aims to explore the interaction among miR-30a-5p, WWP1, and NF-κB and their roles in the regulation of glioma development. We found decreased WWP and increased miR-30a-5p expression and p65 phosphorylation in glioma tissues. Furthermore, WWP1 mRNA level was negatively correlated with miR-30a-5p expression in glioma tissues. Interestingly, miR-30a-5p targeted WWP1 expression. Additionally, NF-κB p65 overexpression increased miR-30a-5p expression through direct binding of NF-κB RelA subunit to the promoter of miR-30a-5p. We also confirmed that WWP1 overexpression decreased phosphorylation of NF-κB p65. Importantly, miR-30a-5p promoted glioma cell proliferation, migration, and invasion via targeting WWP1. Furthermore, NF-κB p65 overexpression inhibited WWP1 expression and promoted glioma cell malignant behaviors via inducing miR-30a-5p transcription. Moreover, WWP1 overexpression decreased miR-30a-5p expression and inhibited glioma cell malignant behaviors via inhibiting NF-κB p65. Our further assay showed that WWP1 inhibited in vivo growth of xenograft tumors of glioma cells, accompanied with a decrease in miR-30-5p expression and phosphorylation of NF-κB p65. In conclusion, there is a "miR-30a-5p-WWP1-NF-κB" positive feedback loop, which plays an important role in regulating glioma development and might provide a potential therapeutic strategy for treating glioma.

Supratentorial Cortical Ependymomas: A Retrospective Series of 13 Cases at a Single Center.

OBJECTIVE: Cortical ependymomas (CEs), supratentorial ependymomas that selectively involve the cerebral cortex, are relatively rare neoplasms that have not been extensively described. The purpose of our study was to identify the clinical features, radiologic characteristics, and treatment of a series of such tumors. METHODS: Thirteen patients with CEs from our hospital were included in this study. Epidemiologic characteristics, clinical features, imaging findings, treatment methods, and clinical outcomes were reviewed retrospectively. RESULTS: The patients consisted of 7 men and 6 women with mean age of 31.1 ± 23.2 years (range, 4-74 years). The most common clinical manifestation was seizure (n = 11; 85%), followed by headache (n = 2; 15%). None of the tumors were incidentally detected. Eight CEs were located in the right hemisphere and 5 in the left side. The 2 most common tumor locations were the frontal (n = 5; 38%) and parietal lobe (n = 5; 38%). All patients underwent surgical resection. Gross total resection was achieved in 12 patients (92%), and subtotal resection was performed in 1 patient (8%). Ten of the 11 patients who presented with seizure are seizure-free after surgery (91% seizure-free rate). According to the World Health Organization classification system, 9 tumors (69%) were Grade II (ependymoma) and 4 (31%) were Grade III (anaplastic ependymoma). The mean follow-up was 52 months (range, 20-88 months). No recurrence was observed in patients with Grade II CEs. Of 4 patients with Grade III CEs, 2 (50%) suffered from tumor recurrence after initial treatment. CONCLUSIONS: CEs are a rare subset of supratentorial ependymomas that selectively involve the cerebral cortex. Most CEs are low grade and present with seizures. Anaplastic CEs show a greater recurrence rate and a relatively poor prognosis. Gross total resection with or without adjuvant radiotherapy is currently the optimal treatment for CEs. CEs seem to have a more favorable prognosis than other supratentorial ependymomas.

Supratentorial extraventricular ependymomas: A retrospective study focused on long-term outcomes and prognostic factors.

OBJECTIVE: Supratentorial extraventricular ependymomas are relatively rare. Long-term outcomes and prognostic factor for this rare tumor have not been well established. The purpose of this study was to demonstrateprogression-freesurvival(PFS),overallsurvival(OS), and prognostic factors of such tumor. PATIENTS AND METHODS: Fifty-five patients with supratentorial extraventricular ependymomas from our hospital were included in this study. Epidemiological characteristics, clinical features, treatment,long-term outcomes, and prognostic factors for PFS and OS were reviewed retrospectively. RESULTS: The patients consisted of 30 males and 25 females with mean age of 30.0 ±â€¯23.6 years (range, 1-74 years). Twenty-nine tumors were located in the right hemisphere, and 26 in the left side. The 2 most common tumor locations were the frontal (n = 19; 35%) and parietal lobe (n = 11; 20%). All patients underwent surgical resection. Gross-total resection (GTR) was achieved in 42 cases (76%) and subtotal resection (STR) was performed in 13 patients (24%). According to the WHO classification system, 38 tumors (69%) were Grade III (anaplastic ependymoma), and 17 (31%) were Grade II (ependymoma). Three-,5-, and 10 year PFS rates were 60%, 49%, and 36%, respectively. Three-,5-, and 10 year OS rates were 79%, 64%, and 49%, respectively. EOR and tumor grade were identified as prognostic factors for PFS and OS on univariate analysis, multivariate analysis, and Kaplan-Meierlog-rank testing. Subtotal resection (STR) predicted a worse PFS (HR = 4.808; 95%, 1.942-11.905; P = .001) and OS (HR = 5.650; 95%, 2.114-15.152; P = .001). WHO Grade III tumors also had worse PFS (HR = 3.922; 95%, 1.429-18.182; P = .012) and OS (HR = 6.329; 95%, 1.328-30.303; P = 0.021). For patients with tumor recurrence, reoperation was significant prognostic factors for OS (HR = 2.091; 95%, 0.939-4.654; p = .000). Age, sex, tumor side, and postoperativeradiotherapy were not prognostic factors for PFS and OS. CONCLUSIONS: Most supratentorial extraventricular ependymomas are WHO grade III tumors. STRandWHO Grade III pathology predicted worse PFS and OS. Gross-total resection remains the optimal treatment for patients with supratentorial extraventricular ependymoma. Reoperation should be considered first in cases of recurrence. The role of postoperative radiotherapy as an adjuvant treatment for supratentorial extraventricular ependymoma needs further investigation.

Successful treatment for giant pituitary adenomas through diverse transcranial approaches in a series of 15 consecutive patients.

OBJECT: Giant pituitary adenomas (GPAs) remain a therapeutic challenge with high mortality and morbidity. We described our experience in a consecutive series of GPAs with extensive suprasellar extension. METHODS: A series of 15 consecutive patients with maximum dimension of more than 4cm was enrolled in present study. These cases were microsurgically treated through diverse transcranial approach in our neurosurgical department from January 2006 to January 2011. Four different transcranial microsurgical approaches were selected based on tumor localization and expansion as well as neurosurgeon's experience. RESULTS: Gross total removal (GTR) was achieved in 10 of all patients (67%), subtotal removal was achieved in 5 of 15 (33%). Nine patients experienced visual improvement postoperatively compared with those of preoperative symptom (82%), no intraoperative or postoperative death was observed in present series. The most striking features of this study indicate that an experienced team can reach 67% with no mortality, no panhypopituitarism and no permanent diabetes insipidus dealing with GPAs. No recurrent tumor was found in the GPAs with GTR, adjuvant radiation therapy had been performed in 5 patients and the continuous shrinkage of the residual adenomas was achieved in 2 out of 5 with radiotherapy. CONCLUSIONS: Transcranial approach was still a relatively reliable and safe management for complex GPAs with extensive suprasellar extension.