Survival strategies in arsenic-contaminated environments: Comparative insights from native and exotic aquatic species.

The aim of this work was to study the sublethal effects, biokinetics, subcellular partitioning and detoxification of arsenic in two native Chinses species, Bellamya quadrata and Cipangopaludina cathayensis, as well as an exotic South American species, Pomacea canaliculata. The exotic species exhibited higher tolerance than native species. Physiologically based pharmacokinetic model results showed that the exotic species P. canaliculata exhibited a lower bioaccumulation rate and a greater metabolism capacity of As. Subcellular partitioning of As revealed that P. canaliculata exhibits superior As tolerance compared to the native species B. quadrata and C. cathayensis. This is attributed to P. canaliculata effective management of the metal sensitive fraction and enhanced accumulation of As in the biologically detoxified metal fraction. Under As stress, the biochemical parameters (superoxide dismutase, malondialdehyde, glutathione and glutathione S-transferase) of the exotic species P. canaliculata changed less in the native species, and they returned to normal levels at the end of depuration period. Our study provides evidence of the superior survival capability of the exotic species P. canaliculata compared to the native species B. quadrata and C. cathayensis under environmentally relevant levels of As contamination.

The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial-to-mesenchymal transition.

BACKGROUND: Perineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve-derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC. METHODS: Immunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH-SY5Y cells were co-cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI-specific therapeutic effects by blocking the GAL/GALR2 axis. RESULTS: GAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p < 0.05). Nerve-derived GAL activated GALR2 expression in SACC cells and induced epithelial-to-mesenchymal transition (EMT) in SACC cells. Adding human recombinant GAL to the co-culture system promoted the proliferation, migration, and invasion of SACC cells significantly, but inhibited the apoptosis of SACC cells. Adding M871, a specific antagonist of GALR2, significantly blocked the above effects (p < 0.05) and inhibited the PNI of SACC cells in vitro and in vivo (p < 0.05). CONCLUSIONS: This study demonstrated that nerve-derived GAL activated GALR2 expression, and promoted EMT in SACC cells, thereby enhancing the PNI process. Interruption of the GAL/GALR2 axis might be a novel strategy for anti-PNI therapy for SACC.

The impacts of COVID-19 on clean energy labor markets: Evidence from multifaceted analysis of public health interventions and COVID-health factors.

COVID-19 pandemic has affected clean energy labor market. Using real-time job vacancy data, this study analyzes the impacts of the pandemic on the U.S. clean energy labor market in 2020, including biomass, energy efficiency (EE), electric vehicle (EV), power/microgrid, solar, and wind industries. This study identifies how COVID-health factors and public health interventions influence clean energy job availability during the early COVID pandemic. Overall, California had the most energy jobs and experienced a significant decrease in April 2020. EV and solar had the highest percentages of job vacancies during the pandemic in general. Still, lockdowns had the most severe influence on EE and wind jobs. Stay-at-home orders negatively affected clean energy job vacancies in biomass, EV, power/microgrid, and wind. Social-gathering restrictions, however, did not have much influence. Increased COVID tests at the state level had the strongest and most positive influence on clean energy job postings, indicating the importance of a state's ability to manage public health infrastructure or crisis issues. COVID hospitalizations negatively influenced the job vacancies in biomass and wind but did not affect the other four sectors; conversely, as COVID death numbers increased, the number of jobs in biomass, EV, power grid, solar, and wind decreased, but not in EE jobs.

Screening of imidazoles in atmospheric aerosol particles using a hybrid targeted and untargeted method based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

The method for identification and quantification of imidazoles in atmospheric aerosol particles with an aerodynamic diameter up to 2.5 µm (PM2.5) is scarce, and the existing method focus on only a few imidazoles. With the goal of measuring more imidazoles, especially some previously unidentified ones, we developed a screening workflow based on data-dependent acquisition (DDA) auto MS/MS with a preferred targeted list containing 421 imidazoles using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). To enable our method to effectively and accurately detect as many imidazoles as possible, we optimized and validated the method based on specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, accuracy, precision and matrix effects using 20 imidazole standards with different functional groups. The method exhibited excellent performance with LOD and LOQ of 0.5-2 ng/mL and 1.5-6 ng/mL, respectively, and spiked recoveries ranging from 64.7 to 98.7% with standard deviations less than 16.0%, and with relatively shorter analytical time. The established method was then used to screen imidazoles in 37 ambient PM2.5 samples. Ten targeted imidazoles were identified and quantified using imidazole standards, while five suspected imidazoles were identified without standards, and three imidazoles have not been reported before. Concentrations of the 10 targeted imidazoles ranged from 0.13 to 0.42 ng/m3. The established method enabled us to identify a wide range of imidazoles in ambient aerosol particles with and without using standards.

Discovery and Engineering of a Novel Baeyer-Villiger Monooxygenase with High Normal Regioselectivity.

Baeyer-Villiger monooxygenases (BVMOs) are remarkable biocatalysts for the Baeyer-Villiger oxidation of ketones to generate esters or lactones. The regioselectivity of BVMOs is essential for determining the ratio of the two regioisomeric products ("normal" and "abnormal") when catalyzing asymmetric ketone substrates. Starting from a known normal-preferring BVMO sequence from Pseudomonas putida KT2440 (PpBVMO), a novel BVMO from Gordonia sihwensis (GsBVMO) with higher normal regioselectivity (up to 97/3) was identified. Furthermore, protein engineering increased the specificity constant (kcat /KM ) 8.9-fold to 484 s-1 mM-1 for 10-ketostearic acid derived from oleic acid. Consequently, by using the variant GsBVMOC308L as an efficient biocatalyst, 10-ketostearic acid was efficiently transformed into 9-(nonanoyloxy)nonanoic acid, with a space-time yield of 60.5 g L-1 d-1 . This study showed that the mutant with higher regioselectivity and catalytic efficiency could be applied to prepare medium-chain ω-hydroxy fatty acids through biotransformation of long-chain aliphatic keto acids derived from renewable plant oils.

Efficient Synthesis of Methyl 3-Acetoxypropionate by a Newly Identified Baeyer-Villiger Monooxygenase.

Baeyer-Villiger monooxygenases (BVMOs) are an emerging class of promising biocatalysts for the oxidation of ketones to prepare corresponding esters or lactones. Although many BVMOs have been reported, the development of highly efficient enzymes for use in industrial applications is desirable. In this work, we identified a BVMO from Rhodococcus pyridinivorans (BVMORp) with a high affinity toward aliphatic methyl ketones (Km < 3.0 µM). The enzyme was highly soluble and relatively stable, with a half-life of 23 h at 30°C and pH 7.5. The most effective substrate discovered so far is 2-hexanone (kcat = 2.1 s-1; Km = 1.5 µM). Furthermore, BVMORp exhibited excellent regioselectivity toward most aliphatic ketones, preferentially forming typical (i.e., normal) products. Using the newly identified BVMORp as the catalyst, a high concentration (26.0 g/liter; 200 mM) of methyl levulinate was completely converted to methyl 3-acetoxypropionate after 4 h, with a space-time yield of 5.4 g liter-1 h-1 Thus, BVMORp is a promising biocatalyst for the synthesis of 3-hydroxypropionate from readily available biobased levulinate to replace the conventional fermentation.IMPORTANCE BVMOs are emerging as a green alternative to traditional oxidants in the BV oxidation of ketones. Although many BVMOs are discovered and used in organic synthesis, few are really applied in industry, especially in the case of aliphatic ketones. Herein, a highly soluble and relatively stable monooxygenase from Rhodococcus pyridinivorans (BVMORp) was identified with high activity and excellent regioselectivity toward most aliphatic ketones. BVMORp possesses unusually high substrate loading during the catalysis of the oxidation of biobased methyl levulinate to 3-hydroxypropionic acid derivatives. This study indicates that the synthesis of 3-hydroxypropionate from readily available biobased levulinate by BVMORp-catalyzed oxidation holds great promise to replace traditional fermentation.

Direct Access to Medium-Chain α,ω-Dicarboxylic Acids by Using a Baeyer-Villiger Monooxygenase of Abnormal Regioselectivity.

Baeyer-Villiger monooxygenases (BVMOs) are versatile biocatalysts in organic synthesis that can generate esters or lactones by inserting a single oxygen atom adjacent to a carbonyl moiety. The regioselectivity of BVMOs is essential in determining the ratio of two regioisomers for converting asymmetric ketones. Herein, we report a novel BVMO from Pseudomonas aeruginosa (PaBVMO); this has been exploited for the direct synthesis of medium-chain α,ω-dicarboxylic acids through a Baeyer-Villiger oxidation-hydrolysis cascade. PaBVMO displayed the highest abnormal regioselectivity toward a variety of long-chain aliphatic keto acids (C16 -C20 ) to date, affording dicarboxylic monoesters with a ratio of up to 95 %. Upon chemical hydrolysis, α,ω-dicarboxylic acids and fatty alcohols are readily obtained without further treatment; this significantly reduces the synthetic steps of α,ω-dicarboxylic acids from renewable oils and fats.

Efficacy of radio frequency thermocoagulation in surgery for giant supratentorial meningiomas: a historical control study.

BACKGROUND: Surgery for giant meningiomas carries a high risk of bleeding and is time-consuming. This historical control study tests the hypothesis that the use of radio frequency thermocoagulation (RFT) during surgery improves outcome. METHODS: From November 2010 to October 2011, 20 giant vascularized meningiomas were surgically resected with intraoperative use of ultrasound-guided RFT prior to resection. The historical control group consisted of 25 patients in whom tumors were removed without RFT by the same surgical team. Blood loss during resection, changes in tumor consistency, time taken for the operation, and the extent of resection were compared between the two groups. RESULTS: There was less blood lost during resection and the duration of the operation was shorter in RFT-assisted surgery than in the historical control group (P<0.05). Apart from the effect of devascularization, the tumor consistency became soft after RFT, which could also be beneficial. CONCLUSIONS: Satisfactory devascularization and tumor softening were achieved after RFT without incremental complications. RFT-assisted surgery for giant vascularized supratentorial meningiomas is easier and safer than non-RFT surgery.

Over-expression of Mash1 improves the GABAergic differentiation of bone marrow mesenchymal stem cells in vitro.

Bone marrow mesenchymal stem cells (BMSCs) have been shown to be a promising cell type for the study of neuronal differentiation; however, few attempts had been made to differentiate these cells into inhibitory gamma-aminobutyric acid (GABA)ergic neurons. In this study, we over-expressed mammalian achaete-scute homologue-1 (Mash1), a basic helix-loop-helix (bHLH) transcription factor, in Sprague-Dawley rat BMSCs via lentiviral vectors, and then induced neuronal differentiation of these cells using conditioned medium. Our Western blot results show that, under conditions of differentiation, Mash1-overexpressing BMSCs exhibit an increased expression of neuronal markers and a greater degree of neuronal morphology compared to control, non-Mash1-overexpressing cells. Using immunocytochemistry, we observed increased expression of glutamic acid decarboxylase 67 (GAD67), as well as neuron-specific nuclear protein (NeuN) and ß3-tubulin, in Mash1-overexpressing BMSCs compared to control cells. Moreover, we also found the differentiated cells showed representative traces of action potentials in electrophysiological characterization. In conclusion, our study demonstrated that over-expression of Mash1 can improve GABAergic differentiation of BMSCs in vitro.

The tropism of neurally differentiated bone marrow stromal cells towards C6 glioma.

Recent studies have indicated that bone marrow stromal cells (BMSCs) have significant tropism towards glioma which makes them play an important role in carrying genes/drugs to inhibit the growth of glioma as cell vehicles. But BMSCs may differentiate into neural cells under entocranial environment and few researches support the idea that neurally differentiated bone marrow stromal cells (N-D-BMSCs) still hold the capacity of migrating to the tumor sites. The aim of our study was to investigate the tropism of N-D-BMSCs towards C6 glioma. In vitro migration assay was employed by transwell co-culture system and Student's t-test analysis indicated that N-D-BMSCs had the significant tropism towards C6 glioma-conditioned medium (GCM) (P<0.01). Furthermore, the vascular endothelial growth factor (VEGF) bioactivity of the C6 GCM was neutralized by the anti-rat VEGF antibody and our data suggested that the VEGF from C6 GCM hold chemoattraction for N-D-BMSCs and some other cytokines from the C6 GCM may be responsible for the chemoattraction for N-D-BMSCs. In vivo migration assay was carried out with cells transplantation and one way ANOVA analysis indicated that the tropism of N-D-BMSCs towards C6 glioma sites presented time variation (P-value=2.9E-20). Moreover, multiple comparisons for the time variables with the Student's t-test and the results suggested that the migration capacity of N-D-BMSCs towards C6 glioma sites reach the peak on the 7th day after transplantation. These results demonstrate that N-D-BMSCs as well as BMSCs have significant tropism towards C6 glioma.