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1.
EcoSal Plus ; : eESP00082020, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34125583

RESUMO

The species Salmonella enterica comprises over 2,600 serovars, many of which are known to be intracellular pathogens of mammals, birds, and reptiles. It is now apparent that Salmonella is a highly adapted environmental microbe and can readily persist in a number of environmental niches, including water, soil, and various plant (including produce) species. Much of what is known about the evolution and diversity of nontyphoidal Salmonella serovars (NTS) in the environment is the result of the rise of the genomics era in enteric microbiology. There are over 340,000 Salmonella genomes available in public databases. This extraordinary breadth of genomic diversity now available for the species, coupled with widespread availability and affordability of whole-genome sequencing (WGS) instrumentation, has transformed the way in which we detect, differentiate, and characterize Salmonella enterica strains in a timely way. Not only have WGS data afforded a detailed and global examination of the molecular epidemiological movement of Salmonella from diverse environmental reservoirs into human and animal hosts, but they have also allowed considerable consolidation of the diagnostic effort required to test for various phenotypes important to the characterization of Salmonella. For example, drug resistance, serovar, virulence determinants, and other genome-based attributes can all be discerned using a genome sequence. Finally, genomic analysis, in conjunction with functional and phenotypic approaches, is beginning to provide new insights into the precise adaptive changes that permit persistence of NTS in so many diverse and challenging environmental niches.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34067389

RESUMO

Green exercise is the combination of physical activity and nature exposure, which has been associated with positive effects on psychophysiological health. This study aimed to investigate the effects of nature video viewing on isometric exercise and find a useful practice for green exercise in urban living. In the current study, 18 male subjects were recruited in a randomized crossover trial and underwent a sequence of wall squat exercises. The whole experiment contained three periods of baseline (before exercise), exercise, and recovery (after exercise), and each period lasted for 2 min. A video of forest walking was played in the exercise and recovery periods as treatment, while a black screen was set as control. The Rate of Perceived Exertion Scale (RPE) and Feeling Scale (FS) were employed to measure perceived exertion and affective responses in the exercise period; heart rate (HR) and heart rate variability (HRV) including the standard deviation of normal-to-normal RR intervals (SDNN), the root mean square of successive differences (RMSSD), and the standard deviations of the Poincaré plot (SD1), were recorded in the three periods. Heart rate recovery (HRR) in the recovery period was further calculated based on 30 s and 60 s time frames. Results demonstrated that during the exercise period nature video viewing was associated with better affective responses (median of 1.00 and an interquartile (IQR) of 2.00, p = 0.017), lower perceived exertion (median = 6.00, IQR = 2.00, p = 0.021), and lower HR (median = 89.60, IQR = 20.94, p = 0.01), but the differences in HRV indices between the experimental settings were not statistically significant. In the recovery period, significantly higher values of RMSSD (median = 34.88, IQR = 24.52, p = 0.004), SD1 (median = 24.75, IQR = 17.41, p = 0.003), and HR (median = 84.18, IQR = 16.58, p = 0.001) were observed in the treatment setting, whereas no statistically significant difference was found for HRR. In general, our findings support that nature video viewing may help reduce perceived exertion, increase exercise pleasure, buffer heart rate, and improve cardiac autonomic recovery for wall squat exercising, which implies the potential of nature-based stimuli in green exercise. However, due to the limited research sample, further study may need to include female participants and focus on various populations to confirm the effectiveness of using virtual and environments depicting nature at home or in public exercise places to promote positive exercise experience.

3.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073831

RESUMO

The mycoparasite fungi of Clonostachys have contributed to the biological control of plant fungal disease and nematodes. The Clonostachys fungi strains were isolated from Ophiocordyceps highlandensis, Ophiocordycepsnigrolla and soil, which identified as Clonostachyscompactiuscula, Clonostachysrogersoniana, Clonostachyssolani and Clonostachys sp. To explore the evolutionary relationship between the mentioned species, the mitochondrial genomes of four Clonostachys species were sequenced and assembled. The four mitogenomes consisted of complete circular DNA molecules, with the total sizes ranging from 27,410 bp to 42,075 bp. The GC contents, GC skews and AT skews of the mitogenomes varied considerably. Mitogenomic synteny analysis indicated that these mitogenomes underwent gene rearrangements. Among the 15 protein-coding genes within the mitogenomes, the nad4L gene exhibited the least genetic distance, demonstrating a high degree of conservation. The selection pressure analysis of these 15 PCGs were all below 1, indicating that PCGs were subject to purifying selection. Based on protein-coding gene calculation of the significantly supported topologies, the four Clonostachys species were divided into a group in the phylogenetic tree. The results supplemented the database of mitogenomes in Hypocreales order, which might be a useful research tool to conduct a phylogenetic analysis of Clonostachys. Additionally, the suitable molecular marker was significant to study phylogenetic relationships in the Bionectriaceae family.

4.
Cancer Med ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955198

RESUMO

Although the association between tumor-infiltrating CD3+ T and CD8+ T cells and superior survival in high-grade serous ovarian cancer (HGSOC) has been observed, the different spatial localization of tumor-infiltrating lymphocytes (TILs) possesses heterogeneous effects. We performed localized measurements in 260 HGSOC from 2 independent cohorts represented in tissue microarray format to determine the localized expression pattern and clinical significance of CD3+ T, CD8+ T, and CD45RO+ cells in HGSOC. Different density of spatial localization of CD3+ T, CD8+ T, and CD45RO+ cells exhibited heterogeneous association with OS. The combination of the center of the tumor and invasive margin localized CD8+ T cells (CD8CT&IM ) with the same margin localized CD45RO (CD45ROCT&IM ) was the most robust prognostic predictor. Immune score (IS) was constructed by integrating FIGO stage with CD8CT&IM and CD45ROIM&CT and had the best prognostic value in HGSOC. The low-, intermediate-, and high-IS groups were observed in 44.7%, 41.6%, and 13.7% of patients, respectively. Low-IS identified patients were at higher risk of death compared to high-IS identified patients (HR = 12.426; 95% CI 5.317-29.039, p < 0.001); meanwhile, we evaluate the RMSTs over 10 years of follow-up and obtained RMST values of 104.09 months (95% CI 96.31-111.87 months) in the high-IS group, 75.26 months (95% CI 59.92-90.60 months) in the intermediate-IS group, and 48.68 months (95%CI 38.82-58.54 months) in the low-IS group. In general, spatial localization can modulate the clinical effects of TILs in HGSOC. Thus, the spatial expression of CD8 and CD45RO could aid clinicians to determine the follow-up plan of patients with HGSOC.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33955739

RESUMO

Superhydrophobic surfaces are imperative in flexible polymer foams for diverse applications; however, traditional surface coatings on soft skeletons are often fragile and can hardly endure severe deformation, making them unstable and highly susceptible to cyclic loadings. Therefore, it remains a great challenge to balance their mutual exclusiveness of mechanical robustness and surface water repellency on flexible substrates. Herein, we describe how robust superhydrophobic surfaces on soft poly(dimethylsiloxane) (PDMS) foams can be achieved using an extremely simple, ultrafast, and environmentally friendly flame scanning strategy. The ultrafast flame treatment (1-3 s) of PDMS foams produces microwavy and nanosilica rough structures bonded on the soft skeletons, forming robust superhydrophobic surfaces (i.e., water contact angles (WCAs) > 155° and water sliding angles (WSAs) < 5°). The rough surface can be effectively tailored by simply altering the flame scanning speed (2.5-15.0 cm/s) to adjust the thermal pyrolysis of the PDMS molecules. The optimized surfaces display reliable mechanical robustness and excellent water repellency even after 100 cycles of compression of 60% strain, stretching of 100% strain, and bending of 90° and hostile environmental conditions (including acid/salt/alkali conditions, high/low temperatures, UV aging, and harsh cyclic abrasion). Moreover, such flame-induced superhydrophobic surfaces are easily peeled off from ice and can be healable even after severe abrasion cycles. Clearly, the flame scanning strategy provides a facile and versatile approach for fabricating mechanically robust and surface superhydrophobic PDMS foam materials for applications in complex conditions.

6.
Drug Metab Dispos ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941543

RESUMO

Givosiran is a N-acetylgalactosamine (GalNAc)-conjugated RNA interference (RNAi) therapeutic that targets 5'-aminolevulinate synthase 1 (ALAS1) messenger RNA (mRNA) in the liver and is currently marketed for the treatment of acute hepatic porphyria (AHP). Herein, nonclinical pharmacokinetic (PK) and absorption, distribution, metabolism, and excretion (ADME) properties of givosiran were characterized. Givosiran was completely absorbed after subcutaneous (SC) administration with relatively short plasma elimination t1/2 (less than 4 hours). Plasma exposure increased approximately dose proportionally with no accumulation after repeat doses. Plasma protein binding (PPB) was concentration dependent across all species tested and was around 90% at clinically relevant concentration in human. Givosiran predominantly distributed to the liver by asialoglycoprotein receptor (ASGPR)-mediated uptake, and the elimination t1/2 in the liver was significantly longer (~1 week). Givosiran was metabolized by nucleases, not cytochrome P450 (CYP) isozymes, across species with no human unique metabolites. Givosiran metabolized to form one primary active metabolite with the loss of 1 nucleotide from the 3' end of antisense strand, AS(N­1)3' givosiran which was equipotent to givosiran. Renal and fecal excretion were minor routes of elimination of givosiran as approximately 10% and 16% of the dose was recovered intact in excreta of rats and monkeys, respectively. Givosiran is not a substrate, inhibitor, or inducer of CYP isozymes, and it is not a substrate or inhibitor of uptake and most efflux transporters. Thus, givosiran has a low potential of mediating drug-drug interactions involving CYP isozymes and drug transporters. Significance Statement Nonclinical PK and ADME properties of givosiran, the first approved GalNAc-conjugated RNAi therapeutic, were characterized. Givosiran shows similar PK and ADME properties across rats and monkeys in vivo and across human and animal matrices in vitro. SC administration results in adequate exposure of givosiran to the target organ (liver). These studies support the interpretation of toxicology studies, help characterize the disposition of givosiran in humans, and support the clinical use of givosiran for the treatment of AHP.

7.
Sci Total Environ ; 787: 147677, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34004538

RESUMO

Metabolic transformations play critical roles in the bioavailability and toxicities of environmental pollutants and toxicants. However, most previous research has focused on the metabolic reactions in host tissues, the gut microbiota-mediated biotransformation of environmental compounds is understudied. Using triclocarban (TCC) as a model environmental compound, here we study the metabolic fate of TCC in gut tissues and determine the roles of gut microbiota involved. We find that compared with other tissues, the colon tissue has a unique metabolic profile of TCC, with high abundance of the parent compound TCC and its free-form metabolites. Using a variety of approaches including antibiotic-mediated suppression of gut bacteria in vivo, germ-free mice, and in vitro culture of fecal bacteria, we found that the unique metabolic profile of TCC in the colon is mediated by the actions of gut microbiota. Overall, our findings support that gut microbiota plays important roles in colonic metabolism of TCC, highlighting the importance to consider the contributions of gut microbiota in toxicology evaluation of environmental compounds.

8.
J Gynecol Oncol ; 32(3): e32, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33825354

RESUMO

OBJECTIVE: To predict the prognosis of cervical cancer, we constructed a novel model with 5 specific cell types and identified a potential biomarker. METHODS: We employed CIBERSORT and xCell method to evaluate the abundances of 23 cells types in tumor microenvironment. Five specific cell types were filtrated to determine different immunotypes by applying least absolute shrinkage and selection operator (LASSO) Cox regression method. The expression of immune checkpoints (ICPs) and effectors were validated by immunohistochemistry. Correlation analysis was performed to examine the relevance between PIK3CA mutational status and ICPs. RESULTS: Unsupervised clustering of patients on the basis of tumor infiltrating lymphocytes and fibroblasts identified patients with shorter overall survival (OS) (hazard ratio [HR]=3.0729; 95% confidence interval [CI]=1.5103-6.2522; p=0.0118). An immunoscore (IS) signature consisting of 5 immune cell types infiltrating in tumor core (CD8T, activated NK cells, neutrophils, activated mast cells, macrophages) was constructed using LASSO Cox regression analysis. Receiver operating characteristic curves confirmed that the area under the curve of IS was significantly higher to that of International Federation of Gynecology and Obstetrics staging alone (0.637 vs. 0.55). Survival analysis revealed patients in high IS group exhibited a poorer OS (HR=3.0113; 95% CI=1.8746-4.8373; p<0.0001). The multivariate analysis indicated the IS was an independent prognostic factor. In addition, the lower IS related to higher expression of ICPs and neoantigen load. CONCLUSIONS: The identification of IS in cervical cancer tissues could facilitate patient risk stratification and selection of immunotherapeutic responses, but more prospective studies are needed to assess its reliability.

9.
Bioresour Technol ; 331: 125025, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33812745

RESUMO

Adding ferric ions (Fe3+) in catholyte can enhance performance of microbial fuel cells (MFCs). This work adopted biocathode with enriched Fe2+ oxidizing microflora to perform in situ Fe2+ oxidization so the MFC could operate with prolonged period with increased cell open circuit voltage (1037 mV) and maximum power density (71.8 Wm-3 at 154 Am-3) but with minimal needs for iron replenishment. The Fe2+-oxidizing microflora was very effective so the Fe3+/Fe2+ could reach high ratio, which was composed of Acidithiobacillus (73.8%), Acidiphilium (12.1%), Mycobacterium (6.92%), Sulfobacillus (2.66%), Ochrobactrum (1.30%), Alicyclobacillus (0.82%), and other minor species. The membrane transport and cell replication were shown to be their most important metabolic activities. The formation of jarosite and hydronium jarosite by Fe3+ and sulfate led to loss of iron ions, which should be minimized in operation.


Assuntos
Acidithiobacillus , Fontes de Energia Bioelétrica , Ferro , Oxirredução , Temperatura
10.
Org Lett ; 23(9): 3541-3545, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33885311

RESUMO

In the presence of [p-cymene)RuCl2]2, (E)-configured alkenyl bromides couple with aromatic carboxylates to form ortho-vinylbenzoic acids. This C-H vinylation proceeds in high yields without any activating phosphine ligands and has an excellent functional group tolerance. Starting from commonly available (E/Z )-mixtures of alkenyl bromides, (E)-configured vinyl arenes or dienes are formed exclusively. Mechanistic studies show that this selectivity is achieved because the (E)-configured alkenyl bromides undergo a smooth coupling, whereas the (Z)-isomers are rapidly eliminated with the formation of alkynes.

11.
Sci Rep ; 11(1): 6854, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767225

RESUMO

Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC-MS-DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.

12.
Environ Sci Technol ; 55(8): 5117-5127, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33691405

RESUMO

Humans are constantly exposed to antimicrobial triclocarban (TCC) via direct skin contact with personal care and consumer products, but the safety of long-term dermal exposure to TCC remains largely unknown. Herein, we used a mouse model to evaluate the potential health risks from the continuous dermal application of TCC at human-relevant concentrations. After percutaneous absorption, TCC circulated in the bloodstream and largely entered the liver-gut axis for metabolic disposition. Nontargeted metabolomics approach revealed that TCC exposure perturbed mouse liver homeostasis, as evidenced by the increased oxidative stress and impaired methylation capacity, leading to oxidative damage and enhancement of upstream glycolysis and folate-dependent one-carbon metabolism. Meanwhile, TCC was transformed in the liver through hydroxylation, dechlorination, methylation, glucuronidation, sulfation, and glutathione conjugation. TCC-derived xenobiotics were subsequently excreted into the gut, and glucuronide and sulfate metabolites could be further deconjugated by the gut microbiota into their active free forms. In addition, microbial community analysis showed that the composition of gut microbiome was altered in response to TCC exposure, indicating the perturbation of gut homeostasis. Together, through tracking the xenobiotic-biological interactions in vivo, this study provides novel insights into the underlying impacts of dermally absorbed TCC on the liver and gut microenvironments.


Assuntos
Carbanilidas , Microbioma Gastrointestinal , Microbiota , Animais , Carbanilidas/toxicidade , Homeostase , Fígado , Camundongos
13.
Cancer Med ; 10(7): 2380-2395, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33694292

RESUMO

OBJECTIVE: Deciphering the determinants of the intralesional immune reaction in cervical carcinogenesis may be conducive to improving the understanding of the disease and then improve outcomes. METHODS: Public gene-expression data and full clinical annotation were searched in Gene Expression Omnibus in the joint analysis of the array-based four eligible cohorts. The infiltrating estimation was quantified using microenvironment cell populations-counter algorithm and absolute-mode CIBERSORT and verified by flow cytometry analysis. An unsupervised classification on immune genes strongly associated with progression, designated by linear mixed-effects regression. We determined immune response and signaling features of the different developmental stages and immune phenotypes by functional annotation and systematically correlated the expression of immune checkpoints with cell-infiltrating characteristics. RESULTS: We identified the lesion-intrinsic immunosuppression mechanism was triggered at precancerous stages, such as genome instability and mutation, aerobic glycolysis, activation of proto-oncogene pathways and so forth. Predominant innate and adoptive cells were increasing from normalcy to cancer (B cell, total T cell, regulatory T cells [Tregs], monocytes, neutrophils, and M2-like macrophages) together with the decrease of CD4+ T cell and CD8+ T cell through the development of cervical cancer. Immune escape initiated on the expression of immunosuppressive molecules from high-grade squamous intraepithelial lesions (HSIL) and culminated in squamous cell carcinoma (SCC). Of note, the expression of immune checkpoints was escalated in the immune-hot and immune-warm phenotype largely encompassed by HSIL and SCC under the stress of both activated and suppressive immune responses. CONCLUSIONS: Immune surveillance is unleashing from low-grade squamous intraepithelial lesions onwards and immune-suppression mechanisms are triggered in HSIL. Thorough knowledge of the immune changing pattern during cervical tumorigenesis contributes to finding the potential therapeutic targets to susceptive patients towards immune checkpoints inhibitors.

14.
Redox Biol ; 42: 101880, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33541845

RESUMO

Oxidative stress is emerging as an important contributor to the pathogenesis of colorectal cancer (CRC), however, the molecular mechanisms by which the disturbed redox balance regulates CRC development remain undefined. Using a liquid chromatography-tandem mass spectrometry-based lipidomics, we found that epoxyketooctadecenoic acid (EKODE), which is a lipid peroxidation product, was among the most dramatically increased lipid molecules in the colon of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. This is, at least in part, due to increased oxidative stress in colon tumors, as assessed by analyzing gene expression of oxidative markers in AOM/DSS-induced CRC mice and human CRC patients in the Cancer Genome Atlas (TCGA) database. Systemic, short-time treatment with low-dose EKODE increased the severity of DSS-induced colitis, caused intestinal barrier dysfunction and enhanced lipopolysaccharide (LPS)/bacterial translocation, and exacerbates the development of AOM/DSS-induced CRC in mice. Furthermore, treatment with EKODE, at nM doses, induced inflammatory responses via JNK-dependent mechanisms in both colon cancer cells and macrophage cells. Overall, these results demonstrate that the lipid peroxidation product EKODE is an important mediator of colonic inflammation and colon tumorigenesis, providing a novel mechanistic linkage between oxidative stress and CRC development.

15.
J Immunother Cancer ; 9(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33452206

RESUMO

BACKGROUND: Most patients with high-grade serous ovarian cancer (HGSC) lack an effective response to immune checkpoint blockade, highlighting the need for more knowledge about what is required for successful treatment. As follicular cytotoxic CXCR5+CD8+ T cells are maintained by reinvigoration by immune checkpoint blockade in tumors, we attempted to reveal the relationship between CXCR5+CD8+ T cells and the tumor microenvironment to predict immunotherapy responses in HGSC. METHODS: 264 patients with HGSC from two cohorts and 340 HGSC cases from The Cancer Genome Atlas cohort were enrolled. Ex vivo and in vivo studies were conducted with human HGSC tumors and murine tumor models. The spatial correlation between CXC-chemokine ligand 13 (CXCL13), CXCR5, CD8, and CD20 was evaluated by immunohistochemistry and immunofluorescence. Survival was compared between different subsets of patients using Kaplan-Meier analysis. The therapeutic effect of CXCL13 and programmed cell death-1 (PD-1) blockade was validated using human HGSC tumors and murine models. RESULTS: High CXCL13 expression was associated with prolonged survival. Tumors with high CXCL13 expression exhibited increased infiltration of activated and CXCR5-expressing CD8+ T cells. Incubation with CXCL13 facilitated expansion and activation of CXCR5+CD8+ T cells ex vivo. CXCR5+CD8+ T cells appeared in closer proximity to CXCL13 in tumors and chemotaxis towards CXCL13 in vitro. The combination of CXCL13, CXCR5, and CD8+ T cells was an independent predictor for survival. In addition, CXCL13 was associated with clusters of CD20+ B cells. CD20+ B cells predicted better patient survival in the presence of CXCL13. Histological evaluation highlighted colocalization of CXCL13 with tertiary lymphoid structures (TLSs). TLSs carried prognostic benefit only in the presence of CXCL13. CXCL13 in combination with anti-PD-1 therapy retarded tumor growth in a CD8+ T-cell-dependent manner, resulting in increased infiltration of cytotoxic CD8+ T cells and CXCR5+CD8+ T cells. CONCLUSIONS: These data define a critical role of CXCL13 in shaping antitumor microenvironment by facilitating the maintenance of CXCR5+CD8+ T cells in TLSs and support a clinical investigation for a combination of CXCL13 and PD-1 blockade therapy in HGSC.

16.
J Pharm Biomed Anal ; 195: 113844, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33388640

RESUMO

Hereditary angioedema (HAE) is a rare genetic disease caused by deficiency or dysfunction of C1 esterase inhibitor (C1-INH). Plasma C1-INH activity and concentrations of C1-INH and complement components 1q and 4 (C1q, C4) are critical to the HAE diagnosis. We describe a novel multiplexed assay to simultaneously measure C1-INH, C1q, and C4 levels in dried blood spot (DBS) of HAE patients. The blood proteins were extracted from 3 mm punches of DBS samples and were subsequently digested by trypsin. The signature peptide derived from each protein was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Analyte-depleted blood was generated as a surrogate matrix for the preparation of calibration curves to overcome the interference of endogenous proteins, and the assay reproducibility was further monitored by assessing the signal of plasma transferrin as a house-keeping protein. The assay was fully validated following regulatory guideline, with a quantification range of 12.5-800 µg/mL for C1-INH and C4 and 3.13-200 µg/mL for C1q. The precision and accuracy ranged from 3.3%-9.8% and -8.2%-12.6%, respectively. All the patient samples exhibited C1-INH levels lower than normal range except the Type II patient and the C4 and C1q concentrations were as expected. Results from the DBS-based LC-MS assay were highly correlated with the ELISA data measured in plasma of the same subjects. The method described here offers unique advantages such as less invasive sampling, minimal blood processing, and easy transportation and sample storage, allowing, for the first time, C1-INH, C4, and C1q levels to be simultaneously determined in a drop of dried blood.

17.
Chem Commun (Camb) ; 57(9): 1113-1116, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33410434

RESUMO

An unprecedented ruthenium catalysed [4+4] annulation of readily available benzoic acids and alkynes is reported for the first time. The carboxylate group acts as both a directing group and an internal nucleophilic reagent to facilitate a C(sp2)-H vinylation/annulation cascade. This reaction avoids the classically oxidative [4+2] annulation, allowing the efficient synthesis of a wide array of eight-membered lactones under oxidant-free conditions. Moreover, this catalytic system can be successfully extended to [4+3] and [4+5] annulations for the assembly of seven- and nine-membered lactones.

18.
J Food Sci ; 86(2): 495-504, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33438200

RESUMO

The objective of this survey was to estimate the prevalence, contamination level, and genetic diversity of Salmonella in selected raw, shelled tree nuts (Brazil nuts, cashews, hazelnuts, macadamia nuts, pecans, pine nuts, pistachios, and walnuts) at retail markets in the United States. A total of 3,374 samples of eight tree nuts were collected from different types of retail stores and markets nationwide between September 2015 and March 2017. These samples (375 g) were analyzed using a modified FDA's BAM Salmonella culture method. Of the 3,374 samples, 15 (0.44%) (95% confidence interval [CI] [0.25, 0.73]) were culturally confirmed as containing Salmonella; 17 isolates were obtained. Among these isolates, there were 11 serotypes. Salmonella was not detected in Brazil nuts (296), hazelnuts (487), pecans (510), pine nuts (500), and walnuts (498). Salmonella prevalence estimates in cashews (510), macadamia (278), and pistachios (295) were 0.20% (95% CI [<0.01, 1.09]), 2.52% (95% CI [1.02, 5.12]), and 2.37% (95% CI [0.96, 4.83]), respectively. The rates of Salmonella isolation from major/big-chain supermarkets (1381), small-chain supermarkets (328), discount/variety/drug stores (1329), and online (336) were 0.29% (95% CI [0.08, 0.74]), 0.30% (95% CI [0.01, 1.69]), 0.45% (95% CI [0.17, 0.98]), and 1.19% (95% CI [0.33, 3.02]), respectively. Salmonella prevalence in organic (530) and conventional (2,844) nuts was not different statistically (P = 0.0601). Of the enumerated samples (15), 80% had Salmonella levels ≤0.0092 most probable number (MPN)/g. The highest contamination level observed was 0.75 MPN/g. The prevalence and contamination levels of Salmonella in the tree nuts analyzed were generally comparable to previous reports. Pulsed-field gel electrophoresis, serotype, and sequencing data all demonstrated that Salmonella population in nuts is very diverse genetically. PRACTICAL APPLICATION: The prevalence, contamination level, and genetic diversity of Salmonella in eight types of tree nuts (3,374 samples collected nationwide) revealed in this survey could help the development of mitigation strategies to reduce public health risks associated with consumption of these nuts.


Assuntos
Microbiologia de Alimentos , Nozes/microbiologia , Salmonella/isolamento & purificação , Anacardium/microbiologia , Carya/microbiologia , Corylus/microbiologia , Eletroforese em Gel de Campo Pulsado , Humanos , Juglans/microbiologia , Macadamia/microbiologia , Pistacia/microbiologia , Prevalência , Estados Unidos
19.
Environ Sci Pollut Res Int ; 28(20): 25241-25254, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33453030

RESUMO

Twenty antibiotics were investigated to evaluate the degree of antibiotic pollution, the temporal and spatial antibiotic distribution and the ecological risks in the Xiaoqing River basin (main stream). The total antibiotic concentrations in surface water and sediment were 0.99 to 832.4 ng L-1 and 9.71 to 7841.61 ng g-1, respectively, and that ofloxacin was the dominant antibiotic. However, ofloxacin, erythromycin, clarithromycin and sulfamethoxazole posed high risks to algae, among which clarithromycin presented the highest risk quotients (23.8). In addition, there were spatial and temporal differences in the antibiotic concentration distribution. Temporally, the following trend was detected: dry season > normal season > wet season; spatially, the following trend was detected: Jinan > Dongying > Binzhou > Zibo > Weifang. Meanwhile, we used the PCA-MLR model to quantify the contribution rate of the four sewage treatment plants A, B, C and D. Factor 1 (co-sources A, B, C, D) contributed 64.1% of the total antibiotic concentration in the Xiaoqing River. According to the estimated flux into the sea, approximately 972.31 kg of antibiotics were discharged into Bohai Bay in 2017, posing a potential threat to the marine ecosystem. As a comprehensive river channel used for flood control, waterlogging, irrigation and shipping, its water quality safety is of great significance to the surrounding residents and ecological safety. Therefore, further investigations of antibiotic pollution and source contribution are necessary.


Assuntos
Rios , Poluentes Químicos da Água , Antibacterianos/análise , China , Cidades , Ecossistema , Monitoramento Ambiental , Medição de Risco , Poluentes Químicos da Água/análise
20.
J Cardiothorac Surg ; 16(1): 2, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407683

RESUMO

BACKGROUND: A large number of studies have shown that BIMA grafting is superior to single internal mammary artery grafting in cardiac function protection and long-term survival after surgery. While, there is still no consensus on how is the best configuration to use BIMA. This study aims to compare intraoperative blood flow, early clinical results and early postoperative patency of different configurations of BIMA. METHODS: There were 74 patients who underwent CABGs with bilateral internal mammary artery with different configurations we included. According to the different target territories that RIMA grafted to, the patients were divided into bilateral group (group I) with 20 cases and left group (group II) with 54 cases. Intraoperative blood flow, early clinical results and early postoperative patency of different configurations of BIMA were compared. RESULTS: There was no difference in the early postoperative death and major complications between group I and Group II(P>0.05). Compared with the LIMA in group II, the LIMA in group I had a slightly higher DF value (76.7 ± 6.2 vs 73.1 ± 6.8, P = 0.040). Compared with the RIMA in group II, the RIMA in group I had a slightly higher MGF (51.7 ± 34.4 ml/min vs 31.4 ± 21.4 ml/min, P = 0.024). There was no difference in the other TTFM parameters of LIMA and RIMA between group I and Group II(P>0.05). Further subgroup analysis revealed that compared with free RIMA in group II, in situ RIMA had a higher DF value (71.4 ± 7.8 vs 61.8 ± 18.1,P = 0.025). The PI of LIMA in free RIMA subgroup was higher than the PI of LIMA in in-situ RIMA subgroup (3.0 ± 1.6 vs 2.1 ± 1.0,P = 0.018). The results of early postoperative CTA examination showed that all IMAs grafts were completely patent. CONCLUSIONS: The use of BIMA for CABG is safe and efficacious, RIMA used in right coronary artery received more satisfactory graft flow. BIMA with no stenosis and occlusion in the early stage, therefore is the ideal and stable coronary bypass graft.


Assuntos
Anastomose de Artéria Torácica Interna-Coronária/métodos , Artéria Torácica Interna/transplante , Idoso , Circulação Coronária , Vasos Coronários/cirurgia , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Grau de Desobstrução Vascular
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