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1.
BMC Public Health ; 24(1): 356, 2024 02 02.
Article in English | MEDLINE | ID: mdl-38308246

ABSTRACT

The working state of firefighters is important for their own safety as well as that of the general public. The purpose of this study is to investigate the correlations between self-concept clarity, resilience, work engagement, and job burnout among firefighters, as well as the impacts of self-concept clarity and resilience as resources that can maintain their working state. Based on data from 2,156 firefighters, analysis showed that self-concept clarity was negatively associated with job burnout and positively associated with work engagement. The results also showed that self-concept clarity had a direct effect on job burnout and work engagement, and an indirect effect by improving the firefighters' resilience. Maintaining and improving their self-concept clarity and resilience promises to be an effective strategy for guaranteeing the working state of firefighters.


Subject(s)
Burnout, Professional , Firefighters , Resilience, Psychological , Humans , Burnout, Professional/prevention & control , Work Engagement , Self Concept , Job Satisfaction , Surveys and Questionnaires
2.
Int J Mol Sci ; 24(24)2023 Dec 17.
Article in English | MEDLINE | ID: mdl-38139398

ABSTRACT

This study reports the whole-genome sequence of Lactiplantibacillus plantarum cqf-43 isolated from healthy sow feces. Based on genomic analysis, we performed a comprehensive safety assessment of strain cqf-43, using both in vitro and in vivo experiments, and explored its probiotic potential. The total genome length measures 3,169,201 bp, boasting a GC content of 44.59%. Through phylogenetic analyses, leveraging both 16S rRNA gene and whole-genome sequences, we confidently categorize strain cqf-43 as a member of Lactiplantibacillus. Genome annotation using Prokka unveiled a total of 3141 genes, encompassing 2990 protein-coding sequences, 71 tRNAs, 16 rRNAs, and 1 tmRNA. Functional annotations derived from COG and KEGG databases highlighted a significant abundance of genes related to metabolism, with a notable emphasis on carbohydrate utilization. The genome also revealed the presence of prophage regions and CRISPR-Cas regions while lacking virulence and toxin genes. Screening for antibiotic resistance genes via the CARD database yielded no detectable transferable resistance genes, effectively eliminating the potential for harmful gene transfer. It is worth highlighting that the virulence factors identified via the VFDB database primarily contribute to bolstering pathogen resilience in hostile environments. This characteristic is particularly advantageous for probiotics. Furthermore, the genome is devoid of menacing genes such as hemolysin, gelatinase, and biogenic amine-producing genes. Our investigation also unveiled the presence of three unannotated secondary metabolite biosynthetic gene clusters, as detected by the online tool antiSMASH, suggesting a great deal of unknown potential for this strain. Rigorous in vitro experiments confirmed tolerance of strain cqf-43 in the intestinal environment, its antimicrobial efficacy, sensitivity to antibiotics, absence of hemolysis and gelatinase activity, and its inability to produce biogenic amines. In addition, a 28-day oral toxicity test showed that the strain cqf-43 did not pose a health hazard in mice, further establishing it as a safe strain.


Subject(s)
Genome, Bacterial , Probiotics , Animals , Female , Swine , Mice , RNA, Ribosomal, 16S , Phylogeny , Anti-Bacterial Agents , Gelatinases/genetics , Sequence Analysis
3.
Front Microbiol ; 14: 1164937, 2023.
Article in English | MEDLINE | ID: mdl-37275176

ABSTRACT

The booming mudflat aquaculture poses an accumulation of organic matter and a certain environmental threat. Protease-producing bacteria are key players in regulating the nitrogen content in ecosystems. However, knowledge of the diversity of protease-producing bacteria in coastal mudflats is limited. This study investigated the bacterial diversity in the coastal mudflat, especially protease-producing bacteria and their extracellular proteases, by using culture-independent methods and culture-dependent methods. The clam aquaculture area exhibited a higher concentration of carbon, nitrogen, and phosphorus when compared with the non-clam area, and a lower richness and diversity of bacterial community when compared with the clam naturally growing area. The major classes in the coastal mud samples were Bacteroidia, Gammaproteobacteria, and Alphaproteobacteria. The Bacillus-like bacterial community was the dominant cultivated protease-producing group, accounting for 52.94% in the non-clam area, 30.77% in the clam naturally growing area, and 50% in the clam aquaculture area, respectively. Additionally, serine protease and metalloprotease were the principal extracellular protease of the isolated coastal bacteria. These findings shed light on the understanding of the microbes involved in organic nitrogen degradation in coastal mudflats and lays a foundation for the development of novel protease-producing bacterial agents for coastal mudflat purification.

4.
Coron Artery Dis ; 34(6): 425-431, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37222213

ABSTRACT

OBJECTIVE: Inflammation and dyslipidemia are important pathophysiological bases for the occurrence and development of coronary artery disease (CAD); however, combination of these two entities is rarely used to diagnose CAD and its severity. Our aim was to determine whether the combination of white blood cell count (WBCC) and LDL cholesterol (LDL-C) can serve as a biomarker for CAD. METHODS: We enrolled 518 registered patients and measured serum WBCC and LDL-C on admission. The clinical data were collected, and the Gensini score was used to assess the severity of coronary atherosclerosis. RESULTS: WBCC and LDL-C levels in the CAD group were higher than in the control group ( P  < 0.01). Spearman correlation analysis showed that WBCC combined with LDL-C was positively correlated with the Gensini score ( r  = 0.708, P  < 0.01) and the number of coronary artery lesions ( r  = 0.721, P  < 0.01). Receiver operating characteristic curve analysis revealed that WBCC combined with LDL-C had a higher predictive value for CAD, severe CAD, and three-vessel CAD [area under the curve (AUC) values were 0.909, 0.867, and 0.811, respectively] than WBCC (AUC values were 0.814, 0.753, 0.716, respectively) and LDL-C (AUC values were 0.779, 0.806, 0.715, respectively) alone (all P  < 0.05). CONCLUSION: WBCC combined with LDL-C is correlated with the degree of coronary artery lesion. It had high sensitivity and specificity in the diagnosis of CAD, severe CAD, and three-vessel CAD.


Subject(s)
Coronary Artery Disease , Humans , Coronary Artery Disease/diagnosis , Cholesterol, LDL , Risk Factors , Leukocyte Count , Biomarkers , Coronary Angiography
5.
Am J Transl Res ; 15(1): 202-212, 2023.
Article in English | MEDLINE | ID: mdl-36777866

ABSTRACT

OBJECTIVE: This study was designed to investigate the clinical efficacy of azithromycin combined with ambroxol in children with Mycoplasma pneumoniae pneumonia (MPP). METHODS: The clinical data of 103 children with MPP treated in Fuyang District Hospital of Traditional Chinese Medicine of Hangzhou from December 2020 to August 2021 were selected and retrospectively analyzed, and these children were divided into a control group (n=51, azithromycin treatment) and a study group (n=52, azithromycin plus ambroxol treatment) according to the different treatment methods. The immunoglobulin level, pulmonary function score, treatment efficacy, serum cytokine level, disappearance time of signs and symptoms, and myocardial enzyme indices were observed and compared between the two groups. Univariate and multivariate analyses were conducted to screen the factors affecting the prognosis of MPP patients. RESULTS: After treatment, the study group showed significantly lower levels of immunoglobulin E, immunoglobulin G, immunoglobulin M and immunoglobulin A; higher pulmonary function scores, and lower levels of interleukin-6, human interferon-gamma, and monocyte chemoattractant protein-4 compared with the control group (all P < 0.05). The total incidence of adverse reactions such as nausea, diarrhea, abdominal pain, and vomiting was 15.38% in the study group, which was slightly lower than that in the control group (17.65%), exhibiting no significant difference (P > 0.05). The disappearance time of cough and lung rales, time required to restore to a normal body temperature, and hospital stay in the study group were shorter than those in the control group (P < 0.05). After treatment, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase isoenzyme in the study group were lower than those in the control group (all P < 0.05). The course of disease before admission, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anemia, albumin < 30 g/L, drug initiation time, pulmonary consolidation, and complications involving multiple systems were the main factors affecting the efficacy of azithromycin combined with ambroxol in the treatment of MPP. CONCLUSION: Azithromycin combined with ambroxol can effectively improve the immunoglobulin level and lung function, reduce the level of inflammatory factors, improve the therapeutic effect, shorten the recovery process, and reduce the degree of myocardial damage, which is effective in the treatment of MPP and is worth promoting.

6.
J Anim Physiol Anim Nutr (Berl) ; 107(3): 867-877, 2023 May.
Article in English | MEDLINE | ID: mdl-36541276

ABSTRACT

The present study investigated the effects of supplementing bioactive peptides derived from rapeseed protein (rapeseed peptide, Rsp) on the growth performance, serum biochemistry and faecal micro-organism composition of weaned piglets. Sixty Duroc × Landrace × Yorkshire weaned piglets of similar weights were randomly divided into three groups. The control group (NC) was fed a basal diet, and the two treatment groups, Rsp-1 and Rsp-2, were fed a basal diet supplemented with 1% or 2% Rsp, respectively, for 28 days. Each treatment consisted of five replicates with four piglets per replicate. The results showed that Rsp treatment significantly improved the average daily gain and had a better feed-to-gain ratio (p < 0.05). The diarrhoea incidence and indices of Rsp-1 and Rsp-2 groups were significantly lower than the NC group (p < 0.05), and the effect of Rsp-2 on reducing the incidence of diarrhoea was significantly higher than that of Rsp-1 (p < 0.05). The serum albumin, serum immunoglobulin A and catalase levels of the Rsp-1 and Rsp-2 groups were significantly better than the NC group (p < 0.05). Additionally, Rsp treatment significantly gained the relative abundance of faecal Lactobacillaceae and decreased the relative abundance of faecal Eubacterium_coprostanoligenes_group, Treponema and Coprococcus (p < 0.05). In summary, Rsp supplementation improved the growth performance, ameliorated the diarrhoea, enhanced the immune and antioxidant functions and changed the composition of faecal micro-organisms in piglets. These findings indicate that Rsp positively affected the health of weaned piglets.


Subject(s)
Brassica napus , Animals , Swine , Dietary Supplements , Diet/veterinary , Peptides , Diarrhea/prevention & control , Diarrhea/veterinary
7.
Children (Basel) ; 9(12)2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36553353

ABSTRACT

OBJECTIVE: This study aims to validate previous structural models of factors influencing dietary behavior changes and construct the knowledge, attitude, and behavioral models of youth school football players. METHODS: 279 school football players aged 12-17 years in Grades 7-12 in Hunan Province, China, completed a questionnaire to collect data on sports nutrition knowledge, attitudes, and behavior. A structural equation model (SEM) was built based on the knowledge-attitude-behavior (KAB) model and the theory of planned behavior (TPB) model to introduce nutritional knowledge directly or by altering attitudes into the dietary behavior path of players. Four factors affecting dietary behaviors were involved in the hypothetical structure, which consists of the following hypotheses: (1) nutrition knowledge affects the attitude towards sports nutrition (H1); (2) nutrition knowledge affects dietary behaviors (H2); (3) nutrition knowledge affects subjective norms (H3); (4) nutrition knowledge affects perceived behavioral control (H4); (5) subjective norms affect dietary behaviors (H5); and 6) perceived behavioral control affects dietary behaviors (H6). RESULTS: Confirmatory factor analysis (CFA) revealed that the reliability, convergent validity, and discriminant validity of the built SEM conformed to the measured relationships in each dimension. In the final structural model, it was found that nutrition knowledge had a direct impact on the attitudes of players and affected their dietary behaviors in a direct manner or through their subjective norms and perceived behavioral control. CONCLUSIONS: The results are in agreement with the TPB-based KAB chain and support the KAB theory for youth school football players in Hunan Province, China.

8.
Biomed Res Int ; 2022: 7802492, 2022.
Article in English | MEDLINE | ID: mdl-36017383

ABSTRACT

The outbreak of the COVID-19 pandemic has caused negative impacts on people's lifestyles, as well as considerable indirect social impacts, which has even overshadowed the direct impact of virus infection itself. This study is aimed at examining the changes in physical health-related indexes of Chinese college students before and after the COVID-19 lockdown. The data of this study are from the National Physical Health Testing Program, covering 43 college students (male: 22) from a class of a Chinese university. Paired t-tests were performed on the physical health test data separately collected in November 2019 before the COVID-19 pandemic and October 2020 after the COVID-19 lockdown was lifted. As shown by the test results, compared to the prelockdown data, college students had an increased body mass index (BMI) (0.43 (SD 0.94) P = 0.004), decreased vital capacity (VC) (-128.98 (SD 310.13) ml P = 0.009), and lowered performance in the 800/1000 m endurance (-6.21 (SD 8.81) points P < 0.001) and standing long jump tests (-2.44 (SD 7.37) points P = 0.036) after the lockdown, and the differences in these regards all were significant. In addition, for the students in the overweight/obese group, their pre- and postlockdown physical fitness test results were found to have no statistically significant difference (P > 0.05), but the students in the control group showed a significantly increased BMI, as well as significantly decreased vital capacity and performance in the 800/1000 m endurance and standing long jump tests (P < 0.05). The findings of this study are expected to help government departments and policymakers better understand the impacts of school closures and online learning on the physical health of adolescents, while providing a basis for the formulation of measures that are aimed at reversing adolescents' physical health decline.


Subject(s)
COVID-19 , Adolescent , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Communicable Disease Control , Humans , Male , Pandemics , Students
9.
Org Lett ; 24(18): 3313-3318, 2022 05 13.
Article in English | MEDLINE | ID: mdl-35499249

ABSTRACT

Herein, we describe the nickel-catalyzed reductive arylation of remote C(sp3)-H bonds with aryl electrophiles. The reaction targets secondary and tertiary C(sp3)-H bonds to deliver all-carbon quaternary centers. The success of this method relies on a novel amidyl radical precursor that tolerates reducing conditions, namely O-oxalate hydroxamic acid esters.


Subject(s)
Carbon , Nickel , Carbon/chemistry , Catalysis , Nickel/chemistry
10.
Materials (Basel) ; 15(9)2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35591542

ABSTRACT

To explore the cooling effect of phase change materials (PCM) on asphalt pavement, a numerical model of the coupled heat transfer process of a typical monolithic subgrade of the G7 Expressway in the eastern Tianshan mountain area was developed. Three types of paraffin materials (OP55E, OP52E, OP47E) were mixed in a 4:3:3 volume ratio and blended into the asphalt upper layer and overall asphalt layer at volume ratios of 5%, 10%, 15% and 20%. The cooling effect of different PCM addition schemes was simulated and analyzed, and the frequency and duration of asphalt pavement high temperature operation status were also measured. The results showed that: (1) Th addition of PCM in the asphalt layer can effectively reduce the frequency of pavement high temperature rutting damage. The number of days and average daily duration of high temperature on the road surface were both reduced. (2) The cooling effect was positively correlated with the PCM volume mixing ratio, and the temperature drop of the pavement also increased with the increase of the PCM blending ratio. As the PCM mixing ratio increased from 5% to 20%, the initial 75 °C pavement cooled by 1.49 °C and 4.66 °C, respectively, and the number of days and hours of pavement temperature over 70 °C decreased to 4 days and 3.3 h, respectively. (3) The cooling effect of the asphalt upper layer PCM scheme was greater at a small mixing ratio (5%), whereas the performance of the overall asphalt layer PCM blended scheme was effectively promoted by increasing the equivalent heat capacity of system under the large mixing ratio (20%).

11.
Chin Med J (Engl) ; 134(24): 2999-3008, 2021 Dec 08.
Article in English | MEDLINE | ID: mdl-34939978

ABSTRACT

BACKGROUND: The association between miR-532-3p and tongue squamous cell carcinoma (TSCC) has been examined in the literature to improve the survival rate of patients with this tumor. However, further studies are needed to confirm the regulatory roles of this microRNA (miRNA) in TSCC. The objective of this study was to investigate the roles played by and the underlying mechanism used by the miR-532-3p/podoplanin (PDPN) axis in TSCC development. METHODS: Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) were performed to evaluate the PDPN expression level in TSCC tissues and cells. The proliferative, adhesive, and migratory capabilities of TSCC cells (CAL-27 and CTSC-3) were examined using cell counting kit-8 (CCK-8), cell adhesion, and wound-healing assays, respectively. The dual-luciferase reporter (DLR) assay was later conducted to confirm the relationship between miR-532-3p and PDPN. RESULTS: The results indicated that PDPN expression was enriched in TSCC tissues and cells, and that the expression of PDPN was associated with some clinicopathological parameters of TSCC, including lymph node metastasis (P = 0.001), tumor-node-metastasis (TNM) staging (P = 0.010), and grading (P = 0.010). Further analysis also showed that PDPN knockdown inhibited the viability, adhesive ability, and migratory capacity of CAL-27 and CTSC-3 cells, effects that could be reversed by the application of a miR-532-3p inhibitor. Additionally, PDPN was found to be a direct target of miR-532-3p. CONCLUSIONS: This research suggested that by targeting PDPN, miR-532-3p could inhibit cell proliferation viability, adhesion, and migration in TSCC. Findings also revealed that the miR-532-3p/PDPN axis might provide more insights into the prognosis and treatment of TSCC.


Subject(s)
Carcinoma, Squamous Cell , Membrane Glycoproteins , MicroRNAs , Tongue Neoplasms , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Tongue Neoplasms/genetics
12.
Article in English | MEDLINE | ID: mdl-33803733

ABSTRACT

High prevalence of physical inactivity and obesity in children and adolescents has become a global problem. This systematic review aimed to examine the existing literature regarding the factors that influence participation in physical activity (PA) in children and adolescents with reference to the social ecological model (SEM) proposed by McLeroy et al. (1988). The SEM provides a framework under which the influencing factors are categorized into five levels: intrapersonal, interpersonal, organizational, community, and public policy. A systematic search of relevant literature published before July 2020 was conducted through Ebsco, ProQuest, PubMed Central, Scopus, and Web of Science. A total of fourteen studies met the inclusion criteria. The selected articles were all of high quality as assessed using the Mixed Methods Appraisal Tool (2018). The results indicated that gender, age, ethnicity, and self-concept were the most common influencing factors at the intrapersonal level. At the interpersonal and organization levels, supports from friends, parents, and teachers were positive predictors of students' PA participation. Accessibility of facilities and safe neighborhoods was a crucial factor that influenced children and adolescents' participation in PA at the community level. Future studies on the effective types of policies or practices that could successfully promote facilities' accessibility and improve neighborhood safety are required. The outcomes of this systematic review are expected to inform practice and support the development and implementation of sound policies for the promotion of PA participation in children or adolescents from a comprehensive social ecological viewpoint.


Subject(s)
Pediatric Obesity , Adolescent , Child , Exercise , Humans , Pediatric Obesity/epidemiology , Pediatric Obesity/prevention & control , Schools , Sedentary Behavior , Social Environment
13.
Mol Cell Biol ; 41(6): e0056520, 2021 05 21.
Article in English | MEDLINE | ID: mdl-33820852

ABSTRACT

Serpin family E member 1 (SERPINE1) is a serine proteinase inhibitor (serpin) upregulated in diverse types of cancer, including oral squamous cell carcinoma (OSCC), and it functions in an oncogenic role. Hence, exploring pathological mechanism underlying high expression of SERPINE1 is crucial to the targeted therapy of OSCC. Bioinformatics analysis was performed to identify the microRNA (miRNA) and the candidate gene contributing to OSCC progression. The viability, proliferation, and apoptosis of the OSCC cell were evaluated using Cell Counting Kit-8 (CCK-8) assay, BrdU assay, and cell apoptosis assay, respectively. The RNA pulldown assay and luciferase reporter assay were conducted to verify the relationship between SERPINE1 and miRNA 617 (miR-617). SERPINE1 was aberrantly upregulated in OSCC tissues and cell lines. Genetically inhibiting SERPINE1 led to reduction of OSCC cell viability and proliferation and elevation of OSCC cell apoptosis. According to bioinformatics analysis, miR-617 contained a response element for SERPINE1 overexpression, which is validated by the RNA pulldown and luciferase reporter assays. Furthermore, miR-617 was detected to be downregulated in OSCC tissues and cell lines, and it displayed a negative correlation with advanced stages. Besides, miR-617 mimic or inhibitor transfection could suppress or boost the SERPINE1 expression. More importantly, miR-617 mimic could block the effect of SERPINE1 overexpression on OSCC cell proliferation, viability, and apoptosis. SERPINE1 acted as a proproliferative oncogenic factor that is partly regulated by miR-167 downregulation in OSCC cells. Therefore, the miR-617/SERPINE1 axis is a potential therapeutic target against OSCC.


Subject(s)
Carcinogenesis/genetics , Gene Expression Regulation, Neoplastic , Mouth Neoplasms/genetics , Plasminogen Activator Inhibitor 1/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Apoptosis , Cell Line, Tumor , Cell Proliferation/genetics , Disease Progression , Drug Delivery Systems , Female , Humans , Male , Middle Aged , Oncogenes , Plasminogen Activator Inhibitor 1/metabolism , Up-Regulation
14.
Org Lett ; 23(3): 808-813, 2021 02 05.
Article in English | MEDLINE | ID: mdl-33443440

ABSTRACT

The site-selective trifluoromethylation of aliphatic systems remains an important challenge. This work describes a light-driven, copper-mediated trifluoromethylation of O-alkyl thiocarbonates. The reaction provides broad functional group tolerance (e.g., alkyne, alkene, phenol, free alcohol, electron-rich and -deficient arenes), thereby offering orthogonality and practicality for trifluoromethylation. A radical organometallic mechanism is proposed.


Subject(s)
Alkenes/chemistry , Alkynes/chemistry , Copper/chemistry , Sulfhydryl Compounds/chemistry , Alcohols/chemistry , Catalysis , Methylation , Molecular Structure
15.
J Sci Food Agric ; 101(5): 1861-1868, 2021 Mar 30.
Article in English | MEDLINE | ID: mdl-32898288

ABSTRACT

BACKGROUND: Soybean meal (SBM) is the most common protein source used in the poultry and livestock industries. It has high-quality protein, an excellent amino acid (AA) profile, and positive isoflavone properties. However, the antigen proteins in SBM are unsuitable for young animals. The objective of this study was to identify a Bacillus strain that can degrade soybean antigen proteins, and to evaluate the feasibility of its application in SBM fermentation. RESULTS: Bacillus velezensis DP-2 was isolated from Douchi, a fermented Chinese food. It degraded 96.14% and 66.51% of glycinin and ß-conglycinin, and increased the trichloroacetic acid-soluble protein (TCAN) content by 5.46 times in the SBM medium. DP-2 could secrete alkaline protease and neutral protease, with productivities of 5.85 and 5.99 U mL-1 . It had broad-spectrum, antibacterial activities against Rhizopus nigricans HR, Fusarium oxysporum ACCC37404, Penicillium digitatum SQ2, Aspergillus flavus C1, Aspergillus niger ACCC30005, Trichoderma viride YZ1, Candida tropicalis CICC1630, and Salmonella sp. ZY. For SBM fermentation, the optimal inoculum rate, temperature, and fermentation time of DP-2 were 2.21 × 107 CFU g-1 , 37 °C, and 48 h, respectively. The fermented soybean meal (FSBM) was cream-colored and glutinous. Its crude protein (CP), soluble protein, and TCA-N content were improved by 13.45%, 12.53%, and 6.37 times, respectively. The glycinin and ß-conglycinin content were reduced by 78.00% and 43.07%, respectively, compared with raw SBM. CONCLUSIONS: Bacillus velezensis DP-2 has potential as a starter culture for SBM fermentation. © 2020 Society of Chemical Industry.


Subject(s)
Bacillus/metabolism , Fermented Foods/microbiology , Glycine max/microbiology , Antigens, Plant/analysis , Antigens, Plant/metabolism , Bacillus/classification , Bacillus/genetics , Bacillus/isolation & purification , Fermentation , Fermented Foods/analysis , Globulins/analysis , Globulins/metabolism , Seed Storage Proteins/analysis , Seed Storage Proteins/metabolism , Soybean Proteins/analysis , Soybean Proteins/metabolism , Glycine max/chemistry
16.
J Am Chem Soc ; 142(1): 581-588, 2020 01 08.
Article in English | MEDLINE | ID: mdl-31809027

ABSTRACT

Herein we describe an unprecedented B(C6F5)3-catalyzed cascade reaction of N-allyl-N-furfurylamides involving an initial intramolecular furan Diels-Alder reaction and subsequent ether cleavage. The reaction has a broad substrate scope, even tolerating a trialkyl-substituted olefin as the dienophile, which has not previously been observed with conventional furan Diels-Alder reactions. In addition, the relative configuration of the product can be controlled by the choice of the silyl group: reactions involving Et3SiH and iPr3SiH gave different diastereomers. Control experiments and the computational studies revealed that the steric bulk of the silyl group plays a key role in determining the reaction pathway and thus the relative configuration of the product.

17.
PDA J Pharm Sci Technol ; 72(6): 574-583, 2018.
Article in English | MEDLINE | ID: mdl-29954921

ABSTRACT

This study compared an adenosine triphosphate (ATP)-based bioluminescence rapid microbial method (RMM) with a conventional sterility method for biologics sample testing. The RMM is based on a comparison of ATP levels in inoculated and uninoculated microbiological growth medium samples following growth enrichment incubation. The biologics samples qualified in this study were recombinant monoclonal antibodies and hybridoma cell culture supernatants. Initially, the lot-to-lot variation in background ATP of these samples posed significant challenges. Two strategies to increase the signal-to-noise ratio (positive result/background ATP) were evaluated: enzyme-based signal amplification and reduction of the broth-based noise through broth selection. Following qualification of the RMM for antibody and cell culture samples, the RMM was also utilized for rapid screening of several sources of purified water. This ATP-based RMM has proved invaluable in routine testing of diverse biologics samples at our discovery research site and plays a key role in the investigation of contaminated samples.LAY ABSTRACT: Biologics research laboratories routinely conduct sterility testing of products in development. However, the lengthy turnaround time for detection of microbial contaminants when using a conventional sterility test is a bottleneck in this fast-paced environment. This study investigated an adenosine triphosphate-based bioluminescence rapid microbial method (RMM) for biologics samples, including monoclonal antibodies and hybridoma cell cultures. The results showed that the RMM allowed detection of antibody sample contaminants after only three days of incubation. In addition to being faster than the standard method, the RMM proved more reliable in detecting contaminants in cell culture samples with antibiotics. Since its initial evaluation, this RMM has accelerated biologics sterility testing across multiple projects at our site.


Subject(s)
Adenosine Triphosphate/analysis , Biological Products/analysis , Luminescent Measurements/methods , Sterilization/methods , Antibodies, Monoclonal/analysis , Biological Products/standards , Culture Media/analysis , Hybridomas/cytology , Recombinant Proteins/analysis
18.
Oncotarget ; 8(37): 61810-61823, 2017 Sep 22.
Article in English | MEDLINE | ID: mdl-28977906

ABSTRACT

Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls. Supernatants from cultured human pancreatic cancer tissues (PC supernatants) induced substance P and calcitonin gene-related peptide release in dorsal root ganglia (DRG) neurons, and FS-NH2, a selective PAR-2 antagonist, inhibited this effect. A BALB/c nude mouse orthotopic tumor model was used to confirm the role of PAR-2 signaling in pancreatic cancer visceral pain, and male Sprague-Dawley rats were used to assess ambulatory pain. FS-NH2 treatment decreased hunch scores, mechanical hyperalgesia, and visceromotor reflex responses in tumor-bearing mice. In rats, subcutaneous injection of PC supernatant induced pain behavior, which was alleviated by treatment with FS-NH2 or FUT-175, a broad-spectrum serine protease inhibitor. Our findings suggest that trypsin-PAR-2 signaling contributes to pancreatic cancer pain in vivo. Treatment strategies targeting PAR-2 or its downstream signaling molecules might effectively relieve pancreatic cancer pain.

19.
Angew Chem Int Ed Engl ; 56(21): 5817-5820, 2017 05 15.
Article in English | MEDLINE | ID: mdl-28418184

ABSTRACT

B(C6 F5 )3 has been found to be an effective catalyst for reduction of pyridines and other electron-deficient N-heteroarenes with hydrosilanes (or hydroboranes) and amines as the reducing reagents. The success of this development hinges upon the realization of a cascade process of dearomative hydrosilylation (or hydroboration) and transfer hydrogenation. The broad functional-group tolerance (e.g. ketone, ester, unactivated olefins, nitro, nitrile, heterocycles, etc.) implies high practical utility.

20.
Angew Chem Int Ed Engl ; 56(14): 4028-4032, 2017 03 27.
Article in English | MEDLINE | ID: mdl-28266171

ABSTRACT

Catalytic amounts of B(C6 F5 )3 promote the ring opening and subsequent isomerization of a series of unactivated cyclopropanes to afford terminal olefins in good yields when a hydrosilane and 2,6-dibromopyridine are employed as additives.

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