Maternal L-carnitine supplementation promotes brown adipose tissue thermogenesis of newborn goats after cold exposure.

Brown adipose tissue (BAT) is an important component of energy expenditure and necessary to maintain body temperature for newborn mammals. In the previous study, we found that L-carnitine was enriched in BAT and promoted BAT adipogenesis and thermogenesis in goat brown adipocytes. However, whether dietary L-carnitine regulates BAT heat production and energy expenditure in lambs remains unclear. In this study, maternal L-carnitine supplementation elevated the rectal temperature, as well as the expression of UCP1 and mitochondrial DNA content to promote BAT thermogenesis in newborn goats. Moreover, maternal L-carnitine supplementation increased the levels of triglycerides (TG), non-esterified fatty acids (NEFA), and lactate in plasma, as well as the content of lipid droplet and glycogen in BAT of newborn goats. Lipidomic analysis showed that maternal L-carnitine supplementation remodeled the lipid composition of BAT in newborn goats. L-carnitine significantly increased the levels of TG and diglyceride (DG) and decreased the levels of glycerophospholipids and sphingolipids in BAT. Further studies showed that L-carnitine promoted TG and glycogen deposition in brown adipocytes through AMPKα. Our results indicate that maternal L-carnitine supplementation promotes BAT development and thermogenesis in newborn goats and provides new evidence for newborn goats to maintain body temperature in response to cold exposure.

NR1H4-mediated circRHOBTB3 modulates the proliferation, metastasis, and Warburg effects of cervical cancer through interacting with IGF2BP3.

Globally, cervical cancer (CC) ranks as the fourth most common cancer and the most lethal malignancy among females of reproductive age. The incidence of CC is increasing in low-income countries, with unsatisfactory outcomes and long-term survival for CC patients. Circular RNAs (CircRNAs) are promising therapeutics that target multiple cancers. In this study, we investigated the tumorigenic role of circRHOBTB3 in CC, showing that circRHOBTB3 is highly expressed in CC cells and circRHOBTB3 knockdown also repressed CC proliferation, migration, invasion, and the Warburg effects. CircRHOBTB3 interacted with the RNA-binding protein, IGF2BP3, to stabilize its expression in CC cells and is putatively transcriptionally regulated by NR1H4. In conclusion, this novel NR1H4/circRHOBTB3/IGF2BP3 axis may provide new insights into CC pathogenesis.

A Clinical Prediction Model of Overall Survival for Patients with Cervical Cancer Aged 25-69 Years.

Aims: This study aims to develop a prediction tool for the overall survival of cervical cancer patients. Methods: We obtained 4116 female patients diagnosed with cervical cancer aged 25-69 during 2008-2019 from the Surveillance, Epidemiology, and End Results Program. The overall survival between groups was illustrated by the Kaplan-Meier method and compared by a log-rank test adjusted by the Bonferroni-Holm method. We first performed the multivariate Cox regression analysis to evaluate the predictive values of the variables. A prediction model was created using cox regression based on the training set, and the model was presented as a nomogram. The proposed nomogram was designed to predict the 1-year, 3-year, and 5-year overall survival of patients with cervical cancer. Besides the c-index, time-dependent receiver operating curves, and calibration curves were created to evaluate the accuracy of the nomogram at the timepoint of one year, three years, and five years. Results: With a median follow-up of 54 (28, 92) months, 1045 (25.39%) patients were deceased. Compared with alive individuals, the deceased were significantly older and the primary site was more likely to be the cervix uteri site, large tumor size, higher grade, and higher combined summary stage (all p values < 0.001). In the multivariate Cox regression, age at diagnosis, race, tumor size, grade, combined summary stage, pathology, and surgery treatment were significantly associated with the all-cause mortality for patients with cervical cancer. The proposed nomogram showed good performance with a C-index of 0.82 in the training set. The 1-year, 3-year, and 5-year areas under the curves (with 95% confidence interval) of the receiver operating curves were 0.88 (0.84, 0.91), 0.84 (0.81, 0.87), and 0.83 (0.80, 0.86), respectively. Conclusions: This study develops a prediction nomogram model for the overall survival of cervical cancer patients with a good performance. Further studies are required to validate the prediction model further.

Integrated application of metabolomics and RNA-seq reveals thermogenic regulation in goat brown adipose tissues.

Brown adipose tissue (BAT) plays an important role on no shivering thermogenesis during cold exposure to maintain animal body temperature and energy homeostasis. However, knowledge of the cellular transition from white adipose tissue (WAT) to BAT is still limited. In this study, we provided a comprehensive metabolomics and transcriptional signatures of goat BAT and WAT. A total of 157 metabolites were significantly changed, including 81 upregulated and 76 downregulated metabolites. In addition, we identified the citric acid cycle, fatty acid elongation, and degradation pathways as coordinately activated in BAT. Interestingly, five unsaturated fatty acids (Eicosadienoic Acid, C20:2; γ-Linolenic acid, C20:3; Arachidonic Acid, C20:4; Adrenic acid, C22:4; Docosahexaenoic acid, C22:6), Succinate, L-carnitine, and L-palmitoyl-carnitine were found to be abundant in BAT. Furthermore, L-carnitine, an intermediate of fatty acid degradation, is required for goat brown adipocyte differentiation and thermogenesis through activating AMPK pathway. However, L-carnitine decreased lipid accumulation through inducing lipolysis and thermogenesis in white adipocytes. These results revealed that there are the significant alterations in transcriptomic and metabolomic profiles between goat WAT and BAT, which may contribute to better understanding the roles of metabolites in BAT thermogenesis process.

HIV incidence and compliance with deferral criteria over three progressively shorter time deferrals for men who have sex with men in Canada.

BACKGROUND: In Canada, the deferral for men who have sex with men (MSM) has been progressively reduced from a permanent deferral for MSM since 1977, to 5 years, 1 year, and, most recently, 3 months. We estimated human immunodeficiency virus (HIV) residual risk and compliance with the MSM time deferral after each change. METHODS: Four anonymous online compliance surveys were carried out before and after each change. HIV incidence and prevalence were monitored from 2010 to 2021. Residual risk was estimated using the incidence-window period model. RESULTS: Human immunodeficiency virus prevalence, incidence, and residual risk did not change with incrementally shorter MSM deferrals. The residual risk per million donations post 3-month deferral was 0.05 (0.001-0.371). Men with temporally remote MSM history became eligible and, therefore, compliant as the deferral periods decreased (Cochran-Armitage p value = <.0001). However, the percentage of men with MSM history in the last 3 months with the indefinite deferral in place was similar to the percentage noncompliant, while the 3-month deferral was in place. MSM donors did not report high-risk behaviors for which they would otherwise be deferred in any survey. Following the change, an estimated 4467 MSM per year were eligible to donate, an increase from 2501 estimated eligible MSM donors following the change to the 1-year deferral. CONCLUSION: With progressively shorter MSM deferral periods, HIV residual risk was unchanged. The proportion of male donors with deferrable MSM history remained low, while those with temporally remote MSM history became eligible, increasing the number of eligible MSM donors.

Selective Raman Enhancement with Electronic Sensitivity in Tip-Enhanced Raman Spectroscopy.

Chemical interaction between the tips and molecules is one of the main contributing mechanisms to tip-enhanced Raman spectroscopy (TERS). In this work, we calculate the TERS spectra of the biphenylene (BP) dimer at 13 nonequivalent tip sites by means of density functional theory and explore the influence of the TERS tip on vibrational mode characters and Raman intensity. The Raman intensity of the vibrational mode involving the antisymmetric stretching of tetra-rings is found to be specifically enhanced. We attribute this specific enhancement to the electronic sensitive atom vibrational character of the mode and infer that the vibrational strength of atoms can be tuned by the TERS tip. The results provide an intuitive interpretation on the effects of tip-induced electronic redistributions on specific vibrational modes in TERS and indicate the possibility to further improve the TERS resolution.

Discovery of potent histone deacetylase inhibitors with modified phenanthridine caps.

In discovery of novel HDAC inhibitory with anticancer potency, pharmacophores of phenanthridine were introduced to the structure of HDAC inhibitors. Fatty and aromatic linkers were evaluated for their solubility and activity. Both enzyme inhibitory and in vitro antiproliferative (against U937 cells) screening results revealed better activities of compounds with aromatic linker than molecules with fatty linker. Compared with SAHA (IC50 values of 1.34, 0.14, 2.58, 0.67 and 18.17 µM), molecule Fb-4 exhibited 0.87, 0.09, 0.32, 0.34 and 17.37 µM of IC50 values against K562, U266, MCF-7, U937 and HEPG2 cells, respectively. As revealed by cell cycle and apoptotic analysis, induction of G2/M phase arrest and apoptosis plays an important role in the inhibition of MCF-7 cells by Fb-4. Generally, a potent HDAC inhibitor was developed in the present study which could be utilised as a lead compound for further anticancer drug design.

Compliance with time-based deferrals for men who have sex with men.

BACKGROUND: The deferral for men who have sex with men (MSM) was reduced from a permanent deferral for MSM if even one time since 1977 to progressively shorter time deferrals of 5 years and 1 year in Canada. We assessed compliance with these deferrals and the impact on safety at Canadian Blood Services. STUDY DESIGN AND METHODS: Three anonymous online compliance surveys of male whole blood donors were carried out before and after implementation of successive changes. HIV rates and incidence were monitored from January 1, 2011, to August 14, 2018. RESULTS: Participation rates in the consecutive surveys were 49.7% before implementation, 36.3% after 5 years and 36.3% after 1 year. There was no difference before versus after implementation in male donors with MSM history in the past year (0.21%, 0.19%, 0.24%; p = 0.70). The percentage of eligible MSM donors increased (0.13%, 0.66%, 1.21%; p < 0.0001), with approximately 2500 eligible MSM donors with the 1-year deferral in place. HIV rates were less than 0.6 per 100,000 donations and unchanged after each policy change (p = 0.14 for trend). Incidence remained unchanged at 0.22 per 100,000 person-years before implementation, 0.54 per 100,000 after 5-year deferral, and no incident cases after 1-year deferral (p = 0.55). CONCLUSION: Progressively shorter time deferrals had no impact on noncompliance of MSM with a male partner in the past year. Contrary to modeling predictions, shorter time deferrals had no impact on HIV rates or incidence. There was a modest increase in eligible MSM in the donor pool after each shorter time deferral. These results support the safety of reducing deferral periods for MSM.

Recombinant Expression and Bioactivity Comparison of Four Typical Fungal Immunomodulatory Proteins from Three Main Ganoderma Species.

BACKGROUND: More than a dozen of fungal immunomodulatory proteins (FIPs) have been identified to date, most of which are from Ganoderma species. However, little is known about the similarities and differences between different Ganoderma FIPs' bioactivities. In the current study, two FIP genes termed FIP-gap1 and FIP-gap2 from G. applanatum, along with LZ-8 and FIP-gsi, another two representative Ganoderma FIP genes from G. lucidum and G. sinense were functionally expressed in Pichia. Subsequently, bioactivities of four recombinant Ganoderma FIPs were demonstrated and compared. RESULTS: All the four Ganoderma FIP genes could be effectively expressed in P. pastoris GS115 at expression levels ranging from 197.5 to 264.3 mg L- 1 and simply purified by one step chromatography using HisTrap™ FF prepack columns. Amino acid sequence analysis showed that they all possessed the FIP conserved fragments. The homologies of different Ganoderma FIPs were from 72.6 to 86.4%. In vitro haemagglutination exhibited that FIP-gap1, FIP-gsi and LZ-8 could agglutinate human, sheep and mouse red blood cells but FIP-gap2 agglutinated none. Besides, the immunomodulation activities of these Ganoderma FIPs were as: rFIP-gap2 > rFIP-gap1 > rLZ-8 and rFIP-gsi in terms of proliferation stimulation and cytokine induction on murine splenocytes. Additionally, the cytotoxic activity of different FIPs was: rFIP-gap1 > rLZ-8 > rFIP-gsi > rFIP-gap2, examined by their inhibition of three human carcinomas A549, Hela and MCF-7. CONCLUSIONS: Taken together, four typical Ganoderma FIP genes could be functionally expressed in P. pastoris, which might supply as feasible efficient resources for further study and application. Both similarities and differences were indeed observed between Ganoderma FIPs in their amino acid sequences and bioactivities. Comprehensively, rFIP-gaps from G. applanatum proved to be more effective in immunomodulation and cytotoxic assays in vitro than rLZ-8 (G. lucidum) and rFIP-gsi (G. sinense).

Molecular cloning, codon-optimized gene expression, and bioactivity assessment of two novel fungal immunomodulatory proteins from Ganoderma applanatum in Pichia.

Fungal immunomodulatory proteins (FIPs) have been identified from a series of fungi, especially in Ganoderma species. However, little is known about the FIPs from G. applanatum. In this study, two novel FIP genes, termed as FIP-gap1 and FIP-gap2, were cloned from G. applanatum, characterized and functionally expressed after codon optimization in Pichia pastoris GS115. Results showed that FIP-gap1 and FIP-gap2 comprised 342-bp encoding peptides of 113 amino acids, which shared a high homology with other Ganoderma FIPs. The yield of recombinant FIP-gap1 and FIP-gap2 increased significantly after codon optimization and reached 247.4 and 197.5 mg/L, respectively. Bioactivity assay in vitro revealed that both rFIP-gap1 and rFIP-gap2 could agglutinate mouse, sheep, and human red blood cells. Besides, rFIP-gap1 and rFIP-gap2 obviously stimulated the proliferation of mouse splenocytes and enhanced IL-2 and IFN-γ release. Cytotoxicity detection indicated that IC50 of rFIP-gap1 towards A549 and HeLa cancer cells were 29.89 and 8.34 µg/mL, respectively, whereas IC50 of rFIP-gap2 to the same cancer cells were 60.92 and 41.05 µg/mL, respectively. Taken together, novel FIP gaps were cloned and functionally expressed in P. pastoris, which can serve as feasible and stable resources of rFIP gaps for further studies and potential applications.

Residual risk of HIV, HCV and HBV in Canada.

BACKGROUND: Residual risk is estimated as the product of the incidence and the infectious window period, the time during which a blood donation could be infectious but the assay may not detect it. In 2011 nucleic acid multiplex testing (MPX) was implemented in 6 unit minipools (previously 24 unit minipools). MPX also included hepatitis B (HBV) NAT for the first time (complementing HBsAg screening) in addition to HIV-1 and hepatitis C (HCV) as before. We aimed to estimate window period risk-day equivalents for MPX, and the residual risk of viral infections in blood donations updated to reflect current incidence and testing. METHODS: Transmissible disease conversions of repeat donations to Canadian Blood Services within the three-year period 2012-2014 divided by person-years estimated incidence for HIV, HCV and HBV (adjusted for transient viremia). Window period risk-day equivalents for MPX were estimated using a published method. Residual risk was the product of incidence and window period risk-day equivalents. 95% confidence intervals were estimated using Monte Carlo simulation of the window period risk-day equivalents and the incidence density 95% confidence intervals. RESULTS: The incidence rate per 100,000 person years for HIV was 0.28, HCV 1.0 and HBV 0.26. The residual risk of HIV was 1 per 21.4 million donations, HCV 1 per 12.6 million donations and HBV 1 per 7.5 million donations. CONCLUSION: The residual risk of infection is very low, similar to 2006-2009. The safety benefit of further shortening of the infectious window period is below the threshold to quantify.

Impact of a 5-year deferral from blood donation for men who have sex with men.

BACKGROUND: The deferral for men who have sex with men (MSM) changed from a permanent deferral since 1977 to a 5-year deferral on July 22, 2013, in Canada. We assessed the impact on safety and adequacy of the blood supply at Canadian Blood Services. STUDY DESIGN AND METHODS: Human immunodeficiency virus (HIV) rates were monitored from January 1, 2010, to July 21, 2015. Risk factors were assessed in notification interviews. Anonymous online surveys of male whole blood donors assessed compliance before and after implementation. RESULTS: HIV rates were 0.2, 0.5, and 0.51 per 100,000 donations in 2010 to 2012; they were 0.54 and 0.22 in the first and second years after implementation (p = 0.8). Of four male HIV-positive donors after implementation, three denied risk factors and one knew he had HIV. Before implementation 9669 of 19,437 (49.7%) donors participated in the survey, and after implementation, 6881 of 18,934 (36.3%). Before implementation 0.67% of male donors were noncompliant, and after implementation, 0.44%. There was no difference before versus after implementation in male donors with MSM history in the past 5 years (0.37% vs. 0.43%, p = 0.54). After implementation, eligible MSM donors increased (0.42% vs. 0.66%, p = 0.04), with approximately 500 more donors in 2014. CONCLUSION: Implementation of a 5-year deferral for MSM had no impact on HIV rates in 2 years of postimplementation monitoring. Donor compliance improved after implementation due to MSM donors who were previously ineligible becoming eligible. There was no change in the percentage of male donors with recent male partners but there was a modest increase in eligible MSM in the donor pool.

Evaluation of selective screening of donors for antibody to Trypanosoma cruzi: seroprevalence of donors who answer "no" to risk questions.

BACKGROUND: Selective testing of donors for Trypanosoma cruzi infection relies on identification of at-risk donors with screening questions. Using risk modeling and a seroprevalence study, we evaluated the risk of questions failing to identify T. cruzi antibody-positive donors. STUDY DESIGN AND METHODS: The rate of donors with unreported risk was estimated by a telephone survey of 2677 donors who answered "no" to risk questions. The number of T. cruzi antibody-positive donors missed by risk questions was estimated from the product of this rate and the selective testing T. cruzi antibody-positive rate. The 95% confidence interval (CI) was estimated by Monte Carlo simulation. To test the model, 60,132 donors were tested for T. cruzi antibody (26% of donors in selected regions, Phase I). In Winnipeg, Manitoba, the highest-risk region, 26,915 donors were tested (92.5% of donors, Phase II). RESULTS: In the telephone survey, 21 (0.8%) donors reported risk factors that would have identified them for selective testing. Seven were born in Mexico or Central or South America, five had travel risk, and nine had mother or maternal grandmother risk. The 95% CI for predicted number of T. cruzi antibody-positive donors answering "no" to risk questions was 0.71 to 4.38. In Phase I, one Winnipeg donor confirmed positive but had answered risk questions correctly. No other positive donations were identified. CONCLUSION: The estimated risk of T. cruzi-positive donors who answer "no" to risk questions is low and is confirmed by the seroprevalence among these donors.

Prevalence of human T-cell lymphotropic virus-1/2 in Canada over 33 years: A unique contribution of blood donors to public health surveillance.

OBJECTIVES: Estimate HTLV-1/2 (human T-cell lymphotropic viruses) prevalence in Canadian blood donors and the association of demographic variables with infection and their corresponding risk factors. METHODS: First-time blood donors in all Canadian provinces (except Quebec) from 1990 to 2022 were included. Blood samples were tested for HTLV-1/2 by enzyme-linked immunoassay, confirmed by Western blot. Multivariable logistic regression with year, age group, sex, region, neighbourhood material deprivation, and ethnocultural composition indices predicted HTLV-1/2. Since 2005, all HTLV-1/2-positive donors (cases) were invited to participate in a risk factor interview, and 4 non-positive donors (controls per case) were matched for age, sex, and region. Case-control predictors of HTLV-1/2 were analyzed using logistic regression. RESULTS: There were 3,085,554 first-time donors from 1990 to 2022. HTLV-1/2 prevalence remained low (12 per 100,000 in 2022, 95% CI 6.4-23.5). The odds ratios predicting HTLV-1/2 were higher in females (2.0, 95% CI 1.5-2.6), older age groups (50 + ; 6.3, 95% CI 4.3-9.2), British Columbia and Ontario, those materially deprived (1.9, 95% CI 1.2-2.9), and those in ethnocultural neighbourhoods (7.5, 95% CI 3.2-17.3). Most HTLV-1/2 in Ontario was HTLV-1, whereas in British Columbia half were HTLV-2. Forty-three of 149 (28.8%) cases and 172 of 413 (41.6%) controls completed an interview. The strongest predictor of HTLV-1/2 in case-control analysis was birth in a high-prevalence country (OR 39.8, 95% CI 7.8-204.3) but about 50% of HTLV-1 and 90% of HTLV-2 were Canadian-born. CONCLUSION: HTLV-1/2 prevalence is low in blood donors. High-prevalence country of birth accounts for about half of HTLV-1; HTLV-2 positives are usually Canadian-born. HTLV-1/2 transmission likely occurs overseas and within Canada.

RéSUMé: OBJECTIFS: Estimer la prévalence des sous-types du virus T-lymphotrope humain (HTLV-1 et HTLV-2) dans le sang des donneurs de sang canadiens, et évaluer le lien avec des variables démographiques et des facteurs de risque donnés. MéTHODES: Cette étude a porté sur toutes les personnes ayant fait leur premier don entre 1990 et 2022 au Canada, sauf au Québec. Les échantillons de sang ont été soumis à un test immunoenzymatique, puis à un test Western Blot de confirmation. Les données ont été analysées au moyen de la régression logistique en utilisant comme indices l'année, la tranche d'âge, le sexe, la région, le quartier, la privation matérielle et la composition ethnoculturelle. Depuis 2005, tous les donneurs positifs au HTLV-1/2 (cas) ont été conviés à un entretien ayant pour but de déterminer leurs facteurs de risque, et quatre donneurs négatifs (cas-témoins) ont été appariés à chaque cas en fonction de l'âge, du sexe et de la région. Les facteurs de prédiction d'infection au HTLV-1/2 des cas-témoins ont été analysés au moyen de la régression logistique. RéSULTATS: Entre 1990 et 2022, le nombre de primodonneurs s'élevait à 3 085 554. La prévalence du HTLV-1/2 est demeurée faible (12,2 sur 100 000 en 2022, IC 95%: 6,4­23,5). Le rapport de cotes était plus élevé chez les femmes (2,0, IC 95% 1,5­2,6), chez les personnes de plus de 50 ans (6,3, IC 95% 4,3­9,2), en Colombie-Britannique et en Ontario, chez les personnes touchées par la privation matérielle (1,9, IC 95% 1,2­2,9) et chez les personnes vivant dans des quartiers ethnoculturels (7,5, IC 95% 3,2­17,3). La plupart des cas de HTLV-1/2 rencontrés en Ontario concernaient le HTLV-1, tandis qu'en Colombie-Britannique, la moitié des cas concernait le HTLV-2. Quarante-trois cas sur 149 (28,8 %) et 172 cas-témoins sur 413 (41,6 %) ont passé l'entretien. L'analyse des cas-témoins a révélé que le facteur de prédiction le plus important d'infection au HTLV-1/2 était le fait d'être né dans un pays à forte prévalence (RC 39,8, IC 95% 7,8­204,3); toutefois environ 50 % des cas-témoins de HTLV-1 et 90 % des cas témoins de HTLV-2 étaient nés au Canada. CONCLUSION: La prévalence du HTLV-1/2 est faible dans le sang des donneurs de sang. Pays de naissance à forte prévalence représente à peu près la moitié des cas de HTLV-1; les donneurs positifs au HTLV-2 la plupart du temps sont nés au Canada. La transmission du HTLV-1/2 survient probablement outre-mer et au Canada.

SARS-CoV-2 vaccination in Canadian blood donors: Insight into donor representativeness of the general population.

Introduction: Blood donors world-wide were indispensable for monitoring anti-SARS-CoV-2 antibodies generated by infection and vaccination during the pandemic. Prior to the pandemic, donor vaccination behaviours were under-studied. We aimed to compare the percentage of Canadian blood donors with SARS-CoV-2 vaccination antibodies with the percentage of the general population who received at least one dose of vaccine each month during initial vaccine deployment. We also report donor attitudes towards SARS-CoV-2 vaccination. Methods: Canadian blood donors were randomly selected for SARS-CoV-2 antibody testing over 2021 (N = 165,240). The percentage of donor samples with vaccination antibodies were compared with the percentage of general population who received at least one dose of vaccine in each month of 2021 except February. A random sample of Canadian blood donors were surveyed about vaccination intent and attitudes (N = 4,558 participated, 30.4 % response rate). Results: The percentages of the general population vaccinated and donors with vaccination antibodies increased from 1 % to over 90 %. General population vaccination was greater early in vaccine deployment than donors (p < 0.05), greater in donors than the general population by mid-2021 (p < 0.05) but they were similar by the end of 2021. While 52.6 % of surveyed donors had received vaccine in May 2021, a further 41.1 % intended to when eligible. Most donors thought COVID-19 infection could be serious (83.5 %) and that it was important to be vaccinated even if previously infected (77.8 %). Conclusion: Early pandemic vaccine prioritization to at-risk individuals and healthcare workers gave rise to higher general population vaccination percentages, while donors had higher vaccine antibody percentages as vaccine was deployed to progressively younger age groups. Since blood donors may be more willing to receive vaccination, under pandemic conditions they may be valuable for monitoring vaccination-induced seroprevalence.

Selective testing for Trypanosoma cruzi: the first year after implementation at Canadian Blood Services.

BACKGROUND: Various testing strategies may reduce the risk of Chagas disease transmission in nonendemic, low-prevalence countries. Results of the first year of selective testing of at-risk donors at Canadian Blood Services are reported. STUDY DESIGN AND METHODS: Since February 2009, platelets were not produced from at-risk donors. Since May 2010, at-risk donors were tested for Trypanosoma cruzi antibodies. Donors testing positive were interviewed about risk factors, and lookback studies were initiated. RESULTS: There were 7255 at-risk donors of 421,979 donors screened (1.72%). Risk factors were born in Latin America (50.6%), mother or maternal grandmother born in Latin America (28%), and 6 months or more travel history or residence in Latin America (19%). Sixteen (16) at-risk donors had T. cruzi repeat-reactive test results of whom 13 confirmed positive. Eleven of 13 were born in Latin America (nine in Paraguay and two in Argentina), and the other two were born in Canada but had short-term travel history and mothers who had been born in Latin America. Ten of the donors spoke German as their first language (all of those born in Paraguay and one born in Canada). There were 148 previous donations (176 components transfused) evaluated by lookback, of which 28% of recipients could be tested. None were positive. CONCLUSION: Selective testing has mitigated a small risk to the blood supply with very few false-positive results. Most positive donors were born in a risk country, with a concentration of German-speaking immigrants from Paraguay. Residency or travel alone were not clear risk factors.

Identifying the critical activated carbon properties affecting the adsorption of effluent organic matter from bio-treated coking wastewater.

Activated carbon is widely used to remove effluent organic matter (EfOM) from bio-treated coking wastewater. However, the critical carbon properties affecting adsorption performance are still unclear. Nine commercial powdered activated carbons (PACs) with different pore structures, surface functional groups, and surface charges were used to adsorb EfOM from bio-treated coking wastewater, which was fractionated according to their molecular weight (MW) and hydrophobicity. Good correlations were observed between the adsorption of biopolymers (MW > 20,000 Da, 7 %) and macropore volume (>50 nm), as well as between the adsorption of humics (MW = 1000 ~ Da, 36 %) and mesopore volume (2-50 nm), suggesting that the adsorption sites of EfOM depended on their molecular size. Higher isoelectric points and fewer acidic groups promoted the adsorption of the most negatively charged hydrophobic acids (HPOA, 39.5 %). According to variation partitioning analysis (VPA), mesopore-macropore greatly contributed to the adsorption capacities of EfOM (71.3 %), whereas the sum of phenolic hydroxyl and carboxyl (26.3 %) and isoelectric point (12.2 %) affected the normalized adsorption capacities of EfOM. In conclusion, PAC with a higher mesopore volume, fewer acidic groups, and a higher isoelectric point was desirable for removing EfOM from bio-treated coking wastewater. This study provides guidance for the selection of PAC for the removal of EfOM from bio-treated coking wastewater.

Integrated enzymes activity and transcriptome reveal the effect of exogenous melatonin on the strain degeneration of Cordyceps militaris.

As a valuable medicinal and edible fungus, Cordyceps militaris has been industrialized with broad development prospects. It contains a lot of bioactive compounds that are beneficial to our health. However, during artificial cultivation, strain degeneration is a challenge that inhibits the industrialization utility of C. militaris. Exogenous melatonin (MT) can scavenge for reactive oxygen species (ROS) in fungus and can alleviate strain degeneration. To establish the significance and molecular mechanisms of MT on strain degeneration, we investigated the third-generation strain (W5-3) of C. militaris via morphological, biochemical, and transcriptomic approaches under MT treatment. Morphological analyses revealed that colony angulation of C. militaris was significantly weakened, and the aerial hypha was reduced by 60 µmol L-1 MT treatment. Biochemical analyses showed low levels of ROS and malondialdehyde (MDA), as well as increasing endogenous MT levels as exogenous MT increased. RNA-Seq revealed that compared with the control, several antioxidant enzyme-related genes were up-regulated under 60 µmol L-1 MT treatment. Among them, glutathione s-transferase genes were up-regulated by a factor of 11.04. In addition, genes that are potentially involved in cordycepin, adenosine and active compound biosynthesis for the growth and development of mycelium were up-regulated. Collectively, these findings provide the basis for further elucidation of the molecular mechanisms involved in C. militaris strain degeneration.

Insights into the response of anammox process to oxytetracycline: Impacts of static magnetic field.

The long-term effects of oxytetracycline (OTC) with a high concentration on the anaerobic ammonium oxidation (Anammox) process were evaluated, and the role of static magnetic field (SMF) was further explored. The stress of OTC at 50 mg/L had little effect on the nitrogen removal of anammox process at the first 16 days. With the continuous addition of OTC and the increase of nitrogen loading, the OTC inhibited the nitrogen removal and anammox activity severely. During the 32 days of recovery period without OTC addition, the nitrogen removal was further deteriorated, indicating the inhibition of OTC on anammox activity was irreversible and persistent. The application of SMF alleviated the inhibition of OTC on anammox to some extent, and the specific anammox activity was enhanced by 47.1% compared to the system without SMF during the OTC stress stage. Antibiotic efflux was the major resistance mechanism in the anammox process, and tetA, tetG and rpsJ were the main functional antibiotic resistance genes. The addition of OTC weakened the metabolic interactions between the anammox bacteria and the symbiotic bacteria involved in the metabolism of cofactors and secondary metabolites, leading to the poor anammox activity. The adaptability of microbes to the OTC stress was improved by the application of SMF, which can enhance the metabolic pathways related to bacterial growth and resistance to environmental stress.

Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors.

In discovery of novel SIRT3 inhibitors for the treatment of cancer, a series of 2-(4-acrylamidophenyl)-quinoline-4-carboxylic acid derivatives were designed and synthesized. Among the derived compounds, molecule P6 exhibited SIRT3 inhibitory selectivity with IC50 value of 7.2 µM over SIRT1 (32.6 µM) and SIRT2 (33.5 µM). molecular docking analysis revealed a specific binding pattern of P6 in the active site of SIRT3 compared with the bindings in the active site of SIRT1 and SIRT2. In the antiproliferative and colony forming assay, molecule P6 showed potent inhibitory activity against a group of MLLr leukemic cell lines. Further analysis revealed that induction of G0/G1 phase cell cycle arrest and cell differentiation, but not apoptosis, makes contributions to the anticancer effects of P6. Collectively, a potent SIRT3 inhibitor (P6) was discovered as a lead compound for the leukemic differentiation therapy.