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Toxic cyanobacterial blooms are a worldwide concern. Nutrients are among the numerous factors that trigger cyanobacterial blooms and the production of cyanotoxins. This study aimed to assess the effect of nitrogen on cyanobacteria and cyanotoxins through a short-term mesocosm experiment. To achieve this, mesocosms were installed in situ in two lakes (the Missisquoi Bay of Lake Champlain and Petit-Lac-St-François) and received 700 μg/L of ammonium or 500 μg/L of nitrate. A shift to Microcystis in the mesocosms with nitrogen addition was observed 2 days after the addition in Missisquoi Bay, where nitrogen was more limited than Petit-Lac-St-François based on nutrient ratios. There was a significant increase of extracellular ΣMCs and MC-LR in mesocosms with the addition of ammonium or nitrate after 48 h compared to control mesocosms. Intracellular and extracellular microcystin concentrations were associated with Microcystis. Microcystis presence was associated with ammonium 48 h after N was added at both sites. Therefore, toxin production following sudden nitrogen addition can occur on short time scales relevant to drinking water treatment plant operations. This information will help treatment plant operators better anticipate the arrival of potentially higher concentrations of cyanotoxins.

Considerable effort by numerous laboratories has resulted in an improved understanding of estrogen and SERM action mediated by the two estrogen receptors, ERα and ERβ. However, many of the targets for ERβ in cell physiology remain elusive. Here, the C4-12/Flag.ERβ cell line which stably expressed Flag.ERβ is used to study ERβ genomic functions without ERα interference. Mapping ERβ binding sites in these cells reveals ERβ unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ERβ target genes. Gene ontology analysis reveals that ERβ targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ERβ binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ERβ binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ERβ binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ERβ genomic functions in our cell model, we confirm the anti-proliferative role of ERβ and discover the novel cross talk of ERβ with EBF1 which has various implications in normal physiology.

Objectives: This study aimed to determine the antibiotic-resistant profile and to identify molecular characterization of some virulence genes of Klebsiella spp. isolated from mastitis samples in Vietnam. Materials and Method: A total of 468 samples from clinical mastitis cases were collected and submitted to the Laboratory. All samples were cultured, and Klebsiella spp. was identified through biochemical reactions and confirmed by Polymerase chain reaction (PCR). Antimicrobial resistance was tested by disk diffusion method, and virulence and resistance genes were tested by PCR. Results: An antibiogram study showed that a high proportion of isolates are multidrug-resistant (94%). All isolates were resistant to lincomycin and sulfamethoxazole, followed by ampicillin (94%), sulphonamide (66%), amoxicillin (56%), streptomycin (52%), polymyxin B (28%), colistin sulfate (12%), tetracycline (6%), ciprofloxacin (4%), florfenicol (4%), enrofloxacin (4%), piperacillin (2%), trimethoprim (2%), nalidixic acid (2%), imipenem (2%), and sulfamethoxazole/trimethoprim (2%). In contrast, all isolates showed sensitivity to gentamicin and ceftiofur. The appearance of an efflux pump system, extended-spectrum beta-lactamase (ESBL), tetracycline, and sulphonamides-resis¬tant genes was reconfirmed using different specific primers. Capsular serotype K1 and virulence genes magA, fimH, and entB, responsible for hypermucoviscosity production, adherence, and enterobactin production, were confirmed in isolates. Multidrug resistance and virulence potential in Klebsiella spp. are changing this mastitis pathogen into a superbug and making its management harder. Conclusions: Klebsiella spp. associated with bovine mastitis in Nghe An province were mostly multidrug-resistant and carried virulence genes including fimH, entB, and antimicrobials resistant genes (blaSHV, acrAKp, tetA, etc.), but these isolates were not ESBL producers. [J Adv Vet Anim Res 2023; 10(1.000): 132-143]

α-Alkylation of β-keto esters is a frequently used reaction for carbon–carbon bond formation, but a general, stereoselective version of this reaction is challenging to realize. Here, the authors report a combined ruthenium and palladium catalytic system for the asymmetric dehydrative condensation between cinnamyl-type allylic alcohols and β-keto esters.

Abstract During the COVID-19 pandemic, many countries implemented international travel restrictions that aimed to contain viral spread while still allowing necessary cross-border travel for social and economic reasons. The relative effectiveness of these approaches for controlling the pandemic has gone largely unstudied. Here we developed a flexible network meta-population model to compare the effectiveness of international travel policies, with a focus on evaluating the benefit of policy coordination. Because country-level epidemiological parameters are unknown, they need to be estimated from data; we accomplished this using approximate Bayesian computation, given the nature of our complex stochastic disease transmission model. Based on simulation and theoretical insights we find that, under our proposed policy, international airline travel may resume up to 58% of the pre-pandemic level with pandemic control comparable to that of a complete shutdown of all airline travel. Our results demonstrate that global coordination is necessary to allow for maximum travel with minimum effect on viral spread.

BackgroundThe coronavirus disease (COVID-19) pandemic has caused a serious global communicable disease burden. Although COVID-19 and its policy responses have significantly influenced older adults, the impact of COVID-19 on depression in the older population is not fully understood. We aimed to investigate whether a history of COVID-19 infection and a decline in outdoor activities during the COVID-19 pandemic were associated with depression among older adults in Vietnam.MethodsThis multicenter cross-sectional study was conducted on 1,004 outpatients (aged ≥60 years; mean age 70.8 ± 7.3 years; men, 33.0%) visiting three hospitals for a comprehensive geriatric assessment between November 2021 and July 2022. Depression over the past week was evaluated using the 15-item Geriatric Depression Scale. History of COVID-19 infection and decline in outdoor activities were included as binary variables. We adjusted these two factors with sociodemographic and geriatric variables and comorbidities using a logistic regression analysis in separate models.ResultsA total of 156 participants (15.5%) experienced depression. The proportion of mild, moderate, and severe depressive symptoms was 14.1%, 44.9%, and 41.0%, respectively. In the multivariate model, decline in outdoor activities (odds ratio [OR] 17.2, 95% confidence interval [CI] 9.15-32.2, p ConclusionsCOVID-19 had a direct and indirect impact on depression in older adults, reflecting an association between both a history of COVID-19 infection and a decline in outdoor activities during the COVID-19 pandemic and depression in the older population.

Objective: A lack of demonstrated clinical benefit precludes radiotherapy (RT) from being recommended for pN1/pN2 penile cancer (PeCa) lesions; but it may be recommended in case of extranodal (pN3) disease or for positive resection margins. Perineal urethrostomy (PU) is a technique of urinary diversion in patients with PeCa requiring total or subtotal penectomy as primary therapy. Prior studies suggest PU failure rates of up to 30%, without specific mention of the potential role of RT. When RT is delivered for PeCa it is usually to the pre-pubic fat, groin and lateral pelvis, and not to the region of the PU. Here we describe the role of perioperative RT in a large, multi-institutional registry of PU for PeCa. Methods: In our cohort, 299 patients from seven international, high-volume centers in Belgium, Brazil, China, Netherlands, United Kingdom and the United States underwent PU as urinary diversion for PeCa between 2000 and 2020. Demographic and clinicopathologic characteristics were reviewed. Results: Median patient age was 67 years and median follow-up was 19 months. Seven patients (2.3%) received pre-operative RT; six of them with chemotherapy. 37 received RT post-operatively, 21 (57%) with chemotherapy. Stenosis of the PU occurred in 35 (12%) of the total population. The majority of these patients (74%) required surgical revision at a median of 6.1 months post-operatively. RT delivery was neither significantly related to PU stenosis (p = 0.16) or to subsequent revision (p = 0.75). Conclusion: Receipt of RT was not significantly associated with increased stenosis risk in PeCa patients who underwent PU.

Chemical profiling for quality monitoring and evaluation of medicinal plants is gaining attention. This study aims to develop an HPLC method followed by multivariate analysis to obtain HPLC profiles of five specific flavonoids, including rutin (1), hyperin (2), isoquercitrin (3), quercitrin (4), and quercetin (5) from Houttuynia cordata leaves and powder products and assess the quality of H. cordata samples. Eventually, we successfully established HPLC-based flavonoid profiles and quantified the contents of 32 H. cordata fresh leave samples and four powder products. The study also quantified the contents of those five essential flavonoids using an optimized RP-HPLC method. Peak areas of samples were then investigated with principal component analysis (PCA) and hierarchical cluster analysis (HCA) to evaluate the similarity and variance. Principal components in PCA strongly influenced by hyperin and quercetin showed that the samples were clustered into subgroups, demonstrating H. cordata samples’ quality. The results of HCA showed the similarity and divided the samples into seven subgroups. In conclusion, we have successfully developed a practical methodology that combined the HPLC-based flavonoid profiling and multivariate analysis for the quantification and quality control of H. cordata samples from fresh leaves and powder products. For further studies, we will consider various environmental factors, including climate and soil factors, to investigate their effects on the flavonoid contents of H. cordata.

One-carbon (C1) chemicals are potential building blocks for cheap and sustainable re-sources such as methane, methanol, formaldehyde, formate, carbon monoxide, and more. These resources have the potential to be made into raw materials for various products used in our daily life or precursors for pharmaceuticals through biological and chemical processes. Among the soluble C1 substrates, methanol is regarded as a biorenewable platform feedstock because nearly all bioresources can be converted into methanol through syngas. Synthetic methylotrophy can be exploited to produce fuels and chemicals using methanol as a feedstock that integrates natural or artificial methanol assimilation pathways in platform microorganisms. In the methanol utilization in methylotrophy, methanol dehydrogenase (Mdh) is a primary enzyme that converts methanol to formaldehyde. The discovery of new Mdhs and engineering of present Mdhs have been attempted to develop synthetic methylotrophic bacteria. In this review, we describe Mdhs, including in terms of their enzyme properties and engineering for desired activity. In addition, we specifically focus on the application of various Mdhs for synthetic methylotrophy.

Tenatoprazole, a newly developed proton pump inhibitor candidate, was developed as an acid inhibitor for gastric acid hypersecretion disorders such as gastric ulcer and reflux esophagitis. It is known that tenatoprazole is metabolized to three major metabolites of 5′-hydroxy tenatoprazole, tenatoprazole sulfide, and tenatoprazole sulfone in human liver, primarily catalyzed by CYPs 2C19 and 3A4. While CYP2C19 prefers the hydroxylation of tenatoprazole at C-5′ position, CYP3A4 is mainly involved in sulfoxidation reaction to make tenatoprazole sulfone. Tenatoprazole sulfide is a major human metabolite of tenatoprazole and is formed spontaneously and non-enzymatically from tenatoprazole. However, its metabolic fate in the human liver is not fully known. Furthermore, no systematic metabolic study has been performed to study tenatoprazole or tenatoprazole sulfide. Here, we studied the functions of human cytochromes P450 in the metabolic pathway of tenatoprazole and tenatoprazole sulfide by using recombinant human P450s and human liver microsomes. Both CYP 2C19 and CYP3A4 showed distinct regioselective and stereospecific monooxygenation activities toward tenatoprazole and tenatoprazole sulfide. Furthermore, a new major metabolite of tenatoprazole sulfide was found, 1′-N-oxy-5′-hydroxytenatoprzole sulfide, which has never been reported. In conclusion, the metabolic fates of tenatoprazole and tenatoprazole sulfide should be considered in the clinical use of tenatoprazole.

The excessive proliferation of cyanobacteria in surface waters is a widespread problem worldwide, leading to the contamination of drinking water sources. Short- and long-term solutions for managing cyanobacterial blooms are needed for drinking water supplies. The goal of this research was to investigate the cyanobacteria community composition using shotgun metagenomics in a short term, in situ mesocosm experiment of two lakes following their coagulation with ferric sulfate (Fe2(SO4)3) as an option for source water treatment. Among the nutrient paramenters, dissolved nitrogen was related to Microcystis in both Missisquoi Bay and Petit Lac St. François, while the presence of Synechococcus was related to total nitrogen, dissolved nitrogen, dissolved organic carbon, and dissolved phosphorus. Results from the shotgun metagenomic sequencing showed that Dolichospermum and Microcystis were the dominant genera in all of the mesocosms in the beginning of the sampling period in Missisquoi Bay and Petit Lac St. François, respectively. Potentially toxigenic genera such as Microcystis were correlated with intracellular microcystin concentrations. A principal component analysis showed that there was a change of the cyanobacterial composition at the genus level in the mesocosms after two days, which varied across the studied sites and sampling time. The cyanobacterial community richness and diversity did not change significantly after its coagulation by Fe2(SO4)3 in all of the mesocosms at either site. The use of Fe2(SO4)3 for an onsite source water treatment should consider its impact on cyanobacterial community structure and the reduction of toxin concentrations.

Phloretin, the major polyphenol compound in apples and apple products, is interesting because it shows beneficial effects on human health. It is mainly found as a form of glucoside, phlorizin. However, the metabolic pathway of phloretin in humans has not been reported. Therefore, identifying phloretin metabolites made in human liver microsomes and the human cytochrome P450 (P450) enzymes to make them is interesting. In this study, the roles of human liver P450s for phloretin oxidation were examined using human liver microsomes and recombinant human liver P450s. One major metabolite of phloretin in human liver microsomes was 3-OH phloretin, which is the same product of a bacterial CYP102A1-catalyzed reaction of phloretin. CYP3A4 and CYP2C19 showed kcat values of 3.1 and 5.8 min−1, respectively. However, CYP3A4 has a 3.3-fold lower Km value than CYP2C19. The catalytic efficiency of a CYP3A4-catalyzed reaction is 1.8-fold higher than a reaction catalyzed by CYP2C19. Whole-cell biotransformation with CYP3A4 was achieved 0.16 mM h−1 productivity for 3-OH phlorein from 8 mM phloretin at optimal condition. Phloretin was a potent inhibitor of CYP3A4-catalyzed testosterone 6β-hydroxylation activity. Antibodies against CYP3A4 inhibited up to 90% of the microsomal activity of phloretin 3-hydroxylation. The immunoinhibition effect of anti-2C19 is much lower than that of anti-CYP3A4. Thus, CYP3A4 majorly contributes to the human liver microsomal phloretin 3-hydroxylation, and CYP2C19 has a minor role.

The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the target enzyme itself yielding the free acid. Detailed kinetic and mass spectrometry studies revealed a reversible covalent binding mode. Theoretical calculations with different density functionals (DFT) as well as wavefunction-based approaches were performed to elucidate the mode of action.

Deletion of transactions in databases is common in real-world applications. Developing an efficient and effective mining algorithm to maintain discovered information is thus quite important in data mining fields. A lot of algorithms have been proposed in recent years, and the best of them is the pre-large-tree-based algorithm. However, this algorithm only rebuilds the final pre-large tree every deleted transactions. After that, the FP-growth algorithm is applied for mining all frequent item sets. The pre-large-tree-based approach requires twice the computation time needed for a single procedure. In this paper, we present an incremental mining algorithm to solve above issues. An itemset tidset-tree structure will be used to maintain large and pre-large item sets. The proposed algorithm only processes deleted transactions for updating some nodes in this tree, and all frequent item sets are directly derived from the tree traversal process. Experimental results show that the proposed algorithm has good performance. [ABSTRACT FROM AUTHOR]

Incremental data mining has been discussed widely in recent years, as it has many practical applications, and various incremental mining algorithms have been proposed. Hong et ah proposed an efficient incremental mining algorithm for handling newly inserted transactions by using the concept of pre-large itemsets. The algorithm aimed to reduce the need to rescan the original database and also cut maintenance costs. Recently, Lin et al. proposed the Pre-FUFP algorithm to handle new transactions more efficiently, and make it easier to update the FP-tree. However, frequent itemsets must be mined from the FP-growth algorithm. In this paper, we propose a Pre-FUT algorithm (Fast-Update algorithm using the Trie data structure and the concept of pre-large itemsets), which not only builds and updates the trie structure when new transactions are inserted, but also mines all the frequent itemsets easily from the tree. Experimental results show the good performance of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Cyanobacterial blooms are a global concern. Chemical coagulants are used in water treatment to remove contaminants from the water column and could potentially be used in lakes and reservoirs. The aims of this study was to: 1) assess the efficiency of ferric sulfate (Fe2(SO4)3) coagulant in removing harmful cyanobacterial cells from lake water with cyanobacterial blooms on a short time scale, 2) determine whether some species of cyanobacteria can be selectively removed, and 3) determine the differential impact of coagulants on intra- and extra-cellular toxins. Our main results are: (i) more than 96% and 51% of total cyanobacterial cells were removed in mesocosms with applied doses of 35 mgFe/L and 20 mgFe/L, respectively. Significant differences in removing total cyanobacterial cells and several dominant cyanobacteria species were observed between the two applied doses; (ii) twelve microcystins, anatotoxin-a (ANA-a), cylindrospermopsin (CYN), anabaenopeptin A (APA) and anabaenopeptin B (APB) were identified. Ferric sulfate effectively removed the total intracellular microcystins (greater than 97% for both applied doses). Significant removal of extracellular toxins was not observed after coagulation with both doses. Indeed, the occasional increase in extracellular toxin concentration may be related to cells lysis during the coagulation process. No significant differential impact of dosages on intra- and extra-cellular toxin removal was observed which could be relevant to source water applications where optimal dosing is difficult to achieve.

Ovarian hormones, such as estrogens and progesterone, are known to exert beneficial effects on cognition and some psychiatric disorders. The basis of these effects is not fully understood, but may involve altered cholinergic neurotransmission. This study aimed to investigate how a lack of ovarian hormones would impact muscarinic receptor-induced deficits in prepulse inhibition (PPI) and muscarinic receptor density in several brain regions. Adult female rats were either ovariectomized, to remove the source of ovarian hormones, or left intact (sham-operated). PPI is a measure of sensorimotor gating that is typically impaired in schizophrenia patients, and similar deficits can be induced in rats by administering scopolamine, a muscarinic receptor antagonist. Our results revealed no significant effects of ovariectomy on PPI after saline or scopolamine treatment. Autoradiography was performed to measure cholinergic muscarinic receptor binding density using [3H]-pirenzepine, [3H]-AF-DX, and [3H]-4-DAMP, to label M1, M2/M4, and M3 receptors, respectively. We examined the amygdala, caudate putamen, dorsal hippocampus, motor cortex, retrosplenial cortex, and ventromedial hypothalamus. There were no significant group differences in any region for any muscarinic receptor type. These results suggest that removing peripheral ovarian hormones does not influence the cholinergic muscarinic receptor system in the context of PPI or receptor binding density.

A wireless body area sensor network (WBASN) consists of a coordinator and multiple sensors to monitor the biological signals and functions of the human body. This exciting area has motivated new research and standardization processes, especially in the area of WBASN performance and reliability. In scenarios of mobility or overlapped WBASNs, system performance will be significantly degraded because of unstable signal integrity. Hence, it is necessary to consider interference mitigation in the design. This survey presents a comparative review of interference mitigation schemes in WBASNs. Further, we show that current solutions are limited in reaching satisfactory performance, and thus, more advanced solutions should be developed in the future.