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"If You're Woke You Dig It" is a research article and elegy for the popular AAVE term, "woke." I attempt to illustrate woke's early uses in the Black Atlantic in connection to its resurgence in the 21st century. I discuss it's usage among non-Black people and the absorption of Black Vernacular Englishes into popular consciousness and its usage by non-Black people. I argue that the "death" of woke is indicative of the lack of possession Black people have over cultural production and the importance of Black Vernacular English as a counter- hegemonic tactic. Black cultural production should be understood as key to global black liberation.

International audience; Vibsatin A is a new neurotrophic vibsane-type diterpenoid comprising a bridged bicyclo[4.2.1]nonane skeleton. Inspired by Sawamura’s works, we generated the bicyclic backbone through a Conia-ene-derived 7-exo-dig cyclization from an enantiomerically enriched TIPS-based silyl enol ether. The reaction, catalyzed by a sensitive gold(I) complex, was efficiently performed on a large scale by glovebox free techniques. Furthermore, the shape of this system was exploited for subsequent installation of all of the stereogenic centers.

Background Drug-induced glaucoma (DIG) is a kind of serious adverse drug reaction that can cause irreversible blindness. Up-to-date, the molecular mechanism of DIG largely remains unclear yet due to the medical complexity of glaucoma onset. Methods In this study, we conducted data mining of tremendous historical adverse drug events and genome-wide drug-regulated gene signatures to identify glaucoma-associated drugs. Upon these drugs, we carried out serial network analyses, including the weighted gene co-expression network analysis (WGCNA), to illustrate the gene interaction network underlying DIG. Furthermore, we applied pathogenic risk assessment to discover potential biomarker genes for DIG. Results As the results, we discovered 13 highly glaucoma-associated drugs, a glaucoma-related gene network, and 55 glaucoma-susceptible genes. These genes likely played central roles in triggering DIGs via an integrative mechanism of phototransduction dysfunction, intracellular calcium homeostasis disruption, and retinal ganglion cell death. Further pathogenic risk analysis manifested that a panel of nine genes, particularly OTOF gene, could serve as potential biomarkers for early-onset DIG prognosis. Conclusions This study elucidates the possible molecular basis underlying DIGs systematically for the first time. It also provides prognosis clues for early-onset glaucoma and thus assists in designing better therapeutic regimens.

We demonstrate a facile approach for the synthesis of gem-disubstituted cyclooctanoids, a motif found in several biologically active compounds. Appropriately substituted 1-alkenyl-5-pentyn-1-ols be...

Mouse-mouse hybridoma cell lines producing stable, highly specific monoclonal antibodies with good affinity for the cardiac glycoside digoxin (DIG) were established to construct an indirect enzyme-linked immunosorbent assay and lateral-flow immunochromatographic strip to detect DIG in human blood. The hapten DIG was coupled to bovine serum albumin or chicken ovalbumin by sodium periodate oxidation. The highest sensitivity and specificity antibody had a median inhibitory concentration (IC50) of 0.45 ng/mL, a linear range of detection of 0.293-0.7 ng/mL, and low cross-reactivity with several DIG analogues. The cut-off value of the lateral-flow immunochromatographic strip was 5 ng/mL when the strip was tested with human blood. The immunochromatographic lateral flow strip test provides a quick and convenient method for determining DIG in plasma which can be visually observed in only 5 min to promote rational drug use.

An efficient approach for the synthesis of immobilized copper (triazole-5-yl)methanamine complexes onto MCM-41 (Cu@TZMA@MCM-41), as a novel recyclable nanocatalyst, is described. This nanocatalyst was used for the synthesis of pyridine-containing pseudopeptides through a sequential Ugi/nucleophilic addition/1,5-enyne cyclization reaction and elicited good-to-excellent yields. The nanocatalyst was fully characterized by SEM, EDS, TEM, BET, ICP-OES, TGA, and XRD techniques. Furthermore, the catalyst was recovered by simple filtration and could be used for at least 5 cycles without significant loss of activity.

Autori predstavljaju projekt nastao suradnjom Konzervatorskog odjela u Trogiru Ministarstva kulture i medija te Javne vatrogasne postrojbe Grada Trogira. Iako je inicijalno zamišljen kao jednogodišnji projekt s primarnim ciljem revidiranja postojeće procjene ugroženosti za povijesnu jezgru, projekt je nadišao prvotno zamišljene okvire i u smislu aktivnosti i broja uključenih partnera. Vatrogasci i konzervatori radili su zajedno kako bi uključili cijeli sektor civilne zaštite grada i aktivirali lokalnu zajednicu kroz DIG (disaster imagination game) i InSight radionice. Štoviše, projekt je prerastao u nacionalni program smanjivanja rizika od požara na baštini koji podupiru Ministarstvo kulture i medija te Hrvatska vatrogasna zajednica., This paper presents a project delivered in collaboration between the Conservation Department of the Ministry of Culture and the Trogir Fire Department. Although originally planned as a one-year project, with the aim of revising the existing Fire Risk Assessment for the historic city core of Trogir, it surpassed its initial framework, both in terms of activities and the partners involved. Fire-fighters and conservators worked together to engage the entire civil protection sector in the city, and to involve the local community through a disaster imagination game and InSight workshops. Moreover, the project has grown into a national programme for fire mitigation in heritage sites, supported by both the Ministry of Culture and the Croatian Fire Association.

Made available in DSpace on 2022-04-29T08:37:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Twelve dose-response trials were conducted to estimate lysine (Lys) and arginine (Arg) requirements of male and female broilers in the starter (1–14 days of age), grower (15–28 days of age), and finisher (29–42 days of age) phase. In each trial, 640 birds were randomly assigned to one of eight treatments (Lys or Arg levels) with four replicates of 20 birds. In Lys trials, for both sexes, digestible (dig) Lys concentration in feeds ranged from 8.73 to 17.5 g/kg in the starter phase, 7.80–15.7 g/kg in the grower phase, and 6.40–12.8 g/kg in the finisher phase. In Arg trials, for both sexes, the dietary dig Arg concentrations investigated ranged from 10.9 to 18.7 g/kg in the starter phase, 8.38 a 16.8 g/kg in the grower phase, and 6.85–13.7 g/kg in the finisher phase. Performance and protein gain (PG) data were fitted to linear-response plateau (LRP), curvilinear-response plateau (CRP), and quadratic polynomial (QP) regression models to estimate the dig Lys and Arg intake required to optimize the responses assessed. For each phase, average daily gain (ADG) was maximized at 0.415, 1.38, 1.79 g dig Lys/day and 0.457, 1.48, and 2.11 g dig Arg/day in male broiler chickens and 0.415, 1.21, and 1.40 g dig Lys/day and 0.446, 1.34, and 1.89 g dig Arg/day in female. For male birds, PG was maximum at 0.496, 1.63, and 1.72 g dig Lys/day, whereas for female birds, maximum values were 0.528, 1.30, and 1.80 g dig Lys/day. In Arg trials, maximum protein gain was reached at 0.518, 1.36, and 2.29 g dig Arg/day in male, and 0.474, 1.28, and 2.03 g Arg/day in female, respectively. The Lys and Arg values reported in this study may be used as a reference to formulate feeds and achieve a maximum response. Department of Animal Science Faculty of Agrarian and Veterinary Science (FCAV) São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N Aquaculture Center of São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N Production Systems Natural Resources Institute Finland (Luke) Department of Animal Science Faculty of Agrarian and Veterinary Science (FCAV) São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N Aquaculture Center of São Paulo State University (Unesp), Via de acesso Prof. Paulo Donato Castellane, S/N CNPq: 142222/2018-6 FAPESP: 2013/25761-4

The paper features linguistic and creative foundations in the German comic book "Dig, Dag, Digedag". Modern linguacultural, cognitive studies, and discursive practices are aimed at studying comics, which are a series of drawings with brief accompanying texts. However, comic books consist of two components – verbal and nonverbal, which means that graphic novels and strips have linguacreative foundations. The author performed philological and semiotic analyzes to identify the linguistic and creative foundations of the German comic book. The algorithm of the philological analysis included literary description of the time and place, the most original and interesting scenes in several editions, lexical expressive means and stylistic devices. The semiotic analysis featured the graphics related to the non-verbal component. The linguistic and creative foundations of the comic are manifested in original plots that allow its readers to escape from everyday and political problems through fun, exciting, and informative trips to Ancient Rome, Sicily, ancient Arab countries, the Moon and Mars, as well as to an uninhabited island. The carefully selected scientific and mundane knowledge is transmitted through verbal means and comic book graphics, making young readers expand their horizon. The use of such tools as hyperbole, metaphor, pun, as well as diverse vocabulary within the text of the comic, also suggests linguistic creativity of the German comic book "Dig, Dag, Digedag".

A series of 4-exo-dig cyclocarbopalladations has been efficiently used to produce molecular complexity in a straightforward manner. Strained 1,2-cyclobutanediols are rapidly obtained, usually under microwave irradiation, in high yields. In many cases, the cyclocarbopalladation cascade reaction is associated with 6π- or 8π-electrocyclic reactions. Polycyclic skeletons of unnatural or natural products can be prepared in a few steps from simple starting materials. Very strained aromatic polycycles, the taxane framework, cyclooctatrienes, cyclooctatetraenes, fenestranes, and fenestrenes have been obtained using this methodology.

Digoxin (DIG) is a positive inotropic drug with a narrow therapeutic window that is used in the clinic for heart failure. The active efflux transporter of DIG, P-glycoprotein (P-gp), mediates DIG absorption and excretion in rats and humans. Up to date, several studies have shown that the ginger and Poria extracts in Zhenwu Tang (ZWT) affect P-gp transport activity. This study aimed to explore the effects of ZWT on the tissue distribution and pharmacokinetics of DIG in rats. The deionized water or ZWT (18.75 g/kg) was orally administered to male Sprague–Dawley rats once a day for 14 days as a pretreatment. On day 15, 1 hour after receiving deionized water or ZWT, the rats were given the solution of DIG at 0.045 mg/kg dose, and the collection of blood samples was carried out from the fundus vein or excised tissues at various time points. HPLC-MS/MS was used for the determination of the DIG concentrations in the plasma and the tissues under investigation. The pharmacokinetic interactions between DIG and ZWT after oral coadministration in rats revealed significant reductions in DIG Cmax and AUC0-∞, as well as significant increases in T1/2 and MRT0-∞. When coadministered with ZWT, the DIG concentration in four of the investigated tissues statistically decreased at different time points except for the stomach. This study found that combining DIG with ZWT reduced not only DIG plasma exposure but also DIG accumulation in tissues (heart, liver, lungs, and kidneys). The findings of our study could help to improve the drug's validity and safety in clinical applications and provide a pharmacological basis for the combined use of DIG and ZWT.

Multi-modal cues presented in videos are usually beneficial for the challenging video-text retrieval task on internet-scale datasets. Recent video retrieval methods take advantage of multi-modal cues by aggregating them to holistic high-level semantics for matching with text representations in a global view. In contrast to this global alignment, the local alignment of detailed semantics encoded within both multi-modal cues and distinct phrases is still not well conducted. Thus, in this paper, we leverage the hierarchical video-text alignment to fully explore the detailed diverse characteristics in multi-modal cues for fine-grained alignment with local semantics from phrases, as well as to capture a high-level semantic correspondence. Specifically, multi-step attention is learned for progressively comprehensive local alignment and a holistic transformer is utilized to summarize multi-modal cues for global alignment. With hierarchical alignment, our model outperforms state-of-the-art methods on three public video retrieval datasets.

A gold(I)-catalyzed 6-endo-dig cyclization of aromatic 1,5-enyne was developed to synthesize 2-(naphthalen-2-yl)aniline. The functional group tolerance of this cyclization was examined systematically and a possible mechanism was proposed. The derivatization of 2-(naphthalen-2-yl)aniline was carried out to facile access to benzo[α]carbazole, benzo[c,h]cinnoline and dibenzo[i]phenanthridine derivatives in a divergent way.

MAPK pathway activation has been recurrently observed in desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA) with reported disproportionally low mutation allele frequencies relative to the apparent high tumor content, suggesting that MAPK pathway alterations may be subclonal. We sought to expand the number of molecularly profiled cases and investigate if tumor cell composition could account for the observed low mutation allele frequencies. Molecular (targeted neuro-oncology next-generation sequencing/RNA sequencing and OncoScan microarray) and immunohistochemical (CD68-PGM1/CD163/CD14/CD11c/lysozyme/CD3/CD20/CD34/PD-L1) studies were performed in 7 DIG. Activating MAPK pathway alterations were identified in 4 (57%) cases: 3 had a BRAF mutation (V600E/V600D/V600_W604delinsDQTDG, at 8%–27% variant allele frequency) and 1 showed a TPM3-NTRK1 fusion. Copy number changes were infrequent and nonrecurrent. All tumors had at least 30% of cells morphologically and immunophenotypically consistent with microglial/macrophage lineage. Two subtotally resected tumors regrew; 1 was re-excised and received adjuvant treatment (chemotherapy/targeted therapy), with clinical response to targeted therapy only. Even with residual tumor, all patients are alive (median follow-up, 83 months; 19–139). This study further supports DIG as another MAPK pathway-driven neuroepithelial tumor, thus expanding potential treatment options for tumors not amenable to surgical cure, and suggests that DIG is a microglia/macrophage-rich neuroepithelial tumor with frequent low driver mutation allele frequencies.

A study was conducted to determine if increasing digestible (dig) amino acid (AA) density or feed allocation of starter diets fed to broilers receiving coccidiosis vaccination can ameliorate poor cumulative growth performance and reduce meat yield. A total of 1,600 Yield Plus Ross × Ross 708 male broilers were assigned to a 2 × 3 factorial arrangement of dig AA density [moderate (1.15% dig Lys) and high (1.25% dig Lys)] and feed allotment (0.45, 0.73, and 1.00 kg/bird) with 2 positive control treatments during the starter period. Diets were formulated to essential AA ratios relative to dig Lys. Vaccinated birds received a 1x dosage of Coccivac- B52 prior to placement, whereas non-vaccinated birds in the positive control groups were fed diets containing diclazuril. Following consumption of the starter diets, birds were provided common grower and finisher diets. Broilers fed the high AA density diet during the starter period had higher cumulative BW gain and lower cumulative feed conversion ratios (P

Activity level, or the amount of action/interaction with a product, can be an indication of interest in a product category and influences purchases. Our goal was to assess the overall market for landscape plants using consumers’ activity level from the active/passive continuum proposed by Pine and Gilmore (2011). An online survey instrument was administered to invitees from a national online panel from 7 to 13 Sept. 2016 yielding 1543 useful responses. Factor analysis of 23 items adapted from a previous study revealed five factors, including one active factor and a separate passive factor. These two factors were used in the present study as a basis for a k-means cluster analysis. Two clusters emerged and were labeled “Active Engagement” and “Obligatory Passive Engagement” in landscape activities. We compared cluster means for all five factors and found the Active cluster purchased more plants of all types as well as had greater landscape pride and desire for a low (water) input landscape. Members of the Active cluster were from higher income and education households which were slightly larger and more likely to have Caucasian residents compared with the Passive cluster. In practice, retail employees and landscape professionals might initially ask about consumers’ activity level desired in the landscape as a screening question. Subsequent assistance in design and/or plant selection/purchase could then be tailored toward the desired activity level.

A series of novel 3-methylphosphonylated [1,2,4]triazolo[4,3-a]pyridines was accessed through a 5-exo-dig-type cyclization of chloroethynylphosphonates and commercially available N-unsubstituted 2-hydrazinylpyridines. In addition, 3-methylphosphonylated [1,2,4]triazolo[4,3-a]quinolines and 1-methylphosphonylated [1,2,4]triazolo[3,4-a]isoquinolines were synthesized in a similar manner. The presence of a NO2 group in the starting hydrazinylpyridine induces a Dimroth-type rearrangement leading to 2-methylphosphonylated [1,2,4]triazolo[1,5-a]pyridines.

The present study planned to dig the potential impacts of long non-coding RNA B3GALT5-AS1 in acute pancreatitis (AP). A total of 66 patients who were diagnosed with AP using ultrasonic imaging were enrolled in the study. Expression levels of B3GALT5-AS1 in the serum of AP patients were determined. Afterwards, rat pancreatic AR42J acinar cells were disposed with caerulein to produce AP-like injury. The role and molecular mechanisms of B3GALT5-AS1 in AP were explored through in vitro cell experiments. The levels of lncRNA B3GALT5-AS1 were observed to be lessened in patients with AP relative to healthy controls. In addition, caerulein was observed to induce injuries in the AR42J cells (depressed cell viability, enhanced cell apoptosis, cytokines production, and levels of amylase). Overexpression of B3GALT5-AS1 alleviated the caerulein-produced injury in the AR42J cells. Moreover, it was determined that miR-203 showed a downside expression by B3GALT5-AS1 regulation, and the overexpression of B3GALT5-AS1 retrained caerulein-produced injury through the suppression of miR-203. In addition, it was observed that miR-203 lessened the level of nuclear factor interleukin-3 (NFIL3) and that NFIL3 was targeted by miR-203. Lastly, the impacts of B3GALT5-AS1 on caerulein-induced cell injury were manifested through the NF-κB signalling pathway. The data from the present study revealed that in patients with AP, B3GALT5-AS1 is expressed in reduced amounts. Overexpression of B3GALT5-AS1 may alleviate caerulein-induced cell injury in AR42J cells through the regulation of miR-203/NFIL3 axis and by inhibiting the activation of the NF-κB signals.

This study was carried out to evaluate the effect of different digestible arginine-to-lysine (dig Arg:Lys) ratio in broiler diets on the occurrence of breast myopathies, productivity, and meat quality traits. A total of 1,755 1-day-old Ross 308 male chicks was randomly divided in 3 experimental groups (9 replications/group): CON, fed a 4 feeding-phases commercial diet (dig Arg:Lys ratio = 1.05, 1.05, 1.06, 1.07, respectively in starter, grower I, grower II and finisher phase), and ARG2 and ARG3 groups fed CON diet supplemented respectively with 20 and 30% higher levels of crystalline L-arginine (dig Arg:Lys ratio = 1.25, 1.25, 1.26, 1.27 and 1.35, 1.35, 1.36, 1.37, respectively). Productive performance was recorded throughout the rearing cycle. At processing (43 d), breasts (n = 150/group) were randomly collected to evaluate the incidence and severity of white striping (WS), wooden breast (WB), and spaghetti meat (SM) defects (3- points scale).Meat quality traits, such as color, pH, drip and cook losses, marinade performances, and proximate composition were determined on 12 fillets/group. Although productive performance and meat quality traits resulted not significantly affected, the occurrence of some breast myopathies was modified by the dietary treatments. ARG2 and ARG3 exhibited a significantly higher percentage of breast without WS compared to CON (28 and 41 vs. 17%, respectively; P < 0.001). ARG3 reported the lowest percentage of breasts with severe WS (11 vs. 27 and 31%, respectively for ARG3, ARG2, and CON; P < 0.001) and the highest of those showing no SM abnormality (81 vs. 69 and 65%, respectively for ARG3, ARG2, and CON; P < 0.01). Furthermore, a numerical reduction of breasts with severe WB was observed in ARG3 (12 vs. 25 and 19%, respectively for ARG3, ARG2, and CON; P = 0.12). In conclusion, the dietary supplementation of arginine to increase the dig Arg:Lys ratio by about 30% in respect to the current recommendations for broiler chickens has positive implications on the occurrence of some breast meat abnormalities.

At the time of the Tohoku Earthquake and Tsunami in Japan (also known as the Great East Japan Earthquake) on March 11th 2011, it is well known that the judgment and behavior of school teachers on that day had a great influence on the safety of school children and students. The improvement of disaster prevention education and disaster prevention countermeasures at schools requires the improvement of awareness as well as a better knowledge of disaster prevention among the teachers themselves. Meanwhile, at the educational level in Japanese schools, the work rate of teachers is hectic due to countless tasks, and there have been stress-related problems that illustrate the necessity of reducing excessive workloads. Based on these circumstances, it can be pointed out that it is important to more effectively conduct teacher training on disaster prevention education and disaster prevention countermeasures. This research conducted investigations in order to devise better teacher training vis-a-vis practical disaster prevention, to properly comprehend the actual condition of teacher training in each prefecture, and to find successful cases. We also conducted a questionnaire-survey related to the above objectives for each prefectural board of education in Japan. As a result of these surveys, we discovered the following information. Most prefectures with a history of severe disasters and those based in the precarious Nankai Trough/ megathrust zone responded to the questionnaire-survey. These areas are categorized as Types A, B and Cl (according to the earthquake risk). In these areas, the law states that prefectures must take disaster prevention and preparation measures. During the research, those prefectures in Japan without a recent history of disasters (Type C2) did not respond to the questionnaire-survey. The research also found that only a few prefectures organized disaster mitigation and preparations for all its teachers. Even in those prefectures that fully prepare and train all their teachers under programs like the "training for newly appointed teachers" and "training for middle-level teachers " (the so-called "ten-years recurrent training"), some but not all teachers participate. This is despite the fact that the participation of all teachers is compulsory under Japanese law. Even among teachers who are school principals and school vice-principals, not all have participated in the required training. Another problem is that training often involves the attendees just sitting passively while listening to lectures. Only a small number of prefectures hold active practical training programs such as the Disaster Imagination Game (DIG) I Hinanjo Unei Game (HUG).

Dig well is one of the clean water supply sources for the society in the countryside, and urban areas. Dig well provides water originating from the soil layer that is relatively close with ground level, therefore susceptible to contamination through seepage originating from human waste, animals, or for domestic household needs. Dig well as clean water source must be supported by construction conditions, location conditions to build a dig well, this thing is needed so that the quality of dig well’s water is safe according to the rules set. The research purpose is to know the physical condition of dig well with incidence of diarrhea in infants at the working area of Kabila Community Health Centre Bone Bolango District. This research used quantitative method, the research instrument uses observation sheet and questionairres to measure the physical condition of dig well. The result show that there was a significant effect between dig well lip height variable, wall of the dig well, septic tank distance with dig well by the incidence of diarrhea in infants. For the variable of dig well floor and closing condition of dig well obtains the result that there was no influence with the incidence of diarrhea in infants. Keywords: Physical condition, Dig well, Diarrhea

Desmoplastic infantile ganglioglioma (DIG) is a rare supratentorial brain tumor, which is usually diagnosed before the age of two and has a favorable prognosis. To date, only a few cases have been reported in the literature. We report a case of DIG in a three-month-old boy who presented to our pediatric emergency department with decreased activity and excessive crying. This case report highlights the computed tomography (CT) and magnetic resonance imaging (MRI) findings of this rare tumor. Non-contrast CT scan findings in our case initially masqueraded as an extra-axial arachnoid cyst; however, the MRI findings after contrast agent administration were typical for the diagnosis of DIG.

In a recent issue of Cell Reports Physical Science, Ye et al. presents a visible-light-promoted cascade involving full cleavage of a triple bond. Two heterocyclic cores, 2-hydroxy-3-indolinones and benzoxazinones, are selectively formed in good yields. Interestingly, these novel transformations appear to involve a sequence of two unusual radical endo-cyclizations.

We herein report the design, synthesis, and photophysical characterization of extended and rigid coumarinyl derivatives showing large two-photon sensitivities (δaΦu ≤ 125 GM) at 740 and 800 nm. To efficiently synthesize these complex photoremovable protecting groups (PPGs), we used step-economic domino reactions. Moreover, those new coumarinyl PPGs display unique bathochromic shifts (≤100 nm) of the uncaging subproducts as a result of the formation of a more conjugated fulvene moiety.

Background. Nowadays, acute intracerebral hemorrhage stroke (AICH) still causes higher mortality. Liangxue Tongyu Formula (LXTYF), originating from a traditional Chinese medicine (TCM) prescription, is widely used as auxiliary treatment for AICH. Objective. To dig into the multicomponent, multitarget, and multipathway mechanism of LXTYF on treating AICH via network pharmacology and RNA-seq. Methods. Network pharmacology analysis was used by ingredient collection, target exploration and prediction, network construction, and Gene Ontology (GO) and KEGG analysis, with the Cytoscape software and ClusterProfiler package in R. The RNA-seq data of the AICH-rats were analyzed for differential expression and functional enrichments. Herb-Compound-Target-Pathway (H-C-T-P) network was shown to clarify the mechanism of LXTYF for AICH. Results. 76 active ingredients (quercetin, Alanine, kaempferol, etc.) of LXTYF and 376 putative targets to alleviate AICH (PTGS2, PTGS1, ESR1, etc.) were successfully identified. The protein-protein interaction (PPI) network indicated the important role of STAT3. The functional enrichment of GO and KEGG pathway showed that LXTYF is most likely to influence MAPK and PI3K-Akt signaling pathways for AICH treatment. From the RNA-seq of AICH-rats, 583 differential mRNAs were identified and 14 of them were consistent with the putative targets of LXTYF for AICH treatment. The KEGG pathway enrichment also implied that the MAPK signaling pathway was the most correlated one among all the related signaling pathways. Many important targets with expression changes of LXTYF for AICH treatment and their related pathways are great markers of antioxidation, anti-inflammatory, antiapoptosis, and lowering blood pressure, which indicated that LXTYF may play mutiroles in the mechanisms for AICH treatment. Conclusion. The LXTYF attenuates AICH partially by antioxidation, anti-inflammatory, and antiapoptosis and lowers blood pressure roles through regulating the targets involved MAPK, calcium, apoptosis, and TNF signaling pathway, which provide notable clues for further experimental validation.

Human papillomavirus (HPV) is a dsDNA virus and its high-risk subtypes increase cancer risks. Yet, the mechanism of HPV infection and pathogenesis still remain unclear. Therefore, understanding the molecular mechanisms, and the pathogenesis of HPV are crucial in the prevention of HPV related cancers. In this study, we analyzed cervix squamous cell carcinoma (CESC) and head and neck carcinoma (HNSC) combined data to investigate various HPV induced cancer common feature. We showed that epidermal growth factor receptor (EGFR) was downregulated in HPV positive (HPV+) cancer, and that HPV+ cancer patients exhibited better prognosis than HPV negative (HPV−) cancer patients. Our study also showed that TP53 mutation rate is lower in HPV+ cancer than in HPV− cancer and that TP53 can be modulated by HPV E7 protein. However, there was no significant difference in the expression of wildtype TP53 in both groups. Subsequently, we constructed HPV-human interaction network and found that EGFR is a critical factor. From the network, we also noticed that EGFR is regulated by HPV E7 protein and hsa-miR-944. Moreover, while phosphorylated EGFR is associated with a worse prognosis, EGFR total express level is not significantly correlated with prognosis. This indicates that EGFR activation will induce a worse outcome in HPV+ cancer patients. Further enrichment analysis showed that EGFR downstream pathway and cancer relative pathway are diversely activated in HPV+ cancer and HPV− cancer. In summary, HPV E7 protein downregulates EGFR that downregulates phosphorylated EGFR and inhibit EGFR related pathways which in turn and consequently induce better prognosis.ImportanceAlthough HPV infection has been studied in various cancer types, there are only limited studies that have focused on the common effect of HPV related cancer. Consequently, this study focused on CESC and HNSC, two cancer types with high HPV infection proportion in cohort, thereby, intending to dig out the common effects and mechanisms of HPV+ cancers.Unlike some virus-human interaction prediction studies, the P-HIPSter database provides virus-human protein interaction based on protein structure prediction. Through this data, our interaction network was able to uncover previously unnoticed protein interactions. Our finding revealed that HPV infection caused various gene expression differences, and a great amount of which interact with EGFR, a cancer related gene. Therefore, since EGFR is associated with HPV+ cancer patients’ survival, some FDA proved EGFR inhibitors would be potential anti-HPV drugs.

The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.

Hepatitis A virus (HAV) is mainly transmitted via contaminated food or water or through person-to-person contact. Here, we describe development and evaluation of a reverse transcription droplet digital PCR (RT-ddPCR) and reverse transcription real-time PCR (RT-qPCR) assay for detection of HAV in food and clinical specimens. The assay was evaluated by assessing limit of detection, precision, matrix effects, sensitivity and quantitative agreement. The 95 % limit of detection (LOD95 %) was 10 % higher for RT-ddPCR than for RT-qPCR. A Bayesian model was used to estimate precision on different target concentrations. From this, we found that RT-ddPCR had somewhat greater precision than RT-qPCR within runs and markedly greater precision between runs. By analysing serum from naturally infected persons and a naturally contaminated food sample, we found that the two methods agreed well in quantification and had comparable sensitivities. Tests with artificially contaminated food samples revealed that neither RT-ddPCR nor RT-qPCR was severely inhibited by presence of oysters, raspberries, blueberries or leafy-green vegetables. For this assay, we conclude that RT-qPCR should be considered if rapid, qualitative detection is the main interest and that RT-ddPCR should be considered if precise quantification is the main interest. The high precision of RT-ddPCR allows for detection of small changes in viral concentration over time, which has direct implications for both food control and clinical studies.

Quorum quenching, which disrupts quorum sensing (QS) by either degradation of QS signals or interference of signal generation or perception, is a promising strategy for the prevention and control of QS-mediated bacterial infections. Diffusible signal factor (DSF) is widely conserved in many Gram-negative bacterial pathogens. In this study, we developed an efficient method for screening of highly active DSF degradation microorganisms. Among them, Pseudomonas sp. strain HS-18 showed a superior DSF degradation activity. Bioinformatics and genetic analyses showed that at least 4 genes, designated digA to digD, encoding fatty acyl coenzyme A ligase homologues, are responsible for DSF signal degradation. Interestingly, all 4 dig genes were induced by exogenous DSF, with digA being the most significantly induced. Expression of the dig genes in Xanthomonas campestris pv. campestris markedly reduced the accumulation of endogenous DSF, decreased production of virulence factors, and attenuated bacterial virulence on host plants. Similarly, application of strain HS-18 as a biocontrol agent could substantially reduce the disease severity caused by X. campestris pv. campestris. These results unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful genes and biocontrol agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens. IMPORTANCE Diffusible signal factor (DSF) represents a family of widely conserved quorum sensing signals involved in the regulation of virulence factor production in many Gram-negative bacterial pathogens. In this study, we developed a novel and efficient method for screening highly active DSF degradation microorganisms. With this method, we identified a bacterial isolate, Pseudomonas sp. strain HS-18, with a superb DSF degradation activity. We further found that strain HS-18 contains 4 genes responsible for DSF signal degradation, and significantly, these were induced by exogenous DSF molecules. These findings unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful methods, genes, and agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens.

Protocol for making DIG-labelled RNA probes suitable for in situ hybridisation

The Essential Thrombocythemia is a Chronic Philadelphia-negative Myeloproliferative Neoplasm characterized by a survival curve that is only slightly worse than that of age- and sex-adjusted healthy population. The criteria for diagnosis were reviewed in 2016 by WHO. The incidence varies from 0.2 to 2.5:100 000 people per year, with a prevalence of 38 to 57 cases per 100 000 people. The main characteristics of ET are the marked thrombocytosis and the high frequency of thrombosis. The spectrum of symptoms is quite wide, but fatigue results to be the most frequent. Thrombosis is frequently observed, often occurring before or at the time of diagnosis. The classification of thrombotic risk has undergone several revisions. Recently, the revised-IPSET-t has distinguished 4 risk classes, from very low risk to high risk. Driver mutations seem to influence thrombotic risk and prognosis, while the role of sub-driver mutations still remains uncertain. Antiplatelet therapy is recommended in all patients aged ⩾ 60 years and in those with a positive history of thrombosis or with cardiovascular risk factors, while cytoreductive therapy with hydroxyurea or interferon is reserved for high-risk patients.