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Abstract Interventions designed to improve medication adherence, and blood pressure control have not been effective globally. There is limited comprehensive understanding regarding the level of drug adherence to antihypertensive medications in Ethiopia, particularly in the study area. This study aimed to assess adherence to antihypertensive medication and associated factors among patients with hypertension on follow-up at public health facilities of Adama town, Oromia, Ethiopia. A multicenter cross-sectional study was conducted among 402 patients with hypertension from January 1 to February 30, 2022. The objectives of the study were explained to participants in the local language and written informed consent was obtained. The level of adherence was measured by Morisky Medication Adherence Scale. Data were entered into Epidata and exported to Statistical Package for the Social Science for analysis. Bivariable and multivariable logistic regression analyses were conducted to determine associations between independent variables and medication adherence. Adjusted Odds ratios with 95% confidence interval were estimated to assess the strength of associations. Statistical significance was declared at a P-value

Abstract The prevalence of obesity is rapidly increasing, contributing to 678 million obese adults and rapidly increasing in lower-income countries. This study assessed the magnitude of central obesity and associated factors among public service office employees in Adama Town in the Oromia Regional State in Ethiopia. An institutional-based cross-sectional study was conducted from January 1 to February 26, 2020, among 590 public service employees. The data were collected by using interviewer-administered questionnaires and anthropometric measurements. The data were coded, entered, cleaned, and entered into Epi Info version 7, and subsequently exported to SPSS version 26 for statistical analysis. Binary logistic regression was used to check the associations between the explanatory and outcome variables. The adjusted odds ratio at a 95% confidence interval was used to estimate the strength of associations. A P value

Structural strengthening solutions typically employ externally bonded reinforcement (EBR) systems with carbon fiber (CF) sheets because of these materials’ lightweight, corrosion resistance, and electromagnetic immunity. However, elevated ambient temperatures can negatively impact the mechanical performance of EBR, as documented in the literature. Therefore, American bridge design specifications assume a concrete surface temperature of 60 °C (140 °F), which reflects the extreme conditions that bridge structures may experience, particularly in regions with intense sunlight and high ambient temperatures. Therefore, sustainable design solutions require a reliable quantification of the effects of temperature. This study extends a recently developed bending test layout and builds the analytical modeling procedure to quantify the stiffness degradation under repeated temperature and mechanical loads. The explicitly obtained equivalent stresses in the tensile concrete determine the stiffness measure independent of the loading condition and sequence. This test program used 12 laboratory samples. All beam samples faced the mechanical load repetitions and entire unloading. Three selected beams were additionally treated at 60 °C for 10 hours in a heating chamber between the loading repetitions. These tests identified a substantial (three times) decrease in the bonding performance of the CF sheets after eight heating rounds. Scanning electron microscopy (SEM) identified the corresponding microstructure changes.

Background and aim: Agarikon pill (AGKP), a traditional Chinese herbal formula, and has been used for chronic obstructive pulmonary disease (COPD) treatment clinically. However, the active components and exact pharmacological mechanisms are still unclear. We aimed to investigate the therapeutic effects and mechanisms of AGKP on COPD and identify the chemical constituents and active compounds. Experimental procedure: The chemical components of AGKP were identified by ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Network pharmacology analysis was performed to uncover the potential mechanism of AGKP. The efficiencies and mechanisms of AGKP were further confirmed in COPD animal models. Results and conclusion: Ninety compounds from AGKP, such as flavonoids, triterpenoids, saponins, anthracenes, derivatives, phenyl propionic acid, and other organic acids, were identified in our study. AGKP improved lung function and pathological changes in COPD model rats. Additionally, inflammatory cell infiltration and proinflammatory cytokine levels were markedly reduced in COPD rats administered AGKP. Network pharmacology analysis showed that the inflammatory response is the crucial mechanism by which AGKP exerts therapeutic effects on COPD rats. WB and PCR data indicated that AGKP attenuated the inflammatory response in COPD model rats. AGKP reduces the pulmonary inflammatory response through the PI3K/AKT and MAPK TLR/NF-κB signaling pathways and exerts therapeutic effects via inhibition of inflammation and mucus hypersecretion on COPD model rats.

Background Cervical cancer (CCa) is the second most common type of cancer and a leading cause of death among adult women in Ethiopia. However, at the moment, there is a lack of evidence that can be generalizable as a whole to the country regarding the uptake of cervical cancer screening. Objective The aim of this review was to assess the pooled estimated uptake of CCa and to identify the major barriers to cervical cancer screening (CCS) uptake among adult women in Ethiopia. Method The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) with a registration number of CRD42022353954. The data were searched electronically using Google Scholar, PubMed, Medline, and Web of Science search engines. The heterogeneity of the literature was assessed using Cochran’s (Q) test and Higgin’s and Thomson’s (I 2 ) statistic. The Rosenthal approach, Fail-safe N method, Egger’s test with a P -value

Abstract Diabetes mellitus (DM) is a prominent global health challenge, characterized by a rising prevalence and substantial morbidity and mortality, especially evident in developing nations. Although DM can be managed with self-care practices despite its complexity and chronic nature, the persistence of poor self-care exacerbates the disease burden. There is a dearth of evidence on the level of poor self-care practices and contributing factors among patients with DM in the study area. Thus, this study assessed the proportion of poor self-care practices and contributing factors among adults with type 2 DM in Adama, Ethiopia. An institution-based cross-sectional study was conducted among 404 patients. Self-care practice was assessed by the summary of diabetes self-care activities questionnaires. Binary logistic regression was used to identify factors associated with poor self-care practices. An adjusted odds ratio with a 95% confidence interval was used to assess the strength of associations. The statistical significance was declared for a p-value

Terminalia chebula Retz. is commonly used in the treatment of diabetes, but its specific ingredients and hypoglycaemic mechanisms remain unclear. In this study, spectrum-effect relationships between common peaks of fingerprint and DPPH, ABTS, PTP1B, α-glucosidase, were used to screen six compounds as the potential hypoglycemic ingredients. Molecular docking studies were conducted on chebulagic acid, chebulinic acid and punicalagin, which were identified by reference standard, revealing the potent in teractions between these bioactive substances and the PTP1B, α-glucosidase protein. Additionally, the cellular level results showed that punicalagin displayed stronger inhibition of PTP1B and α-glucosidase, with IC50 values of 0.0236 and 0.335 μg/mL, respectively, while improving glucose consumption and intracellular glycogen content of insult-resistant L6 muscle cell, and the hypoglycemic effect was achieved by activating the PI3K/AKT signaling pathway. This study demonstrated that T. chebula has the potential to become a hypoglycemic functional food, and offers a strategy for characterization hypoglycemic ingredients.

ObjectiveThis study aimed to estimate the time to viral load suppression and identify its predictors among HIV patients receiving antiretroviral therapy (ART) in the Gebi Resu zone, Afar Region, Ethiopia, 2023.SettingThe study was conducted at public health facilities in the Gebi Resu zone of the Afar region.Study designThis study is a facility-based, retrospective follow-up study.Study participantsThis study included 298 people living with HIV who were receiving ART services at selected health facilities in the Gebi Resu zone. Data were collected by reviewing patient records using a structured checklist. Bivariate and multivariate Cox regression analyses were conducted to assess the relationship between variables and control for confounders.ResultsThe incidence rate of viral load suppression was 9.46 per 100 person-months. The median time to viral load suppression was 7.7 months, with an interquartile range of 3.8 months (IQR = 6.47–10.27). Patients at clinical stages 3 and 4 [AHR = 0.67, 95%CI (0.47, 0.96)], those who received cotrimoxazole prophylaxis therapy [AHR = 1.47, 95%CI (1.12, 1.92)], and patients with poor drug adherence [AHR = 0.40, 95%CI (0.18, 0.90)] were significantly associated with time to viral load suppression among people on antiretroviral therapy.ConclusionThe time to viral load suppression and the median time to viral load suppression among people living with HIV on ART were shorter than those observed in many developing and developed countries. Clinical stage, cotrimoxazole prophylaxis therapy, and drug adherence were significant predictors of viral load suppression.

Abstract Amides are important intermediates in organic chemistry and the pharmaceutical industry, but their low reactivity requires catalysts and/or severe reaction conditions for esterification. Here, a novel approach was devised to convert amides into esters without the use of transition metals. The method effectively overcomes the inherent low reactivity of amides by employing dimethylsulfate-mediated reaction to activate the C-N bonds. To confirm the proposed reaction mechanism, control experiments and density functional theory (DFT) calculations were conducted. The method demonstrates a wide array of substrates, including amides with typical H/alkyl/aryl substitutions, N,N-disubstituted amides, amides derived from alkyl, aryl, or vinyl carboxylic acids, and even amino acid substrates with stereocentres. Furthermore, we have shown the effectiveness of dimethylsulfate in removing acyl protective groups in amino derivatives. This study presents a method that offers efficiency and cost-effectiveness in broadening the esterification capabilities of amides, thereby facilitating their increased utilization as synthetic compounds in diverse transformations.

Background: Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves β-catenin plays a crucial role in promoting the melanin production in melanocytes. Targeted inhibition of the Janus kinase JAK-STAT pathway can effectively diminish the secretion of the chemokine C-X-C motif ligand CXCL10, thereby safeguarding melanocytes. Ferula has been applied as a treatment regimen for a long period; however, its use for the treatment of vitiligo has not been previously documented. Methods: CCK-8 assay, Intracellular melanin content assay, Tyrosinase activity assay, Western blotting, qRT-PCR, and ELISA methods were employed. Using molecular docking verified the inhibitory effects of feshurin on the JAK1. Results: The sesquiterpene coumarin feshurin was separated from Ferula samarcandica. Feshurin was shown to induce GSK-3β phosphorylation, resulting in the translocation of β-catenin into the nucleus. This translocation subsequently upregulated the transcription of microphthalmia-associated transcription factor (MITF), leading to increased tyrosinase activity and melanin production. In addition, feshurin inhibited the production of chemokine CXCL10 via the JAK-STAT signaling pathway, which was verified by molecular docking. Conclusions: Based on these findings, it can be concluded that feshurin exhibits significant potential for the development of novel anti-vitiligo therapeutics.

Background: Inadequate breastfeeding can lead to significant morbidity, mortality, and long-term adverse health outcomes. Key messages promoting optimal breastfeeding are integral to Essential Nutritional Action, aimed at improving children’s nutritional status, especially those under the age of two. However, there is a dearth of data regarding the extent to which lactating mothers adhere to these key messages and the associated factors. Therefore, this study aimed to assess the level of practice of key messages for optimal breastfeeding and identify associated factors among lactating mothers living in the Boset District, Oromia, Ethiopia. Methods: A community-based cross-sectional study was conducted among 418 lactating mothers from January 1st to February 28th, 2022. The participants were selected using a systematic random sampling technique, and data were collected through interviewer-administered questionnaires. The collected data were entered into Epi Info version 7 and exported to SPSS version 25 for analysis. Binary logistic regressions were performed to examine the association between independent and dependent variables. Adjusted Odds Ratios with a 95% confidence interval were used to estimate the strength of the associations and statistical significance was declared at a p -value

In many African countries, land access and tenure insecurity pose significant challenges to agriculture, in particular for the youth. As the farming population ages, young people are expected to take over, but they don't often show much interest in farming, which could harm the future of agriculture in Africa, where the population is the youngest. Land reforms and titling programs are suggested as amongst strategies to make agriculture more attractive to investors and promote youth involvement. As a result, majority African countries undertook reforms such as land titling, ownership mapping and market facilitation as policy prescriptions for promoting youth involvement in agriculture. Nonetheless, the impact of these programs is not well documented in the body of literature thus constraining policy decisions. This study examines the impact of land titling on youth participation in agriculture in Tanzania, using 2020/2021's wave of Tanzania national panel survey data with a sample size of 2725 youth households from 419 enumeration areas. The study finds that land titling is a critical factor in promoting youth participation in agriculture in Tanzania, with young people who have titled land tending to allocate more resources (time) to farming activities. The study also identified farm size, educational level, and land dispute experience as significant factors influencing youth participation in agriculture. Based on these findings, the study recommends interventions to promote youth participation in agriculture in Tanzania, including investing in land titling programs that specifically target young people and promoting educational programs that equip young people with foundational skills. The study also highlights the need for tailored interventions that address the specific needs of different groups of young people. Overall, the study underlines the importance of promoting youth participation in agriculture in Tanzania and by extension to other African countries to contribute to food security and rural development.

Abstract Background Xuelian granule (XL), a traditional Chinese medicine (TCM) formula, has been used for the treatment of diabetic nephropathy for a long time as a hospital preparation. Because the active ingredients in the XL that can help to treat diabetic nephropathy are still unclear, which limits the interpretation for its pharmacological mechanism, further development and subsequent study on the material basis of its efficacy. Methods In this study, a screening method based on inhibition activity against aldose reductase (AR) was employed for activity-directed chemical analysis of XL using ultra-high performance liquid chromatography combined with quadrupole-orbitrap high resolution mass spectrometry (UHPLC-Q-orbitrap-HRMS) technique. Results A total of 178 compounds, including 46 terpenes, 47 organic acids, 25 flavonoids, 29 phenylethanoid glycosides, and 31 other types, were tentatively identified from XL which might responsible for its AR inhibition activity. Conclusion This is the first study for a systematic, rapid, and accurate qualitative analysis of XL. This research provides a scientific and experimental basis for further researches on pharmacodynamics material basis and quality control of XL.

Abstract Background Central obesity is excessive accumulation of fat around the abdomen, which is associated with the risk of coronary heart and cerebrovascular diseases. This study determined the magnitude of central obesity among adult patients using the waist-to-hip ratio, which has a superior capacity to measure the risk of developing non-communicable diseases compared to the body mass index used in previous studies in Ethiopia. Methods Institutional-based cross-sectional study was conducted among a sample of 480 adults from April 1 to May 30, 2022. A systematic random sampling technique was used to select the study participants. Data were collected by using interviewer-administered structured questionnaires and anthropometric measurements. The data were entered into EPI INFO version 7 and analyzed by Statistical Software for Social Science Version 25. The associations between independent and dependent variables were checked using bivariate and multivariate logistic regression analyses. Adjusted odds ratio and 95% confidence interval were used to measure the strengths of the association. Statistical significance was declared at a P value of less than 0.05. Results The magnitude of central obesity in this study was 40% (51.2% and 27.4% among females and males, respectively (95% CI 36–44%)). Being a female (AOR = 9.5, 95% CI 5.22–17.9), age range 35–44 (AOR = 7.0, 95% CI 2.9–16.7), 45–64 years (AOR = 10.1, 95% CI4.0–15.2), married (AOR = 2.5, 95% CI 1.3–4.7), high monthly income (AOR = 3.3, 95% CI 1.5–7.3), high consumption of milk and milk products (AOR = 0.3, 95% CI 0.1–0.6), family history of obesity (AOR = 1.8, 95% CI 1.1–3.2) were significantly associated with central obesity among the study participants. Conclusion The magnitude of central obesity was higher in the study area. Sex, age, marital status, monthly income, consumption of milk and milk products, and family history of obesity were independent determinants of central obesity. Therefore, it is important to raise awareness about central obesity through behavior change communication that targets the high-risk population.

Marek’s disease virus (MDV) is an economic concern for the poultry industry due to its poorly understood pathophysiology. Purinergic receptors (PRs) are potential therapeutic targets for viral infections, including herpesviruses, prompting our investigation into their role in MDV pathogenesis. The current study is part of an experimental series analyzing the expression of PRs during MDV infection. To address the early or short-acting P2 PR responses during natural MDV infection, we performed an “exposure” experiment where age-matched chickens were exposed to experimentally infected shedders to initiate natural infection. In addition, select non-PR regulatory gene responses were measured. Two groups of naïve contact chickens (n = 5/breed/time point) from MD-resistant (White Leghorns: WL) and -susceptible (Pure Columbian) chicken lines were housed separately with experimentally infected PC (×PC) and WL (×WL) chickens for 6 or 24 h. Whole lung lavage cells (WLLC) were collected, RNA was extracted, and RT-qPCR assays were used to measure specific PR responses. In addition, other potentially important markers in pathophysiology were measured. Our study revealed that WL chickens exhibited higher P1 PR expression during natural infection. WL chickens also showed higher expression of P1A3 and P2X3 at 6 and 24 h when exposed to PC-infected chickens. P2X5 and P2Y1 showed higher expression at 6 h, while P2Y5 showed higher expression at 6 and 24 h; regardless of the chicken line, PC chickens exhibited higher expression of P2X2, P2Y8, P2Y10, P2Y13, and P2Y14 when exposed to either group of infected chickens. In addition, MDV infection altered the expression of DDX5 in both WL and PC groups exposed to PC-infected birds only. However, irrespective of the source of exposure, BCL2 and ANGPTL4 showed higher expression in both WL and PC. The expression of STAT1A and STAT5A was influenced by time and breed, with major changes observed in STAT5A. CAT and SOD1 expression significantly increased in both WL and PC birds, regardless of the source of infection. GPX1 and GPX2 expression also increased in both WL and PC, although overall lower expression was observed in PC chickens at 24 h compared to 6 h. Our data suggest systemic changes in the host during early infection, indicated by the altered expression of PRs, DDX5, BCL2, ANGPTL4, and other regulatory genes during early MDV infection. The relative expression of these responses in PC and WL chickens suggests they may play a key role in their response to natural MDV infection in the lungs and long-term pathogenesis and survival.

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but it also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for an HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. A mechanistic study using Biacore and docking analysis revealed that YZH-106 bound directly to the PreS2 domain of L- and M-HBsAg, thereby blocking their entry into the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provides the basis for the design of a novel compound therapy to target HBsAg against HBV infection.

Abstract Purinergic receptors (PRs) have been reported as potential therapeutic targets for many viral infections including herpesviruses, which urges the investigation into their role in Marek’s disease (MD), a herpesvirus induced cancer in chickens that is an important pathogen for the poultry industry. MD is caused by MD virus (MDV) that has a similar viral life cycle as human varicella zoster virus in that it is shed from infected epithelial skin cells and enters the host through the respiratory route. In this report, PR responses during natural MDV infection and disease progression was examined in MD-resistant white Leghorns (WL) and MD-susceptible Pure Columbian (PC) chickens during natural infection. Whole lung lavage cells (WLLC) and liver tissue samples were collected from chickens infected but showing no clinical signs of MD (Infected) or presenting with clinical disease (Diseased). RNA was extracted followed by RT-qPCR analysis with gene specific primers against members of the P1, P2X, and P2Y PR families. Differential expression (p

Abstract Background Land Tenure Formalization (LTF) is long advocated as a policy prescription that fosters growth and reduces poverty in developing countries. However, the empirical evidence on LTF effects is mixed and inconclusive, proving unclear implications for policy. A set of possible conceptual and methodological flaws arising from treating LTF as a dichotomy between formalized and non-formalized alongside potential selectivity biases are amongst the main explanations for the mixed and inconclusive results. Using Tanzania’s National Panel Survey data from the 2014/2015 wave and employing a Selectivity Corrected Multinomial Endogenous Switching Regression, this study models the development outcomes of LTF with clear distinction of LTF between customary and statutory land tenure systems in Tanzania. Findings The study finds that possession of formal land tenure certificates [Certificate of Customary Right of Occupancy (CCRO) or Certificate of Granted Right of Occupancy (CGRO)] improves perceived land tenure security, but the effect is relatively larger and more significant for CGRO holders than CCRO holders especially in economically high potential areas, where land is becoming more individualized and commoditized. With regard to credit access, our results show variations in the effects between general, formal, and informal credit access. While there is no significant effect of LTF on general access to credit, possessing a CGRO significantly reduces the uptake of informal credit and appears to improve access to formal credit. With regard to land investments, our results show positive and significant effects of LTF on organic and inorganic fertilizer use as well as trees and permanent crops investments, but only for CGRO plots. Conclusions The study concludes that the effects of LTF differ significantly between the land tenure systems, thus, treating LTF as a dichotomy between formalized and non-formalized is an oversimplification that could potentially mislead policy decisions. Therefore, the study recommends that the design, implementation and evaluation of LTF programs should recognize this distinction for greater clarity about LFT effects and more meaningful policy messages. The study, further, recommends strategic land policy interventions that aim to enhance land tenure security, especially in high potential areas for more socio-economically optimal outcomes of the interventions.

Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins. However, the underlying mechanism(s) remain not completely understood. The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well. Molecular docking simulations revealed that between catalytic core residues and the compound. The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), TYR-related protein-1 (TRP-1) and TRP-2 in B16 cells. Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells. Also in vivo glabridin therapy significantly reduced hyperpigmentation, epidermal thickening, roughness and inflammation induced by frequent UVA exposure in mice skins, thus beneficial for skin healthcare. These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin, rationalizing the application of the natural compound for skin healthcare.

Previously, from the tannic sumac plant (Rhus coriaria), we developed the Rutan 25 mg oral drug tablets with antiviral activity against influenza A and B viruses, adenoviruses, paramyxoviruses, herpes virus, and cytomegalovirus. Here, our re-purposing study demonstrated that Rutan at 25, 50, and 100 mg/kg provided a very effective and safe treatment for COVID-19 infection, simultaneously inhibiting two vital enzyme systems of the SARS-CoV-2 virus: 3C-like proteinase (3CLpro) and RNA-dependent RNA polymerase (RdRp). There was no drug accumulation in experimental animals’ organs and tissues. A clinical study demonstrated a statistically significant decrease in the C-reactive protein and a reduction of the viremia period. In patients receiving Rutan 25 mg (children) and 100 mg (adults), the frequency of post-COVID-19 manifestations was significantly less than in the control groups not treated with Rutan tablets. Rutan, having antiviral activity, can provide safe treatment and prevention of COVID-19 in adults and children.Clinical Trial RegistrationClinicalTrials.gov, ID NCT05862883.

Abstract Climate change and variability contribute to exacerbating poverty and social unrest in poor countries. Therefore, it becomes important to assess vulnerability and adaptation measures to raise awareness and monitoring of climate change adaptation policy for better decision-making. This research examines how farmers perceive their vulnerability and how they respond to climate change in the semi-arid Far North Region of Cameroon. Using both quantitative and qualitative approaches, data on perceptions with regards to vulnerability and adaptation responses to climate change related hazards were collected based on expert opinions, individual farmers’ interviews, and focus group discussion. The qualitative data were triangulated with direct observations in the field. The results reveal that farmers are mostly concerned about drought and decrease in rainfall. Thus, they have mainly implemented behavioral and locally-made options such as short-cycle varieties, terrace farming, half-moon, and bunds, among others, to overcome water shortages. Nevertheless, these measures were not solely driven by vulnerability; the socioeconomic context might play a role. Moreover, farmers perceive a limited capacity to adapt to climate change, which suggests that the government and policy-makers should focus, not only on implementing planned adaptation strategies, but also on the improvement and promotion of farmers’ autonomous adaptation strategies.

Efficient transmission of herpesviruses is essential for dissemination in host populations; however, little is known about the viral genes that mediate transmission, mostly due to a lack of natural virus-host model systems. Marek's disease is a devastating herpesviral disease of chickens caused by Marek's disease virus (MDV) and an excellent natural model to study skin-tropic herpesviruses and transmission. Like varicella zoster virus that causes chicken pox in humans, the only site where infectious cell-free MD virions are efficiently produced is in epithelial skin cells, a requirement for host-to-host transmission. Here, we enriched for heavily infected feather follicle epithelial skin cells of live chickens to measure both viral transcription and protein expression using combined short- and long-read RNA sequencing and LC/MS-MS bottom-up proteomics. Enrichment produced a previously unseen breadth and depth of viral peptide sequencing. We confirmed protein translation for 84 viral genes at high confidence (1% FDR) and correlated relative protein abundance with RNA expression levels. Using a proteogenomic approach, we confirmed translation of most well-characterized spliced viral transcripts and identified a novel, abundant isoform of the 14 kDa transcript family via IsoSeq transcripts, short-read intron-spanning sequencing reads, and a high-quality junction-spanning peptide identification. We identified peptides representing alternative start codon usage in several genes and putative novel microORFs at the 5' ends of two core herpesviral genes, pUL47 and ICP4, along with strong evidence of independent transcription and translation of the capsid scaffold protein pUL26.5. Using a natural animal host model system to examine viral gene expression provides a robust, efficient, and meaningful way of validating results gathered from cell culture systems.

ABSTRACT: Residual feed intake (RFI) is a moderately heritable trait of feed efficiency in dairy cows. The main objective of the present study was to assess potential differences in the ruminal microbiome, milk fatty acid (FA) composition, and plasma concentrations of glucose, nonesterified fatty acids (NEFA), and β-hydroxybutyrate between the most (M-EFF) and the least efficient (L-EFF) dairy cows during early lactation. Forty-seven multiparous Holstein dairy cows with daily ad libitum access to a total mixed ration from 30 d before calving to 30 d in milk were used. Cows were retrospectively classified into M-EFF (i.e., low RFI, n = 29) and L-EFF (high RFI, n = 18) based on a linear regression model. Ruminal digesta and milk samples were collected from each cow at 15 and 30 d in milk for microbiome analysis using 16S rRNA gene sequencing. Microbiome sequencing data were analyzed with the QIIME 2 platform (http://qiime.org/), whereas the microbiome statistical analyses and visual explorations were performed using the web-based MicrobiomeAnalyst platform. Milk FA composition was measured via gas chromatography-mass spectrometry. The statistical model used in SAS 9.4 (SAS Institute Inc.) included RFI, time, and their interactions as fixed effects. The cor() function in R programming was used to determine Pearson correlations between relative abundance of significant bacteria and milk FA. Overall, daily milk yield did not differ due to RFI and averaged 42 ± 1.6 kg for L-EFF and 43 ± 1.3 kg for M-EFF cows. However, M-EFF cows had lower overall dry matter intake (14.9 ± 0.5 kg/d) compared with L-EFF cows (19.2 ± 0.6 kg/d). No incidence of clinical disease was recorded for cows in the study. Compared with L-EFF, overall glucose concentration was lower, whereas NEFA and β-hydroxybutyrate concentrations were greater in M-EFF cows. Ruminal digesta from both RFI groups had similar bacterial composition, but differed in the relative abundance of some bacteria. Compared with L-EFF, M-EFF cows had greater relative abundance of Lachnospiraceae, Lachnoclostridium, Papillibacter, Desulfovibrio, Sphaerochaeta, Acetobacter, and Histophilus. In contrast, relative abundance of Bifidobacterium, Ruminiclostridium, Prevotellaceae, and Erysipelotrichaceae bacterium was lower in M-EFF cows. Compared with L-EFF, M-EFF cows had greater proportions of long-chain monounsaturated FA, including 16:1 trans-9, 16:1 cis-9, 17:1 trans-10, 17:1 cis-10, 18:1 cis-9, 18:1 cis-11, whereas proportions of medium-chain saturated and 16:0 were lower in M-EFF. Acetate-producing bacteria (Sphaerochaeta and Acetobacter) were positively and significantly correlated (r ≥ 0.24) with concentrations of 16:1 cis-9 and 17:1 cis-10, whereas Prevotellaceae was significantly and negatively correlated (r = −0.25) with these FA. Butyrate-producing bacterium (Papillibacter) had a significant negative correlation (r = −0.27) with concentration of 15:0. Overall, data suggested that feed-efficient cows have unique profiles of ruminal microbiota, some of which are correlated with concentrations of milk FA during early lactation.

The research aimed to describe the development of solar electric cars as a prop in energy conversion learning using the analyze, design, develop, implement, and evaluate (ADDIE) model and to ascertain the effectiveness of an electric car as a prop in energy conversion learning. Utilization of prop in the learning process is one way to support the development of knowledge, skills, and basic needs for delivering material, concepts, and physics information. This research is a descriptive study involving media and pedagogical experts and 40 students of the university in Tasikmalaya. Data collection techniques were carried out through the study of literature, expert validation, and student perception questionnaires. Expert validation and student perception were obtained by using a Likert scale. The expert judgment results were processed using the V value equation developed by Aiken. The results showed a value of 1, meeting the minimum validation requirements. The students also had positive responses to a prop. They have new experience learning in energy conversion and have good media to help their comprehension. It has a significant impact on helping students to achieve their learning goals.

Financial stress can have significant implications for individuals, businesses, asset prices and the economy as a whole. This study examines the nonlinear structure and dynamic changes in the multifractal behavior of cross-correlation between the financial stress index (FSI) and four well-known commodity indices, namely Commodity Research Bureau Index (CRBI), Baltic Dry Index (BDI), London Metal Index (LME) and Brent Oil prices (BROIL), using multifractal detrended cross correlation analysis (MFDCCA). For analysis, we utilized daily values of FSI and commodity index prices from 16 June 2016 to 9 July 2023. The following are the most important empirical findings: (I) All of the chosen commodity market indices show cross correlations with the FSI and have notable multifractal characteristics. (II) The presence of power law cross-correlation implies that a noteworthy shift in FSI is likely to coincide with a considerable shift in the commodity indices. (III) The multifractal cross-correlation is highest between FSI and Brent Oil (BROIL) and lowest with LME. (IV) The rolling windows analysis reveals a varying degree of persistency between FSI and commodity markets. The findings of this study have a number of important implications for commodity market investors and policymakers.

Abstract Background Advocating for and promoting contraception use is critical in reducing mother and child morbidity and mortality. Early Implanon discontinuation may result in unwanted pregnancies and induced abortions. Although there has been research in Ethiopia on long-acting reversible contraceptives, there has been none on early Implanon removal among rural women who have used and removed it. Hence, this study aimed to investigate the magnitude of Implanon discontinuation and related characteristics among women who had the Implanon removed in central Ethiopian public health facilities. Methods A community-based cross-sectional study was conducted among all women of the reproductive age group who had removed Implanon after using it. A simple random sampling technique was used to select 373 women after proportional allocation to each health facility. Data were collected using a pretested semi-structured interviewer-administered questionnaire adapted from previous studies. Data were entered using EpiInfo and exported to SPSS version 21 for analysis. A binary logistic regression model was used to determine the association between the outcome variable and independent variables. A p-value less than 0.25 was used as a cutoff point to select candidate variables for the final model. Then, a p value less than 0.05, AOR, and a 95% confidence level were used to declare statistical significance. Result A total of 360 participants responded to the questionnaires, making a response rate of 96.5%. In this study, the early discontinuation rate was 42% (95% CI 36.9–47.7). No formal education (AOR = 0.53 [95% CI 0.3–0.94], having medium monthly income (AOR = 3.02 [95% CI 1.38–6.6]), inadequate pre-insertion counseling (AOR = 0.55 [95% CI 0.31–0.98]), lack of appointment for follow up (AOR = 0.16 [95% CI 0.05–0.54]), didn`t satisfy with service provided (AOR = 0.067 [95% CI 0.015–0.29] and developed side effect (AOR) = 4.45 [95% CI 2.37–8.36] were significantly associated with Implanon discontinuation. Conclusion The discontinuation rate of Implanon among those who removed it after using it in this study was high. Lack of formal education, having a medium-income, inadequate pre-insertion counseling, lack of appointments for the follow-up, poor satisfaction, and problems with side effects were the factors associated with early discontinuation rate. Hence, quality family planning service provision is essential to reduce the discontinuation rate.

Matricarla chamomilla L. is native to European countries and widely cultivated in China, especially in Xinjiang. It has been used in Uygur medicine for the treatment of cough caused by asthma. In this study, UHPLC-Q-Orbitrap-MS was used to detect and identify the components from the active fraction of M. Chamomile, 64 compounds were identified by combining the standards, related literatures and mass spectrometry fragments, including 10 caffeoyl quinic acids, 38 flavonoids, 8 coumarins, 5 alkaloids and 3 other compounds. Furtherly, the anti-asthma activity of active fraction of M. Chamomile was investigated in OVA-induced allergic asthma rat model. The results showed that the number of EOS in Penh and bronchoalveolar lavage fluid (BALF) in the group of the active fraction of M. Chamomile was significantly lower than that in the model group. Besides, the active fraction of M. Chamomile can significantly reduce the IgE level and increased glutathione peroxidase (GSH-Px) in the serum of OVA-induced rats, and ameliorated OVA-induced lung injury. Hence, M. Chamomile could be used to treat asthma through their in vivo antioxidant and anti-inflammatory effects. This study explored the potential material basis of M. Chamomile for the treatment of asthma.

Marek's disease virus (MDV) establishes latency in chicken T lymphocytes that can lead to T cell transformation and cancer. Transformed Marek's disease chicken cell lines (MDCCs) can be expanded ex vivo and provide a valuable model to study latency, transformation, and reactivation. Here, we developed MDCCs from chickens infected with MDV that fluoresce during lytic replication and reactivation. Sodium butyrate treatment increased fluorescent protein expression as evidenced by fluorescent microscopy, flow cytometry, and western blotting; however, it caused significant apoptosis and necrosis. Treatment of MDCCs by decreasing the temperature resulted in robust MDV reactivation without significant induction of apoptosis and necrosis. Furthermore, MDV reactivation was significantly affected by the time in culture that can affect downstream reactivation analyses. In all, our data show that fluorescent protein expression during reactivation is a robust tool to examine viral replication in live cells ex vivo, and temperature treatment is an efficient technique to induce reactivation without punitive effects on cell viability seen with chemical treatment.

Conserved Herpesviridae protein kinases (CHPK) are conserved among all members of the Herpesviridae. Herpesviruses lacking CHPK propagate in cell culture at varying degrees, depending on the virus and cell culture system. CHPK is dispensable for Marek's disease herpesvirus (MDV) replication in cell culture and experimental infection in chickens; however, CHPK-particularly its kinase activity-is essential for horizontal transmission in chickens, also known as natural infection. To address the importance of CHPK during natural infection in chickens, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) based proteomics of samples collected from live chickens. Comparing modification of viral proteins in feather follicle epithelial (FFE) cells infected with wildtype or a CHPK-null virus, we identified the US10 protein (pUS10) as a potential target for CHPK in vivo. When expression of pUS10 was evaluated in cell culture and in FFE skin cells during in vivo infection, pUS10 was severely reduced or abrogated in cells infected with CHPK mutant or CHPK-null viruses, respectively, indicating a potential role for pUS10 in transmission. To test this hypothesis, US10 was deleted from the MDV genome, and the reconstituted virus was tested for replication, horizontal transmission, and disease induction. Our results showed that removal of US10 had no effect on the ability of MDV to transmit in experimentally infected chickens, but disease induction in naturally infected chickens was significantly reduced. These results show CHPK is necessary for pUS10 expression both in cell culture and in the host, and pUS10 is important for disease induction during natural infection.

Performing the five-time prayer is an obligation for every Muslim, no matter where they are. The provision of prayer rooms in commercial buildings is one of the facilities offered by building managers to accommodate Muslim buyers in most Muslim countries. However, the muṣallá provided is often remote, placed in a small or poorly planned space that most users, especially women, will feel uncomfortable and uncomfortable. This article aims to identify the feasibility of places of worship facilities for women in malls. The method in this study is qualitative with a descriptive-analytical approach. The results showed that the problems that came to the fore included the unresponsiveness of prayer rooms for the needs of women, inadequate entrance locations, uncomfortable ablution places, not being equipped with the necessary facilities, and some even not being child-friendly for parents. From this literature search, several research recommendations to investigate features and facilities in prayer rooms to make the area more responsive to the needs of Muslim female buyers. The results of this research have contributed to the development of Islamic education, namely increasing mutual awareness about the importance of providing decent worship facilities, especially for women.

Historically based systemic oppressions have exacerbated disparities in post-school outcomes among youth with disabilities transitioning to adulthood. Using a community action research (CAR) approach, the Disability Champions Mentoring Network was founded in the United States by a community of diverse stakeholders to address inequities in transition outcomes. Centering transition as a cultural practice, the project connected theoretical frameworks to develop a supportive community through interagency collaboration and mentorship. We conducted a self-examination using deductive category application and an open coding process to identify major themes in the project development process. The themes identified by collaborators include self-determination/mentorship; authentic interagency collaborative processes; identification of needs, barriers, and resources; and promotion of public awareness. Project achievements and barriers recognized by the community network are discussed in the context of the CAR model. Implications for policy, programming, and research are considered.

Contribution: This study presents an innovative experiential learning model utilizing an educational pico satellite kit as a tool for cultivating digital making skills. The distinct approach showcases a positive impact on students' learning experiences and serves as a motivating force, offering valuable implications for engineering and technical education. Background: In response to the dynamic technological landscape and escalating demand for digital making skills, this research addresses the need for cutting-edge educational tools. The UMP STEM Cube, strategically designed to elevate hands-on learning in digital making, emerges as a promising applicable solution across diverse educational programs. Intended Outcomes: An experiential learning module that elevates digital making skills in engineering education, specifically focusing on programming competencies and proficiency in physical computing. This study conducts an evaluation of the UMP STEM Cube's influence on experiential learning and skill development. Application Design: The instructional approach of employing the UMP STEM Cube aligns with Kolb's Experiential Learning Theory. The modular design of the UMP STEM Cube bridges the theoretical-practical gap in digital making education, fostering a holistic and impactful learning experience. Findings: This study establishes a correlation between hands-on engagement with the UMP STEM Cube and a significant learning gain in programming competencies and physical computing skills among students. Participants' positive perceptions, better competency in programming, and increased interest in digital making activities further emphasizes the efficacy of the UMP STEM Cube in fostering digital making skill sets.

Contribution: This study advances the understanding of English as a medium of instruction (EMI) in computer science education by exploring computer instructors' perspectives. Its unique contribution lies in a qualitative approach that uncovers the practical implications for policy and practice in the educational context. Background: The rationale for this study is the increasing global adoption of EMI in higher education, particularly in technical fields like computer science. The need to examine the real-world application and challenges of EMI, from the perspective of those directly involved in teaching, establishes its broad relevance. Intended Outcomes: The intended outcomes are to provide evidence-based recommendations for the EMI policy development and to enhance the quality of computer science education. The study aims to inform policy makers and educators about effective strategies and practices, ensuring a more successful implementation of EMI policies that cater to both instructors' and students' needs. Application Design: The study employs a qualitative methodology, utilizing semi-structured interviews with computer instructors. This design was chosen to deeply explore instructors' experiences, beliefs, and strategies in EMI contexts, thus providing rich, contextualized insights into the practical aspects of the EMI policy implementation. Findings: The findings reveal several key challenges in implementing EMI, including limited English proficiency among instructors and students, and a lack of clear teaching and assessment guidelines. The study also identifies effective management strategies used by instructors, such as incorporating students' mother tongue and adapting personal teaching methods. These findings highlight the need for comprehensive policy planning and support for instructors in EMI programs.

Vitiligo, an acquired depigmentation disorder, is characterized by the loss of functional melanocytes and epidermal melanin. In recent years, research has focused on promoting melanin biosynthesis and protecting melanocytes to reduce stress-related damage for the purpose of applying it to vitiligo treatment. Ruta graveolens L. has been utilized as a medicinal herb in diverse traditional medicine systems to address conditions like vitiligo. In this investigation, we isolated and purified 16 unique alkaloid compounds from the chloroform extracts of R. graveolens, encompassing a new quinoline alkaloid and several recognized compounds. Bioactivity analysis showed that compound 13, an alkaloid derived from R. graveolens, promotes melanin production while protecting PIG3V melanocytes against 4-tert-butylphenol (4-TBP)-induced oxidative damage by downregulating endoplasmic reticulum (ER) stress and pro-inflammatory cytokines through interleukin-6 (IL-6) regulation. Additionally, the compound suppressed the expression of Bip, IRE1, p-IRE1, and XBP-1 proteins, suggesting a potential antioxidant function. These findings suggest that compound 13 isolated from R. graveolens can augment melanogenesis in melanocytes, reduce endoplasmic reticulum (ER) stress, and ameliorate vitiligo exacerbation. The melanogenic activity observed in the chloroform fraction emphasizes R. graveolens’s potential as a novel therapeutic target for vitiligo treatment, warranting further exploration in future studies.

Abstract We have formerly shown that glycoprotein C (gC) of Gallid alphaherpesvirus 2, better known as Marek’s disease (MD) alphaherpesvirus (MDV), is required for interindividual spread in chickens. Since gC is conserved within the Alphaherpesvirinae subfamily, we hypothesized gC was important for interindividual spread of other alphaherpesviruses. To test this hypothesis, we first generated a fluorescent protein tagged clone of Gallid alphaherpesvirus 3 MD vaccine strain 301B/1 to track virus replication in cell culture and chickens using fluorescent microscopy. Following validation of this system, we removed the open reading frame of 301B/1 gC from the genome and determined whether it was required for interindividual spread using experimental and natural infection studies. Interindividual spread of MD vaccine 301B/1 was abrogated by removal of 301B/1 gC. Rescuent virus in which 301B/1 gC was inserted back into the genome efficiently spread among chickens. To further study the conserved function of gC, we replaced 301B/1 gC with MDV gC and this virus also efficiently spread in chickens. These data suggest the essential function of alphaherpesvirus gC proteins is conserved and can be exploited during the generation of future vaccines against MD that affects the poultry industry worldwide.

A monocationic dicopper(I,I) nitrite complex [Cu2(μ-κ1:κ1-O2N)DPFN][NTf2] (2) (DPFN = 2,7-bis(fluoro-di(2-pyridyl)methyl)-1,8-naphthyridine, NTf2- = N(SO2CF3)2-), was synthesized by treatment of a dicopper acetonitrile complex, [Cu2(μ-MeCN)DPFN][NTf2]2 (1), with tetrabutylammonium nitrite ([nBu4N][NO2]). DFT calculations indicate that 2 is one of three linkage isomers that are close in energy and presumably accessible in solution. Reaction of the μ-κ1:κ1-O2N complex with p-TolSH produces nitrous acid (HONO) and the corresponding dicopper thiolate species via an acid-base exchange reaction. Notably, treatment of 2 with HNTf2 results in N-O bond cleavage in the putative, HONO-ligated complex to form the more thermodynamically favorable nitrosyl-bridged dicopper complex [Cu2(μ-NO)(μ-OH)DPFN][NTf2]2 (4). This scission can be reversed via deprotonation of the hydroxy ligand with KOtBu. X-ray diffraction studies confirmed the solid-state molecular structures of 2 and 4. DFT calculations were used to construct a reaction coordinate diagram detailing formation of the μ-NO complex and to describe its electronic structure. The nitrosyl ligand in 4 is chemically labile, as demonstrated by its ready displacement in reactions with CO or NO2-.