MMTV RNA packaging requires an extended long-range interaction for productive Gag binding to packaging signals.

The packaging of genomic RNA (gRNA) into retroviral particles relies on the specific recognition by the Gag precursor of packaging signals (Psi), which maintain a complex secondary structure through long-range interactions (LRIs). However, it remains unclear whether the binding of Gag to Psi alone is enough to promote RNA packaging and what role LRIs play in this process. Using mouse mammary tumor virus (MMTV), we investigated the effects of mutations in 4 proposed LRIs on gRNA structure and function. Our findings revealed the presence of an unsuspected extended LRI, and hSHAPE revealed that maintaining a wild-type-like Psi structure is crucial for efficient packaging. Surprisingly, filter-binding assays demonstrated that most mutants, regardless of their packaging capability, exhibited significant binding to Pr77Gag, suggesting that Gag binding to Psi is insufficient for efficient packaging. Footprinting experiments indicated that efficient RNA packaging is promoted when Pr77Gag binds to 2 specific sites within Psi, whereas binding elsewhere in Psi does not lead to efficient packaging. Taken together, our results suggest that the 3D structure of the Psi/Pr77Gag complex regulates the assembly of viral particles around gRNA, enabling effective discrimination against other viral and cellular RNAs that may also bind Gag efficiently.

Trends and social determinants of the obesity epidemic among reproductive-age women in ten Asian countries.

The rapid epidemiological transition in Asian countries, resulting from the rising trend of urbanisation and lifestyle changes, is associated with an increasing risk of obesity in women of reproductive age. This is the first study to investigate the trends and population-attributable fraction (PAF) of obesity, and the interaction effects of education and wealth on obesity among reproductive-age women aged 15-49 years in ten Asian countries. This cross-sectional study examined the most recent (2000 to 2022) Demographic and Health Surveys (DHS) data from ten Central and Southeast Asian countries. Multilevel multinomial logistic regression models were used to compute odds ratios (ORs). PAFs adjusted for communality were calculated using adjusted ORs and prevalence estimates for each risk factor. This study included a weighted sample of 743,494 reproductive-age women. All the countries showed an increasing trend for obesity and a decreasing trend for underweight, except for the Maldives. The highest PAFs of obesity were associated with women who were married (PAF = 22.2%; 95% CI 22.1, 22.4), aged 35-49 years (PAF = 16.4%; 95% CI 15.5, 17.1), resided in wealthy households (PAF = 14.5%; 95% CI 14.4, 14.5), watched television regularly (PAF = 12.5%; 95% CI 12.1, 12.8), and lived in urban areas (PAF = 7.8%; 95% CI 7.7, 8.0). The combined PAF showed that these five risk factors were associated with 73.3% (95% CI 71.8, 74.9) of obesity among reproductive-age women. Interaction analysis between women's education and household wealth revealed that having a secondary or higher level of education and residing in a wealthier household was associated with a lower risk of obesity (OR = 0.71, 95% CI 0.66, 0.76). The findings of this study suggest that, in order to address the rising rate of obesity among women in Asian countries, education and lifestyle modifications in urban areas should be a priority. Pakistan and the Maldives need to be a priority given the rapidly increasing trends in obesity and underweight subpopulations in their respective countries.

Crystal structure and Hirshfeld surface analysis of 1-[6-bromo-2-(3-bromo-phen-yl)-1,2,3,4-tetra-hydro-quinolin-4-yl]pyrrolidin-2-one.

This study presents the synthesis, characterization and Hirshfeld surface analysis of 1-[6-bromo-2-(3-bromo-phen-yl)-1,2,3,4-tetra-hydro-quinolin-4-yl]pyrrolidin-2-one, C19H18Br2N2O. In the title compound, the pyrrolidine ring adopts a distorted envelope configuration. In the crystal, mol-ecules are linked by inter-molecular N-H⋯O, C-H⋯O and C-H⋯Br hydrogen bonds, forming a three-dimensional network. In addition, pairs of mol-ecules along the c axis are connected by C-H⋯π inter-actions. According to a Hirshfeld surface study, H⋯H (36.9%), Br⋯H/H⋯Br (28.2%) and C⋯H/H⋯C (24.3%) inter-actions are the most significant contributors to the crystal packing.

Intimate partner violence and childhood health outcomes in 37 sub-Saharan African countries: an analysis of demographic health survey data from 2011 to 2022.

BACKGROUND: Understanding the contribution of intimate partner violence (IPV) to childhood health outcomes (eg, morbidity and mortality) is crucial for improving child survival in sub-Saharan Africa. This comprehensive study aimed to explore the associations between maternal exposure to physical, sexual, or emotional violence and adverse childhood health outcomes in sub-Saharan Africa. METHODS: We analysed Demographic Health Survey datasets from 37 sub-Saharan African countries from 2011 to 2022. A generalised linear mixed model was used to examine the associations between maternal physical violence, sexual violence, or emotional violence, and early childhood health outcomes (eg, acute respiratory infection, diarrhoea, undernutrition, and child mortality). A random effects meta-analysis was used to calculate pooled odds ratios (ORs) for adverse childhood health outcomes. The odds of undernutrition and mortality were 55% and 58% higher among children younger than 5 years born to mothers who were exposed to physical and sexual violence, respectively. FINDINGS: 238 060 children younger than 5 years were included. Children whose mothers experienced physical violence (adjusted OR 1·33, 95% CI 1·29-1·42), sexual violence (1·47, 1·34-1·62), emotional violence (1·39, 1·32-1·47), or a combination of emotional and sexual violence (1·64, 1·20-2·22), or a combination of all the three forms of violence (1·88, 1·62-2·18) were associated with an increased odds of developing diarrhoeal disease. Similarly, children whose mothers experienced physical violence (1·43, 1·28-1·59), sexual violence (1·47, 1·34-1·62), emotional violence (1·39, 1·32-1·47), or a combination of emotional and sexual violence (1·48, 1·16-1·89), or a combination of all three forms of violence (1·66, 1·47-1·88) were positively associated with symptoms of acute respiratory infection. INTERPRETATION: We found a strong link between maternal exposure to IPV and health outcomes for children younger than 5 years in sub-Saharan Africa, with minor variations across countries. To address childhood morbidity and mortality attributed to IPV, interventions need to be tailored for specific countries. Burkina Faso, Burundi, Chad, Comoros, Gabon, Liberia, Nigeria, Sierra Leone, South Africa, and Uganda should be priority nations. FUNDING: None.

Enhancing diagnosis: ensemble deep-learning model for fracture detection using X-ray images.

AIM: Orthopedic trauma results in the injury of bone joints and tendons of the body. A radiologist reviews and monitors large numbers of radiographs daily, which can lead to the diagnostic error. Therefore, there is a need to automate the detection of bone fractures in X-ray images, particularly humerus bone fractures. In this paper, we have proposed an ensemble model that can detect the fracture in an x-ray image. MATERIALS AND METHODS: In this paper, we proposed an ensemble model designed for fracture detection in X-ray images. An ensemble model combines multiple diverse models to improve predictive accuracy and robustness by aggregating their individual predictions. The model leverages MobileNetV2, Vgg16, InceptionV3, and ResNet50, using histogram equalization for preprocessing and a Global Average Pooling layer for feature extraction. The entire humerus from the public Mura-v1.1 dataset is utilized for analysis, utilizing a single training-validation split. The dataset is divided into a ratio of 80:20 for experiments for the training and validation datasets. RESULTS: The proposed model outperformed the modified deep-learning models and achieved 92.96%, 91.62%, and 92.14% accuracy, recall, and F1 scores, respectively. CONCLUSION: The ensemble model presented effectively automates bone fracture detection in X-ray images of the humerus, demonstrating superior performance compared to modified deep-learning models. A comparison has been made between a novel ensemble model and state-of-the-art models, bench-marking their performance. These findings underscore its potential for enhancing diagnostic accuracy and efficiency in orthopedic radiology.

Remediation of lead toxicity with waste-bio materials from aqueous solutions in fixed-bed column using response surface methodology.

Heavy metal ions pose significant risks to human health, pelagic, and several other life forms due to perniciousness, tendency to accumulate, and resistance to biodegradation. Waste bio-materials extend a budding alternative as low-cost adsorbent to address the removal of noxious pollutants from wastewater on account of being cost-effective and exhibiting exceptional adsorption capacities. The current exploration was accomplished to gauge the performance of raw and modified human hair concerning lead scavenging in a down-flow fixed bed column. The appraisal of column performance under varying operational parameters encompassing bed height (15-45 cm), influent metal ion concentration (60-140 mg L-1), and a solution flow rate (20-40 mL min-1) was performed by breakthrough curve analysis. The consequences acquired were evaluated using the Yoon Nelson, Thomas, Adam-Bohart, and Bed Depth Service Time (BDST) model. Among these employed models, Bed Depth Service Time (BDST) and Thomas models exhibited the highest R-squared value compared to the Yoon Nelson and Adam-Bohart's model for most cases. In addition, the optimization of lead adsorption was followed using the Box-Behnken design of response surface methodology (RSM). The optimal conditions (desirability-1.00) for achieving a goal of maximum percent removal of lead ions were marked to be a bed height of 42.79 cm, solution flow rate of 20.92 mL min-1, and an initial metal concentration of 139.51 mg L-1. Under these optimized conditions, the percent amputation of lead in a fixed bed was observed to be 82.31 %, while the results of the experiment performed approximately under these optimized conditions revealed a percent removal of 85.05 %, reflecting a reasonable conformity with values acquired through Box-Behnken design.

The Host miR-17-92 Cluster Negatively Regulates Mouse Mammary Tumor Virus (MMTV) Replication Primarily Via Cluster Member miR-92a.

The mouse mammary tumor virus (MMTV) is a well-known causative agent of breast cancer in mice. Previously, we have shown that MMTV dysregulates expression of the host miR-17-92 cluster in MMTV-infected mammary glands and MMTV-induced tumors. This cluster, better known as oncomiR-1, is frequently dysregulated in cancers, particularly breast cancer. In this study, our aim was to uncover a functional interaction between MMTV and the cluster. Our results reveal that MMTV expression led to dysregulation of the cluster in both mammary epithelial HC11 and HEK293T cells with the expression of miR-92a cluster member being affected the most. Conversely, overexpression of the whole or partial cluster significantly repressed MMTV expression. Notably, overexpression of cluster member miR-92a alone repressed MMTV expression to the same extent as overexpression of the complete/partial cluster. Inhibition of miR-92a led to nearly a complete restoration of MMTV expression, while deletion/substitution of the miR-92a seed sequence rescued MMTV expression. Dual luciferase assays identified MMTV genomic RNA as the potential target of miR-92a. These results show that the miR-17-92 cluster acts as part of the cell's well-known miRNA-based anti-viral response to thwart incoming MMTV infection. Thus, this study provides the first evidence highlighting the biological significance of host miRNAs in regulating MMTV replication and potentially influencing tumorigenesis.

Population modifiable risk factors associated with neonatal mortality in 35 sub-Saharan Africa countries: analysis of data from demographic and health surveys.

Background: Sub-Saharan Africa (SSA) has the highest burden of neonatal mortality in the world. Identifying the most critical modifiable risk factors is imperative for reducing neonatal mortality rates. This study is the first to calculate population-attributable fractions (PAFs) for modifiable risk factors of neonatal mortality in SSA. Methods: We analysed the most recent Demographic and Health Surveys data sets from 35 SSA countries conducted between 2010 and 2022. Generalized linear latent and mixed models were used to estimate odds ratios (ORs) along with 95% confidence intervals (CIs). PAFs adjusted for communality were calculated using ORs and prevalence estimates for key modifiable risk factors. Subregional analyses were conducted to examine variations in modifiable risk factors for neonatal mortality across Central, Eastern, Southern, and Western SSA regions. Findings: In this study, we included 255,891 live births in the five years before the survey. The highest PAFs of neonatal mortality among singleton children were attributed to delayed initiation of breastfeeding (>1 h after birth: PAF = 23.88%; 95% CI: 15.91, 24.86), uncleaned cooking fuel (PAF = 5.27%; 95% CI: 1.41, 8.73), mother's lacking formal education (PAF = 4.34%; 95% CI: 1.15, 6.31), mother's lacking tetanus vaccination (PAF = 3.54%; 95% CI: 1.55, 4.92), and infrequent antenatal care (ANC) visits (PAF = 2.45; 95% CI: 0.76, 3.63). Together, these five modifiable risk factors were associated with 39.49% (95% CI: 21.13, 48.44) of neonatal deaths among singleton children in SSA. Our subregional analyses revealed some variations in modifiable risk factors for neonatal mortality. Notably, delayed initiation of breastfeeding consistently contributed to the highest PAFs of neonatal mortality across all four regions of SSA: Central, Eastern, Southern, and Western SSA. Interpretation: The PAF estimates in the present study indicate that a considerable proportion of neonatal deaths in SSA are preventable. We identified five modifiable risk factors that accounted for approximately 40% of neonatal deaths in SSA. The findings have policy implications. Funding: None.

Effects of short birth interval on child malnutrition in the Asia-Pacific region: Evidence from a systematic review and meta-analysis.

Child malnutrition remains a significant concern in the Asia-Pacific region, with short birth intervals recognised as a potential risk factor. However, evidence of this association is inconclusive. This study aimed to systematically review the existing evidence and assess the summary effects of short birth interval on child malnutrition in the Asia-Pacific region. Five electronic databases were searched in May 2023 to identify relevant studies reporting the association between short birth interval and child malnutrition, including stunting, wasting, underweight, anaemia and overall malnutrition, in Asia-Pacific region between September 2000 and May 2023. Fixed-effects or random-effects meta-analysis was performed to estimate the summary effects of short birth interval on child malnutrition. Out of 56 studies meeting the inclusion criteria, 48 were included in quantitative synthesis through meta-analysis. We found a slightly higher likelihood of stunting (n = 25, odds ratio [OR] = 1.13; 95% confidence interval [CI]: 0.97-1.32) and overall malnutrition (n = 3, OR = 2.42; 95% CI: 0.88-6.65) among children born in short birth intervals compared to those with nonshort intervals, although the effect was not statistically significant. However, caution is warranted due to identified heterogeneity across studies. Subgroup analysis demonstrated significant effects of short birth intervals on child malnutrition in national-level studies and studies with larger sample sizes. These findings underscore short birth intervals as a significant contributor to child malnutrition in the Asia-Pacific region. Implementing effective policies and programs is vital to alleviate this burden, ultimately reducing child malnutrition and associated adverse outcomes, including child mortality.

Population modifiable risk factors associated with under-5 acute respiratory tract infections and diarrhoea in 25 countries in sub-Saharan Africa (2014-2021): an analysis of data from demographic and health surveys.

Background: Identifying the critical modifiable risk factors for acute respiratory tract infections (ARIs) and diarrhoea is crucial to reduce the burden of disease and mortality among children under 5 years of age in sub-Saharan Africa (SSA) and ultimately achieving the Sustainable Development Goals (SDGs). We investigated the modifiable risk factors of ARI and diarrhoea among children under five using nationally representative surveys. Methods: We used the most recent demographic and health survey (DHS) data (2014-2021) from 25 SSA countries, encompassing a total of 253,167 children. Countries were selected based on the availability of recent datasets (e.g., DHS-VII or DHS-VIII) that represent the current socioeconomic situations. Generalised linear latent mixed models were used to compute odds ratios (ORs). Population attributable fractions (PAFs) were calculated using adjusted ORs and prevalence estimates for key modifiable risk factors among ARI and diarrhoeal cases. Findings: This study involved 253,167 children, with a mean age of 28.7 (±17.3) months, and 50.5% were male. The highest PAFs for ARI were attributed to unclean cooking fuel (PAF = 15.7%; 95% CI: 8.1, 23.1), poor maternal education (PAF = 13.4%; 95% CI: 8.7, 18.5), delayed initiation of breastfeeding (PAF = 12.4%; 95% CI: 9.0, 15.3), and poor toilets (PAF = 8.5%; 95% CI: 4.7, 11.9). These four modifiable risk factors contributed to 41.5% (95% CI: 27.2, 52.9) of ARI cases in SSA. The largest PAFs of diarrhoea were observed for unclean cooking fuel (PAF = 17.3%; 95% CI: 13.5, 22.3), delayed initiation of breastfeeding (PAF = 9.2%; 95% CI: 7.5, 10.5), household poverty (PAF = 7.0%; 95% CI: 5.0, 9.1) and poor maternal education (PAF = 5.6%; 95% CI: 2.9, 8.8). These four modifiable risk factors contributed to 34.0% (95% CI: 26.2, 42.3) of cases of diarrhoea in SSA. Interpretation: This cross-sectional study identified four modifiable risk factors for ARI and diarrhoea that should be a priority for policymakers in SSA. Enhancing home-based care and leveraging female community health workers is crucial for accelerating the reduction in under-5 mortality linked to ARI and diarrhoea in SSA. Funding: None.

Global burden of 34 cancers among women in 2020 and projections to 2040: Population-based data from 185 countries/territories.

Globally women face inequality in cancer outcomes; for example, smaller improvements in life expectancy due to decreased cancer-related deaths than men (0.5 vs 0.8 years, 1981-2010). However, comprehensive global evidence on the burden of cancer among women (including by reproductive age spectrum) as well as disparities by region, remains limited. This study aimed to address these evidence gaps by considering 34 cancer types in 2020 and their projections for 2040. The cancer burden among women in 2020 was estimated using population-based data from 185 countries/territories sourced from GLOBOCAN. Mortality to Incidence Ratios (MIR), a proxy for survival, were estimated by dividing the age-standardised mortality rates by the age-standardised incidence rates. Demographic projections were performed to 2040. In 2020, there were an estimated 9.3 million cancer cases and 4.4 million cancer deaths globally. Projections showed an increase to 13.3 million (↑44%) and 7.1 million (↑60%) in 2040, respectively, with larger proportional increases in low- and middle-income countries. MIR among women was higher (poorer survival) in rare cancers and with increasing age. Countries with low Human Development Indexes (HDIs) had higher MIRs (69%) than countries with very high HDIs (30%). There was inequality in cancer incidence and mortality worldwide among women in 2020, which will further widen by 2040. Implementing cancer prevention efforts and providing basic cancer treatments by expanding universal health coverage through a human rights approach, expanding early screening opportunities and strengthening medical infrastructure are key to improving and ensuring equity in cancer control and outcomes.

Characteristics and Key Features of Antimicrobial Materials and Associated Mechanisms for Diverse Applications.

Since the Fourth Industrial Revolution, three-dimensional (3D) printing has become a game changer in manufacturing, particularly in bioengineering, integrating complex medical devices and tools with high precision, short operation times, and low cost. Antimicrobial materials are a promising alternative for combating the emergence of unforeseen illnesses and device-related infections. Natural antimicrobial materials, surface-treated biomaterials, and biomaterials incorporated with antimicrobial materials are extensively used to develop 3D-printed products. This review discusses the antimicrobial mechanisms of different materials by providing examples of the most commonly used antimicrobial materials in bioengineering and brief descriptions of their properties and biomedical applications. This review will help researchers to choose suitable antimicrobial agents for developing high-efficiency biomaterials for potential applications in medical devices, packaging materials, biomedical applications, and many more.

Identification of a putative Gag binding site critical for feline immunodeficiency virus genomic RNA packaging.

The retroviral Gag precursor plays a central role in the selection and packaging of viral genomic RNA (gRNA) by binding to virus-specific packaging signal(s) (psi or ψ). Previously, we mapped the feline immunodeficiency virus (FIV) ψ to two discontinuous regions within the 5' end of the gRNA that assumes a higher order structure harboring several structural motifs. To better define the region and structural elements important for gRNA packaging, we methodically investigated these FIV ψ sequences using genetic, biochemical, and structure-function relationship approaches. Our mutational analysis revealed that the unpaired U85CUG88 stretch within FIV ψ is crucial for gRNA encapsidation into nascent virions. High-throughput selective 2' hydroxyl acylation analyzed by primer extension (hSHAPE) performed on wild type (WT) and mutant FIV ψ sequences, with substitutions in the U85CUG88 stretch, revealed that these mutations had limited structural impact and maintained nucleotides 80-92 unpaired, as in the WT structure. Since these mutations dramatically affected packaging, our data suggest that the single-stranded U85CUG88 sequence is important during FIV RNA packaging. Filter-binding assays performed using purified FIV Pr50Gag on WT and mutant U85CUG88 ψ RNAs led to reduced levels of Pr50Gag binding to mutant U85CUG88 ψ RNAs, indicating that the U85CUG88 stretch is crucial for ψ RNA-Pr50Gag interactions. Delineating sequences important for FIV gRNA encapsidation should enhance our understanding of both gRNA packaging and virion assembly, making them potential targets for novel retroviral therapeutic interventions, as well as the development of FIV-based vectors for human gene therapy.

HLA class I associations with the severity of COVID-19 disease in the United Arab Emirates.

SARS-CoV-2 appears to induce diverse innate and adaptive immune responses, resulting in different clinical manifestations of COVID-19. Due to their function in presenting viral peptides and initiating the adaptive immune response, certain Human Leucocyte Antigen (HLA) alleles may influence the susceptibility to severe SARS-CoV-2 infection. In this study, 92 COVID-19 patients from 15 different nationalities, with mild (n = 30), moderate (n = 35), and severe (n = 27) SARS-CoV-2 infection, living in the United Arab Emirates (UAE) were genotyped for the Class I HLA -A, -C, and -B alleles using next-generation sequencing (NGS) between the period of May 2020 to June 2020. Alleles and inferred haplotype frequencies in the hospitalized patient group (those with moderate to severe disease, n = 62) were compared to non-hospitalized patients (mild or asymptomatic, n = 30). An interesting trend was noted between the severity of COVID-19 and the HLA-C*04 (P = 0.0077) as well as HLA-B*35 (P = 0.0051) alleles. The class I haplotype HLA-C*04-B*35 was also significantly associated (P = 0.0049). The involvement of inflammation, HLA-C*04, and HLA-B*35 in COVID-19 severity highlights the potential roles of both the adaptive and innate immune responses against SARS-CoV-2. Both alleles have been linked to several respiratory diseases, including pulmonary arterial hypertension along with infections caused by the coronavirus and influenza. This study, therefore, supports the potential use of HLA testing in prioritizing public healthcare interventions for patients at risk of COVID-19 infection and disease progression, in addition to providing personalized immunotherapeutic targets.

Development of energy demand and carbon emission dataset for Nile University of Nigeria.

The global energy crisis and ozone layer depletion as a result of carbon emissions have increased the awareness and acceptance of renewable energy sources as an alternative form of electric power, resulting in the sizing of renewable energy sources. However, in order to properly size an energy power system, the information being addressed, such as the load demand, is critical. The Load demand data of Nile University campus is obtained from one of its power stations (PS-1) for a period of eight month. The data was measured from the bus bar of the power station using smart meters on a weekly basis. To power the university campus, the diesel generators are synchronized using Genset controllers with suitable communications interfaces and a SMA hybrid controller, which continually checks the power output of the power sources as well as the working condition of all loads in the busbar. The diesel generators are synchronized using SMA hybrid controllers and combined with the other source of the energy at a common bus bar and used to power the university campus. Additionally, carbon emission data were obtained from the PV solar system reading.

Differentially-regulated miRNAs in COVID-19: A systematic review.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease of 2019 (COVID-19) that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID-19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS-CoV-2 alters the host immune response by changing host-transcriptional machinery. MicroRNAs (miRNAs) are regarded as post-transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS-CoV-2 infection. Some of this could occur as an anti-viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro-viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS-CoV-2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other co-morbidities. Having such biomarkers can be vital in not only predicting COVID-19 prognosis, but also the development of novel miRNA-based anti-virals and therapeutics which can become invaluable in case of the emergence of new viral variants with pandemic potential in the future.

Investigating the Properties and Characterization of a Hybrid 3D Printed Antimicrobial Composite Material Using FFF Process: Innovative and Swift.

Novel strategies and materials have gained the attention of researchers due to the current pandemic, the global market high competition, and the resistance of pathogens against conventional materials. There is a dire need to develop cost-effective, environmentally friendly, and biodegradable materials to fight against bacteria using novel approaches and composites. Fused filament fabrication (FFF), also known as fused deposition modeling (FDM), is the most effective and novel fabrication method to develop these composites due to its various advantages. Compared to metallic particles alone, composites of different metallic particles have shown excellent antimicrobial properties against common Gram-positive and Gram-negative bacteria. This study investigates the antimicrobial properties of two sets of hybrid composite materials, i.e., Cu-PLA-SS and Cu-PLA-Al, are made using copper-enriched polylactide composite, one-time printed side by-side with stainless steel/PLA composite, and second-time with aluminum/PLA composite respectively. These materials have 90 wt.% of copper, 85 wt.% of SS 17-4, 65 wt.% of Al with a density of 4.7 g/cc, 3.0 g/cc, and 1.54 g/cc, respectively, and were fabricated side by side using the fused filament fabrication (FFF) printing technique. The prepared materials were tested against Gram-positive and Gram-negative bacteria such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Salmonella Poona (S. Poona), and Enterococci during different time intervals (5 min, 10 min, 20 min, 1 h, 8 h, and 24 h). The results revealed that both samples showed excellent antimicrobial efficiency, and 99% reduction was observed after 10 min. Hence, three-dimensional (3D) printed polymeric composites enriched with metallic particles can be utilized for biomedical, food packaging, and tissue engineering applications. These composite materials can also provide sustainable solutions in public places and hospitals where the chances of touching surfaces are higher.

Global Down-regulation of Gene Expression Induced by Mouse Mammary Tumor Virus (MMTV) in Normal Mammary Epithelial Cells.

Mouse mammary tumor virus (MMTV) is a betaretrovirus that causes breast cancer in mice. The mouse mammary epithelial cells are the most permissive cells for MMTV, expressing the highest levels of virus upon infection and being the ones later transformed by the virus due to repeated rounds of infection/superinfection and integration, leading eventually to mammary tumors. The aim of this study was to identify genes and molecular pathways dysregulated by MMTV expression in mammary epithelial cells. Towards this end, mRNAseq was performed on normal mouse mammary epithelial cells stably expressing MMTV, and expression of host genes was analyzed compared with cells in its absence. The identified differentially expressed genes (DEGs) were grouped on the basis of gene ontology and relevant molecular pathways. Bioinformatics analysis identified 12 hub genes, of which 4 were up-regulated (Angp2, Ccl2, Icam, and Myc) and 8 were down-regulated (Acta2, Cd34, Col1a1, Col1a2, Cxcl12, Eln, Igf1, and Itgam) upon MMTV expression. Further screening of these DEGs showed their involvement in many diseases, especially in breast cancer progression when compared with available data. Gene Set Enrichment Analysis (GSEA) identified 31 molecular pathways dysregulated upon MMTV expression, amongst which the PI3-AKT-mTOR was observed to be the central pathway down-regulated by MMTV. Many of the DEGs and 6 of the 12 hub genes identified in this study showed expression profile similar to that observed in the PyMT mouse model of breast cancer, especially during tumor progression. Interestingly, a global down-regulation of gene expression was observed, where nearly 74% of the DEGs in HC11 cells were repressed by MMTV expression, an observation similar to what was observed in the PyMT mouse model during tumor progression, from hyperplasia to adenoma to early and late carcinomas. Comparison of our results with the Wnt1 mouse model revealed further insights into how MMTV expression could lead to activation of the Wnt1 pathway independent of insertional mutagenesis. Thus, the key pathways, DEGs, and hub genes identified in this study can provide important clues to elucidate the molecular mechanisms involved in MMTV replication, escape from cellular anti-viral response, and potential to cause cell transformation. These data also validate the use of the MMTV-infected HC11 cells as an important model to study early transcriptional changes that could lead to mammary cell transformation.

Molecular Docking Identifies 1,8-Cineole (Eucalyptol) as A Novel PPARγ Agonist That Alleviates Colon Inflammation.

Inflammatory bowel disease, comprising Crohn's disease (CD) and ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available drug therapies are associated with adverse effects when used long-term. Therefore, the search for new drug candidates to treat IBD is imperative. The peroxisome proliferator-activated receptor-γ (PPARγ) is highly expressed in the colon. PPARγ plays a vital role in regulating colonic inflammation. 1,8-cineole, also known as eucalyptol, is a monoterpene oxide present in various aromatic plants which possess potent anti-inflammatory activity. Molecular docking and dynamics studies revealed that 1,8-cineole binds to PPARγ and if it were an agonist, that would explain the anti-inflammatory effects of 1,8-cineole. Therefore, we investigated the role of 1,8-cineole in colonic inflammation, using both in vivo and in vitro experimental approaches. Dextran sodium sulfate (DSS)-induced colitis was used as the in vivo model, and tumor necrosis factor-α (TNFα)-stimulated HT-29 cells as the in vitro model. 1,8-cineole treatment significantly decreased the inflammatory response in DSS-induced colitis mice. 1,8-cineole treatment also increased nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus to induce potent antioxidant effects. 1,8-cineole also increased colonic PPARγ protein expression. Similarly, 1,8-cineole decreased proinflammatory chemokine production and increased PPARγ protein expression in TNFα-stimulated HT-29 cells. 1,8-cineole also increased PPARγ promoter activity time-dependently. Because of its potent anti-inflammatory effects, 1,8-cineole may be valuable in treating IBD.

Influence of Sapindus mukorossi extract in comparison to 17% EDTA as final root canal irrigant on the sealer penetration and microleakage of dentinal tubules.

OBJECTIVE: The study evaluated the effect of Sapindus mukorossi (SM) extract as a final root canal irrigant on sealer penetration (SP) in dentinal tubules and microleakage. MATERIALS AND METHODS: Samples were selected based on inclusion and exclusion criteria. An access opening in all samples was performed and the working length was decided using pro taper for canal finishing along with constant irrigation. Specimens were randomly divided into 3 groups. Group 1 was irrigated with 3 ml of 17% EDTA; group 2 was irrigated with SM irrigant and group 3 samples were irrigated with 0.9% saline. After obturation, samples were vertically placed in 1% methylene blue dye cut in half longitudinally, and viewed under a stereomicroscope. Analysis of SP in the dentinal tubule was assessed using scanning electron microscopy (SEM). For microleakage assessment, mean and standard deviation were reported and One-Way ANOVA was applied. SP was compared using Kruskal-Wallis' test. For inspecting the interaction between SM/EDTA and NaOCl, Fisher's exact test was applied. No statistically significant difference between microleakage in any of the tested groups was observed. The control group showed minimum leakage as compared to EDTA and SM. RESULTS: The results displayed that there was no significant difference, (p=0.67), between dentinal tubule SP at 2 mm. A significant difference between dentinal tubule SP among groups at 5 mm was observed (p<0.05). CONCLUSIONS: SM ethanolic extract showed comparable outcomes of smear layer removal and sealer penetration to 17% EDTA, as a final irrigant in root canal cleaning. Therefore, SM has the potential to be used as an adjuvant final irrigant in conjunction with NaOCl.