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Herpes simplex virus type 1 (HSV-1) is a structurally complex enveloped dsDNA virus that has evolved to replicate in human neurons and epithelia. Viral gene expression, DNA replication, capsid assembly, and genome packaging take place in the infected cell nucleus, which mature nucleocapsids exit by envelopment at the inner nuclear membrane then de-envelopment into the cytoplasm. Once in the cytoplasm, capsids travel along microtubules to reach, dock, and envelope at cytoplasmic organelles. This generates mature infectious HSV-1 particles that must then be sorted to the termini of sensory neurons, or to epithelial cell junctions, for spread to uninfected cells. The focus of this review is upon our current understanding of the viral and cellular molecular machinery that enables HSV-1 to travel within infected cells during egress and to manipulate cellular organelles to construct its envelope.

Female sexual dysfunction (FSD) is a common problem among postpartum women. However, little is known about this topic in Malaysia. This study aimed to determine the prevalence of sexual dysfunction and its associated factors in postpartum women in Kelantan, Malaysia. In this cross-sectional study, we recruited 452 sexually active women at six months postpartum from four primary care clinics in Kota Bharu, Kelantan, Malaysia. The participants were asked to fill in questionnaires consisting of sociodemographic information and the Malay Version of the Female Sexual Function Index-6. The data were analyzed using bivariate and multivariate logistic regression analyses. With a 95% response rate, the prevalence of sexual dysfunction among sexually active, six months postpartum women was 52.4% (n = 225). FSD was significantly associated with the older husband’s age (p = 0.034) and lower frequency of sexual intercourse (p<0.001). Therefore, the prevalence of postpartum sexual dysfunction in women is relatively high in Kota Bharu, Kelantan, Malaysia. Efforts should be made to raise awareness among healthcare providers about screening for FSD in postpartum women and for their counseling and early treatment.

Blockchain technology is widely used in almost every domain of life nowadays including healthcare sector. Although there are existing frameworks to govern healthcare data but they have certain limitations in effectiveness of data governance to ensure security and privacy. This study aimed to evaluate effectiveness of health care data governance frameworks, examining security and privacy concerns and limitations within the existing frameworks of ISO Standards, GDPR, and HIPAA. In this study quantitative research approach was followed. A sample of 250 participants from Islamabad, Lahore and Karachi based healthcare experts, IT specialist, blockchain research and developer, administrator was selected. The collected data was analyzed though frequencies and descriptive statistical tests with the help of SPSS. The results revealed un-satisfaction for data governance frameworks, i.e., ISO standards, GDPR, and HIPAA in terms of security concerns, i.e., data encryption, access controls, audit trails, interoperability and standards, smart contracts for compliance, data integrity, regulatory compliance monitoring and privacy concerns, i.e., consent management, anonymization and pseudonymization, data minimization. The participants agreed that there is a need of integration of reliable data governance framework in health care data management. Various personalized governance techniques, targeted security upgrades, and continuous improvement in the specific customized data governance framework has been presented based on the findings of the study. An implementation of blockchain-based systems is recommended in order to ensure and expand the security and privacy of healthcare data management.

The aim of this work is to develop a predictive model for electrospun based polyvinyl alcohol (PVA) nanofiber diameter. Artificial Neural Network is employed to analyze the key variables such as applied electric field, the polymer concentrations, the rate of injection and nozzle collector distance, involves in the process of electrospinning affecting the diameter of PVA nanofiber. The most suitable network architecture was determined by considering and examining different topologies in artificial neural networks (ANNs) that composed of single and double hidden layers with different numbers of nodes for each layer. Strong prediction capabilities of the developed model are observed in the analysis of the parameters influencing the diameter of spun fibers for ANN configuration of 5-9-1. The findings revealed that PVA fiber diameters’ predicted in our work and the already existing experimental data are significantly correlated with a regression that is around 0.973. Also, a low value of average absolute error i.e., 0.06 is obtained after the evaluation of the developed model.

Ajwa dates ( Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC–MS) and investigated anticancer effects against MDA-MB-231 cells. LC–MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC 50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.

Soil erosion has resulted in removal of the topsoils containing fine soil particles and plant nutrients, causing decrease in soil fertility in the Hindu Kush, Karakoram and Himalaya (HKH) region. The existing production of cereal crop grains has been reduced to one third of the potential crop grains production owing to land degradation and poor farming practices. It is necessary to assess risk of soil loss and identify appropriate controlling measures to address issues of low agriculture productivity and water insecurity in the region. In the present study, severity of soil loss was predicted using Revised Universal Loss Equation (RUSLE) and ecological measures were identified for sustainable mountain agriculture in the HKH region of Upper Indus Basin, Pakistan. Overall 62.6% area was found to have very low risk of soil loss, i.e., <5 t/(ha·yr), 15.8% area low risk, i.e., 5–25 t/(ha·yr) and 7.5% area moderate risk, i.e., 25–50 t/(ha·yr) in the region. The risk was high, i.e., 50–100 t/(ha·yr) and very high, i.e., >100 t/(ha·yr) in about 6.8% and 7.4% areas respectively. The mean rate of soil loss was about 41.9 t/(ha·yr) in the Hindu Kush, 31.1 t/(ha·yr) in the Himalayas, 18.8 t/(ha·yr) in the Karakoram and overall 29.7 t/(ha·yr) in the three HKH ranges. As such no considerable measures have been adopted by the communities for restoration of the degraded areas except raising fruit/farm trees and supporting limited social forestry for their livelihoods. The slopes cleared for cultivation and susceptible to erosion may be stabilized through sowing/planting of multi-purpose plant species and formation of proper bench terraces. The conservation of forest ecosystem and pastures at higher elevations would help in reducing overland water flow, risk of flash flood hazard and minimizing sediment loads in the downstream. It is essential to adopt site-specific resource conservation techniques and restore possible ecosystem health for sustainable agriculture and economic development in the region in future.

Global warming promotes soil calcification and salinization processes. As a result, soil phosphorus (P) is becoming deficient in arid and semiarid areas throughout the world. In this pot study, we evaluated the potential of phosphate-solubilizing bacteria (PSB) for enhancing the growth and P uptake in maize under varying levels of lime (4.8%, 10%, 15% and 20%) and additional P supplements (farmyard manure, poultry manure, single super phosphate and rock phosphate) added at the rate of 45 mg P2O5 kg−1. Inoculation and application of P as organic manures (Poultry and farm yard manures) improved maize growth and P uptake compared to the control and soils with P applied from mineral sources. Liming adversely affected crop growth, but the use of PSB and organic manure significantly neutralized this harmful effect. Mineral P sources combined with PSB were as effective as the organic sources alone. Furthermore, while single supper phosphate showed better results than Rock phosphate, the latter performed comparably upon PSB inoculation. Thus, PSB plus P application as organic manures is an eco-friendly option to improve crop growth and P nutrition in a calcareous soil under changing climate.

Macrophages (Mφ) are long-lived myeloid cells that can polarize towards the proinflammatory M1 or proresolving M2 phenotype to control diverse biological processes such as inflammation, tissue damage, and regeneration. Noncoding RNA are a class of nonprotein-coding transcriptome with numerous interdependent biological roles; however, their functional interaction in the regulation of Mφ polarization and immune responses remain unclear. Here, we show antagonistic relationship between lncRNA (MALAT1) and microRNA (miR-30b) in shaping macrophage polarization and immune functions. MALAT1 expression displays a time-dependent induction during Mφ differentiation and, upon challenge with TLR4 agonist (E. coli LPS). MALAT1 knockdown promoted the expression of M2Mφ markers without affecting M1Mφ markers, suggesting that MALAT1 favors the M1 phenotype by suppressing M2 differentiation. Compared to the control, MALAT1 knockdown resulted in reduced antigen uptake and processing, bacterial phagocytosis, and bactericidal activity, strongly supporting its critical role in regulating innate immune functions in Mφ. Consistent with this, MALAT1 knockdown showed impaired cytokine secretion upon challenge with LPS. Importantly, MALAT1 exhibit an antagonistic expression pattern with all five members of the miR-30 family during M2 Mφ differentiation. Dual-luciferase assays validated a novel sequence on MALAT1 that interacts with miR-30b, a microRNA that promotes the M2 phenotype. Phagocytosis and antigen processing assays unequivocally demonstrated that MALAT1 and miR-30b are functionally antagonistic. Concurrent MALAT1 knockdown and miR-30b overexpression exhibited the most significant attenuation in both assays. In human subjects with periodontal disease and murine model of ligature-induced periodontitis, we observed higher levels of MALAT1, M1Mφ markers and downregulation of miR-30b expression in gingival tissues suggesting a pro-inflammatory function of MALAT1 in vivo . Overall, we unraveled the role of MALAT1 in Mφ polarization and delineated the underlying mechanism of its regulation by involving MALAT-1-driven miR-30b sequestration.

Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.

Peroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.