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The thermal applications of nanofluids are extremely high and researchers have suggested multidisciplinary applications of nanomaterials in heat transfer problems, thermal systems, chemical industries, thermal energy systems, nuclear processes, extrusion mechanism, etc. The aim of this work is to discuss thermal properties of nanofluids for Poiseuille flow with hydrodynamic effects. The magnetohydrodynamic Poiseuille flow of thermo-capillary levels of nanoparticles with apparent viscosity nanofluids is focused. The graphene oxide (GO) nanoparticles are immersed in water-based fluid. The formulated system is solved numerically by using the Chebyshev collocation method. The mathematical technique Qualitat and Zuverlassigkeit (QZ) is applied to find out eigenvalues from comprehensive Orr–Sommerfeld technique. It is noted that the flow of nanofluids becomes stable due to the wave number and magnetic field. The Reynolds and Prandtl numbers have dynamic role on destabilizing the nanofluids transportation. The outcomes of this study are utilized in drug-delivery systems, photodynamic therapy and delivery of antitumor. [ABSTRACT FROM AUTHOR]

Brain metastasis (BrM) is a major threat to the survival of melanoma, breast, and lung cancer patients. Circulating tumor cells (CTCs) cross the blood-brain barrier (BBB) and sustain in the brain microenvironment. Genetic mutations and epigenetic modifications have been found to be critical in controlling key aspects of cancer metastasis. Metastasizing cells confront inflammation and gradually adapt in the unique brain microenvironment. Currently, it is one of the major areas that has gained momentum. Researchers are interested in the factors that modulate neuroinflammation during BrM. We review here various epigenetic factors and mechanisms modulating neuroinflammation and how this helps CTCs to adapt and survive in the brain microenvironment. Since epigenetic changes could be modulated by targeting enzymes such as histone/DNA methyltransferase, deacetylases, acetyltransferases, and demethylases, we also summarize our current understanding of potential drugs targeting various aspects of epigenetic regulation in BrM. [ABSTRACT FROM AUTHOR]

Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM. [ABSTRACT FROM AUTHOR]

Abstract The Pulwama attack and Balakot Airstrike were two major issues that affected Pak India relations in 2019 and both countries indulged in these issues. The present study is conducted to examine Indian press propaganda against Pakistan on these selected incidents.The study aimed to analyze the nature of propaganda of the Indian press to highlight the selected issues.Two national Indian newspapers are selected to conduct this study, The Times of India and The Telegraph, from February 2019 to July 2019. Application of under Propaganda, Agenda and Framing theory, content analysis is used as a research methodology. The results showed that Indian media used black propaganda to influence their audience negatively and create hate among the people for Pakistan. Indian media and the Indian government always seek a chance to speak against Pakistan, showingIndia's abominable face and crooked government. India's Indian press and press misguided the Pulwama attack and Balakot Airstrike failed in hybrid warfare (Media War) against Pakistan. The government policies strongly affect the newspaper's policy and ultimately, it's creating hate against Pakistan among their public. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract This study investigates the impact of the chemical nature of lipids and additive on the formulation and properties of pH sensitive liposomes. The objective is to understand the respective role of the formulation parameters on the liposome properties in order to optimize the conditions for efficient encapsulation of doxorubicin (DOX). These liposomes should be stable at physiological pH, and disrupt in slightly acidic media such as the tumor microenvironment to release their DOX load. The major challenge for encapsulating DOX in pH sensitive liposomes lies in the fact that this drug is soluble at low pH (when the pH-sensitive liposomes are not stable), but the DOX aqueous solubility decreases in the pH conditions corresponding to the stability of the pH-sensitive liposomes. The study of pH-sensitivity of liposomes was conducted using carboxyfluorescein (CF) encapsulated in high concentration, i.e. quenched, and following the dye dequenching as sensor of the liposome integrity. We studied the impact of (i) the chemical nature of lipids (dioleoyl phosphatidyl ethanolamine (DOPE), palmitoyl-oleoyl phosphatidyl ethanolamine (POPE) and dimyristoyl phosphatidyl ethanolamine (DMPE)) and (ii) the lipid/stabilizing agent ratio (alpha-tocopheryl succinate), on the pH sensitivity of the liposomes. Optimized liposome formulations were then selected for the encapsulation of DOX by an active loading procedure, i.e. driven by a difference in pH inside and outside the liposomes. Numerous experimental conditions were explored, in function of the pH gradient and liposome composition, which allowed identifying critical parameters for the efficient DOX encapsulation in pH-sensitive liposomes. [ABSTRACT FROM AUTHOR]

The diagnosis of brain metastasis (BrM) has historically been a dooming diagnosis that is nothing less than a death sentence, with few treatment options for palliation or prolonging life. Among the few treatment options available, brain radiotherapy (RT) and surgical resection have been the backbone of therapy. Within the past couple of years, immunotherapy (IT), alone and in combination with traditional treatments, has emerged as a reckoning force to combat the spread of BrM and shrink tumor burden. This review compiles recent reports describing the potential role of IT in the treatment of BrM in various cancers. It also examines the impact of the tumor microenvironment of BrM on regulating the spread of cancer and the role IT can play in mitigating that spread. Lastly, this review also focuses on the future of IT and new clinical trials pushing the boundaries of IT in BrM. [ABSTRACT FROM AUTHOR]

The incorporation of siRNA into nanocarriers is mandatory to facilitate its intracellular delivery, as siRNA itself cannot enter cells. However, the incorporation of these nanocarriers into oral, solid dosage forms and their fate in the gastrointestinal environment is yet to be explored. In the present work, the fate of, (i) naked siRNA, (ii) freshly prepared siRNA lipoplexes, and (iii) tableted siRNA lipoplexes, in simulated gastric and intestinal fluids was studied. The siRNA, either released from or protected within the lipoplexes, was quantified by gel electrophoresis and siRNA efficacy was assessed in cell transfection. The freshly prepared lipoplexes kept their siRNA load and transfection efficiency totally preserved during 1 h of incubation in simulated gastric fluid at 37 °C. However, in simulated intestinal fluid, despite no release of siRNA from lipoplexes after 6 h of incubation, gene silencing efficacy was dramatically decreased even after 1 h of exposure. The lipoplexes obtained from tablets efficiently protected siRNA in simulated gastric fluid, thus preserving the gene silencing efficacy, whereas their incubation in simulated intestinal fluid resulted in a marked siRNA release and decreased gene silencing efficacy. These results provided a detailed explanation for understanding the fate of siRNA in gastrointestinal conditions, when simply loaded in lipoplexes or formulated in the form of tablets. [ABSTRACT FROM AUTHOR]

Brain metastasis (BrM) is one of the major causes of death in cancer patients and is associated with an estimated 10–40 % of total cancer cases. The survival rate of brain metastatic patients has not improved due to intratumor heterogeneity, the survival adaptations of brain homing metastatic cells, and the lack of understanding of underlying molecular mechanisms that limit the availability of effective therapies. The heterogeneous population of immune cells and tumor-initiating cells or cancer stem cells in the tumor microenvironment (TME) release various factors, such as chemokines that upon binding to their cognate receptors enhance tumor growth at primary sites and help tumor cells metastasize to the brain. Furthermore, brain metastatic sites have unique heterogeneous microenvironment that fuels cancer cells in establishing BrM. This review explores the crosstalk of chemokines with the heterogeneous TME during the progression of BrM and recognizes potential therapeutic approaches. We also discuss and summarize different targeted, immunotherapeutic, chemotherapeutic, and combinatorial strategies (with chemo-/immune- or targeted-therapies) to attenuate chemokines mediated BrM. [ABSTRACT FROM AUTHOR]

Background: Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer. Methods: Here, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue. mRNA levels, protein expressions and cellular localizations of EZH2 and RUNX3 were analyzed using real-time PCR and immunohistochemistry, respectively. DNA methylation was further assessed by the methylation specific-PCR. Results: Compared to normal tissue, a significant increase in expression of RUNX3 mRNA in 31/57 patient's tumor tissue (p < 0.04) was observed. The expression of EZH2 was found to be upregulated compared to normal, and a significant positive correlation between EZH2 and RUNX3 expression was observed (p = 0.002). 22 of the 27 unmethylated cases at the promoter region of the RUNX3 had elevated RUNX3 protein expression (p < 0.001). Conclusion: The data presented in this study provide new insights into the biology of RUNX3 and highlights the need to revisit our current understanding of the role of RUNX3 in cancer. [ABSTRACT FROM AUTHOR]

This paper determines the effect of international remittances on the healthcare utilization of childbearing mothers in Pakistan using the Pakistan Social and Living Standards Measurement (PSLM) survey, 2018–19. The study reports a significant and positive effect of international remittances on the healthcare outcomes of childbearing mothers. Importantly, the remittance-receiving households have 0.615, 0.208 and 0.306 times the odds of the non-receiving households, utilizing prenatal healthcare, postnatal healthcare, and healthcare decision making, respectively, and all of them are statistically significant. Consequently, the analysis confirms that remittance receiving-households do in fact influence and increase the likelihood of utilizing prenatal healthcare, postnatal healthcare and decisions about medical treatment for women. As regression-based estimation of remittances is prone to selection bias due to the nature of the non-experimental data set, we also used propensity score matching methods, which also confirmed a significant and positive effect of international remittances on healthcare outcomes of the childbearing mothers. Thus, financial support or social development programs by the government or non-governmental organization are pivotal in enhancing the healthcare outcomes and ultimately the living standards of childbearing mothers. [ABSTRACT FROM AUTHOR]

Background: YAP, a potent oncogene and major downstream effector of the mammalian Hippo tumor suppressor pathway can act as either oncogene or tumor suppressor gene based on the type of tissue involved. Despite various studies, the role and mechanism through which YAP mediates its tumor suppressor or oncogenic effects are not yet fully understood. Therefore in the present study we aimed to investigate YAP at DNA, mRNA and protein level and also attempted to correlate our molecular findings with various clinicopathological variables of the patients.Methods: The study comprised of a total 137 genetically unrelated women with sporadic breast cancer cases and normal adjacent tissues not infiltrated with tumor. Mutation of YAP gene was analyzed by automated DNA sequencing. YAP promoter methylation was studied using MS-PCR. Expression at mRNA and protein level was studied using qPCR and IHC respectively.Results: In our study YAP mRNA expression was found to be 8.65 ± 6.17 fold downregulated in 67.15% cases. The expression of YAP when analyzed at the protein level by IHC was found to be absent in 78.83% cases. Results from MS-PCR analysis showed that YAP promoter methylation plays an important role in declining the expression of YAP protein. The absence of YAP protein coincided with 86.60% methylated cases thereby showing a very strong correlation (p = 0.001). We also investigated YAP mutation at the major check point sites in the Hippo pathway and observed no mutation. A significant association was observed on correlating mRNA expression with clinical stages (p = 0.038) and protein expression with ER status (p = 0.018) among Indian breast cancer patients.Conclusion: The expression of YAP was found to be downregulated in response to aberrant promoter methylation. The downregulation of YAP are consistent with previous studies suggesting it to have a tumor suppressive role in breast cancer. We did not observe any mutation at the major check point sites in the Hippo pathway. [ABSTRACT FROM AUTHOR]

Polyhydroxyalkanoates (PHAs) are biopolymers with desirable material properties similar to petrochemically derived plastics. PHAs are naturally produced by a wide range of microorganisms as a carbon storage mechanism and can accumulate to significantly high levels. PHAs are an environmentally friendly alternative to their petroleum counterparts because they can be easily degraded, potentially reducing the burden on municipal waste systems. Nevertheless, widespread use of PHAs is not currently realistic due to a variety of factors. One of the major constraints of large-scale PHA production is the cost of carbon substrate for PHA-producing microbes. The cost of production could potentially be reduced with the use of waste carbon from food-related processes. Food wastage is a global issue and therefore harbours immense potential to create valuable bioproducts. This article's main focus is to examine the state of the art of converting food-derived waste into carbon substrates for microbial metabolism and subsequent conversion into PHAs. [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood. Methods: To identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, identified miRNA) in patient serum samples and SCLC cell lines. To assess the therapeutic potential of miR-1, we developed various in vitro models, including miR-1 sponge (miR-1Zip) and DOX-On-miR-1 (Tet-ON) inducible stable overexpression systems. Mouse models derived from intracardiac injection of SCLC cells (miR-1Zip and DOX-On-miR-1) were established to delineate the role of miR-1 in SCLC metastasis. In situ hybridization and immunohistochemistry were used to analyze the expression of miR-1 and target proteins (mouse and human tumor specimens), respectively. Dual-luciferase assay was used to validate the target of miR-1, and chromatin immunoprecipitation assay was used to investigate the protein-gene interactions. Results: A consistent downregulation of miR-1 was observed in tumor tissues and serum samples of SCLC patients compared to their matched normal controls, and these results were recapitulated in SCLC cell lines. Gain of function studies of miR-1 in SCLC cell lines showed decreased cell growth and oncogenic signaling, whereas loss of function studies of miR-1 rescued this effect. Intracardiac injection of gain of function of miR-1 SCLC cell lines in the mouse models showed a decrease in distant organ metastasis, whereas loss of function of miR-1 potentiated growth and metastasis. Mechanistic studies revealed that CXCR4 is a direct target of miR-1 in SCLC. Using unbiased transcriptomic analysis, we identified CXCR4/FOXM1/RRM2 as a unique axis that regulates SCLC growth and metastasis. Our results further showed that FOXM1 directly binds to the RRM2 promoter and regulates its activity in SCLC. Conclusions: Our findings revealed that miR-1 is a critical regulator for decreasing SCLC growth and metastasis. It targets the CXCR4/FOXM1/RRM2 axis and has a high potential for the development of novel SCLC therapies. MicroRNA-1 (miR-1) downregulation in the tumor tissues and serum samples of SCLC patients is an important hallmark of tumor growth and metastasis. The introduction of miR-1 in SCLC cell lines decreases cell growth and metastasis. Mechanistically, miR-1 directly targets CXCR4, which further prevents FOXM1 binding to the RRM2 promoter and decreases SCLC growth and metastasis. [ABSTRACT FROM AUTHOR]

COVID-19 rapidly spread across the world, constituting a public health disaster unlike any other experienced in decades. The impact exerted on workplaces and their employees was dramatic, and an immense burden fell on healthcare provision globally. Along with "front-line" healthcare staff, sanitation workers at hospitals also had to cope with additional workloads, making them vulnerable to psychological trauma and affecting their quality of life at establishments. This study investigated how the factors of occupational stress, self-efficacy (belief in the capacity to carry out a task well) and mental health altered the WRQoL (Work-Related Quality of Life) of employees carrying out sanitation duties at hospitals in Malaysia. To this end, a survey translated into the Malay language was conducted among 449 such workers during a so-called "recovery movement control order", i.e. quarantine and control measures pertaining to an outbreak of Coronavirus disease. Research involved co-variance-based structural equation modeling, performed in IBM-AMOS-26 software, in order to discern the causal relationship of the aforementioned factors on WRQoL. Results revealed a high level of occupational stress, diminished self-efficacy and poor mental health among the employees surveyed. Such stress directly impacted the WRQoL of the second factor alongside an indirect effect on that of the third, i.e. anxiety stemming from potentially catching the virus and the experience of having to disinfect facilities for treating patients, undertake cleaning duties, and move corpses. [ABSTRACT FROM AUTHOR]

• The loss of LIFR protein expression was observed in Indian breast cancer patients included in our study. • LIFR promoter methylation was observed in 76.64% of the breast cancer cases. • Aberrant promoter methylation of LIFR gene showed a significant correlation with the downregulation of LIFR protein expression. • We observed a novel Glu990Gln mutation in exon 20 of LIFR gene. LIFR functions as a tumor suppressor and metastatic suppressor of breast cancer. The present study investigates the status of LIFR gene in Indian breast cancer patients. A total of 137 breast cancer tissue and 137 adjacent normal tissue which served as controls were analyzed for mutation by automated DNA sequencing, methylation through methylation-specific polymerase chain reaction and its corresponding expression at mRNA and protein level using real-time quantitative polymerase chain reaction and immunohistochemistry respectively in Indian breast cancer patients. All the molecular findings were statistically correlated with clinopathological parameters of the patients to identify its association. LIFR mRNA expression was found to be 2.534 ± 3.52 fold downregulated with subsequent absence of protein in 67.15% cases (92/137). The absence of LIFR protein coincided with 80.95% (85/105) methylated cases thereby showing a very strong correlation among the LIFR promoter methylation and LIFR protein expression (p = 0.0001). We also observed G2968C nucleotide change in 6/137 cases of exon 20 of LIFR gene resulting in Glu990Gln mutation. Correlation of LIFR promoter methylation with geographic location and age at menopause and LIFR mutation with age at menarche, age at first live birth, molecular subtypes of breast cancer, and lymph node status remained significant even after bonferroni correction (p ≤ 0.0027). All these data suggests the relevance of these associations in relation to Indian breast cancer patients. The loss of LIFR protein was frequently found in Indian breast cancer patients, and aberrant promoter methylation showed a significant correlation with its downregulation. [ABSTRACT FROM AUTHOR]

This study examines the GHRM practices and the transformational leadership specific to environmental sustainability of Pakistan's dairy industry. It also investigates the mediating role of pro-environmental behaviour in the relationship of GHRM practices, The environmental-specific transformational leadership, and sustainable behavior. Additionally, the study examines the moderating role of the pro-environmental attitude between GHRM practices and The environmental-specific transformational leadership. The target population consists of employees working in dairy organizations of Pakistan. A simple random sampling technique was used for data collection. A survey questionnaire method was used to collect data; after data screening a total of 430 responses were subjected to SEM for analysis. The findings indicated that the GHRM practices play a significant role in improving employee environmental and sustainable behavior. The environmental-specific transformational leadership positively affects the pro-environmental behaviour of employees, but its impact on sustainable performance is insignificant. In addition, GHRM practices and environmental-specific transformational leadership have been shown to indirectly contribute to sustainable performance through environmental behavior. The pro-environmental attitude moderates the effect of GHRM practices and environmental-specific transformational leadership on pro-environmental behavior, and pro-environmental behavior leads to sustainable performance. This study is one of the rare attempts to examine the integrated impact of GHRM practices and environmental-specific transformational leadership on pro-environmental behavior and sustainable performance in the domain of environmental management. It explicitly offers insights into the literature by developing a mechanism to improve sustainable performance through GHRM practices and environmental-specific transformational leadership in the dairy industry. The findings of this study have postulated that a package of GHRM practices and environmental-specific transformational leadership is needed to build pro-environmental behavior and foster sustainable performance. It can help managers in their effort to build environmental friendly behavior under the lens of a pro-environmental attitude that facilitates sustainable performance. Aligned to cope with the increasing environmental concerns of the dairy industry, this study proposes that managers would support specific transformational environmental leadership along with green discipline by raising pro-environmental behaviour under the lens of a pro-environmental attitude for the implication of environmental policies to achieve sustainable performance of dairy firms. [ABSTRACT FROM AUTHOR]