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Reducing human-elephant conflict (HEC) has recently been recognized as one of the important aspects of wildlife conservation worldwide. Hence, a site-specific study of the efficacy of different traditional methods is necessary to mitigate the HEC in a particular area. Data on elephant visits and the efficacy of different deterrent methods were collected from twelve forest villages in Dharamjaigarh Forest Division of Chhattisgarh, India through field surveys during 2017-21. Findings revealed that both the small male and family herds of elephants mostly visit during the evening hours (50.4%). Interestingly, the family herd of the elephants preferred (95%) the agricultural plot while the small male herd visited mostly (80%) the village area during the entire study period. Making noise was the most common (100%) method practiced by all the villages followed by a fireball (80%). However, in 20% of the cases observed, noise, fireballs, and firecrackers were used to chase out elephants. There were variations in success rate attempts where a maximum (41.7%) was observed in Kudelela and a minimum in Potia (26.4%). Hence, the traditional method is found to be efficient in mitigating the HEC to some extent, however, modern technologies need to be integrated for accruing more efficient results.

This study shows a one-pot preparation of carbon dots by a solvothermal method in ethylene glycol. The carbon dots show yellow-colored fluorescence emission in water. The carbon dots showed distinct preference to be present in the hydrophobic environment which was evident from their efficient transfer from aqueous phase to organic phase. They were also found to locate themselves in the vesicle bilayer and micelle core. This inherent lipophilic character of these carbon dots has been successfully utilized for the selective imaging of lipid droplets inside the living cells. The selective imaging of lipid droplets was confirmed by similar staining patterns with other staining dyes and the starvation study.

Endometrial disorders collectively encompass a broad spectrum of pathologies, including but not limited to endometriosis, endometrial cancer and endometritis. The current therapeutic management of these diseases is associated with several limitations. This has prompted interest in the use of plant-based bioactive compounds as alternative strategies to achieve high therapeutic efficacy and avoid adverse effects. In this context, curcumin, a polyphenol abundantly present in turmeric, is gaining increasing attention for its therapeutic potential to restore homeostasis in endometrial dysfunctionality. We comprehensively review the multifaceted role of curcumin, discussing mechanistic insights in various endometrial pathologies. We also provide an in-depth analysis of the concerns and challenges associated with the role of curcumin in endometrial research and outline a road map for future investigations.

The COVID-19 pandemic started out as a very sudden outbreak and took a turn into a prolonged disaster. With the loss of lives, livelihoods, and normalcy, people had to grasp what had happened. Meaning-making has been central to recovery post a range of disasters. The current study examined the meaning-making processes of thirty-five Indian college students through in-depth interviews during the COVID-19 pandemic. The results were qualitatively analyzed using thematic analysis through NVIVO software and indicated that the pandemic had largely impacted college students’ routines, sleep schedules, education, and college life. Most participants appraised the pandemic as a threat rather than a challenge, which resulted in them experiencing a loss of control. However, the participants employed a range of meaning-making processes to cope with the pandemic. Reinforcing global meaning and benefit finding was most commonly used. Denial was the least used. More participants reported having had positive outcomes of the meaning made. Participants used behavioral and emotional coping strategies that were congruent with the meaning they made. The study has implications for designing and developing promotive and preventive programs for college youth during times of distress.

Large scale destruction of the forest along with encroachments has resulted in higher incidences of human-elephant conflict in Northeast India. People living in proximity to the forests are the worst victim. A study was carried out during 2018–19 to find out the people’s perception on human-elephant conflict in 10 selected fringe villages of the Rani-Garbhanga area of Assam, India. A questionnaire was prepared covering different parameters on human-elephant conflict (HEC). Study found that elephants were attracted the most by paddy, followed by home garden vegetables, stored grain, country liquor, and mud chulla (mud-oven used in village kitchens). An increasing trend of conflict over the period was observed where the majority of the respondents experienced significant crop damage annually. Most of the respondents were not very happy with the compensation practices for crop loss through ex-gratia payment from the government agencies which is often delayed or not paid at all. This delay or non-payment of ex-gratia has resulted in intensifying negative attitudes towards elephant and thus one-third of the total people of the area consider elephants as enemies, and do not vouch for their conservation. An immediate conservation initiative is suggested to conserve Asiatic elephants of this region.

In India, there is limited research on the nature of familial relationships and domestic violence that women living with serious mental illness (SMI) experience. Using the self-in-relation theory and through 34 in-depth interviews, I explored narratives related to family, marriage, and violence in familial relationships among women living with SMI at a psychiatric institution in an urban city in India. These narratives are critical because they highlight how the presence of mental illness exacerbates the violence women experience. Informed by participants’ narratives, I offer specific recommendations on creating gender-sensitive mental health care that is mindful of women’s social realities.

Social accountability (SA), a quintessential goal of medical education, has been discussed as a precipitant for the transition toward competency-based medical education (CBME). However, the relationship between SA and CBME remains unclear. A narrative review was conducted to systematically explore the relationship between SA and CBME as described in the literature.Electronic databases, select journals, and medical education organizations were systematically searched. 363 titles and abstracts were screened and 147 full texts were reviewed. The salient text was extracted from 36 records, which were then inductively coded before narrative synthesis and interpretation.The relationship between SA and CBME was described in three manners: (1) CBME as a natural driver of SA where CBME was perceived to be inherently socially accountable, (2) CBME as an opportunistic mechanism for actively changing medical training to better meet standards of SA, and (3) CBME as a tool to measure SA relating to measurable outcomes data provided by CBME.CBME has theoretical potential to assist programs in becoming more socially accountable if the communities they serve are considered key stakeholders in the design, implementation, and evaluation. A paucity of evidence remains which provides empirical evidence of SA within programs that have implemented CBME.

Hypersensitivity pneumonitis (HP) related deaths have increased substantially in recent years. It is important to identify the risk factors of HP significantly associated with mortality to ensure close patient monitoring and assess disease progression. Extensive literature search was conducted in accordance with the PRISMA checklist. Literature search of PubMed, Embase, and Cochrane Library database between January 2009 and April 2021 using the terms ‘hypersensitivity pneumonitis’, ‘hazard ratio’, and ‘mortality’ identified 325 articles. A total of 22 independent original studies focusing on mortality of HP patients were assessed. This systematic review and meta-analysis suggests that increased age, male sex, honeycombing, and traction bronchiectasis patterns on high-resolution computed tomography (HRCT) images are the major mortality-related risk factors of patients with HP. In case of chronic HP, antigen exposure appeared to be an additional risk factor. The clinico-radiological risk factors of mortality identified for HP will enable effective and close monitoring of patients, prognostication, and guide toward appropriate management decisions. However, association between the type of antigen and mortality remains to be explored.

Farmer distress is a widely recognized problem in India induced by multiple causes ranging from climate variability to price volatility and the low risk-bearing ability of farmers. Tracking farmers’ distress in a localized context is a prerequisite for timely action to provide sustainable livelihood options. Therefore, a field survey was conducted with 640 dryland farmers of 10 sub-district units from two states in India with the aim to identify the major indicators based on seven dimensions of distress and to construct a multidimensional Farmers’ Distress Index (FDI) at the farmer and sub-district levels. The FDI was built with seven dimensions of distress: exposure to risk, adaptive capacity, sensitivity, mitigation and adaptation strategies, triggers, psychological factors, and impacts. The study developed a broad-based FDI which can be used as a planning tool that can address the causes of farmers’ distress and also evolve measures to tackle those causes. Based on the result, the study recommends a location-specific distress management package based on various dimensions of the FDI. The paper also suggests an upscaling strategy to identify and prioritize the highly distressed farmers as well as sub-district geographical units by tracking a few sets of variables.

Purpose: Hypersensitivity pneumonitis (HP), an immune-mediated form of diffuse parenchymal lung disease (DPLD), is triggered by inhalation of a wide variety of allergens in susceptible individuals. Several studies suggest that the death rate associated with this disease has increased significantly in recent years. This meta-analysis investigates the significant clinico-radiological characteristics which may be appraised as potential risk factors associated with disease mortality.Methods: Extensive literature search was conducted for original articles published between January 2009 and April 2021 through PubMed, Google Scholar, EMBASE, and Cochrane Library using the keywords: “hypersensitivity pneumonitis”, “hazard ratio” and “mortality”. Results: A total of 21 independent studies related to mortality of HP subjects could be identified. The combined results of univariate and multivariate analysis suggest that older age [univariate odds ratio (OR) 1.038 (1.028-1.048); multivariate OR 1.036, (1.025-1.046)], male subjects [univariate OR 1.508, (1.240- 1.834); multivariate OR 1.396, (1.004-1.943)], honeycombing [univariate OR 1.086 (1.065- 1.108); multivariate OR 1.121 (1.070- 1.175)] and traction bronchiectasis [univariate OR 1.141 (1.092- 1.192); multivariate OR 1.107 (1.048-1.169)] are significantly associated with mortality risk of HP subjects. Further, forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), ground glass opacity (GGO) and mosaic attenuation were associated with lower risk of all-cause mortality. Although smoking status correlated with mortality risk in these patients, the findings appeared to be insignificant. Conclusion: Individual male subjects with older age and presence of extensive fibrosis, i.e., honeycombing and traction bronchiectasis experience an increased mortality risk.

In this experience report, we describe the work of a coalition of community experts and academics who are collaborating to work towards language justice for communities who speak languages other than English in the Puget Sound region. To illustrate this effort, we describe our experience designing a customizable values statement through participatory design. This values statement can be modified and used in government agencies and organizations to help orient language access plans, programs, and processes towards language justice. We begin by defining language justice and describe how this orientation defines the coalition's overall goals. We then outline the participatory design methods we used to collaboratively iterate three versions of the values statement. First, we describe the workshop we conducted to collectively identify the barriers to language access in the region. Based on these critiques, we decided to design a values statement as a concrete deliverable that could work towards language justice via organizational change. To illustrate the process, we show the four iterations and describe four pivotal moments in the design process that led to significant revisions. These include the need to create a statement highlighting language justice instead of language access; the need to revise the values statement to be organizationally effective for its audience; the need to invite a disability expert to create an inclusive statement; and the need to draw attention to the intersectionality of oppression. Finally, we reflect the impact of the statement in the region and speculate about its future use.

Chronic obstructive pulmonary disease (COPD) associated pulmonary hypertension (COPD-PH), one of the most prevalent forms of PH, is a major burden on the healthcare system. Although PH in COPD is usually of mild-to-moderate severity, its presence is associated with shorter survival, more frequent exacerbations and worse clinical outcomes. The pathophysiologic mechanisms responsible for PH development in COPD patients remain unclear. It is envisioned that a better understanding of the underlying mechanism will help in diagnosis and future treatment strategies. The present study aims to determine metabolomic alterations in COPD-PH patients as compared to healthy controls. Additionally, to ensure that the dysregulated metabolites arise due to the presence of PH per se, an independent COPD cohort is included for comparison purposes. Paired serum and exhaled breath condensate (EBC) samples were collected from male patients with COPD-PH (n = 60) in accordance with the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines. Age, sex and BMI matched healthy controls (n = 57) and COPD patients (n = 59) were recruited for comparison purposes. All samples were characterized using 1H nuclear magnetic resonance (NMR) spectroscopy. Fifteen serum and 9 EBC metabolites were found to be significantly altered in COPD-PH patients as compared to healthy controls. Lactate and pyruvate were dysregulated in both the biofluids and were further correlated with echocardiographic systolic pulmonary artery pressure (sPAP). Multivariate analysis showed distinct class separation between COPD-PH and COPD. The findings of this study indicate an increased energy demand in patients with COPD-PH. Furthermore, both lactate and pyruvate correlate with sPAP, indicating their importance in the clinical course of the disease.

Autophagy is an extremely essential cellular process aimed to clear redundant and damaged materials, namely organelles, protein aggregates, invading pathogens, etc. through the formation of autophagosomes which are ultimately targeted to lysosomal degradation. In this study, we demonstrated that mTOR dependent classical autophagy is ubiquitously triggered in differentiating monocytes. Moreover, autophagy plays a decisive role in sustaining the process of monocyte to macrophage differentiation. We have delved deeper into understanding the underlying mechanistic complexities that trigger autophagy during differentiation. Intrigued by the significant difference between the protein profiles of monocytes and macrophages, we investigated to learn that autophagy directs monocyte differentiation via protein degradation. Further, we delineated the complex cross-talk between autophagy and cell-cycle arrest in differentiating monocytes. This study also inspects the contribution of adhesion on various steps of autophagy and its ultimate impact on monocyte differentiation. Our study reveals new mechanistic insights into the process of autophagy associated with monocyte differentiation and would undoubtedly help to understand the intricacies of the process better for the effective design of therapeutics as autophagy and autophagy-related processes have enormous importance in human patho-physiology.

Multidrug resistance (MDR) of bacteria is a major threat to public health globally and its unprecedented increase calls for immediate alternative medical strategies. Antimicrobial photodynamic therapy (aPDT) offers alternative modalities to combat the growing MDR typically by means of targeted cellular internalization of a photosensitizer (PS) capable of producing photoinduced reactive oxygen species (ROS). However, aPDT is severely limited by the self-aggregation behavior and hydrophobicity of PS molecules, which significantly curbs its viability for clinical application. The present study reports the use of modified nanoscale metal-organic frameworks (NMOFs) encapsulating a hydrophobic PS drug squaraine (SQ) to enhance aPDT efficacy against drug-resistant planktonic bacteria and its biofilm for the first time. Zeolitic imidazolate framework (ZIF-8) NMOF nanocrystals are attached postsynthetically with SQ (designated as ZIF8-SQ) and the resultant drug-doped NMOF is characterized by TEM, FESEM, PXRD, Raman spectroscopy, UV-vis spectroscopy, and steady-state and time-resolved fluorescence techniques. The microporous structures of ZIF-8 behave as molecular cages ceasing the self-aggregation of hydrophobic SQ. In addition, the formulated ZIF8-SQ produces cytotoxic ROS under red-light irradiation (650 nm) in a pH sensitive way primarily due to molecular level interaction and charge separation between ZIF-8 and SQ depicting a dual-stimuli-responsive nature. Most notably, ZIF8-SQ provides unparalleled aPDT action against methicillin-resistant

In India, social determinants of health, including poverty, domestic violence, and inadequate social support disproportionately affect women, leaving them more vulnerable to depression than men. We conducted a metaethnography to synthesize qualitative data from 13 studies (1987–2017) that explored women’s experiences and perceptions of depression in India. We used a feminist standpoint to critically examine how gender shapes these experiences and perceptions. Indian women’s experiences of depression were embedded in their social worlds. Women perceived interpersonal conflict, caregiving burden, domestic violence, financial insecurity, adverse reproductive events and widowhood as causes of depression. Women used cultural expressions to describe physical, emotional, and cognitive distress. The detrimental impact of discriminatory social conditions, gender inequalities, and traditional gender roles on Indian women’s mental health highlights the need for gender-sensitive mental health research and practice that can attend to women’s sociocultural context and promote values of gender equality and social justice.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel pharmacological target for hypercholesterolemia and associated cardiovascular diseases owing to its function to mediate the degradation of low-density lipoprotein receptor (LDLR). Findings over the past two decades have identified novel binding partners and cellular functions of PCSK9. Notably, PCSK9 is aberrantly expressed in a broad spectrum of cancers and apparently contributes to disease prognosis, indicating that PCSK9 could be a valuable cancer biomarker. Experimental studies demonstrate the contribution of PCSK9 in various aspects of cancer, including cell proliferation, apoptosis, invasion, metastasis, anti-tumor immunity and radioresistance, strengthening the idea that PCSK9 could be a promising therapeutic target. Here, we comprehensively review the involvement of PCSK9 in cancer, summarizing its aberrant expression, association with disease prognosis, biological functions and underlying mechanisms in various malignancies. Besides, we highlight the potential of PCSK9 as a future therapeutic target in personalized cancer medicine.

Autophagy is an extremely essential cellular process aimed to clear redundant and damaged materials. In this study, we demonstrated that mTOR dependent classical autophagy is ubiquitously triggered in differentiating monocytes. Moreover, autophagy plays a decisive role in sustaining the process of monocyte to macrophage differentiation. We have delved deeper into understanding the underlying mechanistic complexities that trigger autophagy during differentiation. We have also shown that autophagy directs monocyte differentiation via protein degradation. Further, we delineated the complex cross-talk between autophagy and cell-cycle arrest in differentiating monocytes. This study also inspects the contribution of adhesion on various steps of autophagy and its ultimate impact on monocyte differentiation. Our study reveals new mechanistic insights into the process of autophagy associated with monocyte differentiation and would undoubtedly help to understand the intricacies of the process better for the effective design of therapeutics as autophagy and autophagy-related processes have enormous importance in human patho-physiology.Graphical Abstract

Young adults entering into college experience immense shifts in both personal and professional environments and this may result in some of them experiencing a lot of stress and difficulty in coping with their new surroundings. Such potentially stressful events may trigger multiple psychological as well as physiological effects. The current study investigated multiple psychological parameters such as PSS14 (Perceived Stress Scale), K10 (distress scale) and positive mood measures, along with salivary cortisol levels, in a repeated measures longitudinal study of first year students (~ 19 years of age) enrolled at a residential college in India. Six salivary cortisol samples were collected over a one-year period from 20 students. On each sampling day, a questionnaire designed to evaluate (K10, PSS14 and Mood) psychological parameters was also administered.Overall, men showed a significantly lower level of salivary cortisol compared to women. Men also showed a decrease in perceived stress (PSS14) and distress (K10) with time. However, women reported similar perceived stress and distress levels all year round. Academic stress was reported by the students to be the most important stressor, whereas financial stress was reported the least number of times by all participants. Our results suggest that men seem to have a better capability to adjust to the new environment of a residential program with time. In contrast, women show an elevation in salivary cortisol at the end of the semester (the final assessment stage) in spite of a continuous assessment curricular design. This study not only provides an important glimpse into the sex differences in stress response in the first one year of joining an undergraduate program, but it also provides a valuable longitudinal dataset from the Indian undergraduate student cohort which is lacking in literature.

Pericytes are contractile cells that extend along the vasculature to mediate key homeostatic functions of endothelial barriers within the body. In the central nervous system (CNS), pericytes are important contributors to the structure and function of the neurovascular unit, which includes endothelial cells, astrocytes and neurons. The understanding of pericytes has been marred by an inability to accurately distinguish pericytes from other stromal cells with similar expression of identifying markers. Evidence is now growing in favor of pericytes being actively involved in both CNS homeostasis and pathology of neurological diseases, including multiple sclerosis, spinal cord injury, and Alzheimer's disease among others. In this review, we discuss the current understanding on the characterization of pericytes, their roles in maintaining the integrity of the blood-brain barrier, and their contributions to neuroinflammation and neurorepair. Owing to its plethora of surface receptors, pericytes respond to inflammatory mediators such as CCL2 (monocyte chemoattractant protein-1) and tumor necrosis factor-α, in turn secreting CCL2, nitric oxide, and several cytokines. Pericytes can therefore act as promoters of both the innate and adaptive arms of the immune system. Much like professional phagocytes, pericytes also have the ability to clear up cellular debris and macromolecular plaques. Moreover, pericytes promote the activities of CNS glia, including in maturation of oligodendrocyte lineage cells for myelination. Conversely, pericytes can impair regenerative processes by contributing to scar formation. A better characterization of CNS pericytes and their functions would bode well for therapeutics aimed at alleviating their undesirable properties and enhancing their benefits.

The phagocytic ability of macrophages empowers them to enforce innate immunity. RAW264.7, THP-1 and peripheral blood mononuclear cell-derived macrophages display considerable variability with regards to their phagocytic ability. We identify the underlying causes that attenuate the phagocytic abilities of a macrophage. Deformability of the cytoplasm and cortex influences the macrophage's phagocytic ability, and macrophages use the large cell-to-cell variability of their cytoplasmic stiffness to modulate their phagocytic ability. We find that the more-deformable macrophages have a higher phagocytic ability than those that are less deformable. Further, the subcellular spatial variability of cortex stiffness gives rise to more-deformable subdomains on the membrane for pathogen ingestion. We report a previously unknown negative-feedback loop that is triggered by the phagocytic oxidative burst. Macrophages utilize the excess reactive oxygen species to stiffen the cytoplasm, reducing their phagocytic propensity. In organisms, ageing or pathological conditions impair the phagocytic ability of macrophages. Our findings identify the targets that could potentially be utilized for restoring the phagocytic ability of the defunct macrophages.

Apart from blood coagulation, coagulation proteases are involved inextricably in cancer progression/propagation via intra/inter-cellular signaling, mediated predominantly by protease-activated receptors (PARs). Microvesicles (MVs), a plasma membrane shredded component, has recently been identified as an important contributor to human breast cancer metastasis. However, the role of PAR2 in promoting MVs generation from breast cancer cells remains largely unexplored. The objective of this study is to investigate whether coagulation protease-mediated human breast cancer propagation commences via MVs and also to decipher the underlying signaling mechanism. Here, we elicited that coagulation factor-FVIIa and Trypsin activates PAR2, which governs MVs shedding from MDAMB231 cells by altering actomyosin dynamics. Treatment of cells with PAR2 activators facilitate MVs generation by activating three independent (MAPK, P38, and Rho) signaling cascades. MAPK, signals through activating MLCK followed by MLC phosphorylation to alter myosin organization whereas, P38 reorganizes actin dynamics by the sequential activation of MK2 and HSP27. RhoA-dependent ROCK-II activation again contributes to remodeling myosin II activity. Further, both our in vitro and in vivo analyses showed that these MVs potentiate invasive and migratory property to the recipient cells. Breast cancer patients blood show an elevation of TF-bearing, pro-metastatic MVs than normal. These findings give an insight into the detailed signaling mechanism involved in the production of MVs with transforming ability from PAR2-activated human breast cancer cells. Understanding these mechanistic details will certainly help to identify crucial targets for therapeutic interventions in MVs-associated human breast cancer metastasis.

Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signaling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.

[Image: see text] Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein–lipid interactions.

The present work was carried out to find a suitable eco-friendly sustainable technique for remediation of oily sludge generated from the petroleum industry. Hence, three experimental sets, one with simple land degradation serving as C- set (control), the second one with compost (C+ set), and the third one with silver (Ag) nanoparticles (N set) was used to study the remediation of oily sludge. The three experimental sets each with 500 g of sample were sampled initially at 0 days followed by 15, 30, 45, and 60 days for quantifying pH, conductivity, heavy metals (Pb, Ni, As, and Fe), and total petroleum hydrocarbon (TPH). Our study found that the C+ set (compost) has the highest removal efficiency for heavy metals namely Fe (91.77%), Pb (54.44%), Ni (76.11%), and As (33.48%) as well as TPH (65.52%). All the sets exhibited a positive correlation between pH and TPH as well as between As (Arsenic) and Fe (Iron) and a negative correlation between conductivity and TPH. The pollution index (PI) of As (Arsenic) was between 6.7 to 10.7 exhibiting a very strong level of pollution for all the sets under study. The potential ecological risk index depicted a low level of risk for Pb (0.5–0.30) and Ni (0.043–0.064) whereas moderate level of risk for As (67) in N set and a higher level of risk for C- (88) and C+ (107) set. Based on the results of the present experiment, the application of compost for remediation of oily sludge is better than using nanoparticles and simple land degradation. However, the experiment needs to be carried on for a long period to conclude.

Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3β inactivation is involved in these processes and that β-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of β-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. β-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer.

We sought to investigate the relationship of high life satisfaction with important physical health, mental health, social integration and perceived safety factors among midlife and older Mexican adults. We examined 2,200 midlife and older adults (aged 50-101 years) from the Mexican arm of the Study on global AGEing and adult health (SAGE) and used binary logistic regression models to identify key factors associated with high LSA. Our final logistic regression model revealed self-rated health, affect, interpersonal activities and perceived safety on street to be significantly associated with high life satisfaction. Results from this study add to the nascent literature on subjective well-being of midlife and older Mexicans. Although social work with older adults is not well established in Mexico, researchers and practitioners should collaborate on the development and implementation of social worker-led strategies for prevention and intervention to enhance well-being among midlife and older Mexicans.

The migration of leukocytes into the CNS drives the neuropathology of multiple sclerosis (MS). It is likely that this penetration utilizes energy resources that remain to be defined. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined that macrophages within the perivascular cuff of postcapillary venules are highly glycolytic, as manifested by strong expression of lactate dehydrogenase A (LDHA), which converts pyruvate to lactate. These macrophages expressed prominent levels of monocarboxylate transporter-4 (MCT-4), which is specialized in the secretion of lactate from glycolytic cells. The functional relevance of glycolysis was confirmed by siRNA-mediated knockdown of LDHA and MCT-4, which decreased lactate secretion and macrophage transmigration. MCT-4 was in turn regulated by EMMPRIN (also known as CD147), as determined through coexpression and co-IP studies and siRNA-mediated EMMPRIN silencing. The functional relevance of MCT-4–EMMPRIN interaction was confirmed by lower macrophage transmigration in culture using the MCT-4 inhibitor α-cyano-4-hydroxy-cinnamic acid (CHCA), a cinnamon derivative. CHCA also reduced leukocyte infiltration and the clinical severity of EAE. Relevance to MS was corroborated by the strong expression of MCT-4, EMMPRIN, and LDHA in perivascular macrophages in MS brains. These results detail the metabolism of macrophages for transmigration from perivascular cuffs into the CNS parenchyma and identify CHCA and diet as potential modulators of neuroinflammation in MS.

In this article, I revisit my roots in pursuit of my epistemology. I write about how my mother’s story significantly shaped my interest in narrative inquiry. By inviting my mother to tell her story and through the process of shared meaning making, I learn that narrations are temporal and complex. Stories are built on our lived experiences and as our perceptions about those experiences change with time, so do our interpretations of the stories that we live with. Exposing my own limited understanding of a story that is so deeply connected to me, I conclude that the essence of narrative inquiry lies in multiple interpretations and in letting participants have a significant say over the shaping, structuring, and telling of their narratives.

Rearrangement of actin cytoskeleton correlates significantly with the immune responses as the perturbation of cytoskeletal dynamics leads to many immune deficiencies. Mechanistic insights into this correlation remain unknown. Cellular spreading, the most characteristic phenotype associated with monocyte to macrophage differentiation, led us to investigate the contribution of actomyosin dynamics in monocyte differentiation. Our observation revealed that actomyosin reorganization intrinsically governs the process of monocyte to macrophage differentiation. Further, we established that the MAPK-driven signaling pathways regulate the cellular actomyosin dynamics that direct monocyte to macrophage differentiation. We also identified P42/44 Mitogen-Activated Protein Kinase (P42/44 MAPK), P38 Mitogen-Activated Protein Kinase (P38 MAPK), MAP Kinase Activated Protein Kinase 2 (MK-2), Heat Shock Protein 27 (Hsp-27), Lim Kinase (Lim K), non-muscle cofilin (n-cofilin), Myosin Light Chain Kinase (MLCK) and Myosin Light Chain (MLC) as critical components of the signaling network. Moreover, we have shown the involvement of the same signaling cascade in 3D gel-like microenvironment induced spontaneous monocyte to macrophage differentiation and in human blood-derived PBMC differentiation. Our study reveals new mechanistic insights into the process of monocyte to macrophage differentiation.

Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signalling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. Our findings challenge the notion that adhesion is a result of monocyte differentiation. Rather it’s the adhesion which triggers the differentiation of monocytes. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.Summary statementThis article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.

Trehalose is a well-known protein stabilizing osmolyte. The present study has been designed to understand the interaction of trehalose with BSA at ambient temperature. Steady state fluorescence and life-time analysis along with CD, DLS and ITC have been employed to show that trehalose causes surface-associated structural perturbation of BSA to promote its compaction. Trehalose at 0.1M concentration resulted in increased solvent exposure of one of the two tryptophans of BSA with a 5nm redshift in emission and enhanced susceptibility to acrylamide quenching with an increase in KSV from 2.61M-1to 5.16M-1. 0.5M trehalose resulted in reduced accessibility of tryptophan and destabilization of ANS binding (Forster radius increased from 24A to 27.36A for tryptophan-ANS FRET) indicating shielding of BSA in trehalose matrix. Simultaneously, there was compaction of BSA as shown by increased alpha-helicity from 45.85% to 48.81%, decreased thioflavin-T binding and reduction in hydrodynamic radius from 9.69nm to 6.59nm. Trehalose induced solution viscosity resulted in significant decrease in binding affinity of BSA towards curcumin and resveratrol. The results are in unison with the preferential exclusion and vitrification models to explain protein stabilization by trehalose and also points at the structure-function trade-off of proteins in presence of trehalose.