Toxic heavy metal ions contamination in water and their sustainable reduction by eco-friendly methods: isotherms, thermodynamics and kinetics study.

Heavy metal ions can be introduced into the water through several point and non-point sources including leather industry, coal mining, agriculture activity and domestic waste. Regrettably, these toxic heavy metals may pose a threat to both humans and animals, particularly when they infiltrate water and soil. Heavy metal poisoning can lead to many health complications, such as liver and renal dysfunction, dermatological difficulties, and potentially even malignancies. To mitigate the risk of heavy metal ion exposure to humans and animals, it is imperative to extract them from places that have been polluted. Several conventional methods such as ion exchange, reverse osmosis, ultrafiltration, membrane filtration and chemical precipitation have been used for the removal of heavy metal ions. However, these methods have high operation costs and generate secondary pollutants during water treatment. Biosorption is an alternative approach to eliminating heavy metals from water that involves employing eco-friendly and cost-effective biomass. This review is focused on the heavy metal ions contamination in the water, biosorption methods for heavy metal removal and mathematical modeling to explain the behaviour of heavy metal adsorption. This review can be helpful to the researchers to design wastewater treatment plants for sustainable wastewater treatment.

Arsenic exposure to mouse visceral leishmaniasis model through their drinking water linked to the disease exacerbation via modulation in host protective immunity: a preclinical study.

A large body of evidence has shown a direct link between arsenic exposure and drug resistance to Leishmania parasites against antimonial preparations in visceral leishmaniasis (VL) hyper-endemic regions, especially in India and its sub-continent. However, the implicated roles of arsenic on the VL host, pathophysiological changes, and immune function have not yet been clarified, particularly at the reported concentration of arsenic in the VL hyper-endemic area of Bihar, India. Herein, we exposed the mouse VL model to arsenic (0.5 mg/L to 2 mg/L) through their drinking water and analyzed its effect on T cells proliferation, Th1/Th2-mediators, MAPK signaling cascade, and parasite load in preclinical models. Coherently, the parasite count in Giemsa stained spleen imprint has been investigated and found significant positive associations with levels of arsenic exposure. The liver and kidney function tests (AST, ALT, ALP, BUN, Creatinine, Urea, etc.) are apparent to hepatonephric toxicity in arsenic exposed VL mice compared to unexposed. This observation appears to be consistent with the up-regulated expression of immune regulatory Th2 mediators (IL-4, IL-10, TGF-ß) and down-regulated expression of Th1 mediators (IL-12, IFN-γ, TNF-α) with a suppressed leishmanicidal function of macrophage (ROS, NO, iNOS). We also established that arsenic exposure modulated the host ERK-1/2 and p38 MAPK signaling cascade, limited T lymphocyte proliferation, and a lower IgG2a/IgG1 ratio to favor the Leishmania parasite survival inside the host. This study suggests that the contorted Th1-subtype and exacerbated Th2-subtype immune responses are involved in the increased susceptibility and pathogenesis of Leishmania parasite among subjects/individuals regularly exposed to arsenic.

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma.

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.

A Novel Markov Model-Based Traffic Density Estimation Technique for Intelligent Transportation System.

An intelligent transportation system (ITS) aims to improve traffic efficiency by integrating innovative sensing, control, and communications technologies. The industrial Internet of things (IIoT) and Industrial Revolution 4.0 recently merged to design the industrial Internet of things-intelligent transportation system (IIoT-ITS). IIoT sensing technologies play a significant role in acquiring raw data. The application continuously performs the complex task of managing traffic flows effectively based on several parameters, including the number of vehicles in the system, their location, and time. Traffic density estimation (TDE) is another important derived parameter desirable to keep track of the dynamic state of traffic volume. The expanding number of vehicles based on wireless connectivity provides new potential to predict traffic density more accurately and in real time as previously used methodologies. We explore the topic of assessing traffic density by using only a few simple metrics, such as the number of surrounding vehicles and disseminating beacons to roadside units and vice versa. This research paper investigates TDE techniques and presents a novel Markov model-based TDE technique for ITS. Finally, an OMNET++-based approach with an implementation of a significant modification of a traffic model combined with mathematical modeling of the Markov model is presented. It is intended for the study of real-world traffic traces, the identification of model parameters, and the development of simulated traffic.

Amphotericin B Nano-Assemblies Circumvent Intrinsic Toxicity and Ensure Superior Protection in Experimental Visceral Leishmaniasis with Feeble Toxic Manifestation.

In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani, the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite.

Complex Network Analysis of Mass Violation, Specifically Mass Killing.

News reports in media contain news about society's social and political conditions. With the help of publicly available digital datasets of events, it is possible to study a complex network of mass violations, i.e., Mass Killings. Multiple approaches have been applied to bring essential insights into the events and involved actors. Power law distribution behavior finds in the tail of actor mention, co-actor mention, and actor degree tells us about the dominant behavior of influential actors that grows their network with time. The United States, France, Israel, and a few other countries have been identified as major players in the propagation of Mass Killing throughout the past 20 years. It is demonstrated that targeting the removal of influential actors may stop the spreading of such conflicting events and help policymakers and organizations. This paper aims to identify and formulate the conflicts with the actor's perspective at a global level for a period of time. This process is a generalization to be applied to any level of news, i.e., it is not restricted to only the global level.

A simple monophasic LGPY medium for routine maintenance of Leishmania donovani promastigotes.

Here, we report a simple, economic and autoclavable monophasic LGPY medium supplemented with 10% fetal bovine serum (FBS), for routine maintenance of Leishmania donovani promastigotes for laboratory use. In comparison to commercially available M199 and RPMI-1640 media, LGPY has shown approximately seven fold more cell growth. The parasite has been observed to survive in the medium for at least 15 days post-inoculation. The medium also supports long-term sub-passaging of the promastigotes and can also be stored at 4 °C or room temperature for 14 months and 45 days, respectively.

Uncertainty Assisted Robust Tuberculosis Identification With Bayesian Convolutional Neural Networks.

Tuberculosis (TB) is an infectious disease that can lead towards death if left untreated. TB detection involves extraction of complex TB manifestation features such as lung cavity, air space consolidation, endobronchial spread, and pleural effusions from chest x-rays (CXRs). Deep learning based approach named convolutional neural network (CNN) has the ability to learn complex features from CXR images. The main problem is that CNN does not consider uncertainty to classify CXRs using softmax layer. It lacks in presenting the true probability of CXRs by differentiating confusing cases during TB detection. This paper presents the solution for TB identification by using Bayesian-based convolutional neural network (B-CNN). It deals with the uncertain cases that have low discernibility among the TB and non-TB manifested CXRs. The proposed TB identification methodology based on B-CNN is evaluated on two TB benchmark datasets, i.e., Montgomery and Shenzhen. For training and testing of proposed scheme we have utilized Google Colab platform which provides NVidia Tesla K80 with 12 GB of VRAM, single core of 2.3 GHz Xeon Processor, 12 GB RAM and 320 GB of disk. B-CNN achieves 96.42% and 86.46% accuracy on both dataset, respectively as compared to the state-of-the-art machine learning and CNN approaches. Moreover, B-CNN validates its results by filtering the CXRs as confusion cases where the variance of B-CNN predicted outputs is more than a certain threshold. Results prove the supremacy of B-CNN for the identification of TB and non-TB sample CXRs as compared to counterparts in terms of accuracy, variance in the predicted probabilities and model uncertainty.

TAEO-A Thermal Aware & Energy Optimized Routing Protocol for Wireless Body Area Networks.

Wireless Body Area Networks (WBANs) are in the spotlight of researchers and engineering industries due to many applications. Remote health monitoring for general as well as military purposes where tiny sensors are attached or implanted inside the skin of the body to sense the required attribute is particularly prominent. To seamlessly accomplish this procedure, there are various challenges, out of which temperature control to reduce thermal effects and optimum power consumption to reduce energy wastage are placed at the highest priority. Regular and consistent operation of a sensor node for a long-time result in a rising of the temperature of respective tissues, where it is attached or implanted. This temperature rise has harmful effects on human tissues, which may lead to the tissue damage. In this paper, a Temperate Aware and Energy Optimized (TAEO) routing protocol is proposed that not only deals with the thermal aspects and hot spot problem, but also extends the stability and lifetime of a network. Analytical simulations are conducted, and the results depict better performance in terms of the network lifetime, throughput, energy preservation, and temperature control with respect to state of the art WBAN protocols.

Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study.

The arsenic contamination of ground water in visceral leishmaniasis (VL) endemic areas in Bihar, India leads to human exposure through drinking water. Possibly, the consumed arsenic (As) accumulates in the tissues of VL patients, who subsequently internalize intracellular amastigotes to confer resistance against chemotherapy to the parasite, leading to modulation in the host's immune response. This hypothesis appears to be consistent with the in vitro findings that in arsenic-exposed parasites, the mitochondrial membrane potential became depolarized, whereas the reduced thiol and lactate production was overexpressed with enhanced glucose consumption; therefore, the reduced thiol possibly supports an immunosuppressive state in the host cells. This observation was well supported by the down-regulated expression of pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) with a suppressed anti-leishmanial function of macrophage (NO, ROS). In contrast, the pathophysiological mechanism of VL has received ample support by the promotion of Th2 cytokines (IL-4 and IL-10) in the presence of arsenic-exposed Leishmania parasites (LdAS). Dysfunction of mitochondria and the overexpression of lactate production raise the possibility of the Warburg effect being operative through the up-regulation of glucose consumption by parasites to enhance the energy production, possibly augmenting virulence. Therefore, we surmise from our data that arsenic exposure to Leishmania donovani modulates the immune response and infection pattern by impairing parasite function, which may affect the anti-leishmanial effect in VL.

Exploring new immunological insight on SP15 (∼14 kDa) family protein in saliva of Indian sand-fly (Phlebotomus argentipes) in experimental visceral leishmaniasis.

Visceral leishmaniasis (VL) is a disease caused by protozoan species of the genus Leishmania and is transmitted through bites from the Phlebotomus sand fly; it is associated with considerable morbidity and mortality in many parts of world, including India. Reports on the protective role played by saliva proteins of Lutozomyia longipalpis, Phlebotomus papatasi and Phlebotomus duboscqi. are available. However, no studies have explored the salivary proteins of P. argentipes, which is the known proven vector for the transmission of VL in the Indian sub-continent. Herein we revealed the presence of two proteins of 14.2 and one protein of 13.6 kDa in Indian strain P. argentipes which is absolute identical to previously reported protein of SP15 family (PagSP01, PagSP02 and PagSP07) of P. argentipes of NIH colony, USA. In an experimental study on P. argentipes from Bihar, India, we demonstrated that a strong humoral and cellular immune response was triggered to reduce the concomitant Leishmania load in groups of immunized mice. The immunized group produced a considerable amount of IgG antibodies, and their splenocytes generated TH1 cytokines (IL-12, IFN-γ) with the support of delayed-type hypersensitivity (DTH) reactivity in such mice at the challenged site. We summarize from our data that some identical proteins to previous from SP15 family protein of 14.2 and 13.6 kDa molecular size, derived from Indian P. argentipes and reported its first time, can also be significant in resolution of VL infection after modulation of host protective T cell response in VL.

Co-factor-independent phosphoglycerate mutase of Leishmania donovani modulates macrophage signalling and promotes T-cell repertoires bearing epitopes for both MHC-I and MHC-II.

Immunoactivation depends upon the antigen potential to modulate T-cell repertoires. The present study has enumerated the effect of 61 kDa recombinant Leishmania donovani co-factor-independent phosphoglycerate mutase (rLd-iPGAM) on mononuclear cells of healthy and treated visceral leishmaniasis subjects as well as on THP-1 cell line. rLd-iPGAM stimulation induced higher expression of interleukin-1ß (IL-1ß) in the phagocytic cell, its receptor and CD69 on T-cell subsets. These cellular activations resulted in upregulation of host-protective cytokines IL-2, IL-12, IL-17, tumour necrosis factor-α and interferon-γ, and downregulation of IL-4, IL-10 and tumour growth factor-ß. This immune polarization was also evidenced by upregulation of nuclear factor-κ light-chain enhancer of activated B cells p50 and regulated expression of suppressor of mother against decapentaplegic protein-4. rLd-iPGAM stimulation also promoted lymphocyte proliferation and boosted the leishmaniacidal activity of macrophages by upregulating reactive oxygen species. It also induced 1·8-fold higher release of nitric oxide (NO) by promoting the transcription of inducible nitric oxide synthase gene. Besides, in silico analysis suggested the presence of major histocompatibility complex class I and II restricted epitopes, which can proficiently trigger CD8+ and CD4+ cells, respectively. This study reports rLd-iPGAM as an effective immunoprophylactic agent, which can be used in future vaccine design.

Direct evidence for role of anti-saliva antibodies against salivary gland homogenate of P. argentipes in modulation of protective Th1-immune response against Leishmania donovani.

Currently the main concerns regarding control of visceral leishmaniasis (VL) caused by L. donovani are immunosuppression, relating toxicity of anti-leishmanial drug and little development in appropriate vaccine and vector (P. argentipes) control. Reports available from ex-vivo studies reflect significance of vector salivary gland homogenate (SGH) in reverting immunosuppression of infected VL subjects and as such the immunogenic nature of SGH can be a strategy to modulate immune system and anti-leishmanial function to enable immune response to control the disease. Several related studies also identified a better utility of vector anti-saliva antibodies in achieving such effects by an adoptive transfer approach instead of direct stimulation with SGH protein. However, conclusive evidences on VL cases are far beyond satisfactory to suggest role of SGH into modulation of host immune response in VL subjects in India. This study was under taken to make comparison on change in cytokines (TH1 and TH2) response pattern and anti-leishmanial macrophage (Mϕ) function following stimulation of their PBMCS with SGH protein derived from P. argentipes sand fly vector for VL or anti SGH antibodies raised in rabbit. This study reports for the first time that L. donovani sensitized healthy subject demonstrates an up-regulated Interferon-γ (TH1) and down regulate Interleukin-10 (TH2) production following stimulation of their PBMCs by P. argentipes anti-saliva antibodies accompanied with an improvement in anti-leishmanial Mϕ function for nitric oxide (NO) production. Subsequent experiments suggest that P. argentipes based anti-SGH antibodies when used to stimulate LD infected PBMCs in healthy subjects resulted in better clearance of Leishmania amastigotes load compare to SGH protein. Possibly the immunogenic components of anti-saliva an antibody maintains the level of protective cytokine (INF-γ) and seems to restrict the infection by host protection by vector saliva.