Uttaranchal University

Additive Manufacturing (AM) has revolutionized the manufacturing industry in several directions. Laser powder bed fusion (LPBF), a powder bed fusion AM process, has been dramatically accepted in various industries due to its versatility with several materials, including alloys. This comprehensive review article primarily explains the basic principle of the LPBF process, scientific and technological progress of several inter-related parameters, feedstock materials, produced properties/defects, and insights of numerical modelling to virtually understand the process behavior. Specific attention has been given to selective laser-meted (LPBFed) properties, driven through the microstructure formations and, thereby, concerning defects. The scope of the post-processing techniques to refine microstructure has also been discussed in this review paper. It has been identified that the defects are vital in LPBF process and are primarily governed by the process parameters. Therefore, a wisely chosen, optimized set of parameters can play a crucial role in minimizing defects considerably. Finally, the numerical modeling discussed in this review paper will help the researchers understand the LPBF process.

The most popular additive manufacturing (AM) technologies to produce titanium alloy parts are electron beam melting (EBM), selective laser melting (SLM) and directed energy deposition (DED). This investigation explores mainly these three techniques and compares these three methods comprehensively in terms of microstructure, tensile properties, porosity, surface roughness and residual stress based on the information available in the literature. It was found that the microstructure is affected by the highest temperature generated and the cooling rate which can be tailored by the input variables of the AM processes. The parts produced from EBM have strength comparable to that of conventionally fabricated counterparts. SLM and DED yield superior strength, which can be up to 25% higher than traditionally manufactured products. Due to the presence of larger tensile residual stress, surface roughness and porosity, AM fabricated parts have lower fatigue life compared to those of from traditional methods. EBM parts have slightly lower fracture toughness (i.e., lower fatigue life) than conventionally produced parts while SLM and DED have significantly lower fracture toughness. Annealing, hot isostatic pressing, stress relief and additional machining processes improve the characteristics of parts produced from AM. Ti–6Al–4V alloy parts fabricated via AM may have limited applications despite the high demands in aerospace or biomedical engineering. Since rapid product development using 3D printers leads to significant cost reductions more recently, it is expected that more opportunities may soon be available for the AM of titanium alloys with newer AM processes such as cold spray additive manufacturing (CSAM) and additive friction stir deposition (AFSD).

Breast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management. However, recent advances in molecular biology and immunology enable to develop highly targeted therapies for many forms of breast cancer. The primary objective of targeted therapy is to inhibit a specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, and different growth factors have emerged as potential therapeutic targets for specific breast cancer subtypes. Many targeted drugs are currently undergoing clinical trials, and some have already received the FDA approval as monotherapy or in combination with other drugs for the treatment of different forms of breast cancer. However, the targeted drugs have yet to achieve therapeutic promise against triple-negative breast cancer (TNBC). In this aspect, immune therapy has come up as a promising therapeutic approach specifically for TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, and adoptive cell transfer have been extensively studied in the clinical setting of breast cancer, especially in TNBC patients. The FDA has already approved some immune-checkpoint blockers in combination with chemotherapeutic drugs to treat TNBC and several trials are ongoing. This review provides an overview of clinical developments and recent advancements in targeted therapies and immunotherapies for breast cancer treatment. The successes, challenges, and prospects were critically discussed to portray their profound prospects.

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10-20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5' end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.

Neuroinflammation, a protective response of the central nervous system (CNS), is associated with the pathogenesis of neurodegenerative diseases. The CNS is composed of neurons and glial cells consisting of microglia, oligodendrocytes, and astrocytes. Entry of any foreign pathogen activates the glial cells (astrocytes and microglia) and overactivation of these cells triggers the release of various neuroinflammatory markers (NMs), such as the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-1β (IL-10), nitric oxide (NO), and cyclooxygenase-2 (COX-2), among others. Various studies have shown the role of neuroinflammatory markers in the occurrence, diagnosis, and treatment of neurodegenerative diseases. These markers also trigger the formation of various other factors responsible for causing several neuronal diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS), ischemia, and several others. This comprehensive review aims to reveal the mechanism of neuroinflammatory markers (NMs), which could cause different neurodegenerative disorders. Important NMs may represent pathophysiologic processes leading to the generation of neurodegenerative diseases. In addition, various molecular alterations related to neurodegenerative diseases are discussed. Identifying these NMs may assist in the early diagnosis and detection of therapeutic targets for treating various neurodegenerative diseases.

The current advancements in nanotechnology are as an outcome of the development of engineered nanoparticles. Various metallic nanoparticles have been extensively explored for various biomedical applications. They attract lot of attention in biomedical field due to their significant inert nature, and nanoscale structures, with size similar to many biological molecules. Their intrinsic characteristics which include electronic, optical, physicochemical and, surface plasmon resonance, that can be changed by altering certain particle characteristics such as size, shape, environment, aspect ratio, ease of synthesis and functionalization properties have led to numerous applications in various fields of biomedicine. These include targeted drug delivery, sensing, photothermal and photodynamic therapy, imaging, as well as the modulation of two or three applications. The current article also discusses about the various properties of metallic nanoparticles and their applications in cancer imaging and therapeutics. The associated bottlenecks related to their clinical translation are also discussed.

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due to global demographic changes. NDs are mainly represented by degeneration/loss of neurons, which is primarily accountable for severe mental illness. This neuronal degeneration leads to many neuropsychiatric problems and permanent disability in an individual. Moreover, the tight junction of the brain, blood-brain barrier (BBB)has a protective feature, functioning as a biological barrier that can prevent medicines, toxins, and foreign substances from entering the brain. However, delivering any medicinal agent to the brain in NDs (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) is enormously challenging. There are many approved therapies to address NDs, but most of them only help treat the associated manifestations. The available therapies have failed to control the progression of NDs due to certain factors, i.e., BBB and drug-associated undesirable effects. NDs have extremely complex pathology, with many pathogenic mechanisms involved in the initiation and progression; thereby, a limited survival rate has been observed in ND patients. Hence, understanding the exact mechanism behind NDs is crucial to developing alternative approaches for improving ND patients' survival rates. Thus, the present review sheds light on different cellular mechanisms involved in NDs and novel therapeutic approaches with their clinical relevance, which will assist researchers in developing alternate strategies to address the limitations of conventional ND therapies. The current work offers the scope into the near future to improve the therapeutic approach of NDs.

The novelty of this present work is to investigate the anti-bacterial and anti-fungal activity of the green synthesized titanium dioxide (TiO2) nanoparticles using leaf extract of Mentha arvensis, titanium tetraisopropoxide act as the precursor and leaf extract act as the reducing agent. Synthesized nanoparticles were characterized by using X-ray diffraction, UV–Visible absorbance spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy methods. The X-ray diffraction study of the synthesized nanoparticles shows the crystalline structure and the incidence of peaks at 25.27° corresponds to 110 anatase form. Scanning electron microscope study revealed that the synthesized nanoparticle was spherical in shape and the average size of the synthesized nanoparticles was found to be the range of 20–70 nm. Green synthesized TiO2nanoparticle exhibited interesting antibacterial and antifungal activity against selected microorganism.

In the present study we proposed a green approach for the synthesis of ZnO nano particles using Euphorbia hirta leaves extract. ZnO nanoparticles have a very broad range of applications especially as antimicrobial agent. There are various methods are available for the synthesis of ZnO nanoparticles but among them the synthesis of ZnO nanoparticles by using plant material is a very good alternative and eco friendly method. Leaves extract was used as a biological reducing agent for the synthesis of ZnO nano particles from the zinc nitrate. The prepared nano particles were characterized by using various analytical and spectroscopic tools such as UV visible spectroscopy, Fourier transform infrared spectroscopy (FT- IR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis. Along with this study we also investigate the antimicrobial activity of bio synthesized nanoparticles by using disc diffusion method against clinical and standard strains of Streptococcus mutans, Streptococcus aureus, Clostridium absonum, Escherichia coli and Arthogrophis cuboida, Aspergillius fumigates and Aspergillius nigar.

Over the past few decades, there has been a significant increase in population and unsustainable urbanization, resulting in the exploitation of water and energy resources on a large scale. This has led to a rise in the demand for freshwater, which, in turn, has caused water pollution due to the improper disposal of wastewater from various sources such as industries, agriculture, and households. The wastewater from industries often contains toxic heavy metals and harmful emerging contaminants (ECs), which can harm living beings and cannot biodegrade. Hence, it is a severe issue that needs to be addressed. To combat this problem, wastewater treatments are necessary for two main reasons: firstly, to recycle and reuse wastewater to meet future human demand and reduce water scarcity, and secondly, to ensure compliance with wastewater discharge standards for environmental sustainability while minimizing groundwater and soil contamination. In this review, several wastewater treatment technologies comprising physical, chemical, and biological methods have been discussed critically. The state-of-the-art discussion on different existing wastewater treatment techniques and their limitations has been deliberated. Finally, the limitations of the various existing wastewater treatment techniques and contemporary trends in wastewater treatment have been highlighted.

Carbon nanotubes (CNTs), are safe, biocompatible, bioactive, and biodegradable materials, and have sparked a lot of attention due to their unique characteristics in a variety of applications, including medical and dye industries, paper manufacturing and water purification. CNTs also have a strong film-forming potential, permitting them to be widely employed in constructing sensors and biosensors. This review concentrates on the application of CNT-based nanocomposites in the production of electrochemical sensors and biosensors. It emphasizes the synthesis and optimization of CNT-based sensors for a range of applications and outlines the benefits of using CNTs for biomolecule immobilization. In addition, the use of molecularly imprinted polymer (MIP)-CNTs in the production of electrochemical sensors is also discussed. The challenges faced by the current CNTs-based sensors, along with some the future perspectives and their future opportunities, are also briefly explained in this paper.

PURPOSE: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented. METHODS: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling. RESULTS: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only. CONCLUSION: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality.

Environmental pollution has posed a major threat to flora as well as fauna for the past few decades. Industries release effluents into the environment which act as the major source of pollution. The hazardous effects of heavy metals released from these industries impact the soil and due to bioaccumulation of these compounds in the food chain, they ultimately result in a serious human health hazard. The concentration of metals like chromium (Cr), lead (Pb), nickel (Ni), cadmium (Cd), zinc (Zn), titanium (Ti), cobalt (Co), and several others in plants as well as in aquatic animals is above permissible limits according to the World Health Organization (WHO) and the Federal Environmental Protection Agency (FEPA) guidelines. This is why we need to prevent the aquatic ecosystem and human health from detrimental effects. In this review we will be discussing the harmful effects of these metals on soil, plants, aquatic ecosystems, and human health.

Plant-based phytochemicals are known for their potential sources of anti-inflammatory agents. Various studies reported the potential disease-healing efficiency of medicinal plants’ crude extracts, pure compounds, and their metal/metal oxide nanoparticles (M/MONPs) against inflammation. The purpose of this paper is to review the current research status of phytochemicals of medicinal plants and their nanoparticles as anti-inflammatory agents reported by various studies. Phytochemicals representing the class of flavonoids, terpenoids, polyphenols, saponins, tannins, alkaloids, anthraquinones, chemical constituents of essential oils, and some of their M/MONPs were reported from about 50 medicinal plants for the treatment of inflammatory diseases. The natural products of these plants demonstrated promising anti-inflammatory activities to treat skin, liver, cardiovascular, joint, gastrointestinal, neurological, and lung inflammation diseases. Besides, the mechanism of anti-inflammatory actions of phytochemicals and their M/MONPs agents are also summarized briefly. Various studies of phytochemistry, M/MONPs, and anti-inflammatory activities of phytochemicals from medicinal plants have developed novel, safe, and lesser side effects agents. Hence, this review may draw the attention of scholars more toward the investigation of natural products of medicinal plants and their nanoparticles in the treatment of different health disorders.

Centella asiatica is an ethnomedicinal herbaceous species that grows abundantly in tropical and sub-tropical regions of China, India, South-Eastern Asia and Africa. It is a popular nutraceutical that is employed in various forms of clinical and cosmetic treatments. C. asiatica extracts are reported widely in Ayurvedic and Chinese traditional medicine to boost memory, prevent cognitive deficits and improve brain functions. The major bioactive constituents of C. asiatica are the pentacyclic triterpenoid glycosides, asiaticoside and madecassoside, and their corresponding aglycones, asiatic acid and madecassic acid. Asiaticoside and madecassoside have been identified as the marker compounds of C. asiatica in the Chinese Pharmacopoeia and these triterpene compounds offer a wide range of pharmacological properties, including neuroprotective, cardioprotective, hepatoprotective, wound healing, anti-inflammatory, anti-oxidant, anti-allergic, anti-depressant, anxiolytic, antifibrotic, antibacterial, anti-arthritic, anti-tumour and immunomodulatory activities. Asiaticoside and madecassoside are also used extensively in treating skin abnormalities, burn injuries, ischaemia, ulcers, asthma, lupus, psoriasis and scleroderma. Besides medicinal applications, these phytocompounds are considered cosmetically beneficial for their role in anti-ageing, skin hydration, collagen synthesis, UV protection and curing scars. Existing reports and experimental studies on these compounds between 2005 and 2022 have been selectively reviewed in this article to provide a comprehensive overview of the numerous therapeutic advantages of asiaticoside and madecassoside and their potential roles in the medical future.

Air pollution is a major issue all over the world because of its impacts on the environment and human beings. The present review discussed the sources and impacts of pollutants on environmental and human health and the current research status on environmental pollution forecasting techniques in detail; this study presents a detailed discussion of the Artificial Intelligence methodologies and Machine learning (ML) algorithms used in environmental pollution forecasting and early-warning systems; moreover, the present work emphasizes more on Artificial Intelligence techniques (particularly Hybrid models) used for forecasting various major pollutants (e.g., PM2.5, PM10, O3, CO, SO2, NO2, CO2) in detail; moreover, focus is given to AI and ML techniques in predicting chronic airway diseases and the prediction of climate changes and heat waves. The hybrid model has better performance than single AI models and it has greater accuracy in prediction and warning systems. The performance evaluation error indexes like R2, RMSE, MAE and MAPE were highlighted in this study based on the performance of various AI models.

CRISPR-Cas9 has emerged as a revolutionary tool that enables precise and efficient modifications of the genetic material. This review provides a comprehensive overview of CRISPR-Cas9 technology and its applications in genome editing. We begin by describing the fundamental principles of CRISPR-Cas9 technology, explaining how the system utilizes a single guide RNA (sgRNA) to direct the Cas9 nuclease to specific DNA sequences in the genome, resulting in targeted double-stranded breaks. In this review, we provide in-depth explorations of CRISPR-Cas9 technology and its applications in agriculture, medicine, environmental sciences, fisheries, nanotechnology, bioinformatics, and biotechnology. We also highlight its potential, ongoing research, and the ethical considerations and controversies surrounding its use. This review might contribute to the understanding of CRISPR-Cas9 technology and its implications in various fields, paving the way for future developments and responsible applications of this transformative technology.

Background: Impaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes. Purpose of review: Although many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review. Recent findings: Although complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value. Summary: The adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals' patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.

Carcinoma of the lungs is among the most menacing forms of malignancy and has a poor prognosis, with a low overall survival rate due to delayed detection and ineffectiveness of conventional therapy. Therefore, drug delivery strategies that may overcome undesired damage to healthy cells, boost therapeutic efficacy, and act as imaging tools are currently gaining much attention. Advances in material science have resulted in unique nanoscale-based theranostic agents, which provide renewed hope for patients suffering from lung cancer. Nanotechnology has vastly modified and upgraded the existing techniques, focusing primarily on increasing bioavailability and stability of anti-cancer drugs. Nanocarrier-based imaging systems as theranostic tools in the treatment of lung carcinoma have proven to possess considerable benefits, such as early detection and targeted therapeutic delivery for effectively treating lung cancer. Several variants of nano-drug delivery agents have been successfully studied for therapeutic applications, such as liposomes, dendrimers, polymeric nanoparticles, nanoemulsions, carbon nanotubes, gold nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, hydrogels, and micelles. In this Review, we present a comprehensive outline on the various types of overexpressed receptors in lung cancer, as well as the various targeting approaches of nanoparticles.

Electronic trash, often known as E-waste, is a type of garbage generated by electronic in the industrial world, trash is one of the most difficult and rapidly expanding issues. E-waste is made up of old or end-of-life electronic appliances such as computers, laptops, televisions, generators, DVDs, mobile phones, freezers, and other items that are typically discarded by their original owners due to their short lifespan. It contains a number of hazardous constituents that have a negative impact on the environment and, more importantly, human health if not properly managed. Because it includes harmful chemical elements, E-waste proves to be a significant difficulty. Since it is believed that E-waste is a future of communications but due to the short life span of various appliances, they are being trashed and pollutes the environment. Many groups and governments from various nations have implemented a variety of ways to address the problem and threat to the environment and human health. Hence, this review presents a compendium of various sources of E-waste, environmental hazards, its composition and characterization, E-waste scenarios in India and global world. For the sake of the future, techniques of handling and processing, as well as E-waste recycling, should be used. This paper mainly outlines the issue of E-waste also covering the improvement and plan to tackle the issue.