Ligninolytic enzymes: Versatile biocatalysts for the elimination of endocrine‐disrupting chemicals in wastewater

Abstract Direct municipal wastewater effluent discharge from treatment plants has been identified as the major source of endocrine‐disrupting chemicals (EDC) in freshwaters. Consequently, efficient elimination of EDC in wastewater is significant to good water quality. However, conventional wastewater treatment approaches have been deficient in the complete removal of these contaminants. Hence, the exploration of new and more efficient methods for elimination of EDC in wastewater is imperative. Enzymatic treatment approach has been suggested as a suitable option. Nonetheless, ligninolytic enzymes seem to be the most promising group of enzymes for EDC elimination, perhaps, owing to their unique catalytic properties and characteristic high redox potentials for oxidation of a wide spectrum of organic compounds. Therefore, this paper discusses the potential of some ligninolytic enzymes (laccase, manganese peroxidase, and versatile peroxidase) in the elimination of EDC in wastewater and proposes a new scheme of wastewater treatment process for EDC removal.

Runoff and discharge of treated wastewater effluents into freshwaters are the main sources of EDC contamination, perhaps, due to partial elimination of EDC during wastewater treatment. The receiving waterbodies, which serve as the main sources of portable water, are also used for various domestic and agricultural purposes including irrigation, thus exposing the public to biochemical hazards resulting from poor quality wastewater effluents. The U.S. Environmental Protection Agency has described EDC discharged from wastewater treatment plants (WWTPs) as "contaminants of emerging concern with potentially widespread environmental effects." This concern has, consequently, motivated research into EDC including their detection and occurrence in the environment, as well as development of effective method for their elimination in freshwater and wastewater. Recent studies have detected EDC in wastewater (Table 1) and the receiving waterbodies in many countries (Barber, Loyo-Rosales, Rice, Minarik, & Oskouie, 2015;Komesli, Muz, Ak, Bakirdere, & Gokcay, 2015;Noutsopoulos et al., 2015;Vajda et al., 2015). The micropollutants have also been detected in drinking water and sediments (Liu, Kanjo, & Mizutani, 2009). Some examples of EDC detected in water sediments are nonylphenols (NP), bisphenols, hexestrol (HEX), Diethylstilbestrol (DES), dienestrol, androsterone, transdehydrotestosterone (DEHA), 4,5α-dihydrotestosterone (DHT), estrone (E1), 17β-estradiol (E2), trenbolone, 19-norethindrone, and 17α-ethinylestradiol (EE2) (Yuan et al., 2015).
The effect of EDC on the biochemical and physical integrity of water, as well as their impacts on the flora and fauna that depend on freshwaters, has been reported. These effects are profound in fish, wildlife, and humans. Some of the adverse effects in humans include infertility, increase in natal defects, alteration in sexual expression, and cancer (Jobling et al., 2013). Given the ecological risk and adverse health effects associated with exposure of humans to EDC, their removal from the environment should be the utmost priority of stakeholders.  Li et al. (2015) Groundwater and surface water PAHs -Bangladesh Mandal et al. (2015) Surface water Polychlorinated biphenyls (PCBs) 0.93-13.07 ng/l China Yang, Xie, Liu, and Wang (2015) Wastewater and surface water Alkylphenolic chemicals (APs) -USA Barber et al. (2015) Wastewater Pharmaceutical residues 117 μg/l South Africa Matongo, Birungi, Moodley, and Ndungu (2015) Surface water Pharmaceutical residues 84.60 μg/l Unfortunately, removal of EDC by most wastewater treatment plants seems to be inefficient as there is no specific unit designed to eliminate EDC in the present wastewater treatment technology (Zhang, Li, Wang, Niu, & Cai, 2016). Auriol, Filali-Meknassi, Tyagi, Adams, and Surampalli (2006) made the following observations with the use of some conventional treatment processes for removal of EDC in wastewater: Coagulation with the use of "iron and aluminum salts" did not support any EDC removal; however, coagulation involving powdered activated carbon (PAC) removed a significant amount of "small-sized contaminants" including EDC, while filtration processes, which allowed quite high EDC removal, are costly and involve a substantial maintenance in order to prevent membrane clogging. These and some other challenges have led to the development of different treatment methods for EDC removal employing the advanced oxidation processes such as photocatalysis, ozonation, the use of hypochlorites, and chlorine oxides (Silva, Otero, & Esteves, 2012;Taboada-Puig et al., 2015).

TA B L E 1 Detection of EDC in water
Although the advanced oxidation processes have recorded high EDC removal efficiency, they also present some challenges such as increased prices, narrow specificity, and generation of intermediates with unknown or higher estrogenic activity compared to their precursors (Oller, Malato, & Sanchez-Perez, 2011;Silva et al., 2012;Taboada-Puig et al., 2015). It is obvious that most of the conventional treatment methods are characterized by one challenge or the other. Consequently, research efforts should be channeled toward addressing these challenges and developing new wastewater treatment technologies that will effectively remove EDC and other emerging pollutants even at very low concentrations in wastewater. Hence, this paper discusses the potential of ligninolytic enzymes in the elimination of EDC in wastewater and proposes a new scheme of wastewater treatment process for EDC removal. Details of some reported methods of EDC removal are given in the succeeding section.

| CONVENTIONAL ME THODS FOR REMOVAL OF ED C IN WA S TE WATER
Research efforts toward complete removal of EDC in wastewater have continued to increase, and these had led to appreciable progress in recent years. A major progress made so far include the development of new methods for removal of EDC in wastewater.
Some of these methods include but not limited to adsorption, electrochemical oxidation, chemical advanced oxidation, photocatalysis, biodegradation, and enzymatic treatment. Details of these methods are presented as follow:

| Adsorption by activated carbon
Adsorption by activated carbon is one of the most effective techniques for removal of EDC in wastewater (Jeirani, Niu, & Soltan, 2016;Nam, Choi, Kim, Her, & Zoh, 2014). This technique is based on hydrophobic interaction, which is determined by the nature of functional groups on the adsorbent and the adsorbates (Moreno-Castilla, 2004). More so, formation of electron donor-acceptor complex and hydrogen bonding, as well as π-π dispersion interactions, are the major mechanisms reported for adsorption of organic pollutants by carbon in aqueous solutions (Li, Lei, & Huang, 2009;Lladó et al., 2015;Moreno-Castilla, 2004). Jeirani et al. (2016), in a recent review, gave a concise documentation of the major mechanisms involved in adsorption of emerging pollutants on activated carbon.
A major progress in adsorption technique is the exploration of cheap adsorbents for adsorption of emerging organic pollutants. Ifelebuegu, Lester, Churchley, and Cartmell (2006) Li, and Wu (2015) suggested metal-organic frameworks with high porosity and large pore size as potential adsorbents for the removal of EDC in contaminated water.

| Electrochemical oxidation
This approach combines electro-enzymatic catalysis and electrocoagulation as a novel electrochemical approach for the removal of EDC in wastewater, with horseradish peroxidase (HRP) immobilized on graphite felt of titanium electrode as cathode and aluminum plate serving as anode of the working electrode .
Electrochemical approach has been used to remove BPA and reduce

| Chemical advanced oxidation
This approach involves the use of chemical oxidants for the removal of EDC in a process called advanced oxidative process (AOP), which is characterized by the generation of reactive oxygen species (ROS), primarily, hydroxyl radicals (˙OH) that, subsequently, oxidize organic pollutants to carbondioxide (CO 2 ) and inorganic ions (Esplugas, Bila, Gustavo, Krause, & Dezotti, 2007) in wastewater. Another mechanism employed in this approach is the transformation of pollutants to some other metabolic products by some strong oxidizing agents such as chlorine (Cl 2 ), chlorine dioxide (ClO 2 ), hydrogen peroxide (H 2 O 2 ), and ozone (O 3 ) through oxidation-reduction reactions (Liu et al., 2009). The promising potentials of manganese oxide (MnO 2 ) and calcium peroxide (CaO 2 ) as oxidizing agents for EDC removal in wastewater have also been reported (Jiang, Huang, Chen, & Chen, 2009;Zhang, Wang, & Li, 2015). Han, Zhang, Zhao, and Feng (2015) synthesized a new class of stabilized MnO 2 nanoparticles known as carboxymethyl cellulose-stabilized MnO 2 nanoparticles with potential for in situ "oxidative degradation of several emerging contaminants in soil and groundwater" . More so, CaO 2 oxidation has also been employed for effective removal of EDC including E1, E2, EE2, estriol, BPA, and 4-NP in waste-activated sludge . However, the performance of CaO 2 at removing the EDC was dose-dependent . In other words, the efficiency of EDC removal increased with CaO 2 dosage.
The ROS released during CaO 2 oxidation have been identified as the major factor responsible for EDC removal, with hydroxyl radicals (˙OH) playing the most significant role. Interestingly, EDC products from CaO 2 oxidation have shown less estrogenic activity than their precursors, which is an advantage over other advanced oxidation processes that may likely release by-products with higher estrogenic activity than their precursors. CaO 2 treatment has, therefore, been suggested as a promising technology for the removal of EDC in wastewater .
Fenton oxidation is another chemical advanced oxidation employed for removal of EDC in wastewater. Fenton oxidation involves the use of ferrous salt and H 2 O 2 to generate hydroxyl radicals with high redox potential for oxidation of a broad range of organic pollutants (Klavarioti, Mantzavinos, & Kassinos, 2009) including EDC. The effectiveness of this process is enhanced by ultraviolet irradiation in a photo-Fenton reaction, which leads to generation of more hydroxyl radicals (Ifelebuegu & Ezenwa, 2011). Several studies have reported the use of Fenton oxidation in the degradation of organic compounds including pharmaceutical products (Mendez-Arriaga, Esplugas, & Gimenez, 2010;Xu, Wang, Li, & Gu, 2004). Despite the effectiveness of Fenton oxidation, it is characterized by some major setbacks, which include narrow pH range of operation (pH 2-4) and recovery of dissolved ions from treated solutions, which require additional treatment step (Klavarioti et al., 2009). Furthermore, Fenton-like oxidation has been employed for the removal of EDC in wastewater (Ifelebuegu & Ezenwa, 2011). Fenton-like oxidation is the reaction of ferric ion generated from Fenton oxidation with H 2 O 2 to generate ferrous ion and hydroxide radical, which is able to attack aromatic compounds that are protected against hydroxyl radical attack due to the natural organic matters that are present in the treatment plant (Lindsey & Tarr, 2000). Several studies have also reported the use of ozonation in the removal of EDC in water (Bila, Montalvao, & Dezotti, 2005;Huber, Canonica, Park, & von Gunten, 2003;Ternes et al., 2003;Vogna, Marotta, Napolitano, Andreozzi, & d'Ischia, 2004).

| Photocatalysis
This mechanism removes EDC in a photochemical reaction catalyzed by semiconductor metal oxides known as photocatalysts such as titanium dioxide (TiO 2 ), zinc oxide (ZnO), zinc sulfide (ZnS), ferric oxide (Fe 2 O 3 ), and tin oxide (SnO 2 ). During photocatalysis, photon energy absorbed by the catalyst produces an electron excitation, which leads to a change of level from valence to conduction band (Dalrymple, Yeh, & Trotz, 2007 and BPA and their estrogenic activity by UV-LED irradiated TiO 2. All the compounds except E2 were efficiently degraded at a wide pH range as a significant reduction in the total estrogenic activity was also observed. Furthermore, previous studies have also reported reduction and removal of estrogenic activity by photocatalytic treatment with TiO 2 (Coleman, Routledge, Sumpter, Eggins, & Byrne, 2004;Ohko et al., 2001Ohko et al., , 2002.

| Biodegradation
Biodegradation involves the use of microbes including fungi and bacteria for degradation of EDC and other environmental pollutants. Biodegradation has been described as a major removal mechanism that is capable of affecting the fate of EDC in the environment (Yu, Deeb, & Chu, 2013). Over the years, several studies have re- and Agathos (2007a) gave a comprehensive review on the capability of WRF to effectively eliminate EDC in various environmental matrices. In the review, the authors suggested the need to develop "robust and reliable biotechnological processes for the treatment of EDC-contaminated environmental matrices" (Cabana, Jones, and Agathos, 2007a). Cajthaml (2015), in another review, reported the versatility of ligninolytic fungi in the degradation of EDC using the lignin-modifying enzymes system and cytochrome P-450. EDC degradation by ligninolytic fungi occurs through polymerization of the micropollutants or degradation of the original structure by extracellular enzymes system (Cajthaml, 2015). It is worthy of note that ligninolytic fungi are among the very few microbes with the ability to degrade EE2 and PCBs efficiently (Cajthaml, 2015).
Ligninolytic bacteria are also promising candidates for degradation of EDC, perhaps, because of their dexterity in the degradation of recalcitrant compounds and their abilities to produce some ligninmodifying enzymes including laccase and manganese peroxidase, which are mostly responsible for the EDC degradation proficiency manifested by WRF. Bacteria seem to hold stronger potential for EDC degradation, given their striking resilience in diverse environments and the maneuverability of their genome. Furthermore, bacterial degradation has been suggested as an easy way to remove EDC in wastewater (Husain & Qayyum, 2012 On the other hand, the combination of bacteria and physical methods such as adsorption is a novel technique with excellent potential for EDC elimination in an aqueous environment (Zhang et al., 2016). Nevertheless, a major concern on the adoption of biodegradation for EDC removal is the likely introduction of pathogenic microorganisms into the environment, which may also contribute to the problem of antibiotic and multiple drug resistance via horizontal gene transfer. Therefore, enzymatic treatment, involving the use of ligninolytic extracellular enzymes rather than the whole cell culture, will be a suitable alternative. The potential of laccase and MnP for removal of EDC in wastewater has been well studied (Auriol et al., 2008;Ba, Jones, & Cabana, 2014;Cabana, Jones, & Agathos, 2007b, 2009Kim, Yeo, Kim, & Choi, 2008;Lloret et al., 2012;Sei, Takeda, Soda, Fujita, & Ike, 2007).

| PROMIS ING LIG NINOLY TIC ENZ YME S FOR ED C ELIMINATI ON
However, there is dearth of information on the use of VP for EDC elimination. Among the LEs, VP seems to be the most promising for the elimination of EDC in wastewater, given its peculiar attribute of hybrid molecular architecture. Besides, unlike laccase, VP is not dependent on redox mediators for degradation of micropollutants (Ravichandran & Sridhar, 2016). Summary of EDC removal by LEs is presented in Table 2.
The catalytic efficiency of laccases is dependent on the redox potential of the active site type 1 (T1) copper ion (Eldridge et al., 2017), where substrate oxidation occurs in a one-electron reaction.
Usually, microbial laccases exhibit higher redox potential than laccases of plant origin (Gasser et al., 2014). This indicates that laccases from microbes may probably have higher activity and catalytic efficiency when compared to plant laccases. In the other, T2 and T3 form a trinuclear cluster, T2/T3, where molecular oxygen is reduced to water through the electrons transferred from T1 site to the trinuclear site (Gasser et al., 2014;Wong, 2009). Generally, the catalytic reaction of laccases involves oxidation of four molecules of substrate and reduction of molecular oxygen to two water molecules (Gasser et al., 2014). The use of atmospheric oxygen as electron acceptor in a laccase-catalyzed reaction is an advantage over the use of hydrogen peroxide by peroxidases. Nonetheless, laccases depend on redox mediators such as 2,2′-azino-bis (3-ethylbenzthiazoline-6-

Reaction matrix Classes of EDC
Nonetheless, there is limited information on its production by bacteria. Thus, exploitation of bacteria and other fungal genera for VP production is imperative.
The uniqueness of VP is manifested in its hybrid molecular architecture, which combines different substrate binding and oxidation sites (Camarero, Sarkar, Ruiz-Duenas, Martinez, & Martinez, 1999 -Puig et al., 2015). The utilization of MnP pathway by VP commits it to oxidation of phenolic substrates as it is also able to oxidize nonphenolic compounds and other typical substrates of LiP using the normal LiP catalytic reaction mechanism. However, LiP is able to oxidize veratryl alcohol, a typical LiP substrate more effectively than VP. The variation in the catalysis of LiP and VP has been attributed to the variation in the tryptophan environment of the enzymes (Khindaria, Yamazaki, & Aust, 1996).
Specifically, three possible LRET pathways for the oxidation of high redox potential aromatic compounds have been revealed in two VP isozymes (VPL and VPS 1) of Pleurotus eryngii (Caramelo et al., 1999;Perez-Boada et al., 2005;Ruiz-Duenas et al., 1999).  et al., 2005). Therefore, the ability of VP to oxidize high redox potential compounds could, perhaps, be linked to an exposed catalytic tryptophan: Trp-164, which forms a radical on the surface of the enzyme through a LRET to the heme (Ruiz-Dueñas et al., 2009;Saez-Jimenez et al., 2015). Hence, LRET could suffice as a novel mechanism for EDC removal by VP.

| P OTENTIAL OF LE s IN THE ELIMINATI ON OF ED C IN WA S TE WATER
The high environmental and health risk posed by exposure of human to EDC and the inefficiency of the conventional treatment approaches for complete removal of EDC in wastewater, as well as some challenges that characterized the conventional treatment processes, have led to an increased interest in the exploration of alternative treatment processes for elimination of EDC in wastewater.  Garcia-Morales et al., 2015;Ramírez-Cavazos et al., 2014;Taboada-Puig et al., 2011;Touahar et al., 2014;Wen, Jia, & Li, 2009, 2010Zhang & Geissen, 2010).
Immobilized laccase from Cerrena unicolor C-139 eliminated 80% of BPA, 40% of NP, and 60% of triclosan from solutions that contained 50 μmol of each endocrine disruptor, respectively (Songulashvili, Jimenez-tobon, Jaspers, & Penninckx, 2012). Also, Debaste, Songulashvili, and Penninckx (2014)  attributed to the high redox potential of the compound, which hampered its oxidation by the enzyme (Hata, Shintate, Kawai, Okamura, & Nishida, 2010;Ji et al., 2017). Nevertheless, degradation of carbamazepine was enhanced in the presence of BPA, with 40% elimination attained after 24 hr reaction. The authors, therefore, concluded that oxidative products of BPA had a redox mediator effect on the degradation of carbamazepine. The findings from the study suggested that the "presence of more reactive micropollutant can promote the removal of the more recalcitrant pollutants" in a cocktail (Ji et al., 2017).
Moreover, P. ostreatus laccase reduced BPA toxicity from 85% to less than 5%, but there was no decrease in toxicity when treated with laccase from P. pulmonarius. The study indicated that degradation of BPA by P. pulmonarius laccase, probably, generated metabolites with the same toxicity as the parent compound (de Freitas et al., 2017).
Therefore, crude laccase from P. ostreatus was recommended as an efficient degrader of EDC. Besides the use of laccase alone for EDC elimination, Gassara, Brar, Verma, and Tyagi (2013) assessed the effectiveness of free LEs (Laccase, MnP and LiP) and encapsulated LEs in the degradation of BPA. The authors recorded higher degradation efficiency (90%) when the three LEs were encapsulated on polyacrylamide hydrogel and pectin, while only 26% efficiency was observed with the free enzymes.
MnP is another ligninolytic enzyme that has shown effectiveness for elimination of EDC (Inoue, Hata, Kawai, Okamura, & Nishida, 2010;Tamagawa, Yamaki, Hirai, Kawai, & Nishida, 2006;Tsutsumi, Haneda, & Nishida, 2001). In a study by Tsutsumi et al. (2001) in a two-stage (TS) system for continuous removal of the following EDC: BPA, triclosan, E1, E2, and EE2 from synthetic and real wastewaters at degradation rates ranging from 28 to 58 μg/L min, with little enzyme inactivation observed. Interestingly, a 14-fold increase in the EDC removal efficiency of VP in a TS system was observed when compared with a regular enzymatic membrane reactor (EMR) system. Also, some of the operational challenges encountered during EDC removal in an EMR system were prevented, as the TS system was able to separate the complex formation stage from the contaminant oxidation stage. It is noteworthy that VP in a TS enzymatic system exhibited 100% removal efficiency for all the EDC studied, therefore demonstrating the practicability of this approach for removing EDC at both high and environmental concentrations.

| PROP OS ED SCHEME OF WA S TE WATER TRE ATMENT PRO CE SS FOR ED C REMOVAL BY LE s
The present wastewater treatment technology involves three different stages including primary, secondary, and tertiary treatments.
Each stage has specific units for specified treatment (Figure 2a) specific unit is designed to remove EDC during wastewater treatment process. This deficiency has, perhaps, resulted in the occurrence of EDC in wastewater treatment plant effluents (Huang et al., 2014;Ifelebuegu, 2011;Martın, Camacho-Munoz, Santos, Aparicio, & Alonso, 2012;Pessoa et al., 2014;Ra et al., 2011;Zhang et al., 2016). This paper, therefore, proposes a scheme of wastewater treatment process that includes a specific unit for EDC removal at the tertiary treatment stage (Figure 2a). Upon clarification, the liquid is passed through enzymatic treatment unit (ETU) for EDC removal: a three-stage continuous stirred tank reactor (Figure 2b). The first stage is the VP reactor, where Mn 3+ -dicarboxylic acid complex (Mn 3+ -malonate, Mn 3+ -tartrate, or Mn 3+ -oxalate) is generated by immobilized VP, while the second stage (oxidation reactor) involves the oxidation of EDC by the complex generated in stage I (Mendez-Hernandez et al., 2015). In the third stage (laccase-VP reactor), effluent from the oxidation reactor is further treated with laccase coimmobilized with VP to eliminate any residual EDC before passing the effluent through disinfection unit and subsequent disposal.
During the treatment process, the VP reactor will be fed with two different peristaltic pumps. One will be used for the enzyme activator, H 2 O 2 , while the other will be used for the solution of sodium malonate and MnSO 4 (Mendez-Hernandez et al., 2015) at predetermined feeding rates. Another peristaltic pump will be used to feed the laccase-VP reactor with H 2 O 2. However, further research is required to optimize the concentrations of H 2 O 2 , Mn 2+ , and sodium malonate required by VP. It is also imperative to regulate the concentration of H 2 O 2 in the laccase-VP reactor to ensure that laccase activity is not adversely affected as increase in H 2 O 2 may inhibit the enzyme activity (Milton, Giroud, Thumser, Minteer, & Slade, 2013). However, addition of H 2 O 2 may also increase laccase activity during oxidation of some phenolic compounds (Min, Kim, Kim, Jung, & Hah, 2001). Although both enzymes usually perform optimally in slightly acidic pH region (Jarosz-Wilkolazka, Luterek, & Olszewska, 2008;Min et al., 2001;Zdarta et al., 2018), it is important to determine the pH requirements of the enzymes to ensure best performance during application. Likewise, efforts should be geared toward assessing the potential toxicity of Mn 2+ and malonate in the effluent and the chance of recovering them after the enzymatic treatment.
The use of immobilized enzymes is suggested for the proposed technology as immobilization increases enzyme stability and allows the enzymes to be reused in subsequent treatment (Zdarta et al., 2018). A three-stage reaction system is necessary to ensure high efficiency in the elimination of EDC during treatment process. One of the benefits of separating the oxidation process from the Mn 3+ complex generation system is that it allows recirculation of the immobilized enzyme into the VP reactor for reuse (Taboada-Puig et al., 2015). Also, it prevents some operative challenges that characterize conventional enzymatic reactors such as decrease in enzyme activity against time (Rios, Belleville, Paolucci, & Sanchez, 2004;Taboada-Puig et al., 2015). Moreover, a second enzymatic reactor with coimmobilized laccase and VP is essential for complete EDC removal as there is possibility that some more recalcitrant EDC, which may resist oxidation by Mn 3+ complex in stage II (Figure 2b), are present. However, coimmobilized laccase-VP will have a wider EDC removal spectrum through combined advantages. At this stage, VP will catalyze EDC removal in Mn-independent reaction through LRET mechanism, a typical LiP catalytic pathway. Exploitation of the LiP catalytic mechanism by VP will ensure degradation of nonphenolic micropollutants.

| CON CLUS ION
Indeed, LEs have shown great potential for degradation of EDC and other emerging organic micropollutants in wastewater, hence their potential applications in bioremediation and the water sector. More so, a new design of wastewater treatment technology that includes a three-stage continuous stirred tank reactor for EDC removal should be adopted as this will prevent discharge of the micropollutants directly into freshwater environment. Furthermore, coimmobilization or combined cross-linking of laccase and VP will be a promising approach for complete elimination of EDC and other emerging organic pollutants in wastewater as this will provide leverage for laccase in the degradation of nonphenolic pollutants and, consequently, nullifying the cost of redox mediators required by laccase for degradation of nonphenolic compounds.

CO N FLI C T O F I NTE R E S T
Authors declare that there is no conflict of interests.

AUTH O R S' CO NTR I B UTI O N S
Ayodeji O. Falade conceptualized the manuscript and wrote the first draft. Leonard V. Mabinya, Anthony I. Okoh, and Uchechukwu U.
Nwodo contributed to the conception of the manuscript and thoroughly reviewed the manuscript. All authors approved the final version of the manuscript.

DATA ACCE SS I B I LIT Y
No new data were generated in support of this review article.