**Author details**

Rashed Adnan Islam Product Integrity Engineering – Google Devices and Services, Google LLC, Mountain View, CA, United States

\*Address all correspondence to<EMAIL_ADDRESS>
© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**1. Introduction**

Stroke is an unexpected and acute brain disease. It is reported that one of nineteen deaths is related to stroke in the United States, and the mortality rate of stroke is as high as 30% [1]. Stroke is defined by a condition caused by a hemorrhage or occlusion of cerebral blood vessels.  The symptoms of stroke include numbness, confusion, and aphasia, and those signs are related to injured areas in the brain [3]. Since 87% of strokes are related to ischemia in the brain and 13% are involved with the hemorrhage, this review will focus on discussing how nanotechnology improves therapies and diagnosis of ischemia stroke.

Cerebral ischemia initiates a cascade of pathological processes, eventually causing neuron death. Reperfusion is a clinical method to restore the blood flow in the brain by administration of tissue plasminogen activator (t-PA) or mechanical thrombectomy (MT) for treatment of ischemic stroke [4]. However, reperfusion often leads to tissue damage because oxygen influx of reperfusion generates reactive oxygen species (ROS), initiating inflammatory responses including cytokine production and leukocyte infiltration [5]. Many neuroprotectants have been developed to alleviate reperfusion-induced injury, but none of them were clinically approved. There are several reasons for this failure: (1) ineffective drug delivery into the brain because of blood brain barrier (BBB), (2) drugs with short circulation times, poor stability, and toxicity, (3) difficulty in choosing right drugs and doses due to the heterogenicity of stroke (e.g., disease locations and severity).

Recently, nanotechnology emerges as innovative tools in drug delivery and diagnosis to treat a wide range of diseases, such as cancer and inflammatory disorders [6–13]. In the case of ischemic stroke, nanoparticles could possibly deliver therapeutics across BBB, prolong the drug circulation, and increase the drug accumulation at diseased sites. In addition, nanoparticles can be utilized as innovative diagnostic systems to detect several biomarkers (such as ROS and neurotransmitters) in the brain

for early-stage stroke diagnosis. In this review, we firstly describe the physiopathology of ischemic stroke and current limitations in therapy and diagnosis. Then, we discuss how nanotechnology offers opportunities in treating ischemic stroke, highlighting the recent progress on delivering neuroprotective agents, anti-inflammatory drugs, and small interfering RNA (siRNA) to alleviate ischemic injuries. We also review the applications of nanomaterials in stroke diagnosis. Finally, we describe new opportunities in translating nanoparticle-based therapies to clinic in the prevention and treatment of ischemic stroke.

#### **2. Pathology of Stroke and Current Therapies**

#### *2.1. Molecular Mechanisms for Pathology in Stroke*

Acute ischemic stroke and subsequent reperfusion cause a series of pathophysiological changes including neuronal damage, oxidative stress, local inflammation, and loss of blood brain barrier (BBB) integrity [14]. The cellular process and mechanism of ischemic stroke and the ischemic injury cascade is summarized in Figure 1. Herein, we mainly discuss neuronal damage, oxidative stress, and inflammation responses that contribute to the pathogenesis of ischemic stroke. These three events are intertwined, and each can result in brain damage.

**Figure 1.** The cellular process and mechanism of ischemic stroke and the ischemic injury cascade.

#### 2.1.1. Neuronal Damage

Neurons are the major components in brain and are particularly vulnerable to ischemia. Studies have shown that acute cerebral ischemia causes the vasculature infarction, thus leading to neuronal death in rodent models [15]. Due to reduced blood supply in the ischemic brain, adenosine triphosphate (ATP) level drops and lactate acidosis leads to the loss of ionic homeostasis in neurons [14]. Failure to maintain the ion gradients results in depolarization of cell membranes and therefore activating a variety of ion channels such as calcium and sodium channels. Those events also cause the excessive release of glutamate, which initiate more loss of neuronal cells [16]. Glutamate is a major excitatory neurotransmitter in nervous system regulating a variety of excitatory synapses, but high levels of extracellular glutamate can induce the cell death in the late stage. Dead neural cells release damage-associated molecular patterns (DAMPs), which activate the innate and adaptive immune system, initiating inflammatory pathways [17].


*Article* **Simulated Cropping Season Effects on N Mineralization from Accumulated No-Till Crop Residues**

**Rashad S. Alghamdi 1,\*, Larry Cihacek 1 and Qian Wen 2**

**\*** Correspondence<EMAIL_ADDRESS>
**Abstract:** The adoption of no-till management practices has increased in the United States over the last decade. In the state of North Dakota, approximately 5.7 million hectares of cropland is managed under no-till or conservation tillage management practices. Even though conservation tillage is known for building soil health, increasing soil organic matter, capturing soil moisture, and reducing wind and water erosion, it also presents a unique best management practice since an increased mass of crop residue remains on the soil surface. Producers are concerned about whether plant needs are being met by nitrogen fertilizer that is currently being applied based on current North Dakota recommendations for long-term no-till systems. A Forman clay loam soil (fine-loamy, mixed, superactive, frigid Calcic Argiudolls) was used in this study, as it represented glacial till soils of the region. We examined whether N mineralization from surface-applied crop residue would result in similar or different results when compared to crop residue mixed into the soil. Soil freeze-thaw contribution to soil N mineralization was also evaluated. Six residue treatments with different C/N ratios including corn (*Zea mays* L.), soybean (*Glycine max* L.), forage radish (*Raphanus sativus* L.), winter pea (*Pisum sativum* L.), spring wheat (*Triticum aestivum* L.), and winter wheat (*Triticum aestivum* L.) were used. Five 10–14-week cycles with a three-week freeze period between each cycle at 0 ºC were evaluated for NO3-N production. Crop residues with a narrow C/N ratio contributed to greater instances of N mineralization during each incubation cycle, and the accumulation of crop residues with a wide C/N ratio over each incubation cycle following the first incubation did not offset the immobilization trends observed in the first incubation. A change in N mineralized in the untreated control soil during the last two incubation cycles may have been caused by freeze-thaw effects or a shift in microbial population due to a lack of fresh C inputs.

**Keywords:** N mineralization; C/N ratio; crop residue; N availability

**1. Introduction**

In a no-till agricultural system, crop residue remains on the soil surface, whereby in a drier environment with lower soil temperatures may slow and/or reduce nitrogen mineralization, with the potential to affect crop yields. In areas where there is a short growing season, no-till practices have been perceived by producers to delay planting and slow crop emergence as a result of delayed soil warming and drying [1–4]. In a frigid environment, such as that in the Northern Great Plains, these concerns are more pronounced, as crop residue tends to accumulate when high residue crops (corn, small grains) are left on the soil surface as a result of no-till practices. Alghamdi et al. [5] examined soil warming and drying in a frigid environment for corn-soybean systems and provided evidence to suggest that these perceived delays are not related to moisture and temperature of the soil. Daigh et al. [6] have also reported research on full-production scale farms in the Red River Valley of Minnesota and North Dakota (i.e., frigid environment), finding that producer perceptions of delayed warming and drying of the soil do not translate into yield losses. This begs the question of where these perceived losses are coming from.

**Citation:** Alghamdi, R.S.; Cihacek, L.; Wen, Q. Simulated Cropping Season Effects on N Mineralization from Accumulated No-Till Crop Residues. *Nitrogen* **2022**, *3*, 149–160. https:// doi.org/10.3390/nitrogen3020011

Academic Editor: Jacynthe Dessureault-Rompré

Received: 1 March 2022 Accepted: 28 March 2022 Published: 31 March 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

Alghamdi et al. [7] concluded that any differences observed in yield were attributed to fertilizer application methods and rates. Many earlier studies concluded that an addition of nitrogen fertilizer may be necessary under a no-till system to increase nitrogen (N) in the deeper soil profile [8–10], yet modern recommendations often overlook previous decades of research [11]. The rate of soil N mineralization is dependent upon crop residue factors that include, but are not limited to, the type and quantity of residue and other soil factors, such as temperature and moisture in the residue environment and organic matter (OM) in the soil [12]. As residue continues to accumulate on the soil surface in a no-till system, it is necessary to determine if enough N is being provided to subsequent crops to offset the potential immobilization in the system. Schoenau and Campbell [13] reported that conservation tillage such as reduced and no-till systems results in greater surface accumulation of crop residue on top of the soil surface, which slows residue decomposition of wide C/N ratio crops. No-till systems provide added benefits of increased soil moisture and organic matter, although reduced availability of oxygen from aeration needed by microbes may slow the mineralization of nitrogen from the crop residue. In addition to increasing soil moisture, no-till systems can be susceptible to water saturation as a result of increased crop residue on the soil surface. Thus, the activity of microbes may be reduced along with soil shading and slower soil drying due to cooler temperatures [14]. A laboratory study on North Dakotan soils concluded that the type of crop residue and organic matter present may increase N immobilization when crop residue has a wide C/N ratio (>25:1) as compared to crop residue with a narrow C/N ratio (<25:1) [7]. Green and Blackmer [15] examined the rate of N fertilization and its effect on residue decomposition on corn–corn and corn–soybean fields in Iowa. They determined that N immobilization tended to decrease with increased N fertilization as a result of the fertilizer contributing N to the residue biomass. Increasing rates of N fertilization decreased the time required for N mineralization to occur. This process was expedited when soybean residue was the proceeding crop due to the nature of the soybean residue. Li et al. [16] found that N mineralization occurred more quickly with crop residue placed on the soil surface versus crop residues incorporated into the soil. Satchell [17] explained the biological process of decomposition, where plant tissues are broken down by microorganisms. These microorganisms can break down residue more quickly when plant residue is incorporated with the soil [18] as compared to remaining on the soil surface [19]. Coppens et al. [20] found that incorporated crop residues decomposed faster than leaving residue on the soil surface and that higher N fluxes were more pronounced with crop residue incorporation. For the residue that did remain on the soil surface, the absence of moisture was a greater limitation to decomposition than N itself. Often, to aid in the breakdown of high lignin content crop residue, such as corn, many producers apply liquid N to their fields after harvest. Al-Kaisi et al. [21] examined corn residue decomposition and the application rate of liquid urea ammonium nitrate (UAN) following harvest and concluded that increased rates of decomposition were not attributed directly to the application rates of N, but to increased air and soil temperature. They recommended the limiting of liquid N application under less-than-ideal air temperature conditions and/or limited availability of soil moisture during critical periods of residue decomposition. Additional studies have determined similar finding where decomposition effects were attributed to temperature and moisture availability [22–24]. In cooler climates of the Northern Great Plains, such as in North Dakota, highly variable precipitation and temperature conditions during crucial periods of crop N needs can lead to the rate of residue decomposition being less predictable, resulting in less certain N mineralization for crop needs. Vigil and Kissel [25] examined the impact of temperature on nitrogen mineralization and residue decomposition in Kansas soils. Their findings indicated that higher incubation temperatures resulted in increased mineralization. At temperatures lower than 35 ◦C, microbial activity decreased. Nitrogen from sorghum and soybean residues mineralized faster at 35 ◦C than 25 ◦C, 15 ◦C, and 5 ◦C, respectively. Aher et al. [26] examined C/N ratios and the mass of residue on the soil surface near Forman, ND, and indicated potential N deficits to succeeding crops

ranging from 56 to 105 kg N ha−1 following winter weathering of the crop residue. North Dakota has a frigid climate where residue decomposition and nutrient mineralization from crop residues can be limited by the short frost-free period of 100–135 days [27,28]. In the Canadian prairie, an incubation study was conducted to examine the factors influencing the stability of microbes in the soil [29]. Results indicated that freezing and thawing periods had a strong effect on releasing N and other nutrients back into the soil when compared with wetting and drying cycles. The reason for this was that the freeze and thaw periods enabled microorganisms to feed on decomposed residue. During freezing and thawing, soil aggregates are disturbed, exposing sheltered residue to microbes that help release nutrients back to the soil [30,31] or may break up residue particles to provide a greater residue surface area for greater microbial access. During the winter, native soil organic matter mineralizes to release N [32] due to microorganism abate and releases amino acids and simple sugars back into the soil [33]. During thaw periods, surviving microorganisms are active and feed on the nutrients released from dead microorganisms [34]. As a result, many studies have noted the increase in microbial respiration following freezing and thawing periods [33–36]. Current recommendations for N management in North Dakota do not regard temporal residue decomposition and N mineralization and immobilization effects that vary with different types of crop residue in their recommendations. Instead, standardized recommendations are cited for long-term no-till systems (i.e., managed for six or more years) where producers are to take a 34 kg N ha−1 credit [37]. Over the last ten years, recommendations for North Dakota have varied. Standardized N recommendations are useful in warmer and moister climates, which allow for optimum N mineralization from crop residue. Management recommendations for nitrogen fertilization of soil should aim to address concerns of the producer and advance best management practices. The objectives of this study are: (1) evaluate if the type and quantity of crop residue are offsetting the N immobilization, (2) evaluate the influence of freezing and thawing on crop residue decomposition, and (3) evaluate changes in N mineralization due to repeated residue addition over several simulated growing seasons.

### **2. Materials and Methods**


**About the Editors**

**Pavol Bozek ˇ** graduated in 1978 from the Faculty of Mechanical Engineering of the Slovak Technical University in Bratislava. He is currently working in the position of full professor of informatics, automation and mechatronics at the Faculty of Materials Technology based in Trnava of STU in Bratislava. The research activity of Professor Bozek is focused on the area of production ˇ technology, robotics, diagnostics, automation and control of production systems. A total of 11 patents and 16 utility models are registered under his name. He is an expert member of national and international associations (e.g., WAIT—World Association of Innovative Technologies), a scientific board member of the union commission for Manufacturing Technics, a member of the Slovak Institute of Technical Standardization—Industrial Process Management, a member and chairman of the scientific journal Management of Companies' scientific board, and a member of the scientific board ECOLETRA.

**Tibor Krenicky** graduated in Physics at the Faculty of Mathematics and Physics of the Comenius University in Bratislava (Slovakia) in 1999. He completed his PhD in 2005 at the Institute of Experimental Physics of the Slovak Academy of Sciences and the Faculty of Natural Sciences of the UPJS in Kosice. He started teaching in 2005 at the Technical University of Kosice, currently holds an Associate Professor position at the Faculty of Manufacturing Technologies in Presov, Department of Technical Device Design and Monitoring. His work focuses mainly on the simulation, determination and evaluation of operating parameters and the operational status of technical systems using multiparametric monitoring and virtual instrumentation as well as the design and implementation of experimental devices for diagnostics of technical systems. He is an experienced Editorial Board member of several international scientific journals and the Guest Editor of several CCs and indexed Special Issues of scientific papers.

**Yury Nikitin** was born in Izhevsk, Russia. He graduated with a Computer Engineering degree from the Faculty of Instrumentation Engineering of Izhevsk Mechanical Institute in 1988. He received a Candidate of Technical Science degree from the Izhevsk State Technical University (ISTU) in 1994. Yury Nikitin holds the position of Associate Professor of the Department of Mechatronic Systems at ISTU. He has published over 150 journal and conference papers in his field. He has been the principal investigator of several state projects on the research, modelling and diagnosing of mechatronic systems. Yury Nikitin has been awarded the grade of Honorary Worker of Higher Professional Education of the Russian Federation. He is mainly focused on the identification of mechatronic systems, electric motors and equipment, diagnosing and modelling, robotization and automation.