Intestinal Lymphatic Biology, Drug Delivery and Therapeutics: Current status and Future directions.

Historically, the intestinal lymphatics were considered passive conduits for fluids, immune cells, dietary lipids, lipid soluble vitamins and lipophilic drugs. Studies of intestinal lymphatic drug delivery in the late 20th century focussed primarily on the drug physicochemical properties, especially high lipophilicity, that resulted in intestinal lymphatic transport. More recent discoveries have changed our traditional view by demonstrating that the lymphatics are active, plastic and tissue-specific players in a range of biological and pathological processes, including within the intestine. These findings have, in turn, inspired exploration of lymph-specific therapies for a range of diseases, as well as the development of more sophisticated strategies to actively deliver drugs or vaccines to the intestinal lymph, including a range of nanotechnologies, lipid prodrugs and lipid-conjugated materials that 'hitchhike' on lymphatic transport pathways. With the increasing development of novel biological therapeutics there has been interest in whether these novel therapeutics are absorbed and transported through intestinal lymph after oral administration. Here we review the current state of understanding of the anatomy and physiology of the gastrointestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. We summarise the current state-of-the-art approaches to deliver drugs and quantify their uptake into the intestinal lymphatic system. Finally, and excitingly, we discuss recent examples of significant pharmacokinetic and therapeutic benefits achieved via intestinal lymphatic drug delivery. We also propose approaches to advance the development and clinical application of intestinal lymphatic delivery strategies into the future. Significance Statement This comprehensive review details understanding of the anatomy and physiology of the intestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. It highlights current state-of-the-art approaches to deliver drugs to the intestinal lymphatics and the shift toward the use of these strategies to achieve pharmacokinetic and therapeutic benefits for patients.

Enhancing nitrogen use efficiency and yield of maize (Zea mays L.) through Ammonia volatilization mitigation and nitrogen management approaches.

Management of nitrogen (N) fertilizer is a critical factor that can improve maize (Zea mays L.) production. On the other hand, high volatilization losses of N also pollute the air. A field experiment was established using a silt clay soil to examine the effect of sulfur-coated urea and sulfur from gypsum on ammonia (NH3) emission, N use efficiency (NUE), and the productivity of maize crop under alkaline calcareous soil. The experimental design was a randomized complete block (RCBD) with seven treatments in three replicates: control with no N, urea150 alone (150 kg N ha-1), urea200 alone (200 kg N ha-1), urea150 + S (60 kg ha-1 S from gypsum), urea200 + S, SCU150 (sulfur-coated urea) and SCU200. The results showed that the urea150 + S and urea200 + S significantly reduced the total NH3 by (58 and 42%) as compared with the sole application urea200. The NH3 emission reduced further in the treatment with SCU150 and SCU200 by 74 and 65%, respectively, compared to the treatment with urea200. The maize plant biomass, grain yield, and total N uptake enhanced by 5-14%, 4-17%, and 7-13, respectively, in the treatments with urea150 + s and urea200 + S, relative to the treatment with urea200 alone. Biomass, grain yield, and total N uptake further increased significantly by 22-30%, 25-28%, and 26-31%, respectively, in the treatments with SCU150 and SCU200, relative to the treatment with urea200 alone. The applications of SCU150 enhanced the nitrogen use efficiency (NUE) by (72%) and SCU200 by (62%) respectively, compared with the sole application of urea200 alone. In conclusion, applying S-coated urea at a lower rate of 150 kg N ha-1 compared with a higher rate of 200 kg N ha-1 may be an effective way to reduce N fertilizer application rate and mitigate NH3 emission, improve NUE, and increase maize yield. More investigations are suggested under different soil textures and climatic conditions to declare S-coated urea at 150 kg N ha-1 as the best application rate for maize to enhance maize growth and yield.

Computational investigation of pyrazinamide drugs and its transition metal complexes using a DFT approach.

Pyrazinamide, an antituberculosis but documented toxic drug, is subjected to computational investigation along with the metal complexes via a DFT approach to predict the structure-activity and structure-toxicity relationship. 6-31G(d,p) basis set was used for Zn, Ni, Mn, Fe, and Co, while the SDD basis set was applied to Cu, Cr, Cd, and Hg. Several reactivity parameters and charge distribution were calculated and the reactivity profile was estimated. The complexes were found to be soft and polarizable which could be responsible for their binding with bacterial targets to inhibit their growth. In contrast, pyrazinamide which is found to be hard among all is susceptible to being toxic. Moreover, the electronegative nature of the complexes can endow them with a better antibacterial effect. Since metal complexes have been found to be less toxic and more biologically interactive by computational methods, they can be employed as potent drugs for the cure of tuberculosis.

Uniting Synergistic Effect of Single-Ni Site and Electric Field of B- Bridged-N for Boosted Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical conversion of nitrate, a prevalent water pollutant, to ammonia (NH3) is a delocalized and green path for NH3 production. Despite the existence of different nitrate reduction pathways, selectively directing the reaction pathway on the road to NH3 is now hindered by the absence of efficient catalysts. Single-atom catalysts (SACs) are extensively investigated in a wide range of catalytic processes. However, their application in electrocatalytic nitrate reduction reaction (NO3 -RR) to NH3 is infrequent, mostly due to their pronounced inclination toward hydrogen evolution reaction (HER). Here, Ni single atoms on the electrochemically active carrier boron, nitrogen doped-graphene (BNG) matrix to modulate the atomic coordination structure through a boron-spanning strategy to enhance the performance of NO3 -RR is designed. Density functional theory (DFT) study proposes that BNG supports with ionic characteristics, offer a surplus electric field effect as compared to N-doped graphene, which can ease the nitrate adsorption. Consistent with the theoretical studies, the as-obtained NiSA@BNG shows higher catalytic activity with a maximal NH3 yield rate of 168 µg h-1 cm-2 along with Faradaic efficiency of 95% and promising electrochemical stability. This study reveals novel ways to rationally fabricate SACs' atomic coordination structure with tunable electronic properties to enhance electrocatalytic performance.

Multivalent Sulfur Vacancy-Rich NiCo2S4@MnO2 Urchin-Like Heterostructures for Ambient Electrochemical N2 Reduction to NH3.

Innovative advances in the exploitation of effective electrocatalytic materials for the reduction of nitrogen (N2) to ammonia (NH3) are highly required for the sustainable production of fertilizers and zero-carbon emission fuel. In order to achieve zero-carbon footprints and renewable NH3 production, electrochemical N2 reduction reaction (NRR) provides a favorable energy-saving alternative but it requires more active, efficient, and selective catalysts. In current work, sulfur vacancy (Sv)-rich NiCo2S4@MnO2 heterostructures are efficaciously fabricated via a facile hydrothermal approach followed by heat treatment. The urchin-like Sv-NiCo2S4@MnO2 heterostructures serve as cathodes, which demonstrate an optimal NH3 yield of 57.31 µg h-1 mgcat -1 and Faradaic efficiency of 20.55% at -0.2 V versus reversible hydrogen electrode (RHE) in basic electrolyte owing to the synergistic interactions between Sv-NiCo2S4 and MnO2. Density functional theory (DFT) simulation further verifies that Co-sites of urchin-like Sv-NiCo2S4@MnO2 heterostructures are beneficial to lowering the energy threshold for N2 adsorption and successive protonation. Distinctive micro/nano-architectures exhibit high NRR electrocatalytic activities that might motivate researchers to explore and concentrate on the development of heterostructures for ambient electrocatalytic NH3 generation.

Twenty Years of SPARTAN: From Inception to Impact (SPARTAN 2023 Annual Meeting Proceedings).

PURPOSE OF REVIEW: This review takes a look at the past, present, and future of SPARTAN, the Spondyloarthritis Research and Treatment Network, an organization of North American healthcare professionals dedicated to advancing research, education, and patient care in spondyloarthritis. RECENT FINDINGS: In 2022, SPARTAN completed the Classification of Axial SpondyloarthritiS Inception Cohort (CLASSIC) study, a collaboration with the Assessment in SpondyloArthritis International Society (ASAS). CLASSIC aimed to validate the 2009 ASAS classification criteria for axial spondyloarthritis. Other ongoing SPARTAN endeavors include the development of US referral recommendations for axial spondyloarthritis, an update of the 2019 ACR/SAA/SPARTAN treatment recommendations for axial spondyloarthritis and multiple educational initiatives. Twenty years after its inception, SPARTAN continues to grow and broaden its impact, guided by the SPARTAN vision of "a world free of spondyloarthritis through leadership in research and education."

DFT, Molecular Docking, ADME, and Cardiotoxicity studies of Persuasive Thiazoles as Potential Inhibitors of the Main Protease of SARS-CoV-2.

This study explores the capability of thiazoles as potent inhibitors of SARS-CoV-2 Mpro. Seventeen thiazoles (1-17) were screened for their linking affinity with the active site of SARS-CoV-2 Mpro and compared with the FDA-recommended antiviral drugs, Remdesivir and Baricitinib. Density Functional Theory (DFT) calculations provided electronic and energetic properties of these ligands, shedding light on their stability and reactivity. Molecular docking analysis revealed that thiazole derivatives exhibited favorable linking affinities with various functional sites of SARS-CoV-2 proteins, including spike receptor-linking zone, nucleocapsid protein N-terminal RNA linking zone, and Mpro. Notably, compounds 3, 10, and 12 displayed the best interaction with 6LZG as compared to FDA-approved antiviral drugs Remdesivir and Baricitinib, while compounds 1, 10, and 8 exhibited strong linking with 6M3M and also better than Remdesivir and Baricitinib. Additionally, compounds 3, 1, and 6 showed promising interactions with 6LU7 but only compound 3 performed better than Baricitinib. An ADME (Absorption, Distribution, Metabolism, and Excretion) study provided insights into the pharmacokinetics and drug-likeness of these compounds, with all ligands demonstrating good physicochemical characteristics, lipophilicity, water solubility, pharmacokinetics, drug-likeness, and medicinal chemistry attributes. The results suggest that these selected thiazole derivatives hold promise as potential candidates for further drug development.

Influence of agro-wastes derived biochar and their composite on reducing the mobility of toxic heavy metals and their bioavailability in industrial contaminated soils.

The agro-waste derived valuable products are prime interest for effective management of toxic heavy metals (THMs). The present study investigated the efficacy of biochars (BCs) on immobilization of THMs (Cr, Zn, Pb, Cu, Ni and Cd), bioaccumulation and health risk. Agro-wastes derived BCs including wheat straw biochar (WSB), orange peel biochar (OPB), rice husk biochar (RHB) and their composite biochar (CB) were applied in industrial contaminated soil (ICS) at 1% and 3% amendments rates. All the BCs significantly decreased the bioavailable THMs and significantly (p < 0.001) reduced bioaccumulation at 3% application with highest efficiency for CB followed by OPB, WSB and RHB as compared to control treatment. The bioaccumulation factor (BAF), concentration index (CI) and ecological risk were decreased with all BCs. The hazard quotient (HQ) and hazard index (HI) of all THMs were <1, except Cd, while carcer risk (CR) and total cancer risk index (TCRI) were decreased through all BCs. The overall results depicted that CB at 3% application rate showed higher efficacy to reduce significantly (p < 0.001) the THMs uptake and reduced health risk. Hence, the present study suggests that the composite of BCs prepared from agro-wastes is eco-friendly amendment to reduce THMs in ICS and minimize its subsequent uptake in vegetables.

The present study has a scientific research scope, based on reduction of bioavailability and bioaccumulation of toxic heavy metals (THMs) by the addition of biochars derived from agro-wastes and their composite biochar (CB), thereby decreasing the potential health risk. Limited study has been conducted, especially on the impact of CB in THMs-contaminated soil. This study could fill the scientific research gap and provides useful information for mitigation of THMs present in contaminated soil, which could be followed by the Environmental Protection Agency, Ministry of Agriculture and farmers in degraded lands.

Utility-Driven End-to-End Network Slicing for Diverse IoT Users in MEC: A Multi-Agent Deep Reinforcement Learning Approach.

Mobile Edge Computing (MEC) is crucial for reducing latency by bringing computational resources closer to the network edge, thereby enhancing the quality of services (QoS). However, the broad deployment of cloudlets poses challenges in efficient network slicing, particularly when traffic distribution is uneven. Therefore, these challenges include managing diverse resource requirements across widely distributed cloudlets, minimizing resource conflicts and delays, and maintaining service quality amid fluctuating request rates. Addressing this requires intelligent strategies to predict request types (common or urgent), assess resource needs, and allocate resources efficiently. Emerging technologies like edge computing and 5G with network slicing can handle delay-sensitive IoT requests rapidly, but a robust mechanism for real-time resource and utility optimization remains necessary. To address these challenges, we designed an end-to-end network slicing approach that predicts common and urgent user requests through T distribution. We formulated our problem as a multi-agent Markov decision process (MDP) and introduced a multi-agent soft actor-critic (MAgSAC) algorithm. This algorithm prevents the wastage of scarce resources by intelligently activating and deactivating virtual network function (VNF) instances, thereby balancing the allocation process. Our approach aims to optimize overall utility, balancing trade-offs between revenue, energy consumption costs, and latency. We evaluated our method, MAgSAC, through simulations, comparing it with the following six benchmark schemes: MAA3C, SACT, DDPG, S2Vec, Random, and Greedy. The results demonstrate that our approach, MAgSAC, optimizes utility by 30%, minimizes energy consumption costs by 12.4%, and reduces execution time by 21.7% compared to the closest related multi-agent approach named MAA3C.

In-Situ Construction of V2 O5 Nanosheet/Nitrogen-Doped Carbon Nanosheet Heterostructures with Interfacial C─O Bridging Bonds as the Cathode Material for Zn Ion Batteries.

Layered oxides are widely used as the electrode materials for metal ion batteries. However, for large radius size ions, such as Zn2+ and Al3+ , the tightly stacked layers and poor electrical conductivity of layered oxides result in restricted number of active sites and sluggish reaction kinetics. In this work, a facile in-situ construction strategy is provided to synthesize layered oxide nanosheets/nitrogen-doped carbon nanosheet (NC) heterostructure, which shows larger interlayer spacing and better electrical conductivity than the layered oxides. As a result, the Zn2+ ion diffusion inside the interlayer gallery is greatly enhanced and the storage sites inside the gallery can be better used. Meanwhile, the NC layers and oxide nanosheets are bridged by the C─O bonds to form a stable structure, which contributes to a better cycling stability than the pure layered oxides. The optimal V2 O5 @NC-400 cathode shows a capacity of 467 mA h g-1 at 0.1 A g-1 for 300 cycles, and long-term cyclic stability of 4000 cycles at 5 A g-1 with a capacity retention of 92%. All these performance parameters are among the best for vanadium oxide-based cathode materials.

HLA-B27, axial spondyloarthritis and survival.

INTRODUCTION: Ankylosing spondylitis (AS), and carriage of HLA-B27 gene in otherwise healthy individuals, are reportedly associated with increased mortality. We evaluated this hypothesis, using data from both a 35-year AS follow-up study and UK Biobank data. METHODS: In 1985, 363 members of the Swiss AS Patient Society and 806 relatives were screened clinically and then radiographically for AS/axial spondyloarthritis (axSpA). Life expectancy was analysed in 377 axSpA patients having available pelvic radiographs and HLA-B27 status, comparing with matched Swiss population data. Survival in relation to HLA-B27 status in the general population was studied in UK Biobank European-ancestry participants (n=407 480, n=30 419 deaths). RESULTS: AS patients have increased standardised mortality rate (SMR) compared with the general population (1.37, 95% CI 1.11 to 1.62). This increase was significant for HLA-B27-positive AS (SMR 1.38, 95% CI 1.11 to 1.65). Shortened life expectancy was observed among both HLA-B27-positive AS women (SMR 1.77, 95% CI 1.09 to 2.70) and men (SMR 1.31, 95% CI 1.02 to 1.59). Patients with non-radiographic axSpA (nr-axSpA) had significantly lower SMR: 0.44 (95% CI 0.23 to 0.77), compared with the general population. In the UK Biobank European-ancestry population cohort, HLA-B27 carriage was not significantly associated with any change in mortality (HR 1, 95% CI 0.97 to 1.1, p=0.349, adjusted by sex), in either males (HR 1, 95% CI 0.98 to 1.1, p=0.281) or females (HR 0.96, 95% CI 0.9 to 1, p=0.232), and no increase in vascular disease mortality was observed. DISCUSSION: AS patients, but not nr-axSpA patients, have a significantly shortened life expectancy. Increased mortality is particularly significant among women with HLA-B27-positive AS. HLA-B27 carriage in the European-ancestry general population does not influence survival, or the risk of death due to vascular disease.

Unraveling the role of natural functional oils in modulating osteoarthritis related complications.

Osteoarthritis (OA) is a common joint disease and has been studied extensively in recent years as no promising therapy available so far for its treatment and remains a great challenge for health care specialists. Although the identification of some major mechanisms that contribute to this disease suggests a plethora of bioactive agents in tackling the associated complications yet OA's pathophysiology is still poorly understood owing to complex mechanistic changes observed. Experimental research is now exploring a wide range of therapeutically effective agents in an effort to find a way to repair OA-related joint degeneration and halt it from getting worse. Data was acquired and reviewed from most relevant and recent studies. This review summarizes the studies that are currently available and focuses on how various unconventional functional oils affect osteoarthritis and the affected joint tissues. An analysis of the recent scientific literature allowed us to highlight the potential anti-arthritic properties of edible oils and their main constituents, which seems to suggest an interesting new potential therapeutic application. Due to eccentric nature of OA, it is necessary to concentrate initially on the management of symptoms. The evidence supporting functional oils chondroprotective potential is still accumulating, underpinning a global need for more sustainable natural sources of treatment. More clinical research that focuses on the consequences of long-term treatment, possible negative effects, and epigenetic implications is necessary to get optimistic results. However, different animal or clinical studies suggest that linolenic and linoleic fatty acids decreased chondrocyte oxidative stress, cartilage breakdown, and expression of inflammatory markers. Distinct fatty acids along with minor components of oils also reduced the generation of prostaglandins and decreased oxidative stress. Furthermore, the potential roles of the main components of edible oils and possible negative results (if any) are also reported. While no severe side effects have been reported for any edible oils. Overall, these studies identify and support the use of functional oils as an adjuvant therapy for the management of OA and as a means of symptomatic alleviation for OA patients. However, to prove the effectiveness or to draw precise conclusions, high-quality clinical trials are required.

TPGS Decorated Liposomes as Multifunctional Nano-Delivery Systems.

Liposomes are sphere-shaped vesicles that can capture therapeutics either in the outer phospholipid bilayer or inner aqueous core. Liposomes, especially when surface-modified with functional materials, have been used to achieve many benefits in drug delivery, including improving drug solubility, oral bioavailability, pharmacokinetics, and delivery to disease target sites such as cancers. Among the functional materials used to modify the surface of liposomes, the FDA-approved non-ionic surfactant D-alpha-tocopheryl polyethylene glycol succinate (TPGS) is increasingly being applied due to its biocompatibility, lack of toxicity, applicability to various administration routes and ability to enhance solubilization, stability, penetration and overall pharmacokinetics. TPGS decorated liposomes are emerging as a promising drug delivery system for various diseases and are expected to enter the market in the coming years. In this review article, we focus on the multifunctional properties of TPGS-coated liposomes and their beneficial therapeutic applications, including for oral drug delivery, vaccine delivery, ocular administration, and the treatment of various cancers. We also suggest future directions to optimise the manufacture and performance of TPGS liposomes and, thus, the delivery and effect of encapsulated diagnostics and therapeutics.

Axial Spondyloarthritis and Diagnostic Challenges: Over-diagnosis, Misdiagnosis, and Under-diagnosis.

PURPOSE OF REVIEW: This article aims to review the challenges in axial spondyloarthritis diagnosis and identify the possible contributing factors. RECENT FINDINGS: The inability to reach an accurate diagnosis in a timely fashion can lead to treatment delays and worse disease outcomes. The lack of validated diagnostic criteria and the misuse of the currently available classification criteria could be contributing. There is also significant inter-reader variability in interpreting images, and the radiologic definitions of axial spondyloarthritis continue to be re-defined to improve their positive predictive value. The role of inflammatory back pain features, serologic biomarkers, genetics, and their diagnostic contribution to axial spondyloarthritis continues to be investigated. There is still a significant amount of delay in the diagnosis of axial spondyloarthritis. Appreciating the factors that contribute to this delay is of utmost importance to close the gap. It is similarly important to recognize other conditions that may present with symptoms that mimic axial spondyloarthritis so that misdiagnosis and wrong treatment can be avoided.

Retention of methyl iodide on metal and TEDA impregnated activated carbon using indigenously developed setup.

Removal of methyl iodide (CH3I) from the air present within nuclear facilities is a critical issue. In case of any nuclear accident, there is a great need to mitigate the radioactive organic iodide immediately as it accumulates in human bodies, causing severe consequences. Current research focuses on removing organic iodides, for which the surface of activated carbon (AC) was modified by impregnating it with different metals individually, i.e. Ag, Ni, Zn, Cu and with the novel combination of these four metals (AZNC). After the impregnation of metals, triethylenediamine (TEDA) was coated on metal impregnated activated carbon (IAC) surface. The adsorption capacity of the combination of four metals IAC was found to be 276 mg/g as the maximum for the trapping of CH3I. Whereas TEDA-metal impregnation on ACs enhanced the removal efficiency of CH3I up to 352 mg/g. After impregnation, adsorption capacity of AZNC and AZNCT is significantly higher as compared to AC. According to the finding, t5% of AZNCT IAC is 46 min, which is considerably higher than the t5% of other tested adsorbents. According to isotherm fitting data, Langmuir isotherm was found superior for describing CH3I sorption onto AC and IACs. Kinetics study shows that pseudo second order model represented the sorption of CH3I more accurately than the pseudo first order. Thermodynamic studies gave negative value of ΔG which shows that the reaction is spontaneous in nature. Based on the findings, AZNCT IAC appears to have a great potential for air purification applications in order to obtain clean environment.

Design, Synthesis, Characterization and Computational Studies of Mannich Bases Oxadiazole Derivatives as New Class of Jack Bean Urease Inhibitors.

Mannich bases consisting of 1,3,4-oxadiazole-2-thione (3 a-3 l) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 µM. The compound 3 k containing 4-chlorophenyl (-R) and 4-hydroxyphenyl (-R') was most active with IC50 9.45±0.05 µM followed by 3 e (IC50 22.52±0.15 µM) in which -R was phenyl and -R' was isopropyl group. However, when both -R and -R' were either 4-chlorophenyl groups (3 l) or only -R' was 4-nitrophenyl (3 i), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts.

Genome-wide analysis of runs of homozygosity in Pakistani controls with no history of speech or language-related developmental phenotypes.

BACKGROUND: Runs of homozygosity (ROHs) analysis of controls provide a convenient resource to minimize the association of false positive results of disease-associated ROHs and genetic variants for simple and complex disorders in individuals from the same population. Evidence for the value of ROHs to speech or language-related traits is restricted due to the absence of population-matched behaviourally defined controls and limited family-based studies. AIM: This study aims to identify common ROHs in the Pakistani population, focussing on the total length and frequency of ROHs of variable sizes, shared ROHs, and their genomic distribution. SUBJECTS AND METHODS: We performed homozygosity analysis (in PLINK) of 86 individuals (39 males, 47 females) with no history of speech or language-related phenotypes (controls) who had been genotyped with the Illumina Infinium QC Array-24. RESULTS: ROHs of 1-<4 megabases (Mb) were frequent in unrelated individuals. We observed ROHs over 20 Mb among six individuals. Over 30 percent of the identified ROHs were shared among several individuals, indicating consanguinity's effect on the Pakistani population. CONCLUSION: Our findings serve as a foundation for family-based genetic studies of consanguineous families with speech or language-related disorders to ultimately narrow the homozygosity regions of interest to identify pathogenic variants.

Achieving Reliability in Cloud Computing by a Novel Hybrid Approach.

Cloud computing (CC) benefits and opportunities are among the fastest growing technologies in the computer industry. Cloud computing's challenges include resource allocation, security, quality of service, availability, privacy, data management, performance compatibility, and fault tolerance. Fault tolerance (FT) refers to a system's ability to continue performing its intended task in the presence of defects. Fault-tolerance challenges include heterogeneity and a lack of standards, the need for automation, cloud downtime reliability, consideration for recovery point objects, recovery time objects, and cloud workload. The proposed research includes machine learning (ML) algorithms such as naïve Bayes (NB), library support vector machine (LibSVM), multinomial logistic regression (MLR), sequential minimal optimization (SMO), K-nearest neighbor (KNN), and random forest (RF) as well as a fault-tolerance method known as delta-checkpointing to achieve higher accuracy, lesser fault prediction error, and reliability. Furthermore, the secondary data were collected from the homonymous, experimental high-performance computing (HPC) system at the Swiss Federal Institute of Technology (ETH), Zurich, and the primary data were generated using virtual machines (VMs) to select the best machine learning classifier. In this article, the secondary and primary data were divided into two split ratios of 80/20 and 70/30, respectively, and cross-validation (5-fold) was used to identify more accuracy and less prediction of faults in terms of true, false, repair, and failure of virtual machines. Secondary data results show that naïve Bayes performed exceptionally well on CPU-Mem mono and multi blocks, and sequential minimal optimization performed very well on HDD mono and multi blocks in terms of accuracy and fault prediction. In the case of greater accuracy and less fault prediction, primary data results revealed that random forest performed very well in terms of accuracy and fault prediction but not with good time complexity. Sequential minimal optimization has good time complexity with minor differences in random forest accuracy and fault prediction. We decided to modify sequential minimal optimization. Finally, the modified sequential minimal optimization (MSMO) algorithm with the fault-tolerance delta-checkpointing (D-CP) method is proposed to improve accuracy, fault prediction error, and reliability in cloud computing.

Sooty Tern Optimization Algorithm-Based Deep Learning Model for Diagnosing NSCLC Tumours.

Lung cancer is one of the most common causes of cancer deaths in the modern world. Screening of lung nodules is essential for early recognition to facilitate treatment that improves the rate of patient rehabilitation. An increase in accuracy during lung cancer detection is vital for sustaining the rate of patient persistence, even though several research works have been conducted in this research domain. Moreover, the classical system fails to segment cancer cells of different sizes accurately and with excellent reliability. This paper proposes a sooty tern optimization algorithm-based deep learning (DL) model for diagnosing non-small cell lung cancer (NSCLC) tumours with increased accuracy. We discuss various algorithms for diagnosing models that adopt the Otsu segmentation method to perfectly isolate the lung nodules. Then, the sooty tern optimization algorithm (SHOA) is adopted for partitioning the cancer nodules by defining the best characteristics, which aids in improving diagnostic accuracy. It further utilizes a local binary pattern (LBP) for determining appropriate feature retrieval from the lung nodules. In addition, it adopts CNN and GRU-based classifiers for identifying whether the lung nodules are malignant or non-malignant depending on the features retrieved during the diagnosing process. The experimental results of this SHOA-optimized DNN model achieved an accuracy of 98.32%, better than the baseline schemes used for comparison.

A Functional Single Nucleotide Polymorphism in the 3' Untranslated Region of the Porcine JARID2 Gene Is Associated with Aggressive Behavior of Weaned Pigs after Mixing.

In pig production, pigs often show more aggressive behavior after mixing, which adversely affects animal welfare and growth performance. The Jumonji and structural domain-rich AT interaction domain 2 (JARID2) gene plays an important role in neurodevelopment in mice and various psychiatric disorders in humans. The JARID2 gene may impact the aggressive behavior of pigs. By observing the behavior of 500 weaned pigs during the first 72 h after mixing, the ear tissue samples of the 12 most aggressive and 12 least aggressive pigs were selected for DNA resequencing based on the intensity of their aggressive behavior. Large group correlation analysis indicated that the rs3262221458 site located in the 3'-UTR region of the porcine JARID2 gene has a strong relationship with the aggressive behavior of weaned pigs. Pigs with the mutant TT genotype of rs3262221458 have more aggressive behavior than those pigs with the GG and GT genotypes. The dual luciferase assay indicated that the luciferase activity of the plasmids containing the G allele of rs326221458 was significantly less than that of plasmids containing the T allele of rs326221458 and control groups. The binding ability of miR-9828-3p to sequences containing the T allele was less than that of sequences containing the G allele. The overexpression of miR-9828-3p in porcine neuroglial cells (PNGCs) and PK15 cells significantly decreased the mRNA and protein levels of the JARID2 gene. In addition, miR-9828-3p inhibited the proliferation of PNGCs. After inhibiting miR-9828-3p, the mRNA and protein expression levels of JARID2 increased, and the proliferation of PNGCs showed an opposite trend to the cells that forced the expression of miR-9828-3p. In addition, interference with the JARID2 gene by siRNA can effectively inhibit the proliferation of PNGCs. In summary, we found that the rs326221458 locus regulates the expression of the JARID2 gene by affecting the binding of miR-9828-3p and the JARID2 gene, thereby affecting the aggressive behavior of weaned pigs after mixing.