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In this work, fabrication of pure and cobalt (Co) doped zinc sulfide (ZnS) nanoparticles were carried out via facile co-precipitation technique using thioglycolic acid as a surfactant. The synthesized nano powders were employed to characterize using various techniques like X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and UV–Vis spectroscopy, to elucidate the alterations in the structure and morphology of nanomaterials. The XRD analysis revealed wurtzite phase of fabricated nanoparticles. Inclusion of Co dopants failed to modify the lattice structure of host material. Analysis of UV–Vis spectroscopy indicates intensive absorption in the visible region upon doping. FTIR spectroscopy was employed to identify functional groups affiliated with molecular vibrations. The photoactivity and kinetics of photo-products were evaluated by monitoring degradation of methylene blue (MB) by solar irradiation. Photodecomposition of MB was significantly increased when Co doped ZnS was employed relative to pristine ZnS. This novel technique of doped ZnS nanoparticles provide an effectual and sustainable route for treatment of wastewater.

Abstract We give a relatively short proof of the fact that the solution set of a nonlocal semilinear differential inclusion is dense in the weak solution set of the corresponding convexified system. Moreover, we prove a similar result for the solutions with continuous pseudoderivatives when the right-hand side is continuous with nonempty convex closed and bounded values.

Sensor networks feature low-cost sensor devices with wireless network capability, limited transmit power, resource constraints, and limited battery energy. Cooperative routing exploits the broadcast nature of wireless medium and transmits cooperatively using nearby sensor nodes as relays. It is a promising technique that utilizes cooperative communication to improve the communication quality of single-antenna sensor nodes. In this paper, we propose a cooperative transmission scheme for underwater sensor networks (UWSNs) to enhance the network performance. Cooperative diversity has been introduced to combat fading. Cooperative UWSN (Co-UWSN) is proposed, which is a reliable, energy-efficient, and high throughput routing protocol for UWSN. Destination and potential relays are selected that utilize distance and signal-to-noise ratio computation of the channel conditions as cost functions. This contributes to sufficient decrease in path losses occurring in the links and transferring of data with much reduced path loss. Simulation results show that Co-UWSN protocol performs better in terms of end-to-end delay, energy consumption, and network lifetime. Selected protocols for comparison are energy-efficient depth-based routing (EEDBR), improved adaptive mobility of courier nodes in threshold-optimized depth-based routing (iAMCTD), cooperative routing protocol for UWSN, and cooperative partner node selection criteria for cooperative routing Coop (Re and dth).

Underwater Acoustic Sensor Networks (UASNs) offer their practicable applications in seismic monitoring, sea mine detection, and disaster prevention. In these networks, fundamental difference between operational methodologies of routing schemes arises due to the requirement of time-critical applications; therefore, there is a need for the design of delay-sensitive techniques. In this paper, Delay-Sensitive Depth-Based Routing (DSDBR), Delay-Sensitive Energy Efficient Depth-Based Routing (DSEEDBR), and Delay-Sensitive Adaptive Mobility of Courier nodes in Threshold-optimized Depth-based routing (DSAMCTD) protocols are proposed to empower the depth-based routing schemes. The performance of the proposed schemes is validated in UASNs. All of the three schemes formulate delay-efficient Priority Factors (PF) and Delay-Sensitive Holding time ( DSH T ) to minimize end-to-end delay with a small decrease in network throughput. These schemes also employ an optimal weight function ( W F ) for the computation of transmission loss and speed of received signal. Furthermore, solution for delay lies in efficient data forwarding, minimal relative transmissions in low-depth region, and better forwarder selection. Simulations are performed to assess the proposed protocols and the results indicate that the three schemes largely minimize end-to-end delay along with improving the transmission loss of network.

We propose forwarding-function ( F F ) based routing protocol for underwater sensor networks (UWSNs): improved adaptive mobility of courier nodes in threshold-optimized depth-based-routing (iAMCTD). Unlike existing depth-based acoustic protocols, the proposed protocol exploits network density for time-critical applications. In order to tackle flooding, path loss, and propagation latency, we calculate optimal holding time ( H T ) and use routing metrics: localization-free signal-to-noise ratio (LSNR), signal quality index (SQI), energy cost function (ECF), and depth-dependent function (DDF). Our proposal provides on-demand routing by formulating hard threshold ( H th ), soft threshold ( S th ), and prime energy limit ( R prime ). Simulation results verify effectiveness and efficiency of the proposed iAMCTD.

This paper presents mathematical framework for calculating transmission probability in IEEE 802.11 p based networks at Medium access control (MAC) layer, mathematical framework for calculating energy costs of the chosen routing protocols at network layer, and enhancements in optimized link state routing (OLSR), dynamic source routing, (DSR) and fish-eye state routing (FSR) to tackle delay in vehicular ad hoc networks (VANETs). Besides the enhancements, we analyze ad hoc ondemand distance vector (AODV) along with OLSR, DSR, and FSR as well. To evaluate the effect of our proposed transmission probabilities in the selected routing protocols, we choose network throughput, end-to-end delay (E2ED), and normalized routing load (NRL) as performance metrics. We also investigate the effect of different mobilities as well as scalabilities on the overall efficiency of the enhanced and default versions of the selected protocols. Simulations results which are conducted in NS-2 show that overall DSR-mod outperforms rest of the protocols.

Modern health care system is one of the most popular Wireless Body Area Sensor Network (WBASN) applications and a hot area of research subject to present work. In this paper, we present Reliability Enhanced-Adaptive Threshold based Thermal-unaware Energy-efficient Multi-hop ProTocol (RE-ATTEMPT) for WBASNs. The proposed routing protocol uses fixed deployment of wireless sensors (nodes) such that these are placed according to energy levels. Moreover, we use direct communication for the delivery of emergency data and multihop communication for the delivery of normal data. RE-ATTEMPT selects route with minimum hop count to deliver data which downplays the delay factor. Furthermore, we conduct a comprehensive analysis supported by MATLAB simulations to provide an estimation of path loss, and problem formulation with its solution via linear programming model for network lifetime maximization is also provided. In simulations, we analyze our protocol in terms of network lifetime, packet drops, and throughput. Results show better performance for the proposed protocol as compared to the existing one.

Wireless Body Area Networks (WBANs) are widely used for applications such as modern health-care systems, where wireless sensors (nodes) monitor the parameter(s) of interest. Nodes are provided with limited battery power and battery power is dependent on radio activity. MAC protocols play a key role in controlling the radio activity. Therefore, we present Adaptive Medium Access Control (A-MAC) protocol for WBANs supported by linear programming models for the minimization of energy consumption and maximization of dataflow. Our proposed protocol is adaptive in terms of guard band assignment technique and sleep/wakeup mechanism. We focus on specific application to monitor human body with the help of nodes which continuously scan body for updated information. If the current value is within normal range, nodes do not try to access channel. However, if the current value rises or falls beyond the permissible range, nodes switch on their transceiver to access channel. Moreover, A-MAC uses TDMA approach to access channel and well-defined synchronization scheme to avoid collisions. Furthermore, we conduct a comprehensive analysis supported by MATLAB simulations to provide estimation of delay spread. Simulation results justify that the proposed protocol performs better in terms of network lifetime and throughput as compared to the counterpart protocols.

One of the major challenges in design of wireless sensor networks (WSNs) is to reduce energy consumption of sensor nodes to prolong lifetime of finite capacity batteries. In this paper, we propose energy-efficient adaptive scheme for transmission (EAST) in WSNs. EAST is an IEEE 802.15.4 standard compliant. In this scheme, open-looping feedback process is used for temperature-aware link quality estimation and compensation, wherea closed-loop feedback process helps to divide network into three logical regions to minimize overhead of control packets. Threshold on transmitter power loss ( RSSI loss ) and current number of nodes ( n c ( t )) in each region help to adapt transmit power level ( P level ) according to link quality changes due to temperature variation. Evaluation of the proposed scheme is done by considering mobile sensor nodes and reference node both static and mobile. Simulation results show that the proposed scheme effectively adapts transmission P level to changing link quality with less control packets overhead and energy consumption as compared to classical approach with single region in which maximum transmitter P level assigned to compensate temperature variation.

RNA interference (RNAi) is a posttranscriptional gene silencing mechanism acting as an antiviral defense in eukaryotes. During viral replication, intermediate double-stranded RNAs are processed into virus-derived small interfering RNAs (vsiRNAs) by the host enzyme, DICER. These vsiRNAs are incorporated into the RNA-induced silencing complex (RISC), where AGO2 cleaves viral genomic RNAs. However, viruses have evolved mechanisms to suppress this pathway. Here, we report that the nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome virus (SFTSV) interacts with RISC to suppress the RNAi pathway. NSs forms a ternary complex by interacting with both DICER and AGO2 of the RNAi pathway. The interaction between NSs and DICER, facilitated by the two RNase III domains of DICER, is disrupted in the absence of AGO2 or the DICER-interacting domain (PIWI) of AGO2, indicating a direct interaction between NSs and AGO2. Functional assays using shRNA- and siRNA-mediated silencing of GFP signal, along with co-localization studies, demonstrated that NSs competes with siRNA to interact with AGO2, thereby abolishing RNAi activity. Mutational analysis identified an NSs-A26 mutant that no longer interacts with AGO2 and is unable to suppress RNAi activity, suggesting that NSs acts as a viral suppressor of RNAi (VSR) for SFTSV. Viral infection led to the generation of vsiRNA and showed higher replication in AGO2 -/- cells compared to wild-type (WT) cells, confirming the antiviral role of the RNAi pathway against SFTSV infection. These data suggest that the NSs-AGO2 interaction suppresses RNAi, counteracting the antiviral RNAi pathway, thereby facilitating SFTSV infection and pathogenesis.IMPORTANCERNA interference (RNAi) is the main antiviral defense pathway in plants and insects but is not predominant in mammals. While RNAi's role in countering severe fever with thrombocytopenia syndrome virus (SFTSV) infection has been studied in ticks, its role in humans is unknown. The SFTSV nonstructural protein (NSs) forms inclusion bodies (IBs) in the host, sequestering multiple antiviral proteins and facilitating pathogenesis, contributing to SFTSV's high mortality rate. Our study found that SFTSV NSs directly interacts with AGO2, a key RNAi protein, hindering its function. A novel NSs mutant failed to interact with AGO2 and lost its RNAi suppression ability, highlighting NSs as a viral suppressor of RNAi (VSR). Infection studies confirmed the RNAi pathway's critical role in combating SFTSV infection. This study demonstrates NSs's role in viral infection and suggests potential therapeutic approaches.

The human interleukin-1 receptor I (IL-1R1) is a cytokine receptor recognized by interleukin 1β (IL-1β), among other cytokines. Over activation of IL-1R1 has been implicated in various inflammatory conditions. This research aims to identify small-molecule inhibitors targeting the hIL1R1/IL1β interaction, employing a multi-task transfer learning approach for quantitative structure-activity relationship (QSAR) modelling. A comprehensive bioactivity dataset from functionally related proteins was utilised to build a robust ensemble machine learning model for predicting IC 50 values against the target protein. Despite the availability of antibody-based therapies, the absence of orally available small-molecule inhibitors necessitates their development. By combining model predictions with docking and simulation approaches, the interleukin-1 receptor inhibitor (IRI-1) emerged as a lead compound. It potently inhibited human IL1-R1 with micromolar activity in THP-1 and Saos-2 cells and demonstrated good biocompatibility. Western blot analysis revealed that IRI-1 inhibits IL-1β-mediated phosphorylation of IL1-R1, JNK, IRAK-4, and ERK in THP-1 cells. Furthermore, molecular dynamics simulations confirmed the structural stability of the protein-ligand complexes. This study highlights the effectiveness of multi-task transfer learning approaches for building robust QSAR models against novel proteins or those with limited bioactivity data, such as hIL-1β/IL-1R1 protein., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine and its functional homotrimeric form interacts with the TNF receptor (TNFR) to activate downstream apoptotic, necroptotic, and inflammatory signaling pathways. Excessive activation of these pathways leads to various inflammatory diseases, which makes TNF a promising therapeutic target. Here, 12-mer peptides were selected from the interface of TNF-TNFR based upon their relative binding energies and were named 'TNF-inhibiting decoys' (TIDs). These decoy peptides inhibited TNF-mediated secretion of cytokines and cell death, as well as activation of downstream signaling effectors. Effective TIDs inhibited TNF signaling by disrupting the formation of TNF's functional homotrimeric form. Among derivatives of TIDs, TID3c showed slightly better efficacy in cell-based assays by disrupting TNF trimer formation. Moreover, TID3c oligomerized TNF to a high molecular weight configuration. In silico modeling and simulations revealed that TID3c and its parent peptide, TID3, form a stable complex with TNF through hydrogen bonds and electrostatic interactions, which makes them the promising lead to develop peptide-based anti-TNF therapeutics., (© 2024 Federation of European Biochemical Societies.)

Chrozophora sabulosa Kar. & Kir. is a biennial herbaceous plant that belongs to the Euphorbiaceae family and has medicinal properties. This research aimed to identify the genetic characteristics and phylogenetic position of the Chrozophora genus within the Euphorbiaceae family. The evolutionary position of the Chrozophora genus was previously unknown due to insufficient research. Therefore, to determine the evolutionary link between C. sabulosa and other related species, we conducted a study using the NGS Illumina platform to sequence the C. sabulosa chloroplast (cp.) genome. The study results showed that the genome was 156,488 bp in length. It had a quadripartite structure consisting of two inverted repeats (IRb and IRa) of 24,649-bp, separated by an 87,696-bp LSC region and a 19,494-bp SSC region. The CP genome contained 113 unique genes, including four rRNA genes, 30 tRNA genes, and 79 CDS genes. In the second copy of the inverted repeat, there were 18 duplicated genes. The C. sabulosa lacks the petD, petB, rpl2, and rps16 intron. The analysis of simple sequence repeats (SSRs) revealed 93 SSR loci of 22 types and 78 oligonucleotide repeats of four kinds. The phylogenetic investigation showed that the Chrozophora genus evolved paraphyletically from other members of the Euphorbiaceae family. To support the phylogenetic findings, we selected species from the Euphorbiaceae and Phyllanthaceae families to compare with C. sabulosa for Ks and Ka substitution rates, InDels investigation, IR contraction and expansion, and SNPs analysis. The results of these comparative studies align with the phylogenetic findings. We identified six highly polymorphic regions shared by both families, which could be used as molecular identifiers for the Chrozophora genus (rpl33-rps18, rps18-rpl20, rps15-ycf1, ndhG-ndhI, psaI-ycf4, petA-psbJ). The cp. genome sequence of C. sabulosa reveals the evolution of plastid sequences in Chrozophora species. This is the first time the cp. genome of a Chrozophora genus has been sequenced, serving as a foundation for future sequencing of other species within the Chrozophoreae tribe and facilitating in-depth taxonomic research. The results of this research will also aid in identifying new Chrozophora species., (© 2024. The Author(s).)

A platform was designed based on Fe 3 O 4 and CsPbBr 3 @SiO 2 for integrated magnetic enrichment-fluorescence detection of Salmonella typhimurium, which significantly simplifies the detection process and enhances the working efficiency. Fe 3 O 4 served as a magnetic enrichment unit for the capture of S. typhimurium. CsPbBr 3 @SiO 2 was employed as a fluorescence-sensing unit for quantitative signal output, where SiO 2 was introduced to strengthen the stability of CsPbBr 3 , improve its biomodificability, and prevent lead leakage. More importantly, the SiO 2 shell shows neglectable absorption or scattering towards fluorescence, making the CsPbBr 3 @SiO 2 exhibit a high quantum yield of 74.4%. After magnetic enrichment, the decreasing rate of the fluorescence emission intensity of the CsPbBr 3 @SiO 2 supernatant at 527 nm under excitation light at UV 365 nm showed a strong linear correlation with S. typhimurium concentration of 1 × 10 2 ~1 × 10 8 CFU∙mL -1 , and the limit of detection (LOD) reached 12.72 CFU∙mL -1 . This platform has demonstrated outstanding stability, reproducibility, and resistance to interference, which provides an alternative for convenient and quantitative detection of S. typhimurium., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Accurate predictions of stock markets are important for investors and other stakeholders of the equity markets to formulate profitable investment strategies. The improved accuracy of a prediction model even with a slight margin can translate into considerable monetary returns. However, the stock markets' prediction is regarded as an intricate research problem for the noise, complexity and volatility of the stocks' data. In recent years, the deep learning models have been successful in providing robust forecasts for sequential data. We propose a novel deep learning-based hybrid classification model by combining peephole LSTM with temporal attention layer (TAL) to accurately predict the direction of stock markets. The daily data of four world indices including those of U.S., U.K., China and India, from 2005 to 2022, are examined. We present a comprehensive evaluation with preliminary data analysis, feature extraction and hyperparameters' optimization for the problem of stock market prediction. TAL is introduced post peephole LSTM to select the relevant information with respect to time and enhance the performance of the proposed model. The prediction performance of the proposed model is compared with that of the benchmark models CNN, LSTM, SVM and RF using evaluation metrics of accuracy, precision, recall, F1-score, AUC-ROC, PR-AUC and MCC. The experimental results show the superior performance of our proposed model achieving better scores than the benchmark models for most evaluation metrics and for all datasets. The accuracy of the proposed model is 96% and 88% for U.K. and Chinese stock markets respectively and it is 85% for both U.S. and Indian markets. Hence, the stock markets of U.K. and China are found to be more predictable than those of U.S. and India. Significant findings of our work include that the attention layer enables peephole LSTM to better identify the long-term dependencies and temporal patterns in the stock markets' data. Profitable and timely trading strategies can be formulated based on our proposed prediction model., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Abdulaziz Aldegheishem reports financial support was provided by 10.13039/501100002383King Saud University., (© 2024 The Author(s).)

Pakistan is amongst the four countries with the highest number of pneumococcal deaths. While the PCV10 vaccine was introduced in Pakistan in October 2012, data regarding the impact of the vaccine on the population dynamics of Streptococcus pneumoniae in Pakistan remain obscure. Using whole genome sequencing of 190 isolates (nasopharyngeal carriage=75, disease=113, unknown sites=2) collected between 2002 and 2020, this study presents characteristics of pneumococcal strains in Pakistan in the pre- and post-vaccine era. The isolates were characterized on the basis of serotype distribution, genetic lineages (or Global Pneumococcal Sequence Cluster, GPSC) and antibiotic resistance. A high level of diversity in serotype and genetic lineages of pneumococci was observed in Pakistan. Among 190 isolates, we identified 54 serotypes, 67 GPSCs and 116 sequence types (STs) including 23 new STs. The most prevalent GPSCs and their associated serotypes in nasopharyngeal carriage were GPSC54 (expressing serotype 9V), GPSC5 (15A and 7B, and serogroup 24), GPSC25 (15B/15C), GPSC67 (18C) and GPSC376 (6A and 6D). Similarly, among 113 disease-causing isolates, the most prevalent GPSC/serotype combinations were GPSC2 (serotype 1), GPSC10 (serotypes 14, 10A, 19A and 19F), GPSC43 (serotypes 13, 11A, 23B, 35A and 9V), GPSC67 (serotypes 18A and 18C) and GPSC642 (serotype 11A). Of the 190 isolates, the highest levels of resistance were observed against penicillin (58.9 %, n =122), erythromycin (29.5 %, n =56), clindamycin (13.2 %, n =25), co-trimoxazole (94.2 %, n =179) and tetracycline/doxycycline (53.2 %, n =101). A higher proportion of disease-causing isolates were multidrug resistant as compared to carriage isolates (54 % vs 25 %). Our data suggest limited coverage of PCV10 in nasopharyngeal (21.6 %, 16/74) as well as disease-causing (38.1 %, 16/42) isolates among children ≤5 years old; however, higher valent vaccine PCV13 would increase the coverage rates to 33.8 % in nasopharyngeal and 54.8 % in disease-causing isolates, whereas PCV24/25 would offer the highest coverage rates. Owing to the diversity of serotypes observed during the post-vaccine period, the suggested inclusion of serotype in future vaccine formulations will require investigations with larger data sets with an extended temporal window. This article contains data hosted by Microreact.

Introduction: A 38-year-old African American woman presented with right hip pain and movement restriction. Her medical history included a right hip and knee arthroplasty 10 years prior, history of Slipped Capital Femoral Epiphysis and osteonecrosis of the hip. Preoperative assessment was significant for multiple comorbidities such as obesity (BMI > 38), hypertension, asthma., Patient Concerns: The patient presented with right hip pain, rated 7/10, and restricted hip flexion, adduction, and abduction., Diagnosis: Recent imaging showed eccentric deterioration of the polyethylene lining of her prosthesis, acetabular hypertrophy on her right hip prosthesis, and chronic deformity of the pubic bone., Interventions: Based on these findings, a revisional total hip arthroplasty was performed. After the surgical procedure, the WoundVAC and the percutaneous drain were applied outside the tensor fascia lata to reduce seroma and hematoma formation. Postoperative pain control, antibiotics and DVT prophylaxis were given. On post-op day 3, an irrigation and debridement with delayed primary wound closure was performed under sterile conditions., Outcomes: On postoperative assessment, the wound demonstrated adequate healing without any signs of infection. Sutures and staples were removed 4 weeks post-op. Upon palpation there was no edema, effusions, temperature changes, tenderness. Clinical inspection revealed symmetrical alignment of the pelvis and hips. Range of motion testing revealed restriction beyond 80 degrees upon flexion and beyond 5 degrees of adduction and 10 degrees of abduction. The surgical site was noted to be healed at 6 weeks post-op. The patient continued to do well to date, without exacerbations., Conclusion: Obesity increases the risk of post-operative complications and wound healing failure. Therefore, Vacuum-assisted wound closure (WoundVAC), a type of negative pressure wound therapy, was applied outside the tensor fascia lata post-operatively, where the surgical incision was made. Negative pressure wound therapy facilitates wound healing by stimulating angiogenesis and promoting granulation tissue formation, which in turn can reduce the risk of surgical site infection in obese patients undergoing total hip arthroplasty. Highlighted is the mechanism of fat migration in the promotion of wound healing after preoperative weight loss and exercise., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The Aizoaceae family's Sesuvium sesuvioides (Fenzl) Verdc is a medicinal species of the Cholistan desert, Pakistan. The purpose of this study was to determine the genomic features and phylogenetic position of the Sesuvium genus in the Aizoaceae family. We used the Illumina HiSeq2500 and paired-end sequencing to publish the complete chloroplast sequence of S. sesuvioides., Results: The 155,849 bp length cp genome sequence of S. sesuvioides has a 36.8% GC content. The Leucine codon has the greatest codon use (10.6%), 81 simple sequence repetitions of 19 kinds, and 79 oligonucleotide repeats. We investigated the phylogeny of the order Caryophyllales' 27 species from 23 families and 25 distinct genera. The maximum likelihood tree indicated Sesuvium as a monophyletic genus, and sister to Tetragonia. A comparison of S. sesuvioides, with Sesuvium portulacastrum, Mesembryanthemum crystallinum, Mesembryanthemum cordifolium, and Tetragonia tetragonoides was performed using the NCBI platform. In the comparative investigation of genomes, all five genera revealed comparable cp genome structure, gene number and composition. All five species lacked the rps15 gene and the rpl2 intron. In most comparisons with S. sesuvioides, transition substitutions (Ts) were more frequent than transversion substitutions (Tv), producing Ts/Tv ratios larger than one, and the Ka/Ks ratio was lower than one. We determined ten highly polymorphic regions, comprising rpl22, rpl32-trnL-UAG, trnD-GUC-trnY-GUA, trnE-UUC-trnT-GGU, trnK-UUU-rps16, trnM-CAU-atpE, trnH-GUG-psbA, psaJ-rpl33, rps4-trnT-UGU, and trnF-GAA-ndhJ., Conclusion: The whole S. sesuvioides chloroplast will be examined as a resource for in-depth taxonomic research of the genus when more Sesuvium and Aizoaceae species are sequenced in the future. The chloroplast genomes of the Aizoaceae family are well preserved, with little alterations, indicating the family's monophyletic origin. This study's highly polymorphic regions could be utilized to build realistic and low-cost molecular markers for resolving taxonomic discrepancies, new species identification, and finding evolutionary links among Aizoaceae species. To properly comprehend the evolution of the Aizoaceae family, further species need to be sequenced., (© 2023. The Author(s).)

Electricity theft is the largest type of non-technical losses faced by power utilities around the globe. It not only raises revenue losses to the utilities but also leads to lethal fires and electric shocks at distribution side. In the past, field operation groups were sent by the utilities to conduct inspections of suspicions electric equipments stated by the public. Advanced metering infrastructure based recent development in the smart grids makes it easy to detect electricity thefts. However, the conventional supervised learning techniques have low theft detection performance mainly due to imbalance datasets available for training. Therefore, in this paper, we develop a novel theft detection model with twofold contribution. A unique hybrid sampling technique named as hybrid oversampling and undersampling using both classes (HOUBC) is proposed to balance the dataset. HOUBC first performs undersampling and then oversampling using both the majority (normal) and minority (theft) classes. A new deep learning method, fractal network is applied with light gradient boosting method to extract and learn important characteristics from electricity consumption profiles for identifying electricity thieves. The proposed model relies on smart meter's data for theft detection and hence, a rapid and widespread adaption of this model is feasible, which shows its main advantage. The performance of the model is evaluated with real-world smart meter's data, i.e., state grid corporation of China. Comprehensive simulation results describe the effectiveness of the proposed model against conventional schemes in terms of electricity theft detection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Excessive signaling by the proinflammatory cytokine TNF is involved in several autoimmune diseases, including rheumatoid arthritis (RA). However, unlike the approved biologics currently used to treat this and other conditions, commercially available small-molecule inhibitors of TNF trimerization are cytotoxic or exhibit low potency. Here, we report a TNF-inhibitory molecule (TIM) that reduced TNF signaling in vitro and was an effective treatment in a mouse model of RA. The initial lead compound, TIM1, attenuated TNF-induced apoptosis of human and mouse cells by delaying the induction of proinflammatory NF-κB and MAPK signaling and caspase 3- and caspase 8-dependent apoptosis. TIM1 inhibited the secretion of the proinflammatory cytokines IL-6 and IL-8 by disrupting TNF homotrimerization, thereby preventing its association with the TNF receptor. In a mouse model of collagen-induced polyarthritis, the more potent TIM1 analog TIM1c was orally bioavailable and reduced paw swelling, histological indicators of knee joint pathology, inflammatory infiltration of the joint, and the overall arthritis index. Orally delivered TIM1c showed immunological effects similar to those elicited by intraperitoneal injection of the FDA-approved TNF receptor decoy etanercept. Thus, TIM1c is a promising lead compound for the development of small-molecule therapies for the treatment of RA and other TNF-dependent systemic inflammation disorders.

In this paper, a defused decision boundary which renders misclassification issues due to the presence of cross-pairs is investigated. Cross-pairs retain cumulative attributes of both classes and misguide the classifier due to the defused data samples' nature. To tackle the problem of the defused data, a Tomek Links technique targets the cross-pair majority class and is removed, which results in an affine-segregated decision boundary. In order to cope with a Theft Case scenario, theft data is ascertained and synthesized randomly by using six theft data variants. Theft data variants are benign class appertaining data samples which are modified and manipulated to synthesize malicious samples. Furthermore, a K-means minority oversampling technique is used to tackle the class imbalance issue. In addition, to enhance the detection of the classifier, abstract features are engineered using a stochastic feature engineering mechanism. Moreover, to carry out affine training of the model, balanced data are inputted in order to mitigate class imbalance issues. An integrated hybrid model consisting of Bi-Directional Gated Recurrent Units and Bi-Directional Long-Term Short-Term Memory classifies the consumers, efficiently. Afterwards, robustness performance of the model is verified using an attack vector which is subjected to intervene in the model's efficiency and integrity. However, the proposed model performs efficiently on such unseen attack vectors.

The induced pluripotent stem cells (iPSCs) are considered powerful tools in pharmacology, biomedicine, toxicology, and cell therapy. Multiple approaches have been used to generate iPSCs with the expression of reprogramming factors. Here, we generated iPSCs by integrating the reprogramming cassette into a genomic safe harbor, CASH-1, with the use of a precise genome editing tool, CRISPR/Cas9. The integration of cassette at CASH-1 into target cells did not alter the pattern of proliferation and interleukin-6 secretion as a response to ligands of multiple signaling pathways involving tumor necrosis factor- α receptor, interleukin-1 receptor, and toll-like receptors. Moreover, doxycycline-inducible expression of OCT4 , SOX2 , and KLF4 reprogrammed engineered human dermal fibroblasts and human embryonic kidney cell line into iPSCs. The generated iPSCs showed their potential to make embryoid bodies and differentiate into the derivatives of all three germ layers. Collectively, our data emphasize the exploitation of CASH-1 by CRISPR/Cas9 tool for therapeutic and biotechnological applications including but not limited to reprogramming of engineered cells into iPSCs., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Nasir Javaid and Sangdun Choi.)

Background: Farsetia hamiltonii Royle is a medicinally important annual plant from the Cholistan desert that belongs to the tribe Anastaticeae and clade C of the Brassicaceae family. We provide the entire chloroplast sequence of F.hamiltonii, obtained using the Illumina HiSeq2500 and paired-end sequencing. We compared F. hamiltonii to nine other clade C species, including Farsetia occidentalis, Lobularia libyca, Notoceras bicorne, Parolinia ornata, Morettia canescens, Cochlearia borzaeana, Megacarpaea polyandra, Biscutella laevigata, and Iberis amara. We conducted phylogenetic research on the 22 Brassicaceae species, which included members from 17 tribes and six clades., Results: The chloroplast genome sequence of F.hamiltonii of 154,802 bp sizes with 36.30% GC content and have a typical structure comprised of a Large Single Copy (LSC) of 83,906 bp, a Small Single Copy (SSC) of 17,988 bp, and two copies of Inverted Repeats (IRs) of 26,454 bp. The genomes of F. hamiltonii and F. occidentalis show shared amino acid frequencies and codon use, RNA editing sites, simple sequence repeats, and oligonucleotide repeats. The maximum likelihood tree revealed Farsetia as a monophyletic genus, closely linked to Morettia, with a bootstrap score of 100. The rate of transversion substitutions (Tv) was higher than the rate of transition substitutions (Ts), resulting in Ts/Tv less than one in all comparisons with F. hamiltonii, indicating that the species are closely related. The rate of synonymous substitutions (Ks) was greater than non-synonymous substitutions (Ka) in all comparisons with F. hamiltonii, with a Ka/Ks ratio smaller than one, indicating that genes underwent purifying selection. Low nucleotide diversity values range from 0.00085 to 0.08516, and IR regions comprise comparable genes on junctions with minimal change, supporting the conserved status of the selected chloroplast genomes of the clade C of the Brassicaceae family. We identified ten polymorphic regions, including rps8-rpl14, rps15-ycf1, ndhG-ndhI, psbK-psbI, ccsA-ndhD, rpl36-rps8, petA-psbJ, ndhF-rpl32, psaJ-rpl3, and ycf1 that might be exploited to construct genuine and inexpensive to solve taxonomic discrepancy and understand phylogenetic relationship amongst Brassicaceae species., Conclusion: The entire chloroplast sequencing of F. hamiltonii sheds light on the divergence of genic chloroplast sequences among members of the clade C. When other Farsetia species are sequenced in the future, the full F. hamiltonii chloroplast will be used as a source for comprehensive taxonomical investigations of the genus. The comparison of F. hamiltonii and other clade C species adds new information to the phylogenetic data and evolutionary processes of the clade. The results of this study will also provide further molecular uses of clade C chloroplasts for possible plant genetic modifications and will help recognise more Brassicaceae family species., (© 2022. The Author(s).)

Streptococcus pneumoniae is a major human pathogen responsible for over 317000 deaths in children <5 years of age with the burden of the disease being highest in low- and middle-income countries including South Africa. Following the introduction of the 7-valent and 13-valent pneumococcal conjugate vaccine (PCV) in South Africa in 2009 and 2011, respectively, a decrease in both invasive pneumococcal infections and asymptomatic carriage of vaccine-type pneumococci were reported. In this study, we described the changing epidemiology of the pneumococcal carriage population in South Africa, by sequencing the genomes of 1825 isolates collected between 2009 and 2013. Using these genomic data, we reported the changes in serotypes, Global Pneumococcal Sequence Clusters (GPSCs), and antibiotic resistance before and after the introduction of PCV13. The pneumococcal carriage population in South Africa has a high level of diversity, comprising of 126 GPSCs and 49 serotypes. Of the ten most prevalent GPSCs detected, six were predominantly found in Africa (GPSC22, GPSC21, GPSC17, GPSC33, GPSC34 and GPSC52). We found a significant decrease in PCV7 serotypes (19F, 6B, 23F and 14) and an increase in non-vaccine serotypes (NVT) (16F, 34, 35B and 11A) among children <2 years of age. The increase in NVTs was driven by pneumococcal lineages GPSC33, GPSC34, GPSC5 and GPSC22. Overall, a decrease in antibiotic resistance for 11 antimicrobials was detected in the PCV13 era. Further, we reported a higher resistance prevalence among vaccine types (VTs), as compared to NVTs; however, an increase in penicillin resistance among NVT was observed between the PCV7 and PCV13 eras. The carriage isolates from South Africa predominantly belonged to pneumococcal lineages, which are endemic to Africa. While the introduction of PCV resulted in an overall reduction of resistance in pneumococcal carriage isolates, an increase in penicillin resistance among NVTs was detected in children aged between 3 and 5 years, driven by the expansion of penicillin-resistant clones associated with NVTs in the PCV13 era.

The enhancement of Robustness (R) has gained significant importance in Scale-Free Networks (SFNs) over the past few years. SFNs are resilient to Random Attacks (RAs). However, these networks are prone to Malicious Attacks (MAs). This study aims to construct a robust network against MAs. An Intelligent Rewiring (INTR) mechanism is proposed to optimize the network R against MAs. In this mechanism, edge rewiring is performed between the high and low degree nodes to make a robust network. The Closeness Centrality (CC) measure is utilized to determine the central nodes in the network. Based on the measure, MAs are performed on nodes to damage the network. Therefore, the connections of the neighboring nodes in the network are greatly affected by removing the central nodes. To analyze the network connectivity against the removal of nodes, the performance of CC is found to be more efficient in terms of computational time as compared to Betweenness Centrality (BC) and Eigenvector Centrality (EC). In addition, the Recalculated High Degree based Link Attacks (RHDLA) and the High Degree based Link Attacks (HDLA) are performed to affect the network connectivity. Using the local information of SFN, these attacks damage the vital portion of the network. The INTR outperforms Simulated Annealing (SA) and ROSE in terms of R by 17.8% and 10.7%, respectively. During the rewiring mechanism, the distribution of nodes' degrees remains constant.

Aberrant activation of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays an essential role in multiple diseases, including Alzheimer's disease (AD) and psoriasis. We report a novel small-molecule inhibitor, NLRP3-inhibitory compound 7 (NIC7), and its derivative, which inhibit NLRP3-mediated activation of caspase 1 along with the secretion of interleukin (IL)-1β, IL-18, and lactate dehydrogenase. We examined the therapeutic potential of NIC7 in a disease model of AD by analyzing its effect on cognitive impairment as well as the expression of dopamine receptors and neuronal markers. NIC7 significantly reversed the associated disease symptoms in the mice model. On the other hand, NIC7 did not reverse the disease symptoms in the imiquimod (IMQ)-induced disease model of psoriasis. This indicates that IMQ-based psoriasis is independent of NLRP3. Overall, NIC7 and its derivative have therapeutic prospects to treat AD or NLRP3-mediated diseases.

This paper proposes a blockchain-based node authentication model for the Internet of sensor things (IoST). The nodes in the network are authenticated based on their credentials to make the network free from malicious nodes. In IoST, sensor nodes gather the information from the environment and send it to the cluster heads (CHs) for additional processing. CHs aggregate the sensed information. Therefore, their energy rapidly depletes due to extra workload. To solve this issue, we proposed distance, degree, and residual energy-based low-energy adaptive clustering hierarchy (DDR-LEACH) protocol. DDR-LEACH is used to replace CHs with the ordinary nodes based on maximum residual energy, degree, and minimum distance from BS. Furthermore, storing a huge amount of data in the blockchain is very costly. To tackle this issue, an external data storage, named as interplanetary file system (IPFS), is used. Furthermore, for ensuring data security in IPFS, AES 128-bit is used, which performs better than the existing encryption schemes. Moreover, a huge computational cost is required using a proof of work consensus mechanism to validate transactions. To solve this issue, proof of authority (PoA) consensus mechanism is used in the proposed model. The simulation results are carried out, which show the efficiency and effectiveness of the proposed system model. The DDR-LEACH is compared with LEACH and the simulation results show that DDR-LEACH outperforms LEACH in terms of energy consumption, throughput, and improvement in network lifetime with CH selection mechanism. Moreover, transaction cost is computed, which is reduced by PoA during data storage on IPFS and service provisioning. Furthermore, the time is calculated in the comparison of AES 128-bit scheme with existing scheme. The formal security analysis is performed to check the effectiveness of smart contract against attacks. Additionally, two different attacks, MITM and Sybil, are induced in our system to show our system model's resilience against cyber attacks.

In this paper, an encryption and trust evaluation model is proposed on the basis of a blockchain in which the identities of the Aggregator Nodes (ANs) and Sensor Nodes (SNs) are stored. The authentication of ANs and SNs is performed in public and private blockchains, respectively. However, inauthentic nodes utilize the network's resources and perform malicious activities. Moreover, the SNs have limited energy, transmission range and computational capabilities, and are attacked by malicious nodes. Afterwards, the malicious nodes transmit wrong information of the route and increase the number of retransmissions due to which the SNs' energy is rapidly consumed. The lifespan of the wireless sensor network is reduced due to the rapid energy dissipation of the SNs. Furthermore, the throughput increases and packet loss increase with the presence of malicious nodes in the network. The trust values of SNs are computed to eradicate the malicious nodes from the network. Secure routing in the network is performed considering residual energy and trust values of the SNs. Moreover, the Rivest-Shamir-Adleman (RSA), a cryptosystem that provides asymmetric keys, is used for securing data transmission. The simulation results show the effectiveness of the proposed model in terms of high packet delivery ratio.

Background: Malnutrition is common in liver cirrhosis patients that is correlated with early complications, morbidity and mortality., Objective: The purpose of the study was to assess nutritional status, impact of nutritional screening and intervention in liver cirrhosis patients by evaluating their actual energy and protein intake during hospital stay., Methods: A cross sectional study was conducted wherein all patients' nutritional status was defined by Subjective Global Assessment tool. Adequate energy and protein supply were planned and executed by using individualized nutritional plan for patients with dietitian's collaboration. Anthropometric measurements included height, weight, body mass index, mid upper arm circumference, hand grip strength and triceps skin-fold thickness. Biochemical tests included haemoglobin, mean corpuscular haemoglobin, volume and concentration, albumin and liver function tests. To record the daily food intake, a 24-hour dietary recall was used., Results: Overall 83 patients (mean age 55) were included, among them 46% of patients were moderately malnourished, 12% were normal, while 42% of cirrhotic patients were severely depleted according to Subjective Global Assessment. The mean intake of calories and protein was improved during stay in hospital after nutritional intervention and critical monitoring (P<0.05). Anthropometric measurements at baseline and discharge showed significant differences (P <0.05) in weight, body mass index, triceps skin fold thickness and mid upper arm circumference values, but not in hand grip strength that was associated with malnourishment among patients., Conclusion: Providing individualized nutritional intervention and its monitoring by qualified dietitians during hospital stay helps to improve intake in patients that prevent further risk of malnutrition and related complications.

Background : Parkinson's disease (PD) is associated with progressive neuronal damage and dysfunction. Oxidative stress helps to regulate neurodegenerative and neuronal dysfunction. Natural compounds could attenuate oxidative stress in a variety of neurological disorders. B. juncea is a rich source of antioxidants. The present study aimed to evaluate the therapeutic potential of B. juncea leaves for the treatment of PD by applying behavioral, in vivo and in silico studies. For in vivo studies rats were divided into six groups (n = 6). Group-I served as normal control (vehicle control). Group-II was disease control (haloperidol 1 mg/kg). Group-III was kept as a standard group (L-Dopa 100 mg/kg + carbidopa 25 mg/kg). Groups (IV-VI) were the treatment groups, receiving extract at 200-, 400- and 600 mg/kg doses respectively, for 21 days orally. Results : In vivo study results showed that the extract was found to improve muscles strength, motor coordination, and balance in PD. These behavioral outcomes were consistent with the recovery of endogenous antioxidant defence in biochemical analysis which was further corroborated with histopathological ameliorations. Dopamine levels increased and monoamine oxidase B (MAO-B) levels decreased dose-dependently in the brain during the study. Herein, we performed molecular docking analysis of the proposed extracted phytochemicals has explained that four putative phytochemicals (sinapic acid, rutin, ferulic acid, and caffeic acid) have presented very good results in terms of protein-ligand binding interactions as well as absorption, distribution, metabolism, excretion & toxicity (ADMET) profile estimations. Conclusion : The undertaken study concluded the anti-Parkinson activity of B. juncea and further suggests developments on its isolated compounds in PD therapeutics., (© 2021 The Author(s). Published by BRI.)

The diverse applications of genetically modified cells and organisms require more precise and efficient genome-editing tool such as clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas). The CRISPR/Cas system was originally discovered in bacteria as a part of adaptive-immune system with multiple types. Its engineered versions involve multiple host DNA-repair pathways in order to perform genome editing in host cells. However, it is still challenging to get maximum genome-editing efficiency with fewer or no off-targets. Here, we focused on factors affecting the genome-editing efficiency and precision of CRISPR/Cas system along with its defense-mechanism, orthologues, and applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Javaid and Choi.)

Acidovorax avenae is a flagellated, pathogenic bacterium to various plant crops that has also been found in human patients with haematological malignancy, fever, and sepsis; however, the exact mechanism for infection in humans is not known. We hypothesized that the human innate immune system could be responsive to the purified flagellin isolated from A. avenae , named FLA-AA. We observed the secretion of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-8 by treating FLA-AA to human dermal fibroblasts, as well as macrophages. This response was exclusively through TLR5, which was confirmed by using TLR5-overexpression cell line, 293/hTLR5, as well as TLR5-specific inhibitor, TH1020. We also observed the secretion of inflammatory cytokine, IL-1β, by the activation of NLRC4 with FLA-AA. Overall, our results provide a molecular basis for the inflammatory response caused by FLA-AA in cell-based assays.

Bacterial spot, caused by a group of Xanthomonads (Xanthomonas spp.), is a devastating disease. It can adversely affect the Capsicum annum productivity. Scientists are working on the role of antioxidants to meet this challenge. However, research is lacking on the role of antioxidant enzymes and their isoforms in the non-compatible pathogen and host plant interaction and resistance mechanisms in capsicum varieties. The present study was conducted to ascertain the defensive role of antioxidant enzymes and their isoforms in chilli varieties Hybrid, Desi, Serrano, Padron, and Shehzadi against bacterial spot disease-induced Xanthomonas sp. The seedlings were inoculated with bacterial pathogen @ 10 7  CFU/mL, and samples were harvested after regular intervals of 24 h for 4 days followed by inoculation. Total plant proteins were extracted in phosphate buffer and quantified through Bradford assay. The crude protein extracts were analyzed through quantitative enzymatic assays in order to document activity levels of various antioxidant enzymes, including peroxidase (POD), Catalase (CAT), Ascorbate peroxidase (APX), and Superoxide dismutase (SOD). Moreover, the profiles appearance of these enzymes and their isoforms were determined using native polyacrylamide gel electrophoresis (PAGE) analysis. These enzymes exhibited maximum activity in Hybrid (HiR) cultivar followed by Desi (R), Serrano (S), Padron, and Shehzadi (HS). Both the number of isoforms and expression levels were higher in highly resistant cultivars compared to susceptible and highly susceptible cultivars. The induction of POD, CAT, and SOD occurs at the early stages of growth in resistant Capsicum cultivars. At the same time, APX seems to make the second line of antioxidant defense mechanisms. We found that modulating antioxidant enzymes and isoforms activity at the seedling stage was an important mechanism for mitigating plant growth inhibition in the resistant ones.

While antimicrobial resistance (AMR) continues to be a major public health problem in Pakistan, data regarding trends of resistance among pathogenic bacteria remains scarce, with few studies presenting long-term trends in AMR. This study was therefore designed to analyze long-term AMR trends at a national level in Pakistan. We report here results of a comprehensive analysis of resistance, among pathogens isolated from blood and cerebrospinal fluid (CSF), between 2011 and 2015. Susceptibility data was obtained from a local laboratory with collection points all across Pakistan (Chughtai Laboratory). Resistance proportions to most commonly used antimicrobials were calculated for each pathogen over a period of five years. While Acinetobacter species demonstrated highest resistance rates to all tested antimicrobials, a sharp increase in carbapenem resistance was the most noticeable (50%-95%) between 2011-2015. Our results also highlight the presence of third and fourth generation cephalosporins resistance in Salmonella enterica serovar Typhi in Pakistan. Interestingly, where rise in AMR was being observed in some major invasive pathogens, decreasing resistance trends were observed in Staphylococcus aureus, against commonly used antimicrobials. Overall pathogens isolated from blood and CSF between 2011-2015, showed an increase in resistance towards commonly used antimicrobials., Competing Interests: The authors have declared that no competing interests exist.

Background: Cirrhosis is a chronic and progressive liver disease that occurs from prolonged hepatocellular injury. Malnutrition causes complications in cirrhosis patients that worsen the condition to liver failure. Both are closely linked and increase the chances of morbidity and mortality. Regular nutritional screening and monitoring is prime concern for such patients including comprehensive dietary history, laboratory tests, and evaluation of muscle loss and strength capabilities to determine the degree of frailty. For efficient assessment of liver cirrhosis patients Subjective Global Assessment has been used worldwide. The nutritional objectives for such individuals should be to regain liver functions, to prevent complications associated, and to overcome nutritional deficiencies causing malnutrition., Methods: We conducted a literature review using PubMed, Google Scholar and Science Direct for this purpose, a total of 130 articles were reviewed out of which 80 (from the past 5 years) including originally published research, review articles and abstracts were also included. Exclusion criteria of the selected studies was year of publication, irrelevancy and animal studies based on the purpose of current study. The aim of this study was to check nutritional management in patients having complications of liver cirrhosis., Results: According to the guidelines, for the conservation of normal nutritional status of the malnourished patients', energy should be provided 35 kcal/kg/day while to prevent hypoalbuminemia and maintain the protein stores in the body, 1.5 g/kg/day protein has been recommended. Carbohydrates and fats for cirrhosis patients are recommended 50% to 60% and 10% to 20% of the total dietary intake respectively., Conclusion: Initial identification and prevention of malnutrition have the probability to lead to better health outcomes, prevention of complications of the disease, and improving quality of life.

Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead to neuronal cell death. Alzheimer's disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset and gradually worsens. Neuropathology, AD is characterized by the presence of neuroinflammation, mitochondrial dysfunction, increased oxidative stress, decreased antioxidant defense as well as increased acetylcholinesterase activity. Moreover, enhanced expression of amyloid precursor proteins leads to neural apoptosis, which has a vital role in the degeneration of neurons. The inability of commercial therapeutics to treat a single feature of AD pathology leads to the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid; latest studies revealed that ellagic acid can initiate numerous cell signaling transmissions and decrease the progression of neurodegeneration. The neuroprotective effects of ellagic acid to protect the neurons against neurodegenerative events are due to its antioxidant effect, iron chelating, and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mechanism of action of ellagic acid against AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Viral infections such as AIDS, hepatitis, herpes keratitis, and herpes labialis became resistant to drugs and it is difficult to design vaccine. In current era drug-resistant viruses are now treated by nanoparticles (NPs) and this field is known as nanobiotechnology that relates nanoscience with the biological system. NPs due to their antiviral activity are used in the treatment of viral diseases. The advantages of using the NP is its specific target action and increase the efficiency of treatment with minimum side effects. Liposomes, quantum dots, polymeric NPs, solid lipid NPs, silver NPs, gold NPs, and magnetic NPs are used to treat viral infections. NP-based therapeutics have completely replaced the usage of drugs and vaccines for viral diseases treatment. Nano vaccines have been investigated for the delivery of drugs; biomaterials-based NPs are in development to be formulated into nano vaccines. But there are limitations in the manufacturing and stabilization of NPs in the body. This review focuses on the antiviral activity of several NPs, its uptake by different viruses for viral disease treatment, nano vaccines, and the limitation of the NPs as nanotherapeutics.

Reversal in the transcriptional status of desired genes has been exploited for multiple research, therapeutic, and biotechnological purposes. CRISPR/dCas9-based activators can activate transcriptionally silenced genes after being guided by gene-specific gRNA(s). Here, we performed a functional comparison between two such activators, VP64-dCas9-VP64 and dCas9-VP192, in human embryonic kidney cells by the concomitant targeting of POU5F1 and SOX2 . We found 22- and 6-fold upregulations in the mRNA level of POU5F1 by dCas9-VP192 and VP64-dCas9-VP64, respectively. Likewise, SOX2 was up-regulated 4- and 2-fold using dCas9-VP192 and VP64dCas9VP64, respectively. For the POU5F1 protein level, we observed 3.7- and 2.2-fold increases with dCas9-VP192 and VP64-dCas9-VP64, respectively. Similarly, the SOX2 expression was 2.4- and 2-fold higher with dCas9-VP192 and VP64-dCas9-VP64, respectively. We also confirmed that activation only happened upon co-transfecting an activator plasmid with multiplex gRNA plasmid with a high specificity to the reference genes. Our data revealed that dCas9-VP192 is more efficient than VP64-dCas9-VP64 for activating reference genes.

Direct inhibition of tumor necrosis factor-alpha (TNF-α) action is considered a promising way to prevent or treat TNF-α-associated diseases. The trimeric form of TNF-α binds to its receptor (TNFR) and activates the downstream signaling pathway. The interaction of TNF-α with molecular-grade dimethyl sulfoxide (DMSO) in an equal volumetric ratio renders TNF-α inert, in this state, TNF-α fails to activate TNFR. Here, we aimed to examine the inhibition of TNF-α function by various concentrations of DMSO. Its higher concentration led to stronger attenuation of TNF-α-induced cytokine secretion by fibroblasts, and of their death. We found that this inhibition was mediated by a perturbation in the formation of the functional TNF-α trimer. Molecular dynamics simulations revealed a transient interaction between DMSO molecules and the central hydrophobic cavity of the TNF-α homodimer, indicating that a brief interaction of DMSO with the TNF-α homodimer may disrupt the formation of the functional homotrimer. We also found that the sensitizing effect of actinomycin D on TNF-α-induced cell death depends upon the timing of these treatments and on the cell type. This study will help to select an appropriate concentration of DMSO as a working solvent for the screening of water-insoluble TNF-α inhibitors.

The immune system plays a crucial role in the body's defense system against various pathogens, such as bacteria, viruses, and parasites, as well as recognizes non-self- and self-molecules. The innate immune system is composed of special receptors known as pattern recognition receptors, which play a crucial role in the identification of pathogen-associated molecular patterns from diverse microorganisms. Any disequilibrium in the activation of a particular pattern recognition receptor leads to various inflammatory, autoimmune, or immunodeficiency diseases. Aptamers are short single-stranded deoxyribonucleic acid or ribonucleic acid molecules, also termed "chemical antibodies," which have tremendous specificity and affinity for their target molecules. Their features, such as stability, low immunogenicity, ease of manufacturing, and facile screening against a target, make them preferable as therapeutics. Immune-system-targeting aptamers have a great potential as a targeted therapeutic strategy against immune diseases. This review summarizes components of the innate immune system, aptamer production, pharmacokinetic characteristics of aptamers, and aptamers related to innate-immune-system diseases., Competing Interests: The authors declare no conflict of interest.