Preterm birth is a leading cause of infant morbidity and mortality in the world. In 2020, 1 in 10 infants were born prematurely in the United States. Globally, the World Health Or-ganization estimates 15 million infants are born prematurely. The efficacy of current ther-apeutic interventions for preterm birth have been called into question due to limited repli-cable success. Recent advancements in the field of nanomedicine have made it possible to utilize the vaginal administration route to effectively and locally deliver drugs to the fe-male reproductive tract. Also, studies using murine models have provided important in-sights about the cervix as a gatekeeper for pregnancy and parturition. It seems plausible that the field of reproductive biology is on the cusp of a paradigm shift in the context of treating preterm birth. The present review focuses on the complexities associated with treating the condition and novel therapeutics that have produced promising results in pre-clinical studies.

Introduction: Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. Aim: Assessment of selected microRNAs (miRNAs) in chemoresistance in archival material from LAGC. Material and method: The research group consisted of archival material from 10 patients with LAGC. Histological material from each patient was used from a biopsy performed during gastroscopy and after surgery preceded by 4 cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs was assessed in the tissue material, such as miRNA-21-3p, miRNA-21-5p, miRNA-106a-5p, miRNA-122-3p, miRNA-122-5p, miRNA-143-3p, miRNA-143-5p, miRNA-203a-3p, miRNA-203-5p, miRNA-551b-3p, miRNA-551b-5p and miRNA-574-3p. miRNA expression was assessed by quantitative chain reaction polymerase reverse transcriptase (qRT-PCR). The response to NAC was assessed by computed tomography of the abdomen, chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9.The significance limit was set at p

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

Previous research showed that intersex people face specific challenges in their sexual development, including uncertainties or confusion about their gender, a negative genital self-image, and hesitance to engage in romantic and sexual relationships. However, in-depth knowledge of a central period of this development, adolescence, is missing. In our qualitative study, we explore which factors influence the relational and sexual development of intersex youth and what elements contribute to a positive development. We interviewed eighteen intersex persons aged 18-38. We identified three main themes: (1) intersex experiences, (2) the described sexual and relational life course, and (3) factors influencing a positive development. Our findings show that intersex youth face many obstacles to their relational and sexual development, many of which related to healthcare. However, their life stories also illuminate how healthcare professionals but also parents, friends, partners, teachers and others can make a substantial difference in intersex lives by breaking normative, binary thinking on sex and gender.

Myrtus communis L., commonly known as true myrtle, is a medicinal plant native to the Mediterranean area. Since ancient times inhabitants of this area have been using it for its cultural and medicinal properties. Due to the high content of essential oil in its flowers, leaves and fruits, M. communis is an important medicinal and aromatic species from Myrtaceae family. Because of the presence of vast diversity of biomolecules in its aerial parts, it exhibits several biological properties of antioxidant, antimicrobial and anticancer. There has been increasing scientific interest in the field to understand the pleotropic effects of its extracts or essential oils on various ailments and diseases. This purpose of this review is to summarizes the chemical composition, traditional uses, and biological activities of M. communis L. leaves documented in numerous recent studies.

We aim to investigate if serum levels of microRNAs: miR-126, mir-197 and mir-223, previously implicated in cardiometabolic disease, are reproducibly associated with incident-diabetes (inc-DM), incident-cardiovascular disease (inc-CVD) and with carotid atherosclerosis (measured for the maximum thickness of the intima-media of the carotid bulb (IMT)). The microRNAs were measured, one: in serum of 553 subjects from the baseline exam of the Swedish prospective cohort, Malmö Diet and Cancer Study (MDC-CC), with 169 subjects who developed CVD and 140 DM (16 years follow-up) and, two: in 1221 subjects from the Malmö Offspring Study (MOS), with 14 de-veloped CVD and 12 DM (3.7 years follow-up). Multivariate logistic and linear regression models were used to investigate the relationship of serum-concentrations of the microRNAs and inc-DM, inc-CVD, IMT-bulb respectively. In MDC-CC, miR-126 showed significant positive association with inc-DM (p= 0.01) whereas in fully adjusted model, the association was borderline significant (p= 0.05). The results were not replicated in MOS. There was no consistent significant association between the microRNAs with IMT or inc-CVD in any cohort. Our results do not support previous reports on significant associations between these microRNAs and the risk of CMD, as they were not reproducible in our cohorts. In addition, the directionality of any associations found were not consistent with those previously reported.

An integrated approach to active flow control is proposed by finding both the drooping leading edge and the morphing trailing edge for flow management. This strategy aims to manage flow separation control by utilizing the synergistic effects of both control mechanisms, which we call the Combined Morphing Leading Edge and Trailing Edge (CoMpLETE) technique. This design is inspired by a bionic porpoise nose and the flap movements of the cetacean species. The motion of this mechanism achieves a continuous, wave-like, variable airfoil camber. The dynamic motion of the airfoil's upper and lower surface coordinates in response to unsteady conditions is achieved by combining the thickness-to-chord (t/c) distribution with the time-dependent camber line equation. A parameterization model was constructed to mimic the motion around the morphing airfoil at various deflection amplitudes at stall angle of attack and morphing actuation start times. The mean properties and qualitative trends of the flow phenomena are captured by the transition-SST (Shear Stress Transport) model. The effectiveness of the dynamically morphing airfoil as a flow control approach is evaluated by obtaining the flow field data, such as velocity streamlines, vorticity contours, and aerodynamic forces. Different cases are investigated for the CoMpLETE morphing airfoil, which evaluates the airfoil’s parameters, such as its morphing location, deflection amplitude, and morphing starting time. The morphing airfoil’s performance is analyzed to provide further insights into the dynamic lift and drag force variations at pre-defined deflection frequencies of 0.5 Hz, 1 Hz, and 2 Hz. The findings demonstrate that adjusting the airfoil camber reduces streamwise adverse pressure gradients, thus preventing significant flow separation. Although the trailing edge deflection and its location along the chord influence the generation and separation of the Leading-Edge Vortex (LEV), these results show that the combined effect of the morphing leading edge and trailing edge has the potential to mitigate flow separation. The morphing airfoil successfully contributes to the flow reattachment and significantly increases the maximum lift coefficient (c_(l,max))). This work also broadens its focus to investigate the aerodynamic effects of a dynamically morphing leading and trailing edge, which seamlessly transitions along the side edges. The aerodynamic performance analysis is investigated across varying morphing frequencies, amplitudes, and actuation times.

Blockchain and Machine Learning gives the best solutions together in performing various tasks in the Smart Health care system. With these two new emerging technologies, that have materialized in the last decade. In this paper, we proposed secure, transparent and intelligent methods in the Internate of medical things industry using Machine learning models and blockchain technology to enhance security level and train our models to improve diagnostic, prevention, treatment of the patient, patient rights, patient autonomy and equality in the health care system.

Load variations in any power system result in losses escalation and voltage drops. With the sensible and optimal allocation of distributed generators (DGs), these problems could be considerably mitigated. It has been seen in the priorly existing methods that ideally allocation of DGs has been carried out during fixed loads and constant power requirements. However, in real scenarios the loads are always variable and allocation of DGs must be done in accordance to the variations of the connected load. Therefore, the current paper addressed the aforementioned problem by distinctive optimal allocation of DGs for each variability of 24hour load horizon. However, the single exclusive solution is considered among all allocations of 24 hours. The min-max regret concept has been utilized in order to deal with such methodology. Altogether, 24 scenarios are analyzed wherein each scenario corresponds to a specific hour of the respective day. The optimal allocation of DGs in terms of their optimal sizing and placement has been carried out by using three algorithms including battle royal optimization (BRO), accelerated particle swarm optimization (APSO) and genetic algorithm (GA). The multi-objective optimization problem is evaluated on the basis of minimum value criterion of the multi-objective index (MO). MO comprises of active and reactive power losses and voltage deviation. Hence, in order to find robustness of proposed technique, Conseil international des grands réseaux electriques (CIGRE’s) MV benchmark model incorporating 14 buses has been considerably used as a test network. In the end the results of three proposed algorithms have been compared.

(1) Background: This study aims to validate the use of Bloom's revised taxonomy as an instrument for the design of assessment tests; (2) Methods: A validation has been carried out by external judges, as well as by teachers and students, validating the instrument by means of Aiken's V; (3) Results: Judges, teachers and students consider Bloom's revised taxonomy as an effective tool for the design of assessment tests; (4) Conclusions: Using Bloom's revised taxonomy as a model for designing assessment tests promotes learning.

miRNAs are major regulators of eukaryotic gene expression, host immunity, and play an important role in the inflammation-mediated pathways in periodontal disease (PD) pathogenesis. Expanding our previous observation with the global miRNA profiling using partial human mouth microbes and lack of in vivo studies involving oral spirochete Treponema denticola induced miRNAs, this study was designed to delineate the global miRNA expression kinetics during progression of periodontitis in mice infected with T. denticola by using NanoString nCounter® miRNA panels. All the T. denticola-infected male and female mice at 8- and 16 weeks demonstrated bacterial colonization (100%) on the gingival surface, and an increase in alveolar bone resorption (p < 0.0001). A total of 70 miRNAs with at least 1.0-fold differential expression/regulation (DE) miRNAs (26 upregulated and 44 downregulated) were identified. nCounter miRNA expression profiling identified 13 upregulated miRNAs (e.g. miR-133a, miR-378) and 25 downregulated miRNAs (e.g. miR-375, miR-34b-5p) in T. denticola-infected mice mandibles during 8-weeks infection whereas 13 upregulated miRNAs (e.g. miR-486, miR-126-5p) and 19 downregulated miRNAs (miR-2135, miR-142-3p) were observed during 16- weeks of infection. One miRNA (miR-126-5p) showed significant difference between 8-and 16-weeks of infection. Interestingly, miR-126-5p has been presented as a potential biomarker in patients with periodontitis and coronary artery disease. Among the 13 upregulated miRNAs, miR-486, miR-126-3p, miR-126-5p were reported in human gingival plaques samples with periodontitis. KEGG analysis revealed various functional pathways of DE miRNAs such as bacterial invasion of epithelial cells, Ras signaling, Fc gamma R- mediated phagocytosis, osteoclast differentiation, adherens signaling and ubiquitin mediated proteolysis. This is the first study of DE miRNAs in mice mandibles at different time-points of T. denticola infection and the combination of three specific miRNAs miR-486, miR-126-3p, miR-126-5p may serve as an invasive biomarker of T. denticola in PD. These miRNAs may have significant role in PD pathogenesis and establishes a link between miRNA, periodontitis, and systemic diseases.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Today, concepts such as Emotional Education and Emotional Intelligence are recognized by many authors and researchers, emphasizing the importance of their development in all people, but especially in schools, specifically in teachers or educators and children. However, we still find many shortcomings within the schools that are needed to continue working. The aim of this study is to investigate the presence of emotional intelligence and empathy in teachers, through a sample of 42 participants. The research was conducted based on two validated and highly reliable assessment tools, called TMMS-24 and TECA. The results of the TMMS-24 indicate that a large percentage of participants have an adequate score of emotional intelligence. The results of the TECA indicate that most of the participants are in the middle, high or extremely high scores in relation to the level of empathy.

Abstract: Autophagy has a dual role in gliomagenesis in a microRNA-modulated environment. We investigated the potential relevance of autophagy in glioma development and survival by exploring the association of autophagy-associated genes and microRNAs in low- and high-grade gliomas. Real-time PCR (qPCR) was used to determine the expression of genes and microRNAs in 50 fresh glioma tissues while Formalin-fixed paraf-fin-embedded tissues of the same patients were used for immunohistochemistry. The Mann-Whitney U-test test, Spearman correlation test, and Kaplan-Meier survival analysis were performed to evaluate the expression, association, and overall survival in patients respectively. The expression of LC3, AKT, and miR-21 was increased in high-grade glioma compared to low-grade glioma while ULK2 expression was decreased in high-grade glioma. A strong positive correlation was observed for ULK2 with UVRAG, PTEN, miR-7, and miR-100, while the moderate correlation with mTOR, Beclin1, miR-30, miR-204, miR-374, miR-21 and miR-126 in low-grade glioma, while a moderate positive correlation between ULK2 and PI3K, PTEN, ULK1, VPS34, mTOR, Beclin1, UVRAG, AKT and miR-374, and between AKT and ULK1, VPS34, UVRAG, and miR-7 in high-grade gliomas. The low ULK2 and LC3 expression group was significantly associated with better overall survival in gliomas while miR-21 overexpression showed a poor prognosis in glioma patients. Therefore, miR-21, ULK2, and LC3 may serve as prognostic biomarkers for survival outcomes in glioblastoma.

The regulatory mechanism of PCSK7 gene is still unknown, although its encoded protein PC7 is the most ancient and highly conserved of all proprotein convertases and exhibits enzymatic and non-enzymatic functions in liver triglyceride regulation. Bioinformatics algorithms were used to predict regulatory microRNAs (miRNAs) of PCSK7 expression. This led to the identification of 4 miRNAs, namely miR-125a-5p, miR-143-3p, miR-409-3p, and miR-320a-3p, with potential binding sites on the 3’-untranslated region (3′-UTR) of human PCSK7 mRNA. The expression patterns of these miRNAs and PCSK7 mRNA were assessed in three different cell lines with quantitative polymerase chain reaction (qPCR), which revealed reciprocal expression patterns between the expression levels of the four selected miRNAs and PCSK7. Next, the interactions and effects of these miRNAs on PCSK7 expression levels were investigated via cell-based expression analysis, dual-luciferase assay, and Western blot analysis. The data revealed that PCSK7 mRNA levels decreased in cells transfected with vectors overexpressing miR-125a-5p, miR-143-3p, and miR-409-3p, but not miR-320a-3p. The dual-luciferase assay demonstrated that the above 3 miRNAs could directly interact with putative target sites in PCSK7 3′-UTR and regulate its expression, whereas miR-320-3p exhibited no interaction. Western blot analysis further revealed that overexpression of miR-125a-5p in Huh7 cells inhibits the expression and ability of PC7 to cleave human transferrin receptor 1. Our results support a regulatory role of these miRNAs in PCSK7 expression and function and opens the way to assess their roles in the regulation of PC7 activity in vivo in the development of hepatic steatosis.

Recent advances in sensor and platform technologies such as satellite systems, unmanned aerial vehicles (UAV), manned aerial platforms, and ground-based sensor networks have resulted in massive volumes of data is produced and collected about the earth. Processing, managing, and analyzing these data is one of the main challenges in 3D synthetic representation used in modeling and simulation (M&S) of the natural environment. M&S devices, such as flight simulators, traditionally require a variety of different databases to provide a synthetic representation of the world. M&S often requires integration of data from a variety of sources stored in different formats. Thus, for simulation of a complex synthetic environment, such as a 3D terrain model, tackling interoperability among its components (geospatial data, natural and man-made objects, dynamic and static models) is a critical challenge. Conventional approaches used local proprietary data models and formats. These approaches often lacked interoperability and created silos of content within the simulation community. Therefore, open geospatial standards are increasingly perceived as a means to promote interoperability and reusability for 3D M&S. In this paper, the Open Geospatial Consortium (OGC) CDB Standard is introduced. “CDB” originally refers to Common DataBase which is currently considered as a name with no abbreviation in the OGC community. The OGC CDB is an international standard for structuring, modeling, and storing geospatial information required in high performance modeling and simulation applications. CDB defines the core conceptual models, use cases, requirements, and specifications for employing geospatial data in 3D M&S. The main features of the OGC CDB Standard are described as run-time performance, full plug-and-play interoperable geospatial data store, usefulness in 3D and dynamic simulation environment, ability to integrate proprietary and open-source data formats. Furthermore, compatibility with the OGC standards baseline reduces the complexity of discovering, transforming, and streaming geospatial data into the synthetic environment and makes them more widely acceptable to major geospatial data/software producers. This paper includes an overview of OGC CDB version 1.0 which defines a conceptual model and file structure for the storage, access, and modification of a multi-resolution 3D synthetic environment data store. Finally, this paper presents a perspective of future versions of the OGC CDB and what the steps are for humanizing the OGC CDB standard with the other OGC/ISO standards baseline.

Transcriptional regulation constitutes a key step in gene expression regulation. Myocyte enhancer factor 2C (MEF2C) is a transcription factor of MADS box family involved in the early development of several cell types including muscle cells. Over the last decade a novel layer of complexity modulating gene regulation is emerging as non-coding RNAs have been identified, impacting in both transcriptional and post-transcriptional regulation. microRNAs represent the most studied and abundantly expressed subtype of small non-coding RNAs and their functional role have been widely documented. On the other hand, our knowledge on the transcriptional and post-transcriptional regulatory mechanisms that drive microRNA expression is still incipient. We recently demonstrated that MEF2C is able to transactive the long, but not short, regulatory element upstream of miR-23a-miR-27a-miR-24-2 transcriptional start site. However, MEF2C over-expression and silencing, respectively, displayed distinct effects on each of the miR-23a-miR-27a-miR-24-2 mature cluster members, without affecting pri-miRNA expression levels, supporting thus additional MEF2C-driven regulatory mechanisms. Within this study we demonstrated a complex post-transcriptional regulatory mechanisms directed by MEF2C in the regulation of miR-23a-miR-27a-miR-24-2 cluster members, distinctly involving different domains of the MEF2C transcription factor and the physical interaction with pre-miRNAs and RNA interacting proteins such as Ksrp, HnRNPa3 and Ddx17.

MicroRNAs are small non-coding RNAs that are implicated in several physiological processes such as cell development, proliferation, differentiation, apoptosis, immune response and angiogenesis. In the last couple of decades, several studies on miRNA profiling in OSCC have tried to associate miRNAs with clinical characteristics such as relapse, metastasis, and survival, however, the results have been found to vary considerably, sometimes even being contradictory. The main objective of our study was to analyse and verify miRNA expression in oral squamous cell carcinoma in a Spanish population. Second, we attempted to associate the identified deregulated miRNAs with molecular pathways. 8 Oral Squamous Cell Carcinoma patients and 8 healthy control samples were analysed by a microarray Affymetrix® miRNA 4.1 array plate and validated with 8 more cases using RT-qPCR. Deregulated miRNAs were studied using Diana Tools miRPath 3.0 to associate miRNA targets with molecular pathways. Microarray analysis identified 80 deregulated miRNAs (35 over-expressed and 45 under-expressed). Only miR-497-5p and miR-4417 maintained its deregulated expression after validation with qPCR. Among the molecular pathways in which deregulated miRNAs could be implicated, the most statistically significant pathway was ‘proteoglycans in cancer’. No relationship was found between miR-497-5p or miR-4417 expression and clinical or pathological parameters except of nodular affectation (high miR-4417 expression in patients with nodular affectation, p = 0.035) and radiotherapy (diminished miR-497-5p expression in patients who needed radiotherapy, p = 0.05). We have verified the altered expression of miR-497-5p and miR-4417 in Oral Squamous Cell Carcinoma samples and related the deregulated miRNAs with the ‘proteoglycans in cancer’ pathway.

Cardiac development is a complex developmental process that results in the formation of the four-chambered organ from a single linear heart tube. In the early stages of development, the linear heart tube is composed of only two tissue layers, an external myocardium that is internally lined by the endocardium. Subsequently, the proepicardium emerges at the septum transversum and soon thereafter proepicardial cells will migrate into the naked myocardium, leading to the formation of the embryonic epicardium. As cardiac development proceeds, epicardial-derived cells migrate into the subepicardial space and subsequently invade the developing ventricular chambers leading to the contribution of distinct cardiovascular cell types such as the cardiac fibroskeleton and different components of coronary vasculature. At present, the molecular mechanisms that regulate the transitional process from the proepicardium to the embryonic myocardium are largely unexplored. In this study we have implemented an ex vivo proepicardium/septum transversum (PE/ST)-embryonic myocardium explant model and we demonstrated that miR-223, but not miR-195, is capable of modulating PE/ST migration, a process that seems to be mediated by Slug expression. Thus, our study demonstrates for the first time the implication of distinct microRNAs in the PE/ST to embryonic myocardium transition in chicken embryonic hearts.

Hepatocellular carcinoma (HCC) early diagnosis is challenging. Moreover, for patients with al-pha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profile may serve as potential HCC molecular markers. We aimed to assess plasma homo sabines (hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-199a-5p expression levels, as panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), es-pecially AFP-negative HCC cases, a step toward non-protein coding (nc) RNA precision medicine. Subjects and Methods: 79 patients enrolled with CHCV infection with LC, subclassified into LC group without HCC (n=40) and LC with HCC (n=39) in comparison with 15 apparently healthy control subjects. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. Results: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n=39) when compared to LC group (n=40). Hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin re-sistance (r=0.5, p<0.001, r=0.334, p=0.01, and r=0.303, p=0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, re-spectively, vs 69% for AFP alone, with an acceptable specificity of 77.5%, 77.5%, and 80%, respec-tively, and AUC= 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC=0.76 and 0.71, respectively, with sensitivities=94% and 92%, and specifici-ties=48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR=1.198(1.063–1.329), p=0.002]. Conclusion: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made possi-ble to identify HCC development in LC patients’ cohort with higher sensitivity than using AFP alone. Hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are poten-tial HCC molecular markers for AFP-negative HCC patients. Hsa-miR-21-5p was linked to insu-lin metabolism in HCC patients’ group as well as being an upregulated independent risk factor for the emergence of HCC from LC in CHCV patients.

Mesial temporal lobe epilepsy (mTLE) is one of the most common and refractory focal epilepsy syndromes. The molecular mechanisms of TLE are not completely understood. The aim of this study was to investigate the expression and potential function of plasma exosomal miRNAs (miR-483-5p, miR-671-5p, and miR-150-3p) in a mouse mode and in temporal lobe epilepsy patients. It was found that exosomal miRNAs were differentially expressed in three phases of the mouse mode, and exosomal miRNAs were down-regulated in mTLE patients compared with healthy controls. A bioinformatics analysis showed that target genes of exosomal miRNAs were significantly involved in the apoptotic process, cell adhesion, nervous system development, neurotrophin signaling pathway, PI3K-Akt signaling pathway, and metabolic pathways. The areas under the curve of miR-483-5p and miR-150-3p were 0.8714 (sensitivity = 75.00%, specificity = 91.65%) and 0.8213 (sensitivity = 67.50%, specificity = 90.00%), respectively. More importantly, the exosomal miRNAs were significantly associated with clinical parameters. Exosomal miRNAs may have the potential to become diagnostic and therapeutic biomarkers.

This article presents new PEM fuel cell models with hexagonal and pentagonal designs. After observing cell performance improvement in these models, we optimized them. Inlet pressure and temperature were used as input parameters, and consumption and output power were the target parameters of the multi-objective optimization algorithm. Then we used artificial intelligence techniques, including deep neural networks and polynomial regression, to model the data. Next, we employed the RSM (Response Surface Method) method to derive the target functions. Furthermore, we applied the NSGA-II multi-objective genetic algorithm to optimize the targets. Compared to the base model (Cubic), the optimized Pentagonal and Hexagonal models averagely increase the output current density by 21.819\% and 39.931\%, respectively.

The main aim of this article is to examine the inter-relationships among the top cryptocurrencies on the crypto stock market in the presence and absence of the COVID-19 pandemic. The nine chosen cryptocurrencies are Bitcoin, Ethereum, Ripple, Litecoin, Eos, BitcoinCash, Binance, Stellar, and Tron and their daily closing price data are captured from coinmarketcap over the period from 9/13/2017 to 9/21/2020. To determine the order of integration, the Augmented Dickey-Fuller (ADF), Phillips-Perron (PP), and Kwiatkowski, Phillips, Schmidt, and Shin (KPSS) unit root tests were carried out, and all of the cryptocurrencies were found to be integrated of order 1 i.e. I(1). It has been found that there is strong evidence of a long-run relationship between Bitcoin and altcoins irrespective of whether it is pre-pandemic or pandemic period. Hence these cryptocurrencies' prices and their inter-relationship are resilient to the pandemic.

Increasing demand for electricity and modernization of power systems within competitive markets induce power systems to operate close to their stability limits. Therefore, a power system continuous monitoring and control by using voltage stability indices are known exigence. This is the first-ever effort, examined more than 40 voltage stability indices thorough an exhaustive study based in on their formulation, application, performance, and assessment measures. Which is conducted based on a logical and chronological order considering the most recent worldwide applied voltage stability indices. However, the generalizability of such an immense diversity of these indices in term of multivariable objectives subjects to a certain limitation to summate into a deciphered outcome. Despite all these obstacles, this study systematically reviews available indices in the literature within the past three decades to set out an integrated knowledge with an insight up-to-date exposition. That followed with a comparative analysis in term of their similarity, functionality, applicability, formulation, merit, demerit, and overall performances. Also, a broad categorization of voltage stability indices is addressed. This study with an immediate implication in practice as an exhaustive roadmap can be counted a planning and operation reference in the context of voltage stability for students, researchers, scholars, and practitioners.

We investigate the behavior of thermal quantum coherence in the Heisenberg XXX model for a two-qubit system placed in independently controllable Inhomogeneous magnetic fields applied to two qubits respectively. We discuss the behavior of quantum coherence by systematically varying the coupling parameter, magnetic field, and temperature for both ferromagnetic and antiferromagnetic cases. The results show the interesting behavior of quantum coherence in a certain range of parameters. Generally, it is observed that quantum correlations decay with temperature, but in the ferromagnetic case with uniform magnetic interaction, it rises with temperature up to a certain threshold value and ultimately it decreases its value to zero. Moreover, it is observed that preserving the quantum coherence for small temperatures is very hard with the increasing magnetic field because, at small temperatures, quantum coherence decays sharply with the increase in magnetic field whereas at larger temperatures it decays completely at fairly large values of the magnetic field. The variation of quantum coherence with uniform magnetic field in the antiferromagnetic case is observed to be Gaussian for larger temperature but at zero or nearly zero temperature, it behaves as a constant function for uniform magnetic field up to a threshold value and then decays to zero with an infinite slope. This shows the signature of quantum phase transition from quantum nature to classicality.

The research paper examines ‘aporia,’ ‘Différance,’ ‘binary oppositions’ in Ira Trivedi's "The Great Indian Love Story," and India in Love focusing on the characters Riya, Serena, and Permeet's experiences. Derrida’s deconstructive approach is applied to trace out ‘binaries’, ‘aporia’, and ‘Différance’ of sexuality and stigma in literary texts and real human life. It highlights how these characters seem/likely to challenge Indian societal norms and values, societal prejudices and discrimination that lead them to experiences of marginalization and exclusion of the self from other selves. It is observed that deconstruction is an apt approach to literature not a destructive approach.

Wear usually occurs in the loaded part of hydrodynamic bearings and leads the bearing geometry imperfections. This paper investigates the effects of wear-induced geometric imperfections of tilting pad journal bearings (TPJBs) on the dynamic behavior of the system. Furthermore, the effect of wear on the journal-bearing rub-induced contact pressure severity is investigated. A novel tribo-dynamic model is proposed for a flexible rotor-worn TPJB which integrates a mixed elastohydrodynamic model with a rotor-worn TPJB thermal and dynamic model to assess the effects of the bearing wear progression on the rotor-TPJB behavior. Based on the results, wear changes the temperature distribution of the pads and oil film as well as the dynamic behavior of the system. Dynamic simulations reveal a higher vibration level and contact pressure for the worn TPJBs near the system's critical speed and service speed. Finally, thermal and dynamic condition indicators are suggested to detect TPJB wear severity at its early stages.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

We construct a family of two-step optimal fourth order iterative methods for finding single root of non-linear equations. We generalize these methods to simultaneous iterative methods for determining all the distinct as well as multiple roots of single variable non-linear equations. Convergence analysis is present for both cases to show that the order of convergence is four in case of single root finding method and is twelve for simultaneous determination of all roots of non-linear equation. The computational cost, Basin of attraction, efficiency, log of residual and numerical test examples shows, the newly constructed methods are more efficient as compared to the existing methods in literature.

End-stage renal disease (ESRD) is associated with fatigue and physio-somatic symptoms. The aims of this study are to delineate the associations between severity of fatigue and physio-somatic symptoms and glomerular filtration rate, inflammatory biomarkers, and Wnt/catenin-pathway proteins. The Wnt-pathway related proteins β-catenin, Dickkopf-related protein 1 (DKK1), R-spondin-1, and sclerostin were measured by ELISA technique in 60 ESRD patients and 30 controls. The Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to assess severity of FF symptoms. ESRD is characterized by a significant increase in the total FF score, muscle tension, fatigue, sadness, sleep disorders, GI symptoms, and a flu-like malaise. The total FF score was significantly correlated with serum levels of urea, creatinine, phosphate, and copper (positively), and β-catenin, eGFR, hemoglobin, albumin, and zinc (inversely). The total FF score was associated with the number of total dialysis and weekly dialysis sessions, and these dialysis characteristics were more important in predicting FF scores than eGFR measurements. Partial Least Squares analysis showed that the FF score comprised two factors which are differently associated with biomarkers: a) 43.0% of the variance in fatigue, GI symptoms, muscle tension, sadness, and insomnia is explained by hemoglobin, albumin, zinc, β-catenin, and R-spondin-1; and b) 22.3% of the variance in irritability, concentration and memory impairments by increased copper and cations/chloride ratio, and male sex. ESRD patients show high levels of fatigue and physio-somatic symptoms which are associated with hemodialysis and mediated by dialysis-induced changes in inflammatory pathways, the Wnt/catenin pathway, and copper.

The different systems in the nuclear power plants (NPP) are critical and complex which requires a continuous rigorous monitoring for both normal and abnormal conditions. However, due to the nonlinearity of the dynamic behavior of these systems, implementation of artificial intelligence within the NPP components is crucial to enhance the monitoring and the predictability of the key operating parameters trend. On the other hand, lessons learned from large nuclear accident proves that a remote real-time coordination between the different stakeholders involved in the safety of the nuclear reactor is needed. This remote feature can be implemented in the existing power plants by embedding a mobile computing networks within the plant components. This network will send early warning and transmit the NPP data on real-time to different authorities such as the regulatory authority and the decision-making committees, to enhance the interpretability of the nuclear event and deliver a collaborative decision which in return mitigate the risk associated with these events and increase the overall safety of the plant. The integration of AI and mobile computing in NPP would be most of interest in countries where nuclear reactors data are challenged to reach during an accident. For instance, during the meltdown of Chernobyl, the Soviet government covered the accident from the news in an attempt to contain the consequences but there was a spread of radioactive contamination to some other Europe countries. Therefore, in the case of such scenario the implementation of mobile computing and AI would result in different outcomes as the European countries would be notified through the mobile networking and the spread of contamination would be forecasted by the AI algorithms. In this paper, we examine the different modern AI and mobile computing technologies, the different potential application, the associated features and challenges, and future work direction.

Introduction: The goals of this retrospective cohort study of 129,443 persons admitted to Calgary acute care hospitals 2013-2021 were to ascertain correlations of “potentially inappropriate medi-cations” (PIMs), “potential prescribing omissions” (PPOs) and other risk factors with readmissions and mortality. Methods: Processing and analysis codes were built in Oracle Database 19c (PL/SQL), R and Excel. Results: The percentage dying during their hospital stay rose from 3.03% during the first to 7.2% during the 6th admission. The percentage dying within 6 months of discharge rose from 9.4% after the first to 24.9 after the sixth admission. Odds ratios (adjusted for age, gender and comorbidities) for readmission were the post-admission number of medications (1.16; 1.12-1.12), STOPP PIMs (1.16; 1.15-1.16); AGS Beers PIMs (1.11; 1.11-1.11) and START omissions not corrected with a prescription (1.39 (1.35-1.42). Odds ratios for mortality were post-admission number of medications (1.04; 1.04-1.05), STOPP PIMs (0.99; 0.96-1.00); AGS Beers PIMs (1.08; 1.07-1.08) and START omissions not corrected with a prescription (1.56 (1.50-1.63). START omissions corrected with a prescription correlated with a dramatic reduction in mortality (0.51; 0.49-0.53). Odds ratios for readmissions for the second through 39th admission were consistently higher if START PPOs were not corrected for the second admission (1.41; 1.36-1.46), third (1.41;1.35-1.48); fourth 1.35;1.28-1.44); fifth 1.38; 1.28-1.49); sixth (1.47;1.34-1.62) and 7th through 39th admission (1.23; 1.14-1.34). For all admissions when a pre-scription was given to correct START PPOs ORs for mortality within six months of discharge were dramatically improved (0.51; 0.49-0.53). This was also true for the second (0.52; 0.50-0.55; fourth (0.56; 0.52-0.61; fifth (0.63; 0.57-0.68); sixth (0.68; 0.61-0.76); and 7th through 39th admissions (0.71; 0.65-0.78). Conclusions: PPOs should be corrected by prescriptions and teams of family physicians, pharmacists and nurses should focus on patients’ understanding of their illnesses, medications and ability for self-care.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

Single cell proteins are the dead dried cells of microorganisms or purified protein isolated from microorganism’s cell culture, used as a food supplement to humans’ food and animals feed. World suffer from malnutrition particularly developing countries, due to rapid increase in population, increased the demand for protein and nutrients requirement. Bacteria is potential microorganism for SCP production due to high protein content, fast generation time, bio-active secondary metabolites production and can grow on various substrates. Actinobacteria species and strain have capability to produce biological active compounds, produced about two-thirds of antibiotics available in the market, actively used as antibiotics, antiprotozoal, antifungal, antiviral, anticancer, anticholesterol, antihelminth and immunosuppressant. Actinomycetes can be used as probiotic as well as single cell protein that will deal with antibiotic as well as protein source.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The al-tered tumor microenvironment after tuberculosis infection appears to contribute to cancer pro-gression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of select exosomal microRNAs. TPE-derived exosome treatment en-hanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell inva-sion. Exosome-mediated transfer of select microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phos-phorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p sup-pressed the promotion of lung cancer by TPE derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TBE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

Deep neural network (DNN) watermarking is a potential approach for protecting the intellectual property rights of DNN models. Similar to classical watermarking techniques for multimedia content, the requirements for DNN watermarking include capacity, robustness, and transparency, and other factors. Studies have focused on robustness against retraining and fine-tuning. However, less important neurons in the DNN model may be pruned. Moreover, although the encoding approach in renders DNN watermarking robust against pruning attacks, the watermark is assumed to be embedded only into the fully connected layer in the fine-tuning model. In this study, we extended the method such that the model can be applied to any convolution layer of the DNN model and designed a watermark detector based on a statistical analysis of the extracted weight parameters to evaluate whether the model is watermarked. Using a nonfungible token mitigates the overwriting of the watermark and enables checking when the DNN model with the watermark was created.

Membrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: 1) they promote the formation of highly curved membrane domains and 2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).

Diisocyanates, particularly toluene diisocyanate (TDI) are useful for the preparation of various polyurethanes with specific applications as leather-like materials, adhesives, insoles etc. Blocking agents can be used for the operational simplicity and reducing the hazards of TDI. In this paper we reported the use of 3-(4-bromo-phenyl)-1H-pyrazole to block toluene diisocyanate (TDI). FTIR, NMR, thermogravimetric analysis, contact angle and differential scanning calorimetry (DSC) and were used for characterization. Effectiveness of blocking was confirmed by spectroscopic techniques. DSC thermogram shows that blocked adducts deblock at 240 °C causing the regeneration of TDI and blocking agents to react with polyols of different molecular weights forming polyurethanes. The characterization of polyurethanes has been done by Infrared spectroscopy, Nuclear magnetic resonance spectroscopy, thermogravimetric analysis, differential scanning calorimetry and contact angle study.

Adult human thymus degenerates into adipose tissue (TAT). In contrast to subcutaneous adipose tissue (SAT), TAT has been reported to exhibit enhanced angiogenic properties in elderly people. We have previously shown that vascular endothelial growth factor A (VEGFA) is the most abundant angiogenic growth factor in TAT of patients with ischemic cardiomyopathy (IC), and that VEGFA levels are increased in elderly (&gt;70 years) compared with middle-aged patients. This makes TAT a promising candidate for angiogenic therapies and the regeneration of ischemic tissues following coronary surgery. MicroRNAs (miRNAs) have emerged as attractive therapeutic targets, especially those that regulate angiogenic processes. The study's purpose is to determine the miRNA network associated with both VEGFA pathway regulation and enrichment of age-linked angiogenesis in the TAT.

Background: Glioblastoma (GBM), a malignant grade IV tumor, is the most malignant brain tumor due to its hyper-proliferative and apoptosis-evading characteristics. The signal transducer and activators of transcription (STAT) family genes, including STAT3 and STAT5A, have been indicated to play important roles in GBM progression. Increasing number of reports suggest that Garcinol, a polyisoprenylated benzophenone and major bioactive component of Garcinia indica contains potent anti-cancer activities. Material & Methods: The present study investigated the anti-GBM effects of garcinol, focusing on the STAT3/STAT5A activation, using a combination of bioinformatics, in vitro, and ex vivo assays. Results: Our bioinformatics analysis of TCGA - GBM cohort (n=173) showed that STAT3 and STAT5A are preferentially elevated in primary and recurrent GBM, compared to non-tumor brain tissues, and is significantly correlated with reduced overall survival. In support, our immunohistochemical staining of a GBM cohort (n=30) showed an estimated 5.3-fold (p<0.001) elevation in STAT3 and STAT5A protein expression in primary and recurrent GBM versus the non-tumor group. In vitro, garcinol treatment significantly suppressed the proliferative, invasive, and migratory potential of U87MG or GBM8401 cells, dose-dependently. In addition, garcinol anticancer effect significantly attenuated the GBM stem cell-like phenotypes, as reflected by diminished ability of U87MG or GBM8401 to form colonies and tumorspheres and suppressed expression of OCT4 and SOX2. Furthermore, analysis on GBM transcriptome revealed an inverse correlation between the level of STAT3/5A and hsa-miR-181d. Garcinol-mediated anti-GBM effects were associated with an increased hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratio. Conclusion: We present evidence of anti-GBM efficacy of garcinol mediated by enhancing the hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratios in GBM cells. Our findings suggest a potential new therapeutic agent for combating aggressive GBM.

Accurate prediction of defects in software components plays a vital role in administrating the quality of the quality and efficiency of the system to be developed. So we have written a systematic literature review in order to evaluate the four main defect prediction techniques. Defect prediction paves way for the testers to find bugs and modify them in order to achieve input to output conformance. In this paper we have discussed the open issues in predicting software defects and have provided with a detailed analyzation of different methods including Machine Learning, Integrated Approach, Cross-Project and Deep Forest algorithm in order to prevent these flaws. However, it is almost impossible to rule which method is better than the other so every technique can be analyzed separately and the best technique according to the problem at hand can be used or can be altered to create hybrid technique suitable for the cause.

Background: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of β -Lapachone, a novel synthetic compound. Methods: The antibacterial activity of the β -Lapachone compound was examined against laboratory strains by agar well diffusion method, minimal inhibitory concentration (MICs), and minimal bactericidal concentration (MBCs). Growth kinetics inhibition in presence of β -Lapachone on Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa (ATCC 27853) was assessed by MABA. Crystal violet blue assay was used for biofilm inhibition assays, biofilm eradication assay and for molecular modeling PyMOL was used. Results: β -Lapachone exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Molecular modeling predicted the binding of β -Lap at active site and heme binding site of catalase, KatA. The activity of some commercial antibiotics was enhanced in association with β -Lap. In addition, β -Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains.

We study the validity of quantum Fisher information (QFI) as a faithful quantum coherence and correlation quantier by drawing a comparison with subsystem's coherence measure, rst-order coherence (FOC) and the entanglement measure, Negativity to study the behavior of thermal quantum coherence and correlations in two qubit Heisenberg XXX model, placed in independently controllable magnetic eld by systematically varying the coupling parameter, magnetic eld and bath temperature for ferromagnetic and antiferromagnetic case. After carefully observing the prole of quantum coherence and correlation measures, we propose an inequality relations which shows that there may exist a quantitative relationship between QFI, Negativity and FOC in which, the equality exists at zero temperature. We identify QFI to be a more useful coherence quantier, as it quanties coherence of individual subsystems and correlations among the subsystems. On the other hand, FOC identies coherence present in the individual subsystems only. A reciprocal relationship between Negativity and FOC is also observed in dierent cases. We also observe the existence of entanglement in ferromagnetic case, in contrast to simple Heisenberg XXX model in uniform magnetic eld. We show that in the ferromagnetic case, a very small inhomogeneity in magnetic eld is capable of producing large values of thermal entanglement. This shows that the behavior of entanglement in the ferromagnetic Heisenberg system is highly unstable against inhomogeneity of magnetic elds, which is inevitably present in any solid state realization of qubits.

Cement industry is one of the highest energy consuming industries. The quantity of fuel and energy needed accounts for most of the cost of cement manufacturing. Thermal power plants generate electricity but are harmful and ineffective by nature. As a backup mechanism to account for main grid failures, batteries can be utilized. In this paper the first ever investigation on battery’s depth of discharge (DOD) for four different kinds of battery technologies is carried out in the framework of cement industry. The intended battery technologies are the lead-acid battery (LA), lithium-ion battery (Li-ion), vana-dium redox battery (VR), and nickel–iron battery (Ni-Fe). Four hybrid energy generation models (HEGMs) for five cement plants of Pakistan using the HOMER pro software are proposed. Cement plants includes Askari Cement Plant, Wah (ACPW); Bestway Cement Plant, Kalar Kahar (BCPKK); Bestway Cement Plant, Farooqia (BCPF); Bestway Cement Plant, Hattar (BCPH); and DG Cement Plant, Chakwal (DGCPC). HEGM-1 comprises of a diesel generator (DGen), a photovoltaic system (PV), a converter, and a battery system. HEGM-2 comprises of a PV system, a converter, and a battery system. HEGM-3 is the grid-connected version of HEGM-1 and HEGM-4 is the grid-connected version of HEGM-2. A base-model consisting of grid only is used as a reference. A multi-criteria decision analysis (MCDA) is performed by formulating a cumulative objective function (COF) which includes net present cost (NPC), levelized cost of energy (LCOE), and greenhouse gas (GHG) emissions. The principal objective is the maximization of COF while simultaneously minimizing the objectives (NPC, LCOE and GHG emissions), based on optimal battery technology and DOD. The results reveal that VR is the most suitable battery technology with 10% DOD. It is achieved for DGCPC with HEGM-3 with 61.49% of NPC, 78.62% of LCOE and 84.00% of GHG emissions reduction as com-pared to the base model.

Malnutrition is prevalent in patients with chronic kidney disease (CKD), especially those on hemodialysis. Recently, our group described that a new oral nutritional supplement (ONS) for malnourished (or at-risk) hemodialysis patients with a "similar to the Mediterranean diet" model, improved caloric and protein intake, nutritional status and inflammation and oxidation biomarkers. Our aim in this study was to evaluate whether the new ONS, including probiotics, may produce changes in miRNAs expression and its target genes in malnourished hemodialysis patients, compared to individualized diet recommendations. We conducted a randomized, multicenter, parallel-group study in malnourished hemodialysis patients divided in 3 groups (1: Control -C- individualized diet 2: Oral nutritional supplement -ONS- + placebo -ONS-PL- and 3: ONS + probiotics -ONS-PR). Study registration: NCT03924089. The trial was open to the ONS diet or individual dietary advice, but double-blind for the intake of probiotics supplements. MiRNAs and gene expression levels were analyzed by RT-qPCR at baseline and after 3 and 6 months. We observed that the expression of miR-29a and miR-29b increased significantly in patients with ONS-PR at 3 months in comparison with baseline, stabilizing at the sixth month. Moreover, we observed differences between studied groups, where miR-29b expression levels were elevated in patients receiving ONS-PR compared to the control group in the third month. Regarding the gene expression levels, we observed a decrease in the ONS-PR group compared to the control group in the third month for RUNX2 and TNFα. TGFB1 expression was decreased in the ONS-PR group compared to baseline in the third month. PTEN gene expression was significantly elevated in the ONS-PR group at 3-months in comparison with baseline. LEPTIN expression was significantly increased in ONS-PL group at 3-month intervention compared to baseline. The new Oral Nutritional Supplement associated with probiotics; increases the expression levels of miR-29a and miR-29b after 3 months of intervention, modifying the expression of target genes with anti-inflammatory and anti-fibrotic actions. This study highlights the potential benefit of this Oral Nutritional Supplement, especially associated with probiotics, in malnourished patients with chronic renal disease on hemodialysis.

Concrete being one of the most frequently used construction materials in the field of construction. The use of concrete has increased with the passage of time as the more and more construction activities are taking place around the globe. Different materials have been added in to the concrete mix to provide the concrete more strength and make it more durable and long lasting. This paper looks into a detailed comparison of concrete strength when casted with in the presence of carbon fibers, steel fibers and glass fibers. The compressive strength for cubes and cylinder with carbon fibers is the highest as compare to steel fibers as well as glass fibers. The compressive strength of concrete is measured on 3 day, 7 day, 14 day and 28 day strength. The compressive strength of cube on 28th day strength is 37.52 MPa for carbon fiber steel, for steel fiber it is 34.22 MPa and with glass fiber the strength is 29.335 MPa whereas the compressive strength of cylinder with carbon fibers the 34.88 MPa, with steel fiber it is 34.22 MPa and with glass fiber the strength is 27.447 MPa. For the cubes the maximum difference between different fibers inducted concrete sample is 28% approximately and for cylinder it is 27%, respectively. On the other hand, the tensile strength of concrete was also gained with the carbon fiber. It was determined that carbon fiber provided about 16% and 12.8% tensile strength higher than glass and steel fibers respectively.

Sugarcane is an important industrial crop of semitropical and tropical areas. Due to the importance of this crop it is cultivated on nearly 20 million hectares by more than 90 countries. This crop belongs to family Poaceae, a grass family which is economically vital tracheophyte family that has properties much like that of wheat, maize, rice and sorghum. The Poaceae family is globally vital for providing dietary macromolecules, carbohydrates, and different nutrients. The most important item of sugarcane for the consumption is sucrose that gets accumulated in the stalk internodes. Sucrose is taken out and refined by different mills which is used as a sweetener in human food industries and in the fermentation industry. Large production of alcohol is attained by Brazilian sugarcane industries.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

The issue of equipment layout in multi-floor satellites consists of two primary parts: allocating the equipment to the satellite's layers and placing the equipment in each layer individually. In reviewing the past literature in this field, firstly, the issue of assigning equipment to layers is observed in a few articles and next in the layout part, the non-overlapping constraint has always been a challenge, particularly for components that do not have a circular cross-section. In addition to presenting a heuristic method for allocating equipment to different layers of the satellite, this article presents a robust flexible programming model (RFPM) for the placement of equipment at different layers, taking into account the inherent flexibility of the equipment in placement and the subject of uncertainty. This model is based on the existing uncertainty between the distances of cuboid equipment which has not been addressed in any of the previous research, and by comparing its outputs with cases from past studies, it demonstrates a significantly higher efficiency in placing the equipment and meeting the limit of non-overlapping constraints between the equipment. Finally, it would be possible to reduce the design time in the conceptual and preparatory stages, as well as the satellite's overall size, while still satisfying other constraints like stability and thermal limitations, moments of inertia and centre of gravity.

Microgrids are becoming popular nowadays because they provide clean, efficient, and low-cost energy. To use the stored energy in times of emergency or peak loads, microgrids require bulk storage capacity. Since microgrids are the future of renewable energy, the energy storage technology employed should be optimized to generate electricity. Batteries play a variety of essential roles in daily life and are used at peak hours and during a time of emergency. There are different types of batteries i.e., lion batteries, lead-acid batteries, etc. Optimal battery sizing of microgrids is a challenging problem, that limits modern technologies such as electric vehicles, etc. It is important to know different battery features such as battery life, battery throughput, and battery autonomy to get optimal battery sizing for microgrids. Mixed-integer linear programming (MILP) is an established technique for the integration and optimization of different energy sources and parameters for optimal battery sizing. A new MILP based dataset is introduced in this work. Support vector machine (SVM) is the machine learning application used to estimate the optimum battery size. The impact of feature selection algorithms on the proposed machine learning-based model is evaluated. The performance of the six best-performing feature selection algorithms is analyzed. The experimental results show that the feature selection algorithms improve the performance of the proposed methodology. Ranker search shows the best performance with a Spearman’s rank-ordered correlation constant of 0.9756, linear correlation constant of 0.9452, Kendall correlation constant of 0.8488 and root mean squared error of 0.0525.

As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

In recent years, the utilization of machine learning algorithms and advancements in Unmanned Aerial Vehicle (UAV) technology have marked significant shifts in remote sensing practices. In particular, the integration of machine learning with physical models and their application in UAV-satellite data fusion have emerged as two prominent approaches for estimating vegetation biochemistry. This study evaluates the performance of five machine learning regression algorithms (MLRAs) for mapping crop canopy chlorophyll at the Kellogg Biological Station (KBS) in Michigan, USA, across three scenarios: (1) application to Landsat 7, RapidEye, and PlanetScope satellite images; (2) application to UAV-satellite data fusion; and (3) integration with the PROSAIL radiative transfer model (hybrid methods PROSAIL + MLRAs). The results indicate that the majority of the five MLRAs utilized in UAV-satellite data fusion perform better than the five PROSAIL + MLRAs. The general trend suggests that the integration of satellite data with UAV-derived information, including the normalized difference red-edge index (NDRE), canopy height model, and leaf area index (LAI), significantly enhances the performance of MLRAs. The UAV-RapidEye dataset exhibits the highest coefficient of determination (R2) and the lowest root-mean-square errors (RMSE) when employing kernel ridge regression (KRR) and Gaussian processes regression (GPR) (R2 = 0.89 and 0.89 and RMSE = 8.99 µg/cm2 and 9.65 µg/cm2, respectively). Similar performance is closely observed for the UAV-Landsat and UAV-PlanetScope datasets (R2 = 0.86 and 0.87 for KRR, respectively). For the hybrid models, maximum performance is attained with Landsat data using KRR and GPR (R2 = 0.77 and 0.51 and RMSE = 33.10 µg/cm2 and 42.91 µg/cm2, respectively), followed by R2 = 0.75 and RMSE = 39.78 µg/cm2 for PlanetScope data upon integrating partial least squares regression (PLSR) into the hybrid model. Across all hybrid models, RapidEye data yielded the most stable performance, with R2 ranging from 0.45 to 0.71 and RMSE ranging from 19.16 µg/cm2 to 33.07 µg/cm2. The study highlights the importance of synergizing UAV and satellite data which enables effective monitoring of canopy chlorophyll in small agricultural lands.

MicroRNAs (miRNAs) are small and non-coding RNAs displaying aberrant expression in the tissue and plasma of cancer patients in comparison to healthy individuals. In past decades, accumulating data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been identified that miRNAs can act either as oncogenes through silencing of tumor inhibitors or tumor suppressor via targeting oncoproteins. MiR-144 is located in chromosomal region 17q11.2 that was widely destroyed in many types of cancers. Several studies revealed that miR-144 has different target genes including rapamycin, zonula occludens1, SFRP1, and ANO1. MiR-144 acts as a tumor suppressor or oncogene by targeting specific genes. In this review, we define the role of miR‐144 and its targets in different cancers and provide understanding in tumor proliferation, migration, and apoptosis.

Keywords: Electrical power systems, Support vector machines, Random Forest, Machine learning, Wavelet transform, Transmission lines fault, Electrical power quality, Short circuit, Classification of faults, Localization of faults, Decision trees, Ensemble learning, K-nearest neighbors.

This comprehensive review explores the advancements in processing-in-memory (PIM) techniques for deep learning applications. It addresses the challenges faced by monolithic chip architectures and highlights the benefits of chiplet-based designs in terms of scalability, modularity, and flexibility. The review emphasizes the importance of dataflow-awareness, communication optimization, and thermal considerations in designing PIM-enabled manycore architectures. It discusses different machine learning workloads and their tailored dataflow requirements. Additionally, the review presents a heterogeneous PIM system for energy-efficient neural network training and discusses thermally efficient dataflow-aware monolithic 3D (M3D) NoC architectures for accelerating CNN inferencing. The advantages of TEFLON (Thermally Efficient Dataflow-Aware 3D NoC) over performance-optimized SFC-based counterparts are highlighted. Overall, this review provides valuable insights into the development and evaluation of chiplet and PIM architectures, emphasizing improved performance, energy efficiency, and inference accuracy in deep learning applications.

Background: Young adults, particularly university students might be at greater risk of developing psychological distress, and exhibiting symptoms of anxiety and depression during the COVID-19 pandemic. Objective: The primary objective of this study was to explore and compare the determinants and predictors of mental health (anxiety and depression) during and after COVID-19 lockdown among university students. Methods: This was an observational, cross-sectional study with a sample size of 417 students. An online survey utilizing International Physical Activity Questionnaire–Short Form (IPAQ-SF), General Anxiety Disorder–7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) was distributed to Universiti Tunku Abdul Rahman students via Google forms. Results: During lockdown, family income [χ² (1, n=124) = 5.155, p=0.023], and physical activity [χ² (1, n=134) = 6.366, p=0.012] were associated with anxiety, while depression was associated with gender [χ² (1, n=75) = 4.655, p=0.031]. After lockdown, family income was found to be associated with both anxiety [χ2 (1, n=111) = 8.089, p=0.004], and depression [χ2 (1, n=115) =9.305, p=0.002]. During lockdown, family income (OR=1.60, p=0.018), and physical activity (OR=0.59, p=0.011) were predictors for anxiety, and gender (OR=0.65, p=0.046) being the only predictor for depression. After lockdown, family income was a predictor for both anxiety (OR=1.67, p=0.011), and depression (OR=1.70, p=0.009). Conclusion: Significant negative effects attributed to the COVID-19 lockdown, and certain factors predisposed to the worsening of mental health status in university students. Family income, physical activity level, and gender were some of the major determinants that influenced the anxiety and depression.

The inability to efficiently metabolize homocysteine (Hcy), which occurs in nutritional and genetic deficiencies, leads to hyperhomocysteinemia (HHcy) thereby causing endothelial dysfunction, a hallmark of atherosclerosis which underpins cardiovascular disease (CVD). The dysregulation of mammalian target of rapamycin (mTOR) signaling, and impaired autophagy play important roles in CVD. Biochemically, HHcy is characterized by elevated levels of Hcy and its metabolites, Hcy-thiolactone (HTL) and N-Hcy-protein (N-Hcy). However, whether these metabolites can dysregulate mTOR signaling and autophagy in endothelial cells is not known. Here, we examined the influence of HTL, N-Hcy, and Hcy on the PHF8/H4K20me1/mTOR/autophagy pathway in human umbilical vein endothelial cells (HUVEC). We found that treatments with HTL, N-Hcy, or Hcy significantly reduced PHF8 protein and mRNA expression, increased H4K20me1, and upregulated mTOR signaling. Autophagy was also impaired (significantly downregulated BECN1, ATG5, ATG7, and LC3 protein and mRNA levels). We also found that these changes were mediated by PHF8-targeting microRNA (miR): miR-22-3p and miR-1229-3p. The effects of HTL, N-Hcy, or Hcy on the miR expression and on the PHF8/H4K20me1/mTOR/autophagy pathway were abrogated by treatments with an inhibitor of miR-22 or miR-1229. Taken together, these findings show that Hcy metabolites can upregulate miR-22-3p and miR-1229-3p expression, which then dysregulate the PHF8/H4K20me1/mTOR/autophagy pathway, important for vascular homeostasis.

Allama Iqbal Open University (AIOU) is the largest distance learning institute of Pakistan and providing education to 1.4 million students. This is fairly a large setup across the country where students are geographically distributed. Currently the system works on a manual approach which is not efficient. Allocation of tutors and study centers to students plays a key role in distance learning for a better learning environment. Assigning tutors and study centers to distance learning students is a challenging task when there is huge geographical spread. The utilization of geospatial technologies in open and distance learning can fix allocation problems. This research analyzes the real data of twin cities Islamabad and Rawalpindi. The results show that the geospatial technologies can be used for efficient and proper resource utilization and allocation, which in turn can save the time and money. The overall idea fits into improved distance learning framework and related analytics.

The main goal of this paper is to present results of preliminary archaeological research on the south side of Lake Issyk-Kul in Kyrgyzstan. We test the hypothesis that agropastoral land use changed over four millennia from the Bronze Age through the ethnographic Kirghiz period due to economic, socio-political, and religious changes in the prehistoric and historic societies of this region. Our research objectives are to: (1) describe and analyze survey results from Lower Kizil Suu Valley; (2) discuss the results of radiometric and archaeobotanical samples taken from three stratigraphic profiles from three settlements from the Juuku Valley, including these chronological periods: the Wusun period (200 to 400 CE), the Qarakhanid period (1100 to 1200 CE), and the ethnographic Kirghiz period (1700 to 1900 CE); and (3) conduct preliminary GIS spatial analyses on the Iron Age mortuary remains (Saka and Wusun period). This research emerges out of the first archaeological surveys conducted in 2019 - 2021 and includes the Lower Kizil Suu alluvial fan; it is an initial step toward developing a model for agropastoral land use for upland valleys of the Inner Tian Shan Mountains.

Studies have shown that stress such as hypoxia, chemotherapy, radiotherapy can lead to polyploidization of tumor cells, which play an important role in tumor heterogeneity and malignant phenotype. Paclitaxel (PTX) treatment promoted polyploid cancer cells (PCCs) formation, and miR-378d is sharply reduced in PCCs of esophageal squamous cell carcinomas (ESCC) cells, but miR-378d participation PCCs formation and the impact on the biological behavior of ESCC remains unclear. We analyzed the PCCs formation and biological behavior of ESCC cells in vivo and in vitro, and the related proteins regulated by miR-378d. Results showed that miR-378d expression was associated with good prognosis in ESCC patients. miR-378d inhibition promoted PCCs formation, heterogenicity, chemo-resistance, monoclonal formation, EMT, migration, invasion, stemness and metastasis of ESCC cells. miR-378d can target downregulated AKT1, and inactivating the AKT-β-catenin signaling pathway, miR-378d and AKT can also regulated RhoA expression. AKT and RhoA regulated polyploidization and depolyploidization. Therefore, miR-378d expression is a good prognostic factor of ESCC patients and regulates polyploidization and malignant phenotype of tumor cells through AKT and RhoA.

Inhalational anesthetics was previously reported to suppress glioma cell malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 hrs. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNA upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

The present study investigates the relationship between the transmission of COVID-19 infections and climate indicators in Dhaka City, Bangladesh, using coronavirus infections data available from the Institute of Epidemiology, Disease Control and Research (IEDCR), Bangladesh. The Spearman-ranked correlation test was carried out to study the association of seven climate indicators, including humidity, air quality, minimum temperature, precipitation, maximum temperature, mean temperature and wind speed with the COVID-19 outbreak in Dhaka City, Bangladesh. The study found that, among the seven indicators, only three indicators (air quality, minimum temperature and average temperature) have a significant relationship with new COVID-19 cases. The results of this paper will give health regulators and policymakers valuable information to lessen the COVID-19 infection in Dhaka and other countries around the world.

Neuromorphic computing, a brain inspired non-Von Neumann computing system, addresses the challenges posed by the Moore’s law memory wall phenomenon. It has the capability to increasingly enhance performance while maintaining power efficiency. Neuromorphic chip architecture requirements vary depending on the application and optimizing it for large-scale applications remains to be a challenge. Neuromorphic chips are programmed using spiking neural networks which provide them with important properties such as parallelism, asynchronism, and on-device learning. Widely used spiking neuron models include the Hodgkin-Huxley Model, Izhikevich model, integrate-and-fire model and spike response model. Hardware implementation platforms of the chip follow three approaches: analog, digital, or a combination of both. Each platform can be implemented using various memory topologies which interconnects with the learning mechanism. Current neuromorphic computing systems typically use the unsupervised learning spike timing-dependent plasticity algorithms. However, algorithms such as voltage-dependent synaptic plasticity have the potential to enhance performance. This review summarizes the potential neuromorphic chip architecture specifications and highlights which applications they are suitable for.

Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function. Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) in the Saos-2 cell line (null p53) transfected as compared with p53WT transfected cells. The association between these miRNAs and the signaling pathways in which they might participate was performed through the miRPath Software. QRT-PCR was employed to validate the miRNAs profiles. In addition, we explored if the induction of cell migration and invasion by the p53R48Q mutant was dependent on the miR-182-5p. We observed that p53 mutants have an overall negative effect on miRNA expression. Likewise, we found miRNAs differentially expressed associated with regulating Oncogenic signaling pathways. We found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. Our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is also necessary to induce cell migration and invasion by the p53R248Q mutant in a cancer cell model.

Cardiac hypertrophy is an adaptive response to various pathological insults including hypertension. However, sustained hypertrophy can cause impaired calcium regulation, cardiac dysfunction, and remodeling, accompanied by cardiac fibrosis. Our previous study identified miR-25 as a regulator of SERCA2a, and that inhibition of miR-25 improved cardiac function and reduced fibrosis by restoring SERCA2a expression in a murine heart failure model. However, the precise mechanism underlying the reduction of fibrosis by miR-25 inhibition remains unclear. Therefore, we postulate that miR-25 may have additional targets that contribute to regulating cardiac fibrosis. Using in silico analysis, Krüppel-like factor 4 (KLF4) was identified as an additional target of miR-25. Further experiments confirmed that KLF4 was directly targeted by miR-25 and that its expression was reduced by long-term treatment with Angiotensin II, a major hypertrophic inducer. Subsequently, treatment with a miR-25 inhibitor alleviated the cardiac dysfunction, fibrosis, and inflammation induced by Angiotensin II. These findings indicate that inhibiting miR-25 not only enhances calcium cycling and cardiac function via SERCA2a restoration but also reduces fibrosis by restoring KLF4 expression. Therefore, targeting miR-25 may be a promising therapeutic strategy for treating hypertensive heart diseases.

The increasing demand by consumers for popular healthy fruits, such as the watermelon (Citrullus lanatus), generate substantial bio-wastes, making it imperative to harness the value of these by-products. Watermelon has low-calorie content and several other nutritional benefits that make it suitable for weight management and heart-healthy diets. Within this article, the nutritional composition and bioactives of watermelon which are strongly linked to the prevention of cardiovascular disorders (CVD), cancer, and age-related conditions, will be thoroughly reviewed. In addition, the therapeutic potential effects of watermelon consumption, such as anti-inflammatory, cardio-protective and anti-cancer properties, are also examined, with emphasis to the importance of incorporating watermelon into regular diets for overall health improvement. Additionally, the study explores various applications of watermelon by-products in functional foods, contributing to meeting recommended daily nutrient allowances, as well as in other functional products like cosmetics, with health promoting properties. In conclusion, this comprehensive review underscores the role of watermelon and its by-products for the development of products that can contribute to the prevention of chronic diseases and promote overall well-being

Rapid growth of IoT applications and their interference in our daily lives led to many different IoT devices which generates enormous data. The IoT devices’ resources are very limited, so storing and processing IoT data in the devices is very inefficient. Several resources of cloud-computing are efficiently used to handle some IoT resources issues. While using resources in the cloud centers cause some other issues, like latency in the IoT applications, which are time-critical. Thus, the technology of edge cloud has evolved recently. This technology permits storage and data processing at the network edge. This paper studies edge computing in-depth for timeless sensitive devices in IoT. In-depth, cutting-edge IoT computing systems (ECAs-IoT) are evaluated and characterized in this paper according to numerous criteria, such as information placement, improvisation facilities, reliability, and data visualization. Moreover, according to distinctive properties, the paper aims at comparing each structure in detail. The paper also highlights the significant limitations of the new ECAs-IoT and recommends solutions to them. The studies also introduce and propose solutions to some of the most important restrictions of the current ECAs-IoT. Consequently, in the edge computing domain, this survey outlines the IoT implementations. Lastly, with the use of IoT implementations for ECAs-IoT, the paper suggests four distinct scenarios.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

The governance of public sector infrastructure projects became an important topic of interest in the project, programme and portfolio management literature during the last decade. Today, it is becoming a central focus for policymakers seeking to ensure success in selecting, designing and implementing government-sponsored programme of multi-projects. Due to the multiple underlying risks and complexities, the governance of infrastructure programme constitutes a critical element in strategic planning in developing countries. This paper has analyzed infrastructure development programme and revealed shortcomings in the areas of appraisal, decision-making, quality assurance and stakeholder management. Approaches to remedy these shortcomings have been proposed.

Unicellular eukaryotes of the Trypanosomatidae family include human and animal pathogens that belong to the Trypanosoma and Leishmania genera. Diagnosis of the diseases they caused requires the sampling of body fluids (blood, lymph, peritoneal fluid, cerebrospinal fluid, etc.) or organ biopsies (bone marrow, spleen, etc.), which are mostly obtained through invasive methods. Body fluids or appendages can be alternatives to these invasive biopsies but appropriateness remains poorly studied. To further address this question, we perform a systematic review on clues evidencing the presence of parasites, genetic material, antibodies, and antigens in body secretions, appendages, or the organs or proximal tissues that produce these materials. Paper selection was based on searches in PubMed, Web of Science, WorldWideScience, SciELO, Embase, Google. The information of each selected article (n=333) was classified into different sections and data were extracted from 77 papers. The presence of Trypanosomatidae parasites has been tracked in most of organs or proximal tissues that produce body secretions or appendages, in naturally or experimentally infected hosts. The meta-analysis highlights the paucity of studies on Human African Trypanosomiasis and a the absence on animal Trypanosomiasis. Among the collected data high heterogeneity in terms of the I² statistic (100%) is recorded. A high positivity is recorded for antibody and genetic material detection in urine of patients and dogs suffering leishmaniasis, and of antigen for leishmaniasis and Chagas disease. Data on conjunctival swab can be analyzed with molecular methods solely for dogs suffering canine visceral leishmaniasis. Saliva and hair/bristle showed a pretty good positivity that support their potential to be used for leishmaniasis diagnosis. In conclusion, our study pinpoints significant gaps that need to be filled in order to properly address the interest of body secretion and hair or bristle for the diagnosis of infections caused by Leishmania and by other Trypanosomatidae parasites.

The demand of high data rate and ubiquitous coverage in heterogeneous cellular (HetNets) is increasing progressively. In order to meet this demand, sophisticated model having applied interference reduction scheme and cell association technique is needed. The small base station (sBS)are deployed inside the broadcasting area of macro base station (mBS), in heterogeneous cellular networks (HetNets). Since mBS has high transmission power therefore a large number of users get connected with mBS. This causes disproportion of load distribution across the HetNets. For load balancing users from high power mBS are migrated to low power sBS to increase network capacity and to decrease the load from mBS. This results in interference in the communication signal because of strong mBS Interference. Hence, we need interference management technique to mitigate interference and user association and to efficiently use sBSs’ resources. Inter-cell interference (ICI) limit the HetNets’ performance. Additionally, there exist deliberate jamming interference which depends on jammers transmission power and its proximity with the target, which notably degrades the network performance. In this paper, we employ reverse frequency allocation scheme (RFA) to reduce inter cell interference, deliberate jamming interference and to accomplish load balancing. The proposed setup is analyzed inquisitively and with the help of simulations. The result shows reduction in interferences as well as balance of load distribution in the network achieved by employing RFA scheme together with cell association.

Background: Osteoclastic bone resorption in the compression zone of periodontal ligament (PDL) plays a role in orthodontic tooth movement, and is regulated by the balance of RANKL and OPG. Compression downregulates OPG, conversely, tension upregulates OPG in PDL cells. However, the regulatory mechanism of OPG expression in PDL cells under different mechanical stresses remains unclear. Methods: To study microRNA (miRNA) expression profiles, compression (2g/cm²) or tension (15%-elongation) was applied to immortalized human PDL (HPL) cells, and miRNA was extracted. The miRNA expression was analyzed using a human miRNA microarray, and the changes of the miRNA expression were confirmed by real-time RT-PCR. In addition, miR-3198-mimic and -inhibitor were transfected into HPL cells to understand the resulting OPG expression and production. Results: Certain miRNAs were expressed differentially under compression and tension. Some miRNAs including miR-3198 were upregulated only by compression. Real-time RT-PCR confirmed that compression induced miR-3198, but tension reduced it, in HPL cells. miR-3198-inhibitor upregulated and miR-3198-mimic reduced OPG in HPL cells. miR-3198-inhibitor rescued the compression-mediated downregulation of OPG. On the other hand, miR-3198-mimic reduced OPG expression under tension. Conclusion: We conclude that miR-3198 is upregulated by compression and is downregulated by tension, suggesting that miR-3198 downregulates OPG in response to mechanical stress.

Both fibrosis and cirrhosis of the liver are the end results of most kinds of chronic liver damage and present a common but difficult clinical challenge throughout the world. The inhibition of the fibrogenic, proliferative, and migratory effects of hepatic stellate cells (HSCs) has become an experimental therapy for preventing and even reversing hepatic fibrosis. Furthermore, a complete understanding of the function of non-coding RNA-mediated epigenetic mechanisms in HSC activation may improve our perception of liver fibrosis pathogenesis. This review focuses on an evolving view of molecular mechanisms in which HSC activation by miR-29a signaling may moderate their profibrogenic phenotype, thus supporting the use of miR-29a agonists as a potential therapy for treating liver fibrosis in the future.

The current research work illustrates an economic and rapid approach towards biogenic synthesis of silver nanoparticles using aqueous Punica granatum leaves extract (PGL-AgNPs). The optimization of major parameters involved in the biosynthesis process was done using Box-Behnken Design (BBD). The effects of different independent variables (parameters) namely concentration of AgNO3, temperature and ratio of extract to AgNO3on response viz. particle size and polydispersity index were analyzed. As a result of experiment designing, 17 reactions were generated which were further validated experimentally. The statistical and mathematical approaches were employed on these reactions in order to interpret the relationship between the factors and responses. The biosynthesized nanoparticles were initially characterized by UV-vis spectrophotometry followed by physicochemical analysis for determination of particle size, polydispersity index and zeta potential via dynamic light scattering (DLS), SEM and EDX studies. Moreover, the determination of functional group present in the leaves extract and PGL-AgNPs was done by FTIR. Antibacterial and antibiofilm efficacies of PGL-AgNPs against Gram-positive and Gram-negative bacteria were further determined. The physicochemical studies suggested that PGL-AgNPs were round in shape and of ~ 37.5 nm in size with uniform distribution. Our studies suggested that PGL-AgNPs exhibit potent antibacterial, and antibiofilm properties.

This paper is purposed to delineate the current situation around Bangladesh as well as impacts of Coronavirus Disease-2019 (COVID-19) around the country and how the people over here are encountering this threatening pandemic. COVID-19 is an international epidemic that has got rapid wide-spread throughout different countries of the world to date. After its first outbreak in China different continents started to make sense and get aware against COVID-19 though, due to its special strategy of transmission several countries have been quite deteriorated preventing it. All the countries are moving at their best forward to find out any solution so that whole world could get rid of this horrifying situation as soon as possible. The authors here have reported an overview of how the outbreak of COVID-19 had put its commence in Bangladesh and to date how people over here have been tracing the way to tackle this havoc. Also, the changes that have brought around due to the crisis have offered us some fertile lessons that are enunciated here by the authors. To conclude, special considerations are anticipated to be highlighted pertaining COVID-19 outbreak in Bangladesh.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes is attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of pro-inflammatory chemokines; CCL1, 2, 4 and 5 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a normal control group were enrolled. The demographic data, serum levels CCL-1, 2, 4 and 5 and the biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). n controls. We observed that male and female control patients had similar mean serum concentrations of pro-inflammatory chemokines CCL 1, 2, 4, and 5. Chemokines CCL1, CCL2, and CCL4 in the serum of Type 2 Diabetes Mellitus patients with normal or overweight body weights were significantly higher than the control group, regardless of gender. In T2DM individuals with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL1, 2, and 4 in T2DM) patients with increasing BMI. Serum CCL5 levels increased significantly in all T2DM patient groups. The increase in CCL5 was more predominant in normal-weight people as compared to overweight and obese T2DM patients. Conclusions. Male and female control patients had similar serum levels of pro-inflammatory chemokines CCL 1, 2, 4, and 5. The progressive rise in blood concentrations of three Pro-inflammatory chemokines; CCL1, 2, and 4 in T2DM patients with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM patient groups. The selective and more pronounced increase of CCL5 in the T2DM group with normal BMI as compared to patients with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 under-expression in overweight and obese T2DM patients is due to some unexplained counterbalancing processes.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes I attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of interleukins-10 , 19 and 22 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a control group were enrolled. The demographic data, serum levels of IL-10, IL-19, and IL-22, and biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). Both male and female T2DM subjects in Group A showed significant decreases in IL-10 levels as compared to controls; however, there were insignificant changes in IL-10 levels in Groups C and D. T2DM patients in groups C and D, in both males and females, depicted very significant (p 0.001) increases in IL-19 levels as compared to controls and group A. Patient groups A to D displayed a progressive elevation of Il-22 levels irrespective of gender, although significant alterations were seen only in groups B to D, with p 0.05 for group B and p 0.01 for groups C and D respectively, as compared to healthy controls. Conclusions. IL-10 showed a strong relationship with T2DM in males with varying degrees of obesity, but females depicted relatively higher IL-10 levels in obese and highly obese groups, pointing to a protective phenomenon. IL-19 levels showed significant increases in all four groups, irrespective of gender. IL-22 appears to be unrelated to T2DM per se but shows an association with varying degrees of obesity.

This paper uses preliminary studies of archaeological sites (burial mounds and settlements) from the Iron Age through Medieval periods (ca. 800 BCE to 1200 CE) in the Juuku Valley on the South side of Lake Issyk-Kul to model land-use across vertical mountain zones. To do so, we have established a radiometric chronology, conducted test excavations of an Iron Age settlement and a Turkic period burial, undertaken preliminary archaeobotanical research, and pedestrian surveys. Seed remains of wheat (Triticum aestivum), barley (Hordeum vulgare), broomcorn millet (Panicum milaceum) and foxtail millet (Setaria italica) and legumes were recovered in very small quantities from an Iron Age upland settlement at 2100 m asl and a Turkic period burial mound at 1934 m asl. These preliminary archaeobotanical results are compared to the Talgar Iron Age settlements on the north side of the Tian Shan Mountain range in Kazakhstan studied earlier by Robert Spengler. Small samples of faunal remains found at the Turkic period kurgan and from a profile at the upland Iron Age settlement indicate livestock herding of sheep/goats, cattle, and horses in Juuku Valley. The goal of this paper is to test the hypothesis that pastoral transhumance and agropastoralism were economic strategies used by ancient societies during the Iron Age through Medieval periods in mountain-river valley areas between 750 m to 2500 m asl. These economic strategies that combined the pasturing of sheep, goats, cattle and horses with the cultivation of cereals were adapted to the use of different vegetational zones along a vertical gradient. This paper based on preliminary research of upland sites of the Juuku Valley in Kyrgyzstan, initiates a long-term research study of four millennia of settlements that ranged from pastoral transhumance, pastoral nomadism, and combined mountain agriculture using survey data and test excavations.

Relationships among the population abundance of four predator groups for rice insect pests, namely: carabid beetles, staphylinid beetles, green mirid bugs, and spiders in three landscape categories were evaluated. Both rice plots and the associated bund margins of these rice plots found among three Bangladesh landscape categories were sampled by sweep net. The results revealed that the abundance significantly varied across landscapes. The rice landscape of one location harbored higher numbers of a specific predator than other location in other regions of Bangladesh. The results also showed a dependency on the width of the rice bund margins of the rice plots, where spiders populations increased with increased bund widths, but the population abundance of these predators did not depend on the diversity of the number of weed species found on the rice bund margins. The relative abundance of predator populations also significantly differed among the three landscapes, with the green mirid bug having the highest number among the four predators. This study indicates that predators of rice insect pests are highly landscape specific. In order to design integrated pest management systems for different Bangladeshi rice production locales, considerations unique to the characteristics of each locale are necessary. Preliminary efforts to apply variography analyses to the RED spectral band of LANDSAT 8 imagery from December 2016 are presented as first step toward learning a suite of methods which describe useful local characteristics affecting rice pest predators.

Risedronate sodium (RIS) possesses very low bioavailability and several adverse effects in the gastrointestinal tract when administered through an oral route. Thus, this necessitates the need to develop novel formulation. Hence, we had developed RIS-HA-TCS loaded mPEG coated nanoparticles for the treatment of osteoporosis. Chitosan was used to synthesize thiolated chitosan and its characterization was done using DSC and FTIR. Ellman's reagent was used to measure the degree of thiol immobilization. The RIS-HA fabrication was done and was further conjugated with the synthesized TCS. The Box-Behnken design process was used for designing fifteen batches of RIS-HA-TCS nanoparticles, which were formulated by ionic gelation procedure in which tripolyphosphate (TPP) was used as a crosslinking agent. Moreover, RIS and RIS-HA-TCS in-silico activity was compared for farnesyl pyrophosphate synthetase enzyme. The obtained results revealed that the binding affinity of RIS was much more than the conjugated RIS. Successful docking results paved the way for thiolation of chitosan with RIS. The drug entrapment efficiency (%EE), particle size and Polydispersity index (PDI) of RIS-HA-TCS nanoparticles obtained were 85.4 ±2.21%, 252.1 ±2.44 nm and 0.2± 0.01 respectively. The particle size, PDI, and encapsulation efficiency of RIS-HA-TCS were reported to be 264.9 ±1.91 nm, 0.120± 0.01, and 91.1 ±1.17%, respectively, after being further conjugated with mPEG. TEM showed the spherical particle size of RIS-HA-TCS and RIS-HA-TCS-mPEG. The in-vitro release of RIS-HS-TCS-mPEG was found to be significantly higher (95.13±4.64%) as compared to RIS-HA-TCS (91.74 ± 5.13%), RIS suspension (56.12 ± 5.19%) and marketed formulation (74.69 ± 3.98%). In an ex-vivo gut permeation study, RIS-HA-TCS-mPEG nanoparticles was found to have an apparent permeability of 0.5858×10-1 cm/min which was better than the apparent permeabilities of RIS-HA-TCS formulation (0.4011 ×10-4cm/min), RIS suspension (0.2005 ×10-4 cm/min) and marketed preparation (0.3401 ×10-4 cm/min)..

The multidrug efflux transporter ABCB1 is clinically important for drug absorption and distribution and can be a determinant of chemotherapy failure. Recent structure data shows that three glutamines donate hydrogen bonds to co-ordinate taxol in the drug binding pocket. This is consistent with earlier drug structure-activity relationships that implicated the importance of hydrogen bonds in drug recognition by ABCB1. By replacing the glutamines with alanines we have tested whether any or all of Q347, Q725 and Q990 are important for the transport of three different drug classes. Flow cytometric transport assays show that Q347A and Q990A act synergistically to reduce transport of Calcein-AM, BODIPY-verapamil and OREGON GREEN-taxol bisacetate but the magnitude of the effect was dependent on the test drug and no combination of mutations completely abrogated function. Surprisingly, Q725A mutants generally improved transport of Calcein-AM and BODIPY-verapamil, suggesting that engagement of the wild-type Q725 in a hydrogen bond is inhibitory for the transport mechanism. To test transport of unmodified taxol, stable expression of Q347/725A and the triple mutant was engineered and shown to confer equivalent resistance to the drug as the wild-type transporter, further indicating that none of these potential hydrogen bonds between transporter and transport substrate are critical for function of ABCB1. The implications of the data for plasticity of the drug binding pocket are discussed.

The current study emphasizes on optimizing a suitable ratio of enzymatically hydrolyzed potato powder (EHPP) and whole milk powder (WMP) to produce a quality yogurt by evaluating the physicochemical and rheological properties. The results showed that the addition of EHPP decreased the pH towards acidic conditions which resulted in the high acidity of yoghurt. The proximate composition showed that EHPP increased the ash, protein, water holding capacity (WHC) while fat, synersis, color parameters and total solid were decreased when compared to control yoghurt (CY) sample. Moreover, texture profile (TPA) analysis showed that the addition of EHPP decreased the hardness and cohesiveness while springiness did not show significant difference. Furthermore, rheological properties revealed that EHPP decreased the storage modulus (G’) and loss modulus (G”) when compared with control. In addition to this, sensory analysis revealed that the treatment P4M (1:3) was found as optimum ratio regarding taste, flavor, and aroma. Besides this, scanning electron microscopy (SEM) confirms that the high amount of EHPP resulted in the void holes while CY showed dense gel structure. The prepared yogurt with EHPP provides an excellent flavor, satisfying sweetness and homogeneous texture. These findings suggest the optimum formulation ratio of prepared yogurt was found to be P4M (1:3) for desirable attributes and consumer acceptance. The prepared yogurt from the EHPP presents the potential industrial applications.

MiR-204 is a small noncoding RNA with diverse regulatory roles in breast cancer (BC) development and progression. miR-204 is implicated in the instauration of fundamental traits acquired during the multistep development of BC known as hallmarks of cancer. It may act as a potent tumor suppressor by inhibiting key cellular processes like angiogenesis, vasculogenic mimicry, invasion, migration, and metastasis. It achieves this by targeting multiple master genes involved in these processes, including HIF-1α, β-catenin, VEGFA, FAK, FOXA1, among others. Additionally, miR-204 modulates signaling pathways like PI3K/AKT and interacts with HOTAIR and DSCAM-AS1 lncRNAs, further influencing tumor progression. Beyond its direct effects on tumor cells, miR-204 shapes the tumor microenvironment by regulating immune cell infiltration, suppressing pro-tumorigenic cytokine production, and potentially influencing immunotherapy response. Moreover, miR-204 plays a crucial role in metabolic reprogramming by directly suppressing metabolic genes within tumor cells, indirectly affecting metabolism through exosome signaling, and remodeling metabolic flux within the tumor microenvironment. This review aims to present an update on the current knowledge regarding the role of miR-204 in the hallmarks of BC. In conclusion, miR-204 is a potential therapeutic target and prognostic marker in BC, emphasizing the need for further research to fully elucidate its complex roles in orchestrating aggressive BC behavior.

IgA nephropathy (IgAN) is one of the most common forms of glomerular disease. It is diagnosed by the dominant or co-dominant IgA deposition in the mesangial region by histopathological examination of kidney biopsy. Kidney biopsy has its own complication and not performed frequently. microRNA (miRNA) is a small RNA, which plays an important role at the post transcriptional level by downregulating mRNAs. We have tried to establish a miRNA based biomarker for IgAN. We quantified miR-148b and let-7b from plasma in IgAN patients and healthy controls. Logistic regression models and receiver operating curve analysis used to analyze the miRNAs quantity and Oxford MEST-C scoring parameters (M- Mesangial hypercellularity, E- Endocapillary hypercellularity, S- Segmental glomerulosclerosis, T- Tubular atrophy/Interstitial fibrosis, C- Crescents). miR-148b and let-7b levels in IgAN were found to be higher by 2.9 and 5.48 times than the healthy controls, respectively. let-7b was positively correlated with complement C3 levels. Similarly, miR-148b was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with S, T, and blood pressure (BP). The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) for miR-148b against T were 0.87, 0.77, and 0.85, respectively. The threshold value of miR-148b concentration was found to be 8479 to differentiate the severe condition of IgAN. Furthermore, the decrease in miR-148b concentration at a threshold point indicated the progression of the severity of the IgAN. It can also be used to predict the IgAN at an earlier stage.

The purpose of this study was to see how dietary supplementation with phenylpyruvate affected broiler chicken growth, slaughter performance, gut health microbiota, and immunity. A total of 288 day old broiler chickens were randomly assigned to one of four groups (6 replicates each with 12 chicken). NC (basal diet), PC (basal diet plus antibiotic virginiamycin 15ppm), LCP and HCP (basal diet plus phenylpyruvate 1kg/t and 2kg/t, respectively). Results showed that PC had higher ADFI during the first 21 days, and better FCR than the NC, the LCP and HCP also improved broilers’ FCR 0.001 and 0.037% in relation to NC respectively. HCP has a higher all-eviscerated ratio than NC and less abdominal fat than LCP. HCP has increased villus length and crypt depth in the ileum compared to the NC. Bursa was lower in HCP and thymus was lower in LCP and PC. In contrast HCP have lower pro-inflammatory cytokine IL-1, as well as lower TLR4. The phenylpyruvate improved family Selenomonadaceae, genus Megamonas Bacteroides species that are known for beneficial effects like for maintenance of the cell surface structure, regulating aromatic amino acids and C. jejuni-suppressive treatment respectively. Finally, phenylpyruvate feed supplement can be utilized to improve growth performance and positively modulate gut microbiota, however this is less efficient than antibiotics in improving growth performance, although more efficient in improving productive performance and gut morphology. Moreover, high dose of phenylpyruvate is more effective than low dose

Although laccase has been recognized as a wonder molecule, and green enzyme, the use of low yielding fungal strains, poor production, purification, and low enzyme kinetics have hampered its larger-scale applications. Hence the present research was aimed to select high yielding fungal strains and to optimize the production, purification, and kinetics of laccase of Aspergillus sp. HB_RZ4. Aspergillus sp. HB_RZ4 produced a copious amount of laccase on under meso-acidophillic shaking conditions in a medium containing glucose and yeast extract. A 25 µM of CuSO4 enhanced the enzyme yield. The enzyme was best purified on Sephadex G-100 column. Purified enzyme resembled with the laccase of A. flavus. Kinetics of purified enzyme revealed the high substrate specificity and good velocity of reaction with ABTS as substrate. The enzyme was stable over a wide range of pH and temperature. The peptide structure of the purified enzyme resembled with the laccase of A. kawachii IFO 4308. The fungus decolorized various dyes independent of the requirement of a laccase mediator system (LMS). Aspergillus sp. HB_RZ4 came out as a potent natural producer of laccase, it decolorized the dyes even in absence of LMS and thus can be used for bioremediation.

MicroRNAs are small ribonucleotides which act as key gene regulators. Their altered expression is often associated with onset and progression of several human diseases, including cancer. Given their potential use as biomarkers, there is a need to find detection methods of microRNAs suitable for use in clinical setting. Field Effect Transistor based biosensors (bioFETs) appear to be valid tools to detect microRNAs, since they may reliably quantitate the specific binding between the immobilized probe and free target in solution through an easily detectable electrical signal. We have investigated the detection of human microRNA 155 (miR-155) using an innovative cap-turing probe constituted by a synthetic peptide nucleic acid (PNA), which has the advantage to form a duplex even at ionic strengths approaching the physiological conditions. With the aim to develop an optimized BioFET setup, the interaction kinetics between miR-155 and the chosen PNA was preliminary investigated by Surface Plasmon Resonance (SPR). By exploiting both these results and our custom-made bioFET system, we were able to attain a low-cost, real-time, label-free, highly specific detection of miR-155 in the nano-molar range.

This study endeavors the preparation and evaluation of Phenol Furfural Resin (PFR) from bagasse and its nanocomposites for Electrically Conductive Adhesives (ECAs) application. PFR was prepared with the furfural extracted from bagasse using modified acid digestion method. Three different formulations of PFR nanocomposites with conductive nanoparticles i.e., PFR-silver, PFR-graphite, and PFR-silver + graphite were prepared using 20-60 w/w% of fillers via impregnation method. Resultant products were characterized by FT-IR, SEM, EDS and XRD spectroscopy. Electrical conductivity was measured using four probe technique while band gap was calculated via Tauc plot. Virgin PFR has shown poor conductivity up to 2.6 × 10^-4 Scm^-1 while the highest conductivity achieved was 8.2 × 10^-1 Scm^-1 for nanocomposite constituted silver, graphite, and PFR with 40:30:20 ratios respectively. This synergism was exhibited because graphite and Ag NPs supply excellent junctions for building networks. Both tend to coalesce due to van der Waals forces and high surface energies, therefore conductive pathways numbers can be increased, and contact area can be effectively enlarged. This ternary composite has exhibited the lowest bandgap energy value i.e., 3.1 eV. Thermogravimetric temperatures T₀ and T_deg values were increased up to 120 °C and 484 °C respectively, showing significant increase in thermal stability. Therefore, the resultant nanocomposite material has good potential to be employed as ECAs in electronic industry.

Exosomal microRNAs (miRNAs) from cancer cells play a key role in mediating the oral squamous cell carcinoma (OSCC) microenvironment. The objective aimed to investigate how long non-coding RNA (lncRNA) MEG3 affects OSCC angiogenesis through exosomal miR-421. Global miRNA microarray analysis and quantitative real-time PCR (qRT-PCR) were performed to determine the level of miRNAs in OSCC cells-derived exosomes. Cell migration, invasion, tube formation, immunohistochemistry and hemoglobin concentration were used to study the effects of exosomal miR-421 in angiogenesis. Western blotting was used to determine the expression level of HS2ST1 and VEGFR2-related downstream proteins. MiRNA array and qRT-PCR identified upregulation of miR-421 in OSCC cell-derived exosomes. Furthermore, exosome-miR-421 can be taken up by human umbilical vein endothelial cells (HUVEC) and then targets HS2ST1 through VEGF-mediated ERK and AKT phosphorylation, thereby promoting HUVEC migration, invasion, and tube formation. Additionally, enforced expression of lncRNA MEG3 in OSCC cells reduced exosomal miR-421 levels and then increased HS2ST1 expression, thereby reducing the VEGF/VEGFR2 pathway in HUVEC. Our results demonstrate a novel mechanism by which lncRNA MEG3 can act as a tumor suppressor and regulate endothelial angiogenesis through the exosomal miR-421/HS2ST1 axis, which provides a potential therapeutic strategy for OSCC angiogenesis.

In the last decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) which are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e. GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation and also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.

Background: This review aims to explore the regulatory mechanism of microglial exosomes, particularly focusing on the role of miR-124-3p, in modulating neuroinflammation and promoting neuronal repair following traumatic brain injury (TBI). Methods: Multiple studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. The increased expression of miR-124-3p in microglial exosomes after TBI inhibited neuronal inflammation and promoted neurite outgrowth. This effect was achieved by promoting the anti-inflammatory M2 polarization of microglia, suppressing mTOR signaling through downregulation of PDE4B, and inducing autophagy in BMVECs. These actions collectively contributed to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. Conclusion: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. Targeting miR-124-3p and utilizing microglial exosomes as therapeutic agents hold great potential for future clinical translation in TBI management. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

Silybum marianum L. is a well-known medicinal herb, primarily used in liver protection. Light strongly affects several physiological processes along with secondary metabolites biosynthesis in plants. Herein, S. marianum was exploited for in vitro potential under different light regimes in the presence of melatonin. The optimum callogenic response occurred in combination of 1.0 mg/L α-naphthalene acetic acid and 0.5 mg/L 6-Benzylaminopurine under photoperiod. Continuous light associated with melatonin treatment increased total flavonoid content (TFC), total phenolic content (TPC) and antioxidant potential, followed by photoperiod and dark treatments. The increased level of melatonin has a synergistic effect on biomass accumulation under continuous light and photoperiod, while adverse effect was observed under dark condition. More detailed phytochemical analysis showed maximum total silymarin content (11.92 mg/g DW) when placed under continuous light + 1.0 mg/L melatonin. Individually, the level of silybins (A and B), silydianin, isolsilychristin and silychristin was found highest under continuous light. Anti-inflammatory activities were also studied and highest percent inhibition was recorded against 15-LOX for cultures cultivated under continuous light (42.33%). The current study helps to better understand the influence of melatonin and different light regimes on silymarin production as well as antioxidant and anti-inflammatory activities in S. marianum callus extracts.

Cement manufacturing is one of the most energy-intensive industries in the world. Most of the cost of producing cement is accounted by fuel consumption and power expenditures. Thermal power plants are the major source of electricity in Pakistan. But they are not efficient and environmentally friendly. This study simulates four different models for five cement plants of Pakistan on Homer Pro software and compares the optimal solutions based on the net present cost (NPC), levelized cost of electricity (LCOE) and greenhouse gas (GHG) emissions. Model-1 consists of solar panels, electrolyzer, hydrogen tank, hydrogen generator and converter. Model-2 has only a diesel generator and acts as a base case in this study. Model-3 has solar panels and a battery-converter system. In Model-4, diesel generators, solar panels and converters are considered. Based on NPC, the most optimal model is Model-4, having a 0.249 $/KWh LCOE in islanded systems. The NPC and operating costs are US$540 million and US$ 32.5 million per year, respectively, with a 29.80% reduction in CO2 emissions when compared to the base case. Based on GHG emissions, Model-1 and Model-3 are the best models with 0% GHG emissions. Sensitivity analyses is also performed using the parameters of load, inflation rate and discounted rate. The results prove that the proposed hybrid micropower systems (HMS) can sustainably provide electricity for 24 hours a day to the sites under consideration with minimum objectives.

Herein we foremost detailed the numerical modeling of the double absorber layer- methyl ammonium lead iodide– carbon nitride layer solar cell and subsequently provided in-depth insight on the active layer associated with dominant radiative and non-radiative recombination losses limiting the efficiency ( ) of the solar cell. Under recombination kinetics phenomena, we explored the influence of Radiative recombination, Auger recombination, Shockley Read Hall recombination, the energy distribution of defects; Band Tail recombination (Hoping Model), Gaussian distribution, metastable defect states including single donor (0/+), single acceptor (-/0), Double Donor (0/+/2+), double acceptor (2/-/0-), and the interface layer defects on the output characteristics of the solar cell. Setting defect (or trap) density to with uniform energy distribution of defects for all the layers, we achieved the of 24. 16 %. A considerable enhancement in power conversion efficiency was perceived as we reduced the trap density to for the absorber layers. Further, it was observed that for the absorber layer with double donor defect states, the active layer should be carefully synthesized to reduce crystal order defects to keep the total defect density as low as to achieve efficient device characteristics

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. Studies have unveiled that miR-139-5p expression is significantly downregulated in other types of cancers. However, the functions and mechanisms of miR-139-5p in PANC remain unclear. Methods: Bioinformatic analysis was performed to analyze the differentially expressed genes in the TCGA database. PANC cell line with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and has been used to detect cell proliferation, migration, invasion and colony formation in PANC. Subsequently, bioinformatic analysis and luciferase assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mouse model was used to investigate the role of miR-139-5p in PANC tumorigenicity. Results: Through bioinformatic analysis, miR-139-5p was predicted to regulate phosphatidylinositol signaling pathway by targeting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, migration, and invasion could be inhibited by miR-139-5p overexpression and could be promoted by SLC7A11 overexpression. MiR-139-5p could regulate the protein expression level of PI3K and Akt associated with phosphatidylinositol signaling pathway could be by inhibiting the expression of SLC7A11. MiR-139-5p overexpression could suppress PANC tumor growth and the expression of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibiting effect of miR-139-5p to PANC cell proliferation, invasion and migration, at least, was partly due to its inhibiting effect on SLC7A11 expression. Conclusion: These results demonstrated a novel role of miR-139-5p/SLC7A11 in PANC and provided potential prognostic predictors for PANC patients.

This study endeavors the preparation and evaluation of Phenol Furfural Resin (PFR) from bagasse and its nanocomposites for Electrically Conductive Adhesives (ECAs) application. PFR was prepared with the furfural extracted from bagasse using modified acid digestion method. Three different formulations of PFR nanocomposites with conductive nanoparticles i.e., PFR-silver, PFR-graphite, and PFR-silver + graphite were prepared using 20-60 w/w% of fillers via impregnation method. Resultant products were characterized by FT-IR, SEM, EDS and XRD spectroscopy. Electrical conductivity was measured using four probe technique while band gap was calculated via Tauc plot. Virgin PFR has shown poor conductivity up to 2.6 × 10-4 Scm-1 while the highest conductivity achieved was 8.2 × 10-1 Scm-1 for nanocomposite constituted silver, graphite, and PFR with 40:30:20 ratios respectively. This synergism was exhibited because graphite and Ag NPs supply excellent junctions for building networks. Both tend to coalesce due to van der Waals forces and high surface energies, therefore conductive pathways numbers can be increased, and contact area can be effectively enlarged. This ternary composite has exhibited the lowest bandgap energy value i.e., 3.1 eV. Thermogravimetric temperatures T0 and Tdeg values were increased up to 120 °C and 484 °C respectively, showing significant increase in thermal stability. Therefore, the resultant nanocomposite material has good potential to be employed as ECAs in electronic industry.

Gwadar is essential for Pakistan's financial stability. The third deep-water port in Pakistan, Gwadar, plays a significant part in trade between the Gulf countries, Africa, China, United Arab Emirates, and Cordillera Administrative Region. However, the load Shedding of 12-16 hours in Gwadar is the most concerning issue. Pakistan imports 70 MW of electricity from Iran. The wind and solar system are already installed but for a limited residential area. In Gwadar, there are enough renewable energy resources that can be utilized for electricity generation. In this context, a Techno and Economic Analysis is performed using the Hybrid Optimization Model for Multiple Energy Resources (HOMER) Pro. Two models are considered for this study. Model-1 includes PV/Wind Turbine/ and Battery while Model-2 consists of PV/Wind Turbine/Converter and Grid. The yearly energy generated by Model-1 and Model-2 is 57.37 GWh and 81.5 GWh, respectively. The levelized cost of electricity (LCOE) for Model-1 and Model-2 is respectively $0.401/kWh and $0.0347/kWh. It is shown that the simple payback of Model-1 is of 6.70 years, and the simple payback of Model-2 is 7.77 years. Due to the high LCOE of Model-1, its payback year is lesser than model-2. All of these facts indicate that Model 2 is the most optimal solution.

Purpose: This review features a generalized overview of dengue outbreaks, dengue pathogenesis, symptoms, immune response, diagnosis methods and preventive measures which facilitates the better understanding of the global expansion and concerns relating to the disease. Recent Findings: A recent study showed that natural killer cells of the infected person become activated soon after the infection which may help in treatment and vaccine development. A research team has also produced synthetically engineered mosquitoes that can prevent the transmission and dissemination of the dengue virus by the activation of an antibody. Furthermore, a mutation in the protein envelope of the dengue virus leads to variation in shapes, developing resistance towards the vaccine. Summary: The increasing number of reported cases indicated the worldwide distribution of the mosquito vectors, which was further facilitated by the growth in the shipping and commerce industries. The immune system, through activation of the innate and adaptive immune responses, facilitates the recruitment of an array of leukocytes which help neutralize the virus. However, the 4 different viral serotypes increases the risk of a life-threatening secondary infection due to the varying serotypes. Apart from the laboratory standard PRNT method, several other dengue detection methods such as ELISA, RT-LAMP and several optical, microfluidic and electrochemical methods have been developed. Since Dengvaxia® (CYD-TDV) has its own set of drawbacks and limitations, several companies have been investing for the production of more potential vaccines that are currently in trial.

Early detection of PDAC remains challenging due to the lack of early symptoms and absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics sig-natures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening. We used western blot-ting and Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) for protein and miRNA validation. Comparisons between experimental groups with normal dis-tributions were performed using one-way ANOVA followed by Tukey’s post hoc test and pair-wise tests were performed using t tests. P≤0.05 was considered statistically significant. Protein cluster of differentiation 166 (CD166), glycoprotein CD63 (CD63), S100 calcium binding protein A13 (S100A13), and tumor necrosis factor-β (TNF-β) were detected in the proteomics screening. The miRNA assay revealed a differential miRNA 1285 regulation. Previously described in the literature target proteins of miR-1285 cadherin-1 (CDH-1), cellular Jun (c-Jun), p53, mothers against decapentaplegic homolog 4 (Smad4), human transglutaminase 2 (TGM2) and yes-associated protein (YAP), were validated via Western blotting. miR-1285-3p was successfully validated as differentially regulated in PDAC + DM via qRT-PCR. Overall, our data suggest miRNA1285-3p, TGM2, CDH-1, CD166 and S100A13 as potential meaningful biomarker candi-dates to characterize patients with PDAC + DM. Data are available via ProteomeXchange with identifier PXD053169.