Medical data flows in streams as the data related to clinical tests and administered drugs by the doctors flows continuously. The doctors must be immediately alerted if negative associations are found among the drugs they prescribe. Data streams are to be processed in single scans as it is not possible to re-scan the data for any iterative processing. To detect negative drug connections, regular and frequent drug patterns must be processed. Negative correlations between disease-curing medications might create adverse responses that kill patients. This paper proposes an algorithm that finds the negative associations among regular and frequent patterns mined from medical data streams. The negative associations mined are the most effective and reduce the negative associations, which are more critical by 50%.

Abstract: Interrupted-sampling repeater jamming (ISRJ) is a kind of intra-pulse coherent decep-tion jamming that can generate false target peaks in the range profile and interfere with the de-tection and tracking of real targets. In this paper, an anti-ISRJ method based on the intra-pulse orthogonal waveform is proposed, which can recognize common interference signals by com-paring sub-signal matched filtering results. For some special scenes where real targets cannot be directly differentiated from false targets, a new recognition method based on the energy discon-tinuity of the interference signal in the time domain is proposed in this paper. The method pro-posed in this paper can recognize real and false targets in all ISRJ modes without any prior in-formation, such as jammer parameters, with a small amount of calculation, which is suitable for actual radar systems. Simulation experiments using different interference parameters show that although this method has a 3dB loss of pulse compression gain, it can completely suppress dif-ferent kinds of ISRJ interference when the SNR before pulse compression is higher than -20dB, with 100 % target detection probability.

Transcription factors (TFs) are crucial in modulating gene expression and sculpting cellular and organismal phenotypes. The identification of TF-target gene interactions is pivotal for comprehending molecular pathways and disease etiologies but has been hindered by the demanding nature of traditional experimental approaches. This paper introduces a novel web application, utilizing the R programming language, which predicts TF-target gene relationships and vice versa. Our application integrates the predictive power of various bioinformatic tools, leveraging their combined strengths to provide robust predictions. It merges databases for enhanced precision, incorporates gene expression correlation for accuracy, and employs pan-tissue correlation analysis for context-specific insights. The application also enables the integration of user data with established resources to analyze TF-target gene networks. Despite its current limitation to human data, it provides a platform for exploring gene regulatory mechanisms comprehensively. This integrated, systematic approach offers researchers an invaluable tool for dissecting the complexities of gene regulation, with the potential for future expansions to include a broader range of species.

In this paper, we give the Galois adjunction form of the regular relation, and by using residuated mapping, we find the connection between it and order-generating set. Furthermore, we obtain the equivalent conclusion of "regular". In addition, by using the specialization order of topological space and the lower approximate operator in the rough set, we find a continuous homeomorphic mapping from a regular space to a Alexandrov topological space

In pattern recognition domain, deep architectures are widely used nowadays and they have achieved fine grades. However, these deep architectures need special demands, especially big datasets and GPU. Aiming to gain better grades without deep networks, we propose a simplified algorithm framework using fusion features extracted from the salient areas of faces. Furthermore, the proposed algorithm has achieved a better result than some deep architectures. For extracting more effective features, this paper firstly defines the salient areas on the faces. This paper normalizes the salient areas of the same location in the faces to the same size, therefore it can gain more similar features from different subjects. LBP and HOG features are extracted from the salient areas, fusion features’ dimensions are reduced by Principal Component Analysis( PCA) and we apply softmax to classify the six basic expressions at once. This paper proposes a salient areas definitude method which uses peak expressions frames to compare with their neutral faces. This paper also proposes and applies the idea of normalizing the salient areas to align the specific areas which express the different expressions. This makes the salient areas found from different subjects have the same size. Besides, gamma correction method is firstly applied on LBP features in our algorithm framework which improves our recognition rates significantly. By applying this algorithm framework, our research has gained state-of-the-art performances on CK+ database and JAFFE database.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

In this article some important observations have been reported on recent works related to weakly tripotent rings and locally invo-regular rings. Our findings give additional results as well as correct some recent results on weakly tripotent rings and locally invo-regular rings appeared in Rendiconti Sem. Mat. Univ. Pol. Torino (2021) and Azerbaijan Journal of Mathematics (2021) respectively. In addition we exhibit that if the Jacobson radical J(A) of a ring is strongly involution t-clean then the characteristic of J(A) need not be four. This finding improves an important result appeared in Eur. J. Pure Appl. Math (2022).

In this paper, we relate Poisson’s summation formula to Heisenberg’s uncertainty principle. They both express Fourier dualities within the space of tempered distributions and these dualities are furthermore the inverses of one another. While Poisson’s summation formula expresses a duality between discretization and periodization, Heisenberg’s uncertainty principle expresses a duality between regularization and localization. We define regularization and localization on generalized functions and show that the Fourier transform of regular functions are local functions and, vice versa, the Fourier transform of local functions are regular functions.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

In the following article I analyze the determinants of regular internet users in the Italian regions. The data is analyzed both in terms of static analysis and also through the application of the k-Means algorithm optimized with the Elbow method. Subsequently, an econometric model is presented for estimating regular internet users in the Italian regions based on variables that reflect the state of technological innovation and digital culture. The results are analyzed and discussed in light of the implications that digitalisation has for triggering economic growth.

In this paper we provide some important and significant observations on invo-regular rings appeared in Ann. Univ. Mariae Curie-Sklodowska Sect. A Mathematica (2018). In addition we exhibit that strongly invo-regular rings, invo-regular rings and quasi invo-regular rings all coincide with the well known and well characterized tripotent rings and all these rings further coincide with the well known unit regular rings.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Since World War I, the commercial aviation industry has seen many improvements that now allow people and goods to reach the other side of the world in few hours, consuming much less fuel than in recent decades. Improvements in cargo capacity and energy efficiency were significant and, in this scenario, commercial airlines were able to thrive and bring great benefits to world economy. However, this sector is facing environmental challenges due to the intensive use of aviation fuel. Brazil is one of the largest domestic air passenger markets in the world and still has great growth potential, considering its economic potential and territorial dimensions: roughly the same size as the US and twice the size of the European Union. This paper discusses partial productivity of jet fuel in Brazilian domestic aviation and proposes an econometric method to support public regulators and airlines decisions. The proposed model uses variables such as aircraft size, route characteristics and idle flight capacity in a panel data analysis. The results show that reducing idle capacity is one of the best ways to achieve better short-term fuel efficiency and therefore will reduce environmental impacts and have positive economic effects on commercial air transport activities.

A fast algorithm is established to transform points of the unit sphere into fundamental region symmetrically. With the resulting algorithm, a flexible form of invariant mappings is achieved to generate aesthetic patterns with symmetries of the regular polyhedra. This method avoids the order restriction of symmetry groups, which can be similarly extended to treat regular polytopes in n-dimensional space for n>=4.

The three-dimensional morphology of frictional sub-surfaces holds significant importance for studying tribological issues. However, the uniformity of horizontal datum in 3D scanning is limited for curved surfaces, resulting in the inability to obtain accurate contour characterization parameters from the scanning results. This study aims to address this issue by constructing regular surface equations and normalizing the 3D profiler scanning results. By fitting the data, a "plane" surface representative of the surface features is obtained, and the paper demonstrates this approach on the surface morphology of different worn parts in the frictional area of spherical bearings located in the specific environment of the Three Gorges gate. The results indicate that the obtained "plane" effectively reconstructs the three-dimensional morphology map of the regular surface. Moreover, this reconstructed plane not only clearly illustrates the surface characteristics but also provides the foundation for analyzing the wear mechanism.

Regular regimes of oil and oil products pipelines are studied. The problem is to develop an algorithm of effective pipeline system control that ensures the fulfillment of specified boundary conditions at the system boundaries. The product is pumped in batches, the flow is characterized by a change in temperature and pressure flow parameters over time. The developed solution method uses the principle of decomposition in the sense that each computational iteration is im-plemented in 3 stages, in three nested loops. The inner cycle is connected with the material bal-ance relations, at the next cycle the flow equations are introduced and the fulfillment of the 2nd Kirchhoff's law is monitored. If the flow process is significantly affected by temperature, then an external cycle is also implemented, correcting the solution so that the energy conservation equa-tion is satisfied. In the calculation procedure, some computational difficulties may arise, which consist in choosing an appropriate optimization method. On a specific example, the possibility of using various library programs to solve the problem was checked. The developed method is suita-ble for the analysis of systems of arbitrary topology. Since the method is not time-consuming, it can be recommended for online control of oil and oil products supply systems. The paper opens a new direction in the theory of hydraulic circuits. It uses both traditional methods of continuum mechanics and stochastic models.

In this paper, we examine the weak deflection angle and greybody factor of magnetized regular black hole. We implement the Gauss-Bonnet theorem on magnetized regular black hole to get the deflection angle. Moreover, we analyze the influence of plasma and non-plasma mediums on deflection angle of magnetized regular black hole. We observe the graphical behaviour of plasma and non-plasma mediums on deflection angle of magnetized regular black hole. Lastly, we study the rigorous bound phenomenon of the greybody factor of magnetized regular black hole. For this purpose we calculate greybody factor results and analyze the graphical behaviour of greybody bound for the different values of the parameters.

The basic idea is to expand the completed zeta function $\xi(s)$ in MacLaurin series (infinite polynomial), which can be further expressed as infinite product (Hadamard product) by conjugate complex roots. Finally, the functional equation $\xi(s)=\xi(1-s)$ leads to $(s-\alpha_i)^2 = (1-s-\alpha_i)^2, i \in \mathbb{N}$ with solution $\alpha_i= \frac{1}{2}, i \in \mathbb{N}$, where $\alpha_i$ are the real parts of the zeros of $\xi(s)$, i.e., $s_i =\alpha_i\pm j\beta_i, i\in \mathbb{N}$. Therefore, a proof of the Riemann Hypothesis is achieved.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Diacylglycerol kinase (DGK) is a lipid kinase that phosphorylates diacylglycerol (DAG) to generate phosphatidic acid (PA). Based on converting one important signaling molecule (DAG) to another (PA), DGK plays an important role in plant responses to abiotic stress including waterlogging stress. However, no studies have been reported on the characterization of the DGK gene family in the waterlogging-tolerant kiwifruit germplasm, Actinidia valvata Dunn. Here, we identified 18 AvDGK genes in the A. valvata genome. The phylogenetic analysis showed that AvDGKs can be classified into three clusters, and members within the same cluster have similar domain distribution, exon-intron structures and conserved motif compositions. Chromosome localization analysis revealed that all the AvDGK genes are located across 18 different chromosomes. There were 29 duplicated gene pairs in kiwifruit and all had undergone purifying selection during evolution. Promoter cis-element analysis revealed that the cis-elements within AvDGK genes are associated with multiple functions, including phytohormone signal transduction, stress response, and plant growth and development. The expression pattern analyses indicated that AvDGK play an important role in the fruit development and plant response to waterlogging stress. AvDGKs gene family in the tetraploid A. valvata genome might promote PA synthesis and subsequent signal transduction both under short-term and long-term waterlogging stress. These results provide information regarding the structural characteristics and potential function of DGK genes within kiwifruit and lay a fundamental basis for further research into breeding for enhancing the kiwifruit’s tolerance to waterlogging stress.

Zika virus (ZIKV) is a notable arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV infection has been linked to variations in endogenous retroviruses (ERVs) and interleukins within the placenta. ERVs, remnants of ancient viral infections integrated into the genome, include syncytin receptors crucial for placental development. Interleukins, immune response regulators, aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. Since ZIKV can infect trophoblast cells, we investigated the relationship between ZIKV infections and ERV and interleukin modulations. Investigating the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asia-Brazilian) using Taqman and RT2 Profiler PCR Array assays. While early ZIKV infection (24-48 hours) did not induce differential ERV and interleukin expression, future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and cytokines essential for placental formation and function.

Our results demonstrated that SWT stimulates osteoblastogenesis and increase the cell number of osteoblasts, suggesting positive regulatory effects on osteoblast differentiation. However, the effect of SWT on bone formation need further examination, since the expression of alp gene is downregulated. On the other hand, SWT appears to negatively regulate osteoclast differentiation and bone resorption, as number of osteoclasts and the expression of critical bone resorptive genes are all downregulated. Collectively, SWT might change the equilibrium of bone remodeling and increase the bone mass. Our data provided supportive evidences that this medicine formulation can be applied to treat osteoporosis or bone destructive diseases.

This investigation aimed to explore the impact of acute and regular physical exercise on Brain-Derived Neurotrophic Factor (BDNF) levels in individuals with obesity. Using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) approach, the inclusion criteria were defined as follows: i) population - individuals with overweight or obesity of any age or gender; ii) intervention - acute or chronic interventions involving aerobic or anaerobic methodologies; iii) comparator - for acute effect studies, pre- and post-evaluations served as comparators, while interventions included at least one experimental group or the inclusion of a control group; iv) outcome - BDNF variability concerning the applied methodology; v) study design - restricted to experimental studies exclusively. Conducted in August 2022, the searches were carried out on PubMed, Academic Search Complete, and Web of Science. The risk of bias was assessed using the Risk of Bias in Non-randomized Studies (RoBANS) tool. Out of 98 potentially relevant articles, 16 met the eligibility criteria, encompassing 23 trials. Substantial heterogeneity was observed for both acute (I2 = 80.4%) and long-term effects (I2 = 88.7%). Additionally, RoBANS analysis indicated a low risk of bias for the included studies. The study's findings revealed a significant increase in the concentration of circulating BDNF in individuals with obesity compared to the control group following acute exercise. However, such an effect was not evident in the context of long-term physical exercise, with a small effect size (ES = 0.49) recorded in the latter scenario. The observed significant increase in BDNF levels post-acute exercise suggests a potential acute response mechanism contributing to the intricate interplay between exercise and neurotrophic factors in this population. Nevertheless, the absence of a similar effect in the context of long-term physical exercise implies a potential adaptation or ceiling effect. These findings underscore the importance of considering both the duration and nature of exercise interventions when exploring the neurobiological responses associated with obesity and exercise. The study provides valuable insights for future research and clinical implications in understanding the nuanced relationship between exercise, neurotrophic factors, and obesity.

A lot of research studies have been surveyed the completed genomes of prokaryotic and eukaryotic and focused on the correlation between the percentage of microsatellite sequences in completed genomes and the whole size of the organism genomes. There are fewer studies made in repetitive sequences otherwise simple sequence repeats or long tandem repeats of virus genomes. simple sequence repeats (SSRs) are the most important regions for recombination and moving repeats blocks from site to another site in the genomes. A tool was programmed and designed by visual basic 6.0 to find the long tandem repeats in DNA sequences of the small genomes. The tool named “Repeater Finder Regular Expression”, (RFRE) Version 1.0, 2016. The tool was utilized to discover different pattern of long tandem repeats (LTR) motifs on the completed genomes of human corona virus strains by using a joined regular expression language. In this study, a twenty-nine accession numbers of human coronavirus completed genomes, (hku1) strains were retrieved from the Genbank. The researcher can write a different regular expression patterns and joined regular expression patterns through the designed tool to search and find a specific motif of nucleotide sequences inside the complete genomes. The RFRE tool searched and found three different total lengths of a perfect long tandem repeats (240bp, 300bp and 480bp). A Dot plot gave a picture view for the long tandem repeat sequences in the completed genome sequence (KF430201.1) of human coronavirus. The genomic dot plot tool YASS was used as a genomic similarity searching tool to check for the uninterrupted repeats and confirm the sensitivity of the (RFRE) tool. To identify the recombination site in the genomes of human coronavirus the RAT tool was applied to find the recombination sites between the completed genomes of human corona viruses .The RAT tool recognized the recombination site in the nucleotide position (3012) and at the same time this recombination site position (3012) was also recognized as a beginning position of a long tandem repeat. A precise motif was predicted from the translated repeats of Human Corona Virus which found by PRATT tool. There was a relationship between the total length of long tandem repeats and genome size of Human Corona Virus and the correlation value R² was equal to (0,451). In conclusion, this study presented the importance of finding the long tandem repeats of human coronavirus and gives a relationship between the completed genome size of human coronavirus types and long tandem repeats. The nucleotide position (3012) was a hot spot site for a recombination among the complete genomes of human coronavirus and also identified as a repetitive site in the genomes of human corona virus (hku1). The repeats in human coronavirus (hku1) were predicated to be a main major role of virus evolution.

Most of the research in data mining concentrated on finding the positive associations that exist in frequent patterns. Frequent patterns have no bearing on the time duration and, therefore, lose interestingness. The Regularity of an itemset is related to the time at which the transaction occurred and the time distance between the transactions. Frequent Regular item sets can be generated considering the Frequency and the Regularity of the occurrence of the Item Sets. The frequent and regular Item sets will be so huge that they cannot be handled in real time. The count of Frequent and regular item sets gets reduced drastically when the properties “closed” and “Maximality” are applied. Finding negative associations among such patterns are important in the field of medicine. Many drugs administered to cure some diseases have counter reactions leading to many other diseases. Negative associations among the mined patterns are important as they reveal significant contradictions frequently among medical drugs administered by medical practitioners to cure some diseases. This paper proposes a method that mines medical databases to find regular, frequent patterns applied with closed and maximal properties and find negative associations among those patterns. The proposed algorithm is accurate to 98% and performs 9% more efficiently than the other algorithms presented in the literature.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

Background: Histone deacetylases (HDACs) are implicated in carcinogenesis, and HDAC inhibitors (HDACis) are explored as a therapeutic tool in several tumors. The aim of this study was to evaluate the clinical significance of HDAC -2, -4, and -5 expression in epithelial ovarian carcinoma (EOC). Methods: HDAC-2, -4, and -5 immunohistochemical expression was examined in 92 EOC tissue specimens and was correlated with clinicopathological characteristics. Results: HDAC-2 was the most frequently (94.4%) expressed isoform, being marginally higher in serous tumors compared with other types (p=0,08). HDAC-5 was the less frequently expressed (28.1%), being positively associated with HDAC-4. HDAC-4 positivity was associated with lower FIGO-stage (p=0,045) and T-category (p=0.,043) and the absence of lymph node (p=0,05) or distant metastasis (p=0,09) in serous carcinomas. HDAC-2 positivity was correlated with absence of lymph node metastasis in serous tumors (p=0,045). On the contrary, HDAC-5 nuclear positivity was correlated with lymph node metastasis in the entire cohort (p=0,048). HDAC-4 positivity was marginally associated with favorable prognosis in serous carcinomas in univariate survival analysis (p=0,086), a correlation which was not significant in multivariate analysis. Conclusion: These findings suggest a differential expression of HDAC-2, -4 and -5, providing evidence for a potential role in the pathobiology of EOC.

The recent provision of energy-harvesting capabilities to wireless sensor networks has entailed the redefinition of design objectives. Specifically, the traditional goal of maximizing network lifetime has been replaced by optimizing network performance, namely delay and throughput. The present paper contributes to this reformulation by considering the routing problem for the class of time-driven energy-harvesting WSN (EH-WSN) under regular or quasi-periodic energy sources. In particular, this paper shows that the minimum hop count (MHC) criterion maximizes the average duty cycle that can be sustained by nodes in this type of scenarios. This is a primary objective in EH-WSN, since large duty cycles lead to enhanced performance. Based on a previous result, a general expression is first obtained which gives mathematical form to the relationship between duty cycle and traffic load for any node in a time-driven EH-WSN fed by a regular energy source. This expression reveals that the duty cycle achievable by a node decreases as its traffic load increases. Then, it is shown that MHC minimizes the average traffic load over the network, and thus it maximizes the average duty cycle of nodes. This result is numerically validated via simulation by comparison with other well-known routing strategies. Accordingly, this paper suggests assigning top priority to the MHC criterion in the development of routing protocols for time-driven EH-WSN under regular energy sources.

Background: Capsaicinoid are a group of compounds and widely used in the food, medical, and pharmaceutical industries. Capsaicinoid are unique synthesized and accumulated in the pepper fruits. MeJA can enhance the capsaicinoid production. Temporal and spatial expression of capsaicinoid biosynthetic genes are helpful to understand the molecular mechnism of capsaicinoid biosynthesis in the fruits of pepper. Although some of the capsaicinoid biosynthetic genes in pepper have been identified, the expression of these genes at different developing stages of fruit has not been systemically investigated, and little is known about the molecular basis of MeJA inducing capsaicinoid biosynthesis. Results: HPLC study revealed that the capsaicinoid accumulation in the developing fruit of pepper initially appeared at 24 DAP (day after pollination), was actively development at 36 DAP and peaked at 48 DAP. 11 genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the CaCS was unique expressed in placenta and the other 10 genes were expressed in all selected tissues and 9 of 11 genes (except CaCa4H and CaCa3H) were strongly expressed in placenta tissue. Spatial expression analysis demostrated that the 11 gene could be collectively grouped into four categories based on the patterns of relative expression of the genes during fruit development. Category I has 2 and they displayed a bell-shaped expression pattern with the peak expression at 24 DAP, Category II contains 5 genes and expression of the 5 genes was constantly increased from 0 to 36 DAP and peaked at 36 DAP. Category III comprises of 2 genes and both genes reached the peak at 48 DAP. Category IV consists of 2 genes and they showed a high expression at 36 and 48 DAF, but unexpressed from 0 to 12 DAP. The gene expressions of the 11 genes were up-regulated by MeJA. 3 genes showed a high expression at 24 h; 4 genes reached the peak at 12 h; the top expression were observed at 18 h; The last one, CaACYase, achieved the highest level at 8 h. Conclusion: The biosynthesis of capsaicinoid in pepper fruit is developmentally regulated. The expression of the majority of capsaicinoid biosynthetic genes is highly consistent with the development accumulation of capsaicinoid in pepper fruit. These results not only provide the initial information on spatial and temporal expression of capsaicinoid biosynthetic genes in pepper developing fruit, but are also valuable to identify the MeJA-induced genes for capsaicinoid biosynthesis and accumulation during pepper fruit development.

This review deals with the developmental origins of extraocular, jaw and laryngeal muscles, the expression, regulation and functional significance of myosin heavy chains (MyHCs) they express and changes in MyHC expression during phylogeny. Myogenic progenitors from mesoderm in the prechordal plate and branchial arches specify craniofacial muscle allotypes with different repertoires for MyHC expression. To cope with very complex eye movements, extraocular muscles express 11 MyHCs, ranging from the superfast extraocular MyHC to the slowest, non-muscle MyHC IIB. They have distinct global and orbital layers, singly- and multiply-innervated fibres, longitudinal MyHC variations, and palisade endings that mediate axon reflexes. Jaw-closing muscles express the high-force masticatory MyHC, cardiac or limb MyHCs depending on the appropriateness for the acquisition and mastication of their food. Laryngeal muscles express extraocular and limb muscle MyHCs but shift towards slower MyHCs in large animals. During postnatal development, MyHC expression of craniofacial muscles is subject to neural and hormonal modulation. The primary and secondary myotubes of developing EOMs are postulated to induce, via different retrogradely transported neurotrophins, the rich diversity of neural impulse patterns that regulate the specific MyHCs they express. Thyroid hormone shifts 2A MyHC towards 2B in jaw, laryngeal muscles and possibly extraocular muscles.

Recent studies have shown that the prevalence of vegetarianism among the general population in western societies ranges between 2% and 9%. Information regarding the prevalence of vegetarianism among exercisers is lacking. The aim of the present pilot study was to determine the prevalence of vegetarianism among regular exercisers in Greek gyms, as well as assess their dietary habits, exercise habits, and attitudes toward health and environmental issues. 291 regular gym clients completed an anonymous descriptive online questionnaire containing 65 questions divided into five sections (demographic characteristics, dietary habits, physical activity, dietary supplements, environment). Thirty responders (10.3%) identified themselves as vegetarians, spanning the entire spectrum of vegetarianism, from raw vegan to semi-vegetarian. Compared to omnivores, vegetarians had lower body weight, were more concerned about their health and convinced about the health benefits of their dietary choices, were surrounded by more vegetarians socially, consumed fast food and ate out less often, used more dietary supplements, and were better informed about what a sustainable diet is (all p < 0.05). Vegetarians did not differ significantly from omnivores in demographic characteristics, alcohol consumption, smoking habits, prevalence of psychogenic eating disorders, or exercise practices (except for practicing more yoga/Pilates). In conclusion, we report, for the first time, a considerable prevalence of vegetarianism among regular exercisers in gyms. Our findings demonstrate important similarities and differences between exercising vegetarians and omnivores (partly at odds with those seen in the general population) and highlight nutritional and environmental issues on which both groups should be better educated.

Regular physical activity is considered one of the most valid tools able to reduce the risk of on-set of many diseases in humans. However, it is known that intense physical activity is able to induce high levels of genomic damage, while a moderate exercise was found to induce a favora-ble adaptive response by the organism. We evaluated, in a sample of amateur athletes practicing different disciplines, the level of genomic damage by means of the buccal micronuclei assay, comparing obtained data with those of subjects who practiced sport occasionally or that do not practiced any sport. The aim was to evaluate whether physical activity affects background levels of genomic damage and whether the different sports disciplines, as well as some genes poly-morphisms, differentially affect these levels. A total of 206 subjects, 125 athletes and 81 controls, were recruited. Athletes showed significantly lower values of micronuclei, nuclear buds and bi-nucleated cells with respect to controls. Sprinters and martial arts athletes showed significantly higher frequencies of micronuclei than other categories of athletes. Finally, neither sex nor gene polymorphisms seem to influence the levels of genomic damage, confirming that the observed genomic damage is probably due to the type of the sport activity.

In the paper, by a very simple approach, the author establishes an expression in terms of a lower Hessenberg determinant for the Euler polynomials. By the determinantal expression, the author finds a recurrence relation for the Euler polynomials. By the way, the author derives the corresponding expression and recurrence relation for the Euler numbers.

The purpose of this study was to determine the effects of aerobic exercise on carotid to femoral pulse wave velocity (cf-PWV), cell adhesion molecules (intracellular adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), and endothelial selectin (E-selectin), and oxidized-LDL in elderly women aged 70–85 years, and to identify the effect of and correlation with vascular stiffness. Forty participants were recruited and divided into three groups; vascular stiffness (VSG, n=14), obesity (OG, n=14), and normal (NG, n=12). All groups were given a 16-week intervention of aerobic exercise, and the data collected before and after exercise were analyzed using SPSS Ver. 23.0. Two-way repeated-measures ANOVA was used to evaluate between-group and time-dependent interaction effects. One-way ANOVA was used to evaluate between-group variations. In addition, the significance was tested using a post-hoc test (Scheffe). The within-group variations by time before and after exercise were examined using a paired t-test, and correlation analysis was performed using Pearson correlation coefficients. Simple regression analysis was performed for variables showing significant differences. The results indicated interaction effects for cf-PWV (p<.001), VCAM-1 (p<.01), E-selectin (p<.05) and oxidized LDL (p<.001). The rate of change of cf-PWV was positively correlated with that of VCAM-1 (r=.352, p<.05) and that of oxidized-LDL (r=.325, p<.05) with statistical significance. To determine the effect of the rate of change of cf-PWV on the rate of change of VCAM-1, the variables were tested, and the coefficient of determination in the regression analysis was .124, indicating that 12.4% of the tested variables fit the standard regression line. The variables for the effect of the rate of change of cf-PWV on the rate of change of oxidized LDL were also tested, and the coefficient of determination in the regression analysis was .106, indicating that 10.6% of the tested variables fit the standard regression line. Thus, the 16-week regular and consistent aerobic exercise program had significant effects on the cf-PWV, ICAM-1, VCAM-1, E-selectin, and oxidized-LDL in elderly Korean women with vascular stiffness, suggesting improvements in vascular stiffness, based on which the intervention is predicted to contribute to the prevention of vascular dysfunction by lowering the risk of cardiovascular disease due to atherosclerosis, as well as having a positive effect in the prevention of impairment of vascular endothelial cells.

Background: Caffeine is an ergogenic aid that still needs to be investigated in female sports per-formance. Methods: Eight semi-professional female volleyball (Heigth=1.63±0.08 m; Weigth= 66.67 ± 4,.74 kg) players voluntarily participated in this study. A randomised crossover design was carried out. Players went through the caffeine and placebo condition. In the caffeine condi-tion, participants consumed 5 mg/kg of caffeine. The evaluations were performed over two weeks of training. In both conditions, the countermovement jump test, repeated jumps for 15s and hand-grip were performed. Change of direction was assessed using the 505 test. Well-being was also assessed by a wellness questionnaire. A repeated measures Anova and correlation analysis were performed. Results: The repeated-measures ANOVA revealed a main effect of supplementation (F (1.7) = 8.41, p = 0.02, η2 = 0.54) across the training week on physical performance. Besides, there was a positive effect on perceived fatigue (F (1.7) = 7.29, p = 0.03, η2 = 0.51). Conclusions: Caf-feine improved performance and fatigue parameters over one week of training.

The study examines n-balls, regular n-simplices, and n-orthoplices in real dimensions using novel recurrence relations that removed indefiniteness present in known formulas. They show that in the negative, integer dimensions volumes of n-balls are zero if n is even, positive if n = -4k - 1, and negative if n = -4k - 3, for natural k. Volumes and surfaces of n-cubes inscribed in n-balls in negative dimensions are complex, wherein for negative, integer dimensions they are associated with integral powers of the imaginary unit. The relations are continuous for n Î ℝ and show that the constant of π is absent for 0 ≤ n < 2. For n < -1 self-dual n-simplices are undefined in the negative, integer dimensions, and their volumes and surfaces are imaginary in the negative, fractional ones, and divergent with decreasing n. In negative, integer dimensions n-orthoplices reduce to the empty set, and their real volumes and imaginary surfaces are divergent in negative, fractional ones with decreasing n. Out of three regular, convex polytopes present in all natural dimensions, only n-orthoplices, n-cubes (and n-balls) are defined in the negative, integer dimensions.

We enhance Frobenius' method for solving linear ordinary differential equations about regular singular points. Key to Frobenius' approach is the exploration of the derivative with respect to a single parameter; this parameter is introduced through the powers of generalized power series. Extending this approach, we discover that tandem recurrence relations can be derived. These relations render coefficients for series occurring in logarithmic solutions. The method applies to the, practically important, exceptional cases in which the roots of the indicial equation are equal, or differ by a non-zero integer. We demonstrate the method on Bessel's equation and derive previously unknown tandem recurrence relations for coefficients of solutions of the second kind, for Bessel equations of all integer and half-integer order.

Chinese calligraphy, revered globally for its therapeutic and mindfulness benefits, encompasses styles such as Regular (Kai Shu), Running (Xing Shu), Official (Li Shu), and Cursive (Cao Shu) scripts. Beginners often start with Regular script, advancing to more intricate styles like Cursive. Each style, marked by unique historical calligraphers' contributions, requires learners to discern distinct nuances. The integration of AI in calligraphy analysis, collection, recognition, and classification are pivotal. This study introduces an innovative Convolutional Neural Network (CNN) architecture, pioneering the application of CNN in the classification of Chinese calligraphy. Focusing on the four principal calligraphers' styles from the Tang dynasty (690-907 A.D), this research spotlights the era when the traditional regular script font (Kai Shu) was refined. A comprehensive dataset of 8282 samples from these calligraphers, representing the zenith of regular style, was compiled for CNN training and testing. The model distinguishes personal styles for classification, showing superior performance over existing networks. Achieving 89.5-96.2% accuracy in calligraphy classification, our approach underscores the significance of CNN in both font and artistic style categorization. This research paves the way for advanced studies in Chinese calligraphy and its cultural implications.

This paper introduces a novel algorithm for solving the point-to-point shortest path problem in a static regular 8-neighbor connectivity (G8) grid. This algorithm can be seen as a generalization of Hadlock algorithm to G8 grids, and is shown to be theoretically equivalent to the relaxed A* (RA*) algorithm in terms of the provided solution's path length, but with substantial time and memory savings, due to a completely different computation strategy, based on defining a set of lookup matrices. Through an experimental study on grid maps of various types and sizes (1290 runs on 43 maps), it is proven to be 2.25 times faster than RA* and 17 times faster than the original A*, in average. Moreover, it is more memory-efficient, since it does not need to store a G score matrix.

Background: While investigating the real-time impedance at acupuncture points (acupoints), it was found that regular sinusoidal waves were present that corresponded to the pulsing of certain organs, such as respiration and duodenal waves, the stomach’s slow waves, and also the heart’s beating.Methods: This study investigated such respiration waves at lung-related acupoints to clarify their relation to the respiration pacesetter mechanism. The impedance at key acupoints was monitored in real time while the patients’ breathing slowed after exercise.Results: In all 7 patients studied, the respiration and heart-beat waves matched the rates in the corresponding organs at rest, and did not vary markedly due to exercise. In 3 of the 7 patients, their post-exercise respiration rate exactly matched that of their duodenal waves, but then dropped, stepwise, back to their usual respiration rate. In the other 4 patients, their post-exercise respiration rate did not reach that of their duodenal waves, so this pattern was not triggered.Conclusion: The results suggested that as well as the brainstem respiration pacesetter, there was also a separate “pace signal” present which remained constant and seemed to define the respiration rate when at rest. It is currently unknown what mechanism causes the respiration rate to increase due to exercise. But these results suggest that the brainstem pacesetter is sometimes guided by the duodenal pace signal instead of the lung pace signal, which may explain how the pacesetter is able to jump to a higher rate, even though its chemoreceptor inputs may be unchanged.

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions [acidic (AS), basic (BS), and neutral (NS)]. These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.

Background: Sickle cell disease (SCD) is the most common hemoglobinopathy in the Democratic Republic of Congo (DRC) and poses a public health problem. If, without clinical follow-up, more than 50% of children with SCD die before their 5th birthday. A regular medical follow-up is the first simple improvement that can be beneficial for SCD patients in a remote city of an African country. Method: A cohort of 143 children with SCD aged 10 years old (IQR [inter quartile range]: 6–15 years) (sex ratio male: female = 1.3) were clinically followed for 12 months without any specific intervention and then 12 months with a monthly medical visit, a biological follow-up and regular prophylaxis. A paired Student test and pairwise Wilcoxon test were used to compare study outcomes. Results: The median age of patients at the diagnosis of SCD was 2 years (IQR: 1–5). Anemia was noted in 100% of patients at inclusion, with severe and normocytic anemia in 80% of cases (n = 115). The implementation of standardized and regular follow-up has shown an increase in the annual mean hemoglobin level from the percentage of the low limit normal for the age from 54 to 77 % (p = 0.001), and a decrease of the lymphocytes count and spleen size (p < 0.001). The implementation of regular follow-up has also shown a significant decrease (p < 0.001) in the average annual number of hospitalizations and episodes with vaso-occlusive crises, blood transfusions, infections, and acute chest syndromes. Conclusions: This study showed that the regular follow-up of children with SCD and the application of SCD management recommendations are possible and applicable in the context of a remote city in a developing country. Simple and accessible measures included in conventional recommendations can reduce the morbimortality of these patients in remote areas if applied rigorously with regular follow-up.

Dipeptidyl peptidase (DPP) 9, DPP8, DPP4 and fibroblast activation protein (FAP) are the four enzymatically active members of the S9b protease family. Associations of DPP9 with human liver cancer, exonic single nucleotide polymorphisms (SNPs) in DPP9 and loss of function (LoF) variants have not been explored. Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. Survival and gene signature analyses were performed on hepatocellular carcinoma (HCC) data. We found that DPP9 and DPP8 are intolerant to LoF variants. DPP9 LoF variants were most often associated with uterine carcinoma. Two DPP9 intronic SNPs that have been associated with lung fibrosis and COVID-19 were not associated with liver fibrosis or cancer. All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. Increased DPP9 expression was associated with obesity in HCC patients.. High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. This comprehensive data mining suggests that DPP9 is essential for human survival and the DPP4 protease family is important in cancer pathogenesis.

Aims: A community-based multi-component intervention (increasing awareness of the importance of physical activity in chronic illness management through reading comic books, training regarding warm-up stretching exercises, identifying facilitators and barriers to exercise through photosharing, supporting self-reflection and development of action plans) was developed to promote physical activity (PA) among patients with diabetes and hypertension. This study aimed to evaluate the efficacy of this intervention on health behaviour (walking) and health outcomes. Design: A non-randomized controlled trial with waitlisted control and pre- and post-measures. Setting: Community centres for the elderly. Participants: A total of 204 older adults with diabetes and/or hypertension were recruited. They were assigned to either the intervention group (IG) or waitlisted to the control group (CG). Intervention: Under the supervision of a nurse, six weekly group meetings were arranged in community centres for the elderly in which the participants freely exchanged their views regarding the barriers and facilitators of regular physical activity. Participants were encouraged to take photos in their neighbourhood or at home and brought these photos to share at the group meetings. The photos showed both the barriers and the facilitators to PA. In the last meeting, each participant worked out a plan to perform PA in the coming four weeks. Measures: PA referred to the number of steps taken per day and it was measured by a Garmin Accelerometer at baseline, Week 6 and Week 10. Other measures included the nine-item Self-Efficacy Scale for Exercise - Chinese version (SEE-C), the 23-item Chinese Barriers to Exercise Scale and Senior Fitness Tests. Generalised Estimating Equations (GEE) models compared the outcomes over time between IG and CG. Results: A statistically significant difference in the changes in the average number of steps taken daily between the two groups at Week 10 (mean difference = 965.4; 95% confidence interval: 92.2, 1838.6, p = 0.030) was observed, although the difference at Week 6 was non-significant (mean difference = 777.6; 95% confidence interval: −35.3, 1590.5, p = 0.061). IG participants also showed significant improvements in lower body strength (mean difference = 0.967; 95% confidence interval: 0.029, 1.904, p = 0.043) and lower limb flexibility (mean difference = 2.068; 95% confidence interval: 0.404, 3.731, p = 0.015) at Week 10 compared to CG participants. Conclusion: This multi-component intervention improved the participants’ physical activity level and physical fitness, particularly in lower limb flexibility and body strength.

Sepsis is an inflammatory disorder caused by the host’s dysfunctional response to infection. Septic patients present diverse clinical characteristics, and in the recent years it has been the main cause of death in intensive care units (ICU). Aquaporins, membrane proteins with role in water transportation, have been reported to participate in numerous biological processes. Their role in sepsis progression has been studied extensively. This review aims to examine recent literature on aquaporin expression and regulation in clinical sepsis, as well as established experimental models of sepsis. We will present how sepsis affects aquaporin expression at the molecular and protein level. Moreover, we will delve into the importance of aquaporin regulation at the transcriptional, post-transcriptional, translational, and post-translational level in sepsis, by presenting data on aquaporin regulation by non-coding RNAs and selected chemical molecules. Finally, we will focus on the importance of aquaporin single nucleotide polymorphisms in the setting of sepsis.

SET protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair and gene regulation. SET overexpression has been detected in brain neurons of Alzheimer's disease patients, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types. In this study, we characterized the transcriptional activation of human SET transcript 2 promoter in HeLa cells. Promoter deletion experiments and co-transfection assays indicated that ZFX, the Zinc finger and X-linked transcription factor, was able to transactivate the SET promoter. A proximal promoter region containing four ZFX-binding sites was found to be critical for the ZFX-mediated transactivation. Mutagenesis study indicated that the site located closest to the transcription start site accounted for most of the ZFX-mediated transactivity. Manipulation of ZFX levels by overexpression or siRNA knockdown confirmed the significance and specificity of the ZFX-mediated SET promoter activation. Chromatin immunoprecipitation results verified the binding of ZFX to its cognate site in the SET promoter. These findings have led to identification of ZFX as an upstream factor regulating SET gene expression. More studies are required to define the in vivo significance of this mechanism, and specifically, its implication for several benign and malignant diseases related to SET dysregulation.

In recent years, the analysis of macro- and micro-expression has drawn the attention of researchers since they provide visual cues of an individual's emotions for a broad range of potential applications such as lie detection and criminal detection. In this paper, we address the challenge of spotting facial macro- and micro-expression from videos and present compelling results by using a deep learning approach to analyze the optical flow features. Different from other deep learning approaches that are mainly based on Convolutional Neural Networks (CNNs), we propose a Transformer-based deep learning approach that predicts a score indicating the probability of a frame being within an expression interval. In contrast to other Transformer-based models that achieve high performance by being pre-trained on large datasets, our deep learning model, called SL-Swin, which incorporates Shifted Patch Tokenization and Locality Self-Attention into the backbone network Swin Transformer, effectively spots macro- and micro-expressions by being trained from scratch on small-size expression datasets. Our evaluation outcomes surpass the MEGC 2022 spotting baseline result, obtaining an overall F1-score of 0.1366. Additionally, our approach also performs well in the MEGC 2021 spotting task with an overall F1-score of 0.1824 and 0.1357 on CAS(ME)^2 and SAMM Long Videos, respectively. The code is publicly available on GitHub (https://github.com/eddiehe99/pytorch-expression-spotting).

Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of Bergamot Polyphenol Fraction (BPF). CAF diet caused a strong upregulation of the gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6). However, only one -oxidation gene (Cpt1a) and a few autophagy genes were modulated in the CAF group compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca, Fasn and Scd1, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no -oxidation gene expression changes were observed, suggesting minor transcriptional effects on autophagy. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on -oxidation, but profound suppression of de-novo lipogenesis.

A novel effective vibrational mode was discovered in the conventional transducer with an array of orthogonal (square) regular piezoelectric rods in 1-3 piezocomposite, containing the damping backing and front matching layers. The operational resonance in the structure was determined as the Surface Acoustic Wave (SAW) on the backing boundary excited by the adjacent piezo-rods, with its frequency typically near 3 times lower the fundamental half-lambda conventional piezocomposite resonance. Pulse-echo sensitivity and transmitting sound-pressure-level (SPL) in air showed that the signal strength is roughly comparable to the industrial similar air transducers at the frequency range 100…700 kHz, where at these frequencies the lateral and longitudinal piezoelement dimensions in the conventional transducer design are typically close to each other causing interference with unwanted coupling modes. As was determined theoretically and proved in experiments, the backing SAW resonance effect in the transducer performance is inherent just to the regular periodic 1-3 piezocomposite structure, and does occur neither with randomly located/oriented piezo-rods, nor in the homogeneous piezo-plate at least with the same lateral cross-section as the connected to it backing. The purpose of the article is to investigate a newly discovered operational vibrational mode of a SAW type in 1-3 regular piezocomposite, other than piezoelectric resonance. The investigated phenomena can improve the transceiver sensitivity, bandwidth, providing lower drive voltage, and smaller and lighter weight ultrasonic transducers. Based on the piezocomposites with thickness’ 1…1.5 mm (rod resonance near 2…3 MHz), pillar width 0.2…0.8 mm, kerf width 0.1…0.4 mm, the transceivers with an operating frequency from 140 kHz to 650 kHz were designed and fabricated with a conventional backing of a mixture of high-density tungsten powder and epoxy, and a matching layer of a mixture of low-density glass bubbles and epoxy. Experimental evaluation of their acoustical performance showed expected characteristics suitable for practical applications.

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on gram-negative bacteria and can eliminate 99.99% of E. coli within 100 minutes at the minimal MIC concentration. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be disruption of Gram-negative cell membrane.

Body Expression (BE) has been defined in the past decades as a discipline within Physical Education (PE) with very particular characteristics and a strong emotional component. In this study, a programme of this discipline was applied to university Physical Activity and Sports Sciences (PASS) students from six consecutive academic years: three prior to and three during the pandemic. A pre-post design was used to determine how the BE programme affected the university students' self-concept (SC). To do so, a questionnaire with a multidimensional approach to this construct was administered, whose dimensions were closely related to the BE programme's characteristics. The results revealed significant improvements in the final SC, compared to the initial SC. Men reported lower SC values than women before the programme implementation, but higher at the end. Therefore, the change was larger in men, so the programme may have had an equalising effect between groups. It was also verified that the pandemic had particularly affected women.

Water resources worldwide are limited, especially in desert areas like Saudi Arabia. Therefore, the rational and sustainable management of irrigation water supply is an imperative required by the conditions of space and time. This study evaluates the irrigation system through partial root-zone drying (PRD) and regulated deficit irrigation (RDI). The effect of applying the PRD and RDI systems on the efficiency and rationalization of irrigation water consumption in a greenhouse and open field cucumber was studied in addition to using the surface (S) and subsurface (SB) drip irrigation methods on irrigation efficiency. The productivity of the RDI-S regular drip irrigation treatment was considered 100% as the control on which the results of all treatments are measured. The results showed that in terms of irrigation technique, the PRD-SB technique had the highest productivity during the winter season in greenhouse cucumbers, with a general average of 13.8 kg m-2 for all irrigation levels, while the RDI-SB technique had the highest productivity during the summer season, with a general average of 16.1 kg m-2. Regarding irrigation level results, the study showed that an irrigation level of 100% is the highest productivity in all irrigation techniques, with a general average of 14.9 kg m-2 for all irrigation techniques during the winter season and 16.4 kg m-2 during the summer. However, the increase in the irrigation level to 150% did not increase productivity. In comparison, the application of the deficit irrigation technique by reducing the level of irrigation to 50% was not accompanied by a similar decrease in productivity. The study results also showed that irrigation with the PRD-SB system was the most productive in the open field at all irrigation levels, with a general average of 7.3 kg m-2. The general average of the percentage decrease in productivity in all irrigation techniques compared to reducing the irrigation percentage to 50% and 75% was 22% and 3 %. The irrigation efficiencies were higher when applying the PRD (PRD-SB) in winter. In contrast, applying a deficit irrigation system (RDI-SB) in the summer season had the highest efficiency. It could be concluded that using PRD and RDI systems for indoor and outdoor cucumber can save irrigation water.

Few young Japanese adults regularly consume a well-balanced diet composed of staples, course dishes, and sides. We hypothesised that adopting the recommended planetary health diet with regular breakfast consumption would promote well-balanced diets among young Japanese male undergraduates. This study aimed to examine the structural association between a planetary health diet with regular breakfast consumption and well-balanced diet intake. Participants were 142 male undergraduates who completed a 2022 online questionnaire via Google Forms in a cross-sectional study at a public university in Hyogo Prefecture. A planetary health diet comprises the consumption of the recommended eight items. A covariance structure analysis was performed in a hypothetical model with factors (regular breakfast consumption and eight items) potentially associated with the intake of a well-balanced diet at least twice daily. Acceptable goodness-of-fit was obtained by excluding chicken dishes and nuts from the eight recommended items of the planetary health diet. Frequent consumption of the remaining six recommended items (fish, eggs, soybeans/soybean products, dairy foods, vegetables, and fruits) was significantly positively correlated with regular breakfast consumption and a significant positive path to a well-balanced diet. Among male university students, regular breakfast consumption and a planetary health diet may lead to a well-balanced diet.

The prevalence of overweight/obesity in the adult population in the Philippines has doubled in the past 20 years. Zumba exercise has recently been implemented throughout the Philippines. However, there is scarce information on the effects of Zumba on obesity and Zumba participants’ characteristics in the Philippines. This study described the current practice of Zumba in the Philippines, along with the practitioners’ characteristics, and identified factors associated with Zumba participation. In this observational, cross-sectional study, a structured questionnaire was used to survey 10 Zumba locations in September 2019. Anthropometric measurements of participants were assessed. Respondents included 171 women (88.6%) and 22 men (11.4%), with a mean (±SD) age of 44.1 (± 8.9) years. All respondents answered that Zumba was enjoyable, and some answered “very enjoyable.” Determinants of frequent participation were as follows: being older than the mean age of participants, starting Zumba to enjoy dancing, starting Zumba not to lose weight, shopping mall location, and participation fee required. “To enjoy dance” being a motivation for Zumba practice was identified as a determinant of frequent participation, rather than “to lose weight.” The element of “enjoyable” may strongly influence continuation and frequent participation of Zumba exercise in the Philippines.

Many reports showed a dramatic decrease in the levels of physical activity during the current pandemic of SARS-COV-2. This has substantial immunometabolic implications, especially in those at risk or with metabolic diseases including individuals with obesity and Type 2 diabetes. Here we discuss the route from physical inactivity to immnometabolic aberrancies; focusing on how insulin resistance could represent an adaptive mechanism to the low physical activity levels and/or high energy intake and on how such an adaptive mechanism could derail to be a pathognomonic feature of metabolic diseases creating a vicious circle of immune and metabolic aberrancies. We provide a theoretical framework to the severe immunopathology of COVID-19 in patients with metabolic diseases. We finally discuss the idea of exercise as a potential adjuvant against COVID-19 and emphasize how even interrupting prolonged periods of sitting with short time breaks of very light activity could be a feasible strategy to limit the deleterious effects of sedentary behavior.

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1&gt;49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p&lt;0.05). In addition, patients diagnosed with adenocarcinoma, PDL1&lt;49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p&lt;0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Gastric Cancer (GC) is the fifth most frequently diagnosed malignant tumor and the third cause of cancer mortality worldwide. For advanced GC, a large number of novel drugs and combinations have been tested, but results are still disappointing and the disease incurable in the majority of cases. In this regard, it is critical to investigate the molecular mechanisms underlying GC development. Angiogenesis is one of the hallmarks of cancer with a fundamental role in GC growth and progression and ramucirumab, a monoclonal antibody binding to vascular endothelial growth factor-2 (VEGFR-2) is approved in the treatment of advanced and pretreated GC. However, no predictive biomarkers for ramucirumab have been identified so far. MicroRNAs (miRNAs) are a class of evolutionally conserved single-stranded noncoding RNAs playing an important role, via post-transcriptional regulation, in essentially all biologic processes such as cell proliferation, differentiation, apoptosis, survival, invasion, and migration. Notably, in our review, we focused on miRNAs involved in angiogenic pathways in GC. Moreover, we evaluated the possible prognostic and predictive role of angiogenesis-related miRNAs as novel biomarkers of GC.

Previous studies had shown that mRNA, miRNA and lncRNA were associated with cardiovascular diseases. The study was aimed to explore the differential expressions of mRNA, lncRNA and miRNA between coronary artery disease (CAD) and healthy control, and their interaction in CAD. We investigated the differential expression of ceRNA between CAD and healthy control through data collected from Gene Expression Omnibus (GEO) microarrays. Furthermore, we investigated the biological function of these differential expressions of ceRNAs by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Protein-protein interaction (PPI) network was created to identify the hub genes. Biosystems and literature search were performed for signaling pathways and their function of the included differential expression ceRNAs. A total of 456 miRNA expression profiles, 16,325 mRNA expression profiles, and 2,869 lncRNA expression profiles were obtained. Eleven Go and KEGG pathways (count ≥9), top 15 of PPI network node connectivity rank, and top 15 of ceRNA network node degree centrality rank were achieved at the statistical significance level (P<0.05). We further identified that several differential expressions of ceRNAs and their signaling pathways were associated with CAD through biosystems and literature search. Based on eleven Go and KEGG pathways, top 15 of PPI network node connectivity rank, and top 15 of ceRNA network node degree centrality rank in CAD population, our findings would contribute to further exploration for the molecular mechanism of CAD.

Background: Peroxiredoxins (Prxs) comprise antioxidant factors that are widely found in prokaryotes and eukaryotes. Abnormal expression of Prxs is closely related to tumorigenesis. Methods: This study examined the prognostic value and expression of Prxs in lung cancer by Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier Plotter, cBioPortal and Functional Enrichment Analysis Tool (FunRich) databases. Results: We found that Prx1/2/3/4/5 were overexpressed in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) relative to normal lung cells. However, the expression level of Prx6 was lower in LUAD and higher in LUSC than normal lung cells. The level of Prx3 and Prx6 were associated with pathological stage. Prognostic analysis showed that elevated Prx1 and Prx2 expression were correlated with low Overall Survival (OS), whereas high Prx5 and Prx6 expression level predicted high OS. Conclusions: Our results effectively revealed the level of Prxs in lung cancer and its influence on the prognosis of lung carcinoma, contributing to the study of the role of Prxs in tumorigenesis.

Skeletal muscles are crucial for voluntary movements, and impairments in their function significantly impact our activity. Dysferlin, a protein predominantly present in skeletal muscle, is a focal point of extensive research due to its vital role in muscle repair and maintenance. This study investigates Dysferlin's levels and function in skeletal muscles, emphasizing its significance and the potential effects of its dysregulation on fast and slow muscle fibers. We employed Western blotting on two different rat muscles. The results revealed distinct expressions of Dysferlin in fast and slow fibers, as demonstrated by Western blotting. We propose that Dysferlin may have a metabolic role in addition to its involvement in the repair mechanism.

Butyric acid as a histone deacetylase (HDAC) inhibitor was produced by a number of periodontal and root canal microorganisms (such as Porphyromonas, Fusobacterium etc.). Butyric acid may affect the biological activities of periodontal/periapical cells such as osteoblasts, periodontal ligament cells etc., and thus affect periodontal/periapical tissue destruction and healing. The purposes of this study were to study the toxic effects of butyrate on matrix and mineralization markers’ expression of MG-63 osteoblasts. Cell viability and proliferation were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cellular apoptosis and necrosis were analyzed by propidium iodide/Annexin V flow cytometry. Protein and mRNA expression of OPG, and RANKL were analyzed by western blotting and RT-PCR. OPG, soluble RANKL (sRANKL), 8-isoprostane, pro-collagen I, MMP-2, osteonectin (SPARC), osteocalcin and osteopontin secretion into culture medium were measured by enzyme-linked immunosorbant assay. Histone H3 acetylation levels were evaluated by immunofluorescent staining (IF) and western blot. We found that butyrate induced morphologic changes of growing MG-63 cells, with bigger and flattened in appearance. Butyrate activated histone H3 acetylation of MG-63 cells. Exposure of MG-63 cells to butyrate partly decreased cell number with no marked increase in apoptosis and necrosis. Butyrate stimulated RANKL protein expression, whereas it inhibited OPG protein expression. Butyrate also inhibited the secretion of OPG in MG-63 cells, whereas sRANKL level was below detection limit. Butyrate stimulated 8-isoprostane, MMP-2 and osteopontin secretion, but not procollagen I, osteonectin, osteocalcin in MG-63 cells. In conclusion, butyric acid generated by periodontal and root canal microorganisms may potentially induce bony destruction and impair bone repair by alteration of OPG/RANKL expression/secretion, 8-isoprostane, MMP-2, and osteopontin secretion, and affect cell proliferation. These effects are possibly related to increased histone acetylation. These events are important in the pathogenesis of periodontal and periapical destruction.

Background Community infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased rapidly since the emergence of the Omicron strain. During the eighth and ninth pandemic waves—when movement restrictions in the community were eased—the all-case registration system was changed, and the actual status of infection became uncertain. Methods We conducted regular rapid antigen tests (R-RAT) once or twice a week to examine the actual state of coronavirus disease (COVID-19) diagnosis among healthcare employees. Results Overall, 320 (1.42/day) and 299 (1.76/day) employees were infected in the eighth and ninth pandemic waves. During both periods, 59/263 doctors (22.4%), 335/806 nurses (41.6%), 92/194 administrative employees (47.4%), and 129/218 clinical laboratory technicians (59.2%) were infected. In the eighth wave, 56 of 195 employees were infected through close contact; in the ninth wave, 26 of 62 employees were infected. No significant difference was observed in the number of vaccinations between infected and non-infected employees. The positivity rate of R-RAT was 0.41% and 0.45% in the eighth and ninth waves. R-RAT detected infection in 212 and 229 employees during the eighth and ninth waves, respectively; the ratio of R-RAT-detected positive employees to those who reported infection was significantly higher during the ninth wave (odds ratio: 1.67, 95% confidence interval: 1.17–2.37, p

Papillary thyroid carcinoma (PTC) presents a significant health concern, particularly among Hispanic women in the United States, who exhibit a disproportionately higher chance of developing an advanced disease when compared to the non-Hispanic population. Emerging evidence suggests coagulation factor X, encoded by F10 gene, has a potential role in inhibiting cancer cell migration. However, comprehensive investigations into the differential expression patterns of F10 in Hispanic versus non-Hispanic females remain limited. RNA-sequencing data was acquired from the TCGA database for white female patients, 166 non-Hispanic and 25 Hispanic. A statistically significant (p &lt; 0.05) 2.06-fold increase in F10 expression levels was detected in disease-free tumors compared to recurrent PTC tumors. Furthermore, an increase in F10 gene expression levels was also observed corresponding to approximately a 1.74-fold increase in non-Hispanic patients compared to Hispanic patients. The probability of tumor recurrence was 1.82 times higher in the cohort with low expression of F10 compared to the high expression cohort, correlating with the lower disease-free rates observed in Hispanic patients’ cohort when compared to non-Hispanics. This finding underscores the relevance of ethnic disparities in molecular profiles for understanding cancer susceptibility. Identifying F10 as a potential prognostic biomarker highlights avenues for targeted interventions and contributes to improving diagnostic and treatment strategies for diverse patient populations.

(1) Background: Central nervous system (CNS) development is characterized by dynamic changes in cell proliferation and differentiation. Key regulators of these transitions are the transcription factors such as SOX2 and SOX9. SOX2 is involved in the maintenance of progenitor cell state and neural stem cell multipotency, while SOX9, expressed in neurogenic niches, plays an important role in neuron/glia switch with predominant expression in astrocytes in the adult brain. (2) Methods: To validate SOX2 and SOX9 expression pattern in dissociated primary neuronal cultures derived from opossum (Monodelphis domestica), we used immunohistochemistry (IHC) and the isotropic fractionator method on fixed cortical tissue from comparable postnatal ages; (3) Results: Neurons positive for both neuronal (NeuN or TUJ1) and stem cell (SOX2) markers were identified and their presence was confirmed with all methods and postnatal age groups (P4-6, P6-18 and P30) analyzed. SOX9 showed exclusive staining in non-neuronal cells, and it was coexpressed with SOX2. (4) Conclusions: The persistence of SOX2 expression in developing cortical neurons of M. domestica during first post-natal month implies the functional role of SOX2 during neuronal differentiation and maturation, which was not previously reported in opossums.

Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to his-tone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively investigated in the context of cancer research, its association with histone modifiers has received limited attention. This review ex-plores the interplay between histone modifiers and p53 in regulating gene expression. We discussed how histone modifications can influence how p53 binds to target genes and how this interplay can be disrupted in cancer cells. This study provides insights into the complex mechanisms underlying gene regulation and their implications for potential cancer therapy.

Following the central dogma of molecular biology, gene expression variability can aid in predicting and explaining the wide variety of protein products, functions, and, ultimately, variability in phenotypes. There is currently overlapping terminology used to describe the types of variability in gene expression profiles, and overlooking these nuances can misrepresent important biological information. Here, we describe transcriptional diversity as quantifying transcriptional changes as a measure of the variability in 1) the total expression of all genes or a gene across samples (transcriptome diversity) or 2) the isoform-specific expression of a given gene (isoform diversity). We first overview modulators and quantification of gene expression variability. Then, we discuss the role alternative splicing plays in driving transcript isoform expression variability and how isoform diversity can be quantified. Additionally, we overview computational resources for calculating transcriptome and isoform diversity for short- and long-read sequencing data. Finally, we discuss future applications of transcriptional diversity. This review provides a comprehensive overview of how gene expression variability arises, and how measuring it determines a more complete picture of heterogeneity across proteins, cells, tissues, organisms, and species

The expression microarray technique was performed to investigate the differences in gene expression between Czech Large White pigs and wild boars in the longissimus lumborum et thoracis and biceps femoris muscle tissues. The NREP gene (neuronal regeneration related protein homolog) was selected for detailed study as an expressional and functional candidate gene. NREP plays a role in the transformation of neural, muscle and fibroblast cells and in smooth muscle myogenesis. Quantitative real-time PCR results confirmed that the porcine NREP gene was expressed in both skeletal muscles and significantly overexpressed in Czech Large White pigs compared to wild boars (P &lt; 0.05). We identified 9 polymorphic sites in genomic DNA of NREP gene. Six of these polymorphisms were in complete linkage disequilibrium and therefore only 4 polymorphisms were informative. Associations of these 4 polymorphisms (HF571253:g.103G&gt;A, HF571253:g.134G&gt;A, HF571253:g.179T&gt;C and HF571253:g.402_409delT) with meat performance traits were assessed in Czech Large White pigs. New polymorphisms in NREP gene were significantly associated with parameters of daily weight gain, lean meat and backfat thickness in Czech Large White pigs. Our primary study suggested that porcine NREP may play an important role in skeletal muscle growth, fat metabolism and meat performance traits.

KLHL genes and the related KBTBD genes encode components of the Cullin-E3 ubiquitin ligase complex and typically target tissue-specific proteins for degradation, thereby affecting differentiation, homeostasis, metabolism, cell signaling, and the oxidative stress response. Despite their importance in normal cell function and in disease (KLHL40, KLHL41, KBTBD13, KEAP1, and ENC1), previous studies that examined epigenetic factors affecting transcription were predominantly limited to promoter DNA methylation. Using diverse tissue and cell culture whole-genome profiles, we examined 17 KLHL or KBTBD genes preferentially expressed in skeletal muscle or brain to identify tissue-specific enhancer and promoter chromatin, open chromatin (DNaseI hypersensitivity), and DNA hypomethylation. Sixteen of the 17 genes displayed muscle- or brain-specific enhancer chromatin in their gene bodies, and most exhibited specific intergenic enhancer chromatin as well. Seven genes were embedded in a super-enhancer. The enhancer chromatin regions typically displayed foci of DNA hypomethylation at peaks of open chromatin. In addition, we found evidence that gene neighbors (HHATL and FBXO32) of KLHL40 and KLHL38 harbor enhancer chromatin that likely upregulates the adjacent KLHL gene. Many KLHL/KBTBD genes had tissue-specific promoter chromatin at their 5’ ends, but surprisingly, two (KBTBD11 and KLHL31) had constitutively unmethylated promoter chromatin in their 3’ exons that overlaps a retrotransposed KLHL gene. Our findings demonstrate the importance of expanding epigenetic analyses beyond the 5’ ends of genes in studies of normal and abnormal gene regulation.

Using a breast cancer (BC) cellular model: MDA-MB-231 cells with blocked synthesis of galacto-sylceramide (GalCer; MDA.Δ.UGT8.4) and MCF7 and T47D cells that over-produced GalCer (MCF7.UGT8 and T47D.UGT8), we found that GalCer increased resistance to doxorubicin, paclitaxel, and cisplatin serving as an anti-apoptotic molecule. These results were supported by a study using murine mammary carcinoma 4T1 cells over-producing GalCer, which were trans-planted into Balb/c mice and were more resistant to doxorubicin therapy than the control. Sub-sequent studies revealed that GalCer specifically downregulated the level of pro-apoptotic TNFRSF1B and TNFRSF9 genes and increased the level of the anti-apoptotic BCL2 gene expres-sion, suggesting that GalCer regulates their expression at the level of transcription. Consistent with this hypothesis, MDA-MB-231 and MCF7.UGT8 cells with high GalCer content showed lower activity of TNFRSF1B and TNFRSF9 promoters than cells lacking GalCer. In contrast, the activity of the BCL2 promoter in MCF7.UGT8 was higher than in MCF7 cells without GalCer. However, no difference in BCL2 promoter activity was observed between MDA-MB-231 cells with high GalCer level and GalCer-negative MDA.Δ.UGT8.4 cells. Instead, we found that GalCer increased the stability of Bcl-2 mRNA. As a candidate protein that simultaneously increases the expression of TNFRSF1B and TNFRSF9 genes and decreases the expression of BCL2 gene and stability of Bcl-2 transcripts is probably p53, its expression was analysed in BC cells containing various amounts of GalCer. In agreement with this hypothesis, BC cells with high GalCer con-tent are characterized by significantly lower expression of p53, and inhibition of p53 using siR-NA resulted in decreased expression of TNFRS1B and TNFRS9 genes and increased expression of BCL2 gene.

The principal barrier to an HIV-1 cure is the persistence of infected cells harboring replication-competent proviruses despite antiretroviral therapy (ART). HIV-1 transcriptional suppression, referred to as viral latency, is foremost among persistence determinants, as it allows infected cells to evade the cytopathic effects of virion production and killing by cytotoxic T lymphocytes (CTL) and other immune factors. HIV-1 persistence is also governed by cellular proliferation, an innate and essential capacity of CD4+ T cells that both sustains cell populations over time and enables a robust directed response to immunological threats. Yet when HIV-1 infects CD4+ T cells, this capacity for proliferation can counterproductively enable surreptitious HIV-1 propagation without the deleterious effects of viral gene expression in latently infected cells. Over time on ART, the HIV1 reservoir is shaped by both persistence determinants, with selective forces most often favoring clonally expanded infected cell populations harboring transcriptionally quiescent proviruses. Moreover, if HIV latency is incomplete or sporadically reversed in clonal infected cell populations that are replenished faster than they are depleted, such populations could both persist indefinitely and contribute to low-level persistent viremia during ART and viremic rebound if treatment is withdrawn. In this review, select genetic, epigenetic, cellular, and immunological determinants of viral transcriptional suppression and clonal expansion of HIV-1 reservoir T cells, interdependencies among these determinants, and implications for HIV-1 persistence will be presented and discussed.

RNA pol II assembly occurs in the cytoplasm before the translocation of the enzyme to the nucleus. Affecting assembly influences mRNA transcription in the nucleus and mRNA decay in the cytoplasm. However, very little is known about the consequences on ncRNA synthesis. In this work, we show that impairment of RNA pol II assembly leads to a decrease in cryptic non-coding RNAs (preferentially CUTs and SUTs). This alteration is partially restored upon overcoming the assembly defect. Notably, this drop in ncRNAs is only partially dependent on the nuclear exosome, which suggests a major specific effect of enzyme assembly. Our data also point out a defect in transcription termination and lead as to proposes that CTD phosphatase Rtr1 could be involved in this process.

The gravitational constant is equivalent to natural units in its six unit dimensions. Evaluating the classical formulas in each unit dimension shows how inputs of mass and radius are transformed into the correct unit dimensions and magnitude of gravitational potential. Mass and radial distance are equivalent proportions of the Planck scale as the potentials they produce. Gravitational potentials of velocity, acceleration, energy, and force are proportional to a radial density limit of one Planck mass per Planck length of radial distance.

Selenium is a trace metal essential to human health, and its deficiency has been related to, for instance, cardiovascular and myodegenerative diseases, infertility and osteochondropathy Kashin-Beck disease. It is incorporated as selenocysteine to selenoproteins, which protect against reactive oxygen and nitrogen species. They also participate in the activation of thyroid hormone, and play a role in immune system functioning. The synthesis and incorporation of selenocysteine occurs via a special mechanism, which differs from the one used for standard amino acids. The codon for selenocysteine is the regular in-frame stop codon, which can be passed by specific complex machinery participating in translation elongation and termination. This includes the presence of selenocysteine insertion sequence (SECIS) in the 3’-untranslated part of the selenoprotein mRNAs. Selenium deficiency is known to control both selenoprotein and non-selenoprotein transcriptomes. Nonsense-mediated decay is involved in the regulation of selenoprotein mRNA levels, both other mechanisms are also possible.

unlike the volume, the expression for the surface area of a regular conoid has not yet been obtained by means of direct integration or a differential geometry procedure. As this non-developable form is relatively used in engineering, the difficulty to determine its surface, represents a serious shortcoming for several problems which arise in radiative transfer, lighting and construction, to cite just a few. In order to solve the problem, I conceived the surface as a set of linearly dwindling ellipses which remain parallel to a circular directrix, a typical problem appears when searching the length of such ellipses. I employed a new procedure which, in principle, consists in dividing the surface into infinitesimal elliptic strips to which we have successively applied Ramanujan’s second approximation for the longitude of the ellipse. In this manner, we can obtain the perimeter of any transversal curve pertaining to the said form as a function of the radius of the directrix and the position of the ellipse’s center on the X-axis. Integrating the so-found perimeters of the differential strips for the whole span of the conoid, an unexpected solution emerges through the newly found number psi (ψ) which seems like a refined approximation to the third decimal of Pi but derived from a definite integral equation. As the strips are in truth slanted in the symmetry axis, their width is not uniform and we need to perform some adjustments in order to complete the problem with sufficient precision, but this is discussed separately in the annexes. Relevant implications for mathematical symmetry applied to multifarious architectural and engineering forms can be derived from this finding

The mechanism of sex determination and differentiation in animals remains a central focus of reproductive and developmental biology research, and the regulation of sex differentiation in amphioxus remains poorly understood. Cytochrome P450 Family 19 Subfamily A member 1 (CYP19A1) is a crucial sex differentiation gene that catalyzes the conversion of androgens into estrogens. In this study, we identified two aromatase-like genes in amphioxus: cyp19-like1 and cyp19-like2. Cyp19-like1 is more primitive and may represent the ancestral form of cyp19 in zebrafish and other vertebrates. Cyp19-like2, on the other hand, is likely the result of gene duplication within am-phioxus suggesting its potential role as a key gene in sex differentiation. To gain further insights into the expression patterns of these two aromatase-like, we examined their expression in different gonad tissues and during different stages of gonad development. While the expression patterns of the two genes differ in gonad tissues, both are highly expressed in the gonad primordium and are primarily localized to microsomal membrane systems. However, as development proceeds, their expression levels decrease significantly. This study enhances our understanding of sex dif-ferentiation mechanisms in amphioxus and provides valuable insights into the formation and evolution of sex determination mechanisms in vertebrates.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANGPT1, CASR, and PTK2 were examined in myoma and peripheral tissues samples taken from women after myoma surgery and in normal uterine muscle tissue samples in the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANGPT1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CASR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. PTK2 expression was also lower in the myoma and periphery com-pared to healthy uterine myometrium. Calcium supplementation could have an effect on stop-ping the growth of myomas.

Research on Cas9 nucleases from different organisms holds great promise for advancing genome engineering and gene therapy tools as it could provide novel structural insights into CRISPR editing mechanisms, expanding its application area in biology and medicine. The current study focuses on generating a construct to express a compact Cas9 nuclease (AnoCas9) from the thermophilic microorganism Anoxybacillus flavithermus. Next, distinctive AnoCas9 properties are investigated. AnoCas9 gene is expressed in E.coli producing a polypeptide fused with the maltose-binding protein (MBP-AnoCas9). His-Tag in its structure enables purification using metal-chelate chromatography followed by the cleavage of the polypeptide by TEV protease. Bioinformatical analysis of the CRISPR array found in the genome of an Anoxybacillus flavithermus strain helps predict a functional PAM sequence for AnoCas9, which is supported by in vitro experiments. The purified protein demonstrates nuclease activity in the presence of crRNA:tracrRNA duplex in the 37-60 °С range, with maximum activity observed at 45-55 °С. The analysis of FAM-labeled dsDNA substrate cleavage has allowed us to determine the functional AnoCas9 PAM motif as 5’-NNNNCDAA-3’. Thus, AnoCas9 adds to the repertoire of thermophilic Cas9 effectors and its properties suggest application in areas requiring the presence of thermostable CRISPR/Cas systems.

Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, recur-rence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with ominous prognosis and chemotherapy resistance, but the role of DNMTs in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that DNMT1, DNMT3A, DNMT3B and DNMT3L RNA levels were higher and DNMT2 lower in tumors compared to non-neoplastic tissue, and DNMT3A and DNMT2 expression decreased from Stage II to Stage IV carcinomas. Proteomic data also suggested that DNMT1 and DNMT3A levels were increased in tumors. Similarly, DNMT1, DNMT3A and DNMT3L protein levels were overex-pressed and DNMT2 expression was reduced in high grade carcinomas compared to non-neoplastic tissue and low-grade tumors. Moreover, DNMT1 and DNMT3L were increased in relapsed tumors compared to their primaries. DNMT3A, DNMT1 and DNMT3B mRNA lev-els were correlated with overall survival. Conclusions: Our study demonstrates that DNMT1 and DNMT3L are upregulated in primary high grade EOC and further increase in relapses, whereas DNMT3A is upregulated only in the earlier stages of cancer progression. DNMT2 downregulation highlights a presumptive tumor-suppressor activity of this gene in ovarian car-cinoma.

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs, and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area, using the following cut-offs: 0%; <5%; 5-9%; and 10-50%. PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections, using the SP142 and 22C3 antibodies. Results: 82% of the sixty-six patients were hormone receptor-positive; 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs were present in 64% (1%) of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of 1%, and 28% had a positive PD-L1 score of 1 using the 22C3 antibody. There was no correlation of sTILs or PD-L1 expression with tumor size, tumor grade, nodal status, expression of estrogen receptor (ER) or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression, however this was not associated with survival benefit. Additional large trials are needed to understand the immune infiltration in lobular cancer, even more in the pleomorphic subtype.

Normal function of placental extravillous trophoblasts (EVTs), which are responsible for uteroplacental vascular remodeling, is critical for adequate delivery of oxygen and nutrients to the developing fetus and normal fetal programming. Proliferation and invasion of spiral arteries by EVTs depends upon adequate levels of folate. Multidrug resistance-associated protein 1 (MRP1), which is an efflux transporter, is known to remove folate from these cells. We hypothesized that palmitic acid increases MRP1-mediated folate removal from EVTs, thereby interfering with EVTs’ role in early placental vascular remodeling. HTR-8/SVneo and Swan-71 cells, first trimester human EVTs, were grown in the absence or presence of 0.5 mM and 0.7 mM palmitic acid, respectively, for 72 h. Palmitic acid increased ABCC1 gene expression and MRP1 protein expression in both cell lines. The rate of folate efflux from the cells into the media increased with a decrease in migration and invasion functions in the cultured cells. Treatment with N-acetyl cysteine (NAC) prevented the palmitic acid mediated upregulation of MRP1 and restored invasion and migration in the EVTs. Finally, in an ABCC1 knockout subline of Swan-71 cells, there was a significant increase in invasion and migration functions. The novel finding in this study that palmitic acid increases MRP1-mediated folate efflux provides a missing link that helps to explain how maternal consumption of saturated fatty acids compromises the in-utero environment.

The COVID19 coronavirus SARS-CoV2 spreading in Wuhan and now worldwide has been shown to use angiotensin-converting enzyme 2 ACE2 as its host cell receptor, like the severe acute respiratory syndrome coronavirus (SARS-CoV). Epidemiology studies found different sex and age groups have different susceptibility to infection, and very skewed severity and mortality of the virus infection, with male, old age, and comorbidity being the most inflicted. Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found significantly higher expression in Asian females compared to males and other ethnic groups, an age dependent ACE2 expression decrease and a highly significant decrease in type II diabetic patients. Consistently, the most significant expression quantitative loci (eQTLs) contributing to high ACE2 expression are close to 100% in East Asians, >30% higher than other ethnic groups. Together with the shockingly common enrichment of viral infection pathways among ACE2 anti-expressed genes, binding of virus infection-related transcription factors at ACE2 regulatory regions, the repression of ACE2 expression by inflammatory cytokines and by type 2 diabetes, and the induction by estrogen and androgen (both decrease with age) established a negative correlation between ACE2 expression and CovID19 fatality at both population and molecular levels. Our results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general.

CCCTC-binding factor (CTCF) is a conserved transcription factor that performs diverse roles in transcriptional regulation and chromatin architecture. Cancer genome sequencing reveals diverse acquired mutations in CTCF, which we have shown, functions as a tumour suppressor gene. While CTCF is essential for embryonic development, little is known of its absolute requirement in somatic cells and the consequences of CTCF haploinsufficiency. We examined the consequences of CTCF depletion in immortalised human and mouse cells using shRNA knockdown and CRISPR/Cas9 genome editing and examined the growth and development of heterozygous Ctcf (Ctcf^+/-) mice. We also analysed the impact of CTCF haploinsufficiency by examining gene expression changes in CTCF-altered endometrial carcinoma. Knockdown and CRISPR/Cas9-mediated editing of CTCF reduced the cellular growth and colony-forming ability of K562 cells. CTCF knockdown also induced cell cycle arrest and a pro-survival response to apoptotic insult. However, in p53 shRNA-immortalised Ctcf^+/- MEFs we observed the opposite: increased cellular proliferation, colony formation, cell cycle progression and decreased survival after apoptotic insult compared to wild type MEFs. CRISPR/Cas9-mediated targeting in Ctcf^+/- MEFs revealed a predominance of in-frame microdeletions in Ctcf in surviving clones, however protein expression could not be ablated. Examination of CTCF mutations in endometrial cancers showed locus-specific alterations in gene expression due to CTCF haploinsufficiency, in concert with downregulation of tumour suppressor genes and upregulation of estrogen-responsive genes. Depletion of CTCF expression imparts a dramatic negative effect on normal cell function. However, CTCF haploinsufficiency can have growth-promoting effects consistent with known cancer hallmarks in the presence of additional genetic hits. Our results confirm the absolute requirement for CTCF expression in somatic cells and provide definitive evidence of CTCF’s role as a haploinsufficient tumour suppressor gene. CTCF genetic alterations in endometrial cancer indicate that gene dysregulation is a likely consequence of CTCF loss, contributing to, but not solely driving cancer growth.

Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD20, CD22, CD23, CD5, and CD81 serve as reliable prognostic indicators and disease progression factors in CLL. The human leukocyte antigen (HLA) system is a critical genetic variable in many diseases, with well-documented associations between HLA and various cancers. This study aims to investigate, for the first time, potential connections between HLA typing and CD marker expression in CLL. Despite being one of the most prevalent neoplasms in developed regions, there is a need for biomarkers that can improve survival predictions and identify possible genetic determinants. Methods: This study included 66 CLL patients and 100 controls, with all samples analyzed using biochemical methods, flow cytometry, and cytomorphology. Next-generation sequencing (NGS) was performed for HLA typing. Results: The results indicate that several CD markers are statistically associated with different HLA alleles. Specifically, CD20 was associated with HLA-DRB1*11:04:01; CD45 with HLA-C*07:01:01; CD79b with HLA-DPA1*02:01:02; CD23 with HLA-B*39:01:01; CD43 with HLA-DRB1*15:01:01; CD22 with HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02, and HLA-DRB1*07:01:01; and CD81 with HLA-DPB1*04:02:01, HLA-DQA1*01:04:01, and HLA-DQB1*05:03:01.Conclusion: In conclusion, this research demonstrates significant statistical links between HLA genes and immunophenotypic markers in CLL patients, shedding new light on the immunological context of CLL.

3D cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to have anticancer effects in various types of cancer. In this work, B16F1 mouse melanoma cell line was used, from which two-dimensional (2D) monolayer cultures and three-dimensional (3D) organoids were carried out using the hanging drop technique. The expression of p62 was determined by western blot and immunofluorescences. Our results indicate that pentoxifylline reduces p62 expression in both types of culture. While Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.

Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with myeloid-derived suppressor cells (MDSCs) in tumor microenvironments regulates cancer progression. Immunodeficient mice lacking T cells are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The xenograft tumor microenvironment, comprising human cancer and mouse host cells, exhibits more complex bidirectional signaling and function than a syngeneic tumor microenvironment. Here human and mouse colorectal cancer cells were transplanted into nude mice to elucidate differences in macrophage, DC, and MDSC functions in human xenograft and mouse allograft tumor models. Plasma interferon-γ and interleukin-18 concentrations in the former model after intraperitoneal lipopolysaccharide (LPS) administration were significantly higher than those in the latter model and non-transplanted control group. Splenic MHC class I, II, and CD80 expression increased in CD11b+ and MDSC populations after LPS administration in only the xenograft tumor model. The number of CD80- and MRC1-expressing cells decreased upon LPS administration in only the xenograft tumor. These results suggxest that macrophages and DCs function normally in xenograft tumor models, whereas their functions in response to LPS administration vary in allograft tumor models.

Apomictic plants (reproducing via asexual seeds), unlike sexual individuals, avoid meiosis and egg cell fertilization. Consequently, apomixis is very important for fixing maternal genotypes in the next plant generations. Despite the progress in the study of apomixis, molecular and genetic regulation of the latter remains poorly understood. So far APOLLO (Aspartate Glutamate Aspartate Aspartate histidine exonuclease) is one of the very few described genes associated with apomixis in Boechera species. The centromere-specific histone H3 variant encoded by CENH3 gene is essential for cell division. Mutations in CENH3 disrupt chromosome segregation during mitosis and meiosis since the attachment of spindle microtubules to a mutated form of the CENH3 histone fails. This paper presents in silico characteristic of APOLLO and CENH3 genes, which may affect apomixis. Also, we characterize the structure of CENH3, study expression levels of APOLLO and CENH3 in gynoecium/siliques of the natural diploid apomictic and sexual Boechera species at the stages of before and after fertilization. While CENH3 was a single copy gene in all Boechera species, the APOLLO gene have several polymorphic alleles associated with sexual and apomictic reproduction in the Boechera genera. Expression of the APOLLO apo-allele during meiosis was upregulated in gynoecium of apomict B. divaricarpa downregulating after meiosis until 4th day after pollination (DAP). On the 5th DAP, expression in apomictic siliques increased again. In sexual B. stricta gynoecium and siliques APOLLO apo-allele did not express. Expression of the APOLLO sex-allele during and after meiosis in gynoecium of sexual plants was several times higher than that in apomictic gynoecium. However, after pollination the sex-allele was downregulated in sexual siliques to the level of apomicts and increased sharply on the 5th DAP, while in apomictic siliques it almost did not express. At the meiotic stage, the expression level of CENH3 in the gynoecium of apomicts was two times lower than that of the sexual Boechera, decreasing in both species after meiosis and keep remaining very low in siliques of both species for several days after artificial pollination until the 4th DAP, when the expression level raised in sexual B. stricta siliques exceeding 5 times the level in apomictic B. divaricarpa siliques. We also discuss polymorphism and phylogeny of the APOLLO and CENH3 genes.

The article aims to present an alternative perspective on the relativistic expression of energy. This perspective is based on the virtual use of a Dempster mass spectrometer. In this spectrometer, it is possible to simulate Alfred Bucherer's experiment and conclude, using Lienard's relativistic equation, that the classical expression of energy predicted by Special Relativity is a more complete expression than the one presented by high school and college physics textbooks.

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. Also, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated a catalogue of differentially expressed human transcripts encoded by 289 genes in 41 human tissues from 838 adult individuals of the Genotype-Tissue Expression project (GTEx, v8 release) and focused our analysis on relevant transcripts implicated in drug response. We have detected significant sex-differentiated expression of 99 transcripts encoded by 59 genes in the tissues most relevant for human pharmacology (Liver, Lung, Kidney, Small intestine terminal ileum, Skin not sun-exposed, and Whole Blood). Among them, as expected, we observed significant differences in the expression of transcripts encoded by the cytochromes in the liver, CYP2B6, CYP3A7, CYP3A5, and CYP1A1. Our systematic investigation on differences between male and female in the expression of drug response related genes, reinforce the need to overcome the sex bias of clinical trials.

The Brassica family contains several economically important crops, including rapeseed (Brassica napus, 2n = 38, AACC), the second largest source of seed oil and protein meal worldwide. However, research in rapeseed is hampered because it is complicated and time-consuming for researchers to access different types of expression data. We therefore developed the Brassica Expression Database (BrassicaEDB, https://biodb.swu.edu.cn/brassica/) for the research community. We conducted RNA sequencing (RNA-Seq) of 103 tissues from rapeseed cultivar ZhongShuang11 (ZS11) at seven developmental stages (seed germination, seedling, bolting, initial flowering, full-bloom, podding, and maturation). We determined the expression patterns of 101,040 genes via FPKM analysis and displayed the results using the eFP browser. We also analyzed transcriptome data for rapeseed from 70 BioProjects in the SRA database and obtained three types of expression level data (FPKM, TPM, and read counts). We used this information to develop the BrassicaEDB, including eFP, Treatment, Coexpression, and SRA Project modules based on gene expression profiles and Gene Feature, qPCR Primer, and BLAST modules based on gene sequences. The BrassicaEDB provides comprehensive gene expression profile information and a user-friendly visualization interface for Brassica crop researchers. Using this database, researchers can quickly retrieve the expression level data for target genes in different tissues and in response to different treatments to elucidate gene functions and explore the biology of rapeseed at the transcriptome level.

The material derivative is important in continuum physics. This Letter shows that the expression $\frac{d }{dt}=\frac{\partial }{\partial t}+(\bm v\cdot \bm \nabla)$, used in most literature and textbooks, is incorrect. The correct expression $ \frac{d (:)}{dt}=\frac{\partial }{\partial t}(:)+\bm v\cdot [\bm \nabla (:)]$ is formulated. The solution existence condition of Navier-Stokes equation has been proposed from its form-solution, the conclusion is that "\emph{The Navier-Stokes equation has a solution if and only if the determinant of flow velocity gradient is not zero, namely $\det (\bm \nabla \bm v)\neq 0$.}"

Galectins constitute an evolutionarily conserved family of β-galactoside-binding proteins. They regulate innate and adaptive immunity and homeostasis. Expression of Galectins may regulate periparturient immune suppression. Galectin gene expression was studied in goat blood during the periparturient period. Body weight, body condition and FAMACHA scores, and fecal and blood samples were collected from Five BoerXSpanish goats at 14 days and 7 days after parturition. Fecal samples were used to assess parasite load. Total RNA was isolated from blood using Trizol and converted to cDNA for real-time PCR using specific primers for goat LGALs-1, -2, -3, -4, -7, -8, -9, -11, -12, -14, -15, -16, and ligand Gal3bp, T-cell immunoglobulin domain, and mucin domain 3(TIM-3). Beta-actin and GAPDH housekeeping genes were used as internal controls. Fold changes in transcript abundance were compared to non-pregnant goats and calculated using the Livak method. Secretion of GALS-1, -3 and -9 in plasma was detected using ELISA. Data were analyzed using SAS 9.4 and Pearson correlations (p<0.05). Galectins were expressed and correlated to changes in leukocytes and fecal egg counts. Secreted GALS-1 decreased and GALS-3 and -9 increased (p<0.05) postpartum. Differential expression of Gal may have functional implications in animal health and homeostasis and needs further study.

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells. We measured Nlgn3 mRNA neuronal and glial expression via quantitative 3-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single cell RNA sequencing (scRNASeq) data to assess for Nlgn3, Nlgn1, Nlgn2 and their binding partners, Nrxn1-3, MGDA1 and MGDA2, in enteric neural subsets. Most submucosal and myenteric neurons expressed Nlgn3 mRNA. In contrast to other Nlgns and binding partners, Nlgn3 was strongly expressed in enteric glia, suggesting a role for Neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces Nlgn3 mRNA expression in cholinergic but not VIPergic submucosal neurons. In the myenteric plexus, Nlgn3 mRNA levels are reduced in calretinin and NOS labelled neurons and S100ß labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in Nlgn3, which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.

Chemically modified forms of tetraiodothyroacetic acid (tetrac), an L-thyroxine derivative, have been shown to exert their anticancer activity at plasma membrane integrin αvβ3 of tumor cells. Via a specific hormone receptor on the integrin, tetrac-based therapeutic agents modulate expression of genes relevant to cancer cell proliferation, survival and energy metabolism. P-bi-TAT, a novel bivalent tetrac-containing synthetic compound has anticancer activity in vitro and in vivo against Glioblastoma Multiforme (GBM) and other types of human cancers. In the current study, microarray analysis was carried out on a primary culture of human GBM cells exposed to P-bi-TAT (10-6 tetrac equivalent) for 24 h. P-bi-TAT significantly affected expression of a large panel of genes implicated in cancer cell stemness, growth, survival, and angiogenesis. Recent interest elsewhere in ATP synthase as a target in GBM cells caused us to focus attention on expression of genes involved in energy metabolism. Significantly downregulated transcripts included multiple energy metabolism-related genes: electron transport chain genes ATP5A1 (ATP synthase 1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase [ubiquinone] FA8), NDUFV2I and other NDUF genes. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Qualitatively similar actions of P-bi-TAT on expression of energy metabolism-linked genes were also detected in established human GBM and pancreatic cancer cell lines. In conclusion, acting at αvβ3 integrin, P-bi-TAT caused downregulation in human cancer cells of expression of a large number of genes involved in electron transport and oxidative phosphorylation. These observations suggest that cell surface thyroid hormone receptors on αvβ3 regulate expression of genes relevant to tumor cell stemness and energy metabolism.

Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising biomarkers and therapeutic targets for these conditions. This systematic review conducts a thorough analysis of the literature, with a specific focus on investigating miRNA expression patterns in patients with CAD and hypertension. The review encompasses an unspecified number of eligible studies that employed a variety of patient demographics and research methodologies, resulting in diverse miRNA expression profiles. This review highlights the complex involvement of miRNAs in CAD and hypertension and the potential for advances in diagnostic and therapeutic strategies. Future research endeavours are imperative to validate these findings and elucidate the precise roles of miRNAs in disease progression, offering promising avenues for innovative diagnostic tools and targeted interventions.

Immunotherapy, particularly Immune Checkpoint Blockade (ICB), has demonstrated significant efficacy in treating melanoma in recent years. However, accurately predicting treatment success and avoiding ineffective therapies remains an unresolved challenge. Therefore, this study aims to develop statistical models utilizing neural networks to forecast the effectiveness of immune checkpoint therapies for melanoma patients. Our models primarily rely on Artificial Neural Networks (ANN) to anticipate both Overall Survival (OS) and Progression-Free Survival (PFS) among melanoma patients undergoing anti-CTLA4 and anti-PD1/anti-PDL1 therapy. We incorporate gene expression data, measured in Transcripts per Million (TPM), derived from bulk tumor RNA-sequencing datasets. Additionally, clinical variables such as gender, age, and treatment type are factored into our analysis. The ANN underwent optimization to attain the highest feasible precision in anticipating the predetermined survival outcome. Issues stemming from high-dimensional data, such as overfitting, were tackled through regularization and feature selection methods. Consequently, the ANN-based model incorporating feature selection exhibited the capacity to forecast survival (PFS) in response to ICB therapy with a maximal precision of 86%. Conversely, the ANN lacking feature selection but incorporating regularization achieved accuracies of up to 72% for PFS and 71% for OS, correspondingly. In order to confront the challenge posed by limited patient samples and to assess replicability, the model underwent training and validation based on the amalgamation of all five datasets. However, this amalgamation failed to enhance predictive performance, necessitating further investigations.

Accurate and robust deep learning models for facial expression recognition are challenging to achieve, given the diversity of human faces and variations in images, including different facial poses and lighting conditions. In this work, we proposed a clock-driven convolutional Spiking Neural Network (SNN) and STDP fine-tune architecture, meticulously calibrated its hyperpa-rameters, and experimented with various optimization methods. The best model resulted was trained and evaluated on the Fer2013 and FER+ database, obtaining an accuracy of 61.87% and 79.97% without requiring auxiliary training data or face registration. To our best knowledge, the proposed SNN achieved comparable accuracy to CNNs of similar depth and possessed advantages of low energy consumption and high computational efficiency. The computational efficiency of the proposed SNN is approximately three times that of CNNs. Along with this, we introduced the very recent cumulative spike guided encoder visualization technique and revealed the strong encoding capability of the proposed SNN.

Chronic lymphocytic leukemia (CLL) is characterized by dysfunctional B cells. Immune checkpoint molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and programmed death-1 (PD-1) are upregulated in patients with CLL and may correlate with prognostic markers such as beta-2 microglobulin (B2M). The aim of this study was to evaluate the levels of immune checkpoints on B-cell subsets and to further correlate them with B2M levels in patients with CLL. We recruited 21 patients with CLL and 12 controls. B cell subsets and the levels of immune checkpoint expression were determined using conventional multi-color flowcytometry. Basal levels of B2M in patients with CLL were measured using an Enzyme-linked immunosorbent assay. Patients with CLL had increased levels of activated B cells when compared to the control group, p< 0.001. The expression of PD-1 and CTLA-4 were increased on activated B cells and memory B cells, p< 0.05. There were no associations between B2M levels and the measured immune checkpoints on B cell subsets, after adjusting for sex and age. African patients with CLL express elevated levels of PD-1 and CTLA-4 immune checkpoints on activated and memory B cell subsets. However, there is no correlation between these immune checkpoint expressions and B2M levels.

(1) Background: We comprehensively evaluated the expression of therapeutically targetable immune checkpoint molecules on celiac disease. We have focused on the alteration of the CD200/CD200R pathway and Elafin expression in celiac disease and discussed their roles in regulating the immune response. There are limited data related to the expression or function of these molecules in celiac disease. This finding could significantly contribute to the understanding of the clinical manifestation of celiac disease; (2) Methods: CD200, CD200R and Elafin distribution was determined by ELISA and immunohistochemistry analyses in serum and biopsies of CD patients. Analyses of Th1 and Th17 cytokines were determined. PCR amplification of a fragment of the PI3 gene was carried out using genomic DNA isolated from whole blood samples of the study subjects. Different aliquots of the PCR reaction product were subjected to RFLP analysis for SNP genotyping and detection; (3) Results: We characterized the expression and function of the CD200–CD200R axis and PI3 in celiac disease. A significantly higher level of soluble CD200, CD200R and lower expression of PI3 in serum of CD patients was observed compared to healthy controls. Consistent with our results, CD200 expression is regulated by IFN-gamma. Interaction of CD200/CD200R leads to production of type Th1 and Th17 cytokines. Regarding the PI3 genotype, the CT genotype proportion SNP rs1733103 and the GG genotype SNP rs41282752, were predominant in CD patients. SNP rs1733103 showed a significant association between the SNP variables and CD; (4) Conclusions: In celiac disease the immune checkpoint is compromised or dysregulated, which can contribute to inflammation and the autoimmunity process. The study of these checkpoint points will led to the development of targeted therapies aimed at restoring immunological balance in CD. Specific coding regions of the PI3 gene splice variants predispose the Elafin protein, both at the transcriptional and post-translational levels, to modify its expression and function, resulting in reduced differential functional protein levels in patients with active celiac disease.