To examine the role of RNA silencing in defense against viroid, a Dicer-like 2 and 4 (DCL2&4)—double knockdown transgenic tomato line 72E was created. The expression of endogenous DCL2 and DCL4 in line 72E decreased to about a half of the empty cassette line EC. When challenged with potato spindle tuber viroid (PSTVd), 72E allowed significantly higher level of PSTVd accumulation early in infection and showed lethal systemic necrosis. The size distribution of PSTVd-derived small RNA was significantly changed: the numbers of 21 and 22 nucleotides (nt) species in line 72E was approximately 66.7% and 5% of those in line EC, respectively. Conversely, the numbers of 24-nt species increased by 1100%. Furthermore, expression of miR398a-3p and miR398 increased 770–868% in the PSTVd-infected 72E, compared to the PSTVd-infected EC. In parallel, superoxide dismutase (SOD1) in PSTVd-infected 72E showed higher expression levels. In concert with miR398a-3p, SOD1 controls detoxification of reactive oxygen species (ROS) generated in cells. Since high levels of ROS production and its scavenging activity were observed in PSTVd-infected 72E, the lack of full-activity of DCLs was thought to have made the plant incapable to control excessive ROS production and thus resulted in to develop lethal systemic necrosis.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotics carbenicillin on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of gram-positive and gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

In potato, high levels of nitrogen (N) can lead to excessive vegetative growth at the expense of tuber development, resulting in lower yield and poor quality tubers. We found that Solanum tuberosum CLE4 (StCLE4) is expressed most strongly in the roots on N-rich media and positively regulates root growth of potato in N-deficient conditions. We noted that StCLE4 functions as a negative regulator of normal shoot apex development similar to CLV3 in Arabidopsis. Transcriptomic analysis revealed that overexpression of StCLE4 results in repression of the StIT1 gene, a regulator of potato tuber initiation. Overexpressing StCLE4 stolons were transformed into branches that were similar to milder it1 phenotype. We also found that NIN-like proteins, key regulators of nitrate signaling, bind to the regulatory sequence of StIT1 in yeast one-hybrid assay. Taken together, our findings suggest that StCLE4 regulates shoot, root and stolon growth in potato.

Coffee processing generates a huge amount of waste which contains many natural products. Here, we report the discovery of a panel novel cell-penetrating and metal-ion binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and database search, we showed that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif but without a chitin-binding domain. NMR determination of cC1a revealed a compact structure that confers it resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis revealed that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement like ginsentide precursors. Molecular modeling together with experimental validation revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, and which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have potential to target intracellular proteins.

Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1_total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1_total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.

Introduction: A plethora of biological molecules regulate chondrogenesis in the epiphyseal growth plate. Disruptions of quantity and function of these molecules can manifest clinically as stature abnormalities of various etiologies. Traditionally, the growth hormone/insulin-like growth factor 1 (IGF1) axis represents the etiological center of final stature attainment. Of note, little is known about the molecular events that dominate the growth of the craniofacial complex and its correlation with somatic stature. Aim: Given the paucity of the relevant data, this review discusses available information regarding potential applications of lateral cephalometric radiography as a potential clinical indicator of genetic short stature in children. Materials and Methods: A literature search was conducted in the PubMed electronic database using the key words: cephalometric analysis and short stature; cephalometric analysis and achondroplasia; cephalometric analysis and hypochondroplasia; cephalometric analysis and skeletal abnormalities; cephalometr* and SHOX; cephalometr* and CNP; cephalometr* and ACAN; cephalometr* and CNVs; cephalometr* and IHH; cephalometr* and FGFR3; cephalometr* and Noonan syndrome; cephalometr* and “Turner syndrome”; cephalometr* and achondroplasia. Results: In individuals with genetic syndromes causing short stature, linear growth of the craniofacial complex is confined, following the pattern of somatic short stature regardless of its etiology. The angular cephalometric measurements differ from the average height normal individuals and are suggestive of a posterior placement of the jaws and a vertical growth pattern of the face. Conclusion: The greater part of the existing literature regarding cephalometric measurements in short statured children with genetic syndromes provides qualitative data. Furthermore, cephalometric data for individuals affected with specific rare genetic conditions causing short stature, should be the focus of future studies. These quantitative data are required to potentially establish cut-off values to refer for genetic testing based on craniofacial phenotypes.

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy-resistance pathways. The growth hormone (GH) – GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer, and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC. Combinations of gemcitabine with different GHR antagonists (GHRAs) markedly improve therapeutic outcomes in nude mice xenografts. Employing cultured cells, mouse xenografts, and analyses of the human PDAC transcriptome, we identified that attenuation of the multidrug transporter and epithelial-to-mesenchymal transition programs in the tumors underlie the observed augmentation of chemotherapy efficacy by GHRAs. Moreover, in human PDAC patients, GHR expression strongly correlates with a gene signature of tumor-promotion and immune-evasion, which corroborate with that in syngeneic tumors in wild-type vs. GH transgenic mice. Overall, we found that GH action in PDAC promoted a therapy-refractory gene signature in vivo, which can be effectively attenuated by GHR antagonism. Our results collectively present a proof of concept towards considering GHR antagonist to improve chemotherapeutic outcome in the highly chemoresistant PDAC.

This article will continue ansatz gage matrix of Iyer Markoulakis Helmholtz Hamiltonian mechanics points’ fields gage to Pauli Dirac monopole particle fields ansatz gage general formalism at Planck level, by constructing a Pauli Dirac Planck circuit matrix field gradient of particle monopole flow loop. This circuit assembly gage (PDPcag) that maybe operating at the quantum level, demonstrates the power of point fields matrix theoretical quantum general formalism of Iyer Markoulakis Helmholtz Hamiltonian mechanics transformed to Coulomb gage metrics, to form eigenvector fields of magnetic monopoles as well as electron positron particle gage metrics fields. Eigenvector calculations performed based on Iyer Markoulakis quantum general formalism are substituted for gage values of typical eigenvectors of dipolar magnetically biased monopoles with their conjugate eigenvectors, as well as eigenvector fields that are of the electron and positron particles. Then they are compiled to form combinatorial eigenvector matrix bundle of the monopole particle circuit field constructs assembly. Evaluation of this monopole particle fields matrix provided eigenvector fields results like SUSY, having Hermitian quantum matrix with electron-positron annihilation alongside north and south monopoles collapsing to dipolar “stable” magnetism, representing electromagnetic gaging typical metrics fields. Applying experimental observations on magnetic poles with measuring magnetic forces John Hodge’s results were showing asymmetrical pole forces; author has mathematically constructed asymmetric\strings\gage\metrics to characterize electromagnetic gravity, putting together while integrating with stringmetrics gravity that author has been reporting in earlier published articles. Physical Analysis with generalization of mass-charge and charge-fields gage metrics to quantum relativity gage metrics fields are proposed based on author’s proof formalism paper providing derivational algorithmic steps, to determine gage parametric values within the equation of Coulomb gage. Vortex fields’ wavefunctions and the scalar potential characterized by a function and a coupling constant having quantum density matrix together define the gage metrics quantifiable observable measurement physics of electron-positron cross-diagonal fields; contrastingly, diagonal terms of PDPcag matrix characterizes electron-positron particle eigenvector fields, while Hilbert Higgs mass metrics characterizes eigen-matter. Author is already working with Christopher O’Neill about magic square symmetry configurations to quantitatively understand symmetry, structure, and the real space geometry that are expected to form out of vacuum quanta point fields’ quantitative quantum general formalism theory of Iyer Markoulakis. In addition, author is currently collaborating with Manuel Malaver’s astrophysical Einstein Minkowski modified space time metrics evaluations of the sense-time-space relativistic general metrics to have means to account for curving or shaping of spacetime topology of a five-dimensional sense-time-space. Manuel Malaver’s specialization with modified Einstein Maxwell equations for modeling galaxies and stars cosmological physics, utilizing Einstein-Maxwell-Tolman- Schwarzschild and Reissner-Nordström spacetime and black holes theoretical formalisms have author of this paper collaboratively model quantum astrophysics of dark energy Star’s theory with Einstein-Gauss-Bonnet gravity equations.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is reasonable epidemiological cohort data to recommend surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommend that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) should consider HCC surveillance. NITs include fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), can help to identify high risk of incident HCC in NAFLD patients. Innovative parameters including Mac-2 binding protein glycated isomer , type IV collagen 7S, free apoptosis inhibitor of macrophage, combination of single nucleoside polymorphisms are expected to be established. Considering a large number of NAFLD population, optimal screening tests must meet several criteria including high sensitivity, cost effectiveness and availability.

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), may increase LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed de-identified electronic health records of 1,040,341 T2DM patients treated between 2005-2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Hypercholesterolemia accelerates atherosclerosis, and extensive research has been undertaken to ameliorate this abnormality. Plant sterols have been shown to inhibit cholesterol absorption and lower plasma cholesterol level since the 1950s. This ingredient has recently been reappraised as a food additive that can be taken daily in a preclinical period to prevent hypercholesterolemia, considering that cardiovascular-related diseases are the top cause of death globally even with clinical interventions. Intestinal cholesterol handling is still elusive, making it difficult to clarify the mechanism for plant sterol-mediated inhibition. Notably, although the small intestine absorbs cholesterol, it is also the organ that excretes it abundantly, via trans-intestinal cholesterol efflux (TICE). In this review, we show a model where the brush border membrane (BBM) of intestinal epithelial cells stands as the dividing ridge for cholesterol fluxes, making cholesterol absorption and TICE inversely correlated. With this model, we tried to explain the plant sterol-mediated inhibitory mechanism. As well as cholesterol, plant sterols diffuse into the BBM but are effluxed back to the lumen rapidly. We propose that repeated plant sterol shuttling between the BBM and lumen promotes cholesterol efflux, and plant sterol in the BBM may disturb the trafficking machineries that transport cholesterol to the cell interior.

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population as well as an economic load to the health care system, yet treatments of these preventable cancers remain ineffective. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 1960s and 1980s. The increase in cases of NMSCs as well as the lack of effective treatments makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.

Radiation therapy (RT) is one of the main approaches of cancer therapy, including non-small cell lung cancer (NSCLC). Radiation-induced DNA double-stranded breaks (DSBs), single-stranded DNA breaks (SSBs) and oxidized nucleobases cause replication fork stalling, chromosomal instability or point mutagenesis and can lead to cell death. Translesion DNA synthesis (TLS) is one of the DNA damage tolerance (DDT) pathways promoting replication of damaged DNA. Here, we explored the effects of the knockout of primase-polymerase PRIMPOL (PRIMPOL −/−) and TLS polymerase POLI (POLI −/−) genes in two different monoclonal lines derived from human NSCLC A549 cells. Our study aimed to investigate the impact of their absence on the susceptibility of these cells to ionizing radiation (IR)-induced stress. Without IR, cells that do not have PRIMPOL or POLI experience a considerable rise in apoptosis by day 7 of continuous cultivation and a noteworthy decline in cell migration under spatial confinement when compared to the parental wild-type cells. Despite this, we have found that PRIMPOL −/− exhibited higher clonogenic survival compared to wild-type cell lines in response to IR stress. Both of these cell lines demonstrated remarkable resilience to radiation stress, surpassing the survival rate of the original A549 cells. POLI deficiency reduces cellular γH2AX foci accumulation, while the presence of highest number of γH2AX foci in PRIMPOL−/− cells was ATM-independent. We report for the first time that increased post-irradiation clonogenic survival of PRIMPOL −/− A549 cells might be associated with the increase of CD133+ but not CD44+ populations of cancer stem-like cells.

A reduced order model is developed to monitor aeroengines condition (defining their degradation from a baseline state) in real-time, by using data collected in specific sensors. This reduced model is constructed by applying higher order singular value decomposition plus interpolation to appropriate data, organized in tensor form. Such data are obtained using a detailed engine model that takes the engine physics into account. Thus, the method synergically combines the advantages of data-driven (fast online operation) and model-based (the engine physics is accounted for) condition monitoring methods. Using this reduced order model as surrogate of the engine model, two gradient-like condition monitoring tools are constructed. The first tool is extremely fast and able to precisely compute `on the fly’ the turbine inlet temperature, which is a paramount parameter for the engine performance, operation, and maintenance, and can only be roughly estimated by the engine instrumentation in civil aviation. The second tool is not so fast (but still reasonably inexpensive) and precisely computes both, the engine degradation and the turbine inlet temperature at which sensors data have been acquired. These tools are robust in connection with random noise added to the sensors data and can be straight forwardly applied to other mechanical systems.

This paper aims to present the basic assumptions for creation of social Fröhlich condensate and attract attention of other researchers (both from physics and socio-political science) to the problem of modelling of stability and order preservation in highly energetic society coupled with social energy bath of high temperature. The model of social Fröhlich condensation and its analysis are based on the mathematical formalism of quantum thermodynamics and field theory (applied outside of physics). The presented quantum-like model provides the consistent operational model of such complex socio-political phenomenon as Fröhlich condensation. The model of social Fröhlich condensation is heavily based on theory of open quantum systems. Its consistent elaboration needs additional efforts. Evidence of such phenomenon as social Fröhlich condensation is demonstrated by stability of modern informationally open societies Approaching the state of Fröhlich condensation is the powerful source of social stability. Understanding its informational structure and origin may help to stabilize the modern society. Application of the quantum-like model of Frhlich condensation in social and political sciences is really the novel and original approach to mathematical modeling of social stability in society exposed to powerful information radiation from mass-media and internet based sources.

Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

The new coronavirus SARS-CoV-2 is the cause of the COVID-19 pandemic, which has created an incomparable global health problem. PLpro is a key protein involved in viral polyprotein processing and immune system evasion, making it a prime target for the development of antiviral drugs to combat COVID-19. The review begins by elucidating the functional and structural properties of SARS-CoV-2 PLpro, underscoring its significance in viral pathogenicity and replication. Employing homology modeling, a tertiary structure model of PLpro is constructed, laying the groundwork for subsequent investigations. To expedite the search for potential therapeutic candidates, the study harnesses computational methodologies. Molecular docking techniques are employed to explore binding sites for antiviral drugs within the catalytic region of PLpro. This computational approach not only aids in drug development but also provides crucial preliminary data before experimental research commences. The stability of drug-PLpro complexes is assessed through comprehensive all-atom molecular dynamics (MD) simulations, affording dynamic insights into drug-PLpro interactions. By evaluating binding energy estimates from MD simulations, stable drug-PLpro complexes with potential antiviral properties are identified. However, it is emphasized that experimental validation is imperative to confirm these computational findings, necessitating in vitro and in vivo tests to assess safety and efficacy. This pivotal stage bridges the computational realm with real-world clinical applications. The review emphasizes the imperative need for enhancements in the existing PLpro-targeting drugs currently on the market. Their actions are insufficient for clinical use and necessitate thorough characterization and improvement. The Supervised Molecular Dynamics (SuMD) simulation technique reveals critical information about drug unbinding pathways, shedding light on opportunities for refinement. In addition to optimizing existing drugs, the investigation of sub-structurally similar molecules emerges as a promising avenue for drug development. In conclusion, the review underscores the pivotal role of targeting SARS-CoV-2 PLpro in the ongoing battle against COVID-19. By integrating molecular dynamics simulations, structural modeling, and computational insights, a robust foundation is established for identifying promising antiviral drug candidates. The continual need for improvement in existing drugs and the exploration of novel compounds remain paramount in the global effort to combat COVID-19. The evolution and management of COVID-19 hinge on the symbiotic relationship between computational insights and experimental validation, illustrating the interdisciplinary synergy crucial to this endeavor.

Expression of Krüppel–like factor 15 (KLF15), a stress induced transcription factor, is induced during bovine herpesvirus 1 (BoHV-1) reactivation from latency, and KLF15 stimulates BoHV-1 replication. Transient transfection studies revealed KLF15 and glucocorticoid receptor (GR) cooperatively transactivate the BoHV-1 immediate early transcription unit 1 (IEtu1), herpes sim-plex virus type 1 (HSV-1) infected cell protein 0 (ICP0), and ICP4 promoter. The IEtu1 promoter drives expression of bICP0 and bICP4, two key BoHV-1 transcriptional regulatory proteins. Based on these studies, we hypothesized infection is a stressful stimulus that increases KLF15 ex-pression and enhances productive infection. New studies demonstrated that silencing KLF15 impaired HSV-1 productive infection and KLF15 steady state protein levels were increased at late stages of productive infection. KLF15 was primarily localized to the nucleus following in-fection of cultured cells with HSV-1, but not BoHV-1. When cells were transfected with a KLF15 promoter construct and then infected with HSV-1, promoter activity was significantly increased. The ICP0 gene and to a lesser extent bICP0 transactivated the KLF15 promoter in the absence of other viral proteins. In contrast, BoHV-1 or HSV-1 encoded VP16 had no effect on KLF15 pro-moter activity. Collectively, these studies revealed HSV-1 and BoHV-1 productive infection in-creased KLF15 steady state protein levels, which correlated with increased virus production.

Premature ovarian insufficiency (POI) is a highly prevalent disorder, characterized by the development of menopause before age of 40. Most cases are idiopathic; however, in some women the cause of this condition (e.g. anticancer treatment, genetic disorders, and enzymatic defects) may be identified. Although hormone replacement therapy, the principal therapeutic approach for POI, helps to alleviate the related symptoms, this does not effectively solve the issue of fertility. Assisted reproductive techniques also lack efficacy in these women. Thus, the effective approach to manage the patients with POI is highly warranted. Several mechanisms, associated with POI, have been identified, including lack of FSH receptor functioning, alterations in the apoptosis control, mutations in Sal-like 4 genes, thymulin or basonuclin-1 deficiency etc. The above-mentioned may be good targets for gene therapy in order to correct defects, leading to POI. The goal of this review is to summarize the current experience on the POI studies, that employed gene therapy, and to discuss the possible future directions in this field.

Abstract: Background: We previously found that forest bathing significantly reduced the scores for negative emotions and in-creased the score for vigor in the profile of mood states (POMS) test in both males and females and increased the sero-tonin level in males, indicating the potential for beneficial effect on depressive status. In the present study, we investi-gated the effects of forest bathing on the levels of serotonin, oxytocin and insulin-like growth factor I (IGF-1) in blood, Self-Rating Depression Scale (SDS) scores, POMS, subjective fatigue symptoms and subjective sleep quality in female subjects with depression/depressive tendencies. Methods: Thirty-one female subjects aged 40.1±2.4 years with depression/depressive tendencies were recruited after obtaining informed consent. These subjects took day trips to a forest park, the birthplace of forest bathing in Japan named Akasawa Shizen Kyuyourin in Nagano Prefecture, and to a city area of Nagano Prefecture as a control in June 2023. On both trips, they walked 2.2-2.5 km for two hours each in the morning and afternoon on Saturday and Sunday, respectively. Blood was sampled in the afternoon before and after each trip. Concentrations of serotonin, oxytocin, IGF-1 and lactic acid in blood were measured. The SDS scores, POMS test, and questionnaires for subjective fatigue symptoms and subjective sleep quality were conducted before and after the trips. Ambient temperature and humidity were monitoring during the trips. The Nippon Medical School Central Ethics Committee approved this study. Results: Forest bathing significantly decreased SDS scores and the effect lasted for one week after forest bathing. Forest bath-ing also significantly increased the level of serotonin in serum in subjects who were not taking antidepressants, significantly increased the levels of oxytocin and IGF-1 in blood, significantly increased the scores for vigor-activity and friendliness and de-creased the scores for anger-hostility, confusion-bewilderment, fatigue-inertia, tension-anxiety, depression-dejection and total mood disturbance compared with city walking (all p

1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. 2) Methods: Here, we report the effects of long-term treatment with a SPM, maresin like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. 3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced astrogliosis and microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in an-ti-inflammatory Iba1+Arg-1+-M2 microglia, reduced astrogliosis-associated level of neuroin-flammatory TNF-α, inhibited phenotype switching of pro-inflammatory neurotoxic A1 astrocytes and N1 neutrophils, promoted polarization of inflammation-resolving neuroprotective A2 as-trocytes, promoted the blood–brain-barrier-associated tight-junction protein claudin-5 and de-creased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. 4) Conclusion: Long-term administration of MarL1 mit-igates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegen-eration. These findings provided the preclinical leads and mechanistic insights for the develop-ment of MarL1 into an effective modality to ameliorate AD pathogenesis.

Background and Aim. Since virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, post-hepatitis C virus (HCV) infection would be a cause for liver cirrhosis that would progress to HCC. Cytotoxic T cells (Tc) are known to be involved in post-HCV complications and HCC pathogenesis. The inhibitory checkpoint Leukocyte-Associated Immunoglobulin-like Receptor-1 (LAIR-1) is expressed on Tc. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression post-HCV and moreover, to evaluate LAIR-1 expression as a non-invasive biomarker for HCC progression in the context of liver cirrhosis post-HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. We studied LAIR-1 expression on Tc related to the progression of liver cirrhosis in a case-controlled study enrolled 64 patients with post-HCV G4-HCC and 37 patients with post-HCV G4-liver cirrhosis. Methods: LAIR-1 expression was analyzed by flow cytometry. Results: LAIR-1 expression on Tc and the percentage of Tc positive for LAIR-1 (LAIR-1+Tc %) were significantly higher in the post-HCV G4-HCC group compared to the post-HCV G4-liver cirrhosis

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

Cowpea chlorotic mottle virus (CCMV) is a plant virus explored as a nanotechnological platform. The robust self-assembly mechanism of its capsid protein allows for drug encapsulation and targeted delivery. Additionally, the capsid nanoparticle can be used as a programmable platform to display different molecular moieties. In view of future applications, efficient production and purification of plant viruses is a key step. In established protocols, the need for ultracentrifugation is a significant limitation due to cost, difficult scalability, and safety issues. In addition, the purity of the final virus isolate often remains unclear. Here, an advanced protocol for the purification of CCMV from infected plant tissue was developed, focusing on efficiency, economy, and final purity. The protocol involves precipitation with PEG 8000, followed by an affinity extraction using a novel peptide aptamer. The efficiency of the protocol was validated using size exclusion chromatography, MALDI-TOF mass spectrometry, reversed-phase HPLC, and sandwich immunoassay. It was demonstrated that the final eluate of the affinity column is of exceptional purity (98.4%) determined by HPLC and detection at 220 nm. The scale-up of our proposed method seems to be straightforward, which opens the way to the large-scale production of such nanomaterials. This highly improved protocol may facilitate the use and implementation of plant viruses as nanotechnological platforms for in vitro and in vivo applications.

Leukemia, contributing to 3% of all cancer cases in the United States, presents a significant challenge in treatment due to its diverse subtypes, each dis-playing unique genetic and molecular abnormalities. The aggressive growth of ab-normal blood cells compromises immune function and poses challenges in developing effective therapeutic approaches. Unlike solid tumors, surgical resection is not an option, limiting treatment strategies to chemotherapy, immunotherapy, and radiation therapy, which may be nonspecific and lead to organ damage and toxicity. Anthracyclines, widely used in hematological tumors, face limitations due to severe cardiotoxicity, causing progressive cardiomyopathy and, in severe cases, congestive heart failure. Heart failure incidence is significantly higher in cancer patients treated with anthracyclines over 5, 10, and 15 years. Early detection of left ventricular dysfunction and cardiotoxicity is crucial to mitigate progression to congestive heart failure (CHF) in this population. Recent research by Bayrón-Marrero et al. reveals that lower levels of plasma soluble TREM-Like Transcript-1 (s-TLT-1), a platelet-specific receptor, correlate with left ven-tricular dysfunction in cardiovascular disease patients. Those with s-TLT-1 levels ex-ceeding 544 pg/mL exhibit a significant association with congestive heart failure. These findings suggest the potential use of s-TLT-1 as a diagnostic screening tool for early detection and treatment of anthracycline-induced CHF in leukemia patients.

The part of this article dealing with topological insulators and topological superconductors was first written about two years ago - the ideas in the part about the topological universe originated six years ago or more. It’s rather strange that I never put the two parts together in writing before. My belief in unification is unshakeable - I’ve been convinced for years that the universe must be composed of topology. Since Earth is part of the cosmos, entanglement means it must have topological materials. The reverse is also true: topological materials on Earth are well known to science - so in a unification, space and time inevitably possess topological composition. Topological materials (topological insulators, topological superconductors) can be less mystifying if they’re related to the paradigm-shifting deterministic view of quantum mechanics which is described in the universal topology (the “rubber-sheet geometry” of the cosmos): see my previous submission “Hypothesis of Quantum Gravity - Resulting from a Static, Topological Universe Resulting from the Positives and Negatives of the Steady State and Big Bang Theories" at https://www.preprints.org/manuscript/202105.0239/v1 (the first section of this present article is a quick summary of the relevant parts).

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.

The implementation of morphing wing mechanisms holds promise in enhancing aircraft perfor-mance, as indicated in current literature. The Clean Sky 2 AirGreen 2 European project is currently conducting ground and wind tunnel tests to validate innovative studies on morphing wing structures. The project aims to showcase the effectiveness of these morphing architectures on a potentially flying demonstrator at true scale. This article describes design methodology and struc-tural testing of a scaled morphing flap structure capable of 3 different morphing modes required for low-speed (take-off/landing) and high-speed (cruise) conditions. A significant scale factor of 1:3 was selected to enhance the importance and relevance of the wind tunnel test campaign. Geometrical scaling to the real flap prototype was deemed impractical due to limitations associated with scaling the embedded mechanisms and actuators responsible for shape changing. Static analyses were performed using the finite element method to address the most critical loads determined through three-dimensional CFD analysis. The Finite Element (FE) analysis results were briefly outlined, and comparisons were drawn between the obtained results and the empirical data collected during the structural test. Good correlations were observed between the results and numerical predictions, encompassing static deflections under applied loads and elastic deformations. Consequently, the modeling approaches utilized during the design and testing phases were considered highly suc-cessful. Therefore, based on the results extrapolated from simulations under ultimate load condi-tions relevant to the wind tunnel test campaign, the scaled flap prototype was deemed suitable for testing.

In our recent publications, based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. In this paper, we make an attempt to understand and estimate the maximum binding energy associated with any mass number. It can be expressed as, for A > 4, $\left(BE\right)_A\cong \left[A-0.000935A^2-A^{1/3}-A^{-1/2}\right]$ MeV. We are working on refining the 4^th term with even-odd corrections, shell corrections and other microscopic corrections. Proceeding further, stable mass numbers and super heavy mass numbers can be understood with a relation of the form, $\left[\textrm{RoundOff}\left(\left(Z+2.9464\right)^{1.2}-1.7165\right)\right]\pm\left[0,1\right]\pm\left(2n\right)$ where $n \cong 0,1,2$. It needs a review with respect to even-odd proton numbers and other microscopic corrections.Very interesting point to be noted is that based on the concept of “binding energy per nucleon”, the most complicated Avogadro number and Unified atomic mass unit can be estimated in a unified approach.

Fusarium wilt of banana is a devastating disease that has decimated banana production worldwide. Host resistance to Fusarium oxysporum f. sp. cubense (Foc), the causal agent of this disease, is genetically dissected in this study using two Musa acuminata ssp. malaccensis segregating populations segregating for Foc Tropical (TR4) and Subtropical (STR4) race 4 resistance. Marker loci and trait association using 11 SNP-based PCR markers allowed the candidate region to be delimited to a 12.9 cM genetic interval corresponding to a 959 kb region on Chromosome 3 of ‘DH-Pahang’ reference assembly v4. Within this region, there is a cluster of pattern recognition receptors, namely leucine rich repeat ectodomain containing receptor-like protein kinases, cysteine-rich cell wall associated protein kinases, and leaf rust 10 disease-resistance locus receptor-like proteins positioned in an interspersed arrangement. Their transcript levels were rapidly upregulated in the resistant but not in susceptible F2 progenies at the onset of infection. This suggests that one or several of these genes may control resistance at this locus. To confirm the segregation of single-gene resistance, we generated an inter-cross between the resistant parent ‘Ma850’ and a susceptible line ‘Ma848’, to show that the STR4 resistance co-segregated with marker ‘28820’ at this locus. Finally, an informative SNP marker 29730 allowed the locus specific resistance to be assessed in a collection of diploid and polyploid banana plants. Out of the 60 lines screened, 22 lines were predicted to carry resistance at this locus, including lines known to be TR4 resistant, such as ‘Pahang’, ‘SH-3362’, ‘SH-3217’, ‘Ma-ITC0250’, and ‘DH-Pahang/CIRAD 930’. Additional screening in the International Institute for Tropical Agriculture’s collection suggests that the dominant allele is common among in the elite ‘Matooke’ NARITA hybrids, as well as in other triploid or tetraploid hybrids derived from East African highland bananas. Fine-mapping and candidate gene identification will allow characterization of molecular mechanisms underlying TR4 resistance. The markers developed in this study can now aid the marker-assisted selection of TR4 resistance in breeding programs around the world.

Background: Co-treatment of the fetal estrogen estetrol (E4) with androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) may further inhibit endocrine PCa tumor stimulators including testosterone (T), prostate-specific antigen (PSA), follicle-stimulating hormone (FSH), and insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study in advanced PCa patients requiring ADT (the PCombi study) was conducted to assess the effect of E4 co-treatment with LHRH agonist ADT on total T, free T, PSA, FSH, and IGF-1. Patients starting ADT were randomized 2:1 to 40 mg E4 (n=41) or placebo (n=21) for 24 weeks. Analyses were performed on the per-protocol population (PP), using the Wilcoxon-rank sum and the Kruskal-Wallis test. Results: The PP population consisted of 57 patients (37 ADT+E4; 20 ADT+placebo). All individual data of the four endocrine tumor stimulators are presented in figures in the paper and in supplementary tables, showing that E4 co-treatment almost completely suppressed FSH levels in all patients, on average by 98% versus 37% in the placebo group (p

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

In our recent publications pertaining to 4G model of final unification and based on strong and electroweak interactions, we have developed a completely new formula for estimating nuclear binding energy. With reference to currently believed Semi Empirical Mass Formula (SEMF), we call our formula as ‘Strong and Electroweak Mass Formula’ (SEWMF). Our formula constitutes 4 simple terms and only one energy coefficient of magnitude 10.1 MeV. First term is a volume term, second term seems to be a representation of free nucleons associated with electroweak interaction, third term is a radial term and fourth one is an asymmetry term about the mean stable mass number. Considering this kind of approach, nuclear structure can be understood in terms of strong and weak interactions and cold nuclear fusion like complicated concepts can be understood in a theoretical approach positively. In this paper, by considering the accountability of we are making an attempt to improve the applicability and effectiveness of SEWMF. Number 0.00125 being a workable electroweak coefficient for Z=6 to 132 and A=2Z to 3.5Z, number of free nucleons assumed to be associated with electroweak interaction can be expressed as Improved asymmetry term can be expressed as, where represents the light house like stable mass number. With reference to old version, our improved binding energy formula can be expressed as, We are working on its possible modification for mass numbers less than the stable mass numbers. Following this approach, it is possible to show that nuclear binding energy scheme is associated with strong and weak interactions and is practically independent of Coulombic repulsions. Proceeding further, currently believed cold nuclear fusion assumed be associated with hydrated metals can be understood and can be confirmed with strong and weak interactions independent of coulombic repulsions. We are very confident to say that our approach will certainly motivate modern science community in this new direction.

We delve into the axion-dilaton model within the supergravity framework, with a specific focus on the intricacies of domain wall construction and stability. Employing holographic vitrification, we unravel the dynamics of domain wall formation in gauge theories featuring periodic vacuum structures. Our model, incorporating a QCD-like axion term and a stabilizing dilaton, undergoes scrutiny for conductivity variations under weak disorder. The investigation reveals the model's resilience, manifesting near-perfect conductivity under mild disorder conditions. However, the rigorous mathematical motivation for the holographic setup demands further elucidation. The scattered nature of our results prompts the necessity for a more systematic interpretation of QCD phenomena and conductivity transitions. This study contributes to the mathematical understanding of the axion-dilaton model's behavior, highlighting the imperative for a refined holographic framework and a more coherent interpretation of observed phenomena.

We delve into nonrelativistic quantum electrodynamics within a background magnetic field, ensuring gauge invariance via a vector potential. Our exploration extends to the Lagrangian, which incorporates electron self-interactions and electromagnetic field interactions. Through the path integral formalism, we elucidate the effective action, with a specific focus on the photon propagator and screening effects. Examining density and current components reveals Laurent expansions in the hydrodynamic limit. The equations of motion in real space are derived, leading to discussions on phenomena such as Poiseuille-like flow and the Navier-Stokes equation. To ground our theoretical framework at practical contexts, we consider applications such as the fluid dynamics at binary star systems. Depending on the velocity of the expelled fluid, our analysis allows for both nonrelativistic and relativistic treatments, providing a versatile tool for understanding the intricacies of fluid behavior at astrophysical scenarios. Additionally, we recognize that at the presence of a magnetic field, magnetohydrodynamics becomes crucial. While our current focus is at nonrelativistic quantum electrodynamics, the insights gained here contribute to a broader understanding, offering a comprehensive foundation for quantum electrodynamics analysis at diverse physical systems.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.