Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Panel data of our interest consist of a moderate number of panels, while the panels contain a small number of observations. An estimator of common breaks in panel means without a boundary issue for this kind of scenario is proposed. In particular, the novel estimator is able to detect a common break point even when the change happens immediately after the first time point or just before the last observation period. Another advantage of the elaborated change point estimator is that it results in the last observation in situations with no structural breaks. The consistency of the change point estimator in panel data is established. The results are illustrated through a simulation study. As a by-product of the developed estimation technique, a theoretical utilization for correlation structure estimation, hypothesis testing, and bootstrapping in panel data is demonstrated. A practical application to non-life insurance is presented as well.

This paper is aimed at studying the temporal evolution of the surface displacements occurred over the past few years in the ocean-reclaimed platforms of the Shanghai megacity (China), which are mainly ascribable to consolidation processes of large dredger fills and alluvial deposits. With respect to previous analyses carried out over the same area, this work provides a joint multi-platform differential interferometry synthetic aperture radar (DInSAR) analysis, based on the application of the advanced Small BAseline Subset (SBAS) algorithm. This led us to retrieve long-term deformation time-series that are helpful for a better understanding of the on-going deformation phenomena. To this aim, we have exploited two sequences of SAR data collected by the ASAR/ENVISAT and by the COSMO-SkyMed (CSK) sensors, respectively, spanning the whole time period from 2007 to 2016. Unfortunately, the large time gap (of about three years) existing between the available ASAR/ENVISAT and CSK datasets gave rise to additional difficulties for their combination. Nevertheless, this problem has been faced by benefiting from the knowledge of a time-dependent model describing the temporal evolution of the expected deformations affecting the Shanghai ocean-reclaimed platforms.

Cloth wearing seems so natural that everyone is self-deemed knowledgeable and has some expert opinions about it. However to clearly explain the physics involved, and hence to make predictions for clothing design or selection, turns out as demonstrated below to be quite challenging even for experts. Cloth is a multiphased, porous and anisotropic material system and usually in multilayers. Unlike ordinary engineering heat transfer problems, the human body acts as an internal heat source in a clothing situation, thus forming a temperature gradient between body and ambient, and the sign of this gradient often changes as the ambient temperature varies. Our body also perspires and the sweat evaporates, an effective body cooling process via phase change. To bring all the variables into analysis quickly escalates into a formidable task. This work attempts to unravel the problem from a physics perspective, focusing on several rarely noticed yet critically important mechanisms involved so as to offer a clear and accurate depiction of the principles in clothing thermal comfort.

Verticillium wilt is a soil borne disease caused by distinct vegetative compatibility groups (VCG) of the fungus Verticillium dahliae. Two V. dahliae isolates were recovered from symptomatic cot-ton plants in Australian cotton fields and were assigned to two distinct vegetative compatibility groups (VCGs). One corresponding to the defoliating (VCG 1A) and the other non-defoliating (VCG 2A) pathotypes of Verticillium, have been transformed with Red and Green Fluorescent protein genes, respectively. The transformants maintained their ability to infect cotton and both strains were observed to colonise the xylem vessels of cotton plants. Moreover, we observed that the cotton V. dahliae strains could also infect some sampled non-Gossypium species found in the Australian landscape. The fluorescently labelled strains of V. dahliae will allow us to gain a thorough understanding of the infection processes of this important pathogen.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

This paper presents an upcoming nonvolatile memories (NVM) overview. Non-volatile memory devices are electrically programmable and erasable to store charge in a location within the device and to retain that charge when voltage supply from the device is disconnected. The non-volatile memory is typically a semiconductor memory comprising thousands of individual transistors configured on a substrate to form a matrix of rows and columns of memory cells. Non-volatile memories are used in digital computing devices for the storage of data. In this paper we have given introduction including a brief survey on upcoming NVM's such as FeRAM, MRAM, CBRAM, PRAM, SONOS, RRAM, Racetrack memory and NRAM. In future Non-volatile memory may eliminate the need for comparatively slow forms of secondary storage systems, which include hard disks.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, imposing a regime of predation risk. Consequently, prey experience both consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories of prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a great invasive threat to global horticulture. While earlier research has primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated reduced development time in the presence of isolated H. patellifera or H. patellifera odor, yet evidenced significantly increased fecundity. Conversely, males displayed no significant change in development time. Additionally, neither female nor male body weight at death was significantly influenced by predation risk from isolated predators or predator odor. These results indicated adaptive developmental strategies of B. dorsalis when faced with risks from predators and highlight the important role of predator odor, which has the potential to lay the groundwork for improving biological control efforts and innovative approaches within pest control.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

By this contribution we would like to briefly highlight the problems in conceiving the “Hydrogen Bond” (HB) as a real short-range, directional, electrostatic, attractive interaction and to reframe its nature through the non-approximated view of condensed matter offered by a Quantum Electro-Dynamic (QED) perspective. We focus our attention on water, as the paramount case to show the effectiveness of this 40-years’ old theoretical background, which depicts water as a two-fluid system (where one of the two phases is coherent). The HB emerge to be the result of the electromagnetic field gradient in the coherent phase of water, whose vacuum level is lower than the non-coherent (gas-like) fraction. Thus, the HB can be properly looked at, i.e. no more as a “dipolar force” among molecules, but as the phenomenological effect of their collective thermodynamic tendency to occupy a lower ground-state, compatibly with temperature and pressure. This perspective allows to account for many “anomalous” behaviours of water and to understand why the calculated energy associated to HB should change when considering two molecules (water-dimer), or the liquid state, or the several kinds of ice. The emergence of a condensed, liquid, phase at room temperature is indeed the consequence of the boson condensation as described in the framework of spontaneous symmetry breakings (SSB). The switch from a still semi-classical Quantum Mechanical (QM) in the 1st quantization to a Quantum Field Theory (QFT) view embedded in the 2nd quantization is advocated for a more realistic and authentic description of water, condensed matter and living systems.

Entropy generation, formulated by combining the first and second laws of thermodynamics with an appropriate thermodynamic potential, emerges as the difference between a phenomenological entropy function and a reversible entropy function. The phenomenological entropy function is evaluated over an irreversible path through thermodynamic state space via real time measurements of thermodynamic states. The reversible entropy function is calculated along an ideal reversible path through the same state space. Entropy generation models for various classes of systems—thermal, externally loaded, internally reactive, open and closed––are developed via selection of suitable thermodynamic potentials. Here we simplify thermodynamic principles to specify convenient and consistently accurate system governing equations and characterization models. The formulations introduce a new and universal Phenomenological Entropy Generation (PEG) theorem. The systems and methods presented––and demonstrated on grease degradation, battery charging and discharging, metal fatigue and pump flow––can be used for design, analysis, and support of diagnostic monitoring and optimization.

From grape cultivation to ripening and harvest timing to processing, each step can be a critical point when it comes to wine quality and phenolic composition. In this study, the influence of winemaking technology on resveratrol and quercetin content, as well as other polyphenolic compounds, was investigated. Resveratrol is a non-flavonoid polyphenolic stilbene synthesized by grape skin when damaged by infectious diseases or ionizing radiation. Quercetin is a phenol found in grape skins and stems and is produced to protect grapes from UV light damage. Trans-resveratrol and quercetin are known to act as antioxidants, reduce the risk of atherosclerosis and type 2 diabetes, inhibit the growth of cancer cells, and prevent the release of allergic and inflammatory molecules. However, the question was whether red wine could be enriched with these phenols using an innovative winemaking technology. The innovative idea was to completely replace the cold maceration process with maceration with the addition of wild yeast (Torulaspora delbrueckii, Td). Maceration with the addition of wild yeast (Td) offers the following advantages over traditional cold maceration: (1) higher concentrations of trans-resveratrol (>35-40%) and quercetin (>35-40%) in the final wine, (2) the new wine has a higher potential for human health, (3) the wine has a better aroma and stability due to the higher mannoprotein content, and (4) the better energy efficiency in the production process. The study of stability during storage and aging also included derivatives of benzoic acid and hydroxycinnamic acid, piceid, catechin, naringenin, rutin, kaempherol, hesperetin, and anthocyanins. The study found that younger wines had higher phenolic content, while storage of the wine resulted in a decrease in total phenolic content, especially monomeric stilbenes and quercetin.

This article describes the history of research and development of surface-penetrating radar, starting from the 60s in the USSR, and ending today in Russia and neighboring states formed after the collapse of the USSR. The outstanding role played in the initial period of this technology development by Prof. M.I. Finkelstein and his colleagues is highlighted. Their research had a significant impact on subsequent developments in modern Russia and the neighboring countries.

In wireless sensor networks (WSNs), each sensor node can estimate the global parameter from the local data in distributed manner. This paper proposed a robust diffusion estimation algorithm based on minimum error entropy criterion with self-adjusting step-size, which are referred to as diffusion MEE-SAS (DMEE-SAS) algorithm. The DMEE-SAS algorithm has fast speed of convergence and is robust against non-Gaussian noise in the measurements. The detailed performance analysis of the DMEE-SAS algorithm is performed. By combining the DMEE-SAS with diffusion minimum error entropy (DMEE) algorithms, an Improving DMEE-SAS algorithm is proposed, in non-stationary environment where tracking is very important. The Improving DMEE-SAS algorithm can avoid insensitivity of the DMEE-SAS algorithm due to the small effective step-size near the optimal estimator, and obtain a fast convergence speed. Numerical simulations are given to verify the effectiveness and advantages of these proposed algorithms.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

(1) Background: The aim of the research was to present and emphasize the importance of magnetic resonance imaging (MRI) in diagnosing Achilles tendon (AT) ruptures by presenting case reports. (2) Materials and Methods: The sample of respondents included 7 patients (4 males and 3 females, 2 athletes and 5 non-athletes), aged 25 to 58 years, with AT injuries, who were examined and treated at the Institute for Treatment and Rehabilitation "Niška Banja", Niš, Serbia. Ankle examinations with MRI were conducted using the Esaote O-scan 0.3 T machine. The examinations were performed without the application of a paramagnetic contrast agent and without the use of anesthesia. Results: The MRI method's sensitivity and overall diagnostic accuracy were excellent, with 100% true positives. In our study, the method accurately detected the presence, location, and severity of AT injuries in all cases. MRI is an important and reliable method for detecting AT injuries, classifying them, monitoring the course of recovery, and assessing the effects of therapy. Conclusions: An unrecognized or delayed diagnosis of an AT injury can lead to chronic changes. Timely diagnosis (clinical examination, ultrasonography, magnetic resonance imaging) and appropriate treatment (conservative or operative) enable patients to return to normal activities, including sports. Unfortunately, the use of MRI is limited by restricted access and the cost of the examination.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Abstract: Global ecological concern regarding the transfer of fouling organisms to ship hulls is increasing. This study investigated the species composition, dominant species, distribution patterns, community structure, and life-cycle differences of hull-fouling macroinvertebrates on five research vessels (R/Vs: Isabu, Onnuri, Eardo, Jangmok 1, and Jangmok 2) operated by the Korea Institute of Ocean Science and Technology (KIOST). Hull-fouling macroinvertebrates were collected three to five times on quadrats from the upper and middle sectors of the hull sides, bottom, and niche areas (the propellers and shafts and the thrusters). A total of 47 macroinvertebrate species were identified, represented by 8,519 individuals(ind.)/m2 and a biomass of 1,967 gWWt/m2 on the five vessels. The number of species, density, and biomass were greater on the coastal vessels the Eardo, Jangmok 1, and Jangmok 2 than on the ocean-going vessels the Isabu and Onnuri. Among the coastal vessels, barnacles were the most abundant and had the greatest density, while mollusks had the highest biomass. Differences between hull sectors showed that the highest species abundance and density appeared on all hulls in ports and bays where the Jangmok 1 operated, while the highest species abundance, density, and biomass were identified in the niche areas of the Eardo, which operated farther from the coast. The hull-fouling macroinvertebrates that exceeded 1% of all organisms were the barnacles Amphibalanus amphitrite, Balanus trigonus, and Amphibalanus improvisus; the polychaete Hydroides ezoensis; the bivalves Magallana gigas and Mytilus galloprovincialis; and the amphipod Jassa slatteryi. The dominant species were cosmopolitan and globally distributed, and many of them were cryptogenic. Six native species were identified: M. gigas, H. ezoensis, the amphipod Melita koreana, the isopod Cirolana ko-reana, and the barnacle B. trigonus and F. kondakovi. Eight non-indigenous species (NIS) were de-tected: barnacles A. amphitrite and A. improvisus, the bivalve M. galloprovincialis, the polychaete Perinereis nuntia, amphipods J. slatteryi and Caprella californica, and bryozoans Bugulina californica and Bugula neritina. Of the fouling macroinvertebrates found on the vessel hulls, 13% were native and 17% were NIS. The nMDS ordination analysis of the five vessels showed four clusters of fouling macroinvertebrate communities: two ocean clusters (the Isabu and Onnuri), one coastal cluster (the Eardo and Jangmok 2), and one local cluster (the Jangmok 1). More diverse communities developed on the hulls of vessels that operated locally rather than globally or in deep oceans. Spearman rank correlation showed that biological indices such as number of species, density, and biomass correlated highly and positively with the numbers of days on coastal operations and negatively with the number days on ocean operations. The species diversity index correlated positively with the total number of anchoring days and coastal operation days and negatively with the total number of operation days and ocean operation days. The macroinvertebrates differed by the area of operation, the port of anchorage, the number of days in operation and at anchor, and the hull sectors. There is no previous research data on hull-fouling macroinvertebrates in the Republic of Korea, and this study provides a basis for future studies to identify introduced species and their differences based on operation area.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

Positioning based on wireless signals such as mobile communication networks has become an important means to provide high-precision location services in environments where satellite signals are blocked. In complex environments such as indoor and underground, wireless signal propagation is obstructed and non-line-of-sight (NLOS) phenomena appears due to serious occlusion and reflection. The time delay caused by NLOS effects has little impact on communication system but can significantly increase positioning errors in positioning systems. Therefore, effective suppression of NLOS errors is crucial to improving 5G positioning accuracy. To address the insufficient feature extraction of existing NLOS error suppression methods, the neglect of residual NLOS measurement errors, and poor stability of position estimation results, this paper innovatively proposes a NLOS mitigation and location estimation method for 5G positioning terminals. Simulation and experimental test results demonstrate that the proposed method outperforms the comparative methods both theoretically and practically, achieving an average positioning accuracy of 1.85 meters in complex indoor NLOS environments. The method proposed in this paper provides a new strategy for NLOS error suppression in indoor 5G positioning, which can significantly contribute to high-precision location services based on commercial 5G networks.

This study explores the perception of a “sense of place” among tourists visiting Hegra, an archaeological site in northern Saudi Arabia, through reviews on TripAdvisor. The 267 reviews reviewed on TripAdvisor between 2020 and 2023 were analyzed with the VADER sentiment po-larity analysis tool and object modeling using the NMF machine learning algorithm. The results highlight positive factors linked to the history and uniqueness of the place while showing some critical issues related to isolation, cost, privatization, and competitiveness. The originality of the research lies in the type of case study chosen, an archaeological site of a country that has recently opened its doors to tourism, and in the pragmatic nature of the investigation, oriented towards the search for possible solutions to be adopted in terms of heritage management based on the feedback received for the development of the tourist destination.

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

COVID-19 vaccine hesitancy and its enablers would shape community uptake of non-covid vaccines such as oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included characteristics, intention to take OCV and COVID-19, reasons for COVID-19 hesitancy, and thinking and feeling about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude Prevalence Ratio, [cPR]=1.12, 95%CI[1.03-1.21]). Independent predictors of OCV hesitancy were living in semi-urban area (adjusted Prevalence Ratio [aPR]=1.10, 95%CI[1.03-1.12]), religious refusal of vaccines (aPR=1.06, 95%CI[1.02-1.12]), concerns about vaccine safety (aPR=1.05, 95%CI[1.01-1.11]) and adverse effects (aPR=1.06, 95%CI[1.01-1.12]), as well as poor knowledge (aPR=1.07, 95%CI[1.01-1.14]). Conversely, the belief about COVID-19 vaccine effectiveness reduced OCV hesitancy (aPR=0.76, 95%CI[0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibiting a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy interventions would likely improve the introduction of novel non-COVID-19 vaccines in post-COVID-19 era.

The article focuses on mining of non-energy mineral resources with minimum environmental impacts. It issues from research results of a project Competence Centre for Effective and Ecological Mining of Mineral Resources implemented at the Faculty of Mining and Geology at VŠB-Technical University of Ostrava, Czech Geological Survey, a company Watrad ltd., a state enterprise Diamo, a company RPS Ostrava plc and a company Sedlecký kaolin plc. The paper starts with a partial analysis of the existing legal norms related to mining and processing of mineral resources. Next, it analyses mineral resource mining options free of negative environmental impacts. The fundamental tool to assess potential environmental impacts of mining is the implementation of Environmental Impact Assessment (EIA) process for a given mineral resource. In the Czech Republic environmental impact assessment is carried out by course of Act 100/2001 Coll. Its important amendment is Act 39/2015 Coll. claiming, inter alia, that the environmental impact assessment is rigidly connected with other permits and procedures, such as the zoning process and building construction permits. The article describes the environmental impacts of mining of non-energy mineral resources, including the following factors: appropriation of land, impacts on surface water, ground water and soil, noise, influence on the landscape character, and air pollution. The paper also includes a case study summarizing information on the environmental factors that may play a role in potential underground mining of graphite in the deposit Český Krumlov - Městský Vrch and the deposit Lazec - Křenov.

Due to the extraordinary mechanical properties of ultra-high-performance concrete (UHPC), the shear stirrups in UHPC beams could potentially be removed. The aim of this study is to determine the effect of beam height and steel fiber volume content on the shear behavior of non-stirrup UHPC beams under a larger shear span-depth ratio (up to 2.8). Eight beams were designed and fabricated, including six non-stirrup UHPC beams and two comparing stirrup-reinforced normal concrete (NC) beams. The experimental results demonstrated that the volume content of steel fiber could be a crucial factor affecting the ductility, cracking strength, and shear strength of non-stirrup UHPC beams and altering their failure modes. Additionally, the height of the beam had a considerable effect on its shear resistance. This study revealed that the French standard formulae were more accurate for the UHPC beams with larger shear span-depth ratios and PCI-2021 formulae greatly overestimate the shear capacity of UHPC beams with larger shear span-depth ratios. Xu’s formulae were more accurate for the steel fiber-reinforced UHPC beams with larger shear span-depth ratios.

The mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

This paper presents experimental identification and vibration suppression of a flexible manipulator with non-collocated piezoelectric actuators and strain sensors using optimal multi-poles placement control. To precisely identify the system model, a reduced order transfer function with relocated zeros is proposed, and a first-order inertia element is added to the model to compensate the non-collocation. Comparisons show the identified model match closely with the experimental results both in the time and frequency domains, and a fit of 97.2% is achieved. Based on the identified model, a full-state multi-poles placement controller is designed, and the optimal locations of the closed loop poles are determined. The feasibility of the proposed controller is validated by simulations. Moreover, the controller is tested for different locations of the closed loop poles, and an excellent performance of the optimal locations of the closed loop poles is shown. Finally, the effectiveness of the proposed controller is demonstrated by experiments. Results show that the vibrations of the expected modes are significantly diminished. Besides, vibrations of the higher modes are also slightly suppressed. Accordingly, multi-mode vibrations of the manipulator are well attenuated, and the tip displacement converges quickly with the proposed method.

The up-to-date challenge towards clean road transport are non-exhaust emissions. Important advances regarding measurement systems, including well defined characterisation techniques, as well as regulation, will happen in the next few years. In this work we present detailed results of particle emissions from a test bed for wheel suspension and brakes, consisting of aerosol (size distribution, particle number (PN) and mass (PM)) and electron microscopy measurements (EM) under different load conditions. Standard tyres and brakes from series production were tested with a high-load driving cycle while particle measurements were conducted by gravimetric measurements and with a TSI SMPS, a TSI APS and a GRIMM OPS. Furthermore, samples were analyzed by electron microscopy. A bimodal particle size distribution (PSD) was obtained with the SMPS, with peaks at 20nm and around 400nm. EM analysis of >1400 single particles from the electrostatic sampler matches the PSD results. EM analysis also showed ultrafine particles, mainly from O, Fe, Si, Ba, Mg and S and also fractal particles with high C fractions. Our results suggest, in agreement with previously published literature, that particulate emissions are related to brake disc temperature and occur in significant amounts above a threshold temperature.

For 80 years high-intensity focused ultrasound (HIFU) has been a significant area for medical research. It is a non-invasive procedure which causes cell death in a highly localised area at a defined distance from the transducer. Since 2000, the clinical indications have broadened considerable as the technology has improved. This review looks back at the history of HIFU and the current clinical indications.

The rapid emergence of COVID-19 necessitated policy responses worldwide, focusing on vaccination and mobility restrictions. However, studies on individual non-pharmacological preventive measures are less common. In particular, Chile represents a unique scenario for analyzing the adoption of preventive measures and changes amid aggressive communication and vaccination campaigns. This study aims to provide insights into public adherence to non-pharmacological measures in the face of diseases, using a cohort of 386 participants from 2021 to 2022. This was achieved by employing a questionnaire to measure adherence to self-care practices and by analyzing contact tracing data from health authorities. We performed bivariate analysis and a linear regression model. Mask-wearing in public places was the most commonly used measure (95.9% in 2021 and 89.9% in 2022). The median adherence score increased from 18 to 19 for both measurements, respectively. The regression model shows that women are more likely to adopt preventive behaviors in both waves and being a young adult (30-49 years) predicted the adoption of behavioral precautions in 2022. Adherence to preventive measures increased even with high vaccination coverage, likely due to the epidemiological situation with the Omicron variant circulating in 2022.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

Meat serves as a vital component of the human diet, offering a rich source of protein and essential trace elements. China stands as both a significant producer and consumer of meat on a global scale, leading the world in terms of total meat production and consumption. As the standard of living within the country continues to rise, there is a growing emphasis on the nutritional value and safety of meat consumption. The tenderness of meat is a critical factor influencing its overall quality. Traditionally, tenderness has been assessed through shear force testing, a method that is inherently destructive, inefficient, and results in considerable sample wastage. In light of these drawbacks, non-destructive testing techniques have emerged as a preferred alternative, promising greater accuracy, efficiency, and convenience without compromising the integrity of the samples. This paper delves into the application of five advanced non-destructive testing technologies in the realm of meat tenderness assessment. These include near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, airflow optical fusion detection, and nuclear magnetic resonance detection. Each technology is scrutinized for its respective strengths and limitations, providing a comprehensive overview of their current utility and potential for future development. Moreover, the integration of these techniques with the latest advancements in artificial intelligence (AI) technology is explored. The fusion of AI with non-destructive testing offers a promising avenue for the development of more sophisticated, rapid, and intelligent systems for meat tenderness evaluation. This integration is anticipated to significantly enhance the efficiency and accuracy of quality assessment in the meat industry, ensuring a higher standard of safety and nutritional value for consumers. The paper concludes with a set of technical recommendations aimed at guiding the future direction of non-destructive, AI-enhanced meat tenderness detection, thereby contributing to the ongoing improvement of the meat industry in China and beyond.

Rajasthan is a state located in the north-western part of India and it has been cited as a major route of human migration since ancient times. The present study was conducted to find out the genetic affinity of Rajasthani population with the population living in its east and the west. In particular, we compared them with the population of Pakistan which shares the common geographical boundary with the Rajasthan while also having a look at their inter and intra population affinities with the population belonging to other Indian states. We investigated the genetic structure and population parameters of Rajasthani populations obtained for twenty polymorphic autosomal STR loci from 669 unrelated individuals belonging to its three population groups including Mina, Gujjar and the admixed population of Rajasthan. The studied populations showed a wide range of genetic diversity and besides the genetic structure of the studied populations, it was found that the average heterozygosity value was highest among the populations of Rajasthan, possibly, because of gene flow from different directions. Various statistical analyses suggested that the Rajasthani populations had a higher affinity with the North Indian populations rather than with the Pakistani population.

This article develops duality principles and numerical results for a large class of non-convex variational models. The main results are based on fundamental tools of convex analysis, duality theory and calculus of variations. More specifically the approach is established for a class of non-convex functionals similar as those found in some models in phase transition. Finally, in the last section we present a concerning numerical example and the respective software.

Cardiomyopathies (CMPs) are a group of myocardial disorders that are characterized by structural and functional abnormalities of the heart muscle. These abnormalities occur in the absence of coronary artery disease (CAD), hypertension, valvular disease, and congenital heart disease. CMPs are an increasingly important topic in the field of cardiovascular diseases due to the complexity of their diagnosis and management. In 2023, the ESC guidelines on cardiomyopathies were first published, marking significant progress in the field. The growth of techniques such as cardiac magnetic resonance imaging (CMR) and genetics has been fueled by the development of multimodal imaging approaches. For the diagnosis of CMPs, a multimodal imaging approach, including CMR, is recommended. CMR has become the standard for non-invasive analysis of cardiac morphology and myocardial function. This document provides an overview of the role of CMR in CMPs, with a focus on tissue mapping. CMR enables the characterization of myocardial tissues and the assessment of cardiac functions. CMR sequences and techniques, such as late gadolinium enhancement (LGE) and parametric mapping, provide detailed information on tissue composition, fibrosis, edema, and myocardial perfusion. These techniques offer valuable insights for early diagnosis, prognostic evaluation, and therapeutic guidance of CMPs. The use of quantitative CMR markers enables personalized treatment plans, improving overall patient outcomes. This review aims to serve as a guide for the use of these new tools in clinical practice.

Woodland strawberry (Fragaria vesca L.) is an underutilized plant species, appreciated by consumers for its qualitative features. Utilizing technical means of production, such as plant biostimulants, that can increase crop productivity and quality could be highly important in woodland strawberry cultivation. The scope of the present study was to appraise the influence of two biostimulants (Trichoderma atroviride and plant protein hydrolysate) - used either alone or combined - on plant performance and economic profitability of two woodland strawberry genotypes (‘Alpine’ and ‘Regina delle Valli’). Overall, data showed that ‘Alpine’ had the highest productive performances, whereas ‘Regina delle Valli’ revealed the highest fruit qualitative traits. T. atroviride inoculation and V-PH application significantly boosted plant marketable yield (+20.5% for T. atroviride and +12.9% for V-PH), total sugars (+1.9% for Trichoderma and +1.4% for V-PH) and anthocyanins (+14.1% for T. atroviride and +9.8% for V-PH) compared to non-treated plants. Plants supplied with both biostimulants had higher marketable yield (+34.8%), mean fruit weight (+6.0%), fruit dry matter (+13.8%), total sugars (+3.5%), ascorbic acid (+12.7%), flavonoid (+26.3%) and anthocyanins (+29.9%) compared to non-treated plants. Furthermore, our study revealed that the highest fruit polyphenols concentration was recorded in both genotypes treated with the combination of biostimulants and in ‘Regina delle Valli’ sprayed with V-PH, whereas the highest antioxidant activity was found in ‘Regina delle Valli’ fruit when plants were supplied with both biostimulants. Our study pointed out that the application of microbial and non-microbial biostimulants, especially in combination, might be an useful strategy for improving performances of underutilized species and, therefore, encourage its cultivation, valorisation and economic profitability (+10195.3 €/ha when plants were exposed to both biostimulants).

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

Hereditary hemochromatosis (HH) is the main genetic cause of iron overload and is regarded as metal-related human toxicosis. HH may result from HFE and non-HFE gene mutations causing hepcidin deficiency or hepcidin resistance. The disorder has a high biochemical penetrance, but a low clinical prevalence. Unfortunately, the majority of patients with HH remain undiagnosed at their disease-curable stage. The main aim of HH therapy is to prevent iron overload in the early-phase disease and elimination of excess iron from the body by phlebotomy in its late stage. Raising global awareness of HH among health professionals, their training to pay attention to early HH signs and symptoms, and strict patient monitoring are critical management strategies for preventing treatment delays, upgrading its efficacy, and improving patient prognosis.

Oil and petroleum are strategic resources of great importance to national security. Petroleum and hydrothermal gold deposits may form together, with similar evolutionary trends in their formation, migration, and enrichment. Petroleum reservoirs and gold deposits are closely coupled under certain geological conditions. The solubility of gold in crude oil and its forms of occurrence are important in determining the mechanisms of interaction between gold and petroleum and in facilitating the recovery of gold from gold-bearing petroleum. In this study, the occurrence of gold in crude oil from the Linnan Depression in the Bohai Bay Basin, China, was studied using inductively coupled plasma–mass spectrometry and X-ray photoelectron spectroscopy. Concentrations of gold in crude oil from the Linpan and Shanghe oilfields averaged 44.5 ppb, which is well above the minimum concentration required for hydrothermal gold mineralization. Gold has an affinity with carbon, oxygen, and sulfur, and its concentration in crude oil is positively correlated with total acid and sulfur contents. We speculate that gold may exist in crude oil as complexes with organic acids or thiols, with crude oil thus being a transport medium for gold.

The impact of the COVID-19 pandemic and the quarantine measures on children and adolescents’ hospitalization psychiatric has been poorly studied, especially in Italy, the first European country to adopt social restrictions. To fill this gap, this retrospective study examined changes in admissions to our child and adolescent psychiatry ward from the emergency department during the two COVID-19 quarantine periods in Italy (March to June 2020; October 2020 to January 2021) compared with two reference periods (defined as 12 months prior to the respective quarantine periods). Specifically, we examined data on the number of inpatients and the distribution of psychopathological disorders (i.e., psychosis, mood disorder) and self-injurious behaviors. The results revealed significantly fewer admissions during the first quarantine period relative to the first reference period and, conversely, significantly more admissions during the second quarantine period relative to the second reference period. Of note, the results showed an increased frequency of mood disorders, non-suicidal self-injurious behaviors and suicidal ideation during the quarantine periods, compared to the reference periods. The findings underline the need to focus on the psychopathological profile of children and adolescents with patient-tailored therapeutic interventions and suggest the importance of developing psychological healthcare services for future emergency periods..

QSO B0218+357 is a blazar located at a cosmological redshift of 0.944. The source is gravitationally lensed by a spiral galaxy located at the redshift of 0.68. Strong gravitational lensing splits the signals emitted by the source into two components separated by 10-12 days, as observed in radio and gamma-ray bands. In July 2014 a GeV flare was observed by Fermi-LAT, triggering follow-up observations with the MAGIC telescopes at energies above 100 GeV. The expected time delay between the components allowed us to plan broad band MWL observations before, during and after the trailing component of the emission. The MAGIC observations at the expected time of arrival of the trailing component resulted in the first detection of QSO B0218+357 in Very-High-Energy (VHE, >100 GeV) gamma rays. It is both the farthest known VHE object and one of only a few Flat Spectrum Radio Quasars detected in this energy range. We report here the observed multiwavelength spectral and temporal properties of the emission during the 2014 flare.

Single-phase-to-ground fault in non-effectively grounded systems poses serious public safety concern. Along with increasing deployment of low-voltage (LV) sensors, new opportunities and ways are created for solving this traditional problem in distribution systems. A new approach, identifying primary single-phase-to-ground line fault and locating it through measurement data from smart sensors deployed in the secondary side of distribution transformers, is proposed in this paper. When a fault occurs in primary distribution feeder, the transient aerial mode voltage (AMV) of each LV smart sensor is calculated. The fault line can be identified by an abrupt change value of AMV at LV side. Next, by finding the position of the maximum value of this AMV from LV sensors on the fault line, the fault location can be pinpointed to two neighboring distribution transformers. The proposed method has been proven to be efficient and reliable by simulation studies.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

The in silico studies were performed in order to assess the binding affinity of selected organophosphorus compounds towards the acetylcholinesterase enzyme (AChE). Quantum mechanical calculations, molecular docking and molecular dynamics (MD) with molecular mechanics Generalized-Born surface area (MM/GBSA) were applied to assess quantitatively differences between the binding energies of acetylcholine (ACh; the natural agonist of AChE) and neurotoxic, synthetic correlatives (so-called “Novichoks”, and selected compounds from the G- and V-series). Several additional quantitative descriptors like root mean square fluctuation (RMSF) and the solvent accessible surface area (SASA) were briefly discussed to give – to the best of our knowledge – the first quantitative in silico description of AChE – Novichok non-covalent binding process and thus facilitate the search for an efficient and effective treatment for Novichok intoxication and in a broader sense - intoxication with other warfare nerve agents as well.

The current pneumonia epidemic could evolve into a pandemic on a global scale if not effectively contained. The COVID-19 virus possesses a 61-amino acid open reading frame resembling SARS-CoV virulence factor - ORF6 peptide. The isoleucine content is 15.9% in ORF6 of SARS-CoV versus 16.4% of that in SARS-CoV-2. Given the proton affinity in the carbonyl oxygen in isoleucine, augmented proton traffic can enhance proton-ion antiport and prompt cell swelling. Calorie restriction has been confirmed in animal studies to extend lifespan, and its underlying mechanism is not fully known. As the content of essential amino acids in the open reading frame of SARS-CoV-2 reaches 57.4%, a starch/vitamin diet served for short period of time does not give rise to essential amino acids and halts virion production, which could be adopted as prophylactic approach of many viral infections. Plant-based diet or fasting/boiled rice water can also minimize the intake of essential amino acids or all amino acids respectively. Furthermore, several proteins of SARS-CoV-2 possess high valine plus glycine content which is implicated in heart disease, justifying the aforementioned approaches.

Pin1 is a peptidyl-prolyl isomerase responsible for isomerizing phosphorylated S/T-P motifs. Pin1 has two domains that each have a distinct ligand binding site, but only its PPIase domain has catalytic activity. Vast evidence supports interdomain allostery of Pin1, with binding of a ligand to its regulatory WW domain impacting activity in the PPIase domain. Many diverse studies have made mutations in Pin1 in order to elucidate interactions that are responsible for ligand binding, isomerase activity, and interdomain allostery. Here, we summarize these mutations and their impact on Pin1’s structure and function.

Affinity chromatography on procainamide-Sepharose has been an important step in the purification of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) since its introduction in 1978. The procainamide affinity gel has limitations. In the present report a new affinity gel called Hupresin^® was evaluated for its ability to purify truncated, partly-deglycosylated human butyrylcholinesterase (rHuBChE) expressed in a stably transfected CHO cell line. We present a detailed example of the purification of rHuBChE secreted into 3940 mL of serum-free culture medium. The starting material contained 13,163 units of BChE activity (20.9 mg). rHuBChE was purified to homogeneity in a single step by passage over 82 mL of Hupresin^® and elution with 0.1 M tetramethylammonium bromide in 20 mM TrisCl pH 7.5. The fraction with the highest specific activity of 630 units/mg contained 11 mg of BChE. Hupresin^® is superior to procainamide-Sepharose for purification of BChE, but is not suitable for purifying native AChE because Hupresin^® binds AChE so tightly that AChE is desorbed with denaturing solvents such as 50% acetonitrile or 1% trifluoroacetic acid. Procainamide-Sepharose will continue to be useful for purification of AChE.

Aptamers are excellent choices for selective detection of small molecules. However, the previously reported aptamer for chloramphenicol suffers from low affinity, probably as a result of steric hin-drance due to its bulky nature (80 nucleotides) leading to lower sensitivity in analytical assays. The present work was aimed at improving this binding affinity by truncating the aptamer without compromising its stability and three-dimensional folding. Shorter aptamer sequences were designed by systematically removing bases from each or both ends of the original aptamer. Thermodynamic factors were evaluated computationally to give insights into the stability and folding patterns of the modified aptamers. Binding affinities were evaluated by bio-layer interferometry. Among the 11 sequences generated, one aptamer was selected based on its low dissociation constant, length and regression of model fitting with association and dissociation curves. The dissociation constant could be lowered by 86.93% by truncating 30 bases from the 3’ end of the previously reported aptamer. The selected aptamer was used for gold nanospheres based colorimetric detection of chloram-phenicol in real samples. The detection limit could be reduced 32.87 times (1.673 pg mL-1) using the modified length aptamer, indicating its improved affinity as well as suitability in real sample analysis for ultrasensitive detection of chloramphenicol.

From a structural point of view, understanding interfacial electrostatic features of ligand-receptor complexes is crucial for biophysics-based design of therapeutics with improved efficacy and safety. Here, with a high-throughput structural feature extraction approach, this article reports a set of electrostatic structural features from glucagon-like peptide-1 (GLP-1) and GLP-1 receptor (GLP-1R) complex structures determined using experimental tools. Leveraging a set of computational structural biophysical analyses, this article systematically characterized the electrostatic interactions within the GLP-1-GLP-1R complexes with two sets of criteria to identify interfacial salt bridges and hydrogen bonds. Overall, the results here reveal intricate details of electrostatic interactions critical for GLP-1 binding to its receptor GLP-1R, providing biophysical insights into the stabilization of the GLP-1-GLP-1R complex structure and the molecular basis of GLP-1/GLP-1R signaling. Furthermore, the electrostatic structural features extracted from GLP-1 and GLP-1R complex structures are useful in the development of a machine learning-based ligand-receptor binding affinity calculating model, i.e., a GLP-1-GLP-1R-specific general intermolecular binding affinity calculator (GIBAC), paving the way for accelerated discovery and structure-based design of drug candidates targeting the GLP-1/GLP-1R system with improved efficacy and safety.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

Climate change, recognized as a global crisis, is not only altering our environment but also significantly impacting human health. Particularly, its influence on non-communicable diseases (NCDs), a leading cause of global mortality, is becoming increasingly evident yet underexplored. This review aims to synthesize current research on the impact of climate change on NCDs, addressing a critical gap in our understanding of how environmental changes affect human health. We examine the complex interplay between climate change and NCDs, drawing insights from recent studies that highlight the adverse effects of climate variables on chronic diseases, such as cardiovascular and kidney diseases, and the role of food and nutrition security in this nexus. Furthermore, the review explores the disproportionate impact on vulnerable regions and populations, particularly in Pacific Island countries and territories, underscoring the urgent need for context-specific solutions and a cross-sectoral approach. By integrating findings from various disciplines, this review aims to inform policy and public health interventions, highlighting the necessity of collaborative efforts to mitigate the burgeoning burden of NCDs in a rapidly changing climate.

IgY antibodies are found in the blood and yolk of eggs. Several studies show the feasibility of utilising IgY for immunotherapy and immunodiagnosis. These antibodies have been studied because they fulfil the current needs for reducing, replacing, and improving the use of animals. Affinity and avidity represent the strength of the antigen-antibody interaction and directly influence antibody action. The aim of this review was to examine the factors that influence the affinity and avidity of IgY antibodies and the methodologies used to determine these variables. In birds, there are few studies on the maturation of antibody affinity and avidity and these studies suggest that the use of an adjuvant, type of antigen, strain of the animal, number of immunisations, and time interfere with the affinity and avidity of IgY antibodies. Regarding the methodologies, most studies use chaotropic agents to determine the avidity index. Studies involving solution phase and equilibrium titration reactions are also described. These results demonstrate the need for standardisation of methodologies for determination of affinity and avidity so that further studies can be performed to optimise the production of high avidity IgY antibodies.

Significance: Electrophile signaling is coming into focus as a bona fide cell signaling mechanism. The electrophilic regulation occurs typically through a sensing event (i.e., labeling of a protein) and a signaling event (the labeling event having an effect of the proteins activity, association, etc.). Recent advances: Herein, we focus on the first step of this process, electrophile sensing. Electrophile sensing is typically a deceptively simple reaction between the thiol of a protein-cysteine, of which there are around 200,000 in the human proteome, and a Michael acceptor, of which there are numerous flavors, including enals and enones. Recent data overall paint a picture that despite being a simple chemical reaction, electrophile sensing is a discerning process, showing labeling preferences that are often not in line with reactivity of the electrophile. Critical issues: With a view to trying to decide what brings about highly electrophile-reactive protein-cysteines, and how reactive these sensors may be, we discuss aspects of the thermodynamics and kinetics of covalent/non-covalent binding. Data made available by several laboratories indicate that it is likely that specific proteins exhibit highly stereo- and chemoselective electrophile sensing, which we take as good evidence for recognition between the electrophile and the protein prior to forming a covalent bond. Future directions: We propose experiments that could help us gain a better and more quantitative understanding of the mechanisms through which sensing comes about. We further extoll the importance of performing more detailed experiments on labeling and trying to standardize the way we assess protein-specific electrophile sensing.We propose experiments that could help us gain a better and more quantitative understanding of the mechanisms through which sensing comes about. We further extoll the importance of performing more detailed experiments on labeling and trying to standardize the way we assess protein-specific electrophile sensing.

This study sought to investigate steel frames’ performance with dual lateral loader system (Frame bending + bracings of divergent and convergent) in near and far filed to fault. In order to this, four categories of steel frame with dual system with 8, 10 and 12 story are designed with average formation based on existing seismic regulation in 2800 standard of Iran and tenth chapter of national regulations of construction (planning and performing steel construction). Time history non-linear dynamic analysis under the effect of near and far field earthquakes has been done on plan’s models. Then the maximum of floors’ dislocation, floors’ drift, roof dislocation, base shear and energy curves of frames are shown and compared with each other. All non-linear time history analyses have been accomplished using PERFORM 3D software.

Circular RNAs (circRNAs) served as covalently closed single-stranded RNAs have been proposed to influence plant development and stress resistance. Grapevine is the most economically valuable fruit crops cultivated worldwide and threaten by various abiotic stresses. Herein, we reported that a circRNA (Vv-circPTCD1) processed from the second exon of a pentatricopeptide repeat family gene PTCD1 was preferentially expressed in leaves and responded to salt and drought but not heat stress in grapevine. Additionally, the second exon sequence of PTCD1 was highly conserved but the biogenesis of Vv-circPTCD1 is species-dependent in plants. It was further found that the overexpressed Vv-circPTCD1 can slightly decreased abundance of the cognate host gene and the neighboring genes were barely affected in grapevine callus. Furthermore, we also successfully overexpressed the Vv-circPTCD1, and found that the Vv-circPTCD1 deteriorated the growth during heat, salt, and drought stresses in Arabidopsis. However, the biological effects on grapevine callus were not always consistent with that of Arabidopsis. Interestingly, we found that the transgenic plants of linear counterpart sequence also conferred the same phenotypes as that of circRNA during the three stress conditions, no matter what species. Those results imply that although the sequences are conserved, the biogenesis and functions of Vv-circPTCD1 are species-dependent. Our results indicate that the plant circRNA function investigation should be conducted in homologous species, which support valuable reference for further plant circRNA studies.

Background: Dynapenia and non-alcoholic fatty liver disease (NAFLD) are common, especially in the middle and advanced-age diabetic male population. We aimed to examine the clinical features, NAFLD severity, and parameters associated with the presence of dynapenia in type 2 diabetes mellitus (T2DM) cases. Material and Methods: One hundred thirty-five male patients diagnosed with T2DM between 45 and 65 years of age were included. Patients were staged by ultrasonography according to NAFLD status. Results: There were significant differences in muscle strength, upper arm circumference, calf circumference, and up-and-go test scores between the NAFLD groups (p<0.001 for all). The frequency of dynapenia was lower, and arm and calf circumferences were higher in patients without NAFLD. The muscle strength, upper arm circumference, calf circumference, and up-and-go test scores were significantly lower in the dynapenic group compared to the non-dynapenic group (p<0.005 for all). The prevalence of dynapenia increased along with the increase in NAFLD stages (p<0.001). Conclusions: We detected a significant association between NAFLD and dynapenia in middle-aged men with T2DM. As muscle strength decreases, the amount of fat in the liver increases, and as the fat in the liver increases, muscle strength decreases.

Background: Recent research suggests a concerning trend of non-suicidal self-injury (NSSI) and suicidal behaviors emerging at younger ages (as early as age 12). Early onset of NSSI is linked to more severe outcomes. While universal school-based prevention programs have shown promise in addressing suicidal behaviors, there's limited research on their effectiveness in preventing NSSI onset among adolescents. This study aims to evaluate the efficacy of a universal prevention program in schools for NSSI and mental complaints while enhancing resilience and mental health in 11-14-year-old adolescents. Methods: In total, 329 Flemish secondary school students (55.6% female), aged 11 to 14 years, participated in a 4-hour classroom universal prevention, with a focus on emotion regulation, mental health, and specific strategies to prevent NSSI and reduce stigma. For both the intervention and control group (N = 124), a pre-, post- and one-month follow-up questionnaire was administered, containing reliable and valid measures for NSSI and suicidality, emotion regulation, help-seeking behaviors, well-being, and psychological distress. Results: The prevention program effectively reduced NSSI and psychological distress, particularly for adolescents with a history of NSSI. Conclusions: These findings support previous research on the effectiveness of school-based programs in reducing mental complaints and suggest promising outcomes for NSSI prevention.

Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement activating peptide were used to induce selective depletion of ACPA producing B cells. Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a short, neutral spacer. This peptide detects antibodies in RA sera with 66 % sensitivity and 98 % specificity in ELISA and is recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targets and depletes ACPA producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed on the basis of ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.

The prevalence of Noncommunicable Diseases (NCDs) in South Africa is increasing annually, with the burden projected to escalate by 2030. Devastatingly, factors such as lifestyle changes, urbani- sation, and an aging population significantly contribute to a rising burden of Cardiovascular disease (CVDs), diabetes, and cancer which directly impact the mortality and morbidity rates seen in South Africa. Recognising this, the South African government has seen the need for emphasis on developing policies and interventions tar- geting physical inactivity to prevent and manage NCD, particularly cost-free and easy to administer training protocols. However, phys- ical inactivity remains a significant issue, leading to various health concerns in rural communities, including injuries and Fetal Alcohol Spectrum Disorders (FASD). Despite effort to promote physical ac- tivity, the prevalence of NCDs continues to rise, necessitating target- ed interventions to ensure equitable healthcare among South African citizens. On the Contrast, preservation and promotion of traditional games is vital as they offer indigenous populations accessible and culturally relevant means to maintain health and wellness. In this regard, it is important to recognize the importance of preserving and promoting traditional games as they potentially serve as a method for indigenous people to maintain their health and wellness in a way that is accessible and culturally relevant to them. These games have gained popularity in South Africa, with initiatives underway to show- case them globally fostering cultural exchange. Further, revitalizing and conserving these games can cultivate a culture of health and wellbeing in South Africa.

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated bidirectional relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass &lt;0.789 in men and &lt;0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs=1.213, 95% CIs=1.050–1.402). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs=1.564, 95% CIs=1.378–1.775). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a bidirectional relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin precursors. For the past decade, researchers are focusing extensively on miRNA profiles in various plants. However studies on precursor miRNAs (pre-miRNAs) global profiling stay static even in model plants. Here, for the first time in a non-model plant, Abelmoschus esculentus with negligible genome information, we are reporting the global profiling to characterize the miRNAs and their associated pre-miRNAs by applying next generation sequencing approach. Preliminarily we performed sRNA (small RNA) sequencing with five biological replicates of leaf samples to attain 207,285,863 reads and data analysis using miRPlant keyed out 128 known and 845 novel miRNA candidates. With the objective to seize their associated hairpin precursors, we accomplished pre-miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged, adaptor trimmed and the resulting 40-241 nt (nucleotide) sequences were picked out for analysis by using perl scripts from miRGrep tool and in-house built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying stringent criteria of dicer cleavage pattern and perfect stem loop structure revealed precursors for 57 known miRNAs of 15 families and 18 novel miRNAs. Quantitative Real Time (qRT) PCR was performed to determine the expression of selected miRNAs.

Globally, noncommunicable diseases (NCDs) were responsible for 41 million deaths in 2016, with the majority of these occurring in low and middle-income countries. These diseases were on the rise as a result of unhealthy, low-quality, and unbalanced diets, which resulted in overweight and obesity. The National School Nutrition Programme (NSNP) was created to regulate the foods sold to schoolchildren. To ascertain school management teams' perspectives on the relationship between the NSNP and the development of lifestyle diseases. A phenomenological qualitative study using Focus Group Discussions among 16 purposively selected members of the School Management Teams were conducted in Mt Frere, Eastern Cape in 2016. The narrative data was analyzed using Tesch's eight-phase thematic analysis approach. The data analysis revealed two themes (NSNP and the vendor system) and six sub-themes. The NSNP was viewed as making a significant contribution to children's food security, thereby improving academic output. However, reengineering of the NSNP was need through improved budgeting and inclusion of breakfast in the menu to control NCDs risk factors. The current implementation of the vendor system did not support reduction of NCDs risk factors. Improved implementation of the guide to vendor system is needed.

Background: Adolescence is a developmental stage when there is a high risk of engaging in non-suicidal self-injury (NSSI). There is recent interest in the study of thwarted belongingness and perceived burdensome as variables associated with the frequency of NSSI in adolescents. Meaning in life (MIL) could be negatively associated with thwarted belongingness and perceived burdensome. To date, no studies have analyzed whether thwarted belongingness and perceived burdensomeness could be associated with the frequency of NSSI in adolescents. On the other hand, no studies have analyzed the buffering role of MIL in the association between thwarted belongingness and perceived burdensomeness and the frequency of NSSI. Aims: a) to test whether thwarted belongingness and perceived burdensomeness are associated with NSSI frequency; b) to test whether MIL moderates the association between thwarted belongingness and NSSI frequency; and c) to test whether MIL moderates the association between perceived burdensomeness and NSSI frequency. Method: The sample consisted of N = 1531 participants between 12 and 18 years old from Spain. The participants filled out the Inventory of Statements about Self-Injury, Purpose-In-Life Test-Adolescents Version, and Interpersonal Needs Questionnaire. Moderation analysis were performed. Results: Thwarted belongingness and perceived burdensomeness were positively associated with the frequency of NSSI in Spanish adolescents. MIL was a moderating variable between thwarted belongingness and the frequency of NSSI, and between perceived burdensomeness and the frequency of NSSI. Conclusion: Thwarted belongingness and perceived burdensomeness could be a risk factor for NSSI and MIL could be a protective factor against NSSI, and adding these variables to current descriptive theories of NSSI in adolescents would allow us to improve the assessment and treatment protocols for adolescents with NSSI.

Diagnostics and decomposition of atmospheric disturbances in a planar flow are considered and applied to numerical modeling results with the direct possibility to use in atmosphere monitoring especially in such strong events which follow magnetic storms. The study examines a situation in which the stationary equilibrium temperature of a gas may depend on a vertical coordinate, that seriously complicates the problem solution. The relations connecting perturbations for acoustic and entropy modes are analytically established and led to the solvable diagnostic equations. These perturbation structures, found as the equation solutions specify acoustic and entropy modes in an arbitrary stratified gas under the condition of stability. These time-independent diagnostic relations link gas perturbation variables of the acoustic and the entropy modes. Hence, they provide the ability to decompose the total vector of perturbations into acoustic and non-acoustic (entropy) parts uniquely at any instant within the all accessible heights range. As a prospective model, we consider the diagnostics at the height interval [120;180] km, where the equilibrium temperature of a gas depends linearly on the vertical coordinate. For such a heights range it is possible to proceed with analytical expressions for pressure and entropy perturbations of gas variables. Individual profiles of acoustic and entropy parts for some data, obtained by numerical experiment, are illustrated by the plots for the pure numerical data against ones obtained by the model. The total energy of a flow is determined for both approaches and its height profiles are compared.

A supply chain management (SCM) system is a strategic cooperative that organically integrates all supply chains to improve the performance of a company. The greatest critical success factor of SCM is partnership. Without cooperation between companies, SCM performance is limited. Does this imply, therefore, that companies within the supply chain can achieve mutual transactions equally? If the power between companies is unequal, how does this affect their partnership? The focus of this study is to assess whether power types enhance SCM performance through partnerships. We categorize power types as mediated and non-mediated. Mediated power is categorized based on coercion, reward, and legitimate, while non-mediated power is categorized based on information, expert, and reference. Therefore, this study examines how power types form a causal partnership relationship within the supply chain, and performs an empirical investigation on how the partnerships influence SCM performance.

Cause-Related Marketing (CRM) has emerged as a new concept that links CSR activities to marketing, enabling corporations to pursue both building company-consumer partnership and gaining sustainable mutual benefits that are elicited from the partnership. Among various cause-related marketing activities, on-line cause-related advertising is the most commonly used one. The purpose of this study is to examine the effects of on-line cause-related advertising and moderating role of ethical consumption propensity. In particular, this study intends to contribute to successful development of on-line cause-related advertising strategy by focusing on the relationship between the four factors: customers' perception of on-line cause-related advertising, brand-consumer relationship, brand attachment and loyalty. The results of this study are as follows: First, customers' perception of on-line cause-related advertising was related positively to consumer-brand- relationship. Second, brand-consumer relationship was related positively to brand attachment and customer loyalty. Third, brand attachment was related positively to customer loyalty. Furthermore, from the consumer’s psychological viewpoint, ethical consumption propensity had a significant moderating effect to between customers' perception of cause-related advertising and brand-consumer relationship as well as brand attachment. The results of this study may contribute to the existing literature as an new empirical attempt to examine the effect of the on-line cause-related advertising.

The present reality about the Nigerian economy calls for investment and development in the non-oil sector. This becomes necessary as a result of fall in the oil price in the global market. This paper examined the Bayesian Vector Autoregression (BVAR) modeling and forecasting of the dynamic interrelationship between Economic growth and revenue from the oil and non-oil sectors in Nigeria. To achieve this, annual data on Gross Domestic Product (GDP), revenue from oil and non-oil sectors were collected from Central Bank of Nigeria (CBN) bulletin, the sample from 1981 to 2008 was used for analysis, while sample from 2009 to 2014 was used for model validation. Six (6) versions of Sims-Zha BVAR models were compared for out-of-sample forecast, the result revealed the superiority of the BVAR6 model over the other BVAR models. Lastly, evidence from the decomposition forecast errors revealed that revenue of oil sector contributed 7.69% to GDP while revenue from non-oil sector contributed 0.12% to GDP in Nigeria. This paper therefore recommended that the present government should encourage investment that is geared toward development in the non-oil sector, of which it has the capacity to improve the Economic growth of the Nigerian economy.

This paper proposes how to reduce the consumption of active electrical energy (kwh) by 90.3% while maintaining the same mechanical work speed (RPM) at variable torque loads (fans or air-fluid blowers, centrifugal pumps are not included). of water and similar fluids), by using the “Fan Law” in an innovative way in PMSM-type synchronous motors (a comparative study never before carried out on the Fan Law). The work is carried out comparatively between brushless a-synchronous motors with starting loop (or motor with a short-circuited loop) versus brushed a-synchronous motors and PMSM-type synchronous motors without the need to use VDF (variable frequency drives), simplifying technology (electronics) and saving costs in an innovative way (R+D+i). The case study was developed on a design applied to a centrifugal air extractor/blower with PMSM/IPM type synchronous motor. Applying one of the fan affinity laws –with the impeller diameter 10.5 (mm) constant- the electrical power absorbed by the blower motor is proportional to the cube of the shaft speed: . Being “P” power (Watts) and “N” speed (RPM). Carrying out a comparative study between power (watts), active energy consumption (kwh) and rotational speed (RPM). This has a direct impact on the costs of residential and commercial single-phase active electrical energy consumption, measured in kilowatt-hours (kwh). Carrying out a comparative study between three (3) types of alternating current (AC) electrical machines, according to the NEMA (National Electrical Manufacturers Association); AC motors fall into three (3) categories. One (1), synchronous motors (Syncrhonous Motor) of three types: (1a) excitation by DC (DC Excited Motor), (1b) permanent magnet (Permanent Magnet Motor) and (1c) reluctance motor (Reluctance Motor) or motor Step by Step. Two (2), asynchronous induction motors of two types: (2a) Squirrel-Cage Induction Motor and (2b) Wound-Rotor Induction Motor. Three (3) series-wound motor (Series-Wound Motor) also called universal motor (they have carbons).

Hepcidin (DTHFPICIFCCGCCHRSKCGMCCKT), an iron regulatory hormone is a 25 amino acid peptide with 4 intramolecular disulfide bonds, circulating in blood. Its hormonal activity is indirect and consists of marking ferroportin-1 (an iron exporter) for degradation. Hepcidin biosynthesis involves N-terminally extended precursors prepro-hepcidin and pro-hepcidin, processed by peptidases to the final 25-peptide form. A sequence-specific formation of disulfide bonds and export of the oxidized peptide to the bloodstream follows. In this study we considered the fact that prior to export, reduced hepcidin may function as an octathiol ligand bearing some resemblance to the N-terminal part of α-domain of metallothioneins. Consequently, we studied its ability to bind Zn(II) and Cd(II) ions using the original peptide and a model for prohepcidin, extended N-terminally with a stretch of five arginine residues (5R-hepcidin). We found that both form equivalent mononuclear complexes with two Zn(II) or Cd(II) ions saturating all eight Cys residues. The average affinity at pH 7.4, determined from pH-metric spectroscopic titrations, is 1010.1 M-1 for Zn(II) ions, the Cd(II) ions bind with affinities of 1015.2 M-1 and 1014.1 M-1. Using mass spectrometry and 5R-hepcidin we demonstrated that hepcidin can compete for Cd(II) ions with metallothionein-2, a cellular cadmium target. These studied empowered us to conclude that hepcidin binds Zn(II) and Cd(II) sufficiently strongly to participate in zinc physiology and cadmium toxicity under intracellular conditions.

Nonequilibrium work switching simulations and Jarzynski’s equation are a reliable method to compute free energy differences, ΔAlow→high, between two levels of theory, such as a pure molecular mechanical (MM) and a quantum mechanical/molecular mechanical (QM/MM) description of a system of interest. Despite the inherent parallelism, the computational cost of this approach can quickly get very high. This is particularly true for systems where the core region, the part of the system to be described at different levels of theory, is embedded in an environment, such as explicit solvent water. We find that even for relatively simple solute–water systems, switching lengths of at least 5 ps are necessary to compute ΔAlow→high reliably. In this study, we investigate two approaches towards an affordable protocol, with emphasis on keeping the switching length well below 5 ps. Inserting a hybrid charge intermediate state with modified partial charges which resembles the charge distribution of the desired high level makes it possible to obtain reliable calculations with 2 ps switches. Attempts using step-wise linear switching paths, on the other hand, did not lead to improvement, i.e., faster convergence for all systems. To understand these findings, we analyzed the solutes’ properties as a function of partial charges used, the number of waters in direct contact with the solute, and studied the time needed for water molecules to reorient themselves upon a change in the solute’s charge distribution.

The vast majority of antibodies generated against a virus will be non-neutralising1. However, this does not denote an absence of protective capacity. Yet, within the field there is typically a large focus on antibodies capable of directly blocking infection (neutralising antibodies, nAbs) of either specific viral strains or multiple viral strains (broadly-neutralising antibodies, bnAbs). More recently, a focus on non-neutralising antibodies (nnAbs), or neutralisation-independent effects of nAbs, has emerged. These can have additive effects on protection or in some cases, be a major correlate of protection. As their name suggests, nnAbs do not directly neutralise infection but instead, through their Fc domains, may mediate interaction with other immune effectors to induce clearance of viral particles or virally infected cells. nnAbs may also interrupt viral replication within infected cells. Developing technologies of antibody modification and functionalisation may lead to innovative biologics that harness the activities of nnAbs for antiviral prophylaxis and therapeutics. In this review, we discuss specific examples of nnAb actions in viral infections where they have known importance. We also discuss the potential detrimental effects of such responses. Finally, we explore new technologies for nnAb functionalisation to increase efficacy or introduce favourable characteristics for their therapeutic applications.

Prediction of protein-ligand binding affinities is crucial for computational drug discovery. A number of deep learning approaches have been developed in recent years to improve the accuracy of such affinity prediction. While the predicting power of these systems have advanced to some degrees depending on the dataset used for model training and testing, the effects of the quality and quantity of the underlying data have not been thoroughly examined. In this study, we employed erroneous datasets and data subsets of different sizes, created from one of the largest databases of experimental binding affinities, to train and evaluate a deep learning system based on convolutional neural networks. Our results show that data quality and quantity do have significant impacts on the prediction performance of trained models. Depending on the variations in data quality and quantity, the performance discrepancies could be comparable to or even larger than those observed among different deep learning approaches. In particular, the presence of proteins during model training leads to a dramatic increase in prediction accuracy. This implies that continued accumulation of high-quality affinity data, especially for new protein targets, is indispensable for improving deep learning models to better predict protein-ligand binding affinities.

Considering the controversial benefits of video-assisted thoracoscopic surgery (VATS), we intended to evaluate the impact of surgical approach on cardiac function after lung resection using myocardial work analysis. Echocardiographic data of 45 patients (25 thoracotomy vs. 20 VATS) were retrospectively analyzed. All patients underwent transthoracic echocardiography (TTE) 2 weeks before and after surgery, including two-dimensional speckle tracking and tissue doppler imaging. No notable changes in left ventricular (LV) function, assessed mainly using the LV global longitudinal strain (GLS), global myocardial work index (GMWI), and global work efficiency (GWE), were observed. Right ventricular (RV) TTE values, including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TASV), and RV free-wall GLS (RVFWGLS), indicated greater RV function impairment in the thoracotomy group than in the VATS group [TAPSE (mm): 17.90 ± 3.80 vs. 20.60 ± 3.50, p &lt; 0.018; TASV (cm/s): 12.40 ± 2.90 vs. 14.60 ± 2.50, p &lt; 0.010; RVFWGLS (%): −11.50 ± 8.50 vs. −17.50 ± 9.70, p &lt; 0.033), respectively]. Unlike RV function, LV function remained preserved after lung resection. The thoracotomy group exhibited greater RV function impairment than did the VATS group. Further studies should evaluate the long-term impact of surgical approach on cardiac function.

Understanding the binding behavior and conformational dynamics of intrinsically disordered proteins (IDPs) is crucial for unraveling their regulatory roles in biological processes. However, their lack of stable 3D structures poses challenges for analysis. To address this, we propose an algorithm that explores IDP binding behavior with protein complexes by extracting topological and geometric features from the protein surface model. Our algorithm identifies a geometrically favorable binding pose for the IDP and plans a feasible trajectory to evaluate its transition to the docking position. We focus on IDPs from Homo sapiens and Mus-musculus, investigating their interaction with the Plasmodium Falciparum (PF) pathogen associated with malaria-related deaths. We compare our algorithm with HawkDock and HDOCK docking tools for quantitative (computation time) and qualitative (binding affinity) measures. Our results indicate that our method outperforms the compared methods in computation performance and binding affinity of experimental conformations.

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress, and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischaemia. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies.

Non-impregnated small pore graphite (NSPG) with the compact microstructure for using in molten salt reactors (MSR) was prepared by the novel process, and the pore diameter of the obtained graphite was reduced to ~800 nm. The irradiation evaluation of the prepared graphite was carried out by 7 MeV Xe26+ ion irradiation and the microstructural changes of the graphite were investigated with IG-110 as a comparison. The graphitization degree of NSPG was higher than that of IG-110, though it was not subjected to an impregnation process. Under low-dose ion irradiation (

Circulating cell-free DNA (cfDNA) refers to small fragments of DNA molecules released after programmed cell death and necrosis in several body fluids such as blood, saliva, urine, and cerebrospinal fluid. The discovery of cfDNA has revolutionized the field of non-invasive diagnostics in the oncologic field, in prenatal testing, and in organ transplantation. Despite the potential of cfDNA and the solid results published in recent literature, several challenges remain, represented by low abundance, need for highly sensitive assays and analytical issues. In this review, the main technical advances in cfDNA analysis are presented and discussed, with a comprehensive examination of the current available methodologies applied in each field. Considering the potential advantages of cfDNA, this biomarker is increasing its consensus among clinicians, as it consents to monitor patients’ conditions in an easy and non-invasive way, offering a more personalized care. Nevertheless, cfDNA analysis is still considered a research marker to be further validated, and very few centers are implementing its analysis in the real-life assistance. As technical improvements are enhancing the performances of cfDNA analysis, its application will transversally improve patients’ quality of life.

It is unknown whether postprandial plasma glucose measured from blood taken between 4 and 7.9 h (PPG4-7.9h) is associated with mortality from hypertension, diabetes, or cardiovascular disease (CVD). This study aimed to investigate these associations in 4,896 US adults who attended the third National Health and Nutrition Examination Survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PPG4-7.9h for mortality. This cohort was followed up for 106,300 person-years (mean follow-up, 21.7 years). A 1-natural-log-unit increase in PPG4-7.9h was associated with a higher risk of mortality from hypertension (HR, 3.50; 95% CI, 2.34-5.24), diabetes (HR, 11.7; 95% CI, 6.85-20.0), and CVD (HR, 2.76; 95% CI, 2.08-3.68) after adjustment for all the tested confounders except hemoglobin A1c (HbA1c). After further adjustment for HbA1c, PPG4-7.9h remained positively associated with mortality from hypertension (HR, 2.15; 95% CI, 1.13-4.08) and CVD (HR, 1.62; 95% CI, 1.05-2.51), but was no longer associated with diabetes mortality. Subgroup analyses showed that similar results were obtained in the sub-cohort of participants without a prior diagnosis of myocardial infarction or stroke. In conclusion, PPG4-7.9h predicts mortality from hypertension and CVD independent of HbA1c.

A temperature-modulated pyroelectricity measurement system for a small single crystal is developed and applied to standard sample measurements performed on a thin single crystal of lithium niobate. The modulation measurement is based on the AC technique, in which the temperature of the sample is periodically oscillated, and the synchronized pyroelectric signal is extracted using a lock-in amplifier. Temperature modulation is applied by irradiating periodic light on the sample placed in the heat exchange gas. To apply this technique to the transparent reference sample, a commercially available black resin is coated on the sample’s surface to absorb the light energy and transmits it to the specimen. The experimental results are analyzed using a two-layer heat transfer model to verify the effect of the light-absorbing layer as well as the non-contact temperature modulation system.

Quantifying an imaging modality’s ability to reproduce results is important for establishing its utility. In Magnetic Resonance Spectroscopic Imaging (MRSI), new acquisition protocols are regularly introduced, which improve upon their precursors with respect to signal-to-noise ratio (SNR), total acquisition duration, and nominal voxel resolution. This study has quantified the within-subject and between-subject reproducibility of one such new protocol (reduced-Field-of-View-Density-Weighted-Concentric-Ring-Trajectory (rFOV-DW-CRT) MRSI) by calculating the Coefficient of Variance of data acquired from a test-retest experiment. The Posterior Cingulate Cortex (PCC) and the Right Superior Corona Radiata (SCR) were selected as the Regions of Interest (ROIs) for Grey Matter (GM) and White Matter (WM), respectively. CVs for between-subject and within-subject are consistently around or below 15% for Glx, tCho, and Myo-Ins and below 5% for tNAA and tCr.

Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.

The prediction of drug-target interactions plays a fundamental role in facilitating drug discovery, where the goal is to find prospective drug candidates. With the increase in the number of drug-protein interactions, machine learning techniques, especially deep learning methods, have become applicable for drug-target interaction discovery because they significantly reduce the required experimental workload. In this paper, we present a spontaneous formulation of the drug-target interaction prediction problem as an instance of multi-instance learning. We address the problem in three stages, first organizing given drug and target sequences into instances via a private-public mechanism, then identifying the predicted scores of all instances in the same bag, and finally combining all the predicted scores as the output prediction. A comprehensive evaluation demonstrates that the proposed method outperforms other state-of-the-art methods on three benchmark datasets.

Ice-binding proteins (IBPs) have several functions that permit their hosts to thrive in the presence of ice. The ability of IBPs to control ice growth makes them potential additives in various industries ranging from food storage and cryopreservation to anti-icing systems. For IBPs to be used in commercial applications, however, methods are needed to produce sufficient quantities of high-quality proteins. Here, we describe a new method for IBP purification, termed falling water ice purification (FWIP). The method is based on the affinity of IBPs for ice. A crude IBP solution is allowed to flow continuously over the large chilled vertical surface of a commercial ice machine. The temperature of the surface is lowered gradually until ice crystals are produced, to which the IBPs bind but other solutes do not. As in other ice affinity methods, FWIP does not require molecular tags and is suitable for purifying recombinant IBPs as well as IBPs from natural sources. The advantage of FWIP over other ice affinity methods is that it exploits an ice machine designed to produce large volumes of clear ice daily. This system can be easily scaled up and suits the purification of industrial quantities of IBPs. The FWIP method significantly advances the use of IBPs in research and industry.

Thanks to the continued development of experimental structural biology and the half-a-century old Protein Data Bank, 2021 saw a big step forward in the development of protein structure prediction with deep learning algorithms. Recently, DeepMinds AlphaFold has determined the structures of ∼ 200 million proteins from 1 million species. The speed of this progress raise the question of what becomes possible for computational drug discovery and design when we have a systems-wide account of the structures and motions of most proteins. Therefore, this article puts forward the concept of a general intermolecular binding affinity calculator (GIBAC): Kd = f(molA, molB, envPara), towards the acceleration of traditional computer-aided drug design (CADD) and artificial intelligence-integrated drug discovery (AIDD), for both small molecules and biologics such as therapeutic proteins.

Many systems in nature and laboratories are far from equilibrium and exhibit significant fluc- tuations, invalidating the key assumptions of small fluctuations and short memory time in or near equilibrium. A full knowledge of Probability Distribution Functions (PDFs), especially time- dependent PDFs, becomes essential in understanding far-from-equilibrium processes. We consider a stochastic logistic model with multiplicative noise, which has gamma distributions as stationary PDFs. We numerically solve the transient relaxation problem, and show that as the strength of the stochastic noise increases the time-dependent PDFs increasingly deviate from gamma distributions. For sufficiently strong noise a transition occurs whereby the PDF never reaches a stationary state, but instead forms a peak that becomes ever more narrowly concentrated at the origin. The addition of an arbitrarily small amount of additive noise regularizes these solutions, and re-establishes the existence of stationary solutions. In addition to diagnostic quantities such as mean value, standard deviation, skewness and kurtosis, the transitions between different solutions are analyzed in terms of entropy and information length, the total number of statistically distinguishable states that a system passes through in time.

We analyzed the affinity-proteomics data of saliva absorbed to plate-bound Spike protein of SARS-CoV-2, and identified major virus-binding proteins as MUC7, MUC5B, DMBT1, and neutrophil defensins. Furthermore, we found that saliva from healthy donors inhibited the binding of Spike-protein-specific polyclonal antibodies to Spike antigen. These data suggest that the Spike protein’s glycoprotein-binding domains (GBD) may be targeted to block virus adherence or entry of SARS-CoV-2.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

Objetives: Adequate donor-recipient matching is necessary to achieve the best renal function after transplantation. The nephron load received from the donor, which can be reflected in variables such as age, sex and body mass index, may influence the evolution of the graft. Our objetive was develop a combined score according to the donor-recipient pairing in age, sex and body mass index, and assess its influence on the evolution of the renal graft. Materials and methods: Transplant patients between 2013 and 2020 who had at least 1 year of post-transplant follow-up. A ranking of 0 to 2 points was awarded according to the match between donor and recipient for sex, age and body mass index individually, with higher rank to greater mismatch. Subsequently, a Score with value of 0 to 6 points was created with the combined ranking of the indivudual variables, analyzing its influence on the evolution of the graft by multivariate linear regression. Results: 280 patients followed for 4.3 years of median. Worse renal function was observed at the end of follow-up as the range of each variable increased separately, and the Score created, with a worsening of renal function as the combined Score increased in the multivariate analysis: Coefficient B= -2.4 ml/min, p=0.018. Conclusions: An adequate match between donor and recipient in age, sex and body mass index using this combined Score can help achieve better kidney function after transplantation.

The method for quantitative analysis is based on the direct measurement of the analyte using differential pulse voltammetry (DPV), exploiting its oxidation peak. Calibration curves are set up to evaluate the figures of merit of the analytical method (LOD, LOQ, linear range). The application of the sensor for the dosing of GA in real matrices is carried out by analyzing non-alcoholic and alcoholic beverages and comparing the results with those reported in the literature and with the content of total polyphenols determined by the Folin-Ciocalteu method. In all cases, concentrations of GA align with those previously found in the literature for the beverages examined. Moreover, the values are always lower than the total polyphenols content; this demonstrates the good selectivity of the sensor that can discriminate the target molecule from other polyphenols present.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

Increasingly small, non-palpable testicular incidentalomas <1cm are discovered in the clinical practice. The ESUR Scrotal and Penile Imaging Working Group suggests active surveillance with US, and surgery only for nodules that grow. This approach, however, requires validation. A consecutive series of 127 incidentalomas were initially followed-up and operated if they were growing (n=28), or because of preference of the patient and of the referring urologist (n=11). For the lesions that were growing specific growth rate (SGR) and doubling time (DT) were calculated assuming an exponential grow. Also, the velocity of increase of the average diameter (∆Dav) and of the maximum diameter (∆Dmax) were calculated. Of the 127 nodules which were initially followed-up, 6 disappeared, 8 reduced in size, 85 were stable, and 28 increased in size. All 18 malignant tumours, 8/9 benign tumours, and 2/12 surgically proved non-neoplastic lesions were growing. The best cut-off values of the growth indicators to differentiate between malignant and non-malignant histology were 3.47x10-3 %volume/day, ≤179 days, >10x10-3 mm/day, and >5x10-3 mm/day for SGR, DT, ∆Dmax, ∆Dav, respectively. A conservative approach of non-growing small incidentalomas is safe. Malignant and non-malignant small incidentalomas can be effectively differentiated based on growing parameters, even though superimposition exists.

Water pollution, intensified by the release of hard-to-degrade pollutants, poses severe threats to ecosystems, human health, and economic development. The existing advanced oxidation processes often involve high operational costs and may result in secondary pollution, highlighting the necessity for innovative and more sustainable solutions. To address these challenges, our study introduces a cost-effective and eco-friendly corona discharge barrier plasma discharger for wastewater treatment. Through the central composite design/response surface methodology, a high decolorization rate of 98% of methylene blue (MB) within 10 minutes was achieved by optimizing parameters such as pH and voltage. Furthermore, the mechanisms of the generation of reactive oxygen species via this device was discussed in detail and the degradation pathways of MB were described. Moreover, this device is also very energy-efficient, with a low energy density and electrical energy per order of 0.15 watt/mL and 5.79 kWh/m³/order, respectively. In conclusion, the plasma discharger developed in this study provides a cost-effective and environmentally sustainable solution for dye wastewater treatment. This research contributes significantly to the advancement of sustainable dye wastewater management practices, offering an innovative method that meets both environmental and economic objectives.

Phosphorus deficiency highly interferes with plant growth and development. Plants respond to the persistent P deficiency by coordinating the expression of genes involved in the alleviation of the stress. Promoters of phosphate transporter genes are of great choice for the development of genetically modified plants with enhanced phosphate uptake abilities, which improve crop yields in phosphate-deficient soils. In our previous study, the sugarcane phosphate transporter PHT1;2 gene, showed a significantly high expression under salinity stress. In this study, the Erianthus arundinaceus EaPHT1;2 gene was isolated and characterized using various in-silico tools. The deduced 542 amino acid residues have 10 transmembrane domains, with a molecular weight and isoelectric point of 58.9 kDa and 9.80, respectively. They displayed 71–96% similarity with Arabidopsis thaliana, Zea mays, and Saccharum hybrid. To elucidate the function of the 5’ regulatory region, the 1.1kb promoter was isolated and validated in tobacco transgenics under Pi stress. The EaPHT1;2 promoter activity was detected using the β-glucuronidase (GUS) assay. While the EaPHT1;2 promoter showed 3 to 4.2-fold higher expression than the most widely used CaMV35S promoter. The 5’ deletion analysis with and without 5’UTR regions, revealed that a small size 374 bp fragment with the highest promoter activity among 5′ truncated fragments, which was 2.7 and 4.2 times higher than the well-used CaMV35S promoter under normal and Pi-deprivation conditions, respectively. The strong and short promoter of EaPHT1;2 with 374 bp showed significant expression in low Pi-stress conditions and it could be a valuable source for the development of stress-tolerant transgenic crops

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. In this review, we discuss the role of IL-1β in NSCLC, its involvement in inflammatory pathways, and explore its potential role in the treatment of NSCLC.

The preservation of the authenticity of a building artefact is a responsible practice. On the other side, the need to save the building artefact from the natural and anthropic degradation, to ensure the structural reliability to the different actions, to define an efficient maintenance program are big challenges, that involves the cooperation of several professionals, responsible use of innovative techniques and materials that are nowadays available. This paper focuses on a specific design approach for the rehabilitation works of ancient constructions in archaeological sites. The proposed conceptual design approach implies different steps that allow the optimization of the design at an increasing level of knowledge on the existing structures and their materials. The design procedure on historical constructions generally includes the following steps: the collection of data, the structural identification, hazard, and vulnerability analysis, damage and risk analysis, a cost-benefit analysis, so only at the end of the process, the final design is achieved. In the archaeological area, some important design aspects cannot be defined before the execution work phase, since some elements could be revealed and identified during work execution, as a consequence, the final design has been often optimized after all this information has been acquired. A studied case in the archaeological site of Pompeii is herein presented to prove the efficiency of the proposed approach.

Although natural products are an important source of drugs and drug leads, identification and validation of their target proteins have proven difficult. Here, we report the development of a systematic strategy for target identification and validation employing drug affinity responsive target stability (DARTS) and mass spectrometry imaging (MSI) without modifying or labeling natural compounds. Through a validation step using curcumin, which targets aminopeptidase N (APN), we successfully standardized the systematic strategy. Using label-free voacangine, an antiangiogenic alkaloid molecule as the model natural compound, DARTS analysis revealed vascular endothelial growth factor receptor 2 (VEGFR2) as a target protein. Voacangine inhibits VEGFR2 kinase activity and its downstream signaling by binding to the kinase domain of VEGFR2, as was revealed by docking simulation. Through cell culture assays, voacangine was found to inhibit the growth of glioblastoma cells expressing high levels of VEGFR2. Specific localization of voacangine to tumor compartments in a glioblastoma xenograft mouse was revealed by MSI analysis. The overlap of histological images with the MSI signals for voacangine was intense in the tumor regions and showed colocalization of voacangine and VEGFR2 in the tumor tissues by immunofluorescence analysis of VEGFR2. The strategy employing DARTS and MSI to identify and validate the targets of a natural compound as demonstrated for voacangine in this study is expected to streamline the general approach of drug discovery and validation using other biomolecules including natural products.