Dedicator-of-cytokinesis (DOCK), a family of guanine-nucleotide exchange factors (GEFs), comprises four subfamilies, named from A to D. DOCK-D comprises DOCK9, DOCK10, and DOCK11. The GEF activity involves translocation from the cytoplasm to the plasma membrane (PM), as assessed by the transfection of tagged proteins. However, the cellular localization of endogenous DOCK proteins is poorly understood. In this paper, to gain a better understanding of the role of the DOCK-D proteins, we studied their distribution between cytosol and nucleoplasm in 11 cell lines. DOCK-D proteins were distributed with variable cytosolic or nuclear predominance, although the latter was common for DOCK9 and DOCK11. These results suggest that the DOCK-D proteins may perform new nuclear functions, which remain to be discovered. Furthermore, we found that DOCK10 levels are increased by interleukin-4 (IL-4) in B-cell lymphoid neoplasms other than chronic lymphocytic leukemia (CLL) such as mantle cell lymphoma and diffuse large B-cell lymphoma. We also found evidence for an induction of the cytosolic levels of DOCK10 by IL-4 in CLL. Finally, we obtained a valid DOCK10 antiserum for immunofluorescence (IF) microscopy that, as an antibody against the hemagglutinin (HA) tag, marked PM ruffles and filopodia in HeLa cells with inducible expression of HA-DOCK10. Full article

The adsorption of different isotopic ozone mixtures on TiO₂ at 77K was studied using FTIR spectroscopy and DFT calculations of cluster models. In addition to weakly bound ozone with band positions close to those of free or dissolved molecules, the spectrum of chemisorbed species was observed. The splitting of the ν₁₊₃ combination band to eight maxima due to different isotopomers testified to the loss of molecule symmetry. The frequencies of all the isotopic modifications of the ozone molecules which form monodentate or bidentate complexes with four- or five-coordinated titanium atoms were calculated and compared with those of experimentally observed spectra. The four considered complexes adequately reproduced the splitting of the ν₁₊₃ vibration band and the lowered anharmonism of chemisorbed O₃. The energetically most favorable monodentate complex with four-coordinated titanium atoms showed good agreement with the observed spectra, although a large difference between the frequencies of ν₁ and ν₃ modes was found. For better coherence with the experiment, the interaction of the molecule with adjacent cations must be considered. Full article

This article discusses the phenomenon of luminescence in the production and visualization of images from an art-practice standpoint. The theoretical argument is developed through an analysis of artistic work that explores, inserts, expands, articulates, and interrogates the internal contradictions of UV light and the transitivity of light-sensitive materials in installation contexts. This investigation explores complexities in the encounter of antagonistic concepts: the threshold phenomena between materiality and immateriality, visibility and invisibility, light and darkness, disclosure and concealment. It aims to articulate a new perspective on contemporary debates on physiological, psychological, and environmental effects of light and darkness, articulated through aesthetic experience and artistic practice. Methods for engaging in the sensation of light and darkness will be introduced and how it unfolds as experiential qualities within installation projects will be considered. Full article

The development and construction of a prototype device (food parcel locker), consisting of small cooling and freezing chambers (boxes) ensuring temperature conditions (+5 C or −18 °C), enabling food storage were carried out. The innovative solutions have been introduced in the MainBox device: the appropriate construction of the device (materials, cooling installation), properly functioning systems (control of chillers, security, temperature monitoring), and propane as refrigerant (high energy efficiency, low global warming potential). The risk of explosion has been eliminated by closing of the cooling installation and reducing of propane amount. The refrigeration unit has been adapted to work in external conditions by installing additional elements (pressure switches for compressor protection and for condensing pressure control). In real conditions, the operation of the innovative MainBox food storage device allowing the receipt of food products without having to wait for a supplier was verified. The temperature distribution in all chambers of the cooling and freezing module was investigated using a thermal imaging camera and a temperature monitoring system. The correct operation of MainBox devices was verified during their loading with food products that require specific temperature conditions during storage. Full article

The implementation and validation of anti-SARS-CoV-2 IgG serological assays are reported in this paper. S1 and RBD proteins were used to coat ELISA plates, and several secondary antibodies served as reporters. The assays were initially validated with 50 RT-PCR positive COVID-19 sera, which showed high IgG titers of mainly IgG1 isotype, followed by IgG3. Low or no IgG2 and IgG4 titers were detected. Then, the RBD/IgG assay was further validated with 887 serum samples from RT-PCR positive COVID-19 individuals collected at different times, including 7, 14, 21, and 40 days after the onset of symptoms. Most of the sera were IgG positive at day 40, with seroconversion happening after 14–21 days. A third party conducted an additional performance test of the RBD/IgG assay with 406 sera, including 149 RT-PCR positive COVID-19 samples, 229 RT-PCR negative COVID-19 individuals, and 28 sera from individuals with other viral infections not related to SARS-CoV-2. The sensitivity of the assay was 99.33%, with a specificity of 97.82%. All the sera collected from individuals with infectious diseases other than COVID-19 were negative. Given the robustness of this RBD/IgG assay, it received approval from the sanitary authority in Mexico (COFEPRIS) for production and commercialization under the name UDISTEST-V2G^®. Full article

This review paper examines the past, present, and future of sustainable consumption and production (SCP). The history of the Sustainable Development Goal No. 12 (i.e., to ensure sustainable consumption and production patterns) is presented and analyzed. A definition of the sustainable consumption is given and the role of education is explained. The present status and existing trends of SCP are introduced by analyzing unsustainable behavior and the existing dilemma, namely sustainable growth or degrowth. A very broad range of methods is used for measuring and evaluating SCP within sustainable development. To forecast the future of SCP, important trends are presented. The future development of SCP will follow several megatrends and it will require reduced personal and collective consumption (degrowth). Energy usage in buildings, renewable energy sources, and energy storage will be important in that respect. Transportation emissions will continue to be lowered. Waste, especially food waste, shall be reduced, and consumer products shall become more durable. All waste must be collected and separated to be reused. SPC is elaborated in view of the two approaches—Industry 4.0 (smart factory), and the “Sixth Wave� evolution. Net-zero greenhouse gas emissions, resource efficiency, and zero waste will be at the forefront of future activities. A circular economy requires extension of product lifetimes, and the reuse and recycling of products. Reducing emissions, pollution and specific energy, water, and raw material usage (especially critical raw materials), as well as the role of digitalization, will be important. Full article

Virus infection is one of the threats to the health of organisms, and finding suitable antiviral agents is one of the main tasks of current researchers. Metal ions participate in multiple key reaction stages of organisms and maintain the important homeostasis of organisms. The application of synthetic metal-based nanomaterials as an antiviral therapy is a promising new research direction. Based on the application of synthetic metal-based nanomaterials in antiviral therapy, we summarize the research progress of metal-based nanomaterials in recent years. This review analyzes the three inhibition pathways of metal nanomaterials as antiviral therapeutic materials against viral infections, including direct inactivation, inhibition of virus adsorption and entry, and intracellular virus suppression; it further classifies and summarizes them according to their inhibition mechanisms. In addition, the use of metal nanomaterials as antiviral drug carriers and vaccine adjuvants is summarized. The analysis clarifies the antiviral mechanism of metal nanomaterials and broadens the application in the field of antiviral therapy. Full article

Molybdenum-rhenium alloys are usually used as the wall materials for high-temperature heat pipes using liquid sodium as heat-transfer medium. The corrosion of Mo in liquid Na is a key challenge for heat pipes. In addition, oxygen impurity also plays an important role in affecting the alloy resistance to Na liquid. In this article, the adsorption and diffusion behaviors of Na atom on Mo (110) surface are theoretically studied using first-principles approach, and the effects of alloy Re and impurity O atoms are investigated. The result shows that the Re alloy atom can strengthen the attractive interactions between Na/O and the Mo substrate, and the existence of Na or O atom on the Mo surface can slower down the Na diffusion by increasing diffusion barrier. The surface vacancy formation energy is also calculated. For the Mo (110) surface, the Na/O co-adsorption can lead to a low vacancy formation energy of 0.47 eV, which indicates the dissolution of Mo is a potential corrosion mechanism in the liquid Na environment with O impurities. It is worth noting that Re substitution atom can protect the Mo surface by increasing the vacancy formation energy to 1.06 eV. Full article

Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice. Full article

Lipid droplets (LDs) are ubiquitous organelles that fulfill essential roles in response to metabolic cues. The identification of several neutral lipid synthesizing and regulatory protein complexes have propelled significant advance on the mechanisms of LD biogenesis in the endoplasmic reticulum (ER). However, our understanding of signaling networks, especially transcriptional mechanisms, regulating membrane biogenesis is very limited. Here, we show that the nutrient-sensing Target of Rapamycin Complex 1 (TORC1) regulates LD formation at a transcriptional level, by targeting DGA1 expression, in a Sit4-, Mks1-, and Sfp1-dependent manner. We show that cytosolic pH (pHc), co-regulated by the plasma membrane H+-ATPase Pma1 and the vacuolar ATPase (V-ATPase), acts as a second messenger, upstream of protein kinase A (PKA), to adjust the localization and activity of the major transcription factor repressor Opi1, which in turn controls the metabolic switch between phospholipid metabolism and lipid storage. Together, this work delineates hitherto unknown molecular mechanisms that couple nutrient availability and pHc to LD formation through a transcriptional circuit regulated by major signaling transduction pathways. Full article

Technological advances in high-throughput techniques have resulted in tremendous growth of complex biological datasets providing evidence regarding various biomolecular interactions. To cope with this data flood, computational approaches, web services, and databases have been implemented to deal with issues such as data integration, visualization, exploration, organization, scalability, and complexity. Nevertheless, as the number of such sets increases, it is becoming more and more difficult for an end user to know what the scope and focus of each repository is and how redundant the information between them is. Several repositories have a more general scope, while others focus on specialized aspects, such as specific organisms or biological systems. Unfortunately, many of these databases are self-contained or poorly documented and maintained. For a clearer view, in this article we provide a comprehensive categorization, comparison and evaluation of such repositories for different bioentity interaction types. We discuss most of the publicly available services based on their content, sources of information, data representation methods, user-friendliness, scope and interconnectivity, and we comment on their strengths and weaknesses. We aim for this review to reach a broad readership varying from biomedical beginners to experts and serve as a reference article in the field of Network Biology. Full article

Friction anisotropy is one of the important friction behaviors for two-dimensional (2D) van der Waals (vdW) crystals. The effects of normal pressure and thickness on the interfacial friction anisotropy in few-layer graphene, h-BN, and MoSe₂ under constant normal force mode have been extensively investigated by first-principle calculations. The increase of normal pressure and layer number enhances the interfacial friction anisotropy for graphene and h-BN but weakens that for MoSe₂. Such significant deviations in the interfacial friction anisotropy of few-layer graphene, h-BN and MoSe₂ can be mainly attributed to the opposite contributions of electron kinetic energies and electrostatic energies to the sliding energy barriers and different interlayer charge exchanges. Our results deepen the understanding of the influence of external loading and thickness on the friction properties of 2D vdW crystals. Full article

Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug’s anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer; however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential. Full article

Serotonin modulates several physiological and cognitive pathways throughout the human body that affect emotions, memory, sleep, and thermal regulation. The complex nature of the serotonergic system and interactions with other neurochemical systems indicate that the development of depression may be mediated by various pathomechanisms, the common denominator of which is undoubtedly the disturbed transmission in central 5-HT synapses. Therefore, the deliberate pharmacological modulation of serotonergic transmission in the brain seems to be one of the most appropriate strategies for the search for new antidepressants. As discussed in this review, the serotonergic system offers great potential for the development of new antidepressant therapies based on the combination of SERT inhibition with different pharmacological activity towards the 5-HT system. The aim of this article is to summarize the search for new antidepressants in recent years, focusing primarily on the possibility of benefiting from interactions with various 5-HT receptors in the pharmacotherapy of depression. Full article

Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment. Full article

The COVID-19 epidemic surprised economic operators around the world. The very existence of many businesses, and thus jobs, was at stake. However, one year after the WHO declared the outbreak a pandemic, contrary to the pessimistic forecasts of business analysts, some industries did not experience the predicted negative effects of the crisis. This article presents the results of a pilot study on micro and small enterprises in the rubber products industry in Poland during the COVID-19 pandemic, with the aim of analyzing the phenomenon of sustainable resource management that led not only to the survival of these enterprises but also to a significant increase in their turnover. Therefore, the purpose of the study was to analyze the key success factors of the indicated economic entities, with particular emphasis on the perspective of sustainable resource management and relationship management. On the basis of best research practices, a triangulation of research methods was applied (integrative literature review, computer-assisted telephone interviewing, and individual in-depth interview). A relationship was observed between the sustainable management of resources and the structure of the relationship network and the strength of its connections. In micro and small enterprises in the rubber products sector in Poland, sustainable resource management is related to the structure of the network of relations and the strength of connections in the network (relations/networking), as enterprises form a group of entities with a high level of loyalty, especially between the suppliers and buyers of raw materials. The formulated conclusions will become the basis for further in-depth research that can be conducted (a) in the same group of respondents, but using a representative research group, (b) in the same industry among a group of large enterprises, and (c) in a group of small and medium-sized enterprises (SMEs) from other industries. Full article

Background: This study investigated the impact of serum cytokeratin 19 fragment (CYFRA21-1) level on the clinical outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib (SOR) or lenvatinib (LEN). Methods: A total of 71 cases with unresectable HCC taking SOR or LEN were included. Univariate and multivariate analyses were performed to identify the prognostic factors in patients taking SOR or LEN. Results: Among the 71 patients taking SOR or LEN, the frequency of cases showing high CYFRA21-1 levels after administration increased compared to before the administration. There was no association between the CYFRA21-1 level and the result of treatment response using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 12 weeks after the administration. Univariate analysis identified a maximum intrahepatic tumor diameter of 70 mm or more, extrahepatic metastasis, baseline alpha-fetoprotein (AFP) ≥2000 ng/mL, baseline AFP-L3 index ≥15%, baseline des-gamma-carboxy prothrombin (DCP) ≥1000 mAU/mL, baseline CYFRA21-1 >3.5 ng/mL, 12-week mRECIST progressive disease (PD), 12-week DCP ratio ≥ 4, 12-week CYFRA21-1 ratio ≥2, administration period less than 12 weeks, ALBI grade 3 at PD, and no additional treatment after discontinuation of SOR/LEN as prognostic factors. Multivariate analysis revealed that AFP-L3 index ≥ 15%, 12-week mRECIST PD, 12-week DCP ratio ≥4, 12-week CYFRA21-1 ratio ≥2, administration period less than 12 weeks, and no additional treatment after discontinuation of SOR/LEN were independent factors. Conclusions: Patients with a high CYFRA21-1 level at baseline tend to have poor prognosis, and patients with a high CYFRA21-1 ratio 12 weeks after administration have poor prognosis. Serum CYFRA21-1 measurement may have additional effects on prognostic prediction, and it may be necessary to pay close attention to the transition to the next HCC treatment in cases whose CYFRA21-1 level is high. Full article

Since 2014, select states have allowed pharmacists to prescribe hormonal contraception (HC). This study describes student pharmacists’ perceptions of a pharmacist’s scope of practice, education, and interest, and identifies differences between students who have completed didactic HC content in their professional curriculum versus those who have not. A voluntary online survey was emailed to all students in three Georgia pharmacy schools. Descriptive statistics were reported. Likert square responses were dichotomized, and Chi square testing identified differences between groups. A total of 1256 students were invited, 35% completed the survey, of those 68% had received HC didactic content in their curriculum. Regardless of HC education, most students “agree� or “strongly agree� that pharmacists are adequately educated to prescribe HC (92% vs. 86%, p = 0.05) and prescribing HC is within the pharmacist’s scope of practice (89% vs. 84%, p = 0.12). Although not currently permitted in Georgia, most are interested in prescribing (97% vs. 96%, p = 0.5). Of the students who have received HC didactic content, 87% felt “moderately�, “well�, or “extremely well-educated� regarding HC prescribing clinical skills. Regardless of didactic training, pharmacy students believe pharmacists are prepared to prescribe HC and support pharmacist-prescribed HC as a part of their future professional scope of practice. Full article

Hepatocellular carcinoma (HCC) typically presents in patients with a chronic liver disease and rarely develops in healthy liver, especially within an accessory liver lobe. We present a case of a healthy 64-years-old woman who showed a serum alpha-fetoprotein (AFP) value of 226.3 µg/mL during a screening blood test. Past medical history was negative for chronic liver disease or cirrhosis. Intraoperative finding was an ovaloid mass connected with the second hepatic segment by a thin pedicle of hepatic tissue. Lesion was safely resected by laparoscopic approach. Histopathology analysis showed a trabecular hepatocellular carcinoma. After a 6-month follow up, there was no evidence of recurrent disease. This case report showed how serum AFP remains a highly sensitive marker, although the presentation of HCC was unusual. To our knowledge, this is the second case reported in the literature. Full article

Nowadays, a dye-sensitized solar cell (DSSC) attracts attention to its development widely due to its several advantages, such as simple processes, low costs, and flexibility. In this work, we demonstrate the difference in device structures between small size and large size cells (5 cm × 5 cm, 10 cm × 10 cm and 10 cm × 15 cm). The design of the photoanode and dye-sensitized process plays important roles in affecting the cell efficiency and stability. The effects of the TiO₂ electrode, using TiCl_4(aq) pretreatment and post-treatment processes, are also discussed, whereas, the open-circuit voltage (Voc), short-circuit current density (Jsc), and module efficiency are successfully improved. Furthermore, the effects on module performances by some factors, such as dye solution concentration, dye soaking temperature, and electrolyte injection method are also investigated. We have demonstrated that the output power of a 5 cm × 5 cm DSSC module increases from 86.2 mW to 93.7 mW, and the module efficiency achieves an outstanding performance of 9.79%. Furthermore, enlarging the DSSC modules to two sizes (10 cm × 10 cm and 10 cm × 15 cm) and comparing the performance with different module designs (C-DSSC and S-DSSC) also provides the specific application of polymer sealing and preparing high-efficiency large-area DSSC modules. Full article

Combined training (CT) may combine strength and endurance training within a given time period, but it can also encompass additional protocols consisting of velocity, balance, or mobility as part of the same intervention. These combined approaches have become more common in soccer. This systematic review was conducted to (1) characterize the training protocols used in CT studies in soccer, (2) summarize the main physiological and physical effects of CT on soccer players, and (3) provide future directions for research. Methods: A systematic review of Cochrane Library, PubMed, Scopus, SPORTDiscus, and Web of Science databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PICOS were defined as follows: P (soccer players of any age or sex); I (CT combining strength and endurance or sprinting or balance or mobility training); C (the control group (whenever applicable), with or without comparative interventions in addition to usual soccer training); O (acute and/or chronic responses: biochemical, physiological and physical); S (must have at least two groups, either randomized or non-randomized). The database search initially identified 79 titles. From those, eight articles were deemed eligible for the systematic review. Three studies analyzed acute responses to concurrent training, while the remaining five analyzed adaptations to CT. In those tested for acute responses, physiological (hormonal) and physical (strength and power external load, internal load) parameters were observed. Adaptations were mainly focused on physical parameters (strength and power, sprints, jumps, repeated sprint ability, aerobic, change-of-direction), with relatively little focus on physiological parameters (muscle architecture). Short-term responses to CT can affect hormonal responses of testosterone after resistance training with internal and external load. In turn, these responses’ effects on strength and power have produced mixed results, as have adaptations. Specifically, strength and hypertrophy are affected to a lesser extent than speed/power movements. Nevertheless, it is preferable to perform CT before endurance exercises since it is a limiting factor for interference. Volume, intensity, rest between sessions, and athletes’ fitness levels and nutrition dictate the degree of interference. Full article

The spatiotemporal characteristics of river water quality are the key indicators for ecosystem health evaluation in basins. Land use patterns, as one of the main driving forces of water quality change, affect stream water quality differently with the variations in the spatiotemporal scales. Thus, quantitative analysis of the relationship between different land cover types and river water quality contributes to a better understanding of the effects of land cover on water quality, the landscape planning of water quality protection, and integrated water resources management. Based on water quality data of 2006–2018 at 18 typical water quality stations in the Yangtze River basin, this study analyzed the spatial and temporal variation characteristics of water quality by using the single-factor water quality identification index through statistical analysis. Furthermore, the Spearman correlation analysis method was adopted to quantify the spatial-scale and temporal-scale effects of various land uses, including agricultural land (AL), forest land (FL), grassland (GL), water area (WA), and construction land (CL), on the stream water quality of dissolved oxygen (DO), chemical oxygen demand (COD_Mn), and ammonia (NH₃-N). The results showed that (1) in terms of temporal variation, the water quality of the river has improved significantly and the tributaries have improved more than the main rivers; (2) in the spatial variation respect, the water quality pollutants in the tributaries are significantly higher than those in the main stream, and the concentration of pollutants increases with the decrease of the distance from the estuary; and (3) the correlation between DO and land use is low, while that between NH₃-N, COD_Mn, and land use is high. CL and AL have a negative effect on water quality, while FL and GL have a purifying effect on water quality. In particular, AL and CL have a significant positive correlation with pollutants in water. Compared with NH₃-N, COD_Mn has a higher correlation with land use at a larger scale. The results highlight the spatial scale and seasonal dependence of land use on water quality, which can provide a scientific basis for land management and seasonal pollution control. Full article