Background: The present study compared corticospinal excitability to the biceps brachii muscle during arm cycling at a self-selected and a fixed cadence (SSC and FC, respectively). We hypothesized that corticospinal excitability would not be different between the two conditions. Methods: The SSC was initially performed and the cycling cadence was recorded every 5 seconds for one minute. The average cadence of the SSC cycling trial was then used as a target for FC of cycling that the participants were instructed to maintain. Motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the biceps brachii during each trial of SSC and FC arm cycling. Results: Corticospinal excitability as assessed via normalized MEP amplitudes (MEPs were made relative to a maximal compound muscle action potential) were not different between groups. Conclusions: Focusing on maintaining a FC cadence during arm cycling does not influence corticospinal excitability as assessed via TMS-evoked MEPs.

There have been a great number of investigations about the influence of weak magnetic fields on biological systems, such as isolated cells and whole organisms. This is also a subject of considerable medical concern since old epidemiologic observations have indicated a possible tumorigenic effect of these fields. Their mechanism of action, however, is not firmly established. A large number of biological effects of electromagnetic fields have been attributed either to the production of reactive oxygen species (ROS) or to the entrance Ca²⁺ in the cell. A new biochemical pathway is proposed that covers these two possibilities: the primary effect of the magnetic field would be by the mechanism of radical pairs resulting in the production of ROS; these could activate the ion channels TRPM2 producing cellular inflow of Ca²⁺, which would induce the calcium dependent effects. Thus, a large number of biological effects observed up to the present could be explained.

Type 2 diabetes mellitus (T2DM) is frequently accompanied by affective disorders with a prevalence of comorbid depression of around 25%. Nevertheless, the biomarkers of affective symptoms including depression and anxiety due to T2DM are not well established.Aims: This study was conducted to delineate the serum biomarkers predicting affective symptoms due to T2DM above and beyond the effects of insulin resistance and atherogenicity. Methods: The present study delineated the effects of serum levels of copper, zinc, β-arrestin-1, FBXW7, lactosylceramide (LacCer), serotonin, albumin, calcium, magnesium, IR and atherogenicity on severity of depression and anxiety in 58 men with T2DM and 30 healthy male controls. Severity of affective symptoms was assessed using the Hamilton Depression and Anxiety rating scales.Results: We found that 61.7% of the variance in affective symptoms was explained by the multivariate regression on copper, β-arrestin-1, calcium, and insulin resistance coupled with atherogenicity, while 44.4% of the variance in the latter was explained by copper, β-arrestin-1, LacCer (all positively) and calcium and FBXW7 (both negatively). Copper and LacCer (positive) and calcium and BXW7 (inverse) had significant specific indirect effects on affective symptoms which were mediated by insulin resistance and atherogenicity. Copper, β-arrestin-1, and calcium were associated with affective symptoms above and beyond the effects of insulin resistance and atherogenicity.Discussion: T2DM and affective symptoms share common pathways namely increased atherogenicity, insulin resistance, copper, and β-arrestin-1, and lowered calcium, whereas copper, β-arrestin-1, calcium, LacCer, and FBXW7 may modulate depression and anxiety symptoms by affecting T2DM.

Results of geological and geophysical investigations of the Siljan Ring impact structure (central Sweden) revealed complicated relationships between Paleozoic sedimentary succession and the Precambrian basement. Tectonic and depositional evolution caused complex geology. Studies of a new drill core from the C-C-1 well provide information necessary for the reconstruction of the geological setting in the southwestern part of Siljan Ring. The whole interval of the core section is from 32.60 to 634.90 m with almost no breaks. The sedimentary cover is 373.55 m thick in total. The sedimentary sequences are predominantly composed of wackestones, mudstones, and shales. In the lower part of the sedimentary section, limestone layers intercalate with black shales. In a result of the investigations, it has been suggested that sedimentary layers represent Late Ordovician and Silurian deposits and have disturbed stratigraphic relations. The basement section is composed of Precambrian meta-volcanic and meta-sedimentary rocks. The contact between the basement and the sedimentary cover is tectonic, not normal sedimentary, in origin. Tectonic processes caused intensive rock fracturing. Four generations of fractures were identified with analysis of fracture relations and mineralization sequence. Only two of them occur in sedimentary rocks that probably belong to the latest stages of tectonic activity. Highly fractured basement rocks in some cases contain open vugs developed along the fractures. Rock matrix is tight either in sedimentary and basement rocks and only micro-porosity space is recognized in cataclastic zones. Single evidence of bituminous filling of micro-porosity zone and partly cemented vug is established in limestone from the lower part of the sedimentary section. These findings are particularly valuable for stratigraphy refinement and tectonic setting reconstructions as well as oil and gas reservoir forecasts.

Inactivated SARS-CoV-2 vaccine (CoronaVac) is commonly used in national immunization programs. However, the immune response significantly declined within a few months. Our study assessed the immune response against SARS-CoV-2 after receiving booster shots of BNT162b2 or ChAdOx1 among health care workers who previously received CoronaVac as their primary immunization. Fifty-six participants received ChAdOx1 and forty-two participants received BNT162b2 were enrolled into this study which evaluated the immune responses including anti-SARS-CoV-2 spike total antibodies (Elecsys®), surrogated viral neutralization test (sVNT) to ancestral strain (cPass™; GenScript) and five variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) (Luminex; multiplex sVNT) and the ELISpot with spike (S1 and S2) peptide pool against the ancestral SARS-CoV-2 strain. The samples were analyzed at baseline, 4, and 12 weeks after primary immunization as well as 4 and 12 weeks after receiving the booster. This study showed a significantly higher B-cell response among the BNT162b2 than the ChAdOx1 booster group, particularly against the Omicron variant, as well as a trend of good T-cell immune response in the BNT162b2 group. Moreover, the immune response rapidly declined at 12 weeks after the booster. A fourth dose or a second booster should be recommended, especially for reducing Omicron severity.

A new cocrystal salt of metformin, an antidiabetic drug, and N,N’-(1,4-phenylene)dioxalamic acid, was synthesized by mechanochemical synthesis, purified by crystallization from solution and characterized by single X-ray crystallography. The structure revealed a salt-type cocrystal composed of one dicationic metformin unit, two monoanionic units of the acid and four water molecules namely H2Mf(HpOXA)2∙4H2O. X-ray powder, IR, 13C-CPMAS, thermal and BET adsorption-desorption analyses were performed to elucidate the structure of the molecular and supramolecurar structure of the anhydrous microcrystalline mesoporous solid H2Mf(HpOXA)2. The results suggest that their structures, conformation and hydrogen bonding schemes are very similar between them. To the best of our knowledge, the selective formation of the monoanion HpOXA⁻, as well as its structure in the solid, is herein reported for the first time. Regular O(-)∙∙∙C(), O(-)∙∙∙N+ and bifacial O(-)∙∙∙C()∙∙∙O(-) of n→* charge-assisted interactions are herein described in H2MfA cocrystal salts which could be responsible of the interactions of metformin in biologic systems. The results, support the participation of n→* charge-assisted interactions independently, and not just as a short contact imposed by the geometric constraint due to the hydrogen bonding patterns.

The cucumber mosaic virus (CMV) 2b protein is a suppressor of plant defenses and a pathogenicity determinant. Amongst the 2b protein’s host targets is the RNA silencing factor Argonaute 1 (AGO1), which it binds to and inhibits. In Arabidopsis thaliana, if 2b-induced inhibition of AGO1 is too efficient it induces reinforcement of antiviral silencing by AGO2, and triggers increased resistance against aphids, CMV’s insect vectors. These effects would be deleterious to CMV replication and transmission, respectively, but are moderated by the CMV 1a protein by sequestering sufficient 2b protein molecules into P-bodies to prevent excessive inhibition of AGO1. Mutant 2b protein variants were generated and red and green fluorescent protein fusions used to investigate subcellular colocalization with AGO1 and the 1a protein, and the effects of mutations on complex formation with the 1a protein and AGO1 were investigated using bimolecular fluorescence complementation and co-immunoprecipitation assays. Although we found that residues 56-60 influenced the 2b protein’s interactions with the 1a protein and AGO1, it appears unlikely that any single residue or sequence domain is solely responsible. In silico predictions of intrinsic disorder within the 2b protein secondary structure were supported by circular dichroism (CD) but not by nuclear magnetic resonance (NMR) spectroscopy. Intrinsic disorder provides a plausible model to explain the 2b protein’s ability to interact with AGO1, the 1a protein and other factors. However, the reasons for the conflicting conclusions provided by CD and NMR must first be resolved.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease characterized by mature B-cell neoplasms. The standard immunochemotherapy for DLBCL is R-CHOP, which includes rituximab, cyclophosphamide, doxoru-bicin, vincristine, and prednisone. Up to 30-40% of patients with DLBCL either exhibit primary refractory disease to standard treatment or experience relapse after the initial response. A 72-year-old man diagnosed with DLBCL involving chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) showed primary refractory disease after the fourth cycle of R-CHOP. The patient ultimately experienced cardiac involvement by the lymphoma and received salvage chemotherapy. He passed away about 15 months away after the diagnosis of DLBCL. We conducted fluorescence in situ hybridization (FISH) for further analysis of the chromosomal translocations. The breakpoint of chromosome 1q21 was located at a distance of around 151 Mb from the telomeric end of chromosome 1p. The breakpoint in chromosome 22q11 contains the immunoglobulin lambda locus. Furthermore, the breakpoint of chromosome 6p was in the telomeric region of chromosome 6p21. The breakpoint of chromosome 18q21 contains BCL2. This case report presents the first documented co-occurrence of chromosomal translocations t(1;22)(q21;q11.2) and t(6;18)(p25;q21) in a patient with DLBCL. These chromosomal translocations may indicate a worse clinical outcome.

The renin-angiotensin system (RAS) plays a role in cardiovascular homeostasis and hydro-electrolyte balance influencing organ function throughout the body. The classical view of RAS focused on a single biologically active metabolite, the octapeptide angiotensin (Ang)ll, created by the Angiotensin-converting enzyme (ACE). The past two decades have revealed new functions for intermediate products of the RAS beyond their role as substrates. Angiotensin 1-7 (Ang-(1—7), a RAS peptide product with actions at the Mas receptor, reportedly prevents cardiovascular disease-induced cognitive decline and cancer-induced bone pain (CIBP). However, Ang-(1—7) has a short half-life in vivo; here, we hypothesized that activating the MasR1 with a lactoside Ang-(1—7) analogue- PNA6-would attenuate inflammatory, cancer pain confined to the long bones, and chemotherapy-induced peripheral neuropathy (CIPN) for a longer-lasting efficacious therapeutic effect. PNA6, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-Lact)-amide, was successfully synthesized on solid phase peptide synthesis (SPPS). PNA6 significantly reversed inflammatory pain induced by 2% carrageenan in mice. In a second study modeling a complex pain state, E0771 breast adenocarcinoma cells were implanted into the femur of female C57BLK/6J wild-type mice to induce cancer-induced bone pain (CIBP). Both acute and chronic dosing of PNA6 significantly reduced the spontaneous pain behaviors associated with CIBP. A third murine model of platinum drug-induced painful peripheral neuropathy was established using oxaliplatin. Mice in the oxaliplatin-vehicle treatment groups demonstrated significant mechanical allodynia compared to oxaliplatin- PNA6 treatment group mice. These data suggest that PNA6 is a viable lead candidate for treating chronic inflammatory and complex neuropathic pain.

Small RNAs (sRNA) are epigenetic regulators of essential biological processes that have been linked to the onset and progression of leukemia, including acute adult T-cell leukemia-lymphoma (ATLL) caused by the retrovirus Human T-lymphotropic virus type 1. Here, we describe the sRNA profile of a 30-year-old female with ATLL at diagnosis and after maintenance therapy, with the goal of correlating their expression levels with response to therapy.

Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs). Nevertheless, these responses have not been examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, and azelaic acid were determined in 35 healthy controls, and 101 mood disorder patients, namely 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum total peroxides, IgG to oxidized LDL (oxLDL), IgM to nitroso-adducts, and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs were significantly higher in MDD and BP1 as compared with controls and higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, IgM directed to OSEs and nitroso-adducts, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSEs, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSEs and nitroso-adducts, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.

PDEF is expressed in luminal epithelial cells of the prostate gland and associates with luminal phenotype. Hippo pathway regulates cell growth/proliferation, cellular homeostasis, and organ development by modulating phosphorylation of its downstream effectors. In previous studies, we observed decreased levels of PDEF during prostate cancer progression. In the present studies, we evaluated the effects of PDEF on total and phospho (Ser-127)YAP1 protein(a downstream effector of the Hippo pathway) levels in PC3 cells, a line of castrate resistant prostate cancer. We observed that the expression of PDEF in PC3 cells resulted in increased increased phospho(Ser127) -YAP1 protein levels. Our immunofluorescence analysis for YAP1 revealed an increased cytoplasmic/nuclear ratio of YAP1 in PDEF-PC3 cells as compared to VC-PC3 cells, suggesting PDEF may play a critical role in modulating YAP1 phosphorylation, and by extension in the regulation of the Hippo pathway. We also observed a decrease in YAP1 protein levels in prostate cancer tissues as compared to normal prostate tissues. Our analysis of multiple publicly available clinical cohorts revealed a gradual decrease in YAP1 mRNA expression during prostate cancer progression and metastasis. This decrease was similar to the decrease in PDEF levels which we reported earlier. In addition we observed further decreased in PDEF and YAP1 expression in Neuro-Endocrine Prostate Cancer (NEPC), and a direct correlation between PDEF and YAP1 expression. To the best of our knowledge, these results provide the first demonstration of modulation of YAP1 by PDEF in any system and suggest a cross-talk between PDEF and the Hippo pathway.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

Background: Data suggest that food allergies greatly impact a child’s health and growth due to inadequate nutrient intake. Our study aimed to establish the long-term outcome of children with food allergies compared to a control group. Methods: This study was a retrospective cohort study with longitudinal follow-up with a mean period of 4.85 years from the diagnosis to the last study visit. The patients’ nutritional intake was assessed using a three-day food diary and analysed by a dietitian. Patients (61 boys and 33 girls, mean age 6.9 years) had a single food allergy including 21 patients with cow’s milk, 34 with egg, and 39 with peanut allergies. The control group included 36 children (19 boys and 17 girls, mean age 8.03 years). Blood analysis was performed on all participants. Results: Data from our study showed that patients with cow’s milk, egg or peanut allergies had normal growth and achieved catch-up growth from the diagnosis until the last study visit. In the cow's milk allergy group, the allergy was shown to affect calcium intake (p<0.05), while egg and peanut allergies did not impact the dietary intake of nutrients. None of the investigated food allergies affected blood results (p<0.05). Conclusions: In the present study, we showed that single food allergies do not compromise growth in children if they are provided with appropriate support and that the affected children reach catch-up growth from the diagnosis.

: Background: Overweight and obesity are major risk factors for many chronic diseases, and weight-loss interventions often include systematic exercising and nutritional supplements. The purpose of this study was to determine the independent/synergistic effects of Spirulina maxima supplementation (6-week, 4.5 g/day) and a systematic physical exercise program (6 weeks/ 2 times) on body composition and cardiorespiratory fitness of overweight and obese subjects. Methods: 27 overweight and 25 obese sedentary male subjects were assigned to four interventions through a randomized double-blind, crossover controlled trial: Physical exercise program with (SE) or without (Ex) Spirulina maxima or no-exercise program with (Sm) and without (C) Spirulina maxima. Body composition and cardiorespiratory fitness parameters were taken during a maximal intensity test. Results: As compared to C group, SE, Sm and Ex groups reduced (p < 0.05) their body fat percentage while improving their maximal oxygen uptake (VO₂max; r = −0.40), being obese subjects more benefited. Weight loss, time to reach fatigue and onset of blood lactate accumulation were improved in both Spirulina maxima supplemented groups, regardless the subjects’ body composition. Conclusions: Spirulina maxima supplementation synergistically improves the effects of systematic exercise in body composition and cardiorespiratory fitness parameters in overweight but mostly in obese adults.

Nanoparticles of graphene and carbon nanotubes are attractive materials for improvement of mechanical and barrier properties and functionality of biodegradable polymers for food packaging applications. However, the increase of the manufacture and consumption increases the probability of exposure of human and environment to such nanomaterials, this rising questions about the risks of nanomaterials since they can be toxic. For a risk assessment, it is crucial to know whether airborne nanoparticles of graphene and carbon nanotubes can be released from nanocomposites into the environment at their end-life, or they remain embedded in the matrix. In this work the release of graphene and carbon nanotubes from the poly(lactic) acid nanocomposite films were studied for the scenarios of: (i) biodegradation of matrix polymer at the disposal of wastes; and (ii) combustion and fire of nanocomposite wastes. Thermogravimetric analysis in air atmosphere, TEM, AFM and SEM were used to verify the release of nanoparticles from nanocomposite films. The three factors model was applied for the quantitative and qualitative risk assessment to the release of graphene and carbon nanotubes from nanocomposite wastes for these scenarios. Safety concern is discussed in respect to the existing regulations for nanowastes stream.

Although many policosanols from different sources, such as sugar cane, rice bran, and insects, have been marketed worldwide, there has been no comparative study of the in vivo efficacy using a hyperlipidemic animal model. This study compared the efficacy of treating dyslipidemia with four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel®) and three policosanols from China (Xi’an Natural sugar cane, Xi’an Realin sugar cane, and Shaanxi rice bran) in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and high cholesterol diet (HCD, final 4%, wt/wt) in a tetrabit, the Raydel policosanol group and Xi’an Natural policosanol group showed the highest survivability of approximately 81%, whereas the Xi’an Realin policosanol group and Shaanxi policosanol group showed 57% and 67% survivability, respectively. Among five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p<0.001 versus HCD control) and triglyceride (TG, p<0.001 versus HCD control) with the highest percentage of high-density lipoproteins (HDL)-C in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes. In the ovary, the Raydel policosanol group also showed the highest contents of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testis, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis with the least interstitial area and reactive oxygen species (ROS) production in testicular cells. In conclusion, 12 weeks of Raydel policosanol consumption resulted in remarkable improvement of the blood lipid profile, amelioration of inflammation in the liver, and enhancement of the cell morphology in the ovary and testis with the highest survivability under the HCD.

Recent evidence obtained in murine atrial cardiomyocytes suggests that the behavior of tubulin, a constituent of microtubules, is influenced by audible sounds. In the present study, the sequence and the structure of murine and human tubulins were compared with those of human TMC1 (Transmembrane channel-like protein 1), a sound-sensitive protein that is responsible for forming the pore of mechanosensory transduction channels in the hair cells of the inner ear of vertebrates, and with those of bacterial FtsZ (Filamenting temperature-sensitive mutant Z), a bacterial protein homologous to tubulin. The results show that mouse and human alpha-tubulin are 100% identical, whereas sequence homology of human TMC1 and human tubulin alpha 1A chain is scarce, with only 17.31% identity. A higher degree of similarity was observed in the presence of aromatic amino acids as well as in the propensity to form alpha-helices. Based on these results, it is hypothesized that the response of tubulin to audible sounds is mediated by the external alpha-helices as it occurs in TMC1. The sequence homology of human TMC1 and FtsZ from Lactobacillus johnsonii, is moderate with 23.40% identity, however higher than that between TMC1 and tubulin. The overall presence of aromatic amino acids in FtsZ is scarce, but helix propensity is significant. These results are discussed in the context of Orch OR, a theory that postulates that consciousness emerges from quantum computations occurring in microtubules of neurons via information processing mediated by aromatic amino acids of tubulin.

The use of multi-gene panels for germline testing in breast cancer enables the estimation of cancer risk and guides risk-reducing management options for tested individuals and their family members. We performed an analysis in our clinical database to identify breast cancer patients undergoing genetic testing with positive reports. We reviewed positive results with respect to the different levels of information provided in the reports; risk estimation and management, cascade family testing, information from secondary findings and actionable information for treatment decision-making. A total of 415 positive test reports were identified with 57.1%, 18.1%, 10.8% and 13.5% of individuals having pathogenic/likely pathogenic variants in high (BRCA1, BRCA2, PALB2, PTEN, TP53), moderate (ATM, CHEK2, NBN), low (BARD1, BRIP1, CHEK2, MLH1, MSH2, MSH6, NF1, RAD51C) and with insufficient evidence for breast cancer risk genes (FANCA, FANCM, NBN, MRE11, PMS2, RAD50, RAD51B, XRCC2, MUTYH), respectively. 6.7% of individuals were double heterozygotes with two pathogenic variants. Germline findings in 92% of individuals are linked to evidence-based treatment information and receive risk estimates for predisposition to breast and/or other cancer types. The use of germline findings for treatment decision making expands the indication of genetic testing to include individuals that could benefit from targeted treatments.

After globalization, South Korea’s retail landscape has been saturated with large-scale, corporate type retails. However, recently new commercial districts composed of small retail units are returning and bringing about a change. This study sought to take note of this phenomenon and identify its features and meanings from the perspective of urban ecology. A density-distribution analysis was conducted to investigate how they were forms, and an analysis of traces on the Internet and an analysis on the types of businesses were done to identify sociocultural characteristics. Results showed that they had similar type of locations and growth patterns, that they harmoniously congregated in a form of smaller-individual stores, and that their use of similar names for their stores had an impact of branding their entire districts. It was also noted that a shared culture through social networking services served as a growth boost for their unfavorable location. The spontaneous formation of such commercial districts can be an outcome of an urban ecological process geared toward blank niches burgeoning in the current retail structure of Korea. The causes and conditions found in the cases reveal meaningful policy implications for cities facing the same urban crisis diversity.

23-Hydroxy ursolic acid (23-OH UA) is a potent atheroprotective and anti-obesogenic phytochemical, with anti-inflammatory and inflammation resolving properties. In this study, we examined whether dietary 23-OH UA protects mice against the acute onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). Female C57BL/6 mice were fed either a defined low-calorie maintenance diet (MD) or an MD supplemented with 0.2 % wgt/wgt 23-OH UA for 5 weeks prior to actively inducing EAE and during the 30 days post-immunization. We observed no difference in the onset of EAE between both groups of mice, but ataxia and EAE disease severity were suppressed by 52% and 48%, respectively, and disease incidence was reduced by over 49% in mice that received 23-OH UA in their diet. Furthermore, disease-associated weight loss was strikingly ameliorated in 23-OH UA-fed mice. ELISPOT analysis showed no significant differences in frequencies of T cells producing IL-17 or IFN- between 23-OH UA fed mice and control mice, suggesting that 23-OH UA does not appear to regulate peripheral T-cell responses. In summary, our findings demonstrate that dietary 23-OH UA may represent an effective oral adjunct therapy for the prevention and treatment of relapsing-remitting MS.

Introduction: In recent years, platelets have been in short supply and high demand. Approximately one in five cardiac surgery patients require platelets. In our safety-net hospital, however, the incidence is over 40%. Renal dysfunction, long cardiopulmonary bypass (CPB) times, and absence of tranexamic acid (TXA) are common risk factors for requiring platelet transfusions. Methods: Our hypothesis was fewer platelets would be transfused within two hours after bypass under these three conditions: creatinine is low, predicted surgery duration is short, and TXA is uniformly administered. Our anesthesia department designed this retrospective before-and-after observational study when the surgery department decided to narrow preoperative criteria respective to these three elements. The Institutional Review Board of Louisiana State University Health Sciences Center Shreveport approved of the protocol and waived individual informed consent. We compared timing of platelet transfusions (within 7 days) in consecutive patients who had CPB during the first ninety days of 2022 to those in 2023 using t-tests in SAS 9.3. Confounders included age, weight, anticoagulants, gender, and the platelet counts and hemoglobin immediately prior to platelet transfusion. Secondary outcomes were postoperative day two creatinine and other components transfused. Results: Preoperatively creatinine tended to be higher in 2022 at 1.5 vs 1.1, reaching significance postoperatively at 1.9 vs 1.1 (p=0.02). Bypass times decreased from 174 to 124 minutes (p=0.06). TXA use increased from 18 of 28 to 26 of 29 patients. Platelet counts increased on bypass from 142 to 173 (p=0.06). Platelet and hemoglobin nadirs were higher (day 3: 8g/dL vs 8.8, p=0.04; 98 vs 138, p=0.005). Platelet units transfused per patient tended to increase (0.75+/-1 vs 0.93+/-1.5); if exposed, patients tended to receive more units (2.1+/-1.3 vs 2.5+/-1.4) sooner. Changes in transfusions for red cells were nonsignificant at 1.97 per patient to 1.21, cryoprecipitate 0.36 to 0.69, and FFP 0.93 to 0.83. Conclusions: This is the first study examining timing of platelet transfusions after bypass. In the present investigation, we measured platelet count during bypass and prothrombin hours after arrival in the intensive care. Platelets were often administered in sets of two because of scarce immediate supply, partly from lack of an agitator table. More importantly, these data support a need for point-of-care thromboelastograms intraoperatively, but the cost has been prohibitive. Some centers’ algorithms list triggers for transfusion by fibrinogen and prothrombin times, available immediately after separation from bypass.

: The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM from lung adenocarcinoma at our institute for 5 years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

β-cyclodextrin-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, we synthesized well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) acted as theranostic nanoparticles for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX) and superparamagnetic iron oxide particles (SPIO) were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to folate receptor-mediated endocytosis process of the nanoparticles and GSH triggered disulfide-bonds cleaving.Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO showed strong MRI contrast enhancement properties. In conclusion, folate-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). However, some foods, as those containing high oleic acid and a low omega-6/omega-3 ratio show anti-inflammatory properties. The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models. Methods: 3 rat cohorts have been used: vegetable rat feed, control ham and acorn-fed ham (a traditional ham where high oleic acid concentration from acorns is storage in the muscle fat). UC was induced with DSS in drinking water ad libitum for one week. Short-chain fatty acids (SCFAs) and 16S rRNA from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters (inflammatory cell density, mucosa damages, myeloperoxidase). Results: In the acorn-fed ham cohort, a protective effect was observed with respect to UC disease activity index, inflammatory cells density, colon mucosa alterations, myeloperoxidase levels, blood total antioxidant capacity and lower levels of pro-inflammatory cytokines, in comparison with feed cohort. Both ham diets caused a reduction in Firmicutes and an increase in Actinobacteria, Bacteroidetes and Proteobacteria in comparison with rat feed diet. Also, acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera such as Alistipes, Bacteroides, Blautia, Butyricimonas and Parabacteroides. Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed, indicating a valuable effect of this traditional Mediterranean cured meat product.

Recently perovskite solar cells have been paying attention of researchers. This comes from their high efficiency and stability. In this work, the change of some Optical and Electrical Properties of BaxFe(1-x)TiO4 thin films due to the change of the nanocrystal spacing and size were studied. A simple theoretical model based on the string theory was utilized to explain some of these empirical relations. The empirical results obtained indicated that an increase in the efficiency of the nano solar cell requires the energy gap to be narrow. Decreasing the nanocrystal size and spacing caused the energy gap to become narrower. The energy gap decreases also upon increasing the absorption coefficient and decreasing the transmission. This also requires increasing the conductivity and the magnetic permeability. The increase of the nanocrystal spacing decreases the absorption coefficient, electrical conductivity, and magnetic permeability, while it causes the transmission to increase. All these changes are explained using a simple string model beside Newton's laws. The capability of the string theory to explain this Nano quantum behavior comes from the fact that the string theory, like quantum theory, recognizes both the particle and the wave nature of the Nano system.

ECOCLIMAP-SG+ is a new 60~m land use land cover dataset, which covers a continental domain, and represents the 33 labels of the original ECOCLIMAP-SG dataset. ECOCLIMAP-SG is used in HARMONIE-AROME, the numerical weather prediction model used operationally by Met Éireann and other national meteorological services. ECOCLIMAP-SG+ was created using an agreement-based method to combine information from many maps to overcome variations in semantic and geographical coverage, resolutions, formats, accuracies, and representative periods. In addition to ECOCLIMAP-SG+, the process generates an agreement score map, which estimates the uncertainty of the land cover labels in ECOCLIMAP-SG+ at each location in the domain. This work presents the first evaluation of ECOCLIMAP-SG and ECOCLIMAP-SG+ against the following trusted land cover maps: LUCAS 2022, the Irish National Land Cover 2018 dataset, and an Icelandic version of ECOCLIMAP-SG. Using a set of primary labels, ECOCLIMAP-SG+ outperforms ECOCLIMAP-SG regarding the F1-score against LUCAS 2022 over Europe and the Irish national land cover 2018 dataset. Similarly, it outperforms ECOCLIMAP-SG against the Icelandic version of ECOCLIMAP-SG for most of the represented secondary labels. The score map shows that the quality ECOCLIMAP-SG+ is hetereogeneous. It could be improved once new maps once they become available but we do not control when they will be available. Therefore, the second-part of this publication series aims at improving the map using machine learning.

Since cART was introduced to treat AIDS, the mortality rate due to AIDS has markedly decreased and the convalescence of HIV-infected individuals has improved drastically. However, HIV-1 sexual transmission has made HIV become a global epidemic. Sacran is a megamolecular poly-saccharide extracted from cyanobacterium Aphanothece sacrum that exhibits numerous desirable characteristics for transdermic applications, such as safety as a biomaterial, a high moisture re-tention effect, the ability to form a film and hydrogel, and an anti-inflammatory effect. In this study, we evaluated the anti-HIV-1 effects of Sacran as a barrier to HIV transmission. Sacran inhibited HIV-1 infection and envelope-dependent cell-to-cell fusion. Moreover, we used a Transwell assay to confirm that sacran inhibited viral diffusion and captured viruses. The synergistic effects of sacran and other anti-HIV infection drugs were also evaluated.HIV-1 infections can be reduced through the synergistic effects of sacran and anti-HIV-1 drugs. Our study suggests the use of sacran gel to protect against HIV-1 transmission.

Despite advances in our knowledge of systemic lupus erythematosus (SLE) has increased over time, there are still many challenges in deciphering the precise mechanisms involved in the development and progression of the disease. Recent evidence has raised questions about the effectiveness of the programmed cell death protein 1 (PD-1) in suppressing autoreactive CD4+ T cells during the autoimmune response. Research has ventured into investigate the potential impact of PD-1 on various CD4+ T cell subpopulations, including T follicular helper (Tfh) cells, circulating Tfh (cTfh) cells, and T peripheral helper (Tph) cells, all of which exhibit substantial PD-1 expression and have been closely related with several autoimmune disorders including SLE. This review aims to highlight the complex role of PD-1 in autoimmunity and emphasizes the imperative for further research to elucidate its functions during autoreactive T-cell response. Additionally, we address the potential of PD-1 or its ligands as a possible therapeutic target in SLE.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigate pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4 / MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized and evaluated for their antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and ability of inhibiting P-gp-mediated MDR some ten diversely substituted 1-Ph-DHPIQ derivatives bearing at position 2 carboxylate groups (COOH, COOEt), nitriles (CN) and Mannich bases (e.g., morpholinomethyl derivatives). Lipophilicity parametrization and molecular docking calculations improved the understanding of the structure-activity relationships in cytotoxicity and P-gp inhibition of the investigated 1-Ph-DHPIQs, which led us to disclose a novel Mannich base HCl salt (8b’), which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 &lt; 20 M) and to inhibit in-vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 M, respectively.

The present study focuses on the development and optimization of a highly efficient unique hybrid technique — membrane-assisted gas absorption (MAGA) in designing the separation unit, which provides the improvement in mass-transfer of a target component during the natural gas processing in terms of sweetening stage. A novel design of membrane-assisted gas absorption cell is used to enhance the ratio between absorbent amount and membrane surface available for permeation. The performance tests were implemented on example of two gas mixtures separation: one is model ternary gas mixture and the second is quasi real natural gas, which includes number of hydrocarbons, nitrogen, acid impurities and xenon. For both cases, the MAGA unit demonstrated high acid gases removal efficiency, and high recovery of hydrocarbons. The ultimate efficiency of studied system was up to 96 and 61 % of removed acid gases with hydrocarbons losses up to 1 % at highest productivity. In this way, the residual sum of acid gases content may be lowered to 1 vol.% using the heat-free hybrid membrane-assisted gas absorption unit maintaining suitable recovery rate of methane, ethane, propane and n-butane. Nevertheless, the overall efficiency of the process may be enhanced using the specific absorption agents with aqueous amino alcohol solutions.

Background High Mobility Group Box-1 (HMGB-1) is implicated in the pathogenesis of thrombosis and cancer. In the present study, we aimed to evaluate its potential role as a diagnostic biomarker of portal vein thrombosis (PVT) among patients with hepatocellular carcinoma (HCC). Methods The study population included N=100 prospectively recruited patients with a novel diagnosis of HCC. We compared circulating HMGB-1 levels between 34 healthy controls, HCC patients with PVT (N=22), and HCC patients without PVT (N=78). Results HCC patients without PVT showed significantly higher median HMGB-1 serum levels (8.2 [5.5-13.1] ng/ml) than those observed in the case of HCC with PVT (5.5 [4.4-8.5] ng/ml; p=0.012) and in healthy controls (4.1 [3.1-8.2] ng/ml; p&lt;0.001). Among HCC patients, at univariate analysis, the presence of PVT was associated with higher median age (p=0.036), larger major cancer node diameter (p&lt;0.001), and lower HMGB-1 serum level (p=0.012). At multivariate analysis, the presence of PVT maintained a positive association with major node diameter p=0.001) and an inverse association with serum HMGB-1 levels (p=0.003). Conclusions These findings indicate that serum HMGB-1 bears an inverse association with PVT complicating HCC at the time of diagnosis and suggest that serum HMGB-1 depletion may mark PVT development in cirrhotic patients with HCC.

Remote sensing plays a central role in the assessment of environmental phenomena and has increasingly become a powerful tool for monitoring shorelines, rivers morphology, flood waves delineation and floods assessment. Optical based monitoring and characterization of river evolution at long time scales is a key tool in fluvial geomorphology. However, the evolution occurring during extreme events is crucial for the understanding of the river dynamics under severe flow conditions and requires the processing of data from active sensors to overcome cloud obstructions. This work proposes a cloud-based unsupervised algorithm for the intra-event monitoring of river dynamics during extreme flow conditions based on time series of Sentinel-1 SAR data. The method allows the extraction of multi-temporal series of spatially explicit geometric parameters at high time and spatial resolutions, linking them to the hydrometric levels acquired by reference gauge stations. Intra-event reconstruction of inundation dynamics has led to the estimation of the relationship between hydrometric level and wet area extension and the assessment of bank erosion phenomena. Time series of SAR acquisitions, provided by Copernicus Sentinel-1 satellites, were analyzed to quantify changes in the wet area of a reach of the Tagliamento river under different flow conditions. The algorithm, developed within the Python-API of GEE, first empowers the Sentinel-1 images with the hydrometric level, then involves radiometric slope correction and speckle noise filtering. The Otsu method is then used for image segmentation leading to a water and dry land binary classification. Results support many types of analysis about river dynamics, including morphological changes, floods monitoring and relief efforts and bio-physical habitat dynamics. The results encourage future advancements and applications of the algorithm, specifically exploring SAR data from ICEYE and Capella Space constellations, which offer significantly higher spatial and temporal resolutions compared to Sentinel-1 data.

Cluster of differentiation 44 (CD44) is a type I transmembrane glycoprotein, and has been shown as a cell surface marker of cancer stem-like cells in various cancers. Especially, the splicing variants of CD44 (CD44v) are overexpressed in cancers, and play critical roles in cancer stemness, invasiveness, and resistance to chemotherapy and radiotherapy. Therefore, the understanding of the function of each CD44v is indispensable for the CD44-targeting therapy. CD44v9 contains the variant 9-encoded region, and its expression predicts poor prognosis in patients with various cancers. CD44v9 plays critical roles in the malignant progression of tumors. Therefore, CD44v9 is a promising target for cancer diagnosis and therapy. Here, we developed sensitive and specific monoclonal antibodies (mAbs) against CD44 by immunizing mice with CD44v3–10-overexpressed Chinese hamster ovary CHO-K1 (CHO/CD44v3–10) cells. We first determined their critical epitopes using enzyme-linked immunosorbent assay, and characterize their applications to flow cytometry, western blotting, and immunohistochemistry. One of the established clones, C₄₄Mab-1 (IgG₁, kappa) reacted with a peptide of the variant 9-encoded region, indicating that C₄₄Mab-1 recognizes CD44v9. C₄₄Mab-1 reacted with CHO/CD44v3–10 cells or colorectal cancer cell lines (COLO201 and COLO205) by flow cytometry. The apparent dissociation constant (K_D) of C₄₄Mab-1 for CHO/CD44v3–10, COLO201, and COLO205 was 2.5 × 10⁻⁸ M, 3.3 × 10⁻⁸ M, and 6.5 × 10⁻⁸ M, respectively. Furthermore, C₄₄Mab-1 was able to detect the CD44v3–10 in western blotting, and endogenous CD44v9 in immunohistochemistry using colorectal cancer tissues. These results indicated that C₄₄Mab-1 is useful for detecting CD44v9 not only in flow cytometry or western blotting but also in immunohistochemistry against colorectal cancers.

CC chemokine receptor 6 (CCR6) is one of the members of G protein-coupled receptor (GPCR) family that is upregulated in many immune-related cells, including B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. Coordination between CCR6 and its ligand CC motif chemokine ligand 20 (CCL20) is deeply involved in the pathogenesis of various diseases, such as cancer, autoimmune diseases, and psoriasis. Therefore, CCR6 is an attractive target for therapy and is being investigated as a diagnostic marker for patients. In a previous study, we developed an anti-mouse CCR6 (mCCR6) monoclonal antibody (mAb), C6Mab-13 (rat IgG1, kappa), applicable for flow cytometry by immunizing a rat with N-terminal peptide of mCCR6. This study investigated the binding epitope of C6Mab-13 using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) methods with the synthesized point mutated-peptides within 1-20 amino acids region of mCCR6. In ELISA, C6Mab-13 lost the reaction to the alanine-substituted peptide of D11A. The epitope of C6Mab-13 was identified to be Asp11 in ELISA. Furthermore, in SPR analysis, the dissociation constants (KD) could not be calculated for G9A and D11A mutants due to lack of binding. The SPR analysis demonstrated that the C6Mab-13 epitope comprises Gly9 and Asp11. Taken together, the key binding epitope of C6Mab-13 was determined to be around Asp11 on mCCR6. Based on the epitope information, C6Mab-13 could be useful for further functional analysis of mCCR6 in future studies.

Herpes simplex virus type 1 (HSV-1) is among the most widely spread viruses on the planet. However, the rate of binding to the receptor is not among the greatest ones. Gibbs energy of binding, which represents the driving force for antigen-receptor binding, of HSV-1 is less negative than can be expected. Furthermore, the Gibbs energy of biosynthesis of HSV-1 is among the most negative in nature. This implies high rate of multiplication of HSV-1. Obviously, HSV-1 uses specific strategy in virus-host interaction. While most other viruses increase infectivity through a high rate of antigen-receptor binding and cell entry/ highly negative Gibbs energy of binding, HSV-1 uses another strategy. It is related to a relatively slow reaction of antigen-receptor binding, which is followed by a higher rate of multiplication, which is a consequence of a highly negative Gibbs energy of biosynthesis. We can conclude empirically that both strategies are successful.

Several therapeutic monoclonal antibodies are approved by FDA against the PD-1/PD-L1 (programmed death-1/programmed death ligand-1) immune checkpoint, which has been a great success in cancer treatment. However, existing therapeutics, including small molecules inhibitors against PD-L1 checkpoint have certain drawbacks such as high cost and drug resistance that challenge the current available anti-PD-L1 therapy. Thereof, this study presents the screening of 32552 compounds from Natural Product Atlas database against PD-L1, including three steps of structure-based virtual screening and binding free energy refinement for the selection of potent PD-L1 inhibitors. Subsequently, five natural compounds, i.e., Neoenactin B1, Actinofuranone I, Cosmosporin, Ganocapenoid A, and 3-[3-hydroxy-4-(3-methylbut-2-enyl)phenyl]-5-(4-hydroxybenzyl)-4-methyldihydrofuran-2(3H)-one, were collected based on the ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and binding free energy (>-70 kcal/mol) for further computational investigation by comparison to co-crystallised ligand, i.e. JQT inhibitor. Based on interaction mapping, explicit 100 ns molecular dynamics simulation, and post binding free energy calculations, all the compounds exhibited intermolecular interactions (hydrogen and hydrophobic) with essential residues and substantial complex stability by comparison to the JQT inhibitor. Collectively, the calculated results advocate the selected natural compounds as the putative potent inhibitors of PD-L1 and, therefore, can be considered for further development of PD-L1 immune checkpoint inhibitor in cancer immunotherapy.

Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.

Biomedical aspects of tattooing have been extensively discussed in literature, however pathophysiological effects of tattoo inks in the human body are still unexplored. Oxidative stress is considered responsible for the adverse effects of tattooing, however no experimental evidence for tattoo ink-related oxidative stress in the human body currently exists. The aim was to examine the effect of a blue tattoo on skin redox regulatory network (RRN) parameters in a single human subject. Skin surface oxidation-reduction potential (ORP) was analyzed with a PH60F flat probe. Interstitial and intracellular fluid enriched capillary blood from the tattoo and the control area was extracted and analyzed with I₂/KI-stabilized microORP, nitrocellulose redox permanganometry (NRP), carbonato-cobaltate (III) formation-derived H₂O₂ dissociation rate assay, 1,2,3-trihydroxybenzene autoxidation assay, thiobarbituric reactive substances (TBARS) assay and 5,5,’-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based determination of free thiol content in low molecular weight and protein precipitate fractions. Surface ORP analysis revealed a greater antioxidant capacity of tattooed skin in comparison with the control (CTR). Capillary blood analysis confirmed greater reductive capacity in the tattoo sample both by microORP (-4.33mV vs CTR) and NRP (+10.8%). Hydrogen peroxide dissociation rate (+11.8%), and protein sulfhydryl content (+8.5%) were increased, and lipid peroxidation (-15%) was reduced in the tattoo sample in comparison with the CTR. In this N-of-1 study, RRN of tattooed skin was shifted towards a more reductive state with all parameters indicating reduced levels of oxidative stress in comparison with nontattooed skin. The local antioxidant effect of copper(II) phthalocyanine provides one possible explanation of the observed effects.

In this paper, we focus on developing a novel method to extract sea ice cover (i.e., discrimination/classification of sea ice and open water) using Sentinel-1 (S1) cross-polarization (vertical-horizontal, VH or horizontal-vertical, HV) data in extra wide (EW) swath mode based on the machine learning algorithm support vector machine (SVM). The classification basis includes the S1 radar backscatter coefficients and texture features that are calculated from S1 data using the gray level co-occurrence matrix (GLCM). Different from previous methods where appropriate samples are manually selected to train the SVM to classify sea ice and open water, we proposed a method of unsupervised generation of the training samples based on two GLCM texture features, i.e. entropy and homogeneity, that have contrasting characteristics on sea ice and open water. We eliminate the most uncertainty of selecting training samples in machine learning and achieve automatic classification of sea ice and open water by using S1 EW data. The comparison shows good agreement between the SAR-derived sea ice cover using the proposed method and a visual inspection, of which the accuracy reaches approximately 90% - 95% based on a few cases. Besides this, compared with the analyzed sea ice cover data Ice Mapping System (IMS) based on 728 S1 EW images, the accuracy of extracted sea ice cover by using S1 data is more than 80%.

PD-1/PD-L1 axis is one key therapeutic target against tumor cell immune escape. Structurally essential to the PD-1/PD-L1-linked immune escape is the binding interface of the PD-1/PD-L1 complex structure. Incorporating currently available PD-1/PD-L1-related experimental structures, this article unveils two sets of experimentally observed inter-molecular electrostatic interactions which stabilize the binding interface of the PD-1/PD-L1 complex structure. For the first time, this article proposes an evolutionary structural hypothesis that, as a result of natural selection, PD-1 is able to genetically mutate itself to structurally disrupt the PD-1/PD-L1 axis towards the restoration of T cell-mediated anti-tumor immunity.

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

BACKGROUND: During the natural history, the incidence HTLV-1 related diseases were 0.5% until 10% after decades of infection. Despite relative low lethality, previous study observed that HTLV-1 infection is associated with significantly increased mortality. For example, the incidence of ATLL and HAM/TSP, co-infections with HIV and HCV, parasitic co-infection with Strongyloides stercoralis may increase morbidity and mortality. OBJECTIVE: Determine the mortality rate and its major variables as possible risk factors, analyzing the HTLV Clinic at Emilio Ribas Institute, a continuous open cohort of HTLV patients since 1997. METHODS: This cohort open cohort possesses new patients added at a rate of approximately 50 patients/year. There were 1100 HTLV-infected subjects identified by September 30th 2018. All clinical data including clinical and laboratory data, which have been updated on a regular basis over the last 22 years, were entered into a specific REDCap database. The Ethical Board of the IIER approved the protocol. RESULTS: Along 22 years of clinical care in the HTLV-out clinic, 727 HTLV-1-infected subjects and 248 HAM/TSP cases. Four-hundred sixty-eight patients of whom remaining under active follow up. The mean follow-up time of the cohort was 12 years. Twenty-seven patients died (median age of 51,5 years old). From this total, 13 was asymptomatic carriers and 14 HAM/TSP subjects, 12 of asymptomatic and seven HAM/TSP possess co-infected with HIV or/and HCV. Other seven presented HAM/TSP without co-infection, and all was female, and sepsis was the majority cases the majority of cases of sepsis were related to infection of the urinary tract (p=0.058) and to ulcers of decubitus (p=0.021), and it was associated with risk factors for mortality. CONCLUSIONS: Overall, the mortality rate for HAM-TSP patients was six percent. The mean life expectancy in Brazil is about 78 years in 2018, twenty-two years higher than HAM/TSP patients without any other coinfection. This study highlights the possibility of higher death risk among HTLV-1-infected patients and HAM/TSP subjects in Brazil, and identified some risk factors for this outcome. Also, these patients may possess higher risk for morbidity, usually urinary tract infections and decubitus scars, which could increase risk for death.

Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct N^ɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed AGEs are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using MG-H1 as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

This paper focuses on the non-destructive dielectric measurement for low-loss planar materials with a thickness of less than 3 mm using a large coaxial probe with an outer diameter of 48 mm. The aperture probe calibration procedure required only to make a measurement of the half-space air and three offset shorts. The reflection coefficient for the thin material is measured using a Keysight E5071C network analyzer from 0.3 MHz to 650 MHz and then converted to a relative dielectric constant and tangent loss via closed form capacitance model and lift-off calibration process. Measurement error of dielectric constant, Δε_r is less than 2.5 % from 1 MHz to 400 MHz and the resolution of loss tangent, tan δ measurement is capable of achieving 3×10^-3.

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists either in blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-Epigallocatechin-3-gallate, Quercetin, and Rosmarinic acid) with the amyloid-β(1-40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulate the double-layered structure stability.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

This paper analyses the viability of different solutions to passively augment the axial stiffness of a horizontal axis radial levitation passive magnetic bearing (PMB) with topology previously studied. The zero-field cooling (ZFC) of high-temperature superconductor (HTS) bulks promotes higher magnetic impulsion and levitation forces and lower electromagnetic losses than with the field-cooling (FC), but on the other hand, the guiding stability is much lower than with FC. Because of stability reasons, FC was adopted in most superconducting maglev systems. The trend of this research group has been to develop an HTS ZFC horizontal axis radial levitation PMB presenting notable levitation forces with reduced electromagnetic losses, defined by a topology that creates guiding stability. Previous work has shown that even optimizing the bearing geometry to maximize magnetic guidance forces, could not be enough to guarantee the axial stiffness required for many applications. First, the extent to which guidance forces are augmented by increasing the number of HTS bulks in the stator is evaluated. Then, the axial stiffness augmentation by passively adding two limiting permanent magnet (PM) rings is evaluated. Results show that the axial stiffness is highly augmented by adding limiting PM rings with no significant additional investment. This change enables using the studied ZFC superconducting PMB in high-precision axial stability applications, such as precision gyroscopes, horizontal axis propellers and turbines.

Due to a common mode of transmission through infected human blood, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is relatively prevalent. In alignment with this, HCV co-infection is associated with an increased size of the HIV reservoir in highly active antiretroviral therapy (HAART)-treated individuals. Hence, it is crucial to comprehend the physiological mechanisms governing the latency and reactivation of HIV in reservoirs. Consequently, our study delves into the interplay between HCV/HIV coinfection in liver cells and its impact on the modulation of HIV latency. We utilized the latently infected monocytic cell line (U1) and the latently infected T cell line (J-Lat) and found that mediators produced by the infection of hepatic stellate cells and hepatocytes with HIV and HCV, respectively, were incapable of inducing latency reversal under the studied conditions. This may favor the maintenance of the HIV reservoir size among latently infected mononuclear cells in the liver. Further investigations are essential to elucidate the role of the interaction between liver cells in regulating HIV latency and/or reactivation, providing a physiologically relevant model for comprehending reservoir microenvironments in vivo.

Hepatitis E virus is a major etiological agent of chronic hepatitis in immunosuppressed individuals. Studies on HEV in the context of liver transplantation have produced mixed results, most of the data coming from studies conducted in high-income countries. This was a prospective cohort study of liver transplant recipients in southeastern Brazil. Recipients were systematically followed for one year, with the objective of determining the prevalence, incidence, genotype, and natural history of HEV infection in this population. We included 107 liver transplant recipients and 83 deceased donors. Positivity for anti-HEV IgG was detected in 11 (10.2%) of the recipients and in eight (9.7%) of the donors. None of the patients tested positive for HEV RNA at baseline or during follow-up. There were no episodes of reactivation or seroconversion, even in cases of serological donor-recipient mismatch or in recipients with acute hepatitis. Acute and chronic HEV infections seem to be rare events in the region studied. That could be attributable to social, economic, and environmental factors. Our data indicate that, among liver transplant recipients, hepatitis E should be investigated only when there are elevated levels of transaminases with no defined cause, as part of the differential diagnosis of seronegative hepatitis after transplantation.

Background: Systemic treatment options for hepatocellular carcinoma (HCC) after liver transplantation (LT) are limited in patients in whom sorafenib treatment was failed. The purpose of our study was to compare outcomes among sorafenib, regorafenib, and nivolumab treatment groups in patients with recurrent HCC after LT. Methods: This study retrospectively evaluated patients who received sorafenib for recurrent HCC treatment after LT at a single center from March 2007 to December 2018. Some patients received regorafenib or nivolumab after sorafenib treatment failure. Results: Fifty-six patients were treated with sorafenib due to HCC recurrence. Among these, 38 patients (67.9%) continued treatment with sorafenib only; the other 18 patients (32.1%) were converted to regorafenib treatment. Ten patients (17.9%) of these 18 were converted to nivolumab after sorafenib and regorafenib therapy failed. The disease-free survival and overall survival (OS) from LT were not different among the three groups. In addition, OS from HCC recurrence, sorafenib usage, and usage of each systemic therapeutic agent were not different among the three groups. Three cases in the nivolumab group developed acute rejection; one of these led to graft failure and death due to antibody-mediated rejection. Conclusion: Sequential regorafenib or nivolumab treatment in recurrent HCC LT patients does not improve OS compared sorafenib treatment.

Breast cancer is the most common malignant disease in women. Preclinical studies have confirmed that the local anesthetic levobupivacaine has a cytotoxic effect on breast cancer cells. We examined whether postoperative wound infiltration with levobupivacaine influences survival in 120 patients who were operated on for breast cancer and underwent quadrantectomy or mastectomy with axillary lymph node dissection. Groups with continuous levobupivacaine wound infiltration, bolus wound infiltration, and diclofenac analgesia were compared. Long-term outcomes examined were quality of life, shoulder disability, and hand grip strength (HGS) after one year, and survival after 5 and 10 years. Groups that had infiltration analgesia had better shoulder function compared to diclofenac after one year. Levobupivacaine PCA group had the best preserved HGS after 1 year (P=0.022). The most significant predictor of the 5-year outcome was HGS (P=0.03). Although the best survival after 5 and 10 years was registered in the bolus levobupivacaine group, statistical significance was not reached (P=0.36). The extent of the disease at the time of surgery is the most important predictor of long-term survival. A larger prospective clinical study could better confirm the effect of levobupivacaine wound infiltration on outcomes after breast cancer surgery observed in this pilot study. Trial number NCT05829707

A conventionally cast CoNiFeMn0.5Cr1.5 alloy and two versions with 0.25C&amp;3.7Ta or 0.25C&amp;3.7Hf were tested in oxidation at 1000°C for 50h with thermogravimetric recording of the oxidation kinetic. In all cases the obtained mass gain curves are parabolic. Their parabolic constants are much lower than the Kp previously determined for the original alloys with an equimolar base (CoNiFeMnCr). However, the post–mortem exploitation of the oxidized samples revealed analogous oxidation features on surface and subsurface, with here too external oxide strata on surface with different Mn and Cr contents, and rather great Mn–depletion in addition to a moderate Cr–depletion, in subsurface. Globally, the oxidation behavior is significantly better than earlier observed for the equimolar version of these alloys.

In the past decades, one of the most widely reported phenomena on Caribbean reefs is the general fall in coral cover and rise in macroalgae. Reefs with low coral cover and high macroalgal abun-dances are often presumed to provide poorer ecosystem functions and services. In this study, we assessed the condition of coral reefs on the Caribbean Coast of Costa Rica and determined how eight key ecosystem metrics varied in response to differential coral and fleshy macroalgae covers. Most reefs surveyed had high fleshy macroalgae and low live coral covers, with an average (± SD) of 31 ± 28% and 14 ± 13% per site. We found that the rugosity, urchin density, fish richness, total fish biomass, large fish density, and the potential fishery value of the reef were higher in sites with low fleshy macroalgae covers (>10%). The value of many of the ecosystem metrics estimated for coral reefs of the region appears to be lower than what’s been reported for other areas in the Caribbean, which may be related to the high macroalgae covers found on the reefs. Our results concur with the prevailing paradigm that an increase in macroalgae abundance could reduce the ecosystem services provided by coral reefs.

TNF cytokine receptor TNFR1 protein plays an important role in immune response and autoimmune diseases. Previously, we demonstrated that the peptide of the innate immunity protein Tag7 (PGLYRP1), designated as 17.1, is able to perform the functions of a full-size Tag7 protein, namely, to inhibit the transmission of a signal through the TNFR1 receptor and activate this receptor in complex with the major heat shock protein Hsp70. In this study, we show that two peptides derived from 17.1 – 17.1A and 17.1B have different affinities to the TNFR1 receptor and the Hsp70 protein, and each of them is able to perform only one of the above functions: peptide 17.1A is only able to inhibit signal conduction through the TNFR1 receptor, and peptide 17.1B can only activate this receptor is in complex with Hsp70. Thus, it is possible to modulate the activity of TNFR1 receptor and further perform its specific inhibition or activation in the treatment of various autoimmune or oncological diseases.

Pars plana vitrectomy is today a common first-line procedure for treatment of rhegma-togenous retinal detachment (RRD). Removal or preservation of the natural lens at the time of vitrectomy is associated with both advantages and disadvantages. The combi-nation of cataract extraction (i.e., phacoemulsification) with pars plana vitrectomy (PPVc) enhances visualization of the peripheral retina and the surgical management of the vitreous base. However, PPVc prolongs the surgical time and is associated with iatrogenic loss of the accommodation function in younger patients, possible postoperative aniso-metropia, and unexpected refractive results. Performance of pars plana vitrectomy alone (PPVa) requires good technical skills to minimize the risk of lens damage, and quickens cataract development. We retrieved all recent papers that directly compared PPVc and PPVa using parameters that we consider essential when choosing between the two procedures (the success rate of anatomical RRD repair, postoperative refractive error, intra and postoperative complications, and costs). PPVa and PPVc were generally comparable in terms of RRD anatomical repair. PPVc was associated with fewer intraoperative, but more postoperative, complications. Macula-off RRD PPVc treatment was often associated with undesirable myopic refractive error. PPVa followed by phacoemulsification was the most expensive procedure.

The gut plays a key role in drug absorption and metabolism of orally ingested drugs. Additionally, characterization of intestinal disease processes are increasingly gaining more attention as gut health is an important contributor to our overall health. The most recent innovation to study intestinal processes in vitro is the development of gut-on-a-chip (GOC) systems. Compared to conventional in vitro models they offer more translational value, and many different GOC models have been presented over the past years. Here, we reflect on the almost unlimited choices in designing and selecting a GOC for preclinical drug (or food) development research. Four components that largely influence the GOC design are highlighted, namely 1) the biological research questions, 2) chip fabrication and materials, 3) tissue engineering, and 4) the environmental and biochemical cues to add or measure in the GOC. Examples are presented of GOC studies in the two major areas of preclinical intestinal research: 1) intestinal absorption and metabolism to study the oral bioavailability of compounds, and 2) treatment-orientated research for intestinal diseases. The last section of this review presents an outlook on the limitations to overcome in order to accelerate preclinical GOC research.

Conservation of wildlife depends on precise and unbiased knowledge on the abundance and distribution of species. It is challenging to choose appropriate methods to obtain a sufficiently high detectability and spatial coverage matching the species characteristics and spatiotemporal use of the landscape. In remote regions, such as in the Arctic, monitoring efforts are often resource-intensive and there is a need for cheap and precise alternative methods. Here, we compare an uncrewed aerial vehicle (UAV; quadcopter) pilot-survey of the non-gregarious Svalbard reindeer to traditional population abundance surveys from ground and helicopter to investigate whether UAVs can be an efficient alternative technology. We found that the UAV survey underestimated reindeer abundance compared to the traditional abundance surveys when used at management relevant spatial scales. Observer variation in reindeer detection on UAV imagery was influenced by the RGB greenness index and mean blue channel. In future studies, we suggest to test long-range fixed-wing UAVs to increase the sample size of reindeer and area coverage and incorporate detection probability in animal density models from UAV imagery. In addition, we encourage focus on more efficient post-processing techniques, including automatic animal object identification with machine learning and analytical methods that account for uncertainties.

Gobies and their ectoparasitic monogenean flatworms are promising models for species diversification because of their species richness. Recent decades have seen the discovery of several new species of Gyrodactylus (Monogenea: Gyrodactylidae) on European gobies, mostly in the sand goby lineage and especially in the Eastern Mediterranean. However, the monogenean fauna of other gobies is much less understood. Therefore, we scrutinized five gobiid species (34 specimens, vouchered, with some representatives sequenced), sampled in Greece, for monogenean ectoparasites. Only specimens of the giant goby Gobius cobitis were infected; they harbored Xenoligophoroides cobitis (Monogenea: Dactylogyridae) on their gills. Here we provide the first record from Greece, and the first ITS rDNA and COI sequences of the representative of this monotypic genus. Also 28S rDNA was sequenced and compared with published data from across its known distribution, suggesting clinal variation. Lack of sequence data of closely related dactylogyrid monogeneans prevents either proposing a sister-group for Xenoligophoroides, or inferring a scenario explaining the presence of a single known member of this genus on gobies. Possible hypotheses include either the ancestral long-term presence on gobiids but “missing the boat” of the diversification events in the “Gobius-lineage”, or a recent host switch from a non-gobiid host.

A method for calibrating models of agricultural production and resource use presented by Howitt [1] for policy analysis is proposed to leverage multidisciplinary agricultural research at the National Center for Alluvial Aquifer Research (NCAAR). An illustrative example for Sunflower County, MS is presented to show how plot-level research can be extended to draw systemic region or basin wide implications. A hypothetical improvement in yields for dryland soybean varieties is incorporated to the model and shown to have a positive impact on aquifer outcomes and producer profits. The example illustrates that a change in one practice-crop combination can have system-wide impacts as evidenced by the change in acreages for all crops and practices.

This article has explored whether Aid for Trade (AfT) flows that accrue to recipient-countries depend on the latter's level of export product concentration. The analysis covers a sample of 133 countries over the period 2002-2017. The findings indicate that least developed countries (LDCs) receive higher AfT flows when they experience a rise in the level of export product concentration, while NonLDCs enjoy higher AfT flows when they diversify export products. Interestingly, higher amounts of AfT accrue to countries that diversify their export product basket towards manufacturing products, although different result patterns appear for the components of manufactured exports.

In this retrospective report we present five cases of critically ill pregnant or newly delivered women positive for Covid-19 admitted to our obstetrical departments at Karolinska University Hospital. They compose 6% of eighty-three pregnant women that tested positive for SARS-CoV-2 during the period March 25 to May 4, 2020. Three patients were at the time of admission in gestational week between 21+4 to 22+5 and treated during their antenatal period, meanwhile the other two were admitted within 1 week postpartum. All of them were in a need of intensive care, one was treated with high flow oxygen therapy, the other four with invasive mechanical ventilation (three with endotracheal intubation and one with extra corporeal membrane oxygenation). Age above thirty, overweight and gestational diabetes are notable factors in the cases presented. At the time of admission, they all presented with symptoms as fever, cough and dyspnea. Chest imaging with computer tomography scan was performed in each case and demonstrated multifocal pneumonic infiltrates in all of them but no pulmonary embolism was confirmed in any. Neither did the echocardiogram indicates any cardiomyopathy. Four of the patients have been discharged from the hospital, with an average of 20 hospital days. One antenatal pregnant woman needed prolonged ECMO therapy, in gestational week 27+3 she went into cardiac arrest, resulting in an urgent c-section on maternal indication. At the time of writing she is still hospitalized. In coherence with other published reports our cases indicate that critically ill pregnant women infected by SARS-Cov-2 may develop severe respiratory distress syndrome requiring prolonged intensive care. The material is limited for conclusions to be taken, more detailed information on symptoms, treatment, and outcomes for pregnant and postpartum women managed in intensive care is therefore needed.

Users of meteorological forecasts are often faced with the question of whether to make a decision now based on the current forecast or whether to wait for the next and hopefully more accurate forecast before making the decision. One would imagine that the answer to this question should depend on the extent to which there is a benefit in making the decision now rather than later, combined with an understanding of how the skill of the forecast improves, and information about the possible size and nature of forecast changes. We extend the well-known cost-loss model for forecast-based decision making to capture an idealized version of this situation. We find that within this extended cost-loss model, the question of whether to decide now or wait depends on two specific aspects of the forecast, both of which involve probabilities of probabilities. For the special case of weather and climate forecasts in the form of normal distributions we derive a simulation algorithm, and equivalent analytical expressions, for calculating these two probabilities. We apply the algorithm to forecasts of temperature and find that the algorithm leads to better decisions relative to three simpler alternative decision-making schemes. Similar problems have been studied in many other fields, and we explore some of the connections.

The recurrent coronavirus outbreaks in China (SARS-CoV and its relative, SARS-CoV-2) have raised speculations that perhaps Asians are somehow more susceptible to these coronaviruses. Here, we test this possibility based on an analysis of the lung-specific expression of ACE2, which encodes the known cell-entry receptor of both SARS-CoV and SARS-CoV-2. We show that ACE2 expression is not affected during tumorigenesis, supporting that the abundant transcriptomes in cancer genomic studies can be informatively used to study ACE2 expression among diverse individuals without cancer. We find that ACE2 expression in the lung increases with age, but is not associated with sex. Further, Asians do not differ from other populations for ACE2 expression and do not harbor unique genetic polymorphisms in the ACE2 locus. Thus, beyond illustrating an innovative method for assessing the potential impacts of demographic factors for non-cancer diseases from large-scale cancer sample datasets, our statistically robust findings emphasize that individuals of all races require the same level of personal protection against SARS-CoV-2.

The study delves into the Zaalklapspruit valley-bottom wetland in South Africa, a site designed through ecological engineering and currently impacted by acid mine drainage due to an upstream defunct coal mine. The research conducted in 2022, aimed to uncover the dynamics of contaminant dispersal within such a wetland setting, focusing on the origins, routes, and ultimate recipients of various metals and sulfur compounds. Analysis revealed that the bottom sediment is rich in organic material, with pH levels observed between 6.05 and 6.59, and exhibited notably low oxidation-reduction potentials, reaching down to −219.67 mV at sample point S3. Notably, Manganese displayed the highest adsorption rates, whereas Iron was predominantly absorbed by the roots of Typha capensis and the algae Klebsormidium acidophilum. The wetland's macrophyte rhizospheres hosted a rich array of microbiota, including families like Helicobacteraceae and Hydrogenophilaceae, which are crucial in metal and sulfur processing. This investigation sheds light on the intricate biogeochemical processes taking place involving the wetland's sediment, macrophyte root systems, periphyton, and microbial populations, underscoring the potential of ecologically engineered wetlands in the remediation of waters affected by acid mine drainage.

Pathogens that adapt to environmental stress can develop an increased tolerance to some physical or chemical antimicrobial treatments. The main objective of this study was to determine if acid adaptation increased the tolerance of Escherichia coli O157:H7 to high voltage atmospheric cold plasma (HVACP) in raw pineapple juice. Samples (10 ml) of juice were inoculated with non-acid-adapted (NAA) or acid adapted (AA) E. coli to obtain a viable count of ~ 7.00 log10 CFU/ml. The samples were exposed to HVACP (70 kV) for 1 to 7 min with inoculated non-HVACP-treated juice serving as control. Juice samples were analyzed for survivors at 0.1 h, and after 24 h of refrigeration (4 °C). Samples analyzed after 24 h exhibited significant decreases in viable NAA cells with sub-lethal injury detected in both NAA and AA survivors (P&lt;0.05). No NAA survivor in juice exposed to HVACP for 5 or 7 min was detected after 24h. However, numbers of AA survivors were 3.33 and 3.09 log10 CFU/ml in juice treated for 5 and 7 min, respectively (P&lt;0.05). These results indicate that acid adaptation increases the tolerance of E. coli to HVACP in pineapple juice. The potentially higher tolerance of AA E. coli O157:H7 to HVACP should be considered in developing safe juice processing parameters for this novel non-thermal technology.

Background: Feline infectious peritonitis (FIP) is a fatal feline disease classified as either effusive (‘wet’), non-effusive (‘dry’), or a mixture of both forms (‘mixed’). The anti-FIP therapeutic effect of Mutian and molnupiravir, two drugs whose active ingredient is a nucleic acid analog, has been confirmed recently. Methods: Of the cats with FIP, we observed a total of 122 and 56 cases achieved remission after administration of Mutian and molnupiravir as routine treatments, respectively. Changes in clinical indicators suggested to be correlated with FIP remission (weight, hematocrit, and albumin to globulin ratio) before and after the administration of each drug and during follow-up observation were statistically compared for each FIP type. Results: In all three FIP types, administration of either Mutian or molnupiravir resulted in statistically significant increases in these indicators. Furthermore, the effect of Mutian on improving the albumin to globulin ratio was not observed at all in wet FIP, as compared with that of molnupiravir, but statistically significant in mixed and dry (P<0.02 and P<0.003, respectively). These clinical features were all due to differences in fluctuations of circulating globulin levels. Conclusions: These results indicate slight inflammatory responses might be elicited continuously by residual feline coronavirus non-disappeared through molnupiravir treatments.

Chiral semiconductor nanostructures and nanoparticles are promising materials for applications in biological sensing, enantioselective separation, photonics, and spin-polarized devices. Here, we have studied the induction of chirality in atomically thin only 2 monolayers thick CdSe nanoplatelets (NPLs) grown by a colloidal method and exchanged with L-alanine and L-phenylalanine as model thiol-free chiral ligands. We have developed a novel two-step approach to completely exchange the native oleic acid ligands for chiral amino acids at the basal planes of NPLs. We performed an analysis of the optical and chiroptical properties of the chiral CdSe nanoplatelets with amino acids, which was supplemented by an analysis of the composition and coordination of ligands. After the exchange, the nanoplatelets retain HH, LH and SO exciton absorbance and bright HH exciton luminescence. Capping with thiol-free enantiomer amino acid ligands induce pronounced chirality of excitons in the nanoplatelets, as proven by circular dichroism spectroscopy, with high dissymmetry g-factor up to 3.4 × 10−3 achieved for HH excitons in the case of L-phenylalanine.

This study presents the encapsulation of two amino acid-based ionic liquids (AAILs), 1-Ethyl-3-methylimidazolium glycine [Emim][Gly] and 1-Ethyl-3-methylimidazolium alanine [Emim][Ala], in a highly porous metal organic framework (MOF-177), to generate state-of-the-art composites for post-combustion CO2 capture. The thermogravimetric analysis (TGA) demonstrated a successful encapsulation of the AAILs, consequently dramatically reducing the composites' surface area and pore volume. Both [Emim] [Gly]@MOF-177 and [Emim][Ala]@MOF-177 had close to 3 times the CO2 uptake of MOF-177 at 20 wt.% loading, 0.2 bar, and 303 K. Additionally, 20-[Emim][Gly]@MOF-177 and 20-[Emim] [Ala]@MOF-177 enhanced their CO2/N2 selectivity from 5 (pristine MOF-177) to 13 and 11, respectively.

Non-viral gene carriers because of their limited side effects, biocompatibility, simplicity and taking the advantages of electrostatic interactions have shown noticeable potential in gene delivery. The low transfection rate of non-viral vectors under physiological conditions is a significant issue. Here, the aim of this study was to investigate the efficacy of hydrophilic and hydrophobic groups on gene carriers such as two synthesized amphiphilic polymer of dextran-stearic acid-spermine (DSASP) with verified lipid and amine conjugations that associated with Fe3O4 superparamagnetic nanoparticles to promote the target delivery and decrease the transfection time using static magnetic field. Our findings illustrate that magnetic nanoparticles are spherical with positive surface charges and superparamagnetic behaviors. The DSASP–pDNA/MNPs offered a strong pDNA condensation, protection against DNase degradation, significant cell viability in HEK 293T cells and. Although conjugations of spermine play a critical role in transfection efficiency, amphiphilic polymer with more derivatives of stearic acid showed better transfection yields. Therefore, DSASP amphiphilic magnetic carriers offer new insights for gene delivery due to the amine contents and ameliorate the uptake of complexes via cell membrane based on its hydrophilic surface.

Mitochondrial dysfunctions, e.g. abnormal handling of mitochondrial DNA in TFAM mutants or in altered mitophagy, activate innate immunity. Recent reports also showed that deletion of mitochondrial matrix peptidase ClpP in mice transcriptionally upregulates inflammatory factors. Here, we studied ClpP-null mouse brain at two ages and embryonal fibroblasts, to identify which signaling pathways are responsible, employing mass spectrometry, immunoblots, and reverse transcriptase polymerase chain reaction. Anomalies in the mitochondrial unfolded protein responses pathway were prominent for the co-chaperone DNAJA3, and for its known interactor STAT1. Their mitochondrial dysregulation affected also their extra-mitochondrial abundance, as possible innate immune modulators. Increased expression was observed not only for the transcription factors Stat1/2, but also for two interferon-stimulated genes (Ifi44, Gbp3). Inflammatory responses were strongest for RLR pattern recognition receptors (Ddx58, Ifih1, Oasl2, Trim25) and several cytosolic nucleic acid sensors (Ifit1, Ifit3, Oas1b, Ifi204, Mnda). They can be explained by the accumulation of mitoribosomes and mitochondrial nucleoids in ClpP-null cells, which may act as damage-associated molecular patterns. The consistent dysregulation of these factors from early age might influence also human Perrault syndrome, where ClpP loss-of-function leads to early infertility and deafness, with subsequent widespread neurodegeneration.

The effects of mixing orders of tannic acid (TA), starch and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Besides, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol may have an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.

Bacterial indole-3-acetic acid (IAA), an effector molecule in microbial physiology, plays an important role in plant growth-promotion. Here, we comprehensively analyzed about 7282 prokaryotic genomes representing diverse bacterial phyla, combined with root-associated metagenomic data to unravel the distribution of tryptophan-dependent IAA synthesis pathways and to quantify the IAA synthesis-related genes in the plant root environments. We found that 82.2% of the analyzed bacterial genomes were potentially capable of synthesizing IAA from tryptophan (Trp) or intermediates. Interestingly, several phylogenetically diverse bacteria showed a preferential tendency to utilize different pathways and tryptamine and indole-3-pyruvate pathways are most prevalent in bacteria. About 45.3% of the studied genomes displayed multiple coexisting pathways, constituting complex IAA synthesis systems. Furthermore, root-associated metagenomic analyses revealed that rhizobacteria mainly synthesize IAA via IAM and tryptamine (TMP) pathways and might possess stronger IAA synthesis abilities than bacteria colonizing other environments. The obtained results refurbished our understanding of bacterial IAA synthesis pathways and provided a faster and less labor-intensive alternative to physiological screening based on genome collections. The better understanding of IAA synthesis among bacterial communities could maximize the utilization of bacterial IAA to augment the crop growth and physiological function.

Nasopharyngeal carcinoma (NPC) has not been thoroughly studied, and the pathogenesis of NPC is unclear. Scientists have neither discovered effective therapies nor achieved a desirable prognosis. Some studies have found that the regulation of intra- and extracellular ion channels hinges directly on cell apoptosis, and treatment with Gambogenic acid (GNA) brings changes to the volume-sensitive outwardly rectifying chloride (VSOR Cl-) current of CNE-2Z cells recorded by the patch clamp method. Nevertheless, rarely have any researchers probed into the relevance between this variation and the anti-tumor mechanism of GNA. This paper is suggested that GNA activates the VSOR Cl- current on the CNE-2Z cell membrane, and the activation of VSOR Cl- currents by GNA in CNE-2Z cells is blocked by the chloride channel blockers DIDS and DCPIB. GNA induces the down-regulation of GRP78 and up-regulation of ATF4 as well as chop proteins, which is evidence for the induction of CNE-2Z cell apoptosis, and this correlates with ER stress. GNA can activate the VSOR Cl- channel and lead to the occurrence of ER stress, thus inducing the apoptosis of CNE-2Z cells and inhibiting the proliferation of CNE-2Z cells.

The synthesis of new collagen, chitosan and chitosan-collagen coated magnetic nanoparticles have been done. Two types of cross-linkers for polymer shell stabilization were used: glutaraldehyde (Gla) as a standard cross-linker and new one – squaric acid (SqA). Structure and morphology of prepared nanoparticles were characterized by ATR-FT IR, XRD and TEM analysis. The immobilization of lipase from Candida rugosa was performed on the nanoparticles surface. The amount of immobilized enzyme was quantified by the Bradford method. All of lipase-biopolymers coated nanoparticles were characterized with good activity recovery. A little hyperactivation of lipase immobilized on nanoparticles with SqA was observed. All of prepared lipase-immobilized nanoparticles were characterized with very good reusability.

This study provides an in-depth examination of the binary system of n-Nonadecane and 1-Octadecanol, representative of plant cuticular waxes. It emphasizes the crystallization and phase transitions in this hydrocarbon mixture. Using Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FTIR) spectroscopy, the research uncovers detailed thermal properties and phase behaviors. The findings reveal the distinct phase transitions and enthalpy changes of each component in the binary system. This research is significant for its implications in under-standing the structural properties of plant waxes. Such insights are crucial for enhancing the effi-ciency of fertilizer and pesticide absorption in plant leaves, with broad applications in bionics and materials science. This study not only furthers the understanding of identifying specific phase transitions for each compound, facing challenges in detecting subtle changes using DSC. The re-search enhances understanding of plant cuticle waxes through FTIR analysis, revealing intricate molecular interactions and structural complexities. but also opens avenues for improved agri-cultural practices and material engineering, potentially influencing future innovations in these fields.

Background: The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the Vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in Vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact molecular mechanism driving this down-regulation in T1DM is yet to be fully understood. This study aimed to decipher differences in the expression of genes associated with Vitamin D metabolism in T1DM patients and to ascertain if there is a correlation between serum 1,25(OH)2D3 levels and the expression of these genes. We also sought to understand the influence of specific microRNAs (miRNAs) on the expression of Vitamin D metabolism genes in peripheral blood mononuclear cells (PBMCs) of T1DM patients. Furthermore, the study delved into the potential implications of altered Vitamin D metabolism genes and miRNAs on autoimmune processes. Methods: Utilizing real-time PCR, we assessed the expression profiles of genes encoding for 1-hydroxylases (CYP27B1) and 24-hydroxylases (CYP24A1), as well as related miRNAs, in PBMCs from 30 T1DM patients and 23 healthy controls. ELISA tests facilitated the measurement of 1,25(OH)2D3, GAD65, and IA-2 levels. Results: Our findings showcased down-regulated CYP27B1 mRNA levels, while CYP24A1 expression remained stable compared to healthy subjects (CYP27B1, p = 0.0005; CYP24A1, p = 0.205, respectively). In T1DM patients, the levels of has-miR-216b-5p were found to be increased, while the levels of has-miR-21-5p were decreased in comparison to the control group. Notably, no correlation was identified between the expression of CYP27B1 in T1DM patients and the levels of has-miR-216b-5p, has-miR-21-5p, and 1,25(OH)2D3. A significant negative correlation was identified between CYP27B1 mRNA levels in PBMCs of T1DM and IA2, but not with GAD65. Conclusions: The study highlights there were reduced levels of both CYP27B1 mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of CYP27B1, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and CYP27B1 expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM.

The analysis of the key factors which prevent or contribute to the promotion and development of the Power Purchase Agreements (PPAs) in order to meet the sustainability goals represents an important issue which worth being investigated, especially in the situation in which entering in bilateral relations inside this contract has a powerful meaning in achieving new climate targets, developing and improving the use of green energy, and promoting a sustainable green economy. The main goal of this research is to identify and analyze the main factors which help or pre-vent the promotion and development of a PPA, in order to meet the sustainability goals by promoting a green economy. For this research survey based on comparative analysis, questionnaires and interviews with energy experts, Spearman’s correlation matrix and IBM SPSS Statistics for Window are also used. The results suggest that although there are positive interest and an open attitude towards the PPA from both sides (sellers and buyers), but there is still place for improvement, the lack of knowledge or the insufficient measures taken so far being two of the reasons way until now in Romania we do not have a developed PPA market and the level of knowledge regarding this type of mechanism is quite low.

Information and communication technologies (ICT) are increasingly permeating our daily life and we ever more commit our data to the cloud. Events like the COVID-19 pandemic put an exceptional burden upon ICT infrastructures. This involves increasing implementation and use of data centers, which increased energy use and environmental impact. The scope of this work is to take stock on data center impact, opportunities, and assessment. First, we estimate impact entity. Then, we review strategies for efficiency and energy conservation in data centers. Energy use pertain to power distribution, IT-equipment, and non-IT equipment (e.g. cooling): Existing and prospected strategies and initiatives in these sectors are identified. Among key elements are innovative cooling techniques, natural resources, automation, low-power electronics, and equipment with extended thermal limits. Research perspectives are identified and estimates of improvement opportunities are presented. Finally, we present an overview on existing metrics, regulatory framework, and bodies concerned.

The chemical reaction between the quinolone antibiotic oxolinic acid (OA) and Fe(III), Zn(II), Ca(II), and Mg(II) ions results in the formation of metal-based complexes with the following formulas: [Fe(OA)(H2O)2Cl2]2H2O, [Zn(OA)(H2O)Cl]2H2O, [Ca(OA)(H2O)Cl], and [Mg(OA)(H2O)Cl]. We used analytical (C, N, H, Cl, metal analysis) and spectral (FT-IR, 1H NMR, UV-visible) data to structurally characterize the synthesized metal-based complexes of the OA molecule. We found that the OA molecule utilizes the two oxygen atoms of the carboxylate group and the pyridone C=O group to bind the investigated metal ions. The morphological properties of the synthesized OA complexes were assessed using X-ray powder diffractometry (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The biological properties, specifically antibacterial and antifungal activity, of the synthesized complexes were evaluated in vitro using the Kirby-Bauer disc diffusion protocol with five bacterial and three fungal strains. The complex containing Ca(II) ions exhibited remarkable antibacterial and antifungal activity against all tested microbial strains, surpassing or equaling the potency of the standard drugs (streptomycin for antibacterial assays and ketoconazole for antifungal assays).

Fructose in beverages has adverse effects on lipids, glucose and insulin sensitivity after acute and chronic ingestion. There is limited data showing that chronic consumption of fructose in solid foods has harmful effects. We hypothesized that a moderate amount of fructose compared with sucrose in solid food consumed for a month would not adversely influence fasting or postprandial lipids and glucose after an acute fat and carbohydrate load. Twenty-five men and women with prediabetes and/or obesity and overweight consumed in random order two acute test meals of muffins sweetened with either fructose or sucrose, followed by 4-week chronic consumption of 42g/day of either fructose or sucrose in low fat muffins after which the 2 meal tests were repeated. Subjects were randomised to sugar type in the chronic feeding period. Sugar type had no effect on the incremental area under the curve for triglyceride or uric acid at either time point (P=0.4 and P=0.9). There was no overall difference between meal tests at baseline and after 1 month and no effect of consuming sucrose or fructose muffins for 1 month. Fasting triglyceride increased after chronic consumption of fructose by 0.31±0.37 mmol/L compared with sucrose in people with IFG/IGT only (P=0.004). Fructose at a moderate intake of <10% of energy in solid food has no different effects on postprandial triglyceride and uric acid compared with sucrose although fasting triglyceride was increased in people with IFG/IGT after 1 month of fructose muffins suggesting the need for caution.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

Background: Several GLP-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes (T2DM). Their cardio- and renal protective effects and substantial weight loss have been evident and progressively expanded their role in the American Diabetes Association (ADA) guidelines, which are endorsed by the European Association for the Study of Diabetes (EASD). The increased demand leads to a global shortage. Methods: We utilized a repeated cross-sectional design, drawing data from national prescribing databases, to analyze six GLP-1 RAs: Dulaglutide, Enatide, Liraglutide, Lisenatide, Semaglutide, and Tirzepatide. AutoRegressive Integrated Moving Average (ARIMA) models with exogenous variables were applied to assess trends over time and regions. Results: The prescription rates significantly differ between regions. Wales shows the highest prescribing for most GLP-1 RAs. The ARIMA models indicated a significant increase in their prescribing after ADA guidelines 2022 (e.g., Dulaglutide: Post-ADA effect of 15.22, 95% CI: [12.97, 17.47]). Following GLP-1 RAs shortages in July 2023, the prescribing rates, particularly for Semaglutide, increased (Shortage effect: 74.36, 95% CI: [71.92, 76.80]). Model diagnostics, including the Akaike Information Criterion (AIC) and Durbin-Watson statistics, confirmed the robustness of these trends. Conclusion: Informed decisions should be made by considering prescribing trends before and after important events such as the issuing of new guidelines or safety alerts.

FtsZ is a bacterial protein that plays a crucial role in cytokinesis by forming the Z-ring. This ring acts as a scaffold to recruit other division proteins and guide the synthesis of septal peptidoglycan, which leads to cell constriction. In its native state, the FtsZ protein from Escherichia coli (EcFtsZ) exists as a multi-oligomer comprising dimers, trimers, tetramers, and hexamers in dynamic equilibrium of self-association and dissociation is dependent on protein concentration. This study employed classical biochemical techniques, including native PAGE, size-exclusion chromatography, sucrose gradient, and chemical cross-linking with formaldehyde, to characterize the trimeric state of EcFtsZ. The results of size-exclusion chromatography demonstrate that the trimer of EcFtsZ has a mass of 131 kDa and an experimental friction quotient (Rs/Rmin) of 1.9, which is very similar to the theoretical friction quotient (fn/f1) of 1.8 for a linear trimer. Cross-linking EcFtsZ with formaldehyde resulted in the occurrence of a polypeptide band of 128 kDa, which was recognized by anti-FtsZ antibodies. The result of the sedimentation of EcFtsZ cross-linking with formaldehyde returned a value (Smax/S20,w) equal to 1.9. This experimental value was found to be equal to the theoretical calculation of the sedimentation quotient (Sn/S1) for a lateral trimer. These findings indicate that at micromolar concentrations, the EcFtsZ trimer may assume a linear or lateral structure in the protein. Finally, the protein-protein interaction prediction program (PEPPI) indicated the potential for EcFtsZ to form two protein-protein contacts in its C-terminal domain, which may be involved in trimer formation.

Increasingly large numbers of people are using digital weight-loss services (DWLSs) to treat overweight or obesity. Although it is widely agreed that digital modalities improve access to care in general, obesity stakeholders remain concerned that many DWLSs are not comprehensive or sustainable enough to deliver meaningful health outcomes. This study adopted a mixed-methods approach to assess why and after how long patients tend to discontinue Austral-ia’s largest DWLS, a program that combines behavioural and pharmacological therapy under the guidance of a multidisciplinary care team. We found that in a cohort of patients who commenced the Eucalyptus DWLS between January and June 2022 (n=5604), mean program adherence was 171.2 (±158.2). Inadequate supply of a patient’s desired Glucose-like peptide-1 receptor agonist medication was the most common reason for discontinuation (43.7%), followed by program cost (26.2%), result dissatisfaction (9.9%), and service dissatisfaction (7.2%). Statistical tests revealed that ethnicity and age both had a significant effect on patient adherence. These findings suggest that DWLSs have the potential to improve access to comprehensive, continuous obesity care, but that care models need to improve upon the one observed in the Eucalyptus Australia DWLS to maximise program adherence.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

Measuring Marginal Reflex Distance-1 (MRD-1) is a crucial clinical tool used to evaluate the position of the eyelid margin in relation to the cornea. Traditionally, this assessment has been conducted manually by plastic surgeons, ophthalmologists, or trained technicians. However, with the advancements in Artificial Intelligence (AI) technology, there is a growing interest in the development of automated systems capable of accurately measuring MRD-1.In this context, we introduce novel MRD-1 measurement methods based on deep learning algorithms that can simultaneously capture images and compute the results. This prospective observational study involved 154 eyes of 77 patients aged over 18 years who visited Chungnam National University Hospital between September 1, 2023, and July 29, 2023. We collected four different MRD1 da-tasets from patients using three distinct measurement methods, each tailored to the individual patient. The mean MRD1 values, measured through the manual method using a penlight, the deep learning method, ImageJ analysis from RGB eye images, and ImageJ analysis from IR eye images in 56 eyes of 28 patients, were 2.64 ± 1.04 mm, 2.85 ± 1.07 mm, 2.78 ± 1.08 mm, and 3.07 ± 0.95 mm, respectively. Notably, the strongest agreement was observed between MRD1_deep learning (DL) and MRD1_IR (0.822, p < 0.01). In the Bland-Altman plot, the smallest difference was observed between MRD1_DL and MRD1_IR ImageJ, with a mean difference of 0.0611 and △LOA (limits of agreement) of 2.5162, which is the smallest among the other groups. In conclusion, this novel MRD1 measurement method, based on an IR camera and deep learning, demon-strates statistical significance and can be readily applied in clinical settings.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

To clarify whether cryptochrome contributes to stem elongation and flowering promoted by blue lights associated with low phytochrome activity, wild-type Arabidopsis was compared with its cryptochrome-deficient mutants and cryptochrome-overexpressing transgenic plants. Results indicated that the promotion effects were mainly related to low CRY1 activity, despite partial involvement of high-activity CRY2.

Several studies have shown that changes in incoming solar radiation and variations of the diffuse fraction can significantly modify the vegetation carbon uptake. Hence, monitoring the incoming solar radiation at large scale and with high temporal frequency is crucial for this reason along with many others. The EUMETSAT Satellite Application Facility for Land Surface Analysis (LSA SAF) operationally disseminates in near real time estimates of the downwelling shortwave radiation at the surface since 2005. This product is derived from observations provided by the SEVIRI instrument onboard the Meteosat Second Generation series of geostationary satellites, which covers Europe, Africa, the Middle East, and part of South America. However, near real time generation of the diffuse fraction at the surface level has only recently been initiated. The main difficulty towards achieving this goal was the general lack of accurate information on the aerosol particles in the atmosphere. This limitation is nowadays less important thanks to the improvements in atmospheric numerical models. This study presents an upgrade of the LSA-SAF operational retrieval method, which provides the simultaneous estimation of the incoming solar radiation and its diffuse fraction from satellite every 15 minutes. The upgrade includes a comprehensive representation of the influence of aerosols based on physical approximations of the radiative transfer within an atmosphere-surface associated medium. This article explains the retrieval method, discusses its limitations and differences with the previous method, and details the characteristics of the output products. A companion article will focus on the evaluation of the products against independent measurements of solar radiation. Finally, the access to the source code is provided through an open access platform in order to share with the community the expertise on the satellite retrieval of this variable.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

The genetic bases of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have been comprehensively studied, which is not the case for atypical cases not classified into these diagnoses. In the present study, we aim to contribute to the molecular understanding of the development of non-AD and non-FTD dementia by surveying rare pathogenic variants. The analysis was performed on 91 patients, the DNA samples of which were pooled and then subjected to whole exome sequencing. Among detected variants two are rare pathogenic and show significant difference in frequency between the analyzed pool and gnomAD Bulgarian control exomes. The rs373478202, G&gt;T, B9D1 variant, most likely present in heterozygous state; is causative for the autosomal recessive ciliopathy- Joubert syndrome, which involves specific CNS malformation. The rs148918985, C&gt;T, ASS1 variant leads to arginosuccinate enzyme deficiency and in compound heterozygosity with other rare pathogenic variant detected in the same gene causes the late-onset form of citrullinemia type I. This disorder causes high ammonia levels, which can lead to cerebral dysfunction. In conclusion, the detected rare pathogenic variants suggest that, in certain cases, the development of non-AD and non-FTD dementia can be mediated by structural alterations in neuronal cilia or by hyperammoniemia.

The study aimed to estimate the prevalence and association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with Type 2 Diabetes Mellitus (T2DM). According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged: 50–80 years) were divided into three groups: Non-sarcopenia (n = 38), Possible Sarcopenia (n = 31, 28.2%), and Sarcopenia (n = 41, 37.3%). Blood samples were collected and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D3 levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, there was a significant association between sarcopenia with BMI, body fat percentage (BF%), and dietary energy and protein intake. Low serum vitamin D3 is a significant risk factor for possible sarcopenia.

This paper aims to analyze arbitrarily loaded isotropic rectangular thin plates with two opposite edges supported (simply supported or clamped), from which one or both are clamped, and the other edges have arbitrary support conditions. Rectangular thin plates with two opposite edges simply supported are routinely analyzed using for the deflection the simple trigonometric series of Lévy or the double trigonometric series of Navier, while the loads are expanded in Fourier series. In this paper the flexibility method (or force method) of the linear beam theory was applied whereby the unknowns were the bending moments along the opposite edges; in this regard, the primary system was the plate simply supported along the above-mentioned opposite edges and subjected to the external loads, system solved using the Lévy solution, and the redundant system was the plate simply supported along the opposite edges and subjected to bending moments along those edges. In the redundant system, a modified Lévy solution was introduced to account for the edge moments. The compatibility equations (vanishing of the slopes at selected positions of the opposite edges) were set to determine the unknowns and so the efforts in the plate. The results obtained were in good agreement with the exact results.

In the context of carbon emissions peak, environmental issues highlight the importance of the green economy, how does economic agglomeration release growth potential and enable the coordinated development of the economy and environment? There are few works of literature to analyze it within the framework of spatial economy. This paper constructs a theoretical model to clarify the influence mechanism of economic agglomeration on green total factor productivity (GTFP), and then uses a dynamic SDM model to test the theoretical hypothesis. This contribution has three main findings. First, there is a "U-shaped" curve relationship between economic agglomeration and GTFP, and the formation mechanism is that economic agglomeration has a threshold effect on the agglomeration externalities such as infrastructure sharing, knowledge spillover, and labor market upgrading. Second, the mismatch of industrial structure is an important reason that the economic agglomeration in this region has not produced an obvious spatial spillover effect on other regions; Relaxing restrictions on the concentration of economic activity to regional centers would contribute to the improvement of GTFP. Third, GTFP has the classic "snowball effect" in the time dimension, but has the obvious "warning effect" in the space and time dimension. Based on this, this paper believes that at the present stage, it is necessary to adapt to the layout of economic geography, promote the rational allocation of human resources in the territorial space, promote the coordination between economic agglomeration and the development goal of green economy, and at the same time, it is necessary to cultivate the cooperative linkage mechanism of green economy development and transformation among cities.