Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

Despite the strong anticancer activity of SN38 (7-ethyl-10-hydroxy-camptothecin), some defects prevent its clinical application, such as severe side effects and loss of anticancer activity due to lack of selectivity to cancer cells and hydrolysis of ring E, respectively. To address the issue, herein a multifunctional SN38 derivative (compound 9) containing biotin (tumor-targeting group) and valproic acid (histone deacetylase inhibitor, HDACi) was synthesized via click chemistry and evaluated using MTT assay. The in vitro cytotoxicity study showed that compound 9 exhibited superior cytotoxicity as irinotecan against human cervical cancer HeLa cells, albeit inferior to SN38. More significantly, compound 9 significantly reduced toxicity in mouse embryonic fibroblast NIH3T3 cells, indicating that compound 9 had the capacity to enhance tumor targeting due to its cell selectivity. Further studies demonstrated that compared with irinotecan, compound 9 induced similar apoptosis of cancer cells. Consequently, compound 9 can not only improve its tumor-targeting ability mediated by biotin but also exert the potent anticancer activity through the synergism of SN38 and valproic acid, indicating that the design concept is an effective strategy for structural modification of SN38.

Tomato (Solanum lycopersicum), an important vegetable crop, is a host for numerous pests and pathogens. Consequently, tomato breeders are striving to improve pest resistance. Many acces-sions of the wild relative S. habrochaites display high resistance towards arthropod pests such as spider mites and whiteflies and the presence of the sesquiterpene hydrocarbon 7-epi zingiberene in its trichomes has been associated with arthropod resistance. Consequently, tomato breeders are attempting to introgress 7-epi zingiberene from wild to cultivated tomato, which requires the ability to quantify zingiberene. 7-Epi zingiberene has conjugated double bonds causing it to ab-sorb uv light. In fact, de Freitas, et al. [1] have claimed that measurement of absorbance at 270 nm of tomato leaflet washes can be used to quantify zingiberene. However, this claim has never been critically evaluated. We initially evaluated the use of uv absorbance to estimate zingiberene content of leaflet washes from an interspecific hybrid tomato BC4F2 generation that was segre-gating widely for presence and abundance of zingiberene. When absorbances at 270 nm were compared with zingiberene measured by gas chromatography the resulting relationship did not obey the Beer-Lambert law. Consequently, we examined in detail aspects of the uv-absorbance of zingiberenoids by: 1) obtaining uv absorbance spectra for three isolated zingiberenoids and de-termining the relationship between the abundance of each isolated compound and absorbance at single wavelengths; 2) obtaining uv absorbance spectra of leaflet washes of relevant wild acces-sions and parents; 3) obtaining average absorbance spectra for interspecific generations of tomato that were segregating for abundance of zingiberenoids and determining their λmax values in the 250-280 nm region; 4) evaluating by regression the relationship between absorbance at a single wavelength and the concentration of zingiberene and when present, its derivatives, as measured by gas chromatography in several interspecific hybrid generations; and 5) exploring the potential use of absorbances at multiple wavelengths to improve estimates of concentrations of zingi-berenoids. Results indicated that isolated zingiberenoids as well as leaflet washes of wild tomatoes that contain zingiberenoids have broad absorbance spectra in the uv region with a λmax of 264 nm. The relationship between abundance of isolated zingiberenoids and absorbance at a single wavelength of 264 nm did obey the Beer-Lambert Law. Average absorbance spectra for leaflet washes from BC3F5 generation plants sampled by two methods, as well as from a BC5F1 and a BC3F3 generation showed subtle shifts in the λmax away from 264 nm. Furthermore, the rela-tionship between absorbance at 264 nm and zingiberenoid content of these generations did not obey the Beer-Lambert Law in that in each case regression of absorbance on zingiberenoid content of the leaflet washes resulted in non-zero intercept estimates that varied considerably among generations and sampling methods. Use of multiple wavelengths for estimation zingiberenoids in these breeding generations was explored and inclusion of additional absorbances at one or two wavelengths identified by stepwise regression always improved estimates of zingiberenoid content from absorbance data. However, the identified wavelength(s) differed among generations. Taken together the results indicate that measurement of absorbance of tomato leaflet washes at a single wavelength is not a reliable quantitative estimate of zingiberenoids in the leaflet wash. These estimates can be improved by utilizing absorbance at multiple wavelengths, but the par-ticular wavelengths will likely vary among generations. Lastly, measurement of absorbance may be a useful tool in identifying those relatively rare individuals in a generation that is widely segregating for zingiberenoid content. However, even in this situation the determination of the actual zingiberene content e.g., for comparison with the donor parent, would need to be back-stopped by a valid quantitative method such as gas chromatography.

Wounding is a serious environmental stress in plants. Oxylipins such as jasmonic acid play an important role in defense against wounding. Mechanisms to adapt to wounding have been investigated in vascular plants; however, those mechanisms in nonvascular plants remain elusive. To examine the response to wounding in Physcomitrella patens, a model moss, a proteomic analysis of wounded P. patens was conducted. Proteomic analysis showed that wounding increased the abundance of proteins related to protein synthesis, amino acid metabolism, protein folding, photosystem, glycolysis, and energy synthesis. 12-Oxo-phytodienoic acid (OPDA) was induced by wounding and inhibited growth. Therefore, OPDA is considered a signaling molecule in this plant. Proteomic analysis of a P. patens mutant in which the PpAOS1 and PpAOS2 genes, which are involved in OPDA biosynthesis, are disrupted showed accumulation of proteins involved in protein synthesis in response to wounding in a similar way to the wild-type plant. In contrast, the fold-changes of the proteins in the wild-type plant were significantly different from those in the aos mutant. This study suggests that PpAOS gene expression enhances photosynthesis and effective energy utilization in response to wounding in P. patens.

This study examines the behavior of stearic acid (SA) and 12-hydroxystearic acid (12-HSA) aqueous mixtures as a function of temperature and 12-HSA/SA molar ratio (R). Whatever R, the system exhibits a morphological transition at a given threshold temperature, from multilamellar self-assemblies at low temperature towards small micelles at high temperature, as shown by a combination of transmittance measurements, Wide Angle X-ray diffraction (WAXS), small angle neutron scattering (SANS) and differential scanning calorimetry (DSC) experiments. Such transition originates from the melting of the crystallized fatty acids within the lamellar phase. The precise determination of the threshold temperature, which ranges between 20°C and 50°C depending on R, allows for the construction of the whole phase diagram of the system as a function of R. At high temperature the micelles that are formed are oblate for pure SA solutions (R = 0) and prolate for pure 12-HSA solution (R = 1). In the case of mixtures, there is a progressive continuous transition from oblate to prolate shape when increasing R, with micelles that are almost purely spherical for R = 0.33.

Bacterial infections are world-wide problem and resistant bacteria is increasing globally that lead to treatments failure. Thus, it is important to find new techniques that are effective for the treatment antibiotic-resistant microorganisms. Green medicine used for the medication of different bacterial infection. Therefore , the study aimed to evaluate the immunomodulatory activity of essential fatty acid semi carbazide (EFASC) compounds extracted from flaxseed to eradicate resistance pathogens . Crud extracts of Linum usitatissimum was extracted by hexane for extraction of EFASC. The results of LD₅₀ appear that a live suspension of E.coli was 0.49×10⁷ ,while HK E.coli was 10⁸ , 125 mg /ml were the optimum dose in stimulate immune response of EFASC which gave maximum dose of total WBC , Neutrophil and Monocyte count. The immunomodulatory activity appear that E.coli + EFASC released moderate levels of IL-4 . HK E.coli release higher IL-4 lead to increase the hypersensitivity and hyper responses of immune system. HK + EFASC immunogen revealed moderate increased in IL-12 mean level 0.99 pg /ml, HK bacteria recorded 1.49 pg/ml, while the mean of EFASC revealed no significant different compare with control. An effective protection was observed in immunized groups with HK E.coli and EFASC challenged with 100 of LD50 of a live E.coli.

In green chemistry, filamentous fungi are regarded as a kind of robust microorganism for the biotransformation of natural products. Nonetheless, the screening of microorganisms is crucial for the effective biotransformation of natural products such as phenazine compounds. The precursor metabolite of most phenazine derivatives in Pseudomonas spp. is phenazine-1-carboxylic acid (PCA), the key constituent of shenqinmycin, widely used to control rice sheath blight in southern China. In this study, a new fungus strain Aspergillus sclerotiorum was isolated, which can efficiently convert PCA into 3-hydroxy-phenazine 1-carboxylic acid (3-OH-PCA). Moreover, an effective whole cells biotransformation system was constructed by screening optimal reaction conditions and carbon sources. Hence, Aspergillus sclerotiorum exhibited desirable adaptation by consumption of different carbon sources and maximum whole cell biomass (10.6 g/L DCW) was obtained as a biocatalyst from glucose. Optimal conditions for whole-cell biocatalysis of PCA were evaluated, including PCA concentration of 1120 mg/L, pH 7.0, temperature of 25°C, rotation rate 200 rpm and dry cell weight 15 g/L for 60 h, thus 1060 mg/L of 3-OH-PCA was obtained and the conversion efficiency of PCA was 94%. Hence, the results of repeated batch mood revealed that the biotransformation efficiency of fungus pellets reduced with each subsequent cycle but remained stable in all five cycles with the provision of glucose supplement. These findings open the prospective of using filamentous fungi for the whole cell biocatalysis of phenazine in enormous amount and efficient production of 3-OH-PCA. Moreover, these results laid the foundation for further research to disclose the genetic based mechanism of the strain responsible for PCA biotransformation.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

Acne vulgaris is a prevalent skin condition that affects people of all ages and can have significant physical and psychological impacts. Hydroxy acids, such as alpha-hydroxy acids (AHA) and beta-hydroxy acids (BHA), have demonstrated potential as effective ingredients for topical acne treatments due to their exfoliating and skin-rejuvenating properties. This study assessed the effectiveness of encapsulating AHA and BHA in pullulan-collagen nanofibers as a novel approach to acne treatment. The study involved preparing Pullulan and polyvinyl alcohol (PVA) solutions combined with sodium chloride (NaCl) to create a stable mixture. Collagen and Pullulan were then dissolved in deionized water and mixed to form a collagen-pullulan solution. Various weight ratios of Collagen to Pullulan were tested to optimize nanofiber formation. This research achieved electrospinning of nanofibers, confirmed by scanning electron microscopy (SEM) analysis, which revealed well-formed and continuous nanofiber structures in acidic solutions. Fourier transform infrared spectroscopy (FTIR) analysis provided insights into the chemical composition of the nanofibers, indicating the presence of ester, carboxylic acid, hydroxyl, and phenolic groups. Contact angle measurements demonstrated that the pullulan-collagen nanocomposite exhibited hydrophilic properties, albeit less hydrophilic than pure Collagen. Biocompatibility assays using mesenchymal stem cells (MSCs) and human skin fibroblasts (HSFs) revealed that the pullulan-collagen nanocomposite promoted higher cell viability compared to pure Collagen, suggesting its potential as a supportive matrix for cell growth and tissue regeneration. AHA-BHA-infused nanofiber skin masks hold promise as effective topical treatments for acne vulgaris. The successful encapsulation of hydroxy acids within pullulan-collagen nanofibers, in conjunction with their favourable chemical composition, hydrophilicity, and biocompatibility, positions them as promising candidates for delivering active ingredients and enhancing skin health. Further nanofiber formulation optimisation is necessary to exploit their therapeutic potential in skincare applications.

Surfactants are amphiphilic molecules and one of the most versatile products of the chemical industry. They can be absorbed at the air-water interface and can align themselves so that the hydrophobic part is in the air while the hydrophilic part is in water. This alignment lowers the surface or interfacial tension. Gemini surfactants are a modern variety of surfactants with unique properties and a very wide range of potential applications. Hexamethylene-1,6-bis(N-dodecyl-N,N-dimethylammonium bromide) is one such representative compound that is a better alternative to a single analogue. It shows excellent surface, antimicrobial, and anticorrosion properties. With a highly efficient synthetic method and a good ecological profile, it is a potential candidate for numerous applications, including biomedical applications.

Background: Participation is low (43%) in Australia’s National Bowel Cancer Screening Program which provides a biennial Fecal Immunochemical Test kit mailed to the home of Australians aged 50-74 years. While several factors for non-participation have been identified, the role of mental and physical health on screening behaviour has not been assessed. Methods: Participants of the Australasian Colorectal Cancer Family Registry Cohort were asked to complete a questionnaire on their colorectal cancer screening in the past five years and a validated measure of mental and physical health. The association between mental and physical health and screening was determined for Australian participants aged 45-75 years who had never been diagnosed with colorectal cancer. Multivariable logistic regression was used to adjust for measured potential confounders. Results: Of the 1130 eligible participants, 819 reported colorectal cancer screening in the past five years (72%). After adjusting for potential confounders, there was no evidence that overall mental or physical health was associated with colorectal cancer screening. However, one specific scale, general health, was positively associated with colorectal cancer screening (p=0.014) with those reporting higher levels of general health undergoing screening.Conclusion: We found limited evidence that mental and physical health, as measured by a short questionnaire, are associated with colorectal cancer screening. A potential limitation is reverse causation where previous screening may have impacted mental or physical health. A more detailed study of physical and mental health as barriers or enablers of screening is needed.

The MMP-9-1562C/T polymorphism influence incidence and course of many diseases of the central nervous system. We found, using luciferase assays and Q-RT-PCR technique, allele-specific in-fluence of MMP-9-1562C/T polymorphism on the MMP-9 promoter activity and on the expression of MMP-9 mRNA in human neurons derived from SH-SY5Y cells. Then, we have elucidated the mechanism responsible for the allele-specific action of the MMP-9-1562C/T polymorphism on transcriptional regulation of the MMP-9 gene using pull-down assay combined with mass spec-trometry analysis, EMSA and EMSA supershift techniques, as well as DsiRNA-dependent gene silencing. We have found that MMP-9 promoter activity and MMP-9 mRNA expression are reg-ulated in human neurons in the MMP-9-1562C/T allele-specific manner with stronger upregulation conferred by the C allele. Moreover, we have revealed that the allele-specific action of the MMP-9-1562C/T polymorphism on the neuronal MMP-9 expression is related to HDAC1 and ZNF384 transcriptional regulators. We show that HDAC1 and ZNF384 bind differentially to the C and the T alleles forming in vitro different regulatory complexes. Moreover, our data demonstrate that HDAC1 and ZNF384 downregulate differentially the MMP-9 gene promoter activity and MMP-9 mRNA expression in vivo in human neurons acting mostly via the T allele.

Abstract: The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In patients with neurodevelopmental disorders, DNA’s from viruses and bacteria including known teratogens were tested against chromosome anomalies known to cause the disorders. Results support a theory that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis, and sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying non-neurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

Purpose: To assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild to moderate dry eye disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Methods: Tolerability and safety were evaluated in 24 healthy subjects. Participants were in-structed to routinely apply one drop of the formulation three times a day in the study eye, for a period of two weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/ receiving the study formulation) or Control (Group 2/ Receiving HA 0.4% eye lubricant) groups, for 4 weeks. Assessments included MMP-9 positivity, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive tear film breakup time (NIF-BUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer's test, and meibomiography. A crossover design with a four-week follow-up was applied to the control group. Results: Healthy subjects receiving the study formulation exhibited good tolerability and no ad-verse events. Group 1 showed significant MMP-9 reduction (25% positivity rate) unlike Group 2 (87.5% positivity rate). Group 1 displayed improved CIC (33.3% vs. 0% SSD) compared to Group 2 (29.1%). OSDI and NIF-BUT scores improved in both groups (p < 0.001). Only Group 1 showed improved NIAvg-BUT and Schirmer’s test scores (p < 0.001), while Group 2 did not (p > 0.05). MMP-9-positive subjects shifted from 25% to 91.6% in Group 1 and 87.5% to 20.8% in Group 2 after the follow-up. Conclusion: The topical formulation containing helenalin from Arnica montana and hyaluronic acid is well tolerated and has a good safety profile. Our formulation reduces DED sympto-matology and modulates the ocular surface inflammatory process; this is evidenced by the en-hancement of CIC, the improvement of DED-related tear film status, and the reduction of MMP-9 positivity rate.

Overhydration (OH) is a common medical problem found in patients with kidney or heart failure, but still a specific marker has not been found. Clinicians today use bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function like NT-pro-BNP, GFR or creatinine levels. New serum markers such as Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are being researched with promising results. The need to discover a more precise marker of overhydration is dire mainly because physical examination is extremely imprecise. Signs and symptoms of fluid overload like edema or gradual increase of body mass are not always present, especially in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation focusing especially on kidney diseases.

Background: Most sepsis patients died during their first episode and the long-term survival post discharge was low. Major adverse cardiovascular events and repeated infections were regarded as the major causes in such conditions. No definite medications were proven to effectively improve the long-term outcome. We aimed to examine the benefit of statins on the long-term outcome of survived sepsis patients. Methods: Between 1999 and 2013, a total of 220,082 patients with the first episode of sepsis hospitalization were included and 134,448 ones (61.09%) survived to discharge. The survived patients who subsequently had statins use of >30 cumulative defined daily doses (cDDDs) post discharge were defined as the statin users. After propensity score matching of 1:5, a total of 7,356 and 36,780 survived patients were retrieved as the study (statin-users) and comparison cohort (non-statin users), respectively. The main outcome was the long term survival post discharge. HR with 95% CI was calculated using the Cox regression model to evaluate the effectiveness of statins with further stratification analyses according to cDDDs. Results: The study cohort, that is, the statin users had an adjusted HR of 0.29 (95% CI, 0.27-0.31) in long term mortality rate compared with the comparison cohort. For statin users with the cDDDs of 30–180, 180–365, and >365, the adjusted HRs were 0.32, 0.22, and 0.16, respectively, (95% CI, 0.30-0.34, 0.19-0.26, and 0.12-0.23, respectively) compared with the non-statin users (defined as statins use <30 cDDDs post discharge), and the P for trend <.0001. In the sensitivity analysis, after excluding the survived patients who died within three and six months post discharge, the adjusted HR of statins use remained significant (0.35, 95% CI 0.32-0.37 and 0.42, 95% CI 0.39-0.45, respectively). Conclusions: Statins decreased the long-term mortality post sepsis. Further randomized control trial deserved to be conducted to confirm this observation.

Weather radar plays a crucial role in the monitoring of severe convective weather. However, due to its limited detection range, it cannot conduct effective monitoring in remote offshore areas. Therefore, this paper utilized the Unet++ to establish a model for retrieving radar composite reflectivity based on Himawari-9 satellite datasets. In the process of comparative analysis, we found that both satellite and radar data exhibit significant diurnal cycles, but there are notable differences in their variation characteristics. To address this, we established 4 comparative models to test the influence of latitude and diurnal cycles on the inversion results. The results show that adding the distribution map of the minimum cloud-top brightness temperature at the corresponding time in the model can effectively reduce the root mean square error (RMSE) of the model and enhance the accuracy of severe convective weather monitoring. This conclusion can be applied in the future to enhance and improve satellite quantitative precipitation estimation.

Research on titanium oxo complexes (TOCs) are usually focused on their structure and photocatalytic properties. Findings from these investigations spurred our interest in exploring also their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the antimicrobial activity evaluation of the obtained materials. Investigations carried out demonstrated antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, also for producing composite coatings.

The KID (Koopmans in DFT) procedure usually applies in organic molecules of the closed–shell type. We used the KID procedure in an open–shell system for the first time to choose the most suitable density functional to compute global and local reactivity descriptors coming from the Conceptual Density–Functional Theory. From a set of 18 density functionals spread from the second until the fourth rung of the Jacob’s ladder: BP86, B97-D, BLYP, CAM-B3LYP, M06-L, M11-L, MN12-L, B3LYP, PBE0, N12-SX, M06-2X, M11, MN12-SX, CAM-B3LYP, LC-ωHPBE, ωB97X-D, APFD, MN15 and MN15-L, we concluded that CAM-B3LYP provides the best outcome.

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

MicroRNA-155 (miR-155) expression promotes inflammatory responses in macrophages. Activation of macrophages with lipopolysaccharide (LPS) elevates miR-155, while the anti-inflammatory cytokine interleukin-10 (IL10) reduces miR-155 levels. MiR-155 exists in two forms, miR-155-5p and miR-155-3p, produced from the precursor of miR-155 (pre-miR-155). MiR-155-5p is the most abundant strand in activated macrophages, but in response to LPS, the miR-155-3p level is upregulated first, followed by miR-155-5p later. We have previously identified CELF2 protein which interacts with pre-miR-155 and impairs miR-155-5p expression. We now show that CELF2 only regulates the miR-155-5p expression and that another protein FUBP1 controls miR-155-3p levels in response to LPS and IL10.

Natural products are an important source of antibacterial agents. Canthin-6-one alkaloids have displayed potential antibacterial activity based on our previous work. In order to improve the activity, twenty-two new 3-N-benzylated 10-methoxy canthin-6-ones were designed and synthesized through quaternization reaction. The in vitro antibacterial activity against three bacteria was evaluated by double dilution method. Four compounds (6f, 6i, 6p and 6t) displayed 2-fold superiority (minimum inhibitory concentration (MIC) = 3.91 µg/mL) against agricultural pathogenic bacteria R. solanacearum and P. syringae than agrochemical propineb. Moreover, the structure–activity relationships (SARs) were also carefully summarized in order to guide the development of antibacterial canthin-6-one agents.

Muscle mass and strength decrease with aging, but habitual exercise can maintain muscle health. β-Hydroxy-β-methyl butyrate calcium (HMB) and black ginger (BG) are anti-oxidants that have been reported to improve muscle protein metabolism and energy production; these molecules may have synergistic effects. The senescence-accelerated mouse-prone 8 (SAMP8) model is a useful model of muscle aging. Therefore, in this study, we explored how the combination of habitual exercise, HMB, and BG affected muscle aging. We used 28-week-old SAMP8 mice divided into five groups: control, exercise (Ex), Ex+BG, Ex+HMB, and Ex+BG+HMB (Ex+Comb). Mice were required to run on a treadmill for 16 weeks at 5 days per week. In 44-week-old mice, grip strength tests and dissection were conducted. Muscle weight was measured, and the gastrocnemius muscle was subjected to quantitative polymerase chain reaction and immunoblotting. Muscle mass and strength were preserved in the Ex+Comb group, and mitochondrial function was preserved through suppressing oxidative stress. Muscle protein synthesis signaling was improved in the Ex+Comb group. Autophagy and the ubiquitin system were normalized by Ex+Comb treatment. Overall, habitual exercise and HMB plus BG treatment maintained muscle health by suppressing oxidative stress, preserving mitochondrial function, and maintaining muscle protein metabolism in SAMP8 mice.

Adsorption is an effective strategy for the removal of pollutants from the wastewater. Herein, a 2-hydroxyterephthalic acid (HTC) modified hypercrosslinked polymer (HTC-HCP) is successfully synthesized via Friedel-Crafts reactions, and used as an adsorbent for the different types of pollutants including organic contaminants and heavy metal ions from wastewater. Excellent adsorption capacities are observed for amines (aniline, p-methylaniline (p-MA), p-chloroaniline (p-CA), and p-aminobenzoic acid (p-ABA)), phenols (phenol, p-chlorophenol (4-CP) Bisphenol A (BPA), 1-Naphthol (1-NP)), dyes (rhodamine B (RhB) and methyl orange (MO)), and metal ions (Pb2+, Hg2+, and Cd2+). The resulting polymers exhibited excellent adsorption performance towards these pollutants. Especially, the removal rate of aniline is above 95% in the concentration of 2.5 mg/L in 40 min at 25 °C. The interaction mechanism has been investigated, and confirmed by FTIR and the theoretical calculation results. It is due to surface complexation and chemisorption between adsorbent and adsorbate. The polymer exhibits good performance such as high adsorption capacity, high separation efficiency, biodegradable properties, and easy regeneration, suggesting that its potential technological applications for the removal of organic compounds and heavy metal ions from actual industrial effluent.

The reaction mechanism of the carboxylation of K-2-naphthoxide was investigated by density functional theory calculations and spectroscopic studies. The reaction intermediates and products were confirmed by CO₂ adsorbed-FTIR and ¹H-NMR measurements. Four steps of the reaction pathway were identified: CO₂ activation, electrophilic substitution, CO₂-K complex rearrangement, and H-shift, producing 2-hydroxy-1-naphthoic acid (2,1-HNA), 2-hydroxy-3-naphthoic acid (2,3-HNA), and 2-hydroxy-6-naphthoic acid (2,6-HNA). The occurrence of CO₂-K complex rearrangement was also confirmed. These energy profiles of reaction pathways for the reaction intermediates were well consistent the experimental results on the carboxylation of K-2-naphthoxide.

The aim of this study was to investigate the effect of β-Hydroxy-β-methylbutyrate (HMB) supplementation on anti-inflammatory cytokines including IL-4, IL-10 and TGF-β during an acute bout of resistance exercise (RE) in young resistance trained men. Ten resistance-trained men in a randomized, double-blind, placebo-controlled and crossover study, were administered a 7-day HMB supplementation (3×1 g.d-1 of HMB) and placebo (3×1 g.d-1 of Maltodextrin) with a 7 days washout period. After supplementation periods, subjects performed three sets of bench press, lat pull down, leg extension, leg curl, biceps curl, triceps curl and shoulder press to failure with 85% of one repetition to maximum (1RM). Blood samples were obtained before- (Pre), immediately post- (IP) and 1 hour-post RE (1h P) to assess serum concentrations of IL-4, IL-10 and TGF-β1. The data were analyzed using 2 (treatment: HMB and PL) × 3 (time points: Pre, IP and 1hP) repeated measures analysis of variance (ANOVA) followed by the Bonferroni post hoc test with a significant level of p<0.05. Serum IL-4 was significantly higher at IP resistance exercise in HMB compared to placebo. Circulating IL-4 and TGF-β1 were significantly raised at IP compared to Pre in both HMB and placebo treatments. No significant differences between treatments were observed for IL-10 and TGF-β1at any time points. In conclusion, HMB supplementation increased the circulating level of IL-4 during RE in resistance-trained men, which may attenuate inflammation and facilitate adaptation to RE.

Background. Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around eight hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites lead to consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. PubMed, Scopus, Science Direct, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials to systematically identify all relevant studies published up to June 16, 2023. Results. The final analysis included two published retrospective cohort studies; a single site (n = 200) and a multisite study (n = 85) of ‘good’ quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Meta-analysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% CI: 47.6% lower to 6.4 times higher risk, p = 0.342) and inverse-variance method (RR: 1.87, 95% CI: 0.52-6.65, p = 0.336). Conclusions. Dosing metronidazole every 12 hours is as effective as every 8-hour dosing for anaerobic infections. Healthcare systems may consider the adoption of every 12-hour metronidazole dosing with continued evaluation of patient outcomes.

Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli including environmental enrichment (EE) and antidepressant treatment acting through BDNF-TrkB signaling. We have recently identified NPs in meninges, however menigneal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of 4 weeks fluoxetine administration or 1 week EE treatment on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of meningeal cell number and proliferation, we observed, in meninges, an increased number of β3-Tubulin⁺ immature neuronal cells. Lineage-tracing experiment confirmed that EE-induced β3-Tubulin⁺ immature neuronal cells present in meninges originated from GLAST⁺ radial glia cells. To investigate the molecular mechanism responsible for this response, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced increase of β3-Tubulin⁺ immature neuronal cells in meninges.Overall these data showed, for the first time, that the meningeal niche responded to neurogenic stimuli by increasing the immature neuronal population through TrkB-mediated signaling. A better understanding of the neurogenic stimuli effects on NPs in meninges may be useful to improve the effectiveness of depression and mood disorders treatments.

The proposed research study explore the decision tool for cropwise variability of NDVI using RS techniques and GIS tool as a crucial indicators for monitoring vegetation status.A small case study for Parbhani district of Maharashtra, India was conducted using Landsat-9 satellite images of the Rabi season in the year 2022-23 were processed using ArcGIS 10.7 software to derive the NDVI values. During the analysis, the maximum NDVI in the study area was recorded at 0.5857 on February 03, 2023, while the minimum was observed as -0.1018 on February 19, 2023. For specific crops, the average NDVI ranged from 0.1183 to 0.3189 for wheat, 0.1679 to 0.2891 for jowar, and 0.1163 to 0.3367 for gram. The mean NDVI values for wheat, jowar, and gram crops during the Rabi season of 2022-23 were 0.218, 0.219, and 0.217, respectively.Furthermore, the average NDVI values exhibited an increasing from the initial stage to the mid-crop growth stage, followed by a decrease during the end-season stage for wheat, jowar, and gram crops. Interestingly, the mean NDVI values of major Rabi crops, wheat, jowar, and gram for the year 2022-23, is approximately similar to the mean NDVI values observed for of year 2022-23.

Atherosclerosis (AS) is an age-related disease. Mitochondria and telomere links have been considered to play important roles in AS. PinX1 is a potent and highly conserved endogenous telomerase inhibitor. However, the role of pinX1 in AS and its role in oxidative stress have not been reported. In order to investigate the role of pinX1 in AS, we established a classical AS mice model in the present work and increased pinX1 protein expression using pinX1 overexpression adeno-virus by tail vein injection. Then, red-oil O and HE staining were employed to evaluate the severity of AS. Serum lipid profile and oxidative stress were also detected by using its specific chemical testing kit. The results indicated that high-fat diet (HFD) markedly decreased pinX1 and increased p66shc protein expression, whereas overexpression of pinX1 protein expression in mice produced the opposite results. In addition, pinX1 significantly minimized plaque area and alleviated the abnormal serum lipid profile. By using Western blot and Biochemical assay kits, overexpression of pinX1 decreased p66shc and MMP-9 protein expression and reduced oxidative stress. This study showed pinX1 can inhibit p66shc, MMP-9, and related oxidative stress, pinX1 may be considered as a new candidate target for the treatment of AS.

Accumulating evidence suggests that mast cells should play critical roles in disruption and maintenance of intestinal homeostasis, although it remains unknown how they affect local microenvironment. Interleukin-9 (IL-9) was found to play critical roles in intestinal mast cell accumulation induced in various pathological conditions, such as parasite infection and oral allergen-induced anaphylaxis. Newly recruited intestinal mast cells trigger inflammatory responses and damage epithelial integrity through release of a wide variety of mediators including mast cell proteases. We established a novel culture model (mucosal mast cell-like cultured mast cells, MMC-like MCs), in which murine IL-3-dependent bone marrow-derived cultured mast cells (BMMCs) were further cultured in the presence of stem cell factor and IL-9. In MMC-like MCs, drastic up-regulation of Mcpt1 and Mcpt2 was found. Although histamine storage and tryptase activity were significantly downregulated in the presence of SCF and IL-9, it was entirely reversed when mast cells were co-cultured with a murine fibroblastic cell line, Swiss 3T3. MMC-like MCs underwent degranulation upon IgE-mediated antigen stimulation, which was found to less sensitive to lower concentrations of IgE in comparison with BMMCs. This model might be useful for investigation of the spatiotemporal changes of newly recruited intestinal mast cells.

The 10-valent pneumococcal vaccine was introduced in Pakistan’s Expanded Program on Immunization (EPI) in 2013 as a 3+0 schedule without catchup. We conducted three annual cross-sectional surveys from 2014-2016 to measure vaccine-type (VT) carriage in infants from a rural part of Pakistan. Nasopharyngeal specimens were collected by random sampling of infants from 2 union councils of Matiari. Samples were then transported to Infectious Disease Research Laboratory (IDRL) at the Aga Khan University within 6-8 hours of collection. Serotypes were established using sequential multiplex PCR. Of the 665 children enrolled across three surveys, 547 were culture positive for pneumococcus. VT carriage decreased from 21·8% in 2014 to 12·7% in 2016 (p-value for trend <0·001). Those who were not vaccinated or partially vaccinated were found to be at higher risk of carrying a VT serotype (aOR 2·53, 95% CI 1·39, 4·63 for non-vaccinated) and (aOR 3·35, 95% CI 1·82, 6·16 for partially vaccinated). On the other hand, being enrolled in the most recent survey was negatively associated with VT-carriage (aOR 0·51, 95% CI 0·28, 0·93). We found that PCV10 was effective in decreasing the carriage of vaccine-type serotypes in Pakistani infants.

The majority of adults in the world (around 83%) carry antibodies reactive with HCMV and are thought to retain inactive or latent infections lifelong. The virus is transmitted via saliva so infection events are likely to be common. Indeed it is hard to imagine a life without exposure to HCMV. From 45 seronegative individuals (13 renal transplant recipients, 32 healthy adults), we present seven cases who had detectable HCMV DNA in their blood and/or saliva, or a CMV-encoded homologue of IL-10 (vIL-10) in their plasma. One case displayed NK cells characteristic of CMV infection, and HCMV DNA became undetectable. In other cases, the infection may persist with seroconversion blocked by vIL-10. Future research should seek mechanisms that can prevent an individual from seroconverting despite a persistent HCMV infection, as HCMV vaccines may not work well in such people.

Since there is no vaccine or regulatory approved therapy available for treatment of SARS-CoV-2 infection, the medical need to prevent the transition of a mild into the severe COVID-19 stage of infection is of outmost importance. Among several drug candidates, Chloroquine (CQN) and Hydroxy-Chloroquine (H-CQN) have been tested most intensively. However, the therapeutic effect of H-CQN and CQN has been discussed controversially in the light of severe side effects. Originally, H-CQN descended from the natural substance Quinine, a medicinal product used since the Middle Ages and is now regulatory approved for various indications. We hypothesized that Quinine also exerts anti-SARS-CoV-2 activity. First, virus production in Vero B4 cells was analyzed by Western blot, showing that Quinine exerts antiviral activity against SARS-CoV-2 that at 10 µM was even stronger than that of H-CQN or CQN. Second, fluorescence end-point and time lapse analysis of SARS-CoV-2-mNeonGreen-infected Caco-2 cells could confirm a similar antiviral effect of Quinine in a human-derived cell line. Thereby, our in vitro studies revealed, that the antiviral effect appears to be specific, since in Vero cells Quinine impacted cell viability at approximately 50-fold higher concentration, while the therapeutic window of H-CQN and CQN was approximately 10-fold lower. In Caco-2 cells no toxic effect was observed while complete block of infection occurred between 50 and 100 µM at high MOIs. In conclusion, our data indicate that Quinine would have the potential of a well tolerable and widely used treatment option for SARS-CoV-2 infections, with a predictable and significantly better toxicological profile when compared to H-CQN or CQN.

The oxidative stress is one of the main cause for cardiovascular diseases (like Hypertension) also one of the results of these diseases. This study involved 56 subjects matched ages and sex divided into two groups; 28 hypertensive subject and 28 healthy subject as control group. The following analysis was done: 4-Hydroxy-2-nonenal(4HNE) and albumin. The results show that there is a significant increase in (4HNE) between patients group and control group. The increase in 4HNE which is a product of lipid peroxidation is attributed to destruction in body cell caused by due to the increase in stress events. It has been concluded that is important nappy on ideal weight, because obesity considered main factors for heart disease and hardening of the arteries. The aim of this study was to investigate the relationship between of some oxidative stress markers and cardiovascular diseases.

The purported cognitive benefits associated with nicotine and its metabolites in the brain are a matter of debate. In this review, the impact of the pharmacologically active metabolite of a nicotine derivative produced by bacteria (6-hydroxy-L-nicotine) on memory, oxidative stress, and the activity of the cholinergic system in the brain was examined. A search in the PubMed, Science Direct, Web of Science, and Google Scholar databases, limiting entries to those no later than July 2023, was conducted. The search focused specifically on articles pertaining to nicotine metabolites, memory, oxidative stress, cholinergic system activity, as well as enzymes or pathways related to nicotine degradation in bacteria. The preliminary search resulted in 696 articles, and following the application of exclusion criteria, 185 articles were deemed eligible for inclusion. This review focuses on experimental studies supporting nicotine catabolism in bacteria, and the chemical and pharmacological activities of nicotine and its metabolite 6-hydroxy-L-nicotine.

The synthesis, anticancer and antioxidant activity of a series of indole-derived hybrid chalcones are reported here. First, using well known Claisen-Schmidt condensation method a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on the on five cancer (HCT116, HeLa, Jurkat, MDA-MB-231 and MCF7) and two non-cancer (MCF-10A and Bj-5ta) cell lines. Chalcone 18c bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using tree different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals, as well as FRAP method, demonstrated the strong activity of catechol derivatives 18a-c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy substituted chalcones 19a–c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and anticancer activity.

Over the past two decades, a growing body of evidence observations have shown group two innate lymphoid cells (ILC2) to be critical drivers of Type 2 (T2) inflammatory responses associated with allergic inflammatory conditions such as asthma. ILC2 release copious amounts of pro-inflammatory T2 cytokines – interleukin (IL)-4, IL-5, IL-9, and IL-13. This review provides a comprehensive overview of the newly discovered regulatory subtype of ILC2 described in murine and human mucosal tissue and blood. These KLRG1+ILC2 have the capacity to produce the anti-inflammatory cytokine, IL-10. Papers compiled in this review were based on query of PubMed and Google Scholar for articles published from 2000-2023 using keywords “IL-10” and “ILC2”. Studies with topical relevance to IL-10 production by ILC2 were included. ILC2 respond to microenvironmental cues including retinoic acid (RA), IL-2, IL-4, IL-10, IL-33, as well as neuropeptide mediators such as neuromedin-U (NMU), prompting a shift towards IL-10 and away from T2 cytokine production. In contrast, TGF-β attenuates IL-10 production by ILC2. Immune regulation provided by IL-10+ILC2s holds potential significance for management of T2 inflammatory conditions. The observation of context-specific cues which alter phenotype of ILC warrants examining characteristics of ILC subsets to determine the extent of plasticity or whether the current classification of ILCs requires refinement.

Despite the 12-lead electrocardiogram (ECG) being the gold standard in evaluating clinical presentations of arrythmias of various kinds, several notable limitations, namely in accuracy and localization, have recently garnered concern with respect to administering appropriate therapeutic measures. The following text puts these limitations under the spotlight, highlighting the difficulty and challenging nature of standard ECG analysis and therapeutic measures, while simultaneously showing a novel body surface electrocardiographic mapping system that utilizes 3D spatial imaging and pinpoint localization algorithms in order to compensate for the shortcomings of the standard ECG, thereby providing higher precision data collection. We provide a brief overview of the novel device in a selection of arrhythmic demographics, along with its validity and reliability, while illustrating the benefits and positive outcomes of its utility.

The cytoskeleton is a master organizer of cell cortex, organelles positioning and membrane trafficking. Therefore, playing a decisive role in establishment of apico-basal polarity. Septins are critical cytoskeleton components which function in apico-basal polarity remain weakly investigated. Here, using 3D culture system, we demonstrate that septin9 localizes at basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing -catenin at BM and increasing the expression of the transforming growth factor (TGF) and the epithelial-to-mesenchymal transition (EMT) markers. Similar effects were observed upon deleting its two polybasic domains, and the mutant become cytoplasmic and apical. The cysts with an inverted polarity phenotype display an invasive phenotype, with src and cortactin accumulating at the peripheric membrane. Inhibition of TGF-receptor and RhoA rescues the polarized phenotype. Although the cysts from overexpressed-septin 9, overgrowth and present a filled lumen. Both phenotypes correspond to tumor features. This suggests that septin 9 expression and assembly through the two PB domains are essential for establishing and maintaining apico-basal polarity against tumor development through a mechanism involving TGF-dependent EMT and RhoA activity.

In this study, a slow-release urea fertilizer hydrogel was synthesized from hydroxyl propyl methyl cellulose, polyvinyl alcohol and glycerol blends with paper (blended paper) as second layer. The fertilizer hydrogel was characterized by SEM, XRD and FTIR. Its retention in sandy soil, swelling behavior in distilled and tap water as well as slow-release behavior to urea were investigated. The results indicated that the fertilizer had good slow-release properties and ability to retain water in soil. However, the addition of blended paper as a second layer matrix was found to help improve the release properties of the fertilizer. The swelling kinetic of the hydrogel followed the Schott’s Second order model. The release kinetics of urea in water was best described by the Zero order model signifying that the release behavior was independent of fertilizer concentration

Trigonella foenum is one of the oldest medicinal plants that grow in many parts of Iran with the diverse ecological situation. Employing this plant for treating diabetes and high cholesterol has a long history, because of some metabolites. Due to the habitat of fenugreek is a wide range of climatic conditions, it may have power to cope with climate variation. The main intention of this inquiry was to understand the effect of the environmental variables on this therapeutic plant features. It was also interesting for us to understand which environment variables are more impressive for enhancing of trigonelline and 4-hydroxy isoleucine content as the most important metabolites of this plant. For achieving this goal, environmental information and vegetal data were analyzed to discover the role of nature on the seed part of fenugreek life in 50 different regions of Iran. Canonical correspondence analysis (CCA) displayed that high content of metabolites and some morphological characteristics happened in high temperature and solar irradiation. Partial least squares regression (PLSR) and path analysis used to find the best predictors and direct and indirect effect of all variables on 4-hydroxy isoleucine and trigonelline. Ecological condition were the best predictors and had the highest direct and indirect impact on 4-hydroxy isoleucine. However, for trigonelline, the environment did not play a senior role. It seems that the reaction of components of fenugreek does not follow the same way. Studying on morphological, primary and secondary metabolites, and surrounding environment of fenugreek, helped us to have a more precise judgment about the life of this plant.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

Cytokines secreted by individual immune cells regulate tissue regeneration and allow communication between various cell types. Cytokines bind to cognate receptors and trigger the healing process. Determining the orchestration of cytokine interactions with their receptors on their cellular targets is essential to fully understand the process of inflammation and tissue regeneration. To this end, we have investigated the interactions of Interleukin-4 cytokine (IL-4)/Interleukin-4 cytokine receptor (IL-4R) and Interleukin-10 cytokine (IL-10)/Interleukin-10 cytokine receptor (IL-10R) using in situ Proximity Ligation Assays in a regenerative model of skin, muscle and lung tissues in the mini-pig. The pattern of protein-protein interactions was distinct for the two cytokines. IL-4 bound predominantly to receptors on macrophages and endothelial cells around the blood vessels while the target cells of IL-10 were mainly receptors on muscle cells. Our results show that in situ studies of cytokine-receptor interactions can provide unravel the fine details of the mechanism of action of cytokines.

Despite offering free-of-charge COVID-19 vaccines starting July 2021, Guatemala has one of the lowest vaccination rates in Latin America. During September 28, 2021 to April 11, 2022, we conducted a cross-sectional survey of community members adapting a CDC questionnaire to evaluate COVID-19 vaccine access and hesitancy. Of 233 participants ≥12 years, 127 (55%) received >1 dose of COVID-19 and 4 (2%) reported prior COVID-19 illness. Persons ≥12 years old unvaccinated (n=106) were more likely to be female (73% vs 41%, p<0.001) and homemakers (69% vs 24%, p<0.01) compared with vaccinated participants (n=127). Among those ≥18 years, the main reported motivation for vaccination among vaccinated participants was to protect the health of family/friends (101/117, 86%); 40 (55%) unvaccinated persons reported little/no confidence in public health institutions recommending COVID-19 vaccination. Community- and/or home-based vaccination programs, including vaccination of families through the workplace, may better reach female homemakers and reduce inequities and hesitancy.

Here we investigated the acute effects of an exhaustive intermittent exercise session on immunological parameters of the elderly and the subsequent incidence of upper respiratory tract infections and compare with the moderate-intensity. To do so, ixty-three old subjects were divided into three groups HIIT (n=21) submitted at one High-intensity interval training, SCG (n=21) kept in a sedentary state, and MICT (n=21) submitted at moderate intensity walking. Blood were collected at 5 time points, before, immediately after, 2h, 24h, and 48h after the intervention. In result the IL-6 and TNF-α were overexpressed immediately after the IL-10 stood overexpressed and correlated with IL-17, denoting an inflammatory process, and evidencing an immunologic competence without enhancement of the prevalence of upper respiratory infection tract (URTIs). So a modulation in the balance of Th1/Th2/Th17 cytokines and leukocytes, these modifications did not cause the effect characterized as an immunological window. Perhaps, the typical inflammation process, with IL-10 and IL-17 participation could also produce benefits to combat infections, a pertinent discussion during a post-pandemic time; we consider it a safe exercise program for older adults.

Both academic literature and global organizations have emphasized the need for responsible water consumption, as stated in the Sustainable Development Goal 12. However, individuals’ water-saving behaviors in their current state are not enough. This situation entails a resistance to change (RC) in consumer habits and a lack of perceived risk of scarcity. The novelty of this study lies in examining the influence of RC (through its emotional, cognitive, and confidence components) and perceived risk on water-saving intention. Interviews (n = 384) were conducted in the southeast Mediterranean area of Spain by interviewers using a paper-and-pencil questionnaire. The results of the structural equation modeling show that the perceived risk and the components of cognitive rigidity and negative emotions exert a direct influence on water-saving habits and an indirect influence on water-saving intention. None of the components of RC directly influence intention, and a lack of confidence in the outcomes of water saving does not influence water-saving habits or water-saving intention. In addition to the results obtained, the novelty of the work lies in the idea that in order to influence the perception of the risk of water scarcity through awareness campaigns, it is better to use an emotional message rather than showing facts or information, because this does not drive water saving behavior.

The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema (S) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has not been investigated. We recently reported that cyanobacterium Oscillatoria sp. LPS elicited classical and alternative activation of rat microglia in vitro [1]. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria S. javanicum or S. ocellatum LPS might stimulate classical and alternative activation with concomitant release of superoxide anion (O₂⁻), matrix metalloproteinase-9 (MMP-9) and cytokines and chemokines. Microglia were isolated from neonatal rats and treated in vitro with either S. javanicum LPS, S. ocellatum LPS, or E. coli LPS (positive control) in a concentration-dependent manner for 18 hours at 35.9 °C. We observed that treatment of microglia with either E. coli LPS, S. javanicum or S. ocellatum LPS generated statistically significant and concentration-dependent O₂⁻, MMP-9 and pro-inflammatory cytokines IL-6 and TNF-α, pro-inflammatory chemokines MIP-2/CXCL-2, CINC-1/CXCL-1 and MIP-1α/CCL3, and the anti-inflammatory cytokine IL-10. Thus, our results provide experimental support for our working hypothesis because both S. javanicum and S. ocellatum LPS elicited classical and alternative activation of microglia and concomitant release of O₂^-, MMP-9 and cytokines and chemokines in a concentration-dependent manner. To our knowledge this is the first report on the toxicity of cyanobacteria S. javanicum and S. ocellatum LPS to microglia, an immune cell type involved in neuroinflammation and neurotoxicity in the central nervous system.

Japanese pepper (sansho, Zanthoxylum piperitum) contains several types of sanshools belonging to N-alkylamides. Because of long-chain unsaturated fatty acids present in their structure, sanshools are prone to oxidative deterioration, which poses problems in processing. Here, we evaluated the effects of antioxidants from the genus Zanthoxylum in preventing sanshool degradation using accelerated tests. An ethanolic extract of segment membranes of the sansho fruit pericarp was incubated at 70 °C for 7 days with different antioxidants to determine the residual amount of hydroxy-α-sanshool (HαS) in the extract. α-Tocopherol (α-Toc) showed excellent HαS-stabilizing activity at low concentrations. Among phenolic acids, we noted that the HαS-stabilizing activity increased with the number of hydroxy groups per molecule. For example, gallic acid and its derivatives exhibited excellent sanshool-stabilizing activity. Quercetin was found to be a superior HαS stabilizer compared with hesperetin and naringenin. However, the effective concentration was much higher for phenolic compounds than for α-Toc. These substances are believed to play a role in preventing the decomposition of sanshools in the pericarp of sansho. These sanshool stabilizers should be useful in the development of new beverages, foods, cosmetics, and pharmaceuticals that take advantage of the taste and flavor of sansho.

Storing apples for up to a year is a well-established practice aimed at providing a continuous, locally-produced fruit supply to consumers and adapting to market trends for optimized profits. Temperature control is the cornerstone of postharvest conservation and apples are typically kept at temperatures from 0 to 3 °C. However, the energy-intensive process of the initial cool down and subsequent temperature maintenance poses significant financial challenges and contributes to the carbon footprint. Higher storage temperatures could reduce cooling-related energy usage but also pose the risk of enhanced ripening and quality loss. This work explores different storage technologies aiming to reduce energy consumption such as 1-methylcyclopropene, ultra-low oxygen and dynamic controlled atmosphere together with raised temperatures. The integration of advanced monitoring and control systems, coupled with data analytics and energy management in apple storage is also discussed. These sustainable strategies can be implemented without cost-intensive construction measures in standard storage facilities. Furthermore, beneficial side effects of higher storage temperatures in terms of a reduced occurrence of storage disorder symptoms and higher maintenance of quality attributes are also discussed for this special issue on sustainable horticultural production systems and supply chains.

Carbon fiber reinforced polymers (CFRPs) are being used extensively in modern industries that require high strength-to-weight ratio such as aerospace, automotive, motorsport, and sports equipment. However, although reinforcement with carbon fibers improves the mechanical properties of polymer, this comes on the expense of abrasive wear resistance. Therefore, to efficiently utilize CFRPs in dry sliding contacts, solid lubricant is used as a filler. Further, to facilitate fabrication of objects with complex geometries, selective laser sintering (SLS) can be employed. Accordingly, in the present work, graphite-filled carbon fiber-reinforced polyamide 12 (CFR-PA12) specimens were prepared using SLS process to explore the dry sliding friction and wear characteristics of the composite. The test specimens were aligned along four different orientations in the build chamber of SLS machine to determine the orientation-dependent tribological properties. The experiments were conducted using pin-on-disc tribometer to measure the coefficient of friction (COF), interface temperature, friction-induced noise, and specific wear rate. In addition, scanning electron microscopy (SEM) of tribo-surfaces was conducted to specify the dominant wear pattern. The results indicated that the steady state COF, contact temperature, and wear pattern of graphite-filled CFR-PA12 are orientation-independent, and that the contact temperature is likely to approach an asymptote far below the glass transition temperature of amorphous PA12 zones, thus eliminating the possibility of matrix softening. Additionally, the results showed that the Z-oriented specimen exhibits the lowest level of friction-induced noise along with the highest wear resistance. Moreover, SEM of tribo-surfaces determined that abrasive wear is the dominant wear pattern.

This paper explores the dynamic interplay of K-12 education, the Fourth Industrial Revolution (IR 4.0), and internationalization in the Philippines. Through qualitative content analysis, key themes emerged, shedding light on the impact of K-12 education on global competitiveness, challenges in embracing IR 4.0 technologies, and opportunities arising from internationalization efforts. The findings underscore the significance of curriculum alignment with international standards, comprehensive digital literacy training, and fostering a global mindset to prepare students for the digitally-driven, interconnected world. Understanding the implications of these themes is crucial for the Philippines' education system, as it navigates towards a transformative and globally competitive future. Further, this research offers evidence-based recommendations and addresses research gaps, contributing to a broader understanding of how the convergence of these forces shapes the future of Philippine education. Future research avenues may explore long-term impacts on workforce preparedness, innovative IR 4.0 integration, and the effectiveness of internationalization efforts on educational outcomes. Eventually, this study inspires an education system that nurtures learners equipped to thrive in an ever-evolving global landscape.

The bark of Rhus verniciflua Stokes (RVS) is used as a food additive and herbal medicine for various inflammatory disorders and cancer in Eastern Asia. RVS exerted anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, but whether this effect occurs in macrophages after oral administration has not been determined. We used a thioglycollate-induced peritonitis model to obtain macrophages from mice given RVS. We examined the systemic inflammatory response to intraperitoneal LPS. RVS-treated mice had an increased population of peritoneal exudate cells expressing CD11b and SRA. Increased uptake of Alexa Fluor 488-labeled acetylated lipoprotein was observed in monocyte-derived macrophages from RVS-treated mice. When these cells from the RVS group were stimulated with LPS, the levels of tumor necrosis factor (TNF)- and interleukin (IL)-6 in the supernatant decreased, but the level of IL-12 increased. The surface expression of CD86 was reduced, but surface expression of class II MHC molecules was increased. RVS suppressed the serum levels of LPS-induced TNF- and IL-6. RVS enhanced monocyte differentiation in thioglycollate-induced peritonitis by increasing scavenger receptor expression and activity. Macrophages isolated from mice given RVS responded differently to LPS. These findings demonstrate that RVS confers selective anti-inflammatory activity without causing the overall inhibitory effects on immune cells.

The length of stay (LOS) in the hospital emergency department (ED) is a crucial key performance indicator that is used to track and manage the performance of the ED as a whole. Our study had two objectives. Firstly, we aimed to evaluate the association between LOS and the most common primary ICD-10 diagnoses. To achieve this, we examined LOS in groups with specific (internal, surgical, neurological, and traumatic diseases) and non-specific diagnoses in adult ED visits at a tertiary referral hospital between 2017 and 2019 (134,675 visits in total). Our secondary objective was to measure LOS by age, day of the week, time of day, and season. The mean LOS was 254 minutes and was the shortest in the traumatic group (160 minutes), while in other groups it was significantly longer: neurological by 185 minutes, internal medicine by 158 minutes, surgical by 36 minutes, and non-specific by 24 minutes. In conclusion, non-specific diagnoses accounted for 21% of all ICD-10 primary diagnoses. In this group of patients, the percentage of hospitalizations was the highest. Other significant determinants of LOS were the patients’ age, the day of the week, the time of arrival, and repeated visits.

Toxicologically relevant levels of the psychoactive ∆9-tetrahydocannabinol (∆9-THC) as well as high levels of non-psychoactive cannabinoids potentially occur in CBD (cannabidiol) oils. For consumer protection in the fast-growing CBD oil market, facile and rapid quantitative methods to determine the cannabinoid content are crucial. However, the current standard method, i.e., liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS), requires a time-consuming multistep sample preparation. In this study, a quantitative nuclear magnetic resonance spectroscopy (qNMR) method for screening cannabinoids in CBD oils was developed. Contrary to the HPLC-MS/MS method, this qNMR features a facile sample preparation, i.e., only diluting the CBD oil in deuterochloroform. Pulse length-based concentration determination (PULCON) enables a direct quantification using an external standard. The signal intensities of the cannabinoids were enhanced during the NMR spectra acquisition by means of multiple suppression of the triglycerides which are a major component of the CBD oil matrix. The validation confirmed linearity for CBD, cannabinol (CBN), ∆9-THC and ∆8-THC in hemp seed oil with sufficient recoveries and precision for screening. Comparing the qNMR results to HPLC-MS/MS data for 46 commercial CBD oils verified the qNMR accuracy for ∆9-THC and CBD but with higher limits of detection. The developed qNMR method paves the way for increasing the sample throughput as a complementary screening before HPLC-MS/MS.

Cannabis has been used as an herbal remedy for thousands of years and recent research indicates promising new uses in medicine. Researchers have been particularly interested in the potential uses of cannabinoids in treating cancer due their ability to regulate cancer-related cell cycle pathways, leading to many beneficial effects such as tumor growth prevention, cell cycle obstruction, and cell death. The aim of this review is to summarize current knowledge on mechanisms of cannabinoids and their role in treating chemotherapy-induced nausea and vomiting, relieving cancer-associated pain, and obstructing tumor cell growth.

The monitoring of lake waterbody area in the Qinghai Tibet Plateau (QTP) is of great significance to deal with global climate change. As the latest generation of Landsat series satellites, Landsat-9 data not only have higher radiometric resolution, but also cooperate with other Landsat satellites to greatly improve the temporal resolution. It has great application potential in lake waterbody area monitoring. In order to explore the performance of different algorithms for extracting waterbody and lake waterbody area in Landsat-9 data under large-scale QTP regions, this study relies on Google Earth Engine (GEE) platform and selects 10 waterbody extraction algorithms as the basis to realize the quantitative evaluation of QTP lake waterbody area extraction results. The results show that the Random Forest (RF) algorithm performs best in all models. The overall accuracy of waterbody extraction is 95.84%, and the average error of lake waterbody area extraction is 1.505%. Among the traditional threshold segmentation waterbody extraction algorithms, the overall accuracy of the NDWI waterbody extraction method is 89.89%, and the average error of lake waterbody area extraction is 3.501%, which is the highest performance model in this kind of algorithms. This study proves that Landsat-9 data can effectively classify QTP waterbodies. With the development of cloud computing technologies such as Gee, more complex models such as RF can be selected to improve the extraction accuracy of water body and Lake area in large-scale research.

Inhalational anesthetics was previously reported to suppress glioma cell malignancy, but underlying mechanisms remain unclear. The present study aims to investigate the effects of sevoflurane and desflurane on glioma cell malignancy changes via microRNA (miRNA) modulation. The cultured H4 cells were exposed to 3.6% sevoflurane or 10.3% desflurane for 2 hrs. The miR-138, -210 and -335 expression were determined with qRT-PCR. Cell proliferation and migration were assessed with wound healing assay, Ki67 staining and cell count kit 8 (CCK8) assay with/without miR-138/-210/-335 inhibitor transfections. The miRNA downstream proteins, hypoxia inducible factor-1α (HIF-1α) and matrix metalloproteinase 9 (MMP9), were also determined with immunofluorescent staining. Sevoflurane and desflurane exposure to glioma cells inhibited their proliferation and migration. Sevoflurane exposure increased miR-210 expression whereas desflurane exposure upregulated both miR-138 and miR-335 expressions. The administration of inhibitor of miR-138, -210 or -335 inhibited the suppressing effects of sevoflurane or desflurane on cell proliferation and migration, in line with the HIF-1α and MMP9 expression changes. These data indicated that inhalational anesthetics, sevoflurane and desflurane, inhibited glioma cell malignancy via miRNA upregulation and their downstream effectors, HIF-1α and MMP9, downregulation. The implication of the current study warrants further study.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

Objectives: The study aimed to develop a deep learning-based edge AI model deployed on electrocardiograph (ECG) devices for real-time detection of atrial fibrillation (AF)-risk during sinus rhythm (SR) using standard 10-second 12-lead electrocardiograms (ECGs). Methods: A novel approach was used to convert standard 12-lead ECGs into binary images for model input, and a lightweight convolutional neural network (CNN)-based model was trained using data collected by the Japan Agency for Medical and Research Development (AMED) between 2019 and 2022. Patients over 40 years old with digital, SR ECGs were retrospectively enrolled and divided into AF and non-AF groups. Data labeling was supervised by cardiologists. The dataset was randomly allocated into training, validation, and internal testing datasets. External testing was conducted on data collected from other hospitals.　Results: The best-trained model achieved an AUC of 0.82 and 0.80, sensitivity of 79.5% and 72.3%, specificity of 77.8% and 77.7%, precision of 78.2% and 76.4%, and overall accuracy of 78.6% and 75.0% in the internal and external testing datasets, respectively. The deployed model and app package utilized 2.5MB and 40MB of the available ROM and RAM capacity on the edge ECG device, correspondingly. Processing time for AF-risk detection was approximately 2 seconds.　Conclusion: The model maintains comparable performance and improves its suitability for deployment on resource-constrained ECG devices, thereby expanding its potential impact to a wide range of healthcare settings. Its successful deployment enables real-time AF-risk detection during SR, allowing for timely intervention to prevent AF-related serious consequences like stroke and premature death.

In addition to the subject-matter theoretical knowledge acquired during undergraduate and especially postgraduate studies future young scientists must also acquire the accompanying academic skills. This skillset will enable them to plan and conduct research in accordance with the scientific method, but also to present the results of that research in suitable forms. No result and no new knowledge derived from research is valuable in itself, as long as it is not presented to the scientific community and society as a whole. This dissemination is most often done through the peer-reviewed publishing in scientific journals. Hence acquiring the skill of writing scientific publications must be an integral part of education, eg. part of the acquired academic skills. However, currently that is not the case in all scientific environments and a significant number of (young) scientists and researchers do not possess all the necessary knowledge and skills to write academic articles, especially when it comes to the standard form and technical preparations. This skill-gap often results in a significant number of submitted papers to be rejected or sent back for resubmission even before they reach the Editor's desk. In an effort to provide an academic-writing-skill resource for young academics in the field, this article, points out the general principles of a well-written and prepared paper, indicates the most common errors and omissions, and suggests ways to prevent them. In addition, the article is considering the current state of academic skills in, primarily, less developed scientific environments. and the causes of such a state.

In this article, we are interested in a new generic class of nonlocal fractional impulsive differential inclusions with linear sectorial operator and Lipschitz multivalued function in the setting of finite dimensional Banach spaces. By modifying the definition of PC-mild solutions initiated by Shu, we succeeded to determine new conditions that sufficiently guarantee the existence of the solutions. The results are obtained by combining techniques of fractional calculus and fixed point theorem for contraction maps. We also characterize the topological structure of the set of solutions. Finally, we provide a demonstration to address the applicability of the theoretical results.

Thymic stromal lymphopoietin (TSLP) is a cytokine and is closely related to Interleukin (IL) - 7, and hTSLP can activation through the human thymus dendritic cell in thymic to indirectly promote the differentiation of natural Regulatory T cells (Tregs) of the thymus. In this study, we focused on recombinant TSLP to determine its effects on the differentiation of CD4+CD25-T cells separated from the thymus of myasthenia gravis (MG) patients. Our results demonstrated that exogenous TSLP could increase CD4+CD25+T/CD4+T cells ratio, up-regulate the expression of Foxp3 mRNA and protein expression in CD4+CD25+Treg cells. Furthermore, we found that CD4+CD25+ Treg cells induced by exogenous TSLP could secrete IL - 10, Transforming growth factor (TGF) - β and the ability to inhibit CD4+T cell proliferation improved. These results indicate that TSLP may promote the differentiation of thymic CD4+CD25-T cells of MG patient to CD4+CD25+Foxp3+ regulatory T cells and enhance the function of immune suppression.

Regulatory B cells (Bregs) with immunosuppressive function are critical in maintaining immune tolerance. In recent years, Bregs is an essential part of the study due to its therapeutic relevance and function in immune tolerance. The positive and negative regulatory role of human Bregs in immune tolerance is being discussed in several pathologies, including in autoimmune diseases, cancers, chronic infections, strokes in multiple reports. The negative regulatory roles of human Bregs are associated with lesser numbers and functional abnormalities in most of these studies, including myasthenia gravis (MG). In this review, the potential findings regarding human Bregs in MG, and Bregs mediated potential therapeutic strategies with its pros and cons have been discussed based on previous and current reports.

Gastric inflammation-related disorders are commonly observed digestive system illnesses char-acterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric in-flammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol ex-tract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal GES-1 cells. The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α, to examine the anti-inflammatory properties of Lj extracts. The re-sults indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 ac-tivity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflam-mation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH ex-hibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.

Galectins have been shown to have roles in cancer progression via contributions to angiogenesis, metastasis, cell division, and evasion of immune destruction. This study analyses galectin-1, -3, and -9 serum concentrations in breast cancer patients by enzyme-linked immunosorbent assay (ELISA) against the characteristics of the patient and tumor such as stage, molecular subtype, and receptor expression. Galectin-9 was found to be statistically significantly increased in HER2 enriched tumors as well as being reduced in patients with hormone receptor positive tumors and increased in patients with HER2 amplified tissues. Galectin-1 was found to be statistically significantly increased in the serum of patients who had undergone hormonal, immunotherapy, or chemotherapy. These findings provide insight as to the changes in galectin levels during cancer progress, response to treatment and molecular phenotype. These findings are valuable in the further understanding of the relationships of galectin and tumor biology and can inform future research on therapeutic targets for galectin inhibitors and the utility of galectin biomarkers.

Due to the energetic transition at course, new geological exploration technologies are needed to discover mineral deposits containing critical materials such as lithium (Li). The vast majority of European Li deposits are related to Li–Cs–Ta (LCT) pegmatites. Literature review indicates that conventional exploration campaigns are dominated by geochemical surveys and related exploration tools. However, other exploration techniques must be evaluated namely remote sensing (RS) and geophysics. This work presents the results of the INOVMINERAL4.0 project obtained through alternative approaches to traditional geochemistry that were gathered and integrated into a webGIS application. The specific objectives were to: (i) assess the potential of high-resolution elevation data; (ii) evaluate geophysical methods, particularly radiometry; (iii) establish a methodology for spectral data acquisition and build a spectral library; (iv) compare obtained spectra with Landsat 9 data for pegmatite identification; and (v) implement a user-friendly webGIS for data integration and visualization. Radiometric data acquisition using geophysical techniques effectively discriminated pegmatites from host rocks. The developed spectral library provided valuable insights for space-based exploration. Landsat 9 data accurately identified known LCT pegmatite targets, compared to Landsat 8. The user-friendly webGIS facilitated data integration, visualization, and sharing, supporting potential users in similar exploration approaches.

: Submerged aquatic vegetation (SAV) are highly efficient at carbon sequestration and, despite their relatively small distribution globally, are recognized as a potentially valuable component of climate change mitigation. However, SAV mapping in tidal marshes presents a challenge due to optically complex constituents in the water. The emergence and advancement of deep learn-ing-based techniques in the field of habitat mapping with remote sensing imagery provides an opportunity to address this challenge. In this study, an analytical framework was developed to quantify the carbon sequestration of SAV habitats in the Atchafalaya River Delta Estuary from field and remote sensing observations using deep convolutional neural network (DCNN) tech-niques. A U-Net based model, Wetland-SAV Network, was trained to identify SAV percent cover (high, medium, and low) as well as other estuarine habitat types from Landsat 8/9-OLI data. The areal extent of SAV was up to 8% of the total area (47,000 ha) with a significant loss of SAV habitats observed post-Hurricane Barry (~2,300 ha) in 2019. The habitat areas and habitat-specific carbon fluxes were then used to quantify net greenhouse gas (GHG) flux of the study area for with/without SAV scenarios in a Carbon Balance Model. The total net GHG flux was in the range of -0.13 ± 0.06 to -0.86 ± 0.37 ×105 tonne CO2e yr-1 and increased up to 40% (-0.23 ± 0.10 to -0.90 ± 0.39 ×105 tonne CO2e yr-1 ) when SAV was accounted for within the calculation. At the hectare scale, inclusion of SAV resulted in an increase of ~60% for net GHG sink in shallow areas adjacent to emergent marsh where SAV was abundant. This is the first attempt at remotely mapping SAV in coastal Louisiana as well as a first quantification of net GHG flux at the scale of hectares to thousands of hectares, accounting for SAV within these sub-tropical coastal delta marshes. Remote sensing and deep learning models have high potential for mapping and monitoring of SAV in turbid sub-tropical coastal deltas as a component of increasing accuracy of net GHG flux estimates at small (hectare) and large (coastal basin) scales.

Biomineralization has become a research hotspot and attracted widespread attention in the field of carbonate sedimentology. In this study, Bacillus licheniformis DB1-9 was used to induce the calcium carbonate precipitation at different magnesium calcium molar ratios in the laboratory to further explore the biomineralization mechanism. Phylogenetic tree shows that the bacteria belongs to Bacillus licheniformis species. The ammonia and carbonic anhydrase can be released by this bacteria, resulting in the pH increase, and the carbonic anhydrase can also promote the hydration reaction of carbon dioxide and subsequently produce the bicarbonate and carbonate ions to elevate the supersaturation of calcium carbonate in the liquid culture medium to facilitate the precipitation of carbonate minerals. The calcites have a shape of rhombohedron, dumbell, and elongation, and aragonite often appears in the form of mineral aggregates, besides that there are also the spherical and the fusiform minerals. FTIR result shows there are some organic functional groups, such as C-O-C and C=O, beside of the characteristic peaks of the calcite and the aragonite, indicating that microbial metabolism is closely related to the mineral formation. The superthin slices of the bacteria analyzed by HRTEM, SAED, EDS and STEM show that the surface and EPS can adsorb a large number of calcium ions and magnesium ions and EPS may act as the nucleation sites, what’s more, the intracellular nanometer-scale sphere areas show the amorphous structures, and the intracellular calcium ions and magnesium ions suggeste that they can be transported from the outside to inside the cell by diffusion along the concentration grade from high to low. This study may provide some references to further understand the biomineralization mechanism induced by microorganisms in the laboratory and the field, and also helps to explore the reason of the transition of calcite sea to aragonite sea in the geological history.

The emotion of disgust protects individuals against pathogens, and it has been found that during pregnancy, it is elevated. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. The aim of this study is to assess the association between steroids and disgust in pregnancy. In a sample of 179 pregnant women, we have analyzed blood serum steroid concentrations and measured disgust sensitivity by text-based questionnaires in the first and third trimester. We found positive correlations between disgust sensitivity and the levels of C19 steroids, including testosterone, but also its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Furthermore, positive correlations between disgust sensitivity and 5α/β-reduced C19 steroid metabolites were consistently present in both trimesters. In the first trimester, we found a positive association between disgust sensitivity and 17-hydroxypregnanolone as well as some estrogens. In the third trimester, we have observed positive associations between disgust sensitivity and cortisol as well as immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our study has thus shown that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, steroids may reflect potential maternal anxiety-related symptoms.

In the present study we tested the effect of small molecular weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bio-availability compared to NAC, and the thioredoxin mimetics (TXM) peptides, TXM-CB3, TXM-CB13, and TXM-CB30. All compounds significantly inhibited platelet aggregation induced by collagen, with TXM-peptides and AD4 being more effective than NAC. The levels of TxB2 and 12-HETE, the main metabolites derived from the cyclooxygenase and lipoxygenase pathways following platelet activation, were significantly reduced in the presence of AD4, TXM-peptides, or NAC, when tested at the highest concentration (0.6 mM). The effect of AD4, TXM-peptides, and NAC was tested also on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the highest increase of CT. Furthermore, two representative compounds, TXM-CB3, and NAC, showed an increase in the an-ti-oxidant free sulfhydryl groups of plasma detected by Ellman’s method, suggesting a contribution of plasma factors to the antiaggregating effects. Our results suggest that these small molecular weight redox peptides might become useful for the prevention and/or treatment of oxidative stress conditions associated with platelet activation.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Background. The characterization of new biomarkers of COVID-19 is extremely important. Few studies measured the soluble receptor for advanced glycation end product (sRAGE), angiotensin-converting enzyme 2 (ACE2), calcium and magnesium in COVID-19. Aims: To measure sRAGE, ACE2, interleukin (IL)-6, IL-10, CRP, calcium, magnesium, and albumin in COVID-19 patients in association with peripheral oxygen saturation (SpO2) and chest CT scan abnormalities (CCTA) including ground glass opacities. Methods. This study measured sRAGE, ACE2, IL-6, IL-10, CRP using ELISA techniques, and calcium, magnesium, and albumin using a spectrophotometric method in 60 COVID-19 patients and 30 healthy controls.Results. COVID-19 is characterized by significantly increased IL-6, CRP, IL-10, sRAGE, ACE2, and lowered levels of SpO2, albumin, magnesium and calcium. Neural networks showed that a combination of calcium, IL-6, CRP, and sRAGE yielded an accuracy of 100% in detecting COVID-19 patients with calcium being the most important predictor followed by IL-6, and CRP. COVID-19 patients with CCTAs showed lower SpO₂ and albumin levels than those without CCTAs. SpO2 was significantly and inversely correlated with IL-6, IL-10, CRP, sRAGE, and ACE2, and positively with albumin, magnesium and calcium. Patients with positive IgG results showed a significant elevation in the serum level of IL-6, sRAGE, and ACE2 compared to the negatively IgG patient subgroup.Conclusion. The results show that immune-inflammatory and RAGE pathway biomarkers may be used as external validating criterion for the diagnosis COVID-19. Those pathways coupled with lowered SpO2, calcium and magnesium are drug targets that may help to reduce the consequences of COVID-19.

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentration over a prolonged time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation as evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as, the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in the levels of NO, MDA and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

Hypoxia-inducible factor (HIF)-1α represents the oxygen-sensitive subunit of HIF transcriptional factor, usually degraded in normoxia and stabilized in hypoxia to regulate several target gene expression. Nevertheless, in the skeletal muscle satellite stem cells (SCs), an oxygen level-independent regulation of HIF-1α has been observed. Although HIF-1α has been highlighted as SC function regulator, its spatio-temporal expression and role during myogenic progression remain controversial. We herein analyzed HIF-1α expression and localization in differentiating murine C2C12 myoblasts and SCs under normoxia and evaluated matrix metalloproteinase (MMP)-9 as a HIF-1α target, by biomolecular, biochemical, morphological and electrophysiological analyses. HIF-1α expression increased after 24/48 h of differentiating culture and tended to decline after 72 h/5 days. Committed and proliferating mononuclear myoblasts exhibited nuclear HIF-1α expression, differently from the more elongated and parallel-aligned cells, likely ready to fuse with each other, which show mainly a cytoplasmic localization of the factor. Multinucleated myotubes displayed both a nuclear and cytoplasmic HIF-1α expression. The MMP-9 and MyoD (myogenic activation marker) expression synchronized with that of HIF-1α, increasing after 24 h of differentiation. Short-interfering RNA silencing of HIF-1α and MMP-9 and MMP-9 pharmacological inhibition unraveled MMP-9 as HIF-1α downstream effector and HIF-1α/MMP-9 axis essential for the morpho-functional cell myogenic commitment.

In this paper, we make research on fractal characteristics of the superposition of fractal surfaces in the view of fractal dimension. We give the upper bound of the lower and upper Box dimension of the graph of the sum of two bivariate continuous functions and calculate the exact values of them under some particular conditions. Further, it has been proved that the superposition of two continuous surfaces cannot keep the fractal dimensions invariable unless both of them are two-dimensional. A concrete example of numerical experiment has been provided to verify our theoretical results. This study can be applied to the fractal analysis of metal fracture surfaces or computer image surfaces.

Inflammation is the response of the innate immune system to any type of injury. Although acute inflammation is critical for survival, dysregulation of innate immune response leads to chronic in-flammation. Many synthetic anti-inflammatory drugs have side effects, and thus, natural an-ti-inflammatory compounds are still needed. Cannabis sativa L. may provide a good source of in-flammation-reducing molecules. Here, we tested the anti-inflammatory properties of cannabis ex-tracts and pure cannabinoids in lipopolysaccharide (LPS)-induced inflammation in human THP-1 macrophages. We found that pre-treatment with cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), or extracts containing high levels of CBD or THC reduce the level of induction of various cytokines. The CBD was more efficient than THC, and the extracts were more efficient than pure cannabinoids. Finally, IL-6, IL-10 and monocyte chemoattractant protein-1 (MCP-1) were most sensitive to pre-treatments with CBD and THC, while IL-1β, IL-8 and TNF-α were less responsive. Thus, our work demonstrates the potential of use of cannabinoids or/and cannabis extracts for the reduction of inflammation and establishes IL-6 and MCP-1 as the sensitive markers for the analysis of the effect of cannabinoids on inflammation in macrophages.

The article describes the methodology of the experimental analysis of operational and cost-effective assessment using geographic information system (GIS) technologies, as opposed to the assessment of the tourism potential of the nature of the Fergana Valley in Uzbekistan using long term and costly classical approaches. Based on the ArcGIS (10.8) grid index approach of 20 natural geographical indicators of the valley, such as geographical location, relief, climate, hydrographic and biological, the level of tourism comfort was determined and the location of 6 tourist-recreation zones were defined. The level of accuracy of the tourist-recreational zones all situated utilizing GIS technologies was confirmed by field-expedition approaches.

Stabilized melanocortin analog peptide ACTH(6-9)PGP (FRWGPGP) possess a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we studied the pro-proliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6-9 (FRWG) linked with the peptide Prolyl-Glycyl-Proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H2O2, tert-butyl hydroperoxide, and KCN. The mechanism of its action was the modu-lation of proliferation-related (NF-kB and Nrf-2) and antioxidant-related (HO-1, Nqo1, Gclc) genes and apoptosis decrease.

Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl) propanamides were designed and synthesized, combining benzisothiazole and 4-thiazolidinone in one frame. The aim of the study was to verify their effectiveness to contrast the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, advanced glycation products (AGEs), inflammatory cytokines and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level (IC₅₀ = 40 nM).

Abstracts In this article, we describe a simple procedure for evaluating the sterility of nutrient media using a shear-horizontal surface acoustic wave (SH-SAW) biosensor. We used the SH-SAW biosensor platform to monitor the time-dependent phase responses of the material for the media that binds to a monolayer of 3-mercaptopropanyl-N-hydroxy succinimide on the biosensor surface. Increases in the phase shift less than 50% of the starting phase shift recorded 180 minutes after the sterilization indicate a successful sterility test of the media. Our devices were then applied to sterility testing using a viable Escherichia coli (E. coli) K-12 solution to confirm our hypothesis. Filtered LB Broth was the negative control, and a 24-hour culture of E. coli was the positive control. Before testing, the cell solution was pelleted, the media decanted, and then replaced with a 1x phosphate-buffered saline solution (1x PBS). Since we know that the N-hydroxysuccinimide residues will bind to amine groups, only in cases where microbial species are present will the surface binding increase greater than 50%. We confirmed our hypothesis using SH-SAW biosensors and overnight E. coli cultures. The sensitivity for our 250 MHz quartz SH-SAW sensors was calculated based on the response from the E. coli K-12 solution over the linear dynamic range, which appears to be 2x10^4 – 2x10^7 CFU per ml and has a sensitivity of S = 1.655x10^5 o m2 Kg-1. The limit of detection (LOD) for these sensors was calculated to be approximately 2x10^-9 grams (g), which is estimated to be approximately 2,000 Escherichia coli (E. coli) K-12 cells. However, the sensitivity and insertion loss remained approximately unchanged before and after coating the sensor with 3,3'-Dithiobis(succinimidyl) Propionate (DSP).

Background and Objectives: In the current Covid-19 pandemic, children below the age of 12 could manifest Covid-19 symptoms and serve as a reservoir for the virus in the community. The present study was conducted to evaluate the reactogenicity, and immunogenicity of BBIBP-CorV, prior to involving this age group in the vaccination program in the kingdom of Bahrain. Subjects and Methods: The study included 582 children from 3 to 12 years old of Bahraini and non-Bahraini nationality, all of which contributed to the reactogenicity study. Of those, 401 contributed to the immunogenicity study. All children received 2 doses of BBIBP-CorV inactivated virus 3 weeks apart. To assess reactogenicity, children were followed up for 5 weeks to evaluate any vaccine-related adverse events (AE). To assess immunogenicity, blood was collected on day 0 and day 35 to assess antibody titer against S, N, and neutralizing antibody. Results: Of the 582 participants, (45.4%) were female, (54.61%) were male, with 49% in 9-12 age group. Of the 401 children contributing to the immunogenicity study, 274 (68.3%) had no prior exposure to Covid-19. The overall incidence of AE was 27.7%. No significant difference was found among different age groups. The most frequent AE was local (at the injection site) and occurred in 16% of children, followed by fever in 9.3%. No serious adverse events were reported. The Seroconversion rate was 100% among children with no prior exposure to Covid-19. Children with previous Covid-19 exposure had higher averages of anti-S (2379 U/ml compared to 409.1), anti-N (177.6 U/ml compared to 30.9) and neutralizing antibody (93.7 U/ml compared to 77.1) than children with no prior exposure at day 35. Conclusions: Two doses of COVID-19 BBIBP-CorV on the subjects aged between 3 to 12 has good safety and tolerance and can induce an effective immune response and neutralizing antibody titer.

The practice of teaching and scientific research on cadaveric material remains crucial for medical education, especially in surgical disciplines. However, in Italy, this practice has been neglected due to legislative insufficiency and financial constraints. Although innovative methods and tools like simulators and e-learning have been adopted, direct hands-on experience with human cadavers remains irreplaceable for medical and surgical education. The absence of clear legislation governing cadaveric dissection has limited availability for teaching and research, resulting in economic burdens for universities and individuals seeking proper surgical training. To address this issue, the Law No. 10/2020 and the recent implementing decree were introduced in Italy, providing detailed legislation on the donation of bodies for educational and research purposes. The law emphasizes the importance of respecting the donor's specific choices and aligns with constitutional principles promoting culture, research, and health protection. However, some critical issues related to consent procedures, duration of body availability, and preservation of anatomical parts remain. Additionally, the law's dissemination among the population needs improvement. Future optimization could include allowing donors to choose the timing of body donation and considering different timeframes for body availability. Furthermore, the implementation of consent procedures could be simplified to increase donations. The law should also address the need for appropriate reception centers and allocate resources for effective dissemination. Despite these challenges, Law No. 10/2020 represents a significant step forward in enhancing medical-surgical training, scientific research, and the overall quality of patient care in Italy.

Direct femtosecond laser writing or inscription is a useful technique, and it has been 1 employed to engineer various materials in many applications including nonlinear photonic crystals, 2 which are of periodically patterned second-order nonlinearity to get and control the coherent light at 3 new frequencies. By manipulation of second-order nonlinearity, either erased or poled, quasi-phase 4 matching has been achieved in several crystals, especially three-dimensional nonlinear photonic 5 crystals have been originally proposed and proved to be truly three-dimensional. Here we shortly 6 review on the recent advances in the research field of nonlinear photonic crystals inscribed by 7 femtosecond laser. We also discuss some phenomena that not understood yet and the future possible research topics in this field.

Diagnosis of bovine tuberculosis (bTB) may be confounded by immunological cross-reactivity to Mycobacterium bovis antigens when animals are sensitised by certain nontuberculous mycobacteria (NTMs). Therefore, this study aimed to investigate NTM species diversity in African buffalo (Syncerus caffer) respiratory secretions and tissue samples, using a combination of novel molecular tools. Oronasal swabs were collected opportunistically from 120 immobilised buffaloes in historically bTB-free herds. In addition, bronchoalveolar lavage fluid (BALF; n=10) and tissue samples (n=19) were obtained during post-mortem examination. Mycobacterial species were identified directly from oronasal swab samples using the Xpert MTB/RIF Ultra qPCR (14/120 positive) and GenoType CMdirect (104/120 positive). In addition, all samples underwent mycobacterial culture, and PCRs targeting hsp65 and rpoB were performed. Overall, 55 NTM species were identified in 36 mycobacterial culture-positive swab samples with presence of esat-6 or cfp-10 detected in 20 of 36 isolates. The predominant species were M. avium complex and M. komanii. Nontuberculous mycobacteria were also isolated from 6 of 10 culture-positive BALF and 4 of 19 culture-positive tissue samples. Our findings demonstrate that there is a high diversity of NTMs present in buffaloes, and further investigation should determine their role in confounding bTB diagnosis in this species.

For enhancing the maximized profit from bank as well as customer perspective, term deposit can accelerate finance fields. This paper focuses on likelihood of term deposit subscription taken by the customers. Bank campaign efforts and customer details are influential while considering possibilities of taking term deposit subscription. An automated system is provided in this paper that approaches towards prediction of term deposit investment possibilities in advance. Neural network(NN) along with stratified 10-fold cross-validation methodology is proposed as predictive model which is later compared with other benchmark classifiers such as k-Nearest Neighbor (k-NN), Decision tree classifier (DT), and Multi-layer perceptron classifier (MLP). Experimental study concluded that proposed model provides significant prediction results over other baseline models with an accuracy of 88.32% and Mean Squared Error (MSE) of 0.1168.

Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D scaffolds with ideal mechanical and biological properties remains an unattained challenge. In this work, a novel approach is explored to produce synthetic bone grafts mimicking the complex bone structure using additive manufacturing. For the first time, scaffolds were produced, using an extrusion technique, composed of a thermoplastic polymer, polycaprolactone (PCL), hydroxyapatite nanoparticles (HANp), and polyethylene glycol diacrylate (PEGDA). These scaffolds were further compared with two groups of scaffolds: one composed of PCL and another of PCL and HANp. After production, optimisation and characterisation of these scaffolds, an in vitro evaluation was performed using human dental pulp stem/stromal cells (hDPSCs). Through the findings it was possible to conclude that PEGDA scaffolds were successfully produced presenting networks of interconnected channels, presenting hydrophilic properties (15.15 4.06°), adequate mechanical performance (10.41MPa 0.934), and allowing a cell viability significantly superior to the other groups analysed. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes.

Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.

This study addresses the implementation of the International Financial Reporting Standard 9 (IFRS 9) in the European Union as of January 1, 2018, replacing the International Accounting Standard 39 (IAS 39) to introduce a new model for recognizing Loan Loss Provisions (LLP) based on Expected Credit Loss (ECL). This model responds to criticisms of the former Incurred Credit Loss (ICL) system for its inability to reflect credit losses in a timely manner, potentially exacerbating the effects of financial crises (Bushman &amp; Williams, 2015; Gebhardt &amp; Novotny-Farkas, 2011). The study focuses on the effects of adopting the ECL model on the level of Loan Loss Allowances (LLA) in loans, own equity, and the Common Equity Tier 1 (CET1) ratio across 13 Portuguese commercial banks. A mean comparison test is used to evaluate scenarios before and after the application of the ECL model, highlighting the importance of regulator actions and the adequacy of loss recognition policies, including the effects of Regulation (EU) 2017/2395 of December 12. The results obtained demonstrate significant negative impacts on the net values of loans, own equity, and the CET1 ratio upon adopting the IFRS 9 ECL model, due to the widespread increase in LLAs.

This article delves into the pro-cyclicality of Loan Loss Provisions (LLPs) and earnings management, along with equity management, in Portuguese banks against the backdrop of implementing the IFRS 9's Expected Credit Loss (ECL) model. It concentrates on how LLPs mirror economic cycles and financial management practices, providing valuable insights into the operational dynamics of the Portuguese banking sector, marked by distinct economic and regulatory challengesThe research examined a sample of five Portuguese commercial banks, chosen from a group of seventeen in the Portuguese Banking Association. Data spanning from 2013 to 2022 were manually gathered. A multiple linear regression model was employed to scrutinize the relationship between LLPs and variables indicative of economic cycles and the earnings and equity management. The methodology aligns with the approaches of Araújo et al. (2018), Beatty and Liao (2014), and Casta et al. (2019). The analysis indicates a pro-cyclicality in LLPs within the Portuguese context, with a positive response of LLPs to economic indicators like unemployment. Contrarily, the extent of earnings and equity management under the ECL model was less marked compared to the Incurred Credit Loss (ICL) model, suggesting the impact of more stringent regulatory measures. The research corroborates the pro-cyclicality of LLPs in Portuguese banks under the ECL framework, underscoring the necessity for ongoing monitoring and refinement of models for forecasting and recognizing credit losses. The findings point to an area for improvement in financial management practices, despite regulatory enhancements, to promote transparency and ensure financial stability.

Top-down models are defined by hardware architects to provide information on the utilization of the different hardware components. The target is to isolate the users from the complexity of the hardware architecture while giving them insight into how efficiently the code is using the resources. In this paper, we explore the applicability of 4 top-down models defined for different hardware architectures powering state-of-the-art HPC clusters (Intel Skylake, Fujitsu A64FX, IBM Power9, and Huawei Kunpeng 920) and propose a model for AMD Zen 2. We study a parallel CFD code used for scientific production to compare these 5 Top-Down models. We evaluate the level of insight achieved, the clarity of the information, the ease of use, and the conclusions that each one allows us to reach.

Conclusion: When applied to the air-abraded Filtek™ Bulk Fill Flowable Restorative composite surface, 10-MDP-containing adhesives perform better than 10-MDP-free adhesives. The binding strength was unaffected by the 10-MDP-containing adhesives' chemical makeup. The bond strength endurance of adhesives containing 10-MDP decreases with age. Keywords: keyword 1; keyword 2; keywords: low-viscosity bulk fill composite, universal adhesives, self-etch adhesive, 10-MDP, aging, bond strength.

Dentin bonding is a key in restorative dentistry. Herein, we developed self-etching two-bottle adhesive system containing 10-methacryloyloxidecyl dihydrogen phosphate monomer (MDP) and the physical, mechanical, and biocompatible properties were evaluated. The characteristics of MDP were analyzed using nuclear magnetic resonance (NMR). The water sorption and solubility, the shear-bond strengths to dentin and enamel, and cytotoxicity tests were performed. The newly blended experimental group showed the lowest thickness and water sorption and solubility values. The shear bond strength to enamel and dentin were comparable to control groups (the three other products) all test groups showed 60% of cell viability. In this study, the properties of the newly synthesized adhesive are comparable with the others. The fundamental goal of this study is to get the MDP patent released, as it is intended for domestic production. For this purpose, this dentin adhesive was developed and compared with the commercial product.

Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bio-active compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds which were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweeds ex-tracts and their health potential. Both extracts, but more efficiently Aramé extract demonstrated to have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity and to reduce approximately 30 % cholesterol permeation through human Caco-2 cells simulating the intestinal lining, targets for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cells lines exposed to Aramé and Nori extracts revealed changes in the cell’s metabolism as indicators of the extract’s health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated to lipid metabolism, such as phospholipids, and fatty acid metabolism, pathways of amino acid, cofactors and vitamins and cellular respiration metabolism. More profound for Aramé treated cells, but also seen for Nori ex-posed cells, the metabolites modifications were associated with the protection against CVDs and other diseases and, to the improvement of cells oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cells metabolism, are an important contribution for further evaluation of these seaweeds extracts as functional foods or for CVDs prevention.

Alkyl moieties—open chain or cyclic—are common in drug molecules and can be internal or terminal. The open-chain alkyls can be linear or branched; the cyclic alkyls may be substituted. Usually, the branches in open-chain alkyls and substituents in cycloalkyls influence both the pharmacokinetics and pharmacodynamics of a drug molecule. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some parent-drug equiactive hydroxy metabolites have been developed into metabolite ester prodrugs, while some of the parent-drug carboxy metabolites have been developed into metabolite drugs. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. Some subtexts found to manifest from the hydroxy and carboxy functionalization of alkyl moieties in drug molecules are presented and discussed. The review provides basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules; and (ii) whether the resulting metabolites will possess pharmacologic activity or be devoid of it.

This paper presents a concise exploration of the synthetic biology currently to artificially 1 create life, juxtaposed against natural life’s emergence over Earth’s 4.5-billion-year history. It explores 2 the complexities of life’s origins, sustaining factors, and the consequences of synthetic life creation, 3 addressing key scientific milestones such as the Urey-Miller experiment and Jacques Monod’s pro- 4 posals. The narrative navigates through the roles of energy, Maxwell’s demons, bifurcations, and 5 genetic information in the emergence and evolution of complex biological systems. Despite significant 6 strides in genetic engineering, the challenge of creating life from scratch persists, necessitating a deep 7 understanding of diverse scientific disciplines. While synthetic biology holds promise for medicine 8 and biotechnology, the creation of truly autonomous synthetic life forms raises ethical concerns. The 9 paper also stresses the imperative for careful ethical evaluation of the societal and environmental 10 implications arising from these advancements.

Since its post-World War II inception, the science of record linkage has grown exponentially and is used across industrial, governmental, and academic agencies. The academic fields that rely on record linkage are diverse, ranging from history to public health to demography. In this paper, we introduce the different types of data linkage and give a historical context to their development. We then introduce the three types of underlying models for probabilistic record linkage: Fellegi-Sunter based methods, machine learning methods, and Bayesian methods. Practical considerations such as data standardization and privacy concerns are then discussed. Finally, recommendations are given for organizations developing or maintaining record linkage programs, with an emphasis on organizations measuring long-term complications of disasters such as 9/11.

This contribution deals with the assessment of air pollution caused by atmospheric aerosol particulate matter fraction PM10 and benzo[a]pyrene (BaP) in the urban agglomeration of Ostrava, located in the Czech Republic in Central Europe. The motivation for this research was the need to identify the sources of air pollution in the area, particularly in locations where the contribution of different sources to concentrations of pollutants of concern has not been elucidated yet. In this study, source apportionment in the vicinity of the industrial hot-spot was performed by statistically evaluating measured pollutant concentrations as a function of meteorological variables and using the Positive Matrix Factorization (PMF) receptor model. A significant methodological innovation and improvement over previous assessments was the higher monitoring resolution of benzo[a]pyrene, with samples collected at three-hour intervals instead of the standard 24-hour collection period. The key findings indicate that in the cold part of the year, secondary particles - specifically sulphates and ammonium nitrates - were responsible for the most significant portion of PM10 air pollution throughout the area of interest. The contribution of these particles ranged from one third to two fifths of the total concentration, except at the industrial site of Ostrava-Radvanice (TORE), where they accounted for approximately one fifth of the measured pollution concentration level. Emissions from individual household heating were identified as the main source of this type of pollution. With regards to benzo[a]pyrene air pollution, the study found that in the whole area of interest, except for the Ostrava-Radvanice site, it mainly originated from individual heating with coal (90%). In contrast, at the Ostrava-Radvanice site, two-thirds of the benzo[a]pyrene pollution came from the premises of Liberty Ostrava a.s., primarily from coke production, and less than one-third from local domestic heating. This study also determined the spatial extent of the occurrence of extremely high benzo[a]pyrene concentrations (above 5 ng/m3), which are estimated to affect nearly 10,000 inhabitants. The results confirm that the data from the TORE station are only representative of its immediate surroundings and are not applicable to the assessment of air quality and causes of air pollution in the whole city of Ostrava or the urban area of Ostrava-Radvanice as a whole. After years of research, these findings provide the Ministry of the Environment of the Czech Republic and the government with an accurate basis for implementing measures to address the identified pollution sources in the area of interest. The success of this study was made possible by the adoption of a more detailed sampling approach, which involved a resolution of 3 hours instead of 24 hours. This methodological improvement is a significant finding and will be useful for future source apportionment studies.