In the field of 18F-chemistry for the development of radiopharmaceuticals for positron emission tomography (PET), various labeling strategies by the use of prosthetic groups have been im-plemented, including chemoselective 18F-labeling of biomolecules. Among those, chemoselec-tive 18F-fluoroglycosylation methods focus on the sweetening of pharmaceutical radiochemistry by offering a highly valuable tool for the synthesis of 18F-glycoconjugates with suitable in vivo properties for PET imaging studies. A previous review covered the various 18F-fluoroglycosylation methods that have been developed and applied as of 2014 [Maschauer and Prante, BioMed. Res. Int. 2014, 214748]. This paper is an updated review, providing the recent progress in 18F-fluoroglycosylation reactions and the preclinical application of 18F-glycoconjugates, including small molecules, peptides, and high-molecular-weight proteins.

Radiolabelled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection we recently developed the fluorine-18 labelled PSMA-ligand [¹⁸F]PSMA-1007 as next generation radiofluorinated Glu-ureido PSMA inhibitor after [¹⁸F]DCFPyL and [¹⁸F]DCFBC. Since radiosynthesis so far was suffering for rather poor yields novel procedures for the automated radiosyntheses of [¹⁸F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly used radiosynthesisers. Using the novel one-step procedure the [¹⁸F]PSMA-1007 was produced in good radiochemical yields ranging from 30-70 % and synthesis times less than 55 minutes. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and at the same time high yielding production pathway for the next generation PSMA radioligand [¹⁸F]PSMA-1007. Actually it turned out that the radiosynthesis is as easily realised as the well-known [¹⁸F]FDG synthesis and thus transferable onto all currently available radiosynthesisers. Using the new procedures, clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

This work examines the impact of the nozzle-substrate distance (NSD) on the structural, optical and electrical properties of fluorine-doped tin oxide (FTO) thin films. The films were grown by spray pyrolysis with the chemical formulation of “Streaming Process for Electroless and Electrochemical Deposition technology” (SPEED) technique. The characterization technique such as XRD, SEM, UV-spectrophotometry and Hall Effect measurement were employed for studying the structural, optical and electrical properties of the FTO films at various NSD. The NSD was varied from 25-32cm amid the experiment. All FTO films are polycrystalline, tetragonal crystal structure with strong orientation along the (211) reflection. SEM properties study demonstrated slight reliance on NSD and have uniform films which are a disciple to substrate at NSD of 27 and 30 cm, however, crumbled at 25cm and 32cm NSD. They likewise displayed a mud-look like morphology and smooth white appearance. The average optical transmittance of all films is over 80% in the noticeable at UV range. The band gap investigation demonstrates the average value of 3.5eV and the resistivity was found to diminish with increasing NSD at 30 cm. Both mobility and carrier concentration of the FTO films follow a similar trend. The average figure of merit of 4.98 was obtained which is an improvement based on our previous results. The FTO samples grown at 27 and 30 cm NSD in this work are best FTO samples and hence could serve as a promising candidate in dye sensitized solar cells. Therfore, graphene has been employed in different concentrations in our ongoing FTO optimization research so as to further improve on the FTO’s figure of merit.

Background: CK-18 is a serological marker of apoptosis that has been widely associated with fibrosis and steatosis in NASH. Many studies have showed association CK-18 levels with NAFLD. To date, there is a profound lack of rheumatology studies on the effect of MTX therapy with regard to CK-18 levels. The relationship between CK-18 levels and cumulative MTX dose, MTX treatment duration, weekly MTX dose is not available in the literature. Objectives: The main purpose of this study was to determine the relationship between serum cytokeratin-18 (CK-18) and cumulative methotrexate dose in rheumatology patients on methotrexate (MTX) therapy. Besides, we studied the correlations between CK-18 and clinical parameters including age, disease duration , duration of MTX therapy, cumulative steroid dose and biochemical parameters such as alanine transaminase (ALT) and aspartate aminotransferase AST). Methods : We recruited 79 rheumatology patients on methotrexate (MTX) therapy as MTX group and 38 patients not on MTX therapy as non-MTX group . All subjects were tested for their serum CK-18 levels using an enzyme-linked immunosorbent assay (ELISA) test. We identified 20 patients with the highest CK-18 levels and 20 patients with the lowest CK-18 levels and had ultrasound liver performed on them. Results : The median serum CK-18 levels were marginally higher among the patients on MTX (1.20 ng/mL [0.19-37.15]) compared to the non-MTX group (1.17 ng/mL [0.37-34.32]). There was a significantly positive relationship between serum CK-18 levels and cumulative MTX dose (r = 0.329, p = 0.003) and total duration of MTX therapy (r = 0.284, p = 0.011). Apart from the above-mentioned variables, the CK-18 levels in MTX group significantly correlated with age (r = 0.265, p = 0.018), ALT (r = 0.440, p = <0.001) and AST (r = 0.478, p= 0.004). Ultrasound liver findings showed median CK-18 levels was higher among patients with abnormal liver findings although statistical significance was not reached. Conclusion : Among patients on MTX therapy, serum CK-18 levels correlated positively with cumulative MTX dose , total duration of MTX treatment , ALT and AST levels. These findings are preliminary and requires validation by future studies in the field of rheumatology.

High levels of groundwater containing both arsenic and fluorine are prevalent, resulting in serious health problems when consumed as drinking water. This co-pollution phenomenon is widespread and requires urgent attention. The multiple forms of arsenic and arsenic-fluorine co-contamination pose a significant challenge to efficiently co-remove both substances. This research utilized a green and stable synthesis approach to create MgLaFe LDO heterostructures, which were anchored on α-MnO2 nanowires. The materials comprise magnesium and lanthanum elements with a powerful attraction towards fluoride ions, elemental iron, which can establish stable compounds with arsenate, and MnO2, which can effectively oxidize arsenous acid, thereby enabling efficient co-removal of arsenic and fluorine. The efficient oxidation process of the MnO2 nanowire and the prompt ion adsorption process of the LDO work together synergistically. The adsorption performance was assessed through isotherm and kinetic fitting. Chemisorption was found to be the process for As(Ⅲ), As(V), and F- adsorption, with As(Ⅲ) going through monolayer adsorption on the surface of MnO2 nanowires, while As(V) and F- were mainly adsorbed by multilayer process on LDO. The maximum adsorption capacities were 111.76 mg/g, 230.51 mg/g, and 765.10 mg/g for As(Ⅲ), As(V), and F-, respectively. The XPS analysis provided further elucidation on the adsorption mechanism of the MnO2@LDO heterostructure, detailing each component's role in the process. The results confirm the successful construction of the heterostructure and its efficient coupling of oxidation and adsorption.

Identified by the eponym “Edwards’ Syndrome,” trisomy 18 (T18) represents the second most common autosomal trisomy after T21. The pathophysiology underlying the extra chromosome 18 is a nondisjunction error, mainly linked with the advanced maternal age. More frequent in female fetuses, the syndrome portends high mortality, reaching a rate of 80% of miscarriages or stillbirths. The three-step evaluation includes first trimester screening for fetal aneuploidy using a combination of maternal age, fetal nuchal translucency thickness, fetal heart rate and maternal serum free ß-hCG and PAPP-A; followed by the research for fragments of fetal DNA in maternal blood; and, finally, invasive techniques leave to the established diagnosis. Starting with the first trimester scan, selected ultrasound findings should be investigated to define not only the impact of the genetic problem on the fetus, but also to address the prenatal counselling. Previous series underline that T18 is not uniformly lethal. An active dialogue on the choices in the management of infants with T18 has emerged, sustained by the transition from the comfort care to the intervention attitude. Survival rates for individuals with supposedly fatal conditions have increased. In this novel scenario, an ad hoc counselling is pivotal. To support it, a comparative analysis by pictorial assays between ultrasound and autopsy findings could be beneficial. We provide an illustrative tool from a clinical case managed in early second trimester, with the purpose to strive a balanced approach in the hard choice faced by couples of fetuses with T18.

The organo-catalyzed enantioselective benzylation reaction of α-trifluoromethoxy indanones afforded α-benzyl-α-trifluoromethoxy indanones with a tetrasubstituted stereogenic carbon center in excellent yield with moderate enantioselectivity (up to 57% ee). Cinchona alkaloid-based chiral phase transfer catalysts were found to be effective for this transformation, and both enantiomers of α-benzyl-α-trifluoromethoxy indanones were accessed, depended on the use of cinchonidine and cinchonine-derived catalyst. The method was extended to the enantioselective allylation reaction of α-trifluoromethoxy indanones to give the allylation products in moderate yield with good enantioselectivity (up to 76% ee).

Influence of water concentration on the properties of fluorine-doped tin oxide (FTO) thin films was systematically studied in this work. Home made SISOM’s SPEED techniques and its chemical formulation was employed to grow the FTO on quartz substrate. Water concentration in the precursor solution was varied from 0, 0.5, 1.0 and 1.5 mol %. The structural, optical, and electrical properties of the films were studied under these deposition conditions. The results show that the properties of the films varied significantly with water concentration. Scanning electron microscopy (SEM) revealed FTO films whose grain size and uniformity increases significantly with increase in water concentration. The structure of the films was measured by X-ray diffraction (XRD) measurement. It shows polycrystalline films with (110), (101), (200), (211) and (220) orientation; the strength increases as water concentration increases. The optical transmission was determined by UV-Vis spectroscopy at 380–780 nm UV-VIS regions. The optical transmittance varies with water concentration with an average of 84%. The electrical property, measured by Hall Effect revealed n-type semiconductor. The films have the following properties: resistivity, 15 × 10^-4Ω cm; carrier concentration, 18.7 × 10¹⁹ cm^-3 and mobility of 21.86 cm² V^-1 s^-1. The average figure of merit, φ of the FTO film is 1.25. Optimum deposition condition was established after series of experiments and was found to be 1.5% water concentration at 460^oC substrate temperature. The FTO films deposited in this work could be a promising replacement to indium tin oxide (ITO) especially in dye-sensitized solar cells.

Simultaneously being a non-radiative and non-invasive technique makes magnetic resonance imaging (MRI) one of the highly sought imaging techniques for the early diagnosis and treatment of diseases. Despite more than four decades of research on finding a suitable imaging agent from fluorine for clinical applications, it still lingers as a challenge to get the regulatory approval compared to its hydrogen counterpart. The pertinent hurdle is the simultaneous intrinsic hydrophobicity and lipophobicity of fluorine and its derivatives that make them insoluble in any liquids, strongly limiting their application in areas such as targeted delivery. A blossoming technique to circumvent the unfavorable physicochemical characteristics of perfluorocarbon compounds (PFCs) and guarantee a high local concentration of fluorine in the desired body part is to encapsulate them in nanosystems. In this review, we will be emphasizing different types of nanocarrier systems studied to encapsulate various PFCs and fluorinated compounds, headway to be applied as a contrast agent (CA) in fluorine-19 MRI (19F MRI). We would also scrutinize the different types of PFCs and their specific applications and limitations concerning the nanoparticle (NP) system used to encapsulate them studied over the last decade. A critical evaluation for future opportunities would be speculated.

Inhibitory activity of 14 phosphonic analogues of phenylglycine, substituted in aromatic ring by fluorine and chlorine, was determined towards porcine aminopeptidase N. The obtained data served as a basis for studying their interaction with the enzyme as modelled by the use of Schrödinger Release 2018 program. The observed linearity between modelled Gibbs free energy differences and inhibitory constants indicated the usefulness of this program. The obtained binding mode was compared with this modelled for bovine lens leucine aminopeptidase. Although both enzymes differ in the number of zinc ions present in the active site, they are considered to exhibit similar activity towards substrates and inhibitors. Our studies seem to support that supposition since the modes of binding of the studied inhibitors are quite similar. Additionally, inhibitory activity of the phosphonic analogues of phenylglycine towards barley aminopetpidase was determined showing that this enzyme could be considered as neutral aminopeptidase.

In this study, two donor-acceptor (D-A) type conjugated polymers namely PQSeCz and PQSeFl were designed and synthesized. Selenophene was incorporated as a π -bridge, quinoxaline as an acceptor unit while carbazole and fluorene were used as the donor units. Polymers were synthesized via palladium catalyzed Suzuki polymerization reaction. All molecules were characterized by 1H and 13C NMR Spectroscopy. The weight and number average molecular weights of the two polymers were determined by gel permeation chromatography (GPC). Electrochemical and spectroelectrochemical characterizations of the polymers were performed to investigate their optoelectronic properties. Oxidation potentials were 1.15 V/ 0.82 V and 1.11 V/ 0.82 V for PQSeCz and PQSeFl respectively, while reduction potentials were -1.26 V /-1.14 V and -1.48 V/ -1.23 V, respectively. In the visible region, maximum absorption wavelengths for the two polymers were 551 nm and 560 nm, respectively. Optical band gaps (Egop) were found from the lowest energy π – π∗ transition onsets as 1.71 eV and 1.58 eV, respectively. Both polymers showed good solubility in common solvents.

High-power laser facilities necessitate predicting incremental damage to final optics to identify evolving damage trends. In this study, we propose a surface damage detection method utilizing image segmentation employing ResNet-18, and a damage area estimation network employing U-Net++. Paired sets of online and offline images of optics obtained from a large laser facility is used to train the network. The trends of varying damage could be identified by incorporating additional experimental parameters. A key advantage of the proposed method is that the network can be trained end-to-end on small samples, eliminating the need for manual labeling or feature extraction. The software developed based on these models can facilitate the daily inspection and maintenance of optics in large laser facilities.

As an essential synthetic material used in continuous casting of steels, mold fluxes improve the surface quality of steel slabs. In this study, a CaO-SiO₂-Na₂O based low-fluorine mold flux was solidified by an improved water-cooled copper probe with different temperatures of molten flux and different probe immersion times. The heat flux through solid films and the film structures were calculated and inspected, respectively. The results indicate: large internal cracks (formed in the glassy layer of films during solidification) were observed, the formation and evolution of those cracks contributed to the the unstable heat flux density. The roughness of the surface in contacted with the water-cooled copper probe formed as films were still glassy and the roughness have no causal relationship with crystallization or devitrification. Combeite with columnar and faceted dendritic shapes is the main crystal in the film.

Microglia are the resident immune cells of the central nervous system. Upon stimulus presentation microglia polarize from a resting to an activated state. Microglial translocator protein 18 kDa (TSPO) is considered as a marker of inflammation. Here, we characterized the role of TSPO by investigating the impact of TSPO deficiency on human microglia. We used TSPO knockout (TSPO-/-) variants of the human C20 microglia cell line. We found a significant reduction in the TSPO-associated protein VDAC1 in TSPO-/- compared to control cells. Moreover, we assessed the impact of TSPO deficiency on calcium levels and the mitochondrial membrane potential. Cytosolic and mitochondrial calcium concentrations were increased in TSPO-/- cell lines, whereas the mitochondrial membrane potential tended to be lower. Assessment of the mitochondrial DNA copy number via RT-PCR revealed a decreased amount of mtDNA in the TSPO-/- cells when compared to controls. Moreover, metabolic profiles of C20 cells were strongly dependent on the glycolytic pathway. However, TSPO depletion did not affect the cellular metabolic profile. Measurement of the mRNA expression levels of the pro-inflammatory mediators revealed an attenuated response to proinflammatory stimuli in TSPO-depleted cells, implying a role of the TSPO protein in the process of microglial polarization.

In mammals, the role of interleukin-18 (IL-18) in the immune response is to drive inflammatory and, normally therefore, anti-viral responses. IL-18 also shows promise as a vaccine adjuvant in mammals. Chicken IL-18 (chIL-18) has been cloned. The aim of this study was to investigate the potential of chIL-18 to act as a vaccine adjuvant in the context of a live recombinant Fowlpox virus vaccine (fpIBD1) against Infectious bursal disease virus (IBDV). fpIBD1 protects against mortality, but not against damage to the bursa of Fabricius caused by IBDV infection. The Fowlpox virus genome itself contains several candidate immunomodulatory genes, including potential IL-18 binding proteins (IL-18bp). We have knocked out (Δ) the potential IL-18bp genes in fpIBD1 and inserted (::) the cDNA encoding chIL-18 into fpIBD1 in the non-essential ORF030, generating five new viral constructs –fpIBD1::chIL-18, fpIBD1ΔORF073, fpIBD1ΔORF073::chIL-18, fpIBD1ΔORF214 and fpIBD1ΔORF214::chIL-18. The subsequent protection from challenge with virulent IBDV, as measured by viral load and bursal damage, given by these altered fpIBD1 strains, was compared to that given by the original fpIBD1. The results show that chIL-18 can act as a vaccine adjuvant, giving complete protection against challenge, with no detectable virus or damage in the bursa of Fabricius.

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

Herein, we report on a giant thermoelectric figure of merit of a non-degenerate fluorine-doped single-walled carbon nanotube (FSWCNT) using a tractable analytical approach and the phonon lattice Boltzmann model (LBM). We investigate the influence of the doping concentration, and the overlapping integrals on the ZT. The ZT and the temperature range of operation can be tuned using the doping (impurity) concentration and the overlapping integrals, respectively. The lattice thermal conductivity obtained using the phonon LBM was calculated to be 107.2 W/mK which yielded a ZT greater than 20. Interestingly, the ZT obtained is higher than what has been reported in superlattices, (ZT~1.4) and superlattice nanowire, (ZT~ 4) at 300 K, making FSWCNT a potential candidate for thermoelectric applications.

The activation of halogen bonding by the substitution of the pentafluorosulfanyl (SF5) group was studied using a series of SF5-substituted iodobenzenes. The simulated electrostatic potential values of SF5-substituted iodobenzenes, ab initio molecular orbital calculations of intermolecular interactions of SF5-substituted iodobenzenes with pyridine, and the 13C NMR titration experiments of SF5-substituted iodobenzenes in the presence of pyridine or tetra (n-butyl) ammonium chloride (TBAC) indicated the obvious activation of halogen bonding, although this was highly dependent on the position of SF5-substitution on the benzene ring. 3,5-Bis-SF5-iodobenzene was the most effective halogen bond donor followed by o-SF5-substituted iodobenzene, while the m- and p-SF5 substitutions did not activate the halogen bonding of iodobenzenes. The 2:1 halogen bonding complex of 3,5-bis-SF5-iodobenzene and 1,4-diazabicyclo[2.2.2]octane (DABCO) was also confirmed. Since SF5-containing compounds have emerged as promising novel pharmaceutical and agrochemical candidates, the 3,5-bis-SF5-iodobenzene unit should be an attractive fragment of rational drug design capable of halogen bonding with biomolecules.

Background: Cytokines are multifunctional glycoproteins playing a vital role in the tumor microenvironment and in the progression of breast cancer. The immune responses in the tumors restrained by pro- and anti-inflammatory cytokine expressions could be influenced by genetic polymorphisms. Hence, the present study evaluated the contribution of IL6 (rs1800797, rs1800796, and rs1800795), and IL18 (rs1946518, rs187238, and rs549908) genotypes and its haplotypes with risk and progression of breast cancer in south Indian population. Methods: The polymorphisms of IL6 gene -597G>A, -572G>C, -174G>C and IL18 gene -607C>A, -137G>C, and 105A>T were genotyped through PCR-RFLP and As-PCR assays in blood DNA of 600 subjects. We have performed haplotype, LD, univariate, multivariate logistic regression and Kaplan-Meier analyses for the obtained data. Results: The frequency of AA genotype & A-allele of IL6 -597G>A, and CC genotype & C allele of IL6 -174G>C polymorphism was higher in breast cancer patients and was found to be significantly associated with TNM staging, late (advanced) stage, metastasis, etc. While, CG and GG genotypes of IL6 -572 C>G polymorphism had a protective role against breast cancer. Further, IL18 -607C>A, -137G>C & 105A>T polymorphisms were found to be associated with lobular carcinoma subtype, PR-ve and HER2+ve breast cancer patients. Perfect LD was observed between all SNPs of IL6 & IL18 genes under study; G-C-C, A-G-G and A-C-C haplotype combination of IL6 genes had conferred 2.09, 2.25 and 4.72 folds risk for breast cancer respectively. In survival analysis, we observed that the C allele of rs 1800795 was found to be significantly associated with 5years overall survival in breast cancer subjects. Conclusions: Overall, our results suggest the importance of genotypic and haplotype analysis of IL6, and IL18 gene variants in progression and risk identification of breast cancer.

Stable isotope concentrations in the soil, rain and ground water have been used to trace the water extraction zones of plants in different environments. The need to identify the plant water use by plants in afforestation programs to control desertification increases the importance of sap water partitioning of plants in sand dune areas. However, the introduction of new plant covers exerts pressure on the water resources and can affect the local soil water conditions. In this study, we analyzed the isotope concentrations in rain, soil, sap, and ground water after the summer of 2010. Two experimental plots established in the Hailiutu catchment (Shaanxi province, northwest China) were selected to gather the water samples between September and October 2010. One plot is dominated by Salix bushes (Salix psammophila C. Wang \& Chang Y. Yang) and the other by the tree species Willow (Salix matsudana Koidz.). The total precipitation at the experimental site was 401 mm/yr during 2010, while 88.7 mm was collected in total for the period September to October. Willow trees transpired 12.82 kg/d being almost three times larger than Salix shrubs (4.57 kg/d). Despite the transpiration rates of both plant species and the few rain events in the region, the soil water beneath the plant covers is not depleted. Stable isotope signature of soil water beneath both covers shows the fractionation front in Salix at 20 cm depth and at Willow at 40 cm depth. However, soil water signature is closer to the groundwater than the collected rain water.

Drinking water contamination of lead from various environmental sources, leaching consumer products and intrinsic water-pipe infrastructure is still today a matter of great concern. Therefore, new highly sensitive and convenient Pb²⁺ measurement schemes are necessary, especially for in-situ measurements at a low-cost. Within this work dye/ionophore/Pb²⁺ co-extraction and effective water phase de-colorization was utilized for highly sensitive lead measurements and sub-ppb naked-eye detection. A low-cost ionophore Benzo-18-Crown-6-ether was used, and a simple test-tube mix and separate procedure was developed. Instrumental detection limits were in the low ppt region (LOD=3, LOQ=10), and naked-eye detection was 500 ppt. Note, however, that this sensing scheme still has improvement potential as concentrations of fluorophore and ionophore were not optimized. Artificial tap-water samples, leached by a standardized method, demonstrated drinking water application. Implications for this method are convenient in-situ lead ion measurements.

Early stable deep molecular response (DMR) of nilotinib is associated with goal of treatment-free remission (TFR) for patients with chronic-phase chronic myeloid leukemia (CML-CP). It is significant to early distinguish patients who can obtain DMR and fit for TFR. We performed a multicenter study to explore early cumulative MR4.5 rate by 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. From 29 institutes, 106 ND-CML-CP patients received nilotinib (300mg BID). The cumulative MR4.5 rate of nilotinib by 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates of nilotinib by 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with ultra-early molecular response (u-EMR) at 6 weeks were not significantly different to obtain DMR or MMR by 24 months compared to those without u-EMR (P=0.7584, P=0.9543, respectively). Our study demonstrated that treatment with nilotinib in patients with ND-CML-CP contributed to obtain high early MR4.5.

With the COVID-19 pandemic behind us, the U.S. Food and Drug Administration (FDA) has approved 55 new drugs in 2023, a figure consistent with the number authorized in the last five years (53 per year on average). Thus, 2023 is the second-best FDA harvest after 2018 (59 approvals) in all the series. Monoclonal antibodies (mAbs) continue to be the class of drugs with most approvals, with an exceptional 12, a number that makes it the most outstanding year for this class. As in 2022, five proteins/enzymes have been approved in 2023. However, no antibody–drug conjugate (ADC) has been released onto the market. With respect to TIDES (peptides and oligonucleotides), 2023 has proved a spectacular year, with a total of nine approvals, corresponding to five peptides and four oligonucleotides. Natural products continue to be the best source of inspiration for drug development, with 10 new products on the market. Three drugs in this year’s harvest are pegylated, which may indicate the return of pegylation as a method to increase the half-lives of drugs, after the withdrawal of peginesatide from the market in 2013. Following the trends of recent years, two bispecific drugs have been authorized in 2023. As in preceding years, fluorine and/or N-aromatic heterocycles are present in most of the drugs. Herein, the 55 new drugs approved by the FDA in 2023 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins/enzymes); TIDES (peptide and oligonucleotides); combined drugs; pegylated drugs; natural products; nitrogen aromatic heterocycles; fluorine-containing molecules; and other small molecules.

The AT-HOOK MOTIF NUCLEAR LOCALIZED PROTEIN (AHL) gene family encodes embryophyte-specific nuclear proteins with DNA binding activity. They modulate gene expression and affect various developmental processes in plants. We identify AHL18 (At3G60870) as a developmental modulator of root system architecture and growth. AHL18 regulates the length of the proliferation domain and number of dividing cells in the root apical meristem and thereby, cell production. Both primary root growth and lateral root development respond according to AHL18 transcription level. The ahl18 knock-out plants show reduced root systems due to a shorter primary root and a lower number of lateral roots. This change results from a higher number of arrested and non-developing lateral root primordia (LRP) rather than from decreased initiation. Overexpression of AHL18 results in a more extensive root system, longer primary roots, and increased density of lateral root initiation events. Formation of lateral roots is affected during the initiation of LRP and later development. AHL18 regulate root apical meristem activity, lateral root initiation and emergence, which is in accord with localization of its expression.

Hate Speech Detection in Arabic presents a multifaceted challenge due to the broad and diverse linguistic terrain. With its multiple dialects and rich cultural subtleties, Arabic requires particular measures to address hate speech online successfully. To address this issue, academics and developers have used natural language processing (NLP) methods and machine learning algorithms adapted to the complexities of Arabic text. However, many proposed methods were hampered by a lack of a comprehensive dataset/corpus of Arabic hate speech. In this research, we propose a novel multi-class public Arabic dataset comprised of 403,688 annotated tweets categorized as extremely positive, positive, neutral, or negative based on the presence of hate speech. Using our developed dataset, we additionally characterize the performance of multiple machine learning models for Hate speech identification in Arabic Jordanian dialect tweets. Specifically, the Word2Vec, TF-IDF, and AraBert text representation models have been applied to produce word vectors. With the help of these models, we can provide classification models with vectors representing text. After that, seven Machine learning classifiers have been evaluated: Support Vector Machine (SVM), Logistic Regression (LR), Naive Bays (NB), Random Forest (RF), AdaBoost (Ada), XGBoost (XGB), and CatBoost (CatB). In light of this, the experimental evaluation revealed that, in this challenging and unstructured setting, our gathered and annotated datasets were rather efficient and generated encouraging assessment outcomes. This will enable academics to delve further into this crucial field of study.

Background and aim: To explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of Non-Alcoholic Fatty Liver Disease (NAFLD), and cardiovascular disease (CVD) risk in the general population. Methods: Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. Receiver Operating Characteristic (ROC) curve, linear/logistic regression models and Spearman's correlations were used. Results: Intricate associations were found between CK18, FLI and CVD risk scores. While M30 was the only independent predictor of FLI≥60, M65 discriminated best NAFLD individuals at very-high 10-years CVD risk according to SCORE2 (AUC:0.71; p=0.001). Values above the predefined manufacturer cut-off (400 U/l), were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p=0.01), with negative predictive value of 93%. Conclusions: Confirming that NAFLD is associated with an increased CVD risk, our results point to CK18 M65 as a candidate biomarker to identify NAFLD individuals at low CVD risk in European general population.

The cytokine-producing nucleotide-binding domain leucine-rich repeat and pyrin-containing receptor 3 (NLRP3) inflammasome is generally recognized to play a central role in the immune response to vaccination and NLRP3 activity is known to be increased by both aluminum adjuvants and by oxidative stress. Thus, the presence of oxidative stress may place individuals at higher risk for exaggerated or prolonged inflammatory responses and related side effects from vaccination. We here examine the relationship between oxidative stress and NLRP3 inflammasome activity, particularly in the context of aluminum-adjuvanted vaccines, and its implications for subpopulations of individuals with restricted antioxidant capacity.

Metandienone and methyltestosterone are orally active anabolic-androgenic steroids with a 17α-methyl structure that are prohibited in sports but are frequently detected in anti-doping analysis. After the previously reported detection of long-term metabolites with a 17ξ-hydroxymethyl-17ξ-methyl-18-nor-5ξ-androst-13-en-3ξ-ol structure in the chlorinated metandienone analog dehydrochloromethyltestosterone (“Oral Turinabol”), in this study we investigated the formation of similar metabolites of metandienone and 17α-methyltestosterone with a rearranged D-ring and a fully reduced A-ring. Using a semi-targeted approach including synthesis of reference compounds, two diastereomeric substances, viz. 17α-hydroxymethyl-17β-methyl-18-nor-5β-androst-13-en-3α-ol and its 5α-analog, were identified following an administration of methyltestosterone. In post-administration urines of metandienone, only the 5β-metabolite was detected. Additionally, 3α,5β-tetrahydro-epi-methyltestosterone was identified in the urines of both administrations besides the classical metabolites included in the screening procedures. Besides their applicability for anti-doping analysis, the results provide new insights on the metabolism of 17α-methyl steroids with respect to the order of reductions in the A-ring, the participation of different enzymes, and alterations of the D-ring.

Toxoplasmosis is a zoonosis of warm-blooded animals, affecting also humans, caused by Toxo-plasma gondii, an obligate intracellular parasite with a complex biological cycle. Toxoplasmosis is considered a re-emerging zoonosis and an important public health threat, also for the absence, up to now, of efficient vaccines and preventive measures. Sources of transmission to humans are environmental or food-borne, mainly through the consumption of raw and undercooked meat, predominantly of Sus scrofa, considered highly susceptible to T. gondii. Mainly in the last dec-ades, an effective strategy to counter animal infectious diseases was based on the discovery of resistance immuno-genetic markers, possibly to be used for association studies between geno-typic and phenotypic traits and consequently in Marker Assisted Selection. Until now, this gen-otyping approach has never been adopted for T. gondii infection, so this study aimed, for the first time, to fill this gap. In particular, pigs, reared in different farms of Central Italy, were serologically characterized by an ELISA assay performed on diaphragm meat juice. Out of 179 tested animals, 98 resulted seropositive (54.74%), 57 seronegative (31.84%) and 24 doubtful (10.6%), underlining a possible re-emerging diffusion of this protozoan in the investigated areas. Atten-tion was firstly focused on IL-18 gene, encoding for a pro-inflammatory cytokine that plays a key role starting from the upstream steps of the immunity pathway towards T. gondii. A RT-PCR assay followed by Sanger sequencing of IL-18 cDNA was de novo developed. For this interleukin, at this stage, genetic analysis has not highlighted significant polymorphic variations compared to the reference sequence, except for a seropositive animal. However, the outcomes of this pre-liminary innovative study will be investigated in depth analyzing other relevant genetic re-gions and other target genes.

For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scan and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months postoperatively. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. To our knowledge, this is the first report in English on mucin-positive signet-ring cells of CC arising in an intestinal-type IPMNHGD evaluated by SPACE cytology.