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Abstract: The effect of Cu contents on the corrosion resistance of NiAl intermetallic rapidly solidified in 0.5M H2SO4 at room temperature has been evaluated using electrochemical techniques. Cupper contents included 15, 20 and 25wt.% and techniques included potentiodynamic polarization curves, linear polarization resistance and potentiostatic tests. For comparison, the same tests were performed on a 316L type stainless steels. The results showed that all the intermetallics exhibited a better corrosion resistance than the 316L type stainless steel for at least ten times but there was not a big difference between the different NiAl alloys with and without Cu for times longer than 4h. For times shorter than 5h, the corrosion current density of the NiAl alloys increased as the Cu contents decreased up to 20% but it increased when the Cu contents increased further up to 25%. A similar behavior occurred with the passive current density. These results were discussed in terms of the incorporation of cuprus oxide particles in to the external passive layer modifying its electrochemical properties. The pitting potential values decreased with additions of Cu respect to the unalloyed NiAl material. Corrosion morphologies showed a preferential dissolution of a phase respect to another due to the formation of micro galvanic cells due to the addition of Cu. [Copyright &y& Elsevier]

• Al 2 O 3 -Ga 2 O 3 solid solutions were obtained and resulted in high activity. • The Pd deposited resulted in metallic nanoparticles highly dispersed. • Gallium oxide content impact directly on the dehydration activity and selectivity. • The morphology of Pd nanoparticles resulted Ga 2 O 3 content dependent. • The highest activity among series was observed over the Pd/AlGa-50 catalyst. A series of mixed Al 2 O 3 -Ga 2 O 3 oxides were prepared with different Ga 2 O 3 content (labeled as AlGa-x; where x is the wt % of Ga 2 O 3) by precipitation method. The oxides were then used as supports of palladium (2 wt %) catalysts (labeled as Pd/AlGa-x). Both series of samples, AlGa-x and Pd/AlGa-x were characterized by several techniques such as Raman spectroscopy, XPS, XRD, SEM, and HRTEM, and were tested in the 2-propanol dehydration reaction. The steady-state conversions displayed by the Pd/AlGa-x series was almost twice as that obtained for the AlGa-x series in all the range of tested temperatures. It was worth noting that the presence of palladium changed the yield observed for the AlGa-x series mainly at low temperatures. While at high temperatures the Lewis acidity provided by the well dispersed Pd nanoparticles increased the activity considerably and improved the propylene production. A balance between the dispersion of palladium and the surface acidity, both related to the Ga 2 O 3 content was responsible for the observed catalytic behavior. [ABSTRACT FROM AUTHOR]

Silicon photonic devices need to be complemented with other materials for the realization of optically active devices. The unique emission properties of single-walled carbon nanotubes are especially promising for efficient light emitters realization in the telecommunication wavelength ranges and for their integration in silicon photonic devices. However one of the problem of carbon nanotubes is their low quantum efficiency. One of the approach to address this problem is to couple the carbon nanotube emission with micro-resonators in order to the enhance their radiative emission. Here we report on the fabrication and optical characterization of a silicon micro-slot-ring resonator coupled with selected single walled semiconducting carbon nanotubes for high photoluminescence emission in the O band telecommunication wavelength. Hyperspectral photoluminescence maps show spectra with sharp resonances superimposed to the nanotube emission bands which demonstrate the coupling of the nanotubes with the evanescent tails in air of the electric field localized in the photonic modes of the micro-resonator. The enhancement of the photoluminescence is achieved over three different CNTs chirality for more than 30 sharp resonances in a single microring resonator. This work paves the way for the development of integrated light sources based on carbon nanotubes in silicon photonic devices. [ABSTRACT FROM AUTHOR]

Background: DNA polymerase theta (POLQ) is a translesion synthesis polymerase essential for the repair of double strand breaks by the error-prone TMEJ (Theta Mediated End Joining) pathway. Although POLQ participates in maintaining genome stability, several studies have shown that its overexpression correlates with cancer progression and poor prognosis. Due to the fact that its role as a biomarker in pancreatic cancer remains unexplored, we aimed to study the usefulness of POLQ H-score as a prognostic factor in a pancreatic cancer patient cohort., Methods: We evaluated POLQ gene expression using a web-based tool to deliver gene expression profiling and interactive analyses based on TCGA and GTEx (GEPIA) and we examined the POLQ immunostaining in 152 biliopancreatic cancer surgical specimens using tissue microarrays. Association with survival was evaluated by Kaplan Meier curves and uni-multivariate Cox regression., Results: GEPIA analysis showed statistical differences according to POLQ mRNA levels in Disease Free Survival (DFS) (log rank 0.023, HR 2.8, p= 0.029) and Overall Survival (OS) (log rank 0.011, HR 3.1, p= 0.016). For immunohistochemistry (IHC) evaluation, POLQ H-score was calculated, and showed statistical differences for OS in Kaplan Meier curves (log rank 0.001) and uni-multivariate analysis (HR 2.27; 95% CI 1.24-4.15, p =0.008)., Conclusions: Our results indicate that POLQ is an independent prognostic factor in pancreatic cancer when analyzed by immunostaining, which is in agreement with the results shown by the POLQ gene expression analysis (GEPIA)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 del Puerto-Nevado, Fernández-Aceñero, Cebrián, Fatych, Díez-Valladares, Pérez-Aguirre, de la Serna, García-Botella, Martínez-Useros, García-Foncillas and Mateos-Gómez.)

Prostate cancer remains a major health concern, with prostate-specific antigen (PSA) being a key biomarker for its detection and monitoring. However, PSA levels often fall into a "gray zone", where PSA levels are not clearly indicative of cancer, thus complicating early diagnosis and treatment decisions. Glycosylation profiles, which often differ between healthy and diseased cells, have emerged as potential biomarkers to enhance the specificity and sensitivity of cancer diagnosis in these ambiguous cases. We propose the integration of two complementary techniques, namely quartz-crystal microbalance with dissipation (QCM-D) and surface-enhanced Raman scattering (SERS) to study PSA glycan profiles. QCM-D offers real-time operation, PSA mass quantification, and label-free detection with high sensitivity, as well as enhanced specificity and reduced cross-reactivity when using nucleic acid aptamers as capture ligands. Complementary SERS sensing enables the determination of the glycosylation pattern on PSA, at low concentrations and without the drawbacks of photobleaching, thereby facilitating multiplexed glycosylation pattern analysis. This integrated setup could retrieve a data set comprising analyte concentrations and associated glycan profiles in relevant biological samples, which may eventually improve early disease detection and monitoring. Prostate-specific antigen (PSA), a glycoprotein secreted by prostate epithelial cells, serves as our proof-of-concept analyte. Our platform allows multiplex targeting of PSA multiplex glycosylation profiles of PSA at "gray zone" concentrations for prostate cancer diagnosis. We additionally show the use of SERS for glycan analysis in PSA secreted from prostate cancer cell lines after androgen-based treatment. Differences in PSA glycan profiles from resistant cell lines after androgen-based treatment may eventually improve cancer treatment.

Background: In 2021, the European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines issued a new definition of bronchodilator responsiveness, which is now defined as an increase in FEV 1 or FVC by ≥ 10% of the predicted FEV 1 or FVC. The impact of this revised definition on bronchodilator responsiveness prevalence has been relatively understudied., Methods: We retrospectively analyzed data from 2,696 subjects who performed pulmonary function testing at the University of Iowa from 1997 to 2018. We compared the prevalence of bronchodilator responsiveness by using the 2005 (FEV 1 or FVC increase ≥ 12% baseline value and ≥ 200 mL) and 2021 (FEV 1 or FVC increase ≥ 200 mL and ≥ 12% of baseline value) ERS/ATS definitions, across several different respiratory diagnosis categories. We compared the prevalence of bronchodilator responsiveness using the 2 definitions by applying the McNemar test and assessed concordance of bronchodilator responsiveness by calculating kappa coefficients for the whole study population and within each diagnosis category., Results: The prevalence of bronchodilator responsiveness increased from 9% when using the 2005 ERS/ATS definition to 16% when using the 2021 definition within the entire cohort and also within each respiratory diagnosis category. In the subjects with normal pre-bronchodilator spirometry, there was a low prevalence of bronchodilator responsiveness (3%) when using the 2005 definition, and the prevalence increased (8%) when using the 2021 definition. In the subjects with normal pre-bronchodilator spirometry and FEV 1 Z score ≥ 0, 2% had bronchodilator responsivness according to the 2005 guidelines, whereas 7% had bronchodilator responsiveness according to the 2021 guidelines., Conclusions: The prevalence of bronchodilator responsiveness increased when using the new 2021 ERS/ATS definition compared with the 2005 definition. In the subjects with normal pre-bronchodilator spirometry, the prevalence of bronchodilator responsiveness increased when using the 2021 definition, in particular, among those with an FEV 1 Z score ≥ 0, which raises concerns for overdiagnosis. Future investigations should examine the correlation of bronchodilator responsiveness with clinical outcomes in this group of subjects., Competing Interests: Dr Fortis has received grants from the American Thoracic Society and Fisher & Paykel, and has served as consultant for Society of Hospital Medicine. The other authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Neuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate gene expression programs shaping neuronal morphology are poorly understood. To address this, we studied how the paradigmatic RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the human neuronal differentiation. We perform a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we show that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity., (© 2024. The Author(s).)

This case report describes the management of a woman diagnosed with a retroperitoneal cystic tumor during pregnancy. The 29-year-old patient presented at 29 weeks of pregnancy with abdominal pain. A retroperitoneal tumor measuring 224 × 156 × 235 mm was identified on ultrasound and magnetic resonance imaging. The patient underwent cesarean section delivery of a healthy neonate at 37 weeks. Uncomplicated laparoscopic surgery was performed during the postpartum period, resulting in a histologic diagnosis of a retroperitoneal lymphangioma. A review of articles published between 2003 and 2023 on the diagnosis, management, and prognosis of gestational lymphangiomas was conducted using the PubMed, SCOPUS and SpringerLink databases. Ten articles, including case reports of lymphangiomas diagnosed during pregnancy, were identified. The most frequent location was the gastrointestinal tract, with no cases reported in the retroperitoneal area. A good perinatal outcome was reported in the majority of cases. Lymphangiomas are rare benign tumors that are even more uncommon during pregnancy. Watchful waiting can offer a good obstetric and perinatal prognosis., Competing Interests: The authors declare that they have no conflict of interest regarding the publication of this case report., (© 2024 The Authors. Published by Elsevier B.V.)

Lead (Pb 2+ ) toxification is a concerning, unaddressed global public health crisis that leads to 1 million deaths annually. Yet, public policies to address this issue have fallen short. This work harnesses the unique abilities of crown ethers, which selectively bind to specific ions. This study demonstrates the synergistic integration of highly-scalable silicon photonics, with crown ether amine conjugation via Fischer esterification in an environmentally-friendly fashion. This realizes an integrated photonic platform that enables the in-operando, highly-selective and quantitative detection of various ions. The development dispels the existing notion that Fischer esterification is restricted to organic compounds, facilitating the subsequent amine conjugation for various crown ethers. The presented platform is specifically engineered for selective Pb 2+ detection, demonstrating a large dynamic detection range, and applicability to field samples. The compatibility of this platform with cost-effective manufacturing indicates the potential for pervasive implementation of the integrated photonic sensor technology to safeguard against societal Pb 2+ poisoning., (© 2024. The Author(s).)

Genetically modified pigs play a critical role in mimicking human diseases, xenotransplantation, and the development of pigs resistant to viral diseases. The use of programmable endonucleases, including the CRISPR/Cas9 system, has revolutionized the generation of genetically modified pigs. This study evaluates the efficiency of electroporation of oocytes prior to fertilization in generating edited gene embryos for different models. For single gene editing, phospholipase C zeta (PLC ζ) and fused in sarcoma (FUS) genes were used, and the concentration of sgRNA and Cas9 complexes was optimized. The results showed that increasing the concentration resulted in higher mutation rates without affecting the blastocyst rate. Electroporation produced double knockouts for the TPC1/TPC2 genes with high efficiency (79 %). In addition, resistance to viral diseases such as PRRS and swine influenza was achieved by electroporation, allowing the generation of double knockout embryo pigs (63 %). The study also demonstrated the potential for multiple gene editing in a single step using electroporation, which is relevant for xenotransplantation. The technique resulted in the simultaneous mutation of 5 genes (GGTA1, B4GALNT2, pseudo B4GALNT2, CMAH and GHR). Overall, electroporation proved to be an efficient and versatile method to generate genetically modified embryonic pigs, offering significant advances in biomedical and agricultural research, xenotransplantation, and disease resistance. Electroporation led to the processing of numerous oocytes in a single session using less expensive equipment. We confirmed the generation of gene-edited porcine embryos for single, double, or quintuple genes simultaneously without altering embryo development to the blastocyst stage. The results provide valuable insights into the optimization of gene editing protocols for different models, opening new avenues for research and applications in this field., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The application of bacterial metagenomic analysis as a biomarker for cancer detection is emerging. Our aim was to discover gut microbiota signatures with potential utility in the diagnosis of colorectal cancer (CRC) and non-small cell lung cancer (NSCLC). A prospective study was performed on a total of 77 fecal samples from CRC and NSCLC patients and controls. DNA from stool was analyzed for bacterial genomic sequencing using the Ion Torrent™ technology. Bioinformatic analysis was performed using the QIIME2 pipeline. We applied logistic regression to adjust for differences attributable to sex, age, and body mass index, and the diagnostic accuracy of our gut signatures was compared with other previously published results. The feces of patients affected by different tumor types, such as CRC and NSCLC, showed a differential intestinal microbiota profile. After adjusting for confounders, Parvimonas (OR = 53.3), Gemella (OR = 6.01), Eisenbergiella (OR = 5.35), Peptostreptococcus (OR = 9.42), Lactobacillus (OR = 6.72), Salmonella (OR = 5.44), and Fusobacterium (OR = 78.9) remained significantly associated with the risk of CRC. Two genera from the Ruminococcaceae family, DTU089 (OR = 20.1) and an uncharacterized genus (OR = 160.1), were associated with the risk of NSCLC. Our two panels had better diagnostic capacity for CRC (AUC = 0.840) and NSLC (AUC = 0.747) compared to the application of two other published panels to our population. Thus, we propose a gut bacteria panel for each cancer type and show its potential application in cancer diagnosis., Competing Interests: The authors declare that there are no conflicts of interests.

The seed germination, as well as root and shoot growth effect of HKUST-1 MOF, and its derived linear polymer ([Cu 2 (OH)(BTC)(H 2 O)] n ·2nH 2 O) were herein examined. These effects were studied for seven higher plant species: sweet corn (Zea mays L.), black bean (Phaseolus vulgaris L.), tomato (Solanum lycopersicum L.), lettuce (Lactuca sativa L.), celosia (Celosia argentea L.), Aztec marigold (Tagetes erecta L.), and gypsophila (Gypsophila paniculata L.). The studied concentrations of MOFs were 10, 100, 500, or 1000 mg/L, enhancing the percentage of germination and growth of plants in most species. In general, the growth of the root is lower compared to the controls due to the capacity of the MOF to adsorb water and provide micronutrients such as C, O, and Cu, acting as a reserve for the plant. Shoot system growths are more pronounced with HKUST-1 compared with control, and linear polymer, due to the 3D structure adsorbs major water contents. It was found that all studied species are tolerant not only to Cu released from the material, but more evident to Cu structured in MOFs, and this occurs at high concentrations compared to many other systems. Finally, copper fixation was not present, studied by EDX mapping, banning the possibility of metallic phytotoxicity to the tested cultivars., (© 2024. The Author(s).)

Nanoconfined poly(4-methylstyrene) [P(4-MS)] films exhibit reductions in glass transition temperature (Tg) relative to bulk Tg (Tg,bulk). Ellipsometry reveals that 15-nm-thick P(4-MS) films supported on silicon exhibit Tg - Tg,bulk = - 15 °C. P(4-MS) films also exhibit fragility-confinement effects; fragility decreases ∼60% in going from bulk to a 20-nm-thick film. Previous research found that incorporating 2-6 mol  % 2-ethylhexyl acrylate (EHA) comonomer in styrene-based random copolymers eliminates Tg- and fragility-confinement effects in polystyrene. Here, we demonstrate that incorporating 3 mol  % EHA in a 4-MS-based random copolymer, 97/3 P(4-MS/EHA), eliminates the Tg- and fragility-confinement effects. The invariance of fragility with nanoconfinement of 97/3 P(4-MS/EHA) films, hypothesized to originate from the interdigitation of ethylhexyl groups, indicates that the presence of EHA prevents the free surface from perturbing chain packing and the cooperative mobility associated with Tg. This method of eliminating confinement effects is advantageous as it relies on the simplest of polymerization methods and neat copolymer only slightly altered in composition from homopolymer. We also investigated whether we could eliminate the Tg-confinement effect with low levels of 2-ethylhexyl methacrylate (EHMA) in 4-MS-based or styrene-based copolymers. Although EHMA is structurally nearly identical to EHA, 4-MS-based and styrene-based copolymers incorporating 4 mol  % EHMA exhibit Tg-confinement effects similar to P(4-MS) and polystyrene. These results support the special character of EHA in eliminating confinement effects originating at free surfaces., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: This systematic review and meta-analysis aimed to assess the rate of sentinel lymph node (SLN) metastases in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia and endometrial cancer in hysterectomy specimens., Methods: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and the protocol was registered in PROSPERO (CRD42023416769). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2023. The inclusion criteria were patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia undergoing hysterectomy who did or did not undergo SLN assessment., Results: Four studies met the inclusion criteria. All studies were non-randomized studies with a total of 10 217 patients, 1044 in the SLN group and 9173 in the non-nodal assessment group. The unilateral and bilateral detection rate was 89% (I 2 =27.6%, 2 studies, 342 participants, 304 events) and 79% (I 2 =89.2%, 2 studies, 342 participants, 271 events), respectively. The rate of involved SLNs was 1.6% (I 2 =0%, 3 studies, 424 participants, 7 involved SLN) and 3.5% (I 2 =0%, 3 studies, 197 participants, 7 involved SLN) in patients with a pre-operative diagnosis of atypical hyperplasia/endometrial intra-epithelial neoplasia as the denominator and in those with endometrial cancer in the hysterectomy specimen, respectively. The cancer rate in the hysterectomy specimen was 45% (I 2 =72.8%, 3 studies, 503 participants, 224 events) and the most frequent endometrial cancer International Federation of Gynecology and Obstetrics 2009 stage was IA in 199 (89.2%) patients. The complication rate was similar between the groups., Conclusion: The rate of SLN metastases in patients with pre-operative atypical hyperplasia/endometrial intra-epithelial neoplasia is less than 2%, suggesting that routine SLN evaluation may not be necessary in this population., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen accounting for high mortality rates among infected patients. Transcriptomic regulation by small RNAs (sRNAs) has been shown to regulate networks promoting antibiotic resistance and virulence in S. aureus. Yet, the biological role of most sRNAs during MRSA host infection remains unknown. To fill this gap, in collaboration with the lab of Jai Tree, we performed comprehensive RNA-RNA interactome analyses in MRSA using CLASH under conditions that mimic the host environment. Here we present a detailed version of this optimized CLASH (cross-linking, ligation, and sequencing of hybrids) protocol we recently developed, which has been tailored to explore the RNA interactome in S. aureus as well as other Gram-positive bacteria. Alongside, we introduce a compilation of helpful Python functions for analyzing folding energies of putative RNA-RNA interactions and streamlining sRNA and mRNA seed discovery in CLASH data. In the accompanying computational demonstration, we aim to establish a standardized strategy to evaluate the likelihood that observed chimeras arise from true RNA-RNA interactions., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The development of effective recombinant vaccines against parasitic nematodes has been challenging and so far mostly unsuccessful. This has also been the case for Ostertagia ostertagi, an economically important abomasal nematode in cattle, applying recombinant versions of the protective native activation-associated secreted proteins (ASP). To gain insight in key elements required to trigger a protective immune response, the protein structure and N-glycosylation of the native ASP and a non-protective Pichia pastoris recombinant ASP were compared. Both antigens had a highly comparable protein structure, but different N-glycan composition. After mimicking the native ASP N-glycosylation via the expression in Nicotiana benthamiana plants, immunisation of calves with these plant-produced recombinants resulted in a significant reduction of 39% in parasite egg output, comparable to the protective efficacy of the native antigen. This study provides a valuable workflow for the development of recombinant vaccines against other parasitic nematodes., (© 2023. The Author(s).)

Cells use glycans to encode information that modulates processes ranging from cell-cell recognition to programmed cell death. This information is encoded within a glycocode, and its decoding is performed by carbohydrate-binding proteins. Among these, lectins stand out due to their specific and reversible interaction with carbohydrates. Changes in glycosylation patterns are observed in several pathologies, including cancer, where abnormal glycans are found on the surfaces of affected tissues. Given the importance of the bioprospection of promising biomolecules, the current work aimed to determine the structural properties and anticancer potential of the mannose-specific lectin from seeds of Canavalia villosa (Cvill). Experimental elucidation of the primary and 3D structures of the lectin, along with glycan array and molecular docking, facilitated the determination of its fine carbohydrate-binding specificity. These structural insights, coupled with the lectin's specificity, have been combined to explain the antiproliferative effect of Cvill against cancer cell lines. This effect is dependent on the carbohydrate-binding activity of Cvill and its uptake in the cells, with concomitant activation of autophagic and apoptotic pathways.

Colorectal Cancer (CRC) and Obesity constitute two of the most common malignancies in the western world, and previously have been associated with intestinal microbial composition alterations. Our main aim in this study is to provide molecular data on intestinal microbiota patterns in subjects with CRC, as well as to establish possible associations with their Body Mass Index (BMI). A total of 113 samples from 45 subjects were collected and submitted to metagenomics analysis for gut microbiota. This study was performed by 16S ribosomal RNA bacterial gene amplification and sequencing using the Ion Torrent™ technology. The same dominant phyla were observed in feces and colorectal tissues, although a greater proportion of Fusobacteriota was found in tumor samples. Moreover, at the genus level, LEfSe analysis allowed us to detect a significant increase in Fusobacterium and Streptococcus in colorectal tissues with respect to fecal samples, with a significant preponderance of Fusobacterium in tumor tissues. Also, our data revealed relevant associations between gut microbiota composition and tumor location. When comparing bacterial profiles between right and left colon cancers, those from the left-sided colon showed a significant preponderance, among others, of the order Staphylococcales. Moreover, phyla Firmicutes and Spirochaetota were more abundant in the group of right-sided CRCs and phylum Proteobacteria was increased in rectal cancers. In relation to BMI of patients, we detected significant differences in beta diversity between the normal weight and the obese groups of cases. Microbiota from obese patients was significantly enriched, among others, in Bacteroidales. Therefore, our results are useful in the molecular characterization of CRC in obese and non-obese patients, with a clear impact on the establishment of diagnostic and prognosis of CRC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tesolato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

RNA-binding proteins (RBPs) govern the lifespan of nearly all transcripts and play key roles in adaptive responses in microbes. A robust approach to examine protein-RNA interactions involves irradiating cells with UV light to form covalent adducts between RBPs and their cognate RNAs. Combined with RNA or protein purification, these procedures can provide global RBP censuses or transcriptomic maps for all target sequences of a single protein in living cells. The recent development of novel methods has quickly populated the RBP landscape in microorganisms. Here, we provide an overview of prominent UV cross-linking techniques which have been applied to investigate RNA interactomes in microbes. By assessing their advantages and caveats, this technical evaluation intends to guide the selection of appropriate methods and experimental design as well as to encourage the use of complementary UV-dependent techniques to inspect RNA-binding activity., (© 2023 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

The isolation from organisms and readily available glycoproteins has become an increasingly convenient source of N-glycans for multiple applications including glycan microarrays, as reference standards in glycan analysis or as reagents that improve bioavailability of protein and peptide therapeutics through conjugation. A problematic step in the isolation process on a preparative scale can be the attachment of a linker for the improved purification, separation, immobilization and quantification of the glycan structures. Addressing this issue, we firstly aimed for the development of an UV active linker for a fast and reliable attachment to anomeric glycosylamines via urea bond formation. Secondly, we validated the new linker on glycan arrays in a comparative study with a collection of N-glycans which were screened against various lectins. In total, we coupled four structurally varied N-glycans to four different linkers, immobilized all constructs on a microarray and compared their binding affinities to four plant and fungal lectins of widely described specificity. Our study shows that the urea type linker showed an overall superior performance for lectin binding and once more, highlights the often neglected influence of the choice of linker on lectin recognition., (© 2023 Wiley-VCH GmbH.)

m6A methylation provides an essential layer of regulation in organismal development, and is aberrant in a range of cancers and neuro-pathologies. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by RNA binding proteins that recognise methylated sites, the m6A readers. m6A readers include a well-characterised class of dedicated proteins, the YTH proteins, as well as a broader group of multi-functional regulators where recognition of m6A is only partially understood. Molecular insight in this recognition is essential to build a mechanistic understanding of global m6A regulation. In this study, we show that the reader IMP1 recognises the m6A using a dedicated hydrophobic platform that assembles on the methyl moiety, creating a stable high-affinity interaction. This recognition is conserved across evolution and independent from the underlying sequence context but is layered upon the strong sequence specificity of IMP1 for GGAC RNA. This leads us to propose a concept for m6A regulation where methylation plays a context-dependent role in the recognition of selected IMP1 targets that is dependent on the cellular concentration of available IMP1, differing from that observed for the YTH proteins., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The Brussels sprout ( Brassica oleracea var. gemmifera ) is a cruciferous vegetable with high health-promoting value and Mexico is one of the most valuable exporters worldwide (Data Mexico 2023). From September to November 2021, white mold symptoms (Rimmer et al. 2007) were observed in Brussels sprouts (cv. Confidant) fields in Tonatico, Estado de México, Mexico. Irregular, necrotic lesions were observed on leaves, whereas abundant white mycelium, and later black sclerotia were produced outside and inside of stems. Disease incidence ranged from 20 to 40% in five fields. For fungal isolation, symptomatic stem pieces were surface sterilized with 2% sodium hypochlorite for 2 min, rinsed in sterilized distilled water twice, placed on PDA medium, and incubated at 25°C in darkness for 3 days. Sclerotinia -like colonies were consistently obtained and six isolates were purified by the hyphal-tip method. Fungal colonies were white and fluffy. Irregular, black, and small (3 to 6 mm diameter) sclerotia were produced at the edge of colonies after 5 days of incubation. The morphological characters were consistent with those of Sclerotinia sclerotiorum (Saharan and Mehta 2008). Two representative isolates were selected for molecular analysis and pathogenicity tests. The isolates were deposited in the Culture Collection of Phytopathogenic Fungi at the Colegio Superior Agropecuario del Estado de Guerrero under the accession numbers CSAEG50 and CSAEG51. For molecular identification, genomic DNA was extracted, and the internal transcribed spacer (ITS) region was amplified by PCR and sequenced using the primer pair ITS5/ITS4 (White et al. 1990). The sequences were deposited in GenBank (accession nos. OQ878510 and OQ878511). BLASTn searches in GenBank showed 100% identity with the available sequences of Sclerotinia sclerotiorum (accession nos. OQ891471, OQ891472, HQ833448, and MT177216). A phylogenetic analysis using the Maximum Likelihood method placed isolates CSAEG50 and CSAEG51 in the same clade as S. sclerotiorum . Pathogenicity tests were performed by inoculating 10 healthy Brussels sprout seedlings (cv. Confidant) grown in pots. A mycelial plug was directly placed on the stem of each plant. Five uninoculated Brussels sprout seedlings were used as control. All plants were placed in a moist chamber at 25°C with a 12-h photoperiod for 2 days. White mold symptoms appeared on inoculated plants after 3 days, whereas control plants remained symptomless. The fungi were reisolated from the infected plants and found to be morphologically identical to the isolates used for inoculation, fulfilling Koch's postulates. Pathogenicity test was performed twice with similar results. Sclerotinia sclerotiorum has been previously reported to infect Brussels sprouts in the USA (Campbell 1947). To our knowledge, this is the first report of Sclerotinia sclerotiorum causing white mold of Brussels sprouts in Mexico. The disease is widely distributed in Brussels sprouts fields in the central region of Mexico, therefore additional studies are needed to develop effective disease-management strategies.

Objective: The objective of this systematic review was to assess the oncologic outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IVB cervical cancer receiving definitive pelvic radiotherapy compared with systemic chemotherapy (with or without palliative pelvic radiotherapy)., Methods: This study was registered in PROSPERO (registration number CRD42022333433). A systematic literature review was conducted following the MOOSE checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until August 2022. The inclusion criteria were patients with metastatic FIGO 2018 stage IVB cervical cancer, a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma that received definitive pelvic radiotherapy (≥45 Gy) as part of management compared with systemic chemotherapy with or without palliative (30 Gy) pelvic radiotherapy. Randomized controlled trials and observational studies with two arms of comparison were considered., Results: The search identified 4653 articles; 26 studies were considered potentially eligible after removing duplicates, and 8 met the selection criteria. In total, 2424 patients were included. There were 1357 and 1067 patients in the definitive radiotherapy and chemotherapy groups, respectively. All included studies were retrospective cohort studies, and two were database population studies. The median overall survival reported in seven studies for the definitive radiotherapy arm versus systemic chemotherapy groups were 63.7 months versus 18.4 months (p<0.01), 14 months versus 16 months (p value not reported), 17.6 months versus 10.6 months (p<0.01), 32 months versus 24 months (p<0.01), 17.3 months versus 10 months (p<0.01), and 41.6 months versus 17.6 months (p<0.01), and not reached versus 19 months (p=0.13) respectively, favoring the groups that received definitive pelvic radiotherapy. The high clinical heterogeneity precluded the performance of meta-analysis, and all studies were at serious risk of bias., Conclusions: Definitive pelvic radiotherapy as part of treatment in patients with stage IVB cervical cancer may improve oncologic outcomes compared with systemic chemotherapy (with or without palliative radiotherapy); however, this is based on low-quality data. Prospective evaluation would be ideal before the adoption of this intervention in standard clinical practice., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The FimH type-1 fimbrial adhesin allows pathogenic Escherichia coli to adhere to glycoproteins in the epithelial linings of human bladder and intestinal tract, by using multiple fimbriae simultaneously. Pauci- and high-mannose type N-glycans are natural FimH receptors on those glycoproteins. Oligomannose-3 and oligomannose-5 bind with the highest affinity to FimH by using the same Manα1,3Man branch. Oligomannose-6 is generated from oligomannose-5 in the next step of the biogenesis of high-mannose N-glycans, by the transfer of a mannose in α1,2-linkage onto this branch. Using serial crystallography and by measuring the kinetics of binding, we demonstrate that shielding the high-affinity epitope drives the binding of multiple FimH molecules. First, we profiled FimH glycan binding on a microarray containing paucimannosidic N-glycans and in a FimH LEctPROFILE assay. To make the transition to oligomannose-6, we measured the kinetics of FimH binding using paucimannosidic N-glycans, glycoproteins and all four α-dimannosides conjugated to bovine serum albumin. Equimolar mixed interfaces of the dimannosides present in oligomannose-6 and molecular dynamics simulations suggest a positive cooperativity in the bivalent binding of Manα1,3Manα1 and Manα1,6Manα1 dimannosides. The binding of core α1,6-fucosylated oligomannose-3 in cocrystals of FimH is monovalent but interestingly the GlcNAc1-Fuc moiety retains highly flexibility. In cocrystals with oligomannose-6, two FimH bacterial adhesins bind the Manα1,3Manα1 and Manα1,6Manα1 endings of the second trimannose core (A-4'-B). This cooperative switch towards bivalent binding appears sustainable beyond a molar excess of oligomannose-6. Our findings provide important novel structural insights for the design of multivalent FimH antagonists that bind with positive cooperativity., Competing Interests: Conflict of interest N.-C. R. is CEO and shareholder of Asparia Glycomics S.L., a company commercializing glycoscience products and services., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The evolution of some fetal growth indices and arterial blood flow parameters in the umbilical cord of the embryos and fetuses of primiparous pregnant goats of Murciano-Granadina breed were analyzed by ultrasonography. Weekly ultrasonographic sessions took place from 18- to 125-days post-breeding. Fetal measures were carried out by ultrasound B-mode. This mode was used to take a series of measurements in the embryo/fetus throughout pregnancy: crown-rump length (CRL, from 24-days post-mating -dpm- to 61 dpm), trunk diameter (TD, 24-34 dpm), biparietal diameter (BPD, 28-125 dpm) and eye orbit diameter (EOD, 75-125 dpm). Spectral Doppler was used to study blood flow from umbilical artery. Different blood flow parameters were obtained as follows: Arterial Pulse, Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), Mean Velocity (MV), Systolic velocity/Diastolic velocity Ratio (S/D), Pulsatility Index (PI) and Resistance Index (RI). In this study, the umbilical cord was first noticed between 32- and 35-days post-breeding. However, these umbilical arterial blood flow parameters were not conclusive (positive S/D ratios and RI < 1) until 65-80 days of pregnancy. The explanation to these results could be that vascular development related to umbilical arteries elasticity and diameter is not good enough in early pregnancy. Therefore, these vessels have already acquired their appropriate characteristics in order to allow blood flow parameters and Doppler index measures from only 2.5 months of pregnancy. This is the first time that a detailed study of fetal growth indices and umbilical artery flow rates in fetuses from Murciano-Granadina goats has been performed throughout virtually the entire duration of gestation. In conclusion, the evolution of the fetal growth indices in this breed has determined that the umbilical artery velocimetric parameters (PSV, EDV, MV) increase significantly and the AP, S/D, PI and RI indices decrease significantly throughout the analyzed pregnancy period., Competing Interests: The authors declare no conflict of interest.

Objective: To assess the rate of pathological response rate, and the oncological outcomes of preoperative brachytherapy (PBT) in early-stage cervical cancer., Methods: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA) statement. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from inception until April 2022. Only English and French articles were included. Studies containing data about pathology response or oncological outcomes among patients who received PBT as compared to those who underwent up-front surgery in early-stage cervical cancer were included. This study was registered in PROSPERO (CRD42022319036)., Results: Thirteen studies met the inclusion criteria, 3 randomized controlled trials (RCT), and 10 non-randomized studies (NRS). The 5-year survival was significantly higher in the PBT group compared with the up-front surgery group (OR 1.78, 95% CI 1.11-2.84, I 2  = 0%) in the NRS. Recurrence rate was significantly lower in the PBT group compared with in up-front surgery group in the analysis of the RCT but not in NRS, (OR 0.34, 95% CI 0.13-0.91, I 2 not applicable) and (OR 0.72, 95% CI 0.26-1.95, I 2  = 51%) respectively. PBT was associated with a statistically significant lower rate of positive margins (OR 0.28, 95% CI 0.09-0.89; I 2  = 42%) in the RCT and with a significantly higher rate of complete pathology response (CPR) in the RCT analysis (OR 2.55, 95% CI 1.11-5.85, I 2  = 0%) and in the NRS (OR 9.64, 95% CI 1.88-49.48, I 2  = 76%) compared with the up-front surgery group., Conclusion: Preoperative brachytherapy in patients with early-stage cervical cancer could improve pathologic and oncologic outcomes, but it should be assessed in high-quality randomized controlled trials before its implementation in clinical practice., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The Dalbergieae lectin group encompasses several lectins with significant differences in their carbohydrate specificities and biological properties. The current work reports on the purification and characterization of a GalNAc/Gal-specific lectin from Vataireopsis araroba (Aguiar) Ducke, designated as VaL. The lectin was purified from the seeds in a single step using guar gum affinity chromatography. The lectin migrated as a single band of about 35 kDa on SDS-PAGE and, in native conditions, occurs as a homodimer. The purified lectin is stable at temperatures up to 60 °C and in a pH range from 7 to 8 and requires divalent cations for its activity. Sugar-inhibition assays demonstrate the lectin specificity towards N-acetyl-D-galactosamine, D-galactose and related sugars. Furthermore, glycan array analyses show that VaL interacts preferentially with glycans containing terminal GalNAc/Galβ1-4GlcNAc. Biological activity assays were performed using three insect cell lines: CF1 midgut cells from the spruce budworm Choristoneura fumiferana, S2 embryo cells from the fruit fly Drosophila melanogaster, and GutAW midgut cells from the corn earworm Helicoverpa zea. In vitro assays indicated a biostatic effect for VaL on CF1 cells, but not on S2 and GutAW cells. The lectin presented a biostatic effect by reducing the cell growth and inducing cell agglutination, suggesting an interaction with glycans on the cell surface. VaL has been characterized as a galactoside-specific lectin of the Dalbergieae tribe, with sequence similarity to lectins from Vatairea and Arachis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The generation of genetically modified pigs has an important impact thanks its applications in basic research, biomedicine, and meat production. Cloning was the first technique used for this production, although easier and cheaper methods were developed, such as the microinjection, electroporation, or lipofection of oocytes and zygotes. In this study, we analyzed the production of genetically modified embryos via lipofection of zona-pellucida-intact oocytes using Lipofectamine TM CRISPRMAX TM Cas9 in comparison with the electroporation method. Two factors were evaluated: (i) the increment in the concentration of the lipofectamine-ribonucleoprotein complexes (LRNPC) (5% vs. 10%) and (ii) the concentration of ribonucleoprotein within the complexes (1xRNP vs. 2xRNP). We found that the increment in the concentration of the LRNPC had a detrimental effect on embryo development and a subsequent effect on the number of mutant embryos. The 5% group had a similar mutant blastocyst rate to the electroporation method (5.52% and 6.38%, respectively, p > 0.05). The increment in the concentration of the ribonucleoprotein inside the complexes had no effect on the blastocyst rate and mutation rate, with the mutant blastocyst rate being similar in both the 1xRNP and 2xRNP lipofection groups and the electroporation group (1.75%, 3.60%, and 3.57%, respectively, p > 0.05). Here, we showed that it is possible to produce knock-out embryos via lipofection of zona-pellucida-intact porcine oocytes with similar efficiencies as with electroporation, although more optimization is needed, mainly in terms of the use of more efficient vesicles for encapsulation with different compositions.

The co-packaging of optics and electronics provides a potential path forward to achieving beyond 50 Tbps top of rack switch packages. In a co-packaged design, the scaling of bandwidth, cost, and energy is governed by the number of optical transceivers (TxRx) per package as opposed to transistor shrink. Due to the large footprint of optical components relative to their electronic counterparts, the vertical stacking of optical TxRx chips in a co-packaged optics design will become a necessity. As a result, development of efficient, dense, and wide alignment tolerance chip-to-chip optical couplers will be an enabling technology for continued TxRx scaling. In this paper, we propose a novel scheme to vertically couple into standard 220 nm silicon on insulator waveguides from 220 nm silicon nitride on glass waveguides using overlapping, inverse double tapers. Simulation results using Lumerical's 3D Finite Difference Time Domain solver are presented, demonstrating insertion losses below -0.13 dB for an inter-chip spacing of 1 µm; 1 dB vertical and lateral alignment tolerances of approximately 2.6 µm and ± 2.8 µm, respectively; a greater than 300 nm 1 dB bandwidth; and 1 dB twist and tilt tolerances of approximately ± 2.3 degrees and 0.4 degrees, respectively. These results demonstrate the potential of our coupler for use in co-packaged designs requiring high performance, high density, CMOS compatible out of plane optical connections.

Surface microbial colonization and its potential biofilm formation are currently a major unsolved problem, causing almost 75% of human infectious diseases. Pathogenic biofilms are capable of surviving high antibiotic doses, resulting in inefficient treatments and, subsequently, raised infection prevalence rates. Antibacterial coatings have become a promising strategy against the biofilm formation in biomedical devices due to their biocidal activity without compromising the bulk material. Here, we propose for the first time a silver-based metal-organic framework (MOF; here denoted AgBDC ) showing original antifouling properties able to suppress not only the initial bacterial adhesion, but also the potential surface contamination. Firstly, the AgBDC stability (colloidal, structural and chemical) was confirmed under bacteria culture conditions by using agar diffusion and colony counting assays, evidencing its biocide effect against the challenging E. coli , one of the main representative indicators of Gram-negative resistance bacteria. Then, this material was shaped as homogeneous spin-coated AgBDC thin film, investigating its antifouling and biocide features using a combination of complementary procedures such as colony counting, optical density or confocal scanning microscopy, which allowed to visualize for the first time the biofilm impact generated by MOFs via a specific fluorochrome, calcofluor.

Three silver-MOFs were prepared using an optimized, room-temperature methodology starting from AgNO₃ and dicarboxylate ligands in water/ethanol yielding Ag 2 BDC , Ag 2 NDC ( UAM-1 ), and Ag 2 TDC ( UAM-2 ) at 38%-48% (BDC, benzenedicarboxylate; NDC, 1,8-naphthalene-dicarboxylate; TDC, p-terphenyl-4,4″-dicarboxylate). They were characterized by PXRD/FT-IR/TGA/photoluminescence spectroscopy, and the former two by SEM. These materials started decomposing at 330°C, while showing stability. The crystal structure of UAM-1 was determined by PXRD, DFT calculations, and Rietveld refinement. In general, the structure was 3D, with the largest Ag-O bond interlinking 2D layers. The FT-IR spectra revealed 1450 and 1680 bands (cm -1 ) of asymmetrically stretching aniso-/iso-bidentate -COO in coordination with 2/3-Ag atoms, accompanied by Ag-O bands at 780-740 cm -1 , all demonstrating the network formation. XRD and SEM showed nanometric-scale crystals in Ag₂BDC were evaluated in PBS/DMEM/DMEM+FBS media by XRD, which showed that they lost their crystallinity, resulting in AgCl due to soft-soft (Pearson's principle) affinity.UAM-1 developed micrometric single-stranded/agglomerated fibrillar particles of varying nanometric widths. Luminescence spectroscopy showed emission by Ag₂BDC , which was attributed to ligand-to-metal or ligand-to-metal-metal transitions, suggesting energy transfer due to the short distance between adjacent BDC molecules. UAM-1 and UAM-2 did not show luminescence emission attributable to ligand-to-metal transition; rather, they presented only UV emission. The stabilities of Ag₂BDC and UAM-1 were evaluated in PBS/DMEM/DMEM+FBS media by XRD, which showed that they lost their crystallinity, resulting in AgCl due to soft-soft (Pearson's principle) affinity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Celis-Arias, Garduño-Wilchis, Alarcón, González Chávez, Garrido Guerrero, Beltrán and Loera-Serna.)

The molecular recognition features of LSECtin toward asymmetric N-glycans have been scrutinized by NMR and compared to those occurring in glycan microarrays. A pair of positional glycan isomers (LDN3 and LDN6), a nonelongated GlcNAc4Man3 N-glycan (G0), and the minimum binding epitope (the GlcNAcβ1-2Man disaccharide) have been used to shed light on the preferred binding modes under both experimental conditions. Strikingly, both asymmetric LDN3 and LDN6 N-glycans are recognized by LSECtin with similar affinities in solution, in sharp contrast to the results obtained when those glycans are presented on microarrays, where only LDN6 was efficiently recognized by the lectin. Thus, different results can be obtained using different experimental approaches, pointing out the tremendous difficulty of translating in vitro results to the in vivo environment., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Intravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of infliximab [CT-P13] has recently been shown to be as effective as IV infliximab after two doses of IV induction in a randomised trial, but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching programme to SC CT-P13 in patients treated with IV infliximab., Methods: Patients on established maintenance IV infliximab, who switched to SC CT-P13, were included in this retrospective multicentre cohort study. Disease activity was monitored serially with the Harvey-Bradshaw Index [HBI] for Crohn's disease [CD] and the Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis (UC) for up to 12 months at months 3, 6, and 12. Faecal calprotectin [FC] and C-reactive protein [CRP] were recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6, and 12 following switch. The primary outcome measure was treatment persistence at latest follow-up. Secondary outcome measures included infliximab pharmacokinetics [PK], safety, need for corticosteroid rescue therapy, and need for surgery., Results: We included 181 patients, of whom 115 [63.5%] had CD. The majority [72.4%] were on 8-weekly dosing of intravenous infliximab prior to switching, and more than half [59.1%] were on concomitant immunomodulatory therapy. The majority of patients (CD: 106, 92.2%; UC: 46, 76.7%; and IBD unclassified [IBD-U]: 5, 83.3%) were in clinical remission. Treatment persistence rate was high [n = 167, 92.3%] and only 14 patients [7.7%] stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6, or 12 months for HBI, SCCAI, CRP, or FC. Of the total cohort, 25 patients (13.8%) had perianal CD. Of these, only two patients [8%] had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia [EUA]. Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl [range 0.4-16] to 16.0 µg/dl [range 2.3-16, p <0.001] at 3 months. Serum levels stayed stable at 6 months [median 16 µg/dl, range 0.3-17.2] and 12 months [median 16 µg/dl, range 0.3-19.1, both p <0.001 compared with baseline]. Among the variables examined, only antibodies to infliximab [ATI] was associated with infliximab levels (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, p <0.001]. A total of 14 patients [7.7%] developed ATI; of these, nine [64.3%] were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI [p = 0.15]. In a subset of patients receiving escalated IV infliximab dosing frequency prior to switching, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high., Conclusions: Among patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity, with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13, and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Porous materials are currently the basis of many optical sensors because of their ability to provide a higher interaction between the light and the analyte, directly within the optical structure. In this study, mesoporous TiO 2 layers were fabricated using a bottom-up synthesis approach in order to develop optical sensing structures. In comparison with more typical top-down fabrication strategies where the bulk constitutive material is etched in order to obtain the required porous medium, the use of a bottom-up fabrication approach potentially allows increasing the interconnectivity of the pore network, hence improving the surface and depth homogeneity of the fabricated layer and reducing production costs by synthesizing the layers on a larger scale. The sensing performance of the fabricated mesoporous TiO 2 layers was assessed by means of the measurement of several glucose dilutions in water, estimating a limit of detection even below 0.15 mg/mL (15 mg/dL). All of these advantages make this platform a very promising candidate for the development of low-cost and high-performance optical sensors.

Each year, tens of thousands of people worldwide die of end-stage organ failure due to the limited availability of organs for use in transplantation. To meet this clinical demand, one of the last frontiers of regenerative medicine is the generation of humanized organs in pigs from pluripotent stem cells (PSCs) via blastocyst complementation. For this, organ-disabled pig models are needed. As endothelial cells (ECs) play a critical role in xenotransplantation rejection in every organ, we aimed to produce hematoendothelial-disabled pig embryos targeting the master transcription factor ETV2 via CRISPR-Cas9-mediated genome modification. In this study, we designed five different guide RNAs (gRNAs) against the DNA-binding domain of the porcine ETV2 gene, which were tested on porcine fibroblasts in vitro. Four out of five guides showed cleavage capacity and, subsequently, these four guides were microinjected individually as ribonucleoprotein complexes (RNPs) into one-cell-stage porcine embryos. Next, we combined the two gRNAs that showed the highest targeting efficiency and microinjected them at higher concentrations. Under these conditions, we significantly improved the rate of biallelic mutation. Hence, here, we describe an efficient one-step method for the generation of hematoendothelial-disabled pig embryos via CRISPR-Cas9 microinjection in zygotes. This model could be used in experimentation related to the in vivo generation of humanized organs.

Limb girdle muscular dystrophy type R1 (LGMDR1) is an autosomal recessive myopathy described in humans resulting from a deficiency of calpain-3 protein (CAPN3). This disease lacks effective treatment and an appropriate model, so the generation of KO pigs by CRISPR-Cas9 offers a way to better understand disease ethology and to develop novel therapies. Microinjection is the main method described for gene editing by CRISPR-Cas9 in porcine embryo, but electroporation, which allows handling more embryos faster and easier, has also recently been reported. The objective of the current study was to optimize porcine oocyte electroporation to maximize embryo quality and mutation rate in order to efficiently generate LGMDR1 porcine models. We found that the efficiency of generating CAPN3 KO embryos was highest with 4 electroporation pulses and double sgRNA concentration than microinjection. Direct comparison between microinjection and electroporation demonstrated similar rates of embryo development and mutation parameters. The results of our study demonstrate that oocyte electroporation, an easier and faster method than microinjection, is comparable to standard approaches, paving the way for democratization of transgenesis in pigs., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

During the COVID-19 pandemic, there was a growing need to characterise the disease. A very important aspect is the ability to measure the immunisation extent, which can be achieved using antigen microarrays that quantitively measure the presence of COVID-related antibodies. A significant limitation for these tests was the complexity of manually analysing the results, and the limited availability of software for its analysis. In this paper, we describe the development of COVID-BIOCHIP, an ad-hoc web-based solution for the automatic analysis and visualisation of COVID-19 antigen microarray data results.