Tandem Approach Research Articles

(Micro-)Plastics in Saturated and Unsaturated Groundwater Bodies: First Evidence of Presence in Groundwater Fauna and Habitats

Microplastic (MP) pollution is a growing concern in every known ecosystem. However, MP presence in groundwaters and the ecological impact they can have on groundwater fauna is still poorly investigated. Here, we assess the presence of MPs in three Italian groundwater bodies, comprising two karst caves and two monitoring bores of a saturated alluvial aquifer. In addition to water samples, groundwater invertebrates were collected to assess their potential ingestion of MPs. For water samples, chemical characterization of polymers was done by Fourier Transform Infrared Spectroscopy (FTIR) 2D imaging, while fauna samples were analyzed with a tandem microscopy approach (fluorescence microscopy and FTIR). The abundance of MPs in water samples varied from 18 to 911 items/L. The majority of MPs were fibers (91%), with a mean size in the range of 100 µm and 1 mm. Black, red, and blue were the most abundant colors (30%, 25%, and 19%, respectively). The most abundant polymer was artificial/textile cellulose (65%), followed by PET (21%). MPs were found in every groundwater taxon. Pellets were the most abundant in each specimen (87% on average), while the largest were fragments, with a mean dimension of 26 µm. Cellulose was found to be the most abundant polymer (51%). This study is the first to highlight the presence of MPs ingested by groundwater fauna. Further investigations are urgently required to assess the potential ecological impact MPs can have on the resident fauna in these sensitive ecosystems.

Rapid exometabolome footprinting combined with multivariate statistics: A powerful tool for bioprocess optimization

AbstractCorynebacterium glutamicumis used as an industrial platform organism for amino acid production. Previously, the organism was utilized to producel‐histidine with research focusing on metabolic engineering approaches to increase titer and yield. Only a few studies have been published that provide information on bioprocess development, with media optimization and fed‐batch cultivation procedure being particularly promising areas. In this work, we show how experimental setups such as miniature cultivation technology, dynamic and time‐optimized LC‐MS/MS metabolic footprinting tools, and automated workflows for the detection of local and global metabolic patterns can significantly accelerate bioprocess development. Potential media bottlenecks in form of phosphate and magnesium availability were identified by sensitivity analysis in parallelized microscale cultivation assisted by lab automation. A rapid dilute‐and‐shoot flow‐injection‐analysis tandem mass spectrometry approach was used to cope with the resulting cultivation throughput and allowed to quantify amino acids with 1 min per sample. We were able to increase thel‐histidine titer of aC. glutamicumrandom mutagenesis mutant by a factor of 5.8 through process optimization while also identifying both known and previously unknown targets for additional strain improvements. The presented methodology can be seen as a supplement to traditional approaches in the field of bioprocess development.

Tandem clustering with invariant coordinate selection

For multivariate data, tandem clustering is a well-known technique aiming to improve cluster identification through initial dimension reduction. Nevertheless, the usual approach using principal component analysis (PCA) has been criticized for focusing solely on inertia so that the first components do not necessarily retain the structure of interest for clustering. To address this limitation, a new tandem clustering approach based on invariant coordinate selection (ICS) is proposed. By jointly diagonalizing two scatter matrices, ICS is designed to find structure in the data while providing affine invariant components. Certain theoretical results have been previously derived and guarantee that under some elliptical mixture models, the group structure can be highlighted on a subset of the first and/or last components. However, ICS has garnered minimal attention within the context of clustering. Two challenges associated with ICS include choosing the pair of scatter matrices and selecting the components to retain. For effective clustering purposes, it is demonstrated that the best scatter pairs consist of one scatter matrix capturing the within-cluster structure and another capturing the global structure. For the former, local shape or pairwise scatters are of great interest, as is the minimum covariance determinant (MCD) estimator based on a carefully chosen subset size that is smaller than usual. The performance of ICS as a dimension reduction method is evaluated in terms of preserving the cluster structure in the data. In an extensive simulation study and empirical applications with benchmark data sets, various combinations of scatter matrices as well as component selection criteria are compared in situations with and without outliers. Overall, the new approach of tandem clustering with ICS shows promising results and clearly outperforms the PCA-based approach.

Opportunities for CO 2 upgrading to C 3 oxygenates using tandem electrocatalytic-thermocatalytic processes

Catalytic conversion of CO₂ to value-added chemicals represents a pathway for mitigating CO₂ emissions. Many recent studies have demonstrated promising results of CO₂ conversion by either thermocatalysis or electrocatalysis. In this article, we discuss tandem electrocatalytic-thermocatalytic processes that potentially have advantages over either process alone. We use the conversion of CO₂ to propanal/propanol as a case study to illustrate the feasibility of the tandem process. We also discuss opportunities and challenges for converting CO₂ using tandem electrocatalytic-thermocatalytic approaches.

Mass Spectrometry Imaging and Histology for the Analysis of Budding Intestinal Organoids.

Three-dimensional (3D) organoids have been at the forefront of regenerative medicine and cancer biology fields for the past decade. However, the fragile nature of organoids makes their spatial analysis challenging due to their budding structures and composition of single layer of cells. The standard sample preparation approaches can collapse the organoid morphology. Therefore, in this study, we evaluated several approaches to optimize a method compatible with both mass spectrometry imaging (MSI) and immunohistological techniques. Murine intestinal organoids were used to evaluate embedding in gelatin, carboxymethylcellulose (CMC)-gelatin-CMC-sucrose, or hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) solutions. Organoids were assessed with and without aldehyde fixation and analyzed for lipid distributions by MSI coupled with hematoxylin and eosin (H&E) staining and immunofluorescence (IF) in consecutive sections from the same sample. While chemical fixation preserves morphology for better histological outcomes, it can lead to suppression of the matrix-assisted laser desorption/ionization (MALDI) lipid signal. By contrast, leaving organoid samples unfixed enhanced MALDI lipid signal. The method that performed best for both MALDI and histological analysis was embedding unfixed samples in HPMC and PVP. This approach allowed assessment of cell proliferation by Ki67 while also identifying putative phosphatidylethanolamine (PE(18:0/18:1)), which was confirmed further by tandem MS approaches. Overall, these protocols will be amenable to multiplexing imaging mass spectrometry analysis with several histological assessments and help advance our understanding of the biological processes that take place in district subsets of cells in budding organoid structures.

Tandem catalysis enables chlorine-containing waste as chlorination reagents

Chlorinated compounds are ubiquitous. However, accumulation of chlorine-containing waste has a negative impact on human health and the environment due to the inapplicability of common disposal methods, such as landfill and incineration. Here we report a sustainable approach to valorize chlorine-containing hydrocarbon waste, including solids (chlorinated polymers) and liquids (chlorinated solvents), based on copper and palladium catalysts with a NaNO3 promoter. In the process, waste is oxidized to release the chlorine in the presence of N-directing arenes to afford valuable aryl chlorides, such as the FDA-approved drug vismodegib. The remaining hydrocarbon component is mineralized to afford CO, CO2 and H2O. Moreover, the CO and CO2 generated could be further utilized directly. Thus, chlorine-containing hydrocarbon waste, including mixed waste, can serve as chlorination reagents that neither generate hazardous by-products nor involve specialty chlorination reagents. This tandem catalytic approach represents a promising method for the viable management of a wide and diverse range of chlorine-containing hydrocarbon wastes.

Three-Minute Enantioselective Amino Acid Analysis by Ultra-High-Performance Liquid Chromatography Drift Tube Ion Mobility-Mass Spectrometry Using a Chiral Core-Shell Tandem Column Approach.

Fast liquid chromatography (LC) amino acid enantiomer separation of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatives using a chiral core-shell particle tandem column with weak anion exchange and zwitterionic-type quinine carbamate selectors in less than 3 min was achieved. Enantiomers of all AQC-derivatized proteinogenic amino acids and some isomeric ones (24 in total plus achiral glycine) were baseline separated (Rs > 1.5 except for glutamic acid with Rs = 1.3), while peaks of distinct amino acids and structural isomers (constitutional isomers and diastereomers of leucine and threonine) of the same configuration overlapped to various degrees. For this reason, drift tube ion mobility-mass spectrometry was added (i.e., LC-IM-MS) as an additional selectivity filter without extending run time. The IM separation dimension in combination with high-resolution demultiplexing enabled confirmation of threonine isomers (threonine, allo-threonine, homoserine), while leucine, isoleucine, and allo-isoleucine have almost identical collisional cross-section (DTCCSN2) values and added no selectivity to the partial LC separation. Density functional theory (DFT) calculations show that IM separation of threonine isomers was possible due to conformational stabilization by hydrogen bond formation between the hydroxyl side chain and the urea group. Generally, the CCSN2 of protonated ions increased uniformly with addition of the AQC label, while outliers could be explained by consideration of intramolecular interactions and additional structural analysis. Preliminary validation of the enantioselective LC-IM-MS method for quantitative analysis showed compliance of accuracy and precision with common limits in bioanalytical methods, and applicability to a natural lipopeptide and a therapeutic synthetic peptide could be demonstrated.

Urea-Promoted Neat Synthesis of Fused Dihydroisoquinolines and Disubstituted Pyridines: A Mechanistic Observation with Molecular-Sensing Studies.

An efficient and short synthesis of fused dihydroisoquinolines, diaryl substituted pyridine derivatives in good to high yields has been established by using an environmentally safe, solvent-metal-oxidant-free tandem approach. In this article, we discuss how the electrocyclic reaction is more pronounced in the solid phase in the presence of urea, whereas the typical aza-Michael addition is more prominent in presence of arylamine in the solution phase for 3-(2-formylcycloalkenyl)acrylic ester derivative substrates. The wide range of substrates and urea-promoted neat synthesis made our approach more significant in medical and also analytical science. Moreover, an isoquinoline alkaloid decumbenine B analogue has been synthesized by using our newly developed neat methodology. We have also investigated the photophysical properties of the synthesized fused dihydroisoquinoline derivatives. One of the synthesized molecules was used as a sensor for the selective detection of toxic picric acid. Therefore, the effective neat synthesis and molecular sensing applications of these compounds made our approach more exciting in the field of heterocyclic chemistry.

Cucumber mosaic virus-induced gene and microRNA silencing in water dropwort (Oenanthe javanica (Blume) DC)

Water dropwort (Oenanthe javanica (Blume) DC), an aquatic perennial plant from the Apiaceae family, rich in dietary fibert, vitamins, and minerals. It usually grows in wet soils and water. Despite accumulating the transcriptomic data, gene function research on water dropwort is still far behind than that of the other crops. The cucumber mosaic virus (CMV) induced gene silencing was established to study the functions of gene and microRNA (miRNA) in the water dropwort. CMV Fast New York strain (CMV-Fny) genomic RNAs 1, 2, and 3 were individually cloned into pCB301 vectors. We deleted part of the ORF 2b region and introduced recognition sites. A CMV-induced gene silencing vector was employed to suppress the expression of endogenous genes, including phytoene desaturase (PDS). In order to assess the efficacy of gene silencing, we also cloned conserved sequence of gibberellin insensitive dwarf (GID1) cDNA sequences into the vector and inoculated the water dropwort. The height of CMV-GID1-infected plants was marginally reduced as a result of GID1 gene silencing, and their leaves were noticeably longer and thinner. Additionally, we also used a CMV-induced silencing vector to analyze the roles of endogenous miRNAs. We used a short tandem target mimic approach to clone miR319 and miR396 from water dropwort into the CMV vector. Plants with CMV-miRNA infection were driven to exhibit the distinctive phenotypes. We anticipate that functional genomic research on water dropwort will be facilitated by the CMV-induced gene silencing technique.

Comparative transcriptome analysis reveals the contribution of amino acid transporters to acid tolerance in Lactococcus lactis

AbstractAmino acid transporters are promising targets for engineering acid‐tolerant strains of Lactococcus lactis. However, the simple overexpression of transporters alone is insufficient to achieve a highly acid‐resistant phenotype. This study investigated the effects of amino acid transporters on the acid‐stress tolerance of L. lactis. Here, we first verified the contribution of amino acid transporters to acid tolerance by overexpressing the ctrA, glnP, and glnQ genes in L. lactis. Transcriptome analysis revealed that most genes associated with specific amino acid transport, pyrimidine metabolism, and functional proteins, were upregulated in the overexpression strains. Among them, arginine biosynthesis (argG and argH), amino acid transport (yjeM and azlC), and pyrimidine metabolism were considered to be the most important regulatory mechanisms. Importantly, metabolite profiling revealed that the overexpression strains had higher intracellular levels of amino acids, particularly aspartate, glutamate, and arginine at low pH, as well as higher intracellular ATP levels, which was consistent with the corresponding gene‐expression levels. Finally, the simultaneous overexpression of glnP and glnQ led to a further improvement of acid tolerance in L. lactis. This study reveals the regulatory mechanisms of amino acid transporters, and provides a novel strategy for achieving higher acid tolerance via positive tandem expression approaches.

Proteomic analysis of extracellular vesicle cargoes mirror the cardioprotective effects of rivaroxaban in patients with venous thromboembolism.

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality worldwide. Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties; yet, these remain poorly characterized. Extracellular vesicles (EVs) are considered proinflammatory messengers regulating a myriad of (patho)physiological processes and may be highly relevant to the pathophysiology of VTE. The effects of Rivaroxaban on circulating EVs in VTE patients remain unknown. We have established that differential EV biosignatures are found in patients with non-valvular atrial fibrillation anticoagulated with Rivaroxaban versus warfarin. Here, we investigated whether differential proteomic profiles of circulating EVs could also be found in patients with VTE. We performed comparative label-free quantitative proteomic profiling of enriched plasma EVs from VTE patients anticoagulated with either Rivaroxaban or warfarin using a tandem mass spectrometry approach. Of the 182 quantified proteins, six were found to be either exclusive to, or enriched in, Rivaroxaban-treated patients. Intriguingly, these proteins are involved in negative feedback regulation of inflammatory and coagulation pathways, suggesting that EV proteomic signatures may reflect both Rivaroxaban's anti-coagulatory and anti-inflammatory potential. These differences suggest Rivaroxaban may have pleiotropic effects, supporting the reports of its emerging anti-inflammatory and cardiovascular-protective characteristics relative to warfarin.

Supported Pd-catalyzed ring opening and chemoselective aminocarbonylative coupling of benzoxazoles with aryl iodides

A tandem approach using polystyrene supported Pd catalyzed ring opening aminocarbonylative coupling of benzoxazoles with aryl iodides has been developed for the synthesis of N-(2-hydroxyphenyl)benzamides using solid oxalic acid as the CO source.

Unveiling the intricacy of gapmer oligonucleotides through advanced tandem mass spectrometry approaches and scan accumulation for 2DMS.

Antisense oligonucleotides (ASOs) are crucial for biological applications as they bind to complementary RNA sequences, modulating protein expression. ASOs undergo synthetic modifications like phosphorothioate (PS) backbone and locked nucleic acid (LNA) to enhance stability and specificity. Tandem mass spectrometry (MS) techniques were employed to study gapmer ASOs, which feature a DNA chain within RNA segments at both termini, revealing enhanced cleavages with ultraviolet photodissociation (UVPD) and complementary fragment ions from collision-induced dissociation (CID) and electron detachment dissociation (EDD). 2DMS, a data-independent analysis technique, allowed for comprehensive coverage and identification of shared fragments across multiple precursor ions. EDD fragmentation efficiency correlated with precursor ion charge states, with higher charges facilitating dissociation due to intramolecular repulsions. An electron energy of 22.8 eV enabled electron capture and radical-based cleavage. Accumulating multiple scans and generating average spectra improved signal intensity, aided by denoising algorithms. Data analysis utilised a custom Python script capable of handling modifications and generating unique mass lists.

Incidence of Secondary Primary Malignancies after Long-Term Follow up of Multiple Myeloma Patients Treated with Autologous Stem Cell Transplantation - Report from Croatian Cooperative Group for Hematologic Malignancies (KroHem)

Background: Autologous stem cell transplantation (ASCT) after induction treatment is standard of care for multiple myeloma (MM) for the last 30 years. Two transplantations up-front (so-called tandem transplant) were standard of care for all MM patients. With the use of new antimyeloma agents (such as proteasome inhibitors, immunomodulators and especially monoclonal antibodies) this approach has changed and tandem transplant is now reserved mainly for patients with high-risk disease, defined by revised international staging system (R-ISS). There have been reports which cast further doubts on the value of the more aggressive tandem ASCT approach, as well as reports suggesting higher incidence of secondary primary malignancies (SPM) after high dose therapy and ASCT. Aims: To describe long-term outcomes of MM patients treated with ASCT (single, delayed, and tandem) and the rate of secondary primary malignancies. Methods: a retrospective analysis of outcomes of 577 MM patients who underwent 865 ASCT procedures between 1993 and 2017 was performed. Data were collected from 3 transplant centres and 9 other haematological centres in which MM patients were treated pre- and post-transplant. During that period treatment strategies changed significantly from single to tandem to salvage second ASCT. Results: there were 577 patients included. Median age at first transplant was 58 years (range 22 - 74). There were 295 female and 282 male patients. 346 patients received VAD (vincristine, doxorubicin, dexamethasone) and 231 received bortezomib and/or thalidomide (PI/IMiD) based regiments as induction therapy. All patients received high dose melphalan for pretransplant conditioning, 32 in combination with total body irradiation. Tandem ASCT (defined as second transplantation performed within 6 months after the first) was performed in 226 patients, single ASCT in 262 and salvage second (after relapse and/or progression) in 89 patients. Median overall survival (OS) for the entire group is 81.9 months and median progression free survival (PFS) 38.9 months. Tandem ASCT in comparison to single and second salvage transplantation resulted in statistically significant better OS (115 vs. 83 vs. 67 months respectively, p < 0.0001) and PFS (48 vs. 32. vs. 28 months respectively, p < 0.0001). There was no difference in outcomes regarding type of induction therapy, VAD vs. PI/IMiD based: median OS was 83 vs. 80 months, respectively (p=0.39) and median PFS was 39 vs. 38 months, respectively (p=0.15). 17.6% percent of patients who were treated with tandem ASCT are progression-free more than 10 years after the procedure while 10-year OS is 31.9%. 51 patients (8.8%) developed secondary malignancies (SPM). Most common SPM were lung carcinoma (10 patients), colorectal carcinoma (7 patients), myelodysplastic syndrome/acute myeloid leukaemia (6 patients), breast carcinoma (4 patients) and melanoma (4 patients). Of those 19 died due to SPM (3% of the entire patient group). There was no correlation between number of ASCT and SPM (p=0.87). Conclusion: in our group of patients tandem ASCT resulted in superior OS and PFS in comparison to single and/or salvage ASCT. Interestingly, we did not observe benefit of new drugs (PI/IMiD) in induction therapy regarding outcomes. This peculiar result might be due to rather late availability of these drugs in front line settings (bortezomib and thalidomide since 2015) and time period taken for analysis (up to 2018). SPM rate was similar to other reports and did not show significant correlation with number of ASCT. More than 15% of patients treated with tandem ASCT experienced very prolonged PFS and almost 32% had OS longer than 10 years.

Transvenous lead extraction: Experience of the Tandem approach.

Transvenous lead extraction (TLE) is important in the management of cardiac implantable electronic devices but carries risk. It is most commonly completed from the superior access, often with 'bail-out' support via the femoral approach. Superior and inferior access may be used in tandem, which has been proposed as an advance in safety and efficacy. The aim of this study is to evaluate the safety and efficacy of the Tandem approach. The 'Tandem' procedure entailed grasping of the targeted lead in the right atrium to provide countertraction as a rotational dissecting sheath was advanced over the lead from the subclavian access. Consecutive 'Tandem' procedures performed by a single operator between December 2020 and March 2023 in a single large-volume TLE centre were included and compared with the conventional superior approach (control) using 1:1 propensity score matching; patients were statistically matched for demographics. The Tandem in comparison with the conventional approach extracted leads of much greater dwell time (148.9 ± 79 vs. 108.6 ± 77 months, P < 0.01) in a shorter procedure duration (96 ± 36 vs. 127 ± 67 min, P < 0.01) but requiring more fluoroscopy (16.4 ± 10.9 vs. 10.8 ± 14.9 min, P < 0.01). The Tandem and control groups had similar clinical (100% vs. 94.7%, P = 0.07) and complete (94.8% vs. 92.8%, P = 0.42) success, with comparable minor (4% vs. 6.7%, P = 0.72) and major (0% vs. 4%, P = 0.25) complications; procedural (0% vs. 1.3%, P = 1) and 30-day (1.3% vs. 4%, P = 0.62) mortality were also similar. The Tandem procedure is as safe and effective as the conventional TLE. It can be applied to leads of a long dwell time with a potentially shorter procedure duration.

A comprehensive quality evaluation for Huangqi Guizhi Wuwu decoction by integrating UPLC-DAD/MS chemical profile and pharmacodynamics combined with chemometric analysis

Ethnopharmacological relevanceHuangqi Guizhi Wuwu Decoction (HGWD), a classical Chinese formula originally recorded in Jin Kui Yao Lue, was used for the treatment of human “blood impediment” (a type of “Bi” syndrome). In clinical practice, HGWD has been applied to treat rheumatoid arthritis (RA). Aim of the studyThe characterization of chemical markers reflecting both efficacy and chemical characteristics is of great significance for TCM quality control. With the anti-RA effects of HGWD as an example, the aim of this study was to develop a comprehensive strategy combining the overall chemical profile and biological activity data to identify chemical markers. Materials and methodsFirst, an ultra-performance liquid chromatography-diode array detector (UPLC-DAD) fingerprint was established and validated to evaluate the holistic quality of HGWD of different origins. Characteristic markers associated with HGWD from different geographical origins were screened by a combination of UPLC-DAD fingerprint and chemometrics methods. Second, the chemical profiles of the 15 batches of HGWD samples were characterized by UPLC coupled tohybrid linear ion trap-Orbitrap mass spectrometry (UPLC-HRMS). The in vitro anti-RA activities of the 15 HGWD samples were then evaluated. Third, spectrum-effect relationship analysis was performed to identify bioactive compounds that could potentially be used as quality markers. Finally, a UPLC-triple quadrupole tandem mass spectrometry approach was optimized and established for quantitative analysis of the characteristic and quality markers in 15 batches of HGWD. ResultsIn total, 30 common peaks were assigned in the UPLC-DAD fingerprint. Nine peaks were recognized and considered characteristic markers: protocatechuic acid, coumarin, cinnamic acid, oxypaeoniflorin, paeoniflorin, calycosin, formononetin, catechin, and albiflorin. Furthermore, ninety-five common compounds were identified in the UPLC-HRMS chemical profile. The pharmacological analysis indicated that the anti-RA activities of the 15 HGWD samples were vastly different. The spectrum-effect relationship analysis revealed 30 potential bioactive constituents positively correlated with anti-RA activity. Among them, five compounds with relative amounts >1%, paeoniflorin, astragaloside IV, hexahydrocurcumin, formononetin and calycosin-7-glucoside, were selected as quality markers, and their activity was verified in LPS-induced RAW264.7 macrophages. Finally, the above 12 representative components were simultaneously quantified in the 15 batches of HGWD samples. ConclusionCombining a holistic chemical profile with representative component evaluation, this systematic strategy could be a reliable and effective method to improve quality evaluations of HGWD.

Bovine Milk Proteome: Milk Fat Globule Membrane Protein Is the Most Sensitive Fraction in Response to High Somatic Cell Count.

The impacts of high milk somatic cell count (SCC) on different milk fractions are not well understood. In this study, proteins in milk exosomes, milk fat globule membrane (MFGM), and whey from cows with low (<105 cells/mL, CG) and high SCC (>5 × 105 cells/mL, HSG) were identified using a tandem mass tag proteomic approach. In total, 1568, 2160, and 1002 proteins were identified, with 65, 552, and 98 proteins being altered by high SCC in exosomes, MFGM, and whey, respectively. With high SCC, the exosome marker (ACTB) was increased in the exosomes of HSG. The main MFGM proteins (BTN1A1, PLIN3, FABP3, and MFGE8) and functional proteins (MUC1, IGSF5, TLR5, and CD36/14) were decreased, while the lipid/energy metabolism-related proteins were increased in the MFGM of HSG. The glycolysis-related proteins were increased in the whey of HSG. Also, the host defense/inflammation-related proteins were changed in three fractions under high SCCs. MFGM was the most sensitive fraction to a high SCC, followed by whey. These findings provide guidance for the early detection of unhealthy mammary glands.

A comparative proteomic analysis for non-invasive early prediction of hypoxic-ischemic injury in asphyxiated neonates.

Hypoxic Ischemic Encephalopathy (HIE) is one of the principal causes of neonatal mortality and long-term morbidity worldwide. The neonatal signs of mild cerebral injury are subtle, making an early precise diagnosis difficult. Delayed detection, poor prognosis, and lack of specific biomarkers for the disease are increasing mortality rates. In this study, we intended to identify specific biomarkers using comparative proteomic analysis to predict the severity of perinatal asphyxia so that its outcome can also be prevented. A case-control study was conducted on 38 neonates, and urine samples were collected within 24 and 72h of life. A tandem mass spectrometry-based quantitative proteomics approach, followed by validation via sandwich ELISA, was performed. The LC-MS/MS-based proteomics analysis resulted in the identification of 1201 proteins in urine, with 229, 244, and 426 being differentially expressed in HIE-1, HIE-2, and HIE-3, respectively. Axon guidance, Diseases of programmed cell death, and Detoxification of reactive oxygen species pathways were significantly enriched in mild HIE versus severe HIE. Among the differentially expressed proteins in various stages of HIE, we chose to validate four proteins - APP, AGT, FABP1, and FN1 - via sandwich ELISA. Individual and cumulative ROC curves were plotted. AGT and FABP1 together showed high sensitivity, specificity, and accuracy as potential biomarkers for early diagnosis of HIE. Establishing putative urinary biomarkers will facilitate clinicians to more accurately screen neonates for brain injury and monitor the disease progression. Prompt treatment of neonates may reduce mortality and neurodevelopmental impairment.

The Oxygenate-Mediated Conversion of COx to Hydrocarbons─On the Role of Zeolites in Tandem Catalysis.

Decentralized chemical plants close to circular carbon sources will play an important role in shaping the postfossil society. This scenario calls for carbon technologies which valorize CO2 and CO with renewable H2 and utilize process intensification approaches. The single-reactor tandem reaction approach to convert COx to hydrocarbons via oxygenate intermediates offers clear benefits in terms of improved thermodynamics and energy efficiency. Simultaneously, challenges and complexity in terms of catalyst material and mechanism, reactor, and process gaps have to be addressed. While the separate processes, namely methanol synthesis and methanol to hydrocarbons, are commercialized and extensively discussed, this review focuses on the zeolite/zeotype function in the oxygenate-mediated conversion of COx to hydrocarbons. Use of shape-selective zeolite/zeotype catalysts enables the selective production of fuel components as well as key intermediates for the chemical industry, such as BTX, gasoline, light olefins, and C3+ alkanes. In contrast to the separate processes which use methanol as a platform, this review examines the potential of methanol, dimethyl ether, and ketene as possible oxygenate intermediates in separate chapters. We explore the connection between literature on the individual reactions for converting oxygenates and the tandem reaction, so as to identify transferable knowledge from the individual processes which could drive progress in the intensification of the tandem process. This encompasses a multiscale approach, from molecule (mechanism, oxygenate molecule), to catalyst, to reactor configuration, and finally to process level. Finally, we present our perspectives on related emerging technologies, outstanding challenges, and potential directions for future research.

A tandem white shark algorithm approach for optimizing drug–disease and drug–drug interactions in multimorbidity and polypharmacy

Minimizing Drug–disease and drug–drug Interactions in Polypharmacy and Multimorbidity (DIPM) is a challenging problem. The challenge is caused by the large number of similar medications that can be prescribed for each disease and the adverse reactions that may be experienced by the selected medication(s) for one or more of the diseases and medications identified. Therefore, it is a selection problem as to which medication should be prescribed to the patient for each disease while maintaining the least drug–disease and drug–drug interactions. This is an optimization problem, and to the best of our knowledge, it has never been addressed before using search-based algorithms. The aims of this study are to explore and find the best performance among the employed algorithms in providing optimal or near-optimal solutions to this problem, and then to fine-tune an optimization approach to DIPM. Four algorithms are consequently employed, which are: Dragonfly Algorithm (DA), Whale Optimization Algorithm (WOA), Genetic Algorithm (GA), and White Shark Optimization (WSO). To test the most suitable one among the algorithms, two synthetic datasets are used, representing simple and more complex problems. The results, considering only drug–disease interactions, show that GA is outperforming the others for a simple problem. However, WSO is found to outperform the others when the problem is more complex. The WSO is accordingly formed into a tandem approach, considering both drug–disease and drug–drug interactions for a real-world problem dataset. The approach indicates promising results with accuracy of (100%) for drug–drug interaction and (96.6%) for drug–disease interaction in (5.32) seconds.