Search Results (412)

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) affects all cardiac chambers to cause left ventricular (LV) deformation as well as left atrial (LA) remodeling and functional impairment. We investigated the associations of the LA volume index (LAVI):LV ejection fraction (LVEF) ratio with the increased risk of death, heart transplant, or LV assist device implantation (LVAD) in patients with ATTR-CM. Methods: This was a retrospective cohort study involving 69 heart failure (HF) patients with ATTR-CM at an academic medical center between 1 November 2008 and 31 March 2024. ATTR-CM was diagnosed using a technetium–diphosphonate/pyrophosphate scan or an endomyocardial biopsy. The LAVI and LVEF were measured by echocardiography. Cox proportional hazards models were used for the analysis. Results: The mean (SD) age of the participants was 77.5 (9.3) years. Over a median (IQR) follow-up period of 1.96 (0.67–2.82) years, we observed 24 composite events that included twenty-two deaths, two heart transplants, and two LVAD implantations (who subsequently died). In multivariable-adjusted analyses that accounted for age and the glomerular filtration rate, a one-unit increase in the LAVI:LVEF ratio was associated with a doubling of the risk (HR, 95% CI: 2.06, 1.11–3.82) of experiencing the composite outcome. Conclusions: A one-unit increase in the LAVI:LVEF ratio was associated with an increased risk of death, heart transplant, or LVAD implantation in patients with ATTR-CM. Full article

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by a variety of clinical manifestations, mainly affecting joints and entheses, but also skin, nails, the eye, and the intestine. Objectives: In this review, we describe the essential characteristics of both synovial membranes and synovial fluid (SF) in PsA. Similarly to other inflammatory arthritis, the histological peculiarities in PsA synovitis are lining hyperplasia, neoangiogenesis, and sublining infiltration by immune cells and inflammatory mediators. Synovial effusions are frequent in PsA patients and SF analysis allows us to determine the pathological process occurring in the joint. Routine examinations help clinicians in defining the inflammatory status and possibly the detection of specific cell subsets. In addition, pathogenic crystals including monosodium urate and calcium pyrophosphate may be found in PsA SF. Conclusions: SF represents a potential substrate to identify the biomarkers that are useful to predict disease progression and response to medications in PsA patients, thus guiding the choice of appropriate and tailored pharmacological treatment. Full article

Developing flame-retardant epoxy resins (EPs) is essential to broaden their industrial applications, as their inherent flammability restricts their widespread use. In this study, commercial cerium oxide (CeO₂) nanoparticles were modified with oleic acid and successfully assembled onto the surface of pyrophosphate piperazine (PAPP) through a simple solvophobic effect, constructing an integrated superstructure flame retardant, CeO₂@PAPP, with enhanced performance integration. Compared to traditional simple blends, the EP composite with 10 wt% CeO₂@PAPP displayed superior flame retardancy, thanks to the more subtle synergistic effects between flame retardant components and their favorable interface interactions. The EP composite achieved a UL-94 V-0 rating and increased the limiting oxygen index (LOI) to 34.2%. Significant reductions of 56.3% in peak heat release rate (PHRR) and 38.2% in total heat release (THR) were observed. Furthermore, total smoke release (TSR), carbon monoxide yield (COPR), and carbon dioxide yield (CO₂PR) decreased by 52.2%, 50.2%, and 67.3%, respectively. Through comprehensive and detailed characterization, it was discovered that the assembled integrated CeO₂@PAPP flame retardant can perform better in both the gas phase and condensed phase, resulting in superior flame-retardant properties. This study offers an effective strategy for developing highly flame-retardant EPs, thereby expanding their potential applications across various industries. Full article

Background: The gold standard for crystal arthritis diagnosis relies on the identification of either monosodium urate (MSU) or calcium pyrophosphate (CPP) crystals in synovial fluid. With the goal of enhanced crystal detection, we adapted a standard compensated polarized light microscope (CPLM) with a polarized digital camera and multi-focal depth imaging capabilities to create digital images from synovial fluid mounted on microscope slides. Using this single-shot computational polarized light microscopy (SCPLM) method, we compared rates of crystal detection and raters’ preference for image. Methods: Microscope slides from patients with either CPP, MSU, or no crystals in synovial fluid were acquired using CPLM and SCPLM methodologies. Detection rate, sensitivity, and specificity were evaluated by presenting expert crystal raters with (randomly sorted) CPLM and SCPLM digital images, from FOV above clinical samples. For each FOV and each method, each rater was asked to identify crystal suspects and their level of certainty for each crystal suspect and crystal type (MSU vs. CPP). Results: For the 283 crystal suspects evaluated, SCPLM resulted in higher crystal detection rates than did CPLM, for both CPP (51%. vs. 28%) and MSU (78% vs. 46%) crystals. Similarly, sensitivity was greater for SCPLM for CPP (0.63 vs. 0.35) and MSU (0.88 vs. 0.52) without giving up much specificity resulting in higher AUC. Conclusions: Subjective and objective measures of greater detection and higher certainty were observed for SCPLM over CPLM, particularly for CPP crystals. The digital data associated with these images can ultimately be incorporated into an automated crystal detection system that provides a quantitative report on crystal count, size, and morphology. Full article

Background: The early detection of transthyretin cardiac amyloidosis (ATTR-CM) is essential, with Tc-99m pyrophosphate scintigraphy (PYP scan) being a key diagnostic tool. Although a previously validated score has shown promise in predicting PYP scan positivity among patients with HFpEF, further evaluation in diverse cohorts is necessary. Objectives: To assess the effectiveness of the ATTR-CM score in predicting PYP scan positivity within our patient population. Methods: We analyzed patients referred for PYP with SPECT at the Cleveland Clinic from January 2012 to January 2020, all of whom had undergone echocardiography within the previous year. The ATTR-CM score was determined using the following criteria: Age (60–69, +2; 70–79, +3; ≥80, +4), sex (male, +2), hypertension (present, −1), left ventricular ejection fraction (LVEF <60%, +1), posterior wall thickness (≥12 mm, +1), and relative wall thickness (>0.57, +2). A score of ≥6 indicated high risk. Results: Among the 540 patients (32% female, 33% black), 27% had an LVEF <40%. The score demonstrated good discrimination by AUC, with consistent performance across different racial groups, sexes, and LVEF categories. For scores ≥6, sensitivity was lower in women and black patients; however, lowering the cutoff to 5 markedly improved sensitivity. Conclusions: The ATTR-CM score displayed consistently good performance by AUC across our cohort, including patients with HFrEF. Nevertheless, its sensitivity was reduced in black patients and women. Efforts to scale ATTR-CM diagnosis tools should be mindful of demographic differences in risk prediction models. Full article

Construction of the genome of Hericium coralloides, a species of edible mushroom, and identification of the genes involved in terpenoid biosynthesis can determine the biology and genetics of terpenoids. The present study describes the assembly of a high-quality chromosome-scale genome of H. coralloides using Pacbio HiFi sequencing and Hi-C technology. This genome consisted of 13 chromosomes, a total size of 43.6 Mb, contigs of N50 3.6 Mb, GC content at 54%, and BUSCOs integrity of 96.9%. Genes associated with terpenoid biosynthesis were predicted by KEGG enrichment analysis and homologous alignment. The Her011461 and Her008335 genes, encoding proteins in the terpenoid backbone synthesis pathway, were found to encode geranylgeranyl pyrophosphate and farnesyl diphosphate synthases, key enzymes in the biosynthesis of geranylgeranyl diphosphate, a precursor of several diterpenoids. Her011463 was found to be involved in regulating diterpene cyclase. The Her005433, Her006724, Her010605, and Her010608 genes were found to encode sesquiterpene synthesis. Most of these genes were more highly expressed in dikaryotic mycelia than in the primordium and fruiting bodies, indicating that terpenoids may be more abundant in dikaryotic mycelia. To our knowledge, this study is the first to assemble the H. coralloides genome at the chromosome scale and to identify the genes involved in terpenoid biosynthesis. Full article

A general approach is presented for synthesizing alkyne-modified nucleoside triphosphates via the Sonogashira cross-coupling reaction of unprotected halogenated 2ʹ-deoxynucleoside, followed by monophosphorylation and the reaction of the corresponding phosphoromorpholidate with tributylammonium pyrophosphate. A highly efficient approach for the milligram-scale synthesis of base-modified nucleoside triphosphates with an amino acid-like side chain was developed. The present chemical method outweighs the other reported methods of a base-modified nucleoside triphosphates synthesis in terms of it being a protection-free strategy, the shortening of reaction steps, and increased yields (about 70%). The resulting 8-alkynylated dATP was tested as a substrate for DNA polymerases in a primer extension reaction. Full article

Taraxacum kok-saghyz Rodin (TKS) is a recognized alternative source of natural rubber comparable to the rubber tree. The geranylgeranyl pyrophosphate synthase (GGPS) catalyzed the synthesis of geranylgeranyl pyrophosphate (GGPP), which is an important enzyme in the secondary metabolism pathway. In this study, we present the first analysis of the GGPS gene family in TKS, where a total of seven TkGGPS family members were identified. Their core motifs, conserved structural domains, gene structures, and cis-acting elements were described. In addition, two phylogenetic trees were constructed based on the Neighbor-Joining and Maximum-Likelihood methods, and the TkGGPSs were highly conserved and exhibited good collinearity with the other species. Transcriptome data showed that seven TkGGPS gene members were expressed in all the 12 tissues measured, and TkGGPS1, TkGGPS3, and TkGGPS6 were highly expressed in latex, suggesting that they may be associated with natural rubber synthesis. Meanwhile, quantitative real-time PCR (qRT-PCR) showed that the expression levels of the TkGGPS genes were regulated by the ethylene and methyl jasmonate (MeJA) pathways. Subcellular localization results indicated that all the TkGGPS proteins were also located in chloroplasts involved in photosynthesis in plants. This study will provide valuable insights into the selection of candidate genes for molecular breeding and natural rubber biosynthesis in TKS. Full article

Extrusion processing of plasticized cassava starch, a prominent industrial crop, with chemical additives offers a thermo-mechanical approach to modify starch structures through physical and chemical interactions. This research investigates the interaction and morphology of thermoplastic cassava starch (TPS) blended with tetrasodium pyrophosphate (Na₄P₂O₇), sodium tripolyphosphate (Na₅P₃O₁₀), sodium hexametaphosphate (Na₆(PO₃)₆), sodium erythorbate (C₆H₇O₆Na), and sodium nitrite (NaNO₂) via twin-screw extrusion. The effects of these additives on the chemical structure, thermal profile, water absorption, and solubility of the TPS were examined. The high temperature and shearing forces within the extruder disrupted hydrogen bonding at α-(1-4) and α-(1-6) glycosidic linkages within anhydroglucose units. Na₄P₂O₇, Na₅P₃O₁₀ and Na₆(PO₃)₆ induced starch phosphorylation, while ¹H NMR and ATR-FTIR analyses revealed that C₆H₇O₆Na and NaNO₂ caused starch hydrolysis. These additives hindered starch recrystallization, resulting in higher amorphous fractions that subsequently influenced the thermal properties and stability of the extruded TPS. Furthermore, the type and content of the added modifier influenced the water absorption and solubility of the TPS due to varying levels of interaction. These modified starch materials exhibited enhanced antimicrobial properties against Escherichia coli and Staphylococcus aureus in polyester blends fabricated via extrusion, with nitrite demonstrating the most potent antimicrobial efficacy. These findings suggest that starch modification via either phosphorylation or acid hydrolysis impacts the thermal properties, morphology, and hydrophilicity of extruded cassava TPS. Full article

Soluble inorganic pyrophosphatase (s-PPase), a pyrophosphate hydrolase, is crucial for various physiological processes including plant growth and development, metabolic functions, and responses to abiotic stresses. However, research on s-PPase in woody plants is limited. To investigate the potential role of soluble inorganic pyrophosphatase in Eucommia ulmoides Oliver (E. ulmoides) in drought stress, the E. ulmoides soluble inorganic pyrophosphatase 5 (EuSIP5) cDNA sequence was amplified via RT-PCR. A bioinformatic analysis suggested that EuSIP5 may be an unstable amphipathic protein predominantly localized in the cytoplasm. In E. ulmoides, the highest expression of the EuSIP5 gene was detected in the leaves and pericarp of male plants from April to October, and in the leaves in July and September. Under drought conditions, the expression of EuSIP5 in E. ulmoides leaves was significantly greater than that in the control. An overexpression vector containing EuSIP5 was constructed and introduced into Nicotiana tabacum L. cv. Xanthi (N. tabacum L.). Compared with that in wild-type (WT) plants, wilting in N. tabacum L. EuSIP5-overexpressing (OE) plants was delayed by 4 days under drought stress. Additionally, the expression levels of the drought-related genes DET2, CYP85A1, P5CS, ERF1, F-box, and NCED1 were elevated in the leaves of transgenic N. tabacum L. Moreover, the activities of the protective enzymes peroxidase, superoxide dismutase, and catalase were significantly greater, whereas the malondialdehyde content was lower in the transgenic plants than in the WT plants. These findings suggest that the introduction of the EuSIP5 gene into N. tabacum L. enhances drought-related gene expression, increases antioxidant capacity, and reduces oxidative stress damage, thereby improving drought resistance. Full article

As natural bioactive compounds, plant pigments play crucial roles not only in plant phenotype, growth, development, and adaptation to stress but also hold unique value in biotechnology, healthcare, and industrial applications. There is growing interest in the biosynthesis and acquisition of plant pigments. Thus, this paper explores emerging extraction methods of natural pigments and elucidates the biosynthesis pathways of four key plant pigments, chlorophylls, carotenoids, anthocyanins, and betalaine in vivo and in vitro. We comprehensively discuss the application of solvent, supercritical fluid [extraction], ultrasonic, and microwave-assisted extraction techniques, as well as introducing key enzymes, precursors, and synthetic pathways involved in pigment synthesis. δ-Aminolevulinic acid represents a pivotal initiating enzyme for chlorophyll synthesis, whereas isopentenylpyrophosphate, (IPP) and dimethylallyl pyrophosphate, (DMAPP) are closely associated with carotenoid biosynthesis. Phenylalanine and tyrosine are critical substances for anthocyanin and betalaine synthesis, respectively. Hence, crucial genes such as chlI, crtB, PGT8, CYP76AD1, and BvDODA can be employed for heterologous biosynthesis in vitro to meet the demand for increased plant pigment amount. As a pivotal determinant of plant coloration, an in-depth exploration into the high-quality acquisition of plant pigments can provide a basis for developing superior pigments and offer new insights into increasing pigment yield. Full article

During the past 20 years, the use of ultrasound (US) in rheumatology has increased tremendously, and has become a valuable tool in rheumatologists’ hands, not only for assessment of musculoskeletal structures like joints and peri-articular tissues, but also for evaluation of nerves, vessels, lungs, and skin, as well as for increasing the accuracy in a number of US-guided aspirations and injections. The US is currently used as the imaging method of choice for establishing an early diagnosis, assessing disease activity, monitoring treatment efficacy, and assessing the remission state of inflammatory joint diseases. It is also used as a complementary tool for the assessment of patients with degenerative joint diseases like osteoarthritis, and in the detection of crystal deposits for establishing the diagnosis of metabolic arthropathies (gout, calcium pyrophosphate deposition disease). The US has an added value in the diagnostic process of polymyalgia rheumatica and giant-cell arteritis, and is currently included in the classification criteria. A novel use of US in the assessment of the skin and lung involvement in connective tissue diseases has the potential to replace more expensive and risky imaging modalities. This narrative review will take a close look at the most recent evidence-based data regarding the use of US in the big spectrum of rheumatic diseases. Full article

Craniometaphyseal Dysplasia (CMD) is a rare skeletal disorder that can result from mutations in the ANKH gene. This gene encodes progressive anksylosis (ANK), which is responsible for transporting inorganic pyrophosphate (PPi) and ATP from the intracellular to the extracellular environment, where PPi inhibits bone mineralization. When ANK is dysfunctional, as in patients with CMD, the passage of PPi to the extracellular environment is reduced, leading to excess mineralization, particularly in bones of the skull. Zebrafish may serve as a promising model to study the mechanistic basis of CMD. Here, we provide a detailed analysis of the zebrafish Ankh paralogs, Ankha and Ankhb, in terms of their phylogenic relationship with ANK in other vertebrates as well as their spatiotemporal expression patterns during zebrafish development. We found that a closer evolutionary relationship exists between the zebrafish Ankhb protein and its human and other vertebrate counterparts, and stronger promoter activity was predicted for ankhb compared to ankha. Furthermore, we noted distinct temporal expression patterns, with ankha more prominently expressed in early development stages, and both paralogs also being expressed at larval growth stages. Whole-mount in situ hybridization was used to compare the spatial expression patterns of each paralog during bone development, and both showed strong expression in the craniofacial region as well as the notochord and somites. Given the substantial overlap in spatiotemporal expression but only subtle patterning differences, the exact roles of these genes remain speculative. In silico analyses predicted that Ankha and Ankhb have the same function in transporting PPi across the membrane. Nevertheless, this study lays the groundwork for functional analyses of each ankh paralog and highlights the potential of using zebrafish to find possible targeted therapies for CMD. Full article

The burning of Ethylene–Propylene–Diene Monomer (EPDM) rubber generates substantial smoke, posing a severe threat to the environment and personal safety. Considering the growing emphasis on safety and environmental protection, conventional non-smoke-suppressing flame retardants no longer satisfy the present application requirements. Consequently, there is an urgent need to develop a novel flame retardant capable of suppressing smoke formation while providing flame retardancy. Sepiolite (SEP), a porous silicate clay mineral abundant in silica and magnesium, exhibits notable advantages in the realm of flame retardancy and smoke suppression. This research focuses on the synthesis of two highly efficient flame-retardant smoke suppression systems, namely AEGS and PEGS, using Enteromorpha (EN), graphene (GE), sepiolite (SEP), ammonium polyphosphate (APP), and/or piperazine pyrophosphate (PPAP). The studied flame-retardant systems were then applied to EPDM rubber and the flame-retardant and smoke suppression abilities of EPDM/AEGS and EPDM/PEGS composites were compared. The findings indicate that the porous structure of sepiolite plays a significant role in reducing smoke emissions for EPDM composites during combustion. Full article

Background: Pseudoxanthoma elasticum (PXE), a rare genetic disorder presenting with slowly progressing calcification of various tissues, including the arteries, is caused by mutations in the ABCC6 gene that lead to the reduction of pyrophosphate, a natural inhibitor of calcification. We showed that, compared to a placebo, the cyclical administration of etidronate, a stable pyrophosphate analog, significantly reduced arterial calcification assessed by low-dose CT scans after one year. The aim of the present prospective, single center, observational cohort study was the assessment of the efficacy and safety of cyclical etidronate in patients treated for periods longer than one year. Methods: Seventy-three patients were followed for a median of 3.6 years without etidronate and 2.8 years with etidronate, and each patient served as their own control. Results: The median absolute yearly progression of total calcification volume during the period with etidronate (388 [83–838] µL) was significantly lower than that without etidronate (761 [362–1415] µL; p < 0.001). The rates of the relative progression of arterial calcification were 11.7% (95% CI: 9.6–13.9) without etidronate compared to 5.3% (95% CI: 3.7–7.0) with etidronate, after adjustment for confounders. Conclusions: The cyclical administration of etidronate for nearly 3 years significantly reduced the progression rate of arterial calcification in patients with PXE with pre-existing calcifications without any serious adverse effects. Full article