Lineage Differentiation Research Articles

Nr5a2 is dispensable for zygotic genome activation but essential for morula development.

Early embryogenesis is driven by transcription factors (TFs) that first activate the zygotic genome and then specify the lineages constituting the blastocyst. Although the TFs specifying the blastocyst's lineages are well characterized, those playing earlier roles remain poorly defined. Using mouse models of the TF Nr5a2, we show that Nr5a2-/- embryos arrest at the early morula stage and exhibit altered lineage specification, frequent mitotic failure, and substantial chromosome segregation defects. Although NR5A2 plays a minor but measurable role during zygotic genome activation, it predominantly acts as a master regulator at the eight-cell stage, controlling expression of lineage-specifying TFs and genes involved in mitosis, telomere maintenance, and DNA repair. We conclude that NR5A2 coordinates proliferation, genome stability, and lineage specification to ensure correct morula development.

Effect of the polyphenol flavonoids fisetin and quercetin on the adipogenic differentiation of human mesenchymal stromal cells.

Fisetin and quercetin, polyphenol flavonoids, have been shown to have a wide range of beneficial pharmacological effects including anti-inflammatory, anti-oxidative, and anti-cancer. Our previous work shows that fisetin also affects the specification of the adipogenic-osteogenic lineage of human mesenchymal stem cells (hMSCs) by modulating the Hippo-YAP signaling pathway. Although quercetin has a structure similar to that of fisetin, its effects on the functional properties of hMSCs have not yet been investigated. The objective of this study is to determine the effects of quercetin on the various properties of hMSCs, including proliferation, migration, and differentiation capacity toward adipogenic and osteogenic lineages. The results show that while fisetin increases hMSC adipogenic differentiation, quercetin inhibited adipogenic differentiation of hMSCs. The inhibition is mediated, at least in part, by the activation of hippo signaling and up-regulation of miR-27b, which inhibits the expression of genes involved in all critical steps of lipid droplet biogenesis, resulting in a decrease in the number of lipid droplets in hMSCs. It is possible that the lack of hydroxylation of the 5 position on the A ring of quercetin could be responsible for its different effect on the adipogenic-osteogenic lineage specification of hMSCs compared to fisetin. Molecular docking and molecular dynamics simulation suggested that fisetin and quercetin possibly bind to serine / threonine protein kinases 4 (STK4/MST1), which is an upstream kinase responsible for LATS phosphorylation. Taken together, our results demonstrate more insight into the mechanism underlying the role of flavonoid fisetin and quercetin in the regulation of adipogenesis.

Investigating the Genetic Association of 40 Biochemical Indicators with Parkinson's Disease.

The mechanisms of Parkinson's disease (PD) are not fully understood, which hinders the development of effective therapies. Research indicates that lower levels of biochemical indicators like bilirubin, vitamin D, and cholesterol may elevate the risk of PD. However, clinical studies on abnormal levels of biochemical indicators in PD patients' circulation are inconsistent, leading to ongoing debate about their association with PD. Here, we investigate the genetic correlation between 40 biochemical indicators and PD using a bidirectional two-sample Mendelian randomization (MR) approach to uncover potential causal relationships. Data from genome-wide association studies (GWAS) were utilized, with genetic variations from specific lineages serving as instrumental variables (IVs). The methodology followed the STROBE-MR checklist and adhered to the three principal assumptions of MR. Statistical analyses employed methods including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Biochemical indicators including albumin, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) showed significant associations with PD risk. Elevated levels of albumin (OR = 1.246, 95% CI 1.006-1.542, P = 0.043) and SHBG (OR = 1.239, 95% CI 1.065-1.439, P = 0.005) were linked to higher PD risk. Conversely, increased CRP levels (OR = 0.663, 95% CI 0.517-0.851; P = 0.001) could potentially lower PD risk. The robustness of the results was confirmed through various MR analysis techniques, including assessments of directional pleiotropy and heterogeneity using MR-Egger intercept and MR-PRESSO methods. This study systematically reveals, for the first time at the genetic level, the relationship between 40 biochemical indicators and PD risk. Our research verifies the role of inflammation in PD and provides new genetic evidence, further advancing the understanding of PD pathogenesis. The study shows a positive correlation between albumin and SHBG with PD risk and a negative correlation between CRP and PD risk. This study identifies for the first time that SHBG may be involved in the onset of PD and potentially worsen disease progression.

NMNAT1 Is Essential for Human iPS Cell Differentiation to the Retinal Lineage.

The gene encoding nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), a nicotinamide adenine dinucleotide synthetase localized in the cell nucleus, is a causative factor in Leber's congenital amaurosis, which is the earliest onset type of inherited retinal degeneration. We sought to investigate the roles of NMNAT1 in early retinal development. We used human induced pluripotent stem cells (hiPSCs) and established NMNAT1-knockout (KO) hiPSCs using CRISPR/cas9 technology to reveal the roles of NMNAT1 in human retinal development. NMNAT1 was not essential for the survival and proliferation of immature hiPSCs; therefore, we subjected NMNAT1-KO hiPSCs to retinal organoid (RO) differentiation culture. The expression levels of immature hiPSC-specific genes decreased in a similar manner after organoid culture initiation up to 2 weeks in the control and NMNAT1-KO. Neuroectoderm-specific genes were induced in the control and NMNAT1-KO organoids within a few days after starting the organoid culture; PAX6 and TUBB3 were higher in NMNAT1-KO organoids up to 7days than in the control organoids. However, the induction of genes involving retinal early development, such as RAX, which was induced at around day 10 in this culture, was considerably reduced in NMNAT1-KO organoids. Morphological examination also showed failure of retinal primordial structure formation, which became visible at around 2 weeks of the control culture, in the NMNAT1-KO organoids. Decreased intracellular NAD levels and poly(ADP-ribosyl)ation were observed in NMNAT1-KO organoids at 7 to 10days of the culture. Mass spectrometry analysis of inhibited proteins in the poly(ADP-ribosyl)ation pathway identified poly(ADP-ribosyl)ation of poly(ADP-ribose) polymerase 1 (PARP1) as a major protein. These results indicate that NMNAT1 was dispensable for neural lineage differentiation but essential for the commitment of retinal fate differentiation in hiPSCs. The NMNAT1-NAD-PARP1 axis may play a critical role in the appropriate development of human retinal lineage differentiation.

Neuronal lineage tracing from progenitors in human cortical organoids reveals mechanisms of neuronal production, diversity, and disease

The contribution of progenitor subtypes to generating the billions of neurons produced during human cortical neurogenesis is not well understood. We developed the cortical organoid lineage-tracing (COR-LT) system for human cortical organoids. Differential fluorescent reporter activation in distinct progenitor cells leads to permanent reporter expression, enabling the progenitor cell lineage of neurons to be determined. Surprisingly, nearly all excitatory neurons produced in cortical organoids were generated indirectly from intermediate progenitor cells. Additionally, neurons of different progenitor lineages were transcriptionally distinct. Isogenic lines made from an autistic individual with and without a likely pathogenic CTNNB1 variant demonstrated that the variant substantially altered the proportion of neurons derived from specific progenitor cell lineages, as well as the lineage-specific transcriptional profiles of these neurons, suggesting a pathogenic mechanism for this mutation. These results suggest individual progenitor subtypes play roles in generating the diverse neurons of the human cerebral cortex.

CAPP-GPT: A computer-aided process planning-generative pretrained transformer framework for smart manufacturing

Smart manufacturing (SM) constitutes the backbone of Industry 4.0 (I4.0), allowing for heightened autonomy of the various interacting cyber-physical systems, making the various entities on the production floor. Connectivity, a vital enabler, plays a crucial role through state-of-the-art Digital Twinning (DT) technologies driven by underlying innovations like the industrial Internet of Things, Cloud Computing, and advancements in sensory devices. DT, which plays a vital role in the various planning functions under the production and operations management umbrella, is being used in the developed combined CAPP-GPT (Computer-Aided Process Planning-Generative Pretrained Transformer) and production scheduling approach to address disruptions on the shopfloor and in self-healing of the manufacturing processes at a micro-CAPP level by optimally adapting the process parameters and the developed toolpath on the fly based on online process signature measurements. In a leap commensurate with that which has taken place in Natural Language Processing-Large Language Models (Chat-GPT), similar efforts are currently being undertaken to parse CAD data structures and blueprints, fusing operations research and predictive analytics algorithms to carry out setup planning as well as sequencing and grouping manufacturing sub-operations. A hybridized Optimization and Machine Learning (ML) approach is employed where Logical Analysis of Data is used to solve the problem heuristically, exploiting various generative and variant methods at heart. Another extension of this macro-CAPP problem is being tackled by integrating the problem with delayed product differentiation, lot-sizing, and transfer line balance for futuristic batch-production shops employing Hybrid Manufacturing (HM) and Smart Assembly. At the micro-CAPP level, HM process parameters are optimized using a comprehensive approach employing the Taguchi loss function to assess surface roughness, internal failure costs, and other criteria, including greenhouse gas emissions and expended energy. Online measurements of the process signatures are also employed to adapt the initial set of process parameters using different automatic control schemes. ML is used to identify the process parameters carrying simulations on Simulink before the system is deployed.

Dimethyl Sulfoxide Attenuates Ionizing Radiation-induced Centrosome Overduplication and Multipolar Cell Division in Human Induced Pluripotent Stem Cells.

Centrosomes are important organelles for cell division and genome stability. Ionizing radiation exposure efficiently induces centrosome overduplication via the disconnection of the cell and centrosome duplication cycles. Over duplicated centrosomes cause mitotic catastrophe or chromosome aberrations, leading to cell death or tumorigenesis. Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), can differentiate into all organs. To maintain pluripotency, PSCs show specific cellular dynamics, such as a short G1 phase and silenced cell-cycle checkpoints for high cellular proliferation. However, how exogenous DNA damage affects cell cycle-dependent centrosome number regulation in PSCs remains unknown. This study used human iPSCs (hiPSCs) derived from primary skin fibroblasts as a PSC model to address this question. hiPSCs derived from somatic cells could be a useful tool for addressing the radiation response in cell lineage differentiation. After radiation exposure, the hiPSCs showed a higher frequency of centrosome overduplication and multipolar cell division than the differentiated cells. To suppress the indirect effect of radiation exposure, we used the radical scavenger dimethyl sulfoxide (DMSO). Combined treatment with radiation and DMSO efficiently suppressed DNA damage and centrosome overduplication in hiPSCs. Our results will contribute to the understanding of the dynamics of stem cells and the assessment of the risk of genome instability for regenerative medicine.

CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8+ Tcell formation.

Nutrient availability and organelle biology direct tissue homeostasis and cell fate, but how these processes orchestrate tissue immunity remains poorly defined. Here, using invivo CRISPR-Cas9 screens, we uncovered organelle signaling and metabolic processes shaping CD8+ tissue-resident memory T (TRM) cell development. TRM cells depended on mitochondrial translation and respiration. Conversely, three nutrient-dependent lysosomal signaling nodes-Flcn, Ragulator, and Rag GTPases-inhibited intestinal TRM cell formation. Depleting these molecules or amino acids activated the transcription factor Tfeb, thereby linking nutrient stress to TRM programming. Further, Flcn deficiency promoted protective TRM cell responses in the small intestine. Mechanistically, the Flcn-Tfeb axis restrained retinoic acid-induced CCR9 expression for migration and transforming growth factor β (TGF-β)-mediated programming for lineage differentiation. Genetic interaction screening revealed that the mitochondrial protein Mrpl52 enabled early TRM cell formation, while Acss1 controlled TRM cell development under Flcn deficiency-associated lysosomal dysregulation. Thus, the interplay between nutrients, organelle signaling, and metabolic adaptation dictates tissue immunity.

The ecological and evolutionary dynamics of inselbergs.

Islands are fundamental model systems in ecology, biogeography, and evolutionary biology. However, terrestrial islands, unlike their aquatic counterparts, have received comparatively less attention. Among these land islands, inselbergs (i.e. isolated rock outcrops with diverse lithologies and a modest topographical prominence) stand out as iconic examples distributed worldwide across global biomes. Due to their durable lithology, inselbergs change slowly, persisting for tens of millions of years. In this review, we propose a biological definition for inselbergs that captures three fundamental characteristics of inselbergs from the perspective of biota. These are old age, isolation and the presence of unique microhabitats that are rare or absent in the surrounding matrix, fostering distinct communities often with unique and endemic biota. We synthesise the state of the art and formulate a set of testable hypotheses to deepen our understanding of the origins and maintenance of diversity on inselbergs, which are increasingly exposed to anthropogenic threats. By offering different habitats compared to the surrounding habitat matrix (e.g. moist microhabitats in dryland landscapes and xeric environments in humid tropical landscapes), inselbergs may allow specific lineages to thrive beyond their typical geographical limits. Particularly in drylands and degraded landscapes, inselbergs may not just provide different habitats but also act as ecological refuges or evolutionary refugia by providing a wider range of potential microhabitats than the surrounding matrix, enhancing resilience and promoting regional biodiversity. The central role of the matrix ensures that the ecological and evolutionary dynamics of inselbergs differ from those of true islands such as oceanic islands. Given that inselberg biota coexist within a terrestrial matrix, interactions between inselberg and matrix populations impact each other significantly. Over evolutionary timescales, matrix species may contract to inselberg refugia, preserving lineages while cycles of isolation and reconnection may drive speciation via a species pump. Although inselberg biodiversity has been studied predominantly from an island biogeography perspective, we argue that depending on the spatial scale, habitat specificity and mobility of the organisms considered, a range of different theories and paradigms can help explain the biogeography and local distribution patterns of different taxonomic and functional groups of inselberg species.

Meta-analysis of gonadal transcriptome provides novel insights into sex change mechanism across protogynous fishes.

Protogyny, being capable of changing from female to male during their lifetime, is prevalent in 20 families of teleosts but is believed to have evolved within specific evolutionary lineages. Therefore, shared regulatory factors governing the sex change process are expected to be conserved across protogynous fishes. However, a comprehensive understanding of this mechanism remains elusive. To identify these factors, we conducted a meta-analysis using gonadal transcriptome data from seven species. We curated data pairs of ovarian tissue and transitional gonad, and employed ratios of expression level as a unified criterion for differential expression, enabling a meta-analysis across species. Our approach revealed that classical sex change-related genes exhibited differential expression levels between the ovary and transitional gonads, consistent with previous reports. These results validate our methodology's robustness. Additionally, we identified novel genes not previously linked to gonadal sex change in fish. Notably, changes in the expression levels of acetoacetyl-CoA synthetase and apolipoprotein Eb, which are involved in cholesterol synthesis and transport, respectively, suggest that the levels of cholesterol, a precursor of steroid hormones crucial for sex change, are decreased upon sex change onset in the gonads. This implies a potential universal influence of cholesterol dynamics on gonadal transformation in protogyny.

Design of Differential Loudspeaker Line Array for Steerable Frequency-Invariant Beamforming

Differential beamforming has attracted much research since it can utilize an array with a small aperture size to form frequency-invariant beampatterns and achieve high directional gains. It has recently been applied to the loudspeaker line array to produce a broadside frequency-invariant radiation pattern. However, designing steerable frequency-invariant beampatterns for the loudspeaker line array has yet to be explored. This paper proposes a method to design a steerable differential beamformer with a loudspeaker line array. We first determine the target differential beampatterns according to the desired direction, the main lobe width, and the beampattern order. Then, we transform the target beampattern into the modal domain for representation. The Jacobi-Anger expansion is subsequently used to design the beamformer so that the resulting beampattern matches the target differential beampattern. Furthermore, based on the criterion of minimizing the mean square error between the synthesized beampattern and the ideal one, a multi-constraint optimization problem, which compromises between the robustness and the mean square error, is formulated to calculate the optimal desired weighting vector. Simulations and experimental results show that the proposed method can achieve steerable frequency-invariant beamforming from 300 Hz–4 kHz.

Regulation of alternative polyadenylation isoforms of Timp2 is an effector event of RAS signaling in cell transformation.

Alternative polyadenylation (APA) generates mRNA isoforms with different lengths of the 3' untranslated region (3' UTR). The tissue inhibitor of metalloproteinase 2 (TIMP2) plays a key role in extracellular matrix remodeling under various developmental and disease conditions. Both human and mouse genes encoding TIMP2 contain two highly conserved 3'UTR APA sites, leading to mRNA isoforms that differ substantially in 3'UTR size. APA of Timp2 is one of the most significantly regulated events in multiple cell differentiation lineages. Here we show that Timp2 APA is highly regulated in transformation of NIH3T3 cells by the oncogene HRAS G12V . Perturbations of isoform expression with long 3'UTR isoform-specific knockdown or genomic removal of the alternative UTR (aUTR) region indicate that the long 3'UTR isoform contributes to the secreted Timp2 protein much more than the short 3'UTR isoform. The short and long 3'UTR isoforms differ in subcellular localization to endoplasmic reticulum (ER). Strikingly, Timp2 aUTR enhances secreted protein expression but no effect on intracellular proteins in reporter assays. Furthermore, downregulation of Timp2 long isoform mitigates gene expression changes elicited by HRAS G12V . Together, our data indicate that regulation of Timp2 protein expression through APA isoform changes is an integral part of RAS-mediated cell transformation and 3'UTR isoforms of Timp2 can have distinct impacts on expression of secreted vs. intracellular proteins.

Single-cell multi-omics map of human fetal blood in Down syndrome

Down syndrome predisposes individuals to haematological abnormalities, such as increased number of erythrocytes and leukaemia in a process that is initiated before birth and is not entirely understood1–3. Here, to understand dysregulated haematopoiesis in Down syndrome, we integrated single-cell transcriptomics of over 1.1 million cells with chromatin accessibility and spatial transcriptomics datasets using human fetal liver and bone marrow samples from 3 fetuses with disomy and 15 fetuses with trisomy. We found that differences in gene expression in Down syndrome were dependent on both cell type and environment. Furthermore, we found multiple lines of evidence that haematopoietic stem cells (HSCs) in Down syndrome are ‘primed’ to differentiate. We subsequently established a Down syndrome-specific map linking non-coding elements to genes in disomic and trisomic HSCs using 10X multiome data. By integrating this map with genetic variants associated with blood cell counts, we discovered that trisomy restructured regulatory interactions to dysregulate enhancer activity and gene expression critical to erythroid lineage differentiation. Furthermore, as mutations in Down syndrome display a signature of oxidative stress4,5, we validated both increased mitochondrial mass and oxidative stress in Down syndrome, and observed that these mutations preferentially fell into regulatory regions of expressed genes in HSCs. Together, our single-cell, multi-omic resource provides a high-resolution molecular map of fetal haematopoiesis in Down syndrome and indicates significant regulatory restructuring giving rise to co-occurring haematological conditions.

Ultra-Wideband Common-Mode Rejection Structure with Autonomous Phase Balancing for Ultra-High-Speed Digital Transmission.

For ultra-high-speed digital transmission, required by 5G/6G communications, ultra-wideband common-mode rejection (CMR) structures with autonomous phase-balancing capability are proposed. Common-mode noise, caused by phase and amplitude unbalances, is one of the most undesired disturbances affecting modern digital circuits. According to the circuit design guides with a typically used differential line (DL) for high-speed digital transmission, common-mode rejection is achieved using CMR filters, and the unbalanced phase, caused by a length difference between the two signal lines of a DL, is compensated by inserting an additional delay line. However, due to nonlinear phase interactions between the two DLs and unbalanced electromagnetic (EM) interferences, the conventional compensation method is frequency-limited at around 10 GHz. To significantly enhance the common-mode rejection level and extend the phase recovery bandwidth, the proposed CMR structure utilizes a planar balanced line (BL), such as a coplanar stripline (CPS) or a parallel stripline (PSL), along with additional conductor strips arranged laterally near the BL. To demonstrate the performance of the proposed BL-based CMR structures, various types of CMR structures are fabricated, and the measurement results are compared with the 3D EM simulation results. As a result, it is proven that the proposed BL-based CMR structures have the capability to reject the common-mode noise with suppression levels of more than 10 dB and to simultaneously recover the phase balance from near DC to over 40 GHz.

The role of TEAD4 in trophectoderm commitment and development is not conserved in non-rodent mammals.

The first lineage differentiation in mammals gives rise to the inner cell mass and the trophectoderm (TE). In mice, TEAD4 is a master regulator of TE commitment, as it regulates the expression of other TE-specific genes and its ablation prevents blastocyst formation, but its role in other mammals remains unclear. Herein, we have observed that TEAD4 ablation in two phylogenetically distant species (bovine and rabbit) does not impede TE differentiation, blastocyst formation and the expression of TE markers, such as GATA3 and CDX2, although a reduced number of cells in the inner cell mass was observed in bovine TEAD4 knockout (KO) blastocysts. Transcriptional analysis in bovine blastocysts revealed no major transcriptional effect of the ablation, although the expression of hypoblast and Hippo signalling-related genes tended to be decreased in KO embryos. Experiments were conducted in the bovine model to determine whether TEAD4 was required for post-hatching development. TEAD4 KO spherical conceptuses showed normal development of the embryonic disc and TE, but hypoblast migration rate was reduced. At later stages of development (tubular conceptuses), no differences were observed between KO and wild-type conceptuses.

Establishment of methanogen bacterial interactions during the preweaning period of dairy cattle

Ruminant livestock are major contributors to anthropogenic methane emissions in the United States and worldwide. Enteric methane is generated by methanogenic archaea residing in ruminant digestive tracts. Information on when methanogens colonize the gut and when they begin to interact with bacteria during the early phases of the ruminant life cycle is less explored. The objectives of this study were (i) to investigate the composition of the methanogenic archaeal community at birth and through the weaning transition and (ii) to determine if and when the methanogenic archaea begin to interact with bacteria in the lower gut of neonatal dairy calves. Ten female Holstein calves (approximately 45kg birth weight) were enrolled in the study. Fecal samples were collected every two weeks (Wk 2, 4, 6, 8, 10, and 12) between birth and weaning and analyzed for methanogenic archaeal diversity via 16S rRNA amplicon sequencing and quantitative real-time PCR (RT-qPCR). Estimates of alpha diversity (Observed species, and Shannon diversity index) and beta diversity (weighted and unweighted UniFrac distances) showed significant differences (P < 0.05) between archaeal communities across timepoints. Both 16S rRNA amplicon sequencing and RT-qPCR analyses revealed Methanobrevibacter was the most prevalent genus at Wk2, Wk4, and Wk6, whereas Methanosphaera gradually increased with time and was most abundant at Wk10 and Wk12. Correlation analysis revealed that Methanobrevibacter and Methanosphaera were inversely correlated with each other and formed distinct cohorts with specific bacterial lineages similar to those reported in the mature rumen, thus revealing that these associations are established during the preweaning period. Therefore, the preweaning period presents a window of opportunity to interfere with early-life methanogenic colonization with the ultimate goal of reducing enteric methane emissions without perturbing ruminal function later in the life of dairy cattle.

Temporal BMP4 effects on mouse embryonic and extraembryonic development.

The developing placenta, which in mice originates through the extraembryonic ectoderm (ExE), is essential for mammalian embryonic development. Yet unbiased characterization of the differentiation dynamicsof the ExE and its interactions with the embryo proper remains incomplete. Here we develop a temporal single-cell model of mouse gastrulation that maps continuous and parallel differentiation in embryonic and extraembryonic lineages. This is matched with a three-way perturbation approach to target signalling from the embryo proper, the ExE alone, or both. We show that ExE specification involves early spatial and transcriptional bifurcation of uncommitted ectoplacental cone cells and chorion progenitors. Early BMP4 signalling from chorion progenitors is required for proper differentiation of uncommitted ectoplacental cone cells and later for their specification towards trophoblast giant cells. We also find biphasic regulation by BMP4 in the embryo. The early ExE-originating BMP4 signal is necessary for proper mesoendoderm bifurcation and forallantois and primordial germ cell specification. However, commencing at embryonic day 7.5, embryo-derived BMP4 restricts the primordial germ cell pool size by favouring differentiation of their extraembryonic mesoderm precursors towards an allantois fate. ExE and embryonic tissues are therefore entangled in time, space and signalling axes, highlighting the importance of their integrated understanding and modelling in vivo and in vitro.

Leveraging the Physicochemical Attributes of Biomimetic Hydrogel Nanocomposites in Stem Cell Differentiation.

The field of tissue engineering has witnessed significant advancements with the advent of hydrogel nanocomposites (HNC), emerging as a highly promising platform for regenerative medicine. HNCs provide a versatile platform that significantly enhances the differentiation of stem cells into specific cell lineages, making them highly suitable for tissue engineering applications. By incorporating nanoparticles, the mechanical properties of hydrogels, such as elasticity, porosity, and stiffness, are improved, addressing common challenges such as short-term stability, cytotoxicity, and scalability. These nanocomposites also exhibit enhanced biocompatibility and bioavailability, which are crucial to their effectiveness in clinical applications. Furthermore, HNCs are responsive to various triggers, allowing for precise control over their chemical properties, which is beneficial in creating 3D microenvironments, promoting wound healing, and enabling controlled drug delivery systems. This review provides a comprehensive overview of the production methods of HNCs and the factors influencing their physicochemical and biological properties, particularly in relation to stem cell differentiation and tissue repair. Additionally, it discusses the challenges in developing HNCs and highlights their potential to transform the field of regenerative medicine through improved mechanotransduction and controlled release systems.

Fast-response and high figure of merit phase shifter based on polymer- stabilised liquid crystals

ABSTRACT This article presents a novel fast-response and high figure of merit (FoM) phase shifter based on polymer-stabilised liquid crystal (LC) for Ka-band. The developed LC phase shifter (LCPS), utilising a coplanar differential line loading 19 parallel-plate variable capacitors with 4.6 μm LC-cell, adopts polymer-stabilised LC technology in which the parallelly orientated polymer networks facilitate the LC molecules’ return to their initial state upon removal of the bias voltage, thus accelerating response time. The proposed LCPS has been fabricated to evaluate its superior capabilities. The experimental results closely match the simulation results, confirming its good congruity. This design has measured S 11 < −10 dB in 29–31 GHz. LCs with different HCM002 concentrations are injected to LCPS, and the experimental outcomes showed that LCs with 9 wt% HCM002 concentration significantly improve the response time of LCPS to 2.8 ms with a high FoM of 91.2°/dB at 30 GHz.

Virulence variation and pathotypes of Zymoseptoria tritici isolates causing wheat leaf blotch in Oromia, Ethiopia

Leaf blotch, caused by Zymoseptoria tritici, is a fungal disease that poses a severe threat to wheat production worldwide. Knowledge of virulence variability is crucial in choosing effective control measures. However, there have only been a few studies of the pathogenic variability and pathotypes within Ethiopian isolates. Hence, the objective of this study was to assess the virulence spectrum and variability of Z. tritici isolates. Forty-three isolates were tested for their virulence and pathotype against 7 wheat differential lines that have different resistance genes. A pathogenicity assay detected 41 differential line-specific virulent isolates among 301 interactions between a host and pathogen based on the percentage coverage of the leaf area by pycnidia. Some isolates were virulent against 50 %–60 % of the resistant genes, but most of them were virulent against some differential lines. Isolates such as EtA-11, EtSh-1, EtSh-2, EtSh-4, and EtA-19 expressed broad-spectrum virulence, highlighting that such isolates are useful for germplasm screening. The isolates were classified into 25 pathotypes, defined by their differential virulence responses. They were also assigned to two clusters according to their mean pycnidia percent. Pathotypes and principal component analysis detected 58.1 % and 62.2 % pathogenic diversity in Ethiopian isolates, respectively. The current findings provide information that breeders can use to identify and select more resistant varieties for farmers.