BUB1/KIF14 complex promotes anaplastic thyroid carcinoma progression by inducing chromosome instability.

Chromosome instability (CIN) is a common contributor driving the formation and progression of anaplastic thyroid cancer (ATC), but its mechanism remains unclear. The BUB1 mitotic checkpoint serine/threonine kinase (BUB1) is responsible for the alignment of mitotic chromosomes, which has not been thoroughly studied in ATC. Our research demonstrated that BUB1 was remarkably upregulated and closely related to worse progression-free survival. Knockdown of BUB1 attenuated cell viability, invasion, migration and induced cell cycle arrests, whereas overexpression of BUB1 promoted the cell cycle progression of papillary thyroid cancer cells. BUB1 knockdown remarkably repressed tumour growth and tumour formation of nude mice with ATC xenografts and suppressed tumour metastasis in a zebrafish xenograft model. Inhibition of BUB1 by its inhibitor BAY-1816032 also exhibited considerable anti-tumour activity. Further studies showed that enforced expression of BUB1 evoked CIN in ATC cells. BUB1 induced CIN through phosphorylation of KIF14 at serine1292 (Ser1292 ). Overexpression of the KIF14ΔSer1292 mutant was unable to facilitate the aggressiveness of ATC cells when compared with that of the wild type. Collectively, these findings demonstrate that the BUB1/KIF14 complex drives the aggressiveness of ATC by inducing CIN.

Climatic niche evolution and niche conservatism of Nymphaea species in Africa, South America, and Australia.

BACKGROUND: Interest in the evolution of climatic niches, particularly in understanding the potential adaptive responses of species under climate change, has increased both theoretically and within macroecological studies. These studies have provided valuable insights into how climatic traits of species influence their niche evolution. In this study, we aim to investigate whether niche conservatism plays a role in the species diversification of Nymphaea, a group of aquatic plants with a cosmopolitan distribution that is facing severe habitat loss. We will use climatic models and phylogenetic data for 23 species to reconstruct Nymphaea's niche evolution, measure niche overlap, and assess disparity through time while testing for evolutionary models. RESULTS: There was a lot of overlap in niches both within and between groups, especially for species that can be found in many places. The breadth and peaks of the niche profile varied depending on the bioclimatic variables, which suggested that the species evolved differently to cope with changes in climate. The analysis also showed that evolutionary changes happened across the phylogeny, with weak to moderate signals. The morphological disparity index (MDI) values indicated that there were disparities within subclades over time but not between or among them. Niche reconstruction and evolution analysis revealed both convergent and divergent evolution among various variables. For example, N. immutabilis, N. atrans, N. violancea, and N. nouchali evolved towards intermediate temperatures for bio2 and bio3 (isothermity) while moving towards extreme temperatures for bio8 and bio9 (wettest and driest average quarterly temperatures). CONCLUSION: Our study will improve our understanding of how changes in climatic niches are potentially driving the evolution of Nymphaea. It has significant scientific implications for the limits, assemblages, evolution, and diversification of species. This information is crucial for the ongoing efforts of conservation and management, particularly considering the inevitable effects of climate change.

Expression inheritance and constraints on cis- and trans-regulatory mutations underlying lotus color variation.

Both cis- and trans-regulatory mutations drive changes in gene expression that underpin plant phenotypic evolution. However, how and why these two major types of regulatory mutations arise in different genes and how gene expression is inherited and associated with these regulatory changes are unclear. Here, by studying allele-specific expression in F1 hybrids of pink-flowered sacred lotus (Nelumbo nucifera) and yellow-flowered American lotus (N. lutea), we reveal the relative contributions of cis- and trans-regulatory changes to interspecific expression rewiring underlying petal color change and how the expression is inherited in hybrids. Although cis-only variants influenced slightly more genes, trans-only variants had a stronger impact on expression differences between species. In F1 hybrids, genes under cis-only and trans-only regulatory effects showed a propensity toward additive and dominant inheritance, respectively, whereas transgressive inheritance was observed in genes carrying both cis- and trans-variants acting in opposite directions. By investigating anthocyanin and carotenoid coexpression networks in petals, we found that the same category of regulatory mutations, particularly trans-variants, tend to rewire hub genes in coexpression modules underpinning flower color differentiation between species; we identified 45 known genes with cis- and trans-regulatory variants significantly correlated with flower coloration, such as ANTHOCYANIN 5-AROMATIC ACYLTRANSFERASE (ACT), GLUTATHIONE S-TRANSFERASE F11 (GSTF11), and LYCOPENE Ε-CYCLASE (LCYE). Notably, the relative abundance of genes in different categories of regulatory divergence was associated with the inferred magnitude of constraints like expression level and breadth. Overall, our study suggests distinct selective constraints and modes of gene expression inheritance among different regulatory mutations underlying lotus petal color divergence.

Thin-film lithium niobate electro-optic isolator fabricated by photolithography assisted chemo-mechanical etching.

We report an electro-optic isolator fabricated on thin-film lithium niobate by photolithography-assisted chemo-mechanical etching that shows an isolation of 39.50 dB and an overall fiber-to-fiber loss of 2.6 dB.

Fluorinated Polymer Donors for Nonfullerene Organic Solar Cells.

The rapid development of narrow-bandgap nonfullerene acceptors (NFAs) has boosted the efficiency of organic solar cells (OSCs) over 19 %. The new features of high-performance NFAs, such as visible-NIR light absorption, moderate the highest occupied molecular orbitals (HOMO), and high crystallinity, require polymer donors with matching physical properties. This emphasizes the importance of methods that can effectively tune the physical properties of polymers. Owning to very small atom size and strongest electronegativity, the fluorination has been proved the most efficient strategy to regulate the physical properties of polymer donors, including frontier energy level, absorption coefficient, dielectric constant, crystallinity and charge transport. Owing to the success of fluorination strategy, the vast majority of high-performance polymer donors possess one or more fluorine atoms. In this review, the fluorination synthetic methods, the synthetic route of well-known fluorinated building blocks, the fluorinated polymers which are categorized by the type of donor or acceptor units, and the relationships between the polymer structures, properties, and photovoltaic performances are comprehensively surveyed. We hope this review could provide the readers a deeper insight into fluorination strategy and lay a strong foundation for future innovation of fluorinated polymers.

Robust Crystal Phase Separation with Distinct Charge, Orbital, and Spin Orders in AgMn7O12.

An AA'3B4O12-type A-site-ordered quadruple perovskite oxide AgMn7O12 was prepared by high-pressure and high-temperature methods. At room temperature, the compound crystallizes into a cubic Im3̅ symmetry with a charge distribution of AgMn33+Mn43.5+O12. With the temperature decreasing to TCO,OO ≈ 180 K, the compound undergoes a structural phase transition toward a monoclinic C2/m symmetry, giving rise to a B-site charge- and orbital-ordered AgMn33+Mn23+Mn24+O12 phase. Moreover, this charge-/orbital-ordered main phase coexists with the initial cubic AgMn33+Mn43.5+O12 phase in the wide temperature range we measured. The charge-/orbital-ordered phase shows two antiferromagnetic phase transitions near 125 and 90 K, respectively. Short-range ferromagnetic correlations are found to occur for the initial B-site mixed cubic phase around 35 K. Because of the robust phase separation, considerable magnetoresistance effects are observed below TCO,OO in AgMn7O12.

Bibenzyl and naphthalene derivatives from Dendrobium chrysanthum and their anti-hepatic-steatosis activities.

In this study, 16 new compounds, six bibenzyls (1-6) and 10 naphthalenes (7-13), including three pairs of naphthalene enantiomers and three known compounds (14-16), were isolated from Dendrobium chrysanthum. Structurally, compounds 1-5 are previously undescribed dimeric bibenzyls, uniquely linked by unusual carbon bonds. The structures of the compounds were determined using spectroscopy and X-ray crystallography. The screening results indicated that 1, 2, and 5 showed remarkable lipid-lowering activities in FFA-induced HepG2 cells, with EC50 values ranging from 3.13 to 6.57 µM. Moreover, 1, 2, and 5 significantly decreased both the mRNA and protein levels of the target SREBP-1c, and 5 also reduced PPARα mRNA and protein levels. Therefore, 1, 2, and 5 are potential drugs against hepatic steatosis by targeting PPARα or SREBP-1c.

Fibrinogen to HDL-Cholesterol ratio as a predictor of mortality risk in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is characterized by inflammation, oxidative stress, and atherosclerosis, contributing to increased mortality risk. High-density lipoprotein (HDL) takes a crucial part in mitigating atherosclerosis and inflammation through its diverse functionalities. Conversely, fibrinogen is implicated in the development of atherosclerotic plaques. However, the mortality risk predictive capacity of fibrinogen to HDL-cholesterol ratio (FHR) in AMI patients remains unexplored. This research aimed to evaluate the effectiveness of FHR for mortality risk prediction in relation to AMI. METHODS: A retrospective study involving 13,221 AMI patients from the Cardiorenal ImprovemeNt II cohort (NCT05050877) was conducted. Baseline FHR levels were used to categorize patients into quartiles. The assessment of survival disparities among various groups was conducted by employing Kaplan‒Meier diagram. Cox regression was performed for investigating the correlation between FHR and adverse clinical outcomes, while the Fine-Gray model was applied to evaluate the subdistribution hazard ratios for cardiovascular death. RESULTS: Over a median follow-up of 4.66 years, 2309 patients experienced all-cause death, with 1007 deaths attributed to cardiovascular disease (CVD). The hazard ratio (HR) and its 95% confidence interval (CI) for cardiac and all-cause death among individuals in the top quartile of FHR were 2.70 (1.99-3.65) and 1.48 (1.26-1.75), respectively, in comparison to ones in the first quartile, after covariate adjustment. Restricted cubic spline analysis revealed that FHR was linearly correlated with all-cause mortality, irrespective of whether models were adjusted or unadjusted (all P for nonlinearity > 0.05). CONCLUSION: AMI patients with increased baseline FHR values had higher all-cause and cardiovascular mortality, regardless of established CVD risk factors. FHR holds promise as a valuable tool for evaluating mortality risk in AMI patients. TRIAL REGISTRATION: The Cardiorenal ImprovemeNt II registry NCT05050877.

Expression divergence of expansin genes drive the heteroblasty in Ceratopteris chingii.

BACKGROUND: Sterile-fertile heteroblasty is a common phenomenon observed in ferns, where the leaf shape of a fern sporophyll, responsible for sporangium production, differs from that of a regular trophophyll. However, due to the large size and complexity of most fern genomes, the molecular mechanisms that regulate the formation of these functionally different heteroblasty have remained elusive. To shed light on these mechanisms, we generated a full-length transcriptome of Ceratopteris chingii with PacBio Iso-Seq from five tissue samples. By integrating Illumina-based sequencing short reads, we identified the genes exhibiting the most significant differential expression between sporophylls and trophophylls. RESULTS: The long reads were assembled, resulting in a total of 24,024 gene models. The differential expressed genes between heteroblasty primarily involved reproduction and cell wall composition, with a particular focus on expansin genes. Reconstructing the phylogeny of expansin genes across 19 plant species, ranging from green algae to seed plants, we identified four ortholog groups for expansins. The observed high expression of expansin genes in the young sporophylls of C. chingii emphasizes their role in the development of heteroblastic leaves. Through gene coexpression analysis, we identified highly divergent expressions of expansin genes both within and between species. CONCLUSIONS: The specific regulatory interactions and accompanying expression patterns of expansin genes are associated with variations in leaf shapes between sporophylls and trophophylls.

Evolution of isoform-level gene expression patterns across tissues during lotus species divergence.

Both gene duplication and alternative splicing (AS) drive the functional diversity of gene products in plants, yet the relative contributions of the two key mechanisms to the evolution of gene function are largely unclear. Here, we studied AS in two closely related lotus plants, Nelumbo lutea and Nelumbo nucifera, and the outgroup Arabidopsis thaliana, for both single-copy and duplicated genes. We show that most splicing events evolved rapidly between orthologs and that the origin of lineage-specific splice variants or isoforms contributed to gene functional changes during species divergence within Nelumbo. Single-copy genes contain more isoforms, have more AS events conserved across species, and show more complex tissue-dependent expression patterns than their duplicated counterparts. This suggests that expression divergence through isoforms is a mechanism to extend the expression breadth of genes with low copy numbers. As compared to isoforms of local, small-scale duplicates, isoforms of whole-genome duplicates are less conserved and display a less conserved tissue bias, pointing towards their contribution to subfunctionalization. Through comparative analysis of isoform expression networks, we identified orthologous genes of which the expression of at least some of their isoforms displays a conserved tissue bias across species, indicating a strong selection pressure for maintaining a stable expression pattern of these isoforms. Overall, our study shows that both AS and gene duplication contributed to the diversity of gene function during the evolution of lotus.

The tumor ecosystem in head and neck squamous cell carcinoma and advances in ecotherapy.

The development of head and neck squamous cell carcinoma (HNSCC) is a multi-step process, and its survival depends on a complex tumor ecosystem, which not only promotes tumor growth but also helps to protect tumor cells from immune surveillance. With the advances of existing technologies and emerging models for ecosystem research, the evidence for cell-cell interplay is increasing. Herein, we discuss the recent advances in understanding the interaction between tumor cells, the major components of the HNSCC tumor ecosystem, and summarize the mechanisms of how biological and abiotic factors affect the tumor ecosystem. In addition, we review the emerging ecological treatment strategy for HNSCC based on existing studies.

Phylogenomic Analyses of Alismatales Shed Light into Adaptations to Aquatic Environments.

Land plants first evolved from freshwater algae, and flowering plants returned to water as early as the Cretaceous and multiple times subsequently. Alismatales is the largest clade of aquatic angiosperms including all marine angiosperms, as well as terrestrial plants. We used Alismatales to explore plant adaptations to aquatic environments by analyzing a data set that included 95 samples (89 Alismatales species) covering four genomes and 91 transcriptomes (59 generated in this study). To provide a basis for investigating adaptations, we assessed phylogenetic conflict and whole-genome duplication (WGD) events in Alismatales. We recovered a relationship for the three main clades in Alismatales as (Tofieldiaceae, Araceae) + core Alismatids. We also found phylogenetic conflict among the three main clades that was best explained by incomplete lineage sorting and introgression. Overall, we identified 18 putative WGD events across Alismatales. One of them occurred at the most recent common ancestor of core Alismatids, and three occurred at seagrass lineages. We also found that lineage and life-form were both important for different evolutionary patterns for the genes related to freshwater and marine adaptation. For example, several light- or ethylene-related genes were lost in the seagrass Zosteraceae, but are present in other seagrasses and freshwater species. Stomata-related genes were lost in both submersed freshwater species and seagrasses. Nicotianamine synthase genes, which are important in iron intake, expanded in both submersed freshwater species and seagrasses. Our results advance the understanding of the adaptation to aquatic environments and WGDs using phylogenomics.

The dynamic history of plastome structure across aquatic subclass Alismatidae.

BACKGROUND: The rapidly increasing availability of complete plastomes has revealed more structural complexity in this genome under different taxonomic levels than expected, and this complexity provides important evidence for understanding the evolutionary history of angiosperms. To explore the dynamic history of plastome structure across the subclass Alismatidae, we sampled and compared 38 complete plastomes, including 17 newly assembled, representing all 12 recognized families of Alismatidae. RESULT: We found that plastomes size, structure, repeat elements, and gene content were highly variable across the studied species. Phylogenomic relationships among families were reconstructed and six main patterns of variation in plastome structure were revealed. Among these, the inversion from rbcL to trnV-UAC (Type I) characterized a monophyletic lineage of six families, but independently occurred also in Caldesia grandis. Three independent ndh gene loss events were uncovered across the Alismatidae. In addition, we detected a positive correlation between the number of repeat elements and the size of plastomes and IR in Alismatidae. CONCLUSION: In our study, ndh complex loss and repeat elements likely contributed to the size of plastomes in Alismatidae. Also, the ndh loss was more likely related to IR boundary changes than the adaptation of aquatic habits. Based on existing divergence time estimation, the Type I inversion may have occurred during the Cretaceous-Paleogene in response to the extreme paleoclimate changes. Overall, our findings will not only allow exploring the evolutionary history of Alismatidae plastome, but also provide an opportunity to test if similar environmental adaptations result in convergent restructuring in plastomes.

Haplotype-resolved genome assembly provides insights into the evolution of S-locus supergene in distylous Nymphoides indica.

Distyly has evolved independently in numerous animal-pollinated angiosperm lineages. Understanding of its molecular basis has been restricted to a few species, primarily Primula. Here, we investigate the genetic architecture of the single diallelic locus (S-locus) supergene, a linkage group of functionally associated genes, and explore how it may have evolved in distylous Nymphoides indica, a lineage of flowering plants not previously investigated. We assembled haplotype-resolved genomes, used read-coverage-based genome-wide association study (rb-GWAS) to locate the S-locus supergene, co-expression network analysis to explore gene networks underpinning the development of distyly, and comparative genomic analyses to investigate the origins of the S-locus supergene. We identified three linked candidate S-locus genes - NinBAS1, NinKHZ2, and NinS1 - that were only evident in the short-styled morph and were hemizygous. Co-expression network analysis suggested that brassinosteroids contribute to dimorphic sex organs in the short-styled morph. Comparative genomic analyses indicated that the S-locus supergene likely evolved via stepwise duplications and has been affected by transposable element activities. Our study provides novel insight into the structure, regulation, and evolution of the supergene governing distyly in N. indica. It also provides high-quality genomic resources for future research on the molecular mechanisms underlying the striking evolutionary convergence in form and function across heterostylous taxa.

Electro-optically tunable optical delay line with a continuous tuning range of ∼220 fs in thin-film lithium niobate.

We demonstrate fabrication of a 30-cm-long thin-film lithium niobate (TFLN) optical delay line (ODL) incorporated with segmented microelectrodes of 24-cm total length using the femtosecond laser lithography technique. The transmission spectra of the unbalanced Mach-Zehnder interferometers (MZIs) reveal an ultra-low propagation loss of 0.025 dB/cm. The device exhibits a low half-wave voltage of 0.45 V, corresponding to a voltage-length product of 10.8 V·cm, which is equivalent to 5.4 V·cm in the push-pull configuration. We also demonstrate a high electro-optic (EO) tuning efficiency of 3.146 fs/V and a continuous tuning range of 220 fs in the fabricated ODL.

On-chip coherent beam combination of waveguide amplifiers on Er3+-doped thin film lithium niobate.

We demonstrate on-chip coherent beam combination of two waveguide amplifiers on Er3+-doped thin film lithium niobate (Er:TFLN) platform. Our device is built based on an electro-optic modulator fabricated on Er:TFLN. The output power of the coherently combined amplifiers is measured as high as 12.9 mW, surpassing that of previous single waveguide amplifiers based on an Er3+-doped thin film lithium niobate platform.

Iatrogenic pseudoaneurysm rupture of the middle cerebral artery after an intracranial pressure monitor placement: a case report and literature review.

Thalamic hemorrhage (TH) is a devastating disease with a high mortality rate; however, no specific form of therapy has been proven to reduce mortality. Patients with hemorrhagic stroke undergo intracranial pressure (ICP) monitoring. However, cases involving pseudoaneurysms caused by ICP monitoring in patients with intracerebral hemorrhage have not been reported previously. Here, we report a case of pseudoaneurysm caused by an ICP monitor that was fitted due to hypertensive cerebral hemorrhage.

A Multifluorination Strategy Toward Wide Bandgap Polymers for Highly Efficient Organic Solar Cells.

Creating new electron-deficient unit is highly demanded to develop high-performance polymer donors for non-fullerene organic solar cells (OSCs). Herein, we reported a multifluorinated unit 4,5,6,7-tetrafluoronaphtho[2,1-b : 3,4-b']dithio-phene (FNT) and its polymers PFNT-F and PFNT-Cl. The advantages of multifluorination: (1) it enables the polymers to exhibit low-lying HOMO (≈-5.5 eV) and wide band gap (≈2.0 eV); (2) the short interactions (F⋅⋅⋅H, F⋅⋅⋅F) endow the polymers with properties of high film crystallinity and efficient hole transport; (3) well miscibility with NFAs that leads to a more well-defined nanofibrous morphology and face-on orientation in the blend films. Therefore, the PFNT-F/Cl : N3 based OSCs exhibit impressive FF values of 0.80, and remarkable PCEs of 17.53 % and 18.10 %, which make them ranked the best donor materials in OSCs. This work offers new insights into the rational design of high-performance polymers by multifluorination strategy.

CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment.

Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC.

Plastome phylogenomics and historical biogeography of aquatic plant genus Hydrocharis (Hydrocharitaceae).

BACKGROUND: Hydrocharis L. and Limnobium Rich. are small aquatic genera, including three and two species, respectively. The taxonomic status, phylogenetic relationships and biogeographical history of these genera have remained unclear, owing to the lack of Central African endemic H. chevalieri from all previous studies. We sequenced and assembled plastomes of all three Hydrocharis species and Limnobium laevigatum to explore the phylogenetic and biogeographical history of these aquatic plants. RESULTS: All four newly generated plastomes were conserved in genome structure, gene content, and gene order. However, they differed in size, the number of repeat sequences, and inverted repeat borders. Our phylogenomic analyses recovered non-monophyletic Hydrocharis. The African species H. chevalieri was fully supported as sister to the rest of the species, and L. laevigatum was nested in Hydrocharis as a sister to H. dubia. Hydrocharis-Limnobium initially diverged from the remaining genera at ca. 53.3 Ma, then began to diversify at ca. 30.9 Ma. The biogeographic analysis suggested that Hydrocharis probably originated in Europe and Central Africa. CONCLUSION: Based on the phylogenetic results, morphological similarity and small size of the genera, the most reasonable taxonomic solution to the non-monophyly of Hydrocharis is to treat Limnobium as its synonym. The African endemic H. chevalieri is fully supported as a sister to the remaining species. Hydrocharis mainly diversified in the Miocene, during which rapid climate change may have contributed to the speciation and extinctions. The American species of former Limnobium probably dispersed to America through the Bering Land Bridge during the Miocene.