FastBiCmrMLM: a fast and powerful compressed variance component mixed logistic model for big genomic case-control genome-wide association study.

Large sample datasets have been regarded as the primary basis for innovative discoveries and the solution to missing heritability in genome-wide association studies. However, their computational complexity cannot consider all comprehensive effects and all polygenic backgrounds, which reduces the effectiveness of large datasets. To address these challenges, we included all effects and polygenic backgrounds in a mixed logistic model for binary traits and compressed four variance components into two. The compressed model combined three computational algorithms to develop an innovative method, called FastBiCmrMLM, for large data analysis. These algorithms were tailored to sample size, computational speed, and reduced memory requirements. To mine additional genes, linkage disequilibrium markers were replaced by bin-based haplotypes, which are analyzed by FastBiCmrMLM, named FastBiCmrMLM-Hap. Simulation studies highlighted the superiority of FastBiCmrMLM over GMMAT, SAIGE and fastGWA-GLMM in identifying dominant, small α (allele substitution effect), and rare variants. In the UK Biobank-scale dataset, we demonstrated that FastBiCmrMLM could detect variants as small as 0.03% and with α ≈ 0. In re-analyses of seven diseases in the WTCCC datasets, 29 candidate genes, with both functional and TWAS evidence, around 36 variants identified only by the new methods, strongly validated the new methods. These methods offer a new way to decipher the genetic architecture of binary traits and address the challenges outlined above.

Reticular Modulation of Piezofluorochromic Behaviors in Organic Molecular Cages by Replacing Non-Luminous Components.

Organic piezochromic materials that manifest pressure-stimuli-responses are important in various fields such as data storage and anticounterfeiting. The manipulation of piezofluorochromic behaviors for these materials is promising but remains a great challenge. Herein, a non-luminous components regulated strategy is developed and organic molecular cages (OMCs), a burgeoning class of crystalline organic materials with structural dynamics, are first explored for the design of piezofluorochromic materials with tunable luminescence. A series of OMCs based on aggregation-induced emission (AIE) chromophores, termed Cage 1-3, are synthesized and their piezofluorochromic behaviors are investigated by diamond anvil cell technique. Due to the sufficient voids between its flexible chromophores offered by the OMC structure, Cage 1 exhibits thermofluorochromic and piezofluorochromic properties. Moreover, the piezofluorochromic performance of this OMC could be further promoted by replacing its non-luminous components with improved flexibilities, and a remarkable luminescence peak shift by 150 nm together with a response sensitivity of 13.8 nm GPa-1 was achieved upon hydrostatic compression. The cage structure plays a vital role in facilitating efficient and reversible piezofluorochromic behaviors. This study has shed light on the rational design and exploitation of OMCs as an exceptional platform to accomplish customizable piezofluorochromic behaviors and enlarge their potential applications in pressure-based luminescence.

In situ community transcriptomics illuminates CO2-fixation potentials and supporting roles of phagotrophy and proton pump in plankton in a subtropical marginal sea.

Lineage-wise physiological activities of plankton communities in the ocean are important but challenging to characterize. Here, we conducted whole-assemblage metatranscriptomic profiling at continental shelf and slope sites in the South China Sea to investigate carbon fixation potential in different lineages. RuBisCO expression, the proxy of Calvin carbon fixation (CCF) potential, was mainly contributed by Bacillariophyta, Chlorophyta, Cyanobacteria, and Haptophyta, which was differentially affected by environmental factors among lineages. CCF potential exhibited positive or negative correlations with phagotrophy gene expression, suggesting phagotrophy possibly enhances or complements CCF. Our data also reveal significant non-Calvin carbon fixation (NCF) potential, as indicated by the active expression of genes in all five currently recognized NCF pathways, mainly contributed by Flavobacteriales, Alteromonadales, and Oceanospirillales. Furthermore, in Flavobacteriales, Alteromonadales, Pelagibacterales, and Rhodobacterales, NCF potential was positively correlated with proton-pump rhodopsin (PPR) expression, suggesting that NCF might be energetically supported by PPR. The novel insights into the lineage-differential potential of carbon fixation, widespread mixotrophy, and PPR as an energy source for NCF lay a methodological and informational foundation for further research to understand carbon fixation and the trophic landscape in the ocean.IMPORTANCEMarine plankton plays an important role in global carbon cycling and climate regulation. Phytoplankton and cyanobacteria fix CO2 to produce organic compounds using solar energy and mainly by the Calvin cycle, whereas autotrophic bacteria and archaea may fix CO2 by non-Calvin cycle carbon fixation pathways. How active individual lineages are in carbon fixation and mixotrophy, and what energy source bacteria may employ in non-Calvin carbon fixation, in a natural plankton assemblage are poorly understood and underexplored. Using metatranscriptomics, we studied carbon fixation in marine plankton with lineage resolution in tropical marginal shelf and slope areas. Based on the sequencing results, we characterized the carbon fixation potential of different lineages and assessed Calvin- and non-Calvin- carbon fixation activities and energy sources. Data revealed a high number of unigenes (4.4 million), lineage-dependent differential potentials of Calvin carbon fixation and responses to environmental conditions, major contributors of non-Calvin carbon fixation, and their potential energy source.

Glyphosate (Roundup) as phosphorus nutrient enhances carbon and nitrogen accumulation and up-regulates phosphorus metabolisms in the haptophyte Isochrysis galbana.

Inorganic phosphate limitation for phytoplankton may be intensified with water stratification by global warming, and with the increasing nitrogen: phosphorus (N:P) ratio in coastal zones resulting from continuous anthropogenic N overloading. Under these circumstances, phytoplankton's ability to use dissolved organic phosphorus (DOP) will give species a competitive advantage. In our previous study, we have shown that the haptophyte Isochrysis galbana can use glyphosate (Roundup) as a P nutrient source to support growth, but the mechanism of how remains unexplored. Here, we show that three genes encoding PhnC (IgPhnCs), which exhibit up-regulated expression in glyphosate-grown cultures, are probably responsible for glyphosate uptake, while homologs of PhnK and PhnL (IgPhnK and IgPhnL) probably provide auxiliary support for the intracellular degradation of glyphosate. Meanwhile, we found the use efficiency of glyphosate was low compared with phosphate, probably because glyphosate uptake and hydrolysis cost energy and because glyphosate induces oxidative stress in I. galbana. Meanwhile, genes encoding 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, the target of the herbicide, were up-regulated in glyphosate cultures. Furthermore, our data showed the up-regulation of P metabolisms (transcription) in glyphosate-grown cultures, which further induced the up-regulation of nitrate/nitrite transport and biosynthesis of some amino acids. Meanwhile, glyphosate-grown cells accumulated more C and N, resulting in remarkably high C:N:P ratio, and this, along with the up-regulated P metabolisms, was under transcriptional and epigenetic regulation. This study sheds lights on the mechanism of glyphosate utilization as a source of P nutrient by I. galbana, and these findings have biogeochemical implications.

Active viral infection during blooms of a dinoflagellate indicates dinoflagellate-viral co-adaptation.

IMPORTANCE: This study represents the first that investigates in situ virus infection in dinoflagellate blooms. Our findings reveal highly similar viral assemblages that infected the bloom species Prorocentrum shikokuense and a co-adapted metabolic relationship between the host and the viruses in the blooms, which varied between the prolonged and the short-lived blooms of the same dinoflagellate species. These findings fill the gap in knowledge regarding the identity and behavior of viruses in a dinoflagellate bloom and shed light on what appears to be the complex mode of infection. The novel insight will be potentially valuable for fully understanding and modeling the role of viruses in regulating blooms of dinoflagellates and other algae.

A comparative study reveals the relative importance of prokaryotic and eukaryotic proton pump rhodopsins in a subtropical marginal sea.

Proton-pump rhodopsin (PPR) in marine microbes can convert solar energy to bioavailable chemical energy. Whereas bacterial PPR has been extensively studied, counterparts in microeukaryotes are less explored, and the relative importance of the two groups is poorly understood. Here, we sequenced whole-assemblage metatranscriptomes and investigated the diversity and expression dynamics of PPR in microbial eukaryotes and prokaryotes at a continental shelf and a slope site in the northern South China Sea. Data showed the whole PPRs transcript pool was dominated by Proteorhodopsins and Xanthorhodopsins, followed by Bacteriorhodopsin-like proteins, dominantly contributed by prokaryotes both in the number and expression levels of PPR unigenes, although at the continental slope station, microeukaryotes and prokaryotes contributed similarly in transcript abundance. Furthermore, eukaryotic PPRs are mainly contributed by dinoflagellates and showed significant correlation with nutrient concentrations. Green light-absorbing PPRs were mainly distributed in >3 µm organisms (including microeukaryotes and their associated bacteria), especially at surface layer at the shelf station, whereas blue light-absorbing PPRs dominated the <3 µm (mainly bacterial) communities at both study sites, especially at deeper layers at the slope station. Our study portrays a comparative PPR genotype and expression landscape for prokaryotes and eukaryotes in a subtropical marginal sea, suggesting PPR's role in niche differentiation and adaptation among marine microbes.

Correlation between thyroid function indices and urine iodine levels in patients with nodular goiter.

OBJECTIVE: To retrospectively analyze the iodine nutritional status in patients with nodular goiter (NG) and investigate a possible association between urinary iodine levels and thyroid function indices. METHODS: A total of 173 patients diagnosed with nodular goiter in the Fourth Hospital of Hebei Medical University from January 2019 to May 2021 were selected as the NG group, and 172 healthy individuals without thyroid diseases were selected after a physical examination as a control group. The data of all the participants were retrospectively assessed to explore the association between urinary iodine levels and thyroid function indices. The content of urinary iodine in the two groups was compared, and the correlation of urinary iodine levels with thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) in the NG group was evaluated. RESULTS: The level of urinary iodine in the NG group was 163.97 ± 113.75 µg/L, which was higher than 121.47 ± 53.75 µg/L in the control group (P < 0.05). The iodine excess rate in females was higher than that in males (P < 0.05). The results of Pearson correlation analysis showed that the amount of urinary iodine in patients with hyperthyroidism with different urinary iodine statuses was negatively correlated with the level of TSH and positively correlated with levels of FT3 and FT4. CONCLUSION: There is a significant association between urinary iodine levels and thyroid hormone levels in NG patients. Therefore, regular monitoring of urinary iodine levels is essential for the appropriate use of iodine supplementation.

Expression analysis of TRAF2­ and NCK­interacting protein kinase (TNIK) and phosphorylated TNIK in papillary thyroid carcinoma.

The aim of the present study was to evaluate the expression of TRAF2- and NCK-interacting kinase (TNIK) and the levels of the active form of TNIK, phosphorylated (p)-TNIK, in papillary thyroid carcinoma (PTC), and to identify and compare the levels of TNIK and p-TNIK among PTC, benign thyroid tumors and normal tissues. The levels of TNIK and p-TNIK were examined by reverse transcription-quantitative (RT-q)PCR and immunohistochemical analysis (IHC) in PTC, benign thyroid tumors and normal tissues, and their association with clinicopathological features was evaluated. First, analysis of the Gene Expression Profiling Interactive Analysis and The Cancer Genome Atlas datasets suggested that the mRNA expression of TNIK was markedly increased in PTC tissues compared with that in normal tissues. RT-qPCR analyses then indicated that the relative mRNA expression of TNIK in PTC tissues was 4.47±6.16, which was significantly higher than that in adjacent tissues 2.57±5.83. The IHC results suggested that the levels of TNIK and p-TNIK in PTC tissues were markedly elevated compared with those in benign thyroid tumors and normal tissues. The levels of p-TNIK in patients with PTC were significantly associated with extrathyroidal extension (χ2=4.199, P=0.040). Positive staining for TNIK was observed in 187 out of 202 (92.6%) cases in the cytoplasm, nucleus or cytomembrane of PTC cells. Among the 187 positive cases, cytoplasm expression was identified in 162 cases (86.6%), nuclear expression in 17 cases (9.1%) and cytomembrane expression in 8 cases (4.3%). Positive staining for p-TNIK was observed in 179 out of 202 (88.6%) cases in the nuclei, cytoplasm or cytomembrane of PTC cells. In the 179 p-TNIK-positive cases, localization in the nuclei plus cytoplasm was identified in 142 cases (79.3%), nuclear localization in 9 cases (5.0%), presence in the cytoplasm in 21 cases (11.7%) and cytomembrane localization in 7 cases (3.9%). Both TNIK and p-TNIK were upregulated in PTC tissues and p-TNIK was significantly associated with extrathyroidal extension. It may act as a crucial oncogene to participate in PTC carcinogenesis and progression.

Tailoring the high-brightness "warm" white light emission of two-dimensional perovskite crystals via a pressure-inhibited nonradiative transition.

Efficient warm white light emission is an ideal characteristic of single-component materials for light-emitting applications. Although two-dimensional hybrid perovskites are promising candidates for light-emitting diodes, as they possess broadband self-trapped emission and outstanding stability, they rarely achieve a high photoluminescence quantum yield of warm white light emissions. Here, an unusual pressure-induced warm white emission enhancement phenomenon from 2.1 GPa to 9.9 GPa was observed in two-dimensional perovskite (2meptH2)PbCl4, accompanied by a large increase in the relative quantum yield of photoluminescence. The octahedral distortions, accompanied with the evolution of organic cations, triggered the structural collapse, which caused the sudden emission enhancement at 2.1 GPa. Afterwards, the further intra-octahedral collapse promotes the formation of self-trapped excitons and the substantial suppression of nonradiative transitions are responsible for the continuous pressure-induced photoluminescence enhancement. This study not only clearly illustrates the relationship between crystal structure and photoluminescence, but also provides an experimental basis for the synthesis of high-quality warm white light-emitting 2D metal halide perovskite materials.

Cycloaddition enabled mutational profiling of 5-vinyluridine in RNA.

We report the detection of 5-vinyluridine (5-VUrd) in RNA at single nucleotide resolution via mutational profiling. Maleimide cycloadducts with 5-VUrd in RNA cause a stop in primer extension during reverse transcription, and the full-length cDNA product from reverse transcription contains misincorporation across the cycloadduct site.

Transcriptomic-Guided Phosphonate Utilization Analysis Unveils Evidence of Clathrin-Mediated Endocytosis and Phospholipid Synthesis in the Model Diatom, Phaeodactylum tricornutum.

Phosphonates are important components of marine organic phosphorus, but their bioavailability and catabolism by eukaryotic phytoplankton remain enigmatic. Here, diatom Phaeodactylum tricornutum was used to investigate the bioavailability of phosphonates and describe the underlying molecular mechanism. The results showed that 2-aminoethylphosphonic acid (2-AEP) can be utilized as an alternative phosphorus source. Comparative transcriptomics revealed that the utilization of 2-AEP comprised 2 steps, including molecular uptake through clathrin-mediated endocytosis and incorporation into the membrane phospholipids in the form of diacylglyceryl-2-AEP (DAG-2-AEP). In the global ocean, we found the prevalence and dynamic expression pattern of key genes that are responsible for vesicle formation (CLTC, AP-2) and DAG-AEP synthesis (PCYT2, EPT1) in diatom assemblages. This study elucidates a distinctive mechanism of phosphonate utilization by diatoms, and discusses the ecological implications. IMPORTANCE Phosphonates contribute ~25% of total dissolved organic phosphorus in the ocean, and are found to be important for marine phosphorus biogeochemical cycle. As a type of biogenic phosphonate produced by microorganisms, 2-aminoethylphosphonic acid (2-AEP) widely exists in the ocean. It is well known that 2-AEP can be cleaved and utilized by prokaryotes, but its ability to support the growth of eukaryotic phytoplankton remains unclear. Our research identified the bioavailability of 2-AEP for the diatom Phaeodactylum tricornutum, and proposed a distinctive metabolic pathway of 2-AEP utilization. Different from the enzymatic hydrolysis of phosphonates, the results suggested that P. tricornutum utilizes 2-AEP by incorporating it into phospholipid instead of cleaving the C-P bond. Moreover, the ubiquitous distribution of associated representative gene transcripts in the environmental assemblages and the higher gene transcript abundance in the cold regions were observed, which suggests the possible environmental adaption of 2-AEP utilization by diatoms.

The analysis of tumor-infiltrating immune cell and ceRNA networks in laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common forms of head and neck cancers. However, few studies have focused on the correlation between competing endogenous RNA (ceRNAs) and immune cells in LSCC. METHODS: RNAseq expression of LSCC and adjacent tissues were downloaded from The Cancer Genome Atlas to establish a ceRNA network. The key gene in ceRNA was screened by the cox regression analysis to establish a prognostic risk assessment model. The CIBERSORT algorithm was then used to screen important tumor-infiltrating cells related to LSCC. Finally, co-expression analysis was applied to explore the relationship between key genes in the ceRNA network and tumor-infiltrating cells. The external datasets were used to validate critical biomarkers. RESULTS: We constructed a prognostic risk assessment model of key genes in the ceRNA network. As it turned out, Kaplan-Meier survival analysis showed significant differences in overall survival rates between high-risk and low-risk groups (P < .001). The survival rate of the high-risk group was drastically lower than that of the low-risk group, and the AUC of 1 year, 3 years, and 5 years were all above 0.7. In addition, some immune infiltrating cells were also found to be related to LSCC. In the co-expression analysis, there is a negative correlation between plasma cells and TUBB3 (r = -0.33, P = .0013). External dataset validation also supports this result. CONCLUSION: In this study, we found that some key genes (SLC35C1, CLDN23, HOXB7, STC2, TMEM158, TNFRSF4, TUBB3) and immune cells (plasma cells) may correspond to the prognosis of LSCC.

Low-carbon economy and policy implications: a systematic review and bibliometric analysis.

In the face of the rapid increase of carbon emissions, climate warming, and an epidemic situation, low-carbon economy is attracting growing attention. Using bibliometric analysis and machine learning methods, the paper conducts a systematic review in the low-carbon economy. Using the Web of Science Core Collection database, 1433 articles from 1990 to 2021 were selected for review. We find that the trajectories of the low-carbon economy research can be divided into four phases: exploration, fermentation, rising, and flourishing. The low-carbon economy research can be categorized into five clusters: low-carbon energy policy, carbon footprint and carbon trading, energy-economy-environment system, energy efficiency and its decomposition, and carbon emission drivers. The findings of this review study shed light on the role and effects of low-carbon economic policies on energy futures.

An atlas of posttranslational modifications on RNA binding proteins.

RNA structure and function are intimately tied to RNA binding protein recognition and regulation. Posttranslational modifications are chemical modifications which can control protein biology. The role of PTMs in the regulation RBPs is not well understood, in part due to a lacking analysis of PTM deposition on RBPs. Herein, we present an analysis of posttranslational modifications (PTMs) on RNA binding proteins (RBPs; a PTM RBP Atlas). We curate published datasets and primary literature to understand the landscape of PTMs and use protein-protein interaction data to understand and potentially provide a framework for understanding which enzymes are controlling PTM deposition and removal on the RBP landscape. Intersection of our data with The Cancer Genome Atlas also provides researchers understanding of mutations that would alter PTM deposition. Additional characterization of the RNA-protein interface provided from in-cell UV crosslinking experiments provides a framework for hypotheses about which PTMs could be regulating RNA binding and thus RBP function. Finally, we provide an online database for our data that is easy to use for the community. It is our hope our efforts will provide researchers will an invaluable tool to test the function of PTMs controlling RBP function and thus RNA biology.

Physiological and metabolic effects of glyphosate as the sole P source on a cosmopolitan phytoplankter and biogeochemical implications.

Nutrient conditions influence the physiology and stoichiometry of marine phytoplankton. While extensive studies have documented the effects of abundances and types of nutrients such as nitrogen (N) and phosphorus (P), the effect of phosphonates as a P source is less understood and underexplored. Here, with the cosmopolitan coccolithophorid Emiliania huxleyi as a model phytoplankter, we investigated the effect of the phosphonate type of herbicide glyphosate as the sole P source in comparison with the P-depleted and P-replete (with 36 µM dissolved inorganic phosphate [DIP]) cultures. We measured changes in cellular C (carbon):P and N:P ratios and physiological performance and documented the corresponding transcriptomic and miRNAomic responses in E. huxleyi to glyphosate treatment. We found that glyphosate supported population growth but not to the full scale relative to DIP, and this was under the concerted regulation of DNA replication and cell cycle arrest genes as well as the growth-regulating miRNA. Furthermore, our data suggest that E. huxleyi took up glyphosate directly, bypassing extracellular hydrolysis, and this involved ABC transporters. Meanwhile, glyphosate-grown cultures displayed marked increases in cellular particulate organic C (POC) and PON contents, cell size, and transcription of genes for CO2 fixation and citrate cycle, nitrate transport, and protein biosynthesis. However, compared to DIP, the maximum absorption rate of glyphosate was only 33%, and glyphosate-grown E. huxleyi cells exhibited a mild P-stress symptom and elevated cellular C:P and N:P ratios. Interestingly, glyphosate-grown cells showed an increased sinking rate, suggesting that glyphosate as the sole P source might enhance the efficiency of C export by E. huxleyi, which would compensate for the expected decline in primary productivity (and hence carbon efflux) in the future more nutrient-depleted ocean. This biogeochemical implication needs to be further studied and verified, however.

The 3D-structure-mediated growth of zero-dimensional Cs4SnX6 nanocrystals.

Innovations in approaches to synthesize high-quality lead perovskite nanocrystals have enabled the prosperous development of nanocrystal-based optoelectronic devices in recent years. However, the transfer of these approaches to tin perovskite nanocrystals, which are the most promising lead-free perovskite candidates, remains unsuccessful. Herein, based on a three-dimensional (3D)-structure-mediated approach, monodispersed and highly luminescent inorganic zero-dimensional (0D) tin perovskite nanocrystals (NCs) are synthesized. The crystal growth kinetics are revealed via tracking the intermediate structures and using theoretical simulations. The luminescence quantum yield of Cs4SnBr6 NCs is as high as 52%, which is the highest value for inorganic tin perovskite NCs. Cs4SnI6 NCs with a luminescence quantum yield of 27% are synthesized, which is 35 times higher than previous results. Based on the Cs4SnBr6 NCs, an ultraviolet-light-pumped white-light-emitting device (WLED) with an excellent color-rendering index of 92 is fabricated.

A grazing-driven positive nutrient feedback loop and active sexual reproduction underpin widespread Noctiluca green tides.

The mixoplankton green Noctiluca scintillans (gNoctiluca) is known to form extensive green tides in tropical coastal ecosystems prone to eutrophication. In the Arabian Sea, their recent appearance and annual recurrence have upended an ecosystem that was once exclusively dominated by diatoms. Despite evidence of strong links to eutrophication, hypoxia and warming, the mechanisms underlying outbreaks of this mixoplanktonic dinoflagellate remain uncertain. Here we have used eco-physiological measurements and transcriptomic profiling to ascribe gNoctiluca's explosive growth during bloom formation to the form of sexual reproduction that produces numerous gametes. Rapid growth of gNoctiluca coincided with active ammonium and phosphate release from gNoctiluca cells, which exhibited high transcriptional activity of phagocytosis and metabolism generating ammonium. This grazing-driven nutrient flow ostensibly promotes the growth of phytoplankton as prey and offers positive support successively for bloom formation and maintenance. We also provide the first evidence that the host gNoctiluca cell could be manipulating growth of its endosymbiont population in order to exploit their photosynthetic products and meet critical energy needs. These findings illuminate gNoctiluca's little known nutritional and reproductive strategies that facilitate its ability to form intense and expansive gNoctiluca blooms to the detriment of regional water, food and the socio-economic security in several tropical countries.

FOXP4 promotes laryngeal squamous cell carcinoma progression through directly targeting LEF­1.

Forkhead box (FOX) proteins are multifaceted transcription factors that have been shown to be involved in cell cycle progression, proliferation and metastasis. FOXP4, a member of the FOX family, has been implicated in diverse biological processes in tumor initiation and progression. However, the molecular mechanisms of FOXP4 in laryngeal squamous cell carcinoma (LSCC) remain unknown. In the present study, differentially expressed transcripts in transforming growth factor­ß­treated TU177 cells were screened using microarrays and it was found that FOXP4 was significantly upregulated. The high expression of FOXP4 was detected in LSCC tissues and cells, and predicted poor prognosis. The role of FOXP4 in laryngeal cancer cell proliferation, migration and invasion was determined by gain­ and loss­of­function assays. Besides, FOXP4 was demonstrated to participate in the epithelial­mesenchymal transition process at the mRNA and protein levels. Mechanically, FOXP4 directly bound to the promoter of lymphoid enhancer­binding factor 1 and activated Wnt signaling pathway, which was confirmed via chromatin immunoprecipitation and luciferase reporter assays. Consequently, these findings provided novel mechanisms of FOXP4 in LSCC progression, which may be considered as potential therapeutic and prognostic targets for LSCC.

SPX-related genes regulate phosphorus homeostasis in the marine phytoplankton, Phaeodactylum tricornutum.

Phosphorus (P) is an essential nutrient for marine phytoplankton. Maintaining intracellular P homeostasis against environmental P variability is critical for phytoplankton, but how they achieve this is poorly understood. Here we identify a SPX gene and investigate its role in Phaeodactylum tricornutum. SPX knockout led to significant increases in the expression of phosphate transporters, alkaline phosphatases (the P acquisition machinery) and phospholipid hydrolases (a mechanism to reduce P demand). These demonstrate that SPX is a negative regulator of both P uptake and P-stress responses. Furthermore, we show that SPX regulation of P uptake and metabolism involves a phosphate starvation response regulator (PHR) as an intermediate. Additionally, we find the SPX related genes exist and operate across the phytoplankton phylogenetic spectrum and in the global oceans, indicating its universal importance in marine phytoplankton. This study lays a foundation for better understanding phytoplankton adaptation to P variability in the future changing oceans.