Serum SERCA2a levels in heart failure patients are associated with adverse events after discharge.

Calcium homeostasis imbalance is one of the important pathological mechanisms in heart failure. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a), a calcium ATPase on the sarcoplasmic reticulum in cardiac myocytes, is a myocardial systolic-diastolic Ca2 + homeostasis regulating enzyme that is not only involved in cardiac diastole but also indirectly affects cardiac myocyte contraction. SERCA2a expression was found to be decreased in myocardial tissue in heart failure, however, there are few reports on serum SERCA2a expression in patients with heart failure, and this study was designed to investigate whether serum SERCA2a levels are associated with the occurrence of adverse events after discharge in patients hospitalized with heart failure. Patients with heart failure hospitalized in the cardiovascular department of the Second Affiliated Hospital of Guangdong Medical University, China, from July 2018 to July 2019 were included in this study, and serum SERCA2a concentrations were measured; each enrolled patient was followed up by telephone after 6 months (6 ±â€…1 months) for general post-discharge patient status. The correlation between serum SERCA2a levels and the occurrence of adverse events (death or readmission due to heart failure) after hospital discharge was assessed using multiple analysis and trend analysis. Seventy-one patients with heart failure were finally included in this study, of whom 38 (53.5%) were men and 33 (46.5%) were women (All were postmenopausal women). Multiple analysis revealed no correlation between serum SERCA2a levels and the occurrence of adverse events in the total study population and in male patients, but serum SERCA2a levels were associated with the occurrence of adverse outcome events after hospital discharge in female patients (OR = 1.02, P = .047). Further analysis using a trend analysis yielded a 4.0% increase in the risk of adverse outcomes after hospital discharge for each unit increase in SERCA2a in female patients (OR = 1.04; P = .02), while no significant difference was seen in men. This study suggests that serum SERCA2a levels at admission are associated with the occurrence of post-discharge adverse events in postmenopausal female patients hospitalized with heart failure.

Structured 3' UTRs destabilize mRNAs in plants.

BACKGROUND: RNA secondary structure (RSS) can influence the regulation of transcription, RNA processing, and protein synthesis, among other processes. 3' untranslated regions (3' UTRs) of mRNA also hold the key for many aspects of gene regulation. However, there are often contradictory results regarding the roles of RSS in 3' UTRs in gene expression in different organisms and/or contexts. RESULTS: Here, we incidentally observe that the primary substrate of miR159a (pri-miR159a), when embedded in a 3' UTR, could promote mRNA accumulation. The enhanced expression is attributed to the earlier polyadenylation of the transcript within the hybrid pri-miR159a-3' UTR and, resultantly, a poorly structured 3' UTR. RNA decay assays indicate that poorly structured 3' UTRs could promote mRNA stability, whereas highly structured 3' UTRs destabilize mRNA in vivo. Genome-wide DMS-MaPseq also reveals the prevailing inverse relationship between 3' UTRs' RSS and transcript accumulation in the transcriptomes of Arabidopsis, rice, and even human. Mechanistically, transcripts with highly structured 3' UTRs are preferentially degraded by 3'-5' exoribonuclease SOV and 5'-3' exoribonuclease XRN4, leading to decreased expression in Arabidopsis. Finally, we engineer different structured 3' UTRs to an endogenous FT gene and alter the FT-regulated flowering time in Arabidopsis. CONCLUSIONS: We conclude that highly structured 3' UTRs typically cause reduced accumulation of the harbored transcripts in Arabidopsis. This pattern extends to rice and even mammals. Furthermore, our study provides a new strategy of engineering the 3' UTRs' RSS to modify plant traits in agricultural production and mRNA stability in biotechnology.

The effect of weak π-π interactions on single-molecule electron transport properties of the tetraphenylethene molecule and its derivatives: a first-principles study.

Intramolecular π-π interactions are a significant research focus in fields such as chemistry, biology, and materials science. Different configurations of benzene-benzene moieties within a molecule can affect the magnitude of their π-π interactions, consequently influencing the electronic transport capabilities of the molecule. In this study, we designed three π-conjugated molecules, TPEM, TPEEM, and TEEPM, based on tetraphenylethene (TPE). These three molecules exhibit three distinct π-conjugated structures: linear cis-π-conjugation, linear trans-π-conjugation, and cross-π-conjugation. Thereinto, TPEM and TPEEM molecules share the same TPE core, with identical π-π interaction distances, while the TEEPM molecule has acetylene groups between the TPE units, thereby increasing the π-π interaction distances between the benzene moieties. Using density functional theory calculations combined with non-equilibrium Green's function (DFT+NEGF), our results reveal that the conductance order of different π-conjugated structures in TPEM and TPEEM molecules is as follows: cis > cross ≈ trans. Through analysis of transmission spectra, transmission pathways, and the innermost π orbitals, we find that in TPEM and TPEEM molecules, the cis- and cross-π-conjugated structures exhibit π-π interactions between benzene moieties and provide special through-space electron transport pathways, enhancing their electronic transport capabilities in coordination with the bonded molecular framework, whereas their trans-conjugated structures only allow electron transport along the molecular backbone. In contrast, in TEEPM molecule, due to the absence of π-π interactions, the conductance of different π-conjugated structures is primarily determined by the molecular backbone and follows the order: trans > cis > cross. These findings provide a theoretical basis for designing single-molecule electronic devices with multiple electron channels based on intramolecular π-π interactions.

Effect of S⋯π interactions on the charge transport properties of the DPP framework.

In this work, we designed and synthesized two similar π-conjugated molecules, N-alkyl (DPP-R) and N-aryl (DPP-B), to comparatively explore the S⋯π interactions using a scanning tunneling microscopy-based break junction (STM-BJ) technique. The conductance results of the STM-BJ experiments indicated that DPP-R has a 66% greater conductance (G) than DPP-B. Combined with molecular simulations, it was demonstrated that the presence of S⋯π interactions led to a certain degree of orbital overlap of the highest occupied molecular orbital (HOMO), and created a favorable channel for electron transport in the DPP-B junction.

Identification of miRNA858 long-loop precursors in seed plants.

MicroRNAs (miRNAs) are a class of nonprotein-coding short transcripts that provide a layer of post-transcriptional regulation essential to many plant biological processes. MiR858, which targets the transcripts of MYB transcription factors, can affect a range of secondary metabolic processes. Although miR858 and its 187-nt precursor have been well studied in Arabidopsis (Arabidopsis thaliana), a systematic investigation of miR858 precursors and their functions across plant species is lacking due to a problem in identifying the transcripts that generate this subclass. By re-evaluating the transcript of miR858 and relaxing the length cut-off for identifying hairpins, we found in kiwifruit (Actinidia chinensis) that miR858 has long-loop hairpins (1,100 to 2,100 nt), whose intervening sequences between miRNA generating complementary sites were longer than all previously reported miRNA hairpins. Importantly, these precursors of miR858 containing long-loop hairpins (termed MIR858L) are widespread in seed plants including Arabidopsis, varying between 350 and 5,500 nt. Moreover, we showed that MIR858L has a greater impact on proanthocyanidin and flavonol levels in both Arabidopsis and kiwifruit. We suggest that an active MIR858L-MYB regulatory module appeared in the transition of early land plants to large upright flowering plants, making a key contribution to plant secondary metabolism.

A new and effective two-step clustering approach for single cell RNA sequencing data.

BACKGROUND: The rapid devolvement of single cell RNA sequencing (scRNA-seq) technology leads to huge amounts of scRNA-seq data, which greatly advance the research of many biomedical fields involving tissue heterogeneity, pathogenesis of disease and drug resistance etc. One major task in scRNA-seq data analysis is to cluster cells in terms of their expression characteristics. Up to now, a number of methods have been proposed to infer cell clusters, yet there is still much space to improve their performance. RESULTS: In this paper, we develop a new two-step clustering approach to effectively cluster scRNA-seq data, which is called TSC - the abbreviation of Two-Step Clustering. Particularly, by dividing all cells into two types: core cells (those possibly lying around the centers of clusters) and non-core cells (those locating in the boundary areas of clusters), we first clusters the core cells by hierarchical clustering (the first step) and then assigns the non-core cells to the corresponding nearest clusters (the second step). Extensive experiments on 12 real scRNA-seq datasets show that TSC outperforms the state of the art methods. CONCLUSION: TSC is an effective clustering method due to its two-steps clustering strategy, and it is a useful tool for scRNA-seq data analysis.

Recovery and utilization of waste filtrate from industrial biological fermentation: Development and metabolite profile of the Bacillus cereus liquid bio-fertilizer.

Most fermentation waste filtrates can be used as raw materials for producing bio-fertilizers to reduce wastewater emissions and environmental pollution, but their bio-fertilizer utilization depends on the nutrients contained and their metabolized by functional microorganism. To achieve bio-fertilizer utilization of Acremonium terricola fermented waste filtrate, this study systematically explored the functional microbial species for making good use of waste liquid, optimized material process parameters for bio-fertilizer production based on D-optimal mixture design method, and analyzed the composition of the waste filtrate and its metabolism by functional microorganisms using a non-targeted LC-MS metagenomics technique. The results showed that Bacillus cereus was the functional microbial candidate for producing bio-fertilizer because of its more efficiently utilize the waste filtrate than other Bacillus sp. The optimal material process parameters of the liquid bio-fertilizer were the inoculum dose of 5% (v:v, %), 80% of waste filtrate, 0.25% of N, 3.5% of P2O5, 3.25% of K2O of mass percentage. Under these conditions, the colony forming unit (CFU) of Bacillus cereus could reach (1.59 ± 0.01) × 108 CFU/mL, which met the bio-fertilizer standard requirements of the People's Republic of China (NY/T798). Furthermore, the potential functions of bio-fertilizer were studied based on comparison of raw materials and production components: on the one hand, waste filtrate contained abundant of nitrogen and carbon sources, and bioactive substances secreted by Acremonium terricola, such as ß-alanyl-L-lysine, anserine, UMP, L-lactic acid and etc., which could meet the nutrient requirements of the growth of Bacillus cereus; On the other hand, some compounds of waste filtrate with the potential to benefit the plant growth and defense, such as betaine aldehyde, (2E,6E)-farnesol, homogentisic acid and etc., were significantly up regulated by Bacillus cereus utilization of the filtrate. To sum up, this work highlighted that the waste filtrate could be efficiently developed into liquid bio-fertilizer by Bacillus cereus.

Rice chromatin protein OsHMGB1 is involved in phosphate homeostasis and plant growth by affecting chromatin accessibility.

Although phosphorus is one of the most important essential elements for plant growth and development, the epigenetic regulation of inorganic phosphate (Pi) signaling is poorly understood. In this study, we investigated the biological function and mode of action of the high-mobility-group box 1 protein OsHMGB1 in rice (Oryza sativa), using molecular and genetic approaches. We determined that OsHMGB1 expression is induced by Pi starvation and encodes a nucleus-localized protein. Phenotypic analysis of Oshmgb1 mutant and OsHMGB1 overexpression transgenic plants showed that OsHMGB1 positively regulates Pi homeostasis and plant growth. Transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing indicated that OsHMGB1 regulates the expression of a series of phosphate starvation-responsive (PSR) genes by binding to their promoters. Furthermore, an assay for transposase-accessible chromatin followed by sequencing revealed that OsHMGB1 is involved in maintaining chromatin accessibility. Indeed, OsHMGB1 occupancy positively correlated with genome-wide chromatin accessibility and gene expression levels. Our results demonstrate that OsHMGB1 is a transcriptional facilitator that regulates the expression of a set of PSR genes to maintain Pi homeostasis in rice by increasing the chromatin accessibility, revealing a key epigenetic mechanism that fine-tune plant acclimation responses to Pi-limited environments.

Why Ligand Doping Increases the Fluorescence of an Anthracene-Based Metal-Organic Framework.

Metal-organic frameworks (MOFs) built from fluorescent ligands frequently exhibit enhanced fluorescence when doped with inert ligands. This study focuses on a MOF of the UiO-68 structure, which is built from a fluorescent dibenzoate-anthracene ligand doped with a dibenzoate-benzene ligand. Our investigation aims to understand the mechanism behind the doping-enhanced emission of this MOF. We rule out several possible mechanisms, including exciton coupling, electron transfer between ligand and metal center, and ligand intersystem crossing induced by the metal center. Inhibition of the interligand charge transfer is considered a possible way to enhance emission. Furthermore, we propose that the conformational change of the anthracene-based ligand in the MOF cavity is also a way for enhancement. Our molecular dynamics simulations of the MOF structure filled with solvents reveal that the steric crowding in the cavity induces a conformational change at different doping levels, affecting the rate of intersystem crossing of the ligand.

Mutagenesis and structural studies reveal the basis for the specific binding of SARS-CoV-2 SL3 RNA element with human TIA1 protein.

Viral RNA-host protein interactions are indispensable during RNA virus transcription and replication, but their detailed structural and dynamical features remain largely elusive. Here, we characterize the binding interface for the SARS-CoV-2 stem-loop 3 (SL3) cis-acting element to human TIA1 protein with a combined theoretical and experimental approaches. The highly structured SARS-CoV-2 SL3 has a high binding affinity to TIA1 protein, in which the aromatic stacking, hydrogen bonds, and hydrophobic interactions collectively direct this specific binding. Further mutagenesis studies validate our proposed 3D binding model and reveal two SL3 variants have enhanced binding affinities to TIA1. And disruptions of the identified RNA-protein interactions with designed antisense oligonucleotides dramatically reduce SARS-CoV-2 infection in cells. Finally, TIA1 protein could interact with conserved SL3 RNA elements within other betacoronavirus lineages. These findings open an avenue to explore the viral RNA-host protein interactions and provide a pioneering structural basis for RNA-targeting antiviral drug design.

Assessment of groundwater vulnerability by applying the improved DRASTIC model: a case in Guyuan City, Ningxia, China.

Groundwater is the main source of production and living in most arid and semi-arid areas, and it plays an increasingly critical role in achieving local urban development. There is a serious issue regarding the contradiction between urban development and groundwater protection. In this study, we used three different models to assess the groundwater vulnerability of Guyuan City, including DRASTIC model, analytical hierarchy process-DRASTIC model (AHP-DRASTIC) and variable weight theory-DRASTIC model (VW-DRASTIC). The groundwater vulnerability index (GVI) of the study area was calculated in ArcGIS. Based on the magnitude of GVI, the groundwater vulnerability was classified into five classes: very high, high, medium, low, and very low using the natural breakpoint method, and the groundwater vulnerability map (GVM) of the study area was drawn. In order to validate the accuracy of groundwater vulnerability, the Spearman correlation coefficient was used, and the results showed that the VW-DRASTIC model performed best among the three models (ρ=0.83). The improved VW-DRASTIC model shows that the variable weight model effectively improves the accuracy of the DRASTIC model, which is more suitable for the study area. Finally, based on the results of GVM combined with the distribution of F- and urban development planning, suggestions were proposed for further sustainable groundwater management. This study provides a scientific basis for groundwater management in Guyuan City, which can be an example for similar areas, particularly in arid and semi-arid areas.

Intrinsically disordered proteins SAID1/2 condensate on SERRATE for dual inhibition of miRNA biogenesis in Arabidopsis.

Intrinsically disordered proteins (IDPs) SAID1/2 are hypothetic dentin sialophosphoprotein-like proteins, but their true functions are unknown. Here, we identified SAID1/2 as negative regulators of SERRATE (SE), a core factor in miRNA biogenesis complex (microprocessor). Loss-of-function double mutants of said1; said2 caused pleiotropic developmental defects and thousands of differentially expressed genes that partially overlapped with those in se. said1; said2 also displayed increased assembly of microprocessor and elevated accumulation of microRNAs (miRNAs). Mechanistically, SAID1/2 promote pre-mRNA processing 4 kinase A-mediated phosphorylation of SE, causing its degradation in vivo. Unexpectedly, SAID1/2 have strong binding affinity to hairpin-structured pri-miRNAs and can sequester them from SE. Moreover, SAID1/2 directly inhibit pri-miRNA processing by microprocessor in vitro. Whereas SAID1/2 did not impact SE subcellular compartmentation, the proteins themselves exhibited liquid-liquid phase condensation that is nucleated on SE. Thus, we propose that SAID1/2 reduce miRNA production through hijacking pri-miRNAs to prevent microprocessor activity while promoting SE phosphorylation and its destabilization in Arabidopsis.

A competition-attenuation mechanism modulates thermoresponsive growth at warm temperatures in plants.

Global warming has profound impact on growth and development, and plants constantly adjust their internal circadian clock to cope with external environment. However, how clock-associated genes fine-tune thermoresponsive growth in plants is little understood. We found that loss-of-function mutation of REVEILLE5 (RVE5) reduces the expression of circadian gene EARLY FLOWERING 4 (ELF4) in Arabidopsis, and confers accelerated hypocotyl growth under warm-temperature conditions. Both RVE5 and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) accumulate at warm temperatures and bind to the same EE cis-element presented on ELF4 promoter, but the transcriptional repression activity of RVE5 is weaker than that of CCA1. The binding of CCA1 to ELF4 promoter is enhanced in the rve5-2 mutant at warm temperatures, and overexpression of ELF4 in the rve5-2 mutant background suppresses the rve5-2 mutant phenotype at warm temperatures. Therefore, the transcriptional repressor RVE5 finetunes ELF4 expression via competing at a cis-element with the stronger transcriptional repressor CCA1 at warm temperatures. Such a competition-attenuation mechanism provides a balancing system for modulating the level of ELF4 and thermoresponsive hypocotyl growth under warm-temperature conditions.

Molecular mechanisms and genetic improvement of low-phosphorus tolerance in rice.

Phosphorus (P) is a macronutrient required for plant growth and reproduction. Orthophosphate (Pi), the preferred P form for plant uptake, is easily fixed in the soil, making it unavailable to plants. Limited phosphate rock resources, low phosphate fertilizer use efficiency and high demands for green agriculture production make it important to clarify the molecular mechanisms underlying plant responses to P deficiency and to improve plant phosphate efficiency in crops. Over the past 20 years, tremendous progress has been made in understanding the regulatory mechanisms of the plant P starvation response. Here, we systematically review current research on the mechanisms of Pi acquisition, transport and distribution from the rhizosphere to the shoot; Pi redistribution and reuse during reproductive growth; and the molecular mechanisms of arbuscular mycorrhizal symbiosis in rice (Oryza sativa L.) under Pi deficiency. Furthermore, we discuss several strategies for boosting P utilization efficiency and yield in rice.

High-temperature adaptation of an OsNRT2.3 allele is thermoregulated by small RNAs.

Climate change negatively affects crop yield, which hinders efforts to reach agricultural sustainability and food security. Here, we show that a previously unidentified allele of the nitrate transporter gene OsNRT2.3 is required to maintain high yield and high nitrogen use efficiency under high temperatures. We demonstrate that this tolerance to high temperatures in rice accessions harboring the HTNE-2 (high temperature resistant and nitrogen efficient-2) alleles from enhanced translation of the OsNRT2.3b mRNA isoform and the decreased abundance of a unique small RNA (sNRT2.3-1) derived from the 5' untranslated region of OsNRT2.3. sNRT2.3-1 binds to the OsNRT2.3a mRNA in a temperature-dependent manner. Our findings reveal that allelic variation in the 5' untranslated region of OsNRT2.3 leads to an increase in OsNRT2.3b protein levels and higher yield during high-temperature stress. Our results also provide a breeding strategy to produce rice varieties with higher grain yield and lower N fertilizer input suitable for a sustainable agriculture that is resilient against climate change.

Complete Genome Sequence of Pythium oligandrum, Isolated from Rhizosphere Soils of Chinese Angelica sinensis.

Most of the Pythium species are pathogenic to a wide range of economically important crops and, sometimes, can even cause diseases in animals and humans. An exception is that the soil-inhabiting P. oligandrum is an effective biocontrol agent against a diverse suite of pathogens and promotes plant growth. In this work, we sequenced the whole genome of P. oligandrum PO-1, isolated from rhizosphere soils of Chinese Angelica sinensis, using a combination of long-read single-molecule real-time sequencing technology (Pacific Biosciences [PacBio]) and Illumina sequencing. The 2.5-Gb and 5.2-Gb bases were generated respectively. The sequencing depths were 93× with PacBio and 145× with Illumina sequencing. With the PacBio sequencing results further corrected by Illumina sequencing, the genome was assembled into 71 scaffolds with a total size of 39.10 Mb (N50 = 1.45 Mb; L50 = 9)and the longest scaffold is 3.49 Mb. Genome annotation identifies 15,632 protein-coding genes and 0.47 Mb of transposable elements. Our genomic assembly and annotation have been greatly improved compared with the already released three genomes of P. oligandrum. This genomic data will provide valuable information to understand the mechanism underlying its biocontrol potentials and will also facilitate the dissection of genome evolution and environmental adaptation within the genus Pythium. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.

Roughage biodegradation by natural co-cultures of rumen fungi and methanogens from Qinghai yaks.

Anaerobic fungus-methanogen co-cultures from rumen liquids and faeces can degrade lignocellulose efficiently. In this study, 31 fungus-methanogen co-cultures were first obtained from the rumen of yaks grazing in Qinghai Province, China, using the Hungate roll-tube technique. The fungi were identified according to morphological characteristics and internal transcribed spacer (ITS) sequences. The methanogens associated with each fungus were identified by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and 16S rRNA gene sequencing. They were five co-culture types: Neocallimastix frontalis + Methanobrevibacter ruminantium, Neocallimastix frontalis + Methanobrevibacter gottschalkii, Orpinomyces joyonii + Methanobrevibacter ruminantium, Caecomyces communis + Methanobrevibacter ruminantium, and Caecomyces communis + Methanobrevibacter millerae. Among the 31 co-cultures, during the 5-day incubation, the N. frontalis + M. gottschalkii co-culture YakQH5 degraded 59.0%-68.1% of the dry matter (DM) and 49.5%-59.7% of the neutral detergent fiber (NDF) of wheat straw, corn stalk, rice straw, oat straw and sorghum straw to produce CH4 (3.0-4.6 mmol/g DM) and acetate (7.3-8.6 mmol/g DM) as end-products. Ferulic acid (FA) released at 4.8 mg/g DM on corn stalk and p-coumaric acid (PCA) released at 11.7 mg/g DM on sorghum straw showed the highest values, with the following peak values of enzyme activities: xylanase at 12,910 mU/mL on wheat straw, ferulic acid esterase (FAE) at 10.5 mU/mL on corn stalk, and p-coumaric acid esterase (CAE) at 20.5 mU/mL on sorghum straw. The N. frontalis + M. gottschalkii co-culture YakQH5 from Qinghai yaks represents a new efficient combination for lignocellulose biodegradation, performing better than previously reported fungus-methanogen co-cultures from the digestive tract of ruminants.

Refined Zoning of Landslide Susceptibility: A Case Study in Enshi County, Hubei, China.

At present, landslide susceptibility assessment (LSA) based on the characteristics of landslides in different areas is an effective prevention measure for landslide management. In Enshi County, China, the landslides are mainly triggered by high-intensity rainfall, which causes a large number of casualties and economic losses every year. In order to effectively control the landslide occurrence in Enshi County and mitigate the damages caused by the landslide. In this study, eight indicators were selected as assessment indicators for LSA in Enshi County. The analytic hierarchy process (AHP) model, information value (IV) model and analytic hierarchy process-information value (AHP-IV) model were, respectively, applied to assess the landslide distribution of landslides in the rainy season (RS) and non-rainy season (NRS). Based on the three models, the study area was classified into five levels of landslide susceptibility, including very high susceptibility, high susceptibility, medium susceptibility, low susceptibility, and very low susceptibility. The receiver operating characteristic (ROC) curve was applied to verify the model accuracy. The results showed that the AHP-IV model (ROC = 0.7716) was more suitable in RS, and the IV model (ROC = 0.8237) was the most appropriate model in NRS. Finally, combined with the results of landslide susceptibility in RS and NRS, an integrated landslide susceptibility map was proposed, involving year-round high susceptibility, RS high susceptibility, NRS high susceptibility and year-round low susceptibility. The integrated landslide susceptibility results provide a more detailed division in terms of the different time periods in a year, which is beneficial for the government to efficiently allocate landslide management funds and propose effective landslide management strategies. Additionally, the focused arrangement of monitoring works in landslide-prone areas enable collect landslide information efficiently, which is helpful for the subsequent landslide preventive management.