An Effective and Promising Strategy for Plant Protection: Synthesis of L-Carvone-Based Thiazolinone-Hydrazone/Nanochitosan Complexes with Antifungal Activity and Sustained Releasing Performance.

The development of novel natural product-derived nano-pesticide systems with loading capacity and sustained releasing performance of bioactive compounds is considered an effective and promising plant protection strategy. In this work, 25 L-carvone-based thiazolinone-hydrazone compounds 4a~4y were synthesized by the multi-step modification of L-carvone and structurally confirmed. Compound 4h was found to show favorable and broad-spectrum antifungal activity through the in vitro antifungal activity evaluation of compounds 4a~4y against eight phytopathogenic fungi. Thus, it could serve as a leading compound for new antifungal agents in agriculture. Moreover, the L-carvone-based nanochitosan carrier 7 bearing the 1,3,4-thiadiazole-amide group was rationally designed for the loading and sustained releasing applications of compound 4h, synthesized, and characterized. It was proven that carrier 7 had good thermal stability below 200 °C, dispersed well in the aqueous phase to form numerous nanoparticles with a size of~20 nm, and exhibited an unconsolidated and multi-aperture micro-structure. Finally, L-carvone-based thiazolinone-hydrazone/nanochitosan complexes were fabricated and investigated for their sustained releasing behaviors. Among them, complex 7/4h-2 with a well-distributed, compact, and columnar micro-structure displayed the highest encapsulation efficiency and desirable sustained releasing property for compound 4h and thus showed great potential as an antifungal nano-pesticide for further studies.

Modeling single cell trajectory using forward-backward stochastic differential equations.

Recent advances in single-cell sequencing technology have provided opportunities for mathematical modeling of dynamic developmental processes at the single-cell level, such as inferring developmental trajectories. Optimal transport has emerged as a promising theoretical framework for this task by computing pairings between cells from different time points. However, optimal transport methods have limitations in capturing nonlinear trajectories, as they are static and can only infer linear paths between endpoints. In contrast, stochastic differential equations (SDEs) offer a dynamic and flexible approach that can model non-linear trajectories, including the shape of the path. Nevertheless, existing SDE methods often rely on numerical approximations that can lead to inaccurate inferences, deviating from true trajectories. To address this challenge, we propose a novel approach combining forward-backward stochastic differential equations (FBSDE) with a refined approximation procedure. Our FBSDE model integrates the forward and backward movements of two SDEs in time, aiming to capture the underlying dynamics of single-cell developmental trajectories. Through comprehensive benchmarking on multiple scRNA-seq datasets, we demonstrate the superior performance of FBSDE compared to other methods, highlighting its efficacy in accurately inferring developmental trajectories.

Long-term variations of air pollutants and public exposure in China during 2000-2020.

Since 2000, China has faced severe air pollution challenges，prompting the initiation of comprehensive emission control measures post-2013. The subsequent implementation of these measures has led to remarkable enhancements in air quality. This study aims to enhance our understanding of the long-term trends in fine particulate matter (PM2.5) and gaseous pollutants of ozone (O3) and nitrogen dioxide (NO2) across China from 2000 to 2020. Utilizing the Community Multiscale Air Quality (CMAQ) model, we conducted a nationwide analysis of air quality, systematically quantifying model predictions against observations for pollutants. The CMAQ model effectively captured the trends of air pollutants, meeting recommended performance benchmarks. The findings reveal variations in pollutant concentrations, with initial increases in PM2.5 followed by a decline after 2013. The proportion of the population living in high PM2.5 concentrations (>75 µg/m3) decreased to <5 % after 2015. However, during the period from 2017 to 2020, around 40 % of the population continued to live in regions that did not meet the criteria for Chinese air quality standards (35 µg/m3). From 2000 to 2019, fewer than 20 % of the population met the WHO standard (100 µg/m3) for MDA8 O3. In 2000, 77 % of the population met the NO2 standard (<20 µg/m3), a figure that declined to 60 % between 2005 and 2014, nearly reaching 70 % in 2020. This study offers a comprehensive analysis of the changes in pollutants and public exposure in 2000-2020. It serves as a foundational resource for future efforts in air pollution control and health research.

scGREAT: Transformer-based deep-language model for gene regulatory network inference from single-cell transcriptomics.

Gene regulatory networks (GRNs) involve complex and multi-layer regulatory interactions between regulators and their target genes. Precise knowledge of GRNs is important in understanding cellular processes and molecular functions. Recent breakthroughs in single-cell sequencing technology made it possible to infer GRNs at single-cell level. Existing methods, however, are limited by expensive computations, and sometimes simplistic assumptions. To overcome these obstacles, we propose scGREAT, a framework to infer GRN using gene embeddings and transformer from single-cell transcriptomics. scGREAT starts by constructing gene expression and gene biotext dictionaries from scRNA-seq data and gene text information. The representation of TF gene pairs is learned through optimizing embedding space by transformer-based engine. Results illustrated scGREAT outperformed other contemporary methods on benchmarks. Besides, gene representations from scGREAT provide valuable gene regulation insights, and external validation on spatial transcriptomics illuminated the mechanism behind scGREAT annotation. Moreover, scGREAT identified several TF target regulations corroborated in studies.

Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes.

Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) towards precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifiers genes and activated signaling/myeloid transcription factor (AS/MTF), with disease progression and treatment failure in CML patients following tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis, and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes with a limit of detection of 0.2%. A total of 70 mutations were detected in 57 (22.4%) diagnostic samples, while 64 mutations were detected in 39 (27.9%) of the follow-up samples. Carrying any mutation at initial diagnosis was associated with worse outcomes following TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with Imatinib showed higher risks of treatment failure (HR 2.53, 95% CI [1.13-5.66], p=0.0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs (2G-TKI). The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival (FFS), and progression risk. Additionally, there was an observable non-significant trend indicating a heightened risk of progression to advanced disease and worse overall survival (OS). Conclusion: Mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression, even from initial diagnosis, and may help upfront TKI selection.

Polygenic risk for triglyceride levels in the presence of a high impact rare variant.

BACKGROUND: Elevated triglyceride (TG) levels are a heritable and modifiable risk factor for cardiovascular disease and have well-established associations with common genetic variation captured in a polygenic risk score (PRS). In young adulthood, the 22q11.2 microdeletion conveys a 2-fold increased risk for mild-moderate hypertriglyceridemia. This study aimed to assess the role of the TG-PRS in individuals with this elevated baseline risk for mild-moderate hypertriglyceridemia. METHODS: We studied a deeply phenotyped cohort of adults (n = 157, median age 34 years) with a 22q11.2 microdeletion and available genome sequencing, lipid level, and other clinical data. The association between a previously developed TG-PRS and TG levels was assessed using a multivariable regression model adjusting for effects of sex, BMI, and other covariates. We also constructed receiver operating characteristic (ROC) curves using logistic regression models to assess the ability of TG-PRS and significant clinical variables to predict mild-moderate hypertriglyceridemia status. RESULTS: The TG-PRS was a significant predictor of TG-levels (p = 1.52E-04), along with male sex and BMI, in a multivariable model (pmodel = 7.26E-05). The effect of TG-PRS appeared to be slightly stronger in individuals with obesity (BMI ≥ 30) (beta = 0.4617) than without (beta = 0.1778), in a model unadjusted for other covariates (p-interaction = 0.045). Among ROC curves constructed, the inclusion of TG-PRS, sex, and BMI as predictor variables produced the greatest area under the curve (0.749) for classifying those with mild-moderate hypertriglyceridemia, achieving an optimal sensitivity and specificity of 0.746 and 0.707, respectively. CONCLUSIONS: These results demonstrate that in addition to significant effects of sex and BMI, genome-wide common variation captured in a PRS also contributes to the variable expression of the 22q11.2 microdeletion with respect to elevated TG levels.

Studying Fluorescence Sensing of Acetone and Tryptophan and Antibacterial Properties Based on Zinc-Based Triple Interpenetrating Metal-Organic Skeletons.

Two triple interpenetrating Zn(II)-based MOFs were studied in this paper. Named [Zn6(1,4-bpeb)4(IPA)6(H2O)]n (MOF-1) and {[Zn3(1,4-bpeb)1.5(DDBA)3]n·2DMF} (MOF-2), {1,4-bpeb = 1,4-bis [2-(4-pyridy1) ethenyl]benze, IPA = Isophthalic acid, DDBA = 3,3'-Azodibenzoic acid}, they were synthesized by the hydrothermal method and were characterized and stability tested. The results showed that MOF-1 had good acid-base stability and solvent stability. Furthermore, MOF-1 had excellent green fluorescence and with different phenomena in different solvents, which was almost completely quenched in acetone. Based on this phenomenon, an acetone sensing test was carried out, where the detection limit of acetone was calculated to be 0.00365% (volume ratio). Excitingly, the MOF-1 could also be used as a proportional fluorescent probe to specifically detect tryptophan, with a calculated detection limit of 34.84 µM. Furthermore, the mechanism was explained through energy transfer and competitive absorption (fluorescence resonance energy transfer (FRET)) and internal filtration effect (IFE). For antibacterial purposes, the minimum inhibitory concentrations of MOF-1 against Escherichia coli and Staphylococcus aureus were 19.52 µg/mL and 39.06 µg/mL, respectively, and the minimum inhibitory concentrations of MOF-2 against Escherichia coli and Staphylococcus aureus were 68.36 µg/mL and 136.72 µg/mL, respectively.

Significant Reductions in Secondary Aerosols after the Three-Year Action Plan in Beijing Summer.

Air quality in China has continuously improved during the Three-Year Action Plan (2018-2020); however, the changes in aerosol composition, properties, and sources in Beijing summer remain poorly understood. Here, we conducted real-time measurements of aerosol composition in five summers from 2018 to 2022 along with WRF-Community Multiscale Air Quality simulations to characterize the changes in aerosol chemistry and the roles of meteorology and emission reductions. Largely different from winter, secondary inorganic aerosol and photochemical-related secondary organic aerosol (SOA) showed significant decreases by 55-67% in summer, and the most decreases occurred in 2021. Comparatively, the decreases in the primary aerosol species and gaseous precursors were comparably small. While decreased atmospheric oxidation capacity as indicated by ozone changes played an important role in changing SOA composition, the large decrease in aerosol liquid water and small increase in particle acidity were critical for nitrate changes by decreasing gas-particle partitioning substantially (∼28%). Analysis of meteorological influences demonstrated clear and similar transitions in aerosol composition and formation mechanisms at a relative humidity of 50-60% in five summers. Model simulations revealed that emission controls played the decisive role in reducing sulfate, primary OA, and anthropogenic SOA during the Three-Year Action Plan, while meteorology affected more nitrate and biogenic SOA.

Complete chloroplast genome of Adonis pseudoamurensis W.T.Wang (Ranunculaceae).

Adonis pseudoamurensis W.T. Wang 1980 is an important traditional medicinal plant used for the treatment of cardiac diseases. The complete chloroplast (cp) genome of Adonis pseudoamurensis is reported for the first time in this study. The circular cp genome is 156,917 bp in length, consisting of a large single-copy region (86,262 bp), a small single-copy region (18,067 bp), and two inverted repeat regions (26,294 bp). The genome encodes 129 genes, comprising 84 protein-coding genes, 37 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis showed that A. pseudoamurensis is closely related to A. amurensis.

Validation of the shotgun metabarcoding approach for comprehensively identifying herbal products containing plant, fungal, and animal ingredients.

Identifying plant, fungal, and animal ingredients in a specific mixture remains challenging during the limitation of PCR amplification and low specificity of traditional methods. Genomic DNA was extracted from mock and pharmaceutical samples. Four type of DNA barcodes were generated from shotgun sequencing dataset with the help of a local bioinformatic pipeline. Taxa of each barcode was assigned by blast to TCM-BOL, BOLD, and GenBank. Traditional methods including microscopy, thin layer chromatography (TLC), and high-performance liquid chromatography (HPLC) were carried out according to Chinese pharmacopoeia. On average, 6.8 Gb shotgun reads were sequenced from genomic DNA of each sample. Then, 97, 11, 10, 14, and one operational taxonomic unit (OTU) were generated for ITS2, psbA-trnH, rbcL, matK, and COI, respectively. All the labeled ingredients including eight plant, one fungal, and one animal species were successfully detected in both the mock and pharmaceutical samples, in which Chebulae Fructus, Poria, and Fritilariae Thunbergia Bulbus were identified via mapping reads to organelle genomes. In addition, four unlabeled plant species were detected from pharmaceutical samples, while 30 genera of fungi, such as Schwanniomyces, Diaporthe, Fusarium were detected from mock and pharmaceutical samples. Furthermore, the microscopic, TLC, and HPLC analysis were all in accordance with the standards stipulated by Chinese Pharmacopoeia. This study indicated that shotgun metabarcoding could simultaneously identified plant, fungal, and animal ingredients in herbal products, which has the ability to serve as a valuable complement to traditional methods.

Comparative analysis of 17 complete chloroplast genomes reveals intraspecific variation and relationships among Pseudostellaria heterophylla (Miq.) Pax populations.

Pseudostellaria heterophylla (Miq.) Pax is a well-known medicinal and ecologically important plant. Effectively distinguishing its different genetic resources is essential for its breeding. Plant chloroplast genomes can provide much more information than traditional molecular markers and provide higher-resolution genetic analyses to distinguish closely related planting materials. Here, seventeen P. heterophylla samples from Anhui, Fujian, Guizhou, Hebei, Hunan, Jiangsu, and Shandong provinces were collected, and a genome skimming strategy was employed to obtain their chloroplast genomes. The P. heterophylla chloroplast genomes ranged from 149,356 bp to 149,592 bp in length, and a total of 111 unique genes were annotated, including 77 protein-coding genes, 30 tRNA genes, and four rRNA genes. Codon usage analysis showed that leucine had the highest frequency, while UUU (encoding phenylalanine) and UGC (encoding cysteine) were identified as the most and least frequently used codons, respectively. A total of 75-84 SSRs, 16-21 short tandem repeats, and 27-32 long repeat structures were identified in these chloroplast genomes. Then, four primer pairs were revealed for identifying SSR polymorphisms. Palindromes are the dominant type, accounting for an average of 47.86% of all long repeat sequences. Gene orders were highly collinear, and IR regions were highly conserved. Genome alignment indicated that there were four intergenic regions (psaI-ycf4, ycf3-trnS, ndhC-trnV, and ndhI-ndhG) and three coding genes (ndhJ, ycf1, and rpl20) that were highly variable among different P. heterophylla samples. Moreover, 10 SNP/MNP sites with high polymorphism were selected for further study. Phylogenetic analysis showed that populations of Chinese were clustered into a monophyletic group, in which the non-flowering variety formed a separate subclade with high statistical support. In this study, the comparative analysis of complete chloroplast genomes revealed intraspecific variations in P. heterophylla and further supported the idea that chloroplast genomes could elucidate relatedness among closely related cultivation materials.

Channel Modeling and Characteristics Analysis under Different 3D Dynamic Trajectories for UAV-Assisted Emergency Communications.

This study involved channel modeling and characteristics analysis of unmanned aerial vehicles (UAVs) according to different operating trajectories. Based on the idea of standardized channel modeling, air-to-ground (AG) channel modeling of a UAV was carried out, taking into consideration that both the receiver (Rx) and the transmitter (Tx) ran along different types of trajectories. In addition, based on Markov chains and a smooth-turn (ST) mobility model, the influences of different operation trajectories on typical channel characteristics-including time-variant power delay profile (PDP), stationary interval, temporal autocorrelation function (ACF), root mean square (RMS) delay spread (DS), and spatial cross-correlation function (CCF)-were studied. The multi-mobility multi-trajectory UAV channel model matched well with actual operation scenarios, and the characteristics of the UAV AG channel could be analyzed more accurately, thus providing a reference for future system design and sensor network deployment of sixth-generation (6G) UAV-assisted emergency communications.

Channel Characterization and Modeling for 6G UAV-Assisted Emergency Communications in Complicated Mountainous Scenarios.

Regarding the new demands and challenges of sixth-generation (6G) mobile communications, wireless networks are undergoing a significant shift from traditional terrestrial networks to space-air-ground-sea-integrated networks. Unmanned aerial vehicle (UAV) communications in complicated mountainous scenarios are typical applications and have practical implications, especially in emergency communications. In this paper, the ray-tracing (RT) method was applied to reconstruct the propagation scenario and then acquire the wireless channel data. Channel measurements are also conducted in real mountainous scenarios for verification. By setting different flight positions, trajectories, and altitudes, channel data in the millimeter wave (mmWave) band was obtained. Important statistical properties, such as the power delay profile (PDP), Rician K-factor, path loss (PL), root mean square (RMS) delay spread (DS), RMS angular spreads (ASs), and channel capacity were compared and analyzed. The effects of different frequency bands on channel characteristics at 3.5 GHz, 4.9 GHz, 28 GHz, and 38 GHz bands in mountainous scenarios were considered. Furthermore, the effects of extreme weather, especially different precipitation, on the channel characteristics were analyzed. The related results can provide fundamental support for the design and performance evaluation of future 6G UAV-assisted sensor networks in complicated mountainous scenarios.

Synthesis, Antifungal Activity, and Molecular Simulation Study of L-Carvone-Derived 1,3,4-Oxadiazole-Thioether Compounds.

To discover potent antifungal molecules with new and distinctive structures, 20 novel L-carvone-derived 1,3,4-oxadiazole-thioether compounds 5 a-5 t were synthesized through multi-step reaction of L-carvone, and their structures were confirmed by FT-IR, 1 H-NMR, 13 C-NMR, and HR-MS. The antifungal activities of compounds 5 a-5 t were preliminarily tested by in vitro method, and the results indicated that all of the title compounds displayed certain antifungal activities against the eight tested plant fungi, especially for P. piricola. Among them, compound 5 i (R=p-F) with the most significant antifungal activity deserved further study for discovering and developing novel natural product-based antifungal agents. Moreover, two molecular simulation technologies were employed for the investigation of their structure-activity relationships (SARs). Firstly, a reasonable and effective 3D-QSAR model was established by the comparative molecular field (CoMFA) method, and the relationship of the substituents linked with the benzene rings and the inhibitory activities of the title compounds against P. piricola was elucidated. Then, the binding mode of compound 5 i (R=p-F) and its potential biological target (CYP51) was simulated by molecular docking, and it was found that compound 5 i could readily bind with CYP51 in the active site, and the ligand-receptor interactions involved three hydrogen bonds and several hydrophobic effects.

The complete chloroplast genome and phylogenetic analysis of Lemmaphyllum carnosum var. drymoglossoides (baker) X. P. Wei, 2013.

Lemmaphyllum carnosum var. drymoglossoides (Baker) X. P. Wei, 2013 is a valuable medicinal fern in China. Its complete chloroplast genome was determined using Illumina paired-end sequencing. The genome was 157,571 bp in length with 130 genes, including 87 protein-coding genes, eight ribosomal RNA genes, and 35 tRNA genes. It displayed a quadripartite structure consisting of a small single-copy (SSC) of 21,691 bp, a large single-copy (LSC) of 81,106 bp, and two inverted repeats (IRs) of 27,387 bp, respectively. The phylogenetic results indicated that L. carnosum var. drymoglossoides exhibited the closest relationship with L. intermedium, and this study provided new information for the phylogenetic relationship of the Polypodiaceae family.

Comparative analysis of chloroplast genomes of 29 tomato germplasms: genome structures, phylogenetic relationships, and adaptive evolution.

In order to compare and analyze the chloroplast (cp) genomes of tomato germplasms and understand their phylogenetic relationships, the cp genomes of 29 tomato germplasms were sequenced and analyzed in this study. The results showed highly conserved characteristics in structure, number of gene and intron, inverted repeat regions, and repeat sequences among the 29 cp genomes. Moreover, single-nucleotide polymorphism (SNP) loci with high polymorphism located at 17 fragments were selected as candidate SNP markers for future studies. In the phylogenetic tree, the cp genomes of tomatoes were clustered into two major clades, and the genetic relationship between S. pimpinellifolium and S. lycopersicum was very close. In addition, only rps15 showed the highest average K A/K S ratio in the analysis of adaptive evolution, which was strongly positively selected. It may be very important for the study of adaptive evolution and breeding of tomato. In general, this study provides valuable information for further study of phylogenetic relationships, evolution, germplasm identification, and molecular marker-assisted selection breeding of tomato.

Multilevel interrogation of H3.3 reveals a primordial role in transcription regulation.

BACKGROUND: Eukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts. RESULTS: We used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes. CONCLUSION: Our results provide an evolutionary perspective on H3.3's conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways.

The complete chloroplast genome of Pseudostellaria davidii (franch.) Pax, 1934.

Pseudostellaria davidii (Franch.) Pax belongs to subseries distancs of Pseudostellaria (Caryophyllaceae), and is mainly distributed in north-eastern Asia. The complete chloroplast (cp) genome of P. davidii was assembled and annotated for the first time in this study. The cp genome of P. davidii is 149,732 bp in length with the GC content of 36.57%, and it consists of four subregions: a large single-copy (LSC) region of 81,156 bp, a small single-copy (SSC) region of 16,894 bp and two inverted repeats (IR) regions of 25,841 bp each. The cp genome of P. davidii encodes a total of 111 unique genes, which are 77 protein-coding genes, four rRNA genes, and 30 tRNA genes. The results of phylogenetic analysis strongly suggested that Pseudostellaria was a monophyletic group and P. davidii forms an independent sister clade to other species of Pseudostellaria.

A central chaperone-like role for 14-3-3 proteins in human cells.

14-3-3 proteins are highly conserved regulatory proteins that interact with hundreds of structurally diverse clients and act as central hubs of signaling networks. However, how 14-3-3 paralogs differ in specificity and how they regulate client protein function are not known for most clients. Here, we map the interactomes of all human 14-3-3 paralogs and systematically characterize the effect of disrupting these interactions on client localization. The loss of 14-3-3 binding leads to the coalescence of a large fraction of clients into discrete foci in a client-specific manner, suggesting a central chaperone-like function for 14-3-3 proteins. Congruently, the engraftment of 14-3-3 binding motifs to nonclients can suppress their aggregation or phase separation. Finally, we show that 14-3-3s negatively regulate the localization of the RNA-binding protein SAMD4A to cytoplasmic granules and inhibit its activity as a translational repressor. Our work suggests that 14-3-3s have a more prominent role as chaperone-like molecules than previously thought.