Genome-wide analysis of FRF gene family and functional identification of HvFRF9 under drought stress in barley.

FHY3 and its homologous protein FAR1 are the founding members of FRS family. They exhibited diverse and powerful physiological functions during evolution, and participated in the response to multiple abiotic stresses. FRF genes are considered to be truncated FRS family proteins. They competed with FRS for DNA binding sites to regulate gene expression. However, only few studies are available on FRF genes in plants participating in the regulation of abiotic stress. With wide adaptability and high stress-resistance, barley is an excellent candidate for the identification of stress-resistance-related genes. In this study, 22 HvFRFs were detected in barley using bioinformatic analysis from whole genome. According to evolution and conserved motif analysis, the 22 HvFRFs could be divided into subfamilies I and II. Most promoters of subfamily I members contained abscisic acid and methyl jasmonate response elements; however, a large number promoters of subfamily II contained gibberellin and salicylic acid response elements. HvFRF9, one of the members of subfamily II, exhibited a expression advantage in different tissues, and it was most significantly upregulated under drought stress. In-situ PCR revealed that HvFRF9 is mainly expressed in the root epidermal cells, as well as xylem and phloem of roots and leaves, indicating that HvFRF9 may be related to absorption and transportation of water and nutrients. The results of subcellular localization indicated that HvFRF9 was mainly expressed in the nuclei of tobacco epidermal cells and protoplast of arabidopsis. Further, transgenic arabidopsis plants with HvFRF9 overexpression were generated to verify the role of HvFRF9 in drought resistance. Under drought stress, leaf chlorosis and wilting, MDA and O2 - contents were significantly lower, meanwhile, fresh weight, root length, PRO content, and SOD, CAT and POD activities were significantly higher in HvFRF9-overexpressing arabidopsis plants than in wild-type plants. Therefore, overexpression of HvFRF9 could significantly enhance the drought resistance in arabidopsis. These results suggested that HvFRF9 may play a key role in drought resistance in barley by increasing the absorption and transportation of water and the activity of antioxidant enzymes. This study provided a theoretical basis for drought resistance in barley and provided new genes for drought resistance breeding.

Enantioselective Toxicity of Tetramethrin to Different Developmental Stages of Zebrafish (Danio rerio).

Chiral pesticides exhibit enantioselective differences in processes such as biological absorption, metabolism, and toxic effects. Organisms have different physiological characteristics at different developmental stages. Therefore, conducting enantiomeric toxicity studies at different developmental stages of organisms can help deepen the understanding of the ecological effects of chiral pesticides. This study focused on trans-tetramethrin (Tet) and investigated the enantioselectivity in bioconcentration, developmental toxicity, estrogenic effects, and immunotoxicity of Tet's racemate ((±)-Tet) and its two enantiomers ((+)-Tet and (-)-Tet) in three developmental stages of zebrafish: embryos, yolk sac larvae, and juveniles. The results showed that Tet exhibited different enantioselectivity in lethal, bioconcentration, and teratogenic effects on zebrafish at different developmental stages. The LC50 value was (+)-Tet > (±)-Tet > (-)-Tet, with embryos being the most sensitive, followed by juveniles and yolk sac larvae. The enantioselective bioconcentration was (±)-Tet > (+)-Tet > (-)-Tet, and the bioconcentration effect was greater in embryos than that in yolk sac larvae and juveniles. Developmental toxicity indicated that (+)-Tet and (±)-Tet had higher teratogenic effects on yolk sac larvae than on embryos. Tet exhibited different enantioselective effects on the expression of zebrafish estrogen-related genes and innate immune-related genes at different developmental stages. These results will contribute to a more comprehensive assessment of the aquatic toxicity and environmental risks of chiral pesticides.

Neuroimaging changes in the pregeniculate visual pathway and chiasmal enlargement in Leber hereditary optic neuropathy.

PURPOSE: To describe the pattern of MRI changes in the pregeniculate visual pathway in Leber hereditary optic neuropathy (LHON). METHOD: This retrospective observational study enrolled 60 patients with LHON between January 2015 and December 2021. The abnormal MRI features seen in the pregeniculate visual pathway were investigated, and then correlated with the causative mitochondrial DNA (mtDNA) mutation, the distribution of the MRI lesions and the duration of vision loss. RESULT: The cohort included 48 (80%) males and 53 (88%) had bilateral vision loss. The median age of onset was 17.0 years (range 4.0-58.0). 28 (47%) patients had the m.11778G>A mutation. 34 (57%) patients had T2 hyperintensity (HS) in the pregeniculate visual pathway and 13 (22%) patients with chiasmal enlargement. 20 patients (71%) carrying the m.11778G>A mutation had T2 HS, significantly more than the 14 patients (44%) with T2 HS in the other LHON mutation groups (p=0.039). Furthermore, significantly more patients in the m.11778G>A group (16 patients (57%)) had T2 HS in optic chiasm (OCh)/optic tract (OTr) than the other LHON mutation groups (7 patients (22%), p=0.005). Optic chiasmal enlargement was more common in patients with vision loss duration <3 months compared with those ≥3 months (p=0.028). CONCLUSION: T2 HS in the pregeniculate visual pathway is a frequent finding in LHON. Signal changes in the OCh/OTr and chiasmal enlargement, in particular within the first 3 months of visual loss, were more commonly seen in patients carrying the m.11778G>A mtDNA mutation, which may be of diagnostic significance.

Immune checkpoint inhibitors for multiple myeloma immunotherapy.

Multiple myeloma (MM) is related to immune disorders, recent studys have revealed that immunotherapy can greatly benefit MM patients. Immune checkpoints can negatively modulate the immune system and are closely associated with immune escape. Immune checkpoint-related therapy has attracted much attention and research in MM. However, the efficacy of those therapies need further improvements. There need more thoughts about the immune checkpoint to translate their use in clinical work. In our review, we aggregated the currently known immune checkpoints and their corresponding ligands, further more we propose various ways of potential translation applying treatment based on immune checkpoints for MM patients.

Research trends of worldwide ophthalmologic randomized controlled trials in the 21st century: A bibliometric study.

Background: Randomized controlled trials (RCTs) are often considered the gold standard and the cornerstone for clinical practice. However, bibliometric studies on worldwide RCTs of ophthalmology published in the 21st century have not been reported in detail yet. This study aims to perform a bibliometric study and visualization analysis of worldwide ophthalmologic RCTs in the 21st century. Methods: Global ophthalmologic RCTs from 2000 to 2022 were searched in the Web of Science Core Collection. The number of publications, country/region, institution, author, journal, and research hotspots of RCTs were analyzed using HistCite, VOSviewer, CiteSpace, and Excel software. Results: 2366 institutions and 90 journals from 83 countries/regions participated in the publication of 1769 global ophthalmologic RCTs, with the United States leading in the number of volumes and research field, and the Moorfields Eye Hospital contributing to the most publications. Ophthalmology received the greatest number of publications and co-citations. Jeffrey S. Heier owned the most publications and Jost B. Jonas owned the most co-citations. The knowledge foundations of global ophthalmologic RCTs were mainly retinopathy, glaucoma, dry eye disease (DED), and cataracts, and anti-vascular endothelial growth factor (VEGF) therapy (ranibizumab), topical ocular hypotensive medication, laser trabeculoplasty. Anti-VEGF therapy for age-related macular degeneration (AMD), DME (diabetic macular edema), and DED, the use of new diagnostic tools, and myopia were the hottest research highlights. Anti-VEGF therapy, prompt laser, triamcinolone, and verteporfin photodynamic therapy for AMD, DME, and CNV (choroidal neovascularization), DED, myopia, and open-angle glaucoma were the research hotspots with the longest duration. The future research hotspots might be DED and the prevention and control of myopia. Conclusions: Overall, the number of global ophthalmologic RCTs in the 21st century was keeping growing, there was an imbalance between the regions and institutions, and more efforts are required to raise the quantity, quality, and global impact of high-quality clinical evidence in developing countries/regions.

Quality of life considerations and management in patients with myelodysplastic syndrome.

INTRODUCTION: This study aimed to identify the factors affecting the quality of life (QOL) and functional status of patients with MDS. AREAS COVERED: We reviewed the literature published in PUBMED over the past 30 years and searched for keywords such as 'quality of life' and 'myelodysplastic syndromes'. By observing the influence of their symptoms, the possibility of improving patients' QOL was considered by improving these related factors. Concurrently, the effects of related clinical treatments based on the unique disease characteristics of MDS on the patients' QOL were examined, and lifestyle factors were considered in clinical practice, providing an important path to improve the QOL and functional status of patients with MDS. EXPERT OPINION: This review summarized several areas that can improve the quality of survival of MDS patients and discusses them in depth. Although the clinical benefits may be minimal, we still hope to improve patients' daily life outcomes and enhance their quality of life at minimal cost. Also, we hope more researchers will focus on this area in the future to find more factors that may exist to supplement the limitations of these understanding and thinking, and to provide assistance in clinical work.

An H2 S-BMP6 Dual-Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy.

Critical limb ischemia, the final course of peripheral artery disease, is characterized by an insufficient supply of blood flow and excessive oxidative stress. H2 S molecular therapy possesses huge potential for accelerating revascularization and scavenging intracellular reactive oxygen species (ROS). Moreover, it is found that BMP6 is the most significantly up-expressed secreted protein-related gene in HUVECs treated with GYY4137, a H2 S donor, based on the transcriptome analysis. Herein, a UIO-66-NH2 @GYY4137@BMP6 co-delivery nanoplatform to strengthen the therapeutic effects of limb ischemia is developed. The established UIO-66-NH2 @GYY4137@BMP6 nanoplatform exerts its proangiogenic and anti-oxidation functions by regulating key pathways. The underlying molecular mechanisms of UIO-66-NH2 @GYY4137@BMP6 dual-loading system lie in the upregulation of phosphorylated YAP/TAZ and Jun to promote HUVECs proliferation and downregulation of phosphorylated p53/p21 to scavenge excessive ROS. Meanwhile, laser-doppler perfusion imaging (LDPI), injury severity evaluation, and histological analysis confirm the excellent therapeutic effects of UIO-66-NH2 @GYY4137@BMP6 in vivo. This work may shed light on the treatment of critical limb ischemia by regulating YAP, Jun, and p53 signaling pathways based on gas-protein synergistic therapy.

Combinatorial Synthesis of Covalent Organic Framework Particles with Hierarchical Pores and Their Catalytic Application.

Precise tailoring of the aggregation state of covalent organic frameworks (COFs) to form a hierarchical porous structure is critical to their performance and applications. Here, we report a one-pot and one-step strategy of using dynamic combinatorial chemistry to construct imine-based hollow COFs containing meso- and macropores. It relies on a direct copolymerization of three or more monomers in the presence of two monofunctional competitors. The resulting particle products possess high crystallinity and hierarchical pores, including micropores around 0.93 nm, mesopores widely distributed in the range of 3.1-32 nm, and macropores at about 500 nm, while the specific surface area could be up to 748 m2·g-1, with non-micropores accounting for 60% of the specific surface area. The particles demonstrate unique advantages in the application as nanocarriers for in situ loading of Pd catalysts at 93.8% loading efficiency in the copolymerization of ethylene and carbon monoxide. The growth and assembly of the copolymer could thus be regulated to form flower-shaped particles, efficiently suppressing the fouling of the reactor. The copolymer's weight-average molecular weight and the melting temperature are also highly improved. Our method provides a facile way of fabricating COFs with hierarchical pores for advanced applications in catalysis.

Multiple Bound State Soliton Pulses in the All Polarization Maintaining Fiber Laser.

The bound state soliton pulse, a novel mode-locked output state of fiber lasers, has been studied extensively to gain a better understanding of soliton interactions and to explain the mechanism behind the generation of mode-locked pulses. In this particular research, we utilized a self-made saturable absorber (SA) consisting of single-walled carbon nanotubes (SWCNT) in a fully polarization maintaining (PM) erbium-doped fiber optical path. Through this setup, we observed various bound state pulse phenomena, including the double bound state with different phase differences, the bound state formed by two double pulse bound states, the multi-pulse bound state, etc. The abundant bound soliton pulse states demonstrated the excellent nonlinear absorption characteristics of the SA as well as the excellent optical properties of the all-PM fiber laser. It contributed to exploring the relationship between sub pulses and mode-locked pulses in the future. Additionally, due to the strong interaction between bound state solitons and the inherent stability of the PM optical path, there was potential for utilizing this setup as a seed source to enhance the stability of high-power fiber lasers.

Imaging the electron charge density in monolayer MoS2 at the Ångstrom scale.

Four-dimensional scanning transmission electron microscopy (4D-STEM) has recently gained widespread attention for its ability to image atomic electric fields with sub-Ångstrom spatial resolution. These electric field maps represent the integrated effect of the nucleus, core electrons and valence electrons, and separating their contributions is non-trivial. In this paper, we utilized simultaneously acquired 4D-STEM center of mass (CoM) images and annular dark field (ADF) images to determine the projected electron charge density in monolayer MoS2. We evaluate the contributions of both the core electrons and the valence electrons to the derived electron charge density; however, due to blurring by the probe shape, the valence electron contribution forms a nearly featureless background while most of the spatial modulation comes from the core electrons. Our findings highlight the importance of probe shape in interpreting charge densities derived from 4D-STEM and the need for smaller electron probes.

Therapeutic strategies to enhance immune response induced by multiple myeloma cells.

Multiple myeloma (MM)as a haematological malignancy is still incurable. In addition to the presence of somatic genetic mutations in myeloma patients, the presence of immunosuppressive microenvironment greatly affects the outcome of treatment. Although the discovery of immunotherapy makes it possible to break the risk of high toxicity and side effects of traditional chemotherapeutic drugs, there are still obstacles of ineffective treatment or disease recurrence. In this review, we discuss therapeutic strategies to further enhance the specific anti-tumor immune response by activating the immunogenicity of MM cells themselves. New ideas for future myeloma therapeutic approaches are provided.

Cellular immunity in the era of modern multiple myeloma therapy.

Multiple myeloma (MM) is a relapsing clonal plasma cell malignancy and incurable thus far. With the increasing understanding of myeloma, highlighting the critical importance of the immune system in the pathogenesis of MM is essential. The immune changes in MM patients after treatment are associated with prognosis. In this review, we summarize currently available MM therapies and discuss how they affect cellular immunity. We find that the modern anti-MM treatments enhance antitumour immune responses. A deeper understanding of the therapeutic activity of individual drugs offers more effective treatment approaches that enhance the beneficial immunomodulatory effects. Furthermore, we show that the immune changes after treatment in MM patients can provide useful prognostic marker. Analysing cellular immune responses offers new perspectives for evaluating clinical data and making comprehensive predictions for applying novel therapies in MM patients.

Pan-genome of Citrullus genus highlights the extent of presence/absence variation during domestication and selection.

The rich genetic diversity in Citrullus lanatus and the other six species in the Citrullus genus provides important sources in watermelon breeding. Here, we present the Citrullus genus pan-genome based on the 400 Citrullus genus resequencing data, showing that 477 Mb contigs and 6249 protein-coding genes were absent in the Citrullus lanatus reference genome. In the Citrullus genus pan-genome, there are a total of 8795 (30.5%) genes that exhibit presence/absence variations (PAVs). Presence/absence variation (PAV) analysis showed that a lot of gene PAV were selected during the domestication and improvement, such as 53 favorable genes and 40 unfavorable genes were identified during the C. mucosospermus to C. lanatus landrace domestication. We also identified 661 resistance gene analogs (RGAs) in the Citrullus genus pan-genome, which contains 90 RGAs (89 variable and 1 core gene) located on the pangenome additional contigs. By gene PAV-based GWAS, 8 gene presence/absence variations were found associated with flesh color. Finally, based on the results of gene PAV selection analysis between watermelon populations with different fruit colors, we identified four non-reference candidate genes associated with carotenoid accumulation, which had a significantly higher frequency in the white flesh. These results will provide an important source for watermelon breeding.

Identification of core cuprotosis-correlated biomarkers in abdominal aortic aneurysm immune microenvironment based on bioinformatics.

Background: The occurrence of abdominal aortic aneurysms (AAAs) is related to the disorder of immune microenvironment. Cuprotosis was reported to influence the immune microenvironment. The objective of this study is to identify cuprotosis-related genes involved in the pathogenesis and progression of AAA. Methods: Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in mouse were identified following AAA through high-throughput RNA sequencing. The enrichment analyses of pathway were selected through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). The validation of cuprotosis-related genes was conducted through immunofluorescence and western blot analyses. Results: Totally, 27616 lncRNAs and 2189 mRNAs were observed to be differentially expressed (|Fold Change| ≥ 2 and q< 0.05) after AAA, including 10424 up-regulated and 17192 down-regulated lncRNAs, 1904 up-regulated and 285 down-regulated mRNAs. Gene ontology and KEGG pathway analysis showed that the DElncRNAs and DEmRNAs were implicated in many different biological processes and pathways. Furthermore, Cuprotosis-related genes (NLRP3, FDX1) were upregulated in the AAA samples compared with the normal one. Conclusion: Cuprotosis-related genes (NLRP3,FDX1) involved in AAA immune environment might be critical for providing new insight into identification of potential targets for AAA therapy.

In Situ Thermal Polymerization of a Succinonitrile-Based Gel Polymer Electrolyte for Lithium-Oxygen Batteries.

For lithium-oxygen batteries (LOBs), the leakage and volatilization of a liquid electrolyte and its poor electrochemical performance are the main reasons for the slow industrial advancement. Searching for more stable electrolyte substrates and reducing the use of liquid solvents are crucial to the development of LOBs. In this work, a well-designed succinonitrile-based (SN) gel polymer electrolyte (GPE-SLFE) is prepared by in situ thermal cross-linking of an ethoxylate trimethylolpropane triacrylate (ETPTA) monomer. The continuous Li+ transfer channel, formed by the synergistic effect of an SN-based plastic crystal electrolyte and an ETPTA polymer network, endows the GPE-SLFE with a high room-temperature ionic conductivity (1.61 mS cm-1 at 25 °C), a high lithium-ion transference number (tLi+ = 0.489), and excellent long-term stability of the Li/GPE-SLFE/Li symmetric cell at a current density of 0.1 mA cm-2 for over 220 h. Furthermore, cells with the GPE-SLFE exhibit a high discharge specific capacity of 4629.7 mAh g-1 and achieve 40 cycles.

Defect-rich Mo2S3 loaded wood-derived carbon acts as a spacer in lithium-sulfur batteries: forming a polysulfide capture net and promoting fast lithium flux.

Due to the sluggish kinetics of sulfur conversion and the large volume change of the lithium anode, along with the formation of lithium dendrites, lithium-sulfur batteries (LSBs) usually exhibit severe capacity decay and poor cycle life. It is necessary to consider the factors associated with cathodes, separators and anodes in an integrated manner to solve the problems existing in LSBs. In this paper, a vertically aligned porous carbon decorated with transition metal sulfides was introduced between a cathode and an anode to comprehensively solve the problems of LSBs. Widely existing natural wood was used as the framework structure, and Mo2S3 with abundant sulfur vacancies was deposited into its channels. Theoretical calculations and experimental results have confirmed a low energy barrier for sulfur conversion and the presence of a strong electric field around the spacer, which benefits fast ion transportation. As a result, on employing the multifunctional spacer, LSB full cells delivered a high initial capacity and a long cycle life. This study provides a reference for reducing development cost, simplifying optimization steps and promoting the commercial application of LSBs.

A novel sesquiterpene lactone fraction from Eupatorium chinense L. suppresses hepatocellular carcinoma growth by triggering ferritinophagy and mitochondrial damage.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive tumor with limited treatment options, and it is the third leading cause of cancer-related deaths. Hence, novel therapeutic strategies are required to treat HCC. Eupatorium chinense L. is a traditional Chinese medicine (TCM) that can effectively neutralize heat and smoothen the flow of "Qi" through the liver. However, the anti-HCC effects of Eupatorium chinense L. remain unknown. PURPOSE: The present study investigated the anti-HCC effects and the underlying mechanisms of the electrophilic sesquiterpenes isolated from E. chinense L. (EChLESs) in the regulation of ferroptosis and apoptosis in HCC cells. STUDY DESIGN/METHODS: Cell viability was assessed by the MTT assay. Cell apoptosis was confirmed by flow cytometry and western blotting assay. Ferroptosis was assessed by flow cytometry, transmission electron microscopy, and western blotting assay. Ferritinophagy was detected by acridine orange staining and western blotting assay. Small interfering RNA of nuclear receptor coactivator 4 (NCOA4) was used to confirm the role of ferritinophagy in the therapeutic effect of EChLESs on HCC cells. A mouse xenograft model was constructed to determine the inhibitory effect of EChLESs on HCC in vivo. RESULTS: EChLESs induced apoptosis by disrupting mitochondrial membrane potential depolarization and mitochondrial reactive oxygen species. EChLESs induced ferroptosis as noted by a significant increase in mitochondrial disruption, lipid peroxidation, and intracellular iron level and decreased glutathione level. The apoptosis inhibitor Z-VAD-FMK and lipid reactive oxygen species scavenger ferrostatin 1 attenuated EChLESs-induced cell death. NCOA4-mediated ferritinophagy through autophagic flux was the crucial pathway for ferroptosis induced by EChLESs. NCOA4 knockdown alleviated EChLESs-induced cell death. EChLESs controlled the expression of NCOA4 at the transcriptional and post-transcriptional levels. In the in vivo experiment, EChLESs suppressed HCC growth in the xenograft tumor mouse model. CONCLUSION: EChLESs enhances cell apoptosis through mitochondrial dysfunction and ferroptosis through NCOA4-mediated ferritinophagy. Thus, Eupatorium chinense L. could be a potential TCM for treating HCC.

Immunogenic Cell Death in Hematological Malignancy Therapy.

Although the curative effect of hematological malignancies has been improved in recent years, relapse or drug resistance of hematological malignancies will eventually recur. Furthermore, the microenvironment disorder is an important mechanism in the pathogenesis of hematological malignancies. Immunogenic cell death (ICD) is a unique mechanism of regulated cell death (RCD) that triggers an intact antigen-specific adaptive immune response by firing a set of danger signals or damage-associated molecular patterns (DAMPs), which is an immunotherapeutic modality with the potential for the treatment of hematological malignancies. This review summarizes the existing knowledge about the induction of ICD in hematological malignancies and the current research on combining ICD inducers with other treatment strategies for hematological malignancies.

Biochar amendments and climate warming affected nitrification associated N2O and NO production in a vegetable field.

Soil nitrification driven by ammonia-oxidizing microorganisms is the most important source of nitrous oxide (N2O) and nitric oxide (NO). Biochar amendment has been proposed as the most promising measure for combating climate warming; both have the potential to regulate the soil nitrification process. However, the comprehensive impacts of different aged biochars and warming combinations on soil nitrification-related N2O and NO production are not well understood. Here, 1-octyne and acetylene were used to investigate the relative contributions of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to potential nitrification-mediated N2O and NO production from the fertilized vegetable soil with different aged biochar amendments and soil temperatures in microcosm incubations. Results demonstrated that AOB dominated nitrification-related N2O and NO production across biochar additions and climate warming. Biochar amendment did not significantly influence the relative contribution of AOB and AOA to N2O and NO production. Field-aged biochar markedly reduced N2O and NO production via inhibiting AOB-amoA gene abundance and AOB-dependent N2O yield while fresh- and lab-aged biochar produced negligible effects on AOB-dependent N2O yield. Climate warming significantly increased N2O production and AOB-dependent N2O yield but less so on NO production. Notably, the relative contribution of AOB to N2O production was enhanced by climate warming, whereas AOB-derived NO showed the opposite tendency. Overall, the results revealed that field-aged biochar contributed to mitigating warming-induced increases in N2O and NO production via inhibiting AOB-amoA gene abundance and AOB-dependent N2O yield. Our findings provided guidance for mitigating nitrogen oxide emissions in intensively managed vegetable production under the context of biochar amendments and climate warming.