The BEL1-like homeodomain protein OsBLH4 regulates rice plant height, grain number, and heading date by repressing the expression of OsGA2ox1.

Gibberellins (GAs) play crucial roles in regulating plant architecture and grain yield of crops. In rice, the inactivation of endogenous bioactive GAs and their precursors by GA 2-oxidases (GA2oxs) regulates stem elongation and reproductive development. However, the regulatory mechanisms of GA2ox gene expression, especially in rice reproductive organs, are unknown. The BEL1-like homeodomain protein OsBLH4, a negative regulatory factor for the rice OsGA2ox1 gene, was identified in this study. Loss of OsBLH4 function results in decreased bioactive GA levels and pleiotropic phenotypes, including reduced plant height, decreased grain number per panicle, and delayed heading date, as also observed in OsGA2ox1-overexpressing plants. Consistent with the mutant phenotype, OsBLH4 was predominantly expressed in shoots and young spikelets; its encoded protein was exclusively localized in the nucleus. Molecular analysis demonstrated that OsBLH4 directly bound to the promoter region of OsGA2ox1 to repress its expression. Genetic assays revealed that OsBLH4 acts upstream of OsGA2ox1 to control rice plant height, grain number, and heading date. Taken together, these results indicate a crucial role for OsBLH4 in regulating rice plant architecture and yield potential via regulation of bioactive GA levels, and provide a potential strategy for genetic improvements of rice.

Structure and antitumor activity of a polysaccharide from Rosa roxburghii.

It is proverbial that Rosa roxburghii, as a homology of medicine and food, is rich in polysaccharides. To discover bioactive macromolecules for combating cancer, the polysaccharides in R. roxburghii were investigated, leading to the purification of a polysaccharide (RRTP80-1). RRTP80-1 was measured to have an average molecular weight of 8.65 × 103 g/mol. Monosaccharide composition analysis revealed that RRTP80-1 was formed from three types of monosaccharides including arabinose, glucose, and galactose. Combination of methylation and GC-MS analysis suggested that the backbone of RRTP80-1 consisted of →5)-α-l-Araf-(1→, →6)-α-d-Glcp-(1→, →2,5)-α-l-Araf-(1→, →4,6)-ß-d-Galp-(1→, and →3)-α-l-Araf-(1→, with branch chains, α-l-Araf-(1→. In vivo studies indicated that RRTP80-1 exhibited inhibitory activity against the growth and proliferation of neoplasms in the zebrafish tumor xenograft model by suppressing angiogenesis. Additionally, RRTP80-1 was found to upregulate reactive oxygen species (ROS) and nitric oxide (NO) production levels in zebrafish models. All these studies suggest that RRTP80-1 activates the immune system to inhibit tumors. The potential role of the newly discovered homogeneous polysaccharide RRTP80-1 in cancer treatment was preliminarily clarified in this study.

Ultrasound-assisted modification of soybean protein isolate with L-histidine: Relationship between structure and function.

Herein, the effects of ultrasound-assisted L-histidine (L-His) on the physicochemical properties and conformation of soybean protein isolate (SPI) were investigated. Particle size, zeta potential, turbidity, and solubility were used to evaluate protein aggregation, and the relationship between structural and functional changes of the proteins was characterized using spectral analysis, surface hydrophobicity, emulsification, and antioxidant properties. After ultrasound-assisted L-His treatment, SPI exhibited a smaller particle size, higher solubility, and more homogeneous micromorphology owing to the decrease in alpha-helix content and subsequent increases in zeta potential and active sulfhydryl content. In addition, spectral analysis showed that L-His and SPI could form a complex, which changed the microenvironment of the amino acid residues in SPI, thus improving its emulsification and antioxidant properties. At the concentration of L-His was 0.3 % w/w, the nanocomplex had a smaller particle size (140.03 nm), higher ζ-potential (-23.63 mV), and higher emulsification stability (22.48 min).

Stereocontrolled Synthesis of Aryl C-Nucleosides under Ambient Conditions.

A stereocontrolled synthesis of an aryl C-nucleoside has been developed using D-ribals and arylboronic acids catalyzed by palladium without additional ligands in common solvents under an open-air atmosphere at room temperature. This protocol features very mild conditions, simplicity in operation, exclusive ß-stereoselectivity, broad substrate scopes, and good compatibility with reactive amino and hydroxyl groups. The functionalization of unsaturated C-nucleosides and the late-stage glycosylation of natural products/drugs demonstrated the high practicality of this strategy.

Heterogeneous distribution of kinesin-streptavidin complexes revealed by mass photometry.

Kinesin-streptavidin complexes are widely used in microtubule-based active-matter studies. The stoichiometry of the complexes is empirically tuned but experimentally challenging to determine. Here, mass photometry measurements reveal heterogenous distributions of kinesin-streptavidin complexes. Our binding model indicates that heterogeneity arises from both the kinesin-streptavidin mixing ratio and the kinesin-biotinylation efficiency.

RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila.

Histone modification and nucleosome assembly play important roles in chromatin-related processes. Histone chaperones form different complexes and coordinate histone transportation and assembly. Various histone chaperone complexes have been identified in different organisms. The ciliate protozoa (ciliates) have various chromatin structures and different nuclear morphology. However, histone chaperone components and functions of different subunits remain unclear in ciliates. Tetrahymema thermophila contains a transcriptionally active macronucleus (MAC) and a transcriptionally inactive micronucleus (MIC) which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental stages. Here, we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental stages. REBL1 knockdown inhibited cellular proliferation. The macronuclear morphology became bigger in growing mutants. The abnormal macronuclear structure also occurred in the starvation stage. Furthermore, micronuclear meiosis was disturbed during sexual development, leading to a failure to generate new gametic nuclei. RebL1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental stages. REBL1 knockdown affected expression levels of the genes involved in chromatin organization and transcription. Taken together, RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in T. thermophila. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00219-z.

Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates inflammatory response ulcerative colitis through TLR4/NF-κB signaling pathway.

BACKGROUND: Ulcer colitis (UC) is a chronic, nonspecific, and noninfectious inflammatory bowel disease. Recently, Toll-like receptors (TLRs) have been found to be closely associated with clinical inflammatory diseases. Achieving complete remission in patients with intermittent periods of activity followed by dormancy is challenging. Moreover, no study has explored the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. AIM: To explore the mechanism by which Kuicolong-yu enema decoction retains traditional Chinese medicine enemas to attenuate the inflammatory response in UC. METHODS: This prospective clinical study included patients who met the exclusion criteria in 2020 and 2021. The patients with UC were divided into two groups (control and experimental). The peripheral blood of the experimental and control groups were collected under aseptic conditions. The expression of TLR4 protein, NF-κB, IL-6, and IL-17 was detected in the peripheral blood of patients in the experimental group and control group before and 1 month after taking the drug. Linear correlation analysis was used to analyze the relationship between the expression level of TLR4 protein and the expression levels of downstream signal NF-κB and inflammatory factors IL-6 and IL-17, and P < 0.05 was considered statistically significant. RESULTS: There were no significant differences in the patient characteristics between the control and experimental groups. The results showed that the expression levels of TLR4 and NF-κB in the experimental group were significantly lower than those in the control group (P < 0.05). The levels of IL-6 and IL-17 in the experimental group were significantly lower than those in the control group (P < 0.05). The TLR4 protein expression in the experimental group was positively correlated with the expression level of downstream signal NF-κB and was positively correlated with the levels of downstream inflammatory cytokines IL-6 and IL-17 (r = 0.823, P < 0.05). CONCLUSION: Kuicolong-yu enema decoction retains traditional Chinese medicine enema attenuates the inflammatory response of UC through the TLR4/NF-κB signaling pathway.

Endoscopic treatment of bleeding gastric ulcer causing gastric wall necrosis: A case report.

BACKGROUND: Gastric wall necrosis is a rare complication of endoscopic treatment for bleeding gastric ulcer, which may exacerbate the patient's condition once it occurs and may even require surgical intervention for treatment. CASE SUMMARY: A 59-year-old man was admitted to our department with melena. Endoscopy revealed a giant ulcer in the gastric antrum with a visible vessel in its center, which was treated with sclerosants and tissue glue injection and resulted in necrosis of the gastric wall. CONCLUSION: Injection of sclerosants and tissue glue may lead to gastric wall necrosis, which is a serious complication. Therefore, before administering this treatment to patients, we should consider other more effective methods of hemostasis to avoid gastric wall necrosis.

Heart Failure with Normal Natriuretic Peptide Levels and Preserved Ejection Fraction: A Prospective Clinical and Cardiac MRI Study.

Purpose To describe the clinical presentation, comprehensive cardiac MRI characteristics, and prognosis of individuals with predisposed heart failure with preserved ejection fraction (HFpEF). Materials and Methods This prospective cohort study (part of MISSION-HFpEF [Multimodality Imaging in the Screening, Diagnosis, and Risk Stratification of HFpEF]; NCT04603404) was conducted from January 1, 2019, to September 30, 2021, and included individuals with suspected HFpEF who underwent cardiac MRI. Participants who had primary cardiomyopathy and primary valvular heart disease were excluded. Participants were split into a predisposed HFpEF group, defined as HFpEF with normal natriuretic peptide levels based on an HFA-PEFF (Heart Failure Association Pretest Assessment, Echocardiography and Natriuretic Peptide, Functional Testing, and Final Etiology) score of 4 from the latest European Society of Cardiology guidelines, and an HFpEF group (HFA-PEFF score of ≥ 5). An asymptomatic control group without heart failure was also included. Clinical and cardiac MRI-based characteristics and outcomes were compared between groups. The primary end points were death, heart failure hospitalization, or stroke. Results A total of 213 participants with HFpEF, 151 participants with predisposed HFpEF, and 100 participants in the control group were analyzed. Compared with the control group, participants with predisposed HFpEF had worse left ventricular remodeling and function and higher systemic inflammation. Compared with participants with HFpEF, those with predisposed HFpEF, whether obese or not, were younger and had higher plasma volume, lower prevalence of atrial fibrillation, lower left atrial volume index, and less impaired left ventricular global longitudinal strain (-12.2% ± 2.8 vs -13.9% ± 3.1; P < .001) and early-diastolic global longitudinal strain rate (eGLSR, 0.52/sec ± 0.20 vs 0.57/sec ± 0.15; P = .03) but similar prognosis. Atrial fibrillation occurrence (hazard ratio [HR] = 3.90; P = .009), hemoglobin level (HR = 0.94; P = .001), and eGLSR (per 0.2-per-second increase, HR = 0.28; P = .002) were independently associated with occurrence of primary end points in participants with predisposed HFpEF. Conclusion Participants with predisposed HFpEF showed relatively unique clinical and cardiac MRI features, warranting greater clinical attention. eGLSR should be considered as a prognostic factor in participants with predisposed HFpEF. Keywords: Heart Failure with Preserved Ejection Fraction, Normal Natriuretic Peptide Levels, Cardiovascular Magnetic Resonance, Myocardial Strain, Prognosis Clinical trial registration no. NCT04603404 Supplemental material is available for this article. © RSNA, 2024.

The role of aldehydes on sulfur based-new particle formation: a theoretical study.

Aldehydes play a crucial role in the formation of atmospheric particles, attracting significant attention due to their environmental impact. However, the microscopic mechanisms underlying the formation of aldehyde-involved particles remain uncertain. In this study, through quantum chemical calculations and molecular dynamics (MD) simulations, we investigate the microscopic formation mechanisms of binary and ternary systems composed of three representative aldehydes, two sulfur-based acids, water, and two bases. Our research findings reveal that the most stable structures of acid-aldehyde clusters involve the connection of acids and aldehyde compounds through hydrogen bonds without involving proton transfer reactions, indicating relatively poor cluster stability. However, with the introduction of a third component, the stability of 18 clusters significantly increase. Among these, in ten systems, acids act as catalysts, facilitating reactions between aldehyde compounds and water or alkaline substances to generate glycols and amino alcohols. However, according to MD simulations conducted at 300 K, these acids readily dissociate from the resulting products. In the remaining eight systems, the most stable structural feature involves ion pairs formed by proton transfer reactions between acids and aldehyde compounds. These clusters exhibit remarkable thermodynamic stability. Furthermore, the acidity of the acid, the nature of nucleophilic agents, and the type of aldehyde all play significant roles in cluster stability and reactivity, and they have synergistic effects on the nucleation process. This study offers microscopic insights into the processes of new particle formation involving aldehydes, contributing to a deeper understanding of atmospheric chemistry at the molecular level.

Downregulation of HHATL promotes cardiac hypertrophy via activation of SHH/DRP1.

HHATL, previously implicated in cardiac hypertrophy in the zebrafish model, has emerged as a prioritized HCM risk gene. We identified six rare mutations in HHATL, present in 6.94 % of nonsarcomeric HCM patients (5/72). Moreover, a decrease of HHATL in the heart tissue from HCM patients and cardiac hypertrophy mouse model using transverse aortic constriction was observed. Despite this, the precise pathogenic mechanisms underlying HHATL-associated cardiac hypertrophy remain elusive. In this study, we observed that HHATL downregulation in H9C2 cells resulted in elevated expression of hypertrophic markers and reactive oxygen species (ROS), culminating in cardiac hypertrophy and mitochondrial dysfunction. Notably, the bioactive form of SHH, SHHN, exhibited a significant increase, while the mitochondrial fission protein dynamin-like GTPase (DRP1) decreased upon HHATL depletion. Intervention with the SHH inhibitor RU-SKI 43 or DRP1 overexpression effectively prevented Hhatl-depletion-induced cardiac hypertrophy, mitigating disruptions in mitochondrial morphology and membrane potential through the SHH/DRP1 axis. In summary, our findings suggest that HHATL depletion activates SHH signaling, reducing DRP1 levels and thereby promoting the expression of hypertrophic markers, ROS generation, and mitochondrial dysfunction, ultimately leading to cardiac hypertrophy. This study provides additional compelling evidence supporting the association of HHATL with cardiac hypertrophy.

Chemoradiotherapy-induced ACKR2+ tumor cells drive CD8+ T cell senescence and cervical cancer recurrence.

Tumor recurrence after chemoradiotherapy is challenging to overcome, and approaches to predict the recurrence remain elusive. Here, human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) analyzed by single-cell RNA sequencing reveal that CCRT specifically promotes CD8+ T cell senescence, driven by atypical chemokine receptor 2 (ACKR2)+ CCRT-resistant tumor cells. Mechanistically, ACKR2 expression is increased in response to CCRT and is also upregulated through the ligation of CC chemokines that are produced by activated myeloid and T cells. Subsequently, ACKR2+ tumor cells are induced to produce transforming growth factor ß to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis reveals that ACKR2 expression and CD8+ T cell senescence are enhanced in patients with cervical cancer who experienced recurrence after CCRT, indicating poor prognosis. Overall, we identify a subpopulation of CCRT-resistant ACKR2+ tumor cells driving CD8+ T cell senescence and tumor recurrence and highlight the prognostic value of ACKR2 and CD8+ T cell senescence for chemoradiotherapy recurrence.

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

Consensus for nonlinear multi-agent systems with actuator saturation by adaptive event-triggered scheme.

This paper studies the leader-follower consensus problem for nonlinear multi-agent systems with actuator saturation by adaptive event-triggered scheme. This adaptive mechanism allows parameters in triggered mechanism to change automatically compared to fixed ones in traditional strategies. The paper introduces two distinct approaches to address the issue of saturation. The first approach is sector bounded condition, while the second relies on convex hull representation. Compared with the former one, the latter one can reduce the conservatism of controller design effectively. Furthermore, it is assumed that the nonlinear function adheres to incremental quadratic limitations, thereby offering a more comprehensive depiction of its nonlinear properties. Finally, the validity of the proposed approaches is demonstrated by one numerical example in the background of mechanical systems.

Association between PM2.5 constituents and cardiometabolic risk factors: Exploring individual and combined effects, and mediating inflammation.

BACKGROUND: The individual and combined effects of PM2.5 constituents on cardiometabolic risk factors are sparsely investigated. Besides, the key cardiometabolic risk factor that PM2.5 constituents targeted and the biological mechanisms remain unclear. METHOD: A multistage, stratified cluster sampling survey was conducted in two typically air-polluted Chinese cities. The PM2.5 and its constituents including sulfate, nitrate, ammonium, organic matter, and black carbon were predicted using a machine learning model. Twenty biomarkers in three category were simultaneously adopted as cardiometabolic risk factors. We explored the individual and mixture association of long-term PM2.5 constituents with these markers using generalized additive model and quantile-based g-computation, respectively. To minimize potential confounding effects, we accounted for covariates including demographic, lifestyle, meteorological, temporal trends, and disease-related information. We further used ROC curve and mediation analysis to identify the key subclinical indicators and explore whether inflammatory mediators mediate such association, respectively. RESULT: PM2.5 constituents was positively correlated with HOMA-B, TC, TG, LDL-C and LCI, and negatively correlated with PP and RC. Further, PM2.5 constituent mixture was positive associated with DBP, MAP, HbA1c, HOMA-B, AC, CRI-1 and CRI-2, and negative associated with PP and HDL-C. The ROC analysis further reveals that multiple cardiometabolic risk factors can collectively discriminate exposure to PM2.5 constituents (AUC>0.9), among which PP and CRI-2 as individual indicators exhibit better identifiable performance for nitrate and ammonium (AUC>0.75). We also found that multiple blood lipid indicators may be affected by PM2.5 and its constituents, possibly mediated through complement C3 or hsCRP. CONCLUSION: Our study suggested associations of individual and combined PM2.5 constituents exposure with cardiometabolic risk factors. PP and CRI-2 were the targeted markers of long-term exposure to nitrate and ammonium. Inflammation may serve as a mediating factor between PM2.5 constituents and dyslipidemia, which enhance current understanding of potential pathways for PM2.5-induced preclinical cardiovascular responses.

Knockdown of YTHDF2 initiates ERS-induced apoptosis and cancer stemness suppression by sustaining GLI2 stability in cervical cancer.

Cervical cancer ranks fourth in women in terms of incidence and mortality. The RNA-binding protein YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) contributes to cancer progression by incompletely understood mechanisms. We show how YTHDF2 controls the fate of cervical cancer cells and whether YTHDF2 could be a valid target for the therapy of cervical cancer. Sphere formation and alkaline phosphatase staining assays were performed to evaluate tumor stemness of cervical cancer cells following YTHDF2 knockdown. Apoptosis was detected by flow cytometry and TUNEL assay. The compounds 4PBA and SP600125 were used to investigate the correlation between JNK, endoplasmic reticulum stress, tumor stemness, and apoptosis. Data from The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) revealed that GLI family zinc finger 2 (GLI2) might be the target of YTHDF2. The transcription inhibitor actinomycin D and dual-luciferase reporter gene assays were employed to investigate the association between the GLI2 mRNA and YTHDF2. Nude mouse xenografts were generated to assess the effects of YTHDF2 knockdown on cervical cancer growth in vivo. Knockdown of YTHDF2 up-regulated the expression of GLI2, leading to JNK phosphorylation and endoplasmic reticulum stress. These processes inhibited the proliferation of cervical cancer cells and their tumor cell stemness and promotion of apoptosis. In conclusion, the knockdown of YTHDF2 significantly affects the progression of cervical cancer cells, making it a potential target for treating cervical cancer.

Highly sensitive mapping of in vitro type II topoisomerase DNA cleavage sites with SHAN-seq.

Type II topoisomerases (topos) are a ubiquitous and essential class of enzymes that form transient enzyme-bound double-stranded breaks on DNA called cleavage complexes. The location and frequency of these cleavage complexes on DNA is important for cellular function, genomic stability, and a number of clinically important anticancer and antibacterial drugs, e.g., quinolones. We developed a simple high-accuracy end-sequencing (SHAN-seq) method to sensitively map type II topo cleavage complexes on DNA in vitro. Using SHAN-seq, we detected Escherichia coli gyrase and topoisomerase IV cleavage complexes at hundreds of sites on supercoiled pBR322 DNA, approximately one site every ten bp, with frequencies that varied by two-to-three orders of magnitude. These sites included previously identified sites and 20-50 fold more new sites. We show that the location and frequency of cleavage complexes at these sites are enzyme-specific and vary substantially in the presence of the quinolone, ciprofloxacin, but not with DNA supercoil chirality, i.e., negative vs. positive supercoiling. SHAN-seq's exquisite sensitivity provides an unprecedented single-nucleotide resolution view of the distribution of gyrase and topoisomerase IV cleavage complexes on DNA. Moreover, the discovery that these enzymes can cleave DNA at orders of magnitude more sites than the relatively few previously known sites resolves the apparent paradox of how these enzymes resolve topological problems throughout the genome.

Tandem Fields Facilitating Directional Carrier Migration in Van der Waals Heterojunction for Efficient Overall Piezo-Synthesis of H2O2.

Piezo-synthesis of H2O2 utilizing sustainable mechanical energy as well as earth-abundant water and oxygen is a green, cost-effective, and promising approach. However, achieving simultaneous two-electron water oxidation reaction (2e- WOR) and two-electron oxygen reduction reaction (2e- ORR) faces huge challenges due to insufficient synergistic active sites and slow/messy carrier transfer. Herein, a novel 2D/2D van der Waals heterojunction consisting of BiOIO3 and carbon nitride (BIO/CN) is elaborately designed for highly efficient overall H2O2 piezo-synthesis. Theoretical/experimental results reveal that a Z-scheme electron transfer is formed and facilitated by the tandem interfacial electric field and the bulk piezo-polarization field. On this basis, the carriers are efficiently separated while the oxidation/reduction capacity is preserved, thus providing the strong driving force for the 2e- WOR and 2e- ORR on BIO and CN, respectively. Furthermore, the kinetic and thermodynamic processes of WOR and ORR for H2O2 synthesis improve remarkably. Therefore, BIO/CN exhibits an excellent H2O2 yield of 259.8 µM within 30 min in pure water and air atmosphere (without any sacrificial agents and aeration). This study provides a new idea on strategically controlling electron transfer toward high-efficiency H2O2 piezo-synthesis and expands the avenue for developing effective environmental purification materials.