The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity: A Meta-Analysis.

Objective: Recent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on asthma, which is often comorbid with type 2 diabetes mellitus (T2DM) and obesity. Therefore, we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1 (GLP-1) receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. Methods: PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were systematically searched from inception to July 2023. Randomized controlled trials (RCTs) of GLP-1 receptor-based agonists (GLP-1RA, GLP-1 based dual and triple receptor agonist) with reports of asthma events were included. Outcomes were computed as risk ratios ( RR) using a fixed-effects model. Results: Overall, 39 RCTs with a total of 85,755 participants were included. Compared to non-GLP-1 receptor-based agonist users, a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments, although the difference was not statistically significant [ RR = 0.91, 95% confidence interval ( CI): 0.68 to 1.24]. Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users ( RR = 0.65, 95% CI: 0.43 to 0.99, P = 0.043). We also performed sensitivity analyses for participant characteristics, study design, drug structure, duration of action, and drug subtypes. However, no significant associations were observed. Conclusion: Compared with non-users, a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments. Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

Patrinia villosa (Thunb.) Juss alleviates CCL4-induced acute liver injury by restoring bile acid levels and inhibiting apoptosis/autophagy.

Background: Patrinia villosa (Thunb.) Juss is one of the plant resources of the famous traditional Chinese medicine "Bai jiang cao (herba patriniae)," and it is considered to function at the liver meridian, thereby treating diseases of the liver as demonstrated by the traditional theory of TCM. Unfortunately, the therapeutic mechanism of the whole plant of PV is so far unknown. Method: UPLC QTOF-MS/MS was used to analyze the profile of PV. Male Sprague-Dawley rats were categorized into five groups, and PV groups (125 and 375 mg/kg) were administered by oral gavage for seven consecutive days. The model of liver injury was induced by intraperitoneal injection of 40% CCl4 oil solution. H&E staining was performed for histological evaluation. The ELISA method was used to assess the serum level of ALT, AST, and T-BIL. Serum and liver bile acid (BA) profiling was analyzed by LC-MS/MS. TUNEL-stained liver sections were used to monitor apoptosis caused by CCl4. HepG2 cells were used to detect autophagy caused by CCl4. Results: A total of 16 compounds were identified from the 70% methanol extract of PV. PV (125 and 375 mg/kg) could reverse the ectopic overexpression of AST, ALT, and T-BIL caused by CCl4 administration. H&E staining indicated that PV (125 and 375 mg/kg) could reduce the infiltration of inflammatory cells and restore liver tissue and hepatocyte structures. Six bile acids, including DCA, HDCA, GCA, TCA, TCDCA, and TUDCA, were significantly altered both in the serum and liver tissue after CCl4 administration, and the level of all these six bile acids was restored by PV treatment. Moreover, PV inhibited apoptosis caused by CCl4 stimulation in liver tissue and suppressed autophagy in HepG2 cells treated with CCl4. Conclusion: The results in this paper for the first time reveal the alteration of the bile acid profile in CCl4-induced liver injury and demonstrate that inhibiting apoptosis and autophagy was involved in P. villosa-elicited liver protection, providing a scientific basis for the clinical utilization of P. villosa as a natural hepatic protective agent.

Expression, Prognostic Value, and Immune Infiltration of MTHFD Family in Bladder Cancer.

BACKGROUND: The Methylenetetrahydrofolate Dehydrogenase (MTHFD) family plays an important role in the development and prognosis of a variety of tumors; however, the role of the MTHFD family in bladder cancer is unclear. METHODS: R software, cBioPortal, GeneMANIA, and online sites such as String-LinkedOmics were used for bioinformatics analysis. RESULTS: MTHFD1/1L/2 was significantly upregulated in bladder cancer tissues compared with normal tissues, high expression of the MTHFD family was strongly associated with poorer clinical grading and staging, and bladder cancer patients with upregulated expression of MTHFD1L/2 had a significantly worse prognosis. Gene function and PPI network analysis revealed that the MTHFD family and related genes play synergistic roles in the development of bladder cancer. 800 co-expressed genes related to the MTHFD family were used for functional enrichment analysis, and the results showed that many genes were associated with various oncogenic pathways such as cell cycle and DNA replication. More importantly, the MTHFD family was closely associated with multiple infiltrating immune lymphocytes, including Treg cells, and immune molecules such as TNFSF9, CD274, and PDCD1. CONCLUSION: Our study shows that MTHFD family genes may be potential prognostic markers and therapeutic targets for patients with bladder cancer.

The potential role of ribonucleic acid methylation in the pathological mechanisms of fragile X syndrome.

Fragile X syndrome (FXS) is a common inherited cause of intellectual disabilities and single-gene cause of autism spectrum disorder (ASD), resulting from the loss of functional fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein (RBP) encoded by the fragile X messenger ribonucleoprotein 1 (FMR1) gene. Ribonucleic acid (RNA) methylation can lead to developmental diseases, including FXS, through various mechanisms mediated by 5-hydroxymethylcytosine, 5-methylcytosine, N6-methyladenosine, etc. Emerging evidence suggests that modifications of some RNA species have been linked to FXS. However, the underlying pathological mechanism has yet to be elucidated. In this review, we reviewed the implication of RNA modification in FXS and summarized its specific characteristics for facilitating the identification of new therapeutic targets.

Plant-on-chip: Core morphogenesis processes in the tiny plant Wolffia australiana.

A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.

Carboxymethyl cellulose/poly(vinyl alcohol) blended films reinforced by buckypapers of carbon nanotubes and 2D material (MoS2): Enhancing mechanical strength, toughness, and barrier properties.

Plastic waste is one cause of climate change. To solve this problem, packaging films are increasingly produced from biodegradable polymers. Eco-friendly carboxymethyl cellulose and its blends have been developed for such a solution. Herein, a unique strategy is demonstrated to improve the mechanical and barrier properties of carboxymethyl cellulose/poly(vinyl alcohol) (CMC/PVA) blended films for the packaging of nonfood dried products. The blended films were impregnated with buckypapers containing different combinations of multiwalled carbon nanotubes, two-dimensional molybdenum disulfide (2D MoS2) nanoplatelets, and helical carbon nanotubes (HCNTs). Compared to the blend, the polymer composite films exhibit significant increases in tensile strength (~105 %, from 25.53 to 52.41 MPa), Young's modulus (~297 %, from 155.48 to 617.48 MPa), and toughness (~46 %, from 6.69 to 9.75 MJ m-3). Polymer composite films containing HCNTs in buckypapers offer the highest toughness. For barrier properties, the polymer composite films are opaque. The water vapor transmission rate of the blended films decreases (~52 %, from 13.09 to 6.25 g h-1 m-2). Moreover, the maximum thermal-degradation temperature of the blend rises from 296 to 301 °C, especially for the polymer composite films with buckypapers containing MoS2 nanosheets that contribute to the barrier effect for both water vapor and thermal-decomposition gas molecules.

Incidence, Prognostic Factors, and Survival of Patients with Renal Cancer: A Population-Based Study.

BACKGROUND: The main objective of this article is to understand trends in the incidence of renal cancer and to construct a nomogram to predict the prognosis of patients with renal cancer by analyzing clinical parameters. METHODS: We extracted data from the Surveillance, Epidemiology and End Results (SEER) database for patients with renal cancer from 2010 to 2015. The incidence rate was calculated to understand the trend of renal cancer in recent years, and the Kaplan-Meier method was used to analyze the relationship between patients' clinical variables and overall survival. Nomogram and calibration curves were constructed based on factors predicted by multivariate Cox regression. RESULTS: Data from 68,496 eligible renal cancer patients were included in the study. The incidence of renal cancer was higher in men than women and tended to stabilize over time. We further found that age, gender, marital status, AJCC stage, histological type, metastatic disease, and surgery were independent parameters for prognosis in renal cancer patients. Finally, a nomogram was constructed based on the above parameters, and its validity was verified with the agreement index and calibration curve. CONCLUSION: Renal cancer incidence trend gradually stabilized. Seven independent parameters for renal cancer patients were obtained by analysis and utilized to construct a nomogram that could provide guidance for clinical practice.

Multiscale simulation and experimental measurements of the elastic response for constructional steel.

The multiscale elastic response to the macroscopic stress was simulated to reveal the multi-scale correlation of elastic properties of the medium carbon steel. Based on the multiscale correlation constitutive equations derived from this constitutive model, the effective elastic constants (EECs) of medium carbon steel are predicted. In addition, the diffraction elastic constants (DECs) of the constituents of the medium carbon steel are also evaluated. And then, the simple in-situ X-ray diffraction experiments were performed for the measurements of DECs and EECs of treated 35CrMo steel during the four-point bending. Compared with the experimental measurements and different existing models, the results demonstrated that the developed constitutive model was in good agreement with the measured values of the EECs and DECs, and that the feasibility and reliability of the constitutive model used to simulate multiscale elastic response could reveal the correlation between the material and its constitutes.

Magnetically Driven Muco-Inert Janus Nanovehicles for Enhanced Mucus Penetration and Cellular Uptake.

One of the main challenges of transmucosal drug delivery is that of enabling particles and molecules to move across the mucosal barrier of the mucosal epithelial surface. Inspired by nanovehicles and mucus-penetrating nanoparticles, a magnetically driven, mucus-inert Janus-type nanovehicle (Janus-MMSN-pCB) was fabricated by coating the zwitterionic polymer poly(carboxybetaine methacrylate) (pCB) on the mesoporous silica nanorod, which was grown on one side of superparamagnetic Fe3O4 nanoparticle using the sol-gel method. X-ray diffraction, transmission electron microscopy, vibrating sample magnetometry, and Fourier infrared spectroscopy were used to characterize the structure and morphology of the nanovehicles, proving the success of each synthesis step. The in vitro cell viability assessment of these composites using Calu-3 cell lines indicates that the nanovehicles are biocompatible in nature. Furthermore, the multiparticle tracking, Transwell® system, and cell imaging experimental results demonstrate that both the modification of pCB and the application of a magnetic field effectively accelerated the diffusion of the nanovehicles in the mucus and improved the endocytosis through Calu-3. The favorable cell uptake performance of Janus-MMSN-pCB in mucus systems with/without magnetic driving proves its potential role in the diagnosis, treatment, and imaging of mucosal-related diseases.

Enlarged perivascular spaces, neuroinflammation and neurological dysfunction in NMOSD patients.

Background and objectives: Cerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the 'glymphatic system'. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients. Methods: We conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity. Results: The median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p<0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p<0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5). Discussion: In our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.

Origins of the seed: The "golden-trio hypothesis".

The seed is an evolutionary innovation in the plant kingdom. While human civilization depends heavily on seed production, how the seed trait emerged remains elusive. In this opinion article, a "golden-trio hypothesis" is proposed based on our investigations of LEC1 gene functions in Adiantum capillus-veneris. This hypothesis posits that a "seed program" arose from spatiotemporal integration of three key components: assimilate flow, ABA-mediated stress responses, and stress-induced LEC1 expression. Thus, the evolutionary innovation of seeds should be considered not a simple event resulting from new genes; rather, it represents the outcome of a series of physiological and morphological innovations that emerged prior to and regardless of the origin of the seed program. This new perspective could help us tackle some long-standing questions around the puzzling origin of seeds.

Di-, tri- and tetraphosphine-substituted Fe/Se carbonyls: synthesis, characterization and electrochemical properties.

The active sites of [FeFe]-hydrogenase promoted by Fe/E (E = S, Se) clusters have attracted considerable interest due to their significance in understanding the interconversion of hydrogen with protons and electrons. As an extension of the study on Fe/Se clusters related to H-cluster model compounds of [FeFe]-hydrogenase, a series of tertiary phosphine substituted Fe/Se carbonyls were successfully prepared. The treatment of Fe2(µ-SePh)2(CO)6 (A) and excess PR3 resulted in the ferrous bis(selenolate) carbonyls Fe(SePh)2(CO)2(PR3)2 (PR3 = PPhMe2, 1; PMe3, 2) in moderate yields. In striking contrast, the reaction of Fe2(µ-SeCH2Ph)2(CO)6 (B) with the same PR3 ligand resulted in the PR3-disubstituted models Fe2(µ-SeCH2Ph)2(CO)4(PR3)2 (PR3 = PPhMe2, 3; PMe3, 4) as the principal products. The more interesting finding is that two independent isomers (anti- and syn-) can be isolated according to different reaction temperatures. Further reactions of 3 or 4 with PR3 under UV irradiation afforded the first PR3-trisubstituted 2Fe2Se derivatives Fe2(µ-SeCH2Ph)2(CO)3(PR3)3 (PR3 = PPhMe2, 5; PMe3, 6). 6 could be further converted into the tetrasubstituted product Fe2(µ-SeCH2Ph)2(CO)2(PMe3)4 (7), while no further substitution was observed with 5 and excess of PPhMe2. All the prepared compounds were fully characterized by elemental analysis, various spectroscopic techniques and X-ray crystallography. In addition, some electrochemical properties of these models were studied by cyclic voltammetry (CV) in MeCN. Compounds 4, 6 and 7 were found to be catalysts for the H2 evolution reaction under electrochemical conditions.

Cerebellum neuropathology and motor skill deficits in fragile X syndrome.

Fragile X syndrome (FXS) is a leading form of inherited intellectual disability and single-gene cause of autism spectrum disorder (ASD) and is characterized by core deficits in cognitive flexibility, sensory sensitivity, emotion, and social interactions. Motor deficits are a shared feature of FXS and autism. The cerebellum has emerged as one of the target brain areas affected by neurodevelopmental diseases. Alterations in the cerebellar structure, circuits, and function may be the key drivers of impaired fine and gross motor skills in FXS and fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we briefly examined recent findings in FXS and present a discussion on the literature supporting motor skill deficits in FXS. Subsequently, we focused on neuropathological alterations in the cerebellum in FXS and FXTAS. We highlight studies that have directly examined the function of fragile X mental retardation protein and related epigenetic variations in the cerebellum. Overall, we obtained considerable supporting evidence for the hypothesis that cerebellar dysfunction is evident in FXS and FXTAS; however, compared with studies on other ASD models, studies on motor skills related to fragile X disorders are particularly rare and inconclusive. Hence, future research should address FXS-related motor and behavioral trajectories and examine the underlying mechanisms at both the cell and circuit levels.

Characterization of a heptapeptide-modified microsphere for oriented antibody immobilization.

Oriented immobilization of antibodies is important for the effective recognition of target antigens. In this paper, a heptapeptide ligand, HWRGWVC (HC7), was modified onto non-porous monosized poly(glyceryl methacrylate) (pGMA) microspheres (named pGMA-HC7) to explore the antibody immobilization behaviors. Characterization of the microspheres by particle size analyzer, scanning electron microscopy, Fourier transform infrared spectroscopy, and reversed-phase chromatography proved the success of each fabrication step. The capacity and activity of antibody immobilization through HC7 were studied using immunoglobulin G (IgG) as a model antibody and horseradish peroxidase (HRP) as a model antigen. Additionally, IgG immobilizations on pGMA microspheres by nonspecific adsorption and covalent coupling through carbodiimide chemistry were conducted for comparison. pGMA-HC7 exhibited an IgG adsorption capacity of 3-4 mg/g in 10 min by the specific binding of HC7 without nonspecific interactions. Notably, the ligand HC7 showed a by two orders of magnitude stronger affinity for IgG than its original hexapeptide ligand HWRGWV. Moreover, the capacity and activity of the immobilized anti-HRP antibody on pGMA-HC7 were 1.6-fold and 3-fold higher than those of the covalent coupling, respectively. The results proved the superior role of HWRGWVC in the affinity binding of antibody and the potential of pGMA-HC7-25 in immunoassay and immunodiagnostic applications.

SKF38393 prevents high glucose (HG)-induced endothelial dysfunction by inhibiting the effects of HG on cystathionine γ-lyase/hydrogen sulfide activity and via a RhoA/ROCK1 pathway.

BACKGROUND: Endothelial dysfunction plays a crucial role in diabetic vascular complications. A decrease in hydrogen sulfide (H2S) levels is increasingly becoming a vital factor contributing to high glucose (HG)-induced endothelial dysfunction. Dopamine D1-like receptors (DR1) activation has important physiological functions in the cardiovascular system. H2S decreases the dysfunction of vascular endothelial cells. However, no studies have reported whether DR1 protects the function of vascular endothelial cells by regulating H2S levels. AIM: The present study aimed to determine whether DR1 regulates the levels of endogenous H2S, which exerts protective effects against HG-induced injury of human umbilical vein endothelial cells (HUVECs) via Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing kinase 1 (ROCK1) signalling. METHODS: HUVECs were exposed to HG (30 mM) or normal glucose (5.5 mM) after different treatments. Cell viability, proliferation and migration were measured by Cell Counting Kit-8, EdU cell proliferation assay, transwell assay and wound healing assay, respectively. H2S probe (7-Azido-4-Methylcoumarin) was used to detect levels of H2S. The intracellular calcium concentration ([Ca2+]i) were measured using Fluo-4 AM. The protein expressions were quantified by Western blot. RESULTS: We found that HG decreased the expression of DR1 and cystathionine γ-lyase (CSE) and H2S production. The DR1 agonist SKF38393 significantly increased DR1 and CSE expression and H2S production, whereas NaHS (a H2S donor) only increased CSE expression and H2S production but had no effect on DR1 expression. Meanwhile, SKF38393 further increased the [Ca2+]i induced by HG. In addition, HG reduced cell viability and the expression of Cyclin D1 and proliferating cell nuclear antigen and increased the expression of p21C⁢i⁢p/W⁢A⁢F-1, collagen I, collagen III, matrix metalloproteinase 9, osteopontin and α-smooth muscle actin and the activity of phosphorylated RhoA and ROCK1. SKF38393 and NaHS reversed these effects of HG. PPG (a CSE inhibitor) abolished the beneficial effect of SKF38393. These effects of SKF38393 were similar to those of Y-27632 (a ROCK inhibitor). CONCLUSION: Taken together, our results suggest that DR1 activation upregulates the CSE/H2S pathway by increasing the [Ca2+]i, which protects endothelial cells from HG-induced injury by inhibiting the RhoA/ROCK1 pathway.

Rice Cell Division Cycle 20s are required for faithful chromosome segregation and cytokinesis during meiosis.

Chromosome segregation must be under strict regulation to maintain chromosome euploidy and stability. Cell Division Cycle 20 (CDC20) is an essential cell cycle regulator that promotes the metaphase-to-anaphase transition and functions in the spindle assembly checkpoint, a surveillance pathway that ensures the fidelity of chromosome segregation. Plant CDC20 genes are present in multiple copies, and whether CDC20s have the same functions in plants as in yeast and animals is unclear, given the potential for divergence or redundancy among the multiple copies. Here, we studied all three CDC20 genes in rice (Oryza sativa) and constructed two triple mutants by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated genome editing to explore their roles in development. Knocking out all three CDC20 genes led to total sterility but did not affect vegetative development. Loss of the three CDC20 proteins did not alter mitotic division but severely disrupted meiosis as a result of asynchronous and unequal chromosome segregation, chromosome lagging, and premature separation of chromatids. Immunofluorescence of tubulin revealed malformed meiotic spindles in microsporocytes of the triple mutants. Furthermore, cytokinesis of meiosis I was absent or abnormal, and cytokinesis II was completely prevented in all mutant microsporocytes; thus, no tetrads or pollen formed in either cdc20 triple mutant. Finally, the subcellular structures and functions of the tapetum were disturbed by the lack of CDC20 proteins. These findings demonstrate that the three rice CDC20s play redundant roles but are indispensable for faithful meiotic chromosome segregation and cytokinesis, which are required for the production of fertile microspores.

Dynamic regulation and key roles of ribonucleic acid methylation.

Ribonucleic acid (RNA) methylation is the most abundant modification in biological systems, accounting for 60% of all RNA modifications, and affects multiple aspects of RNA (including mRNAs, tRNAs, rRNAs, microRNAs, and long non-coding RNAs). Dysregulation of RNA methylation causes many developmental diseases through various mechanisms mediated by N 6-methyladenosine (m6A), 5-methylcytosine (m5C), N 1-methyladenosine (m1A), 5-hydroxymethylcytosine (hm5C), and pseudouridine (Ψ). The emerging tools of RNA methylation can be used as diagnostic, preventive, and therapeutic markers. Here, we review the accumulated discoveries to date regarding the biological function and dynamic regulation of RNA methylation/modification, as well as the most popularly used techniques applied for profiling RNA epitranscriptome, to provide new ideas for growth and development.

[Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway].

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.