ADO09, a co-formulation of pramlintide and insulin A21G, lowers body weight versus insulin lispro in type 1 diabetes.

AIM: To study safety, efficacy and weight loss with ADO09, a co-formulation of insulin A21G and pramlintide, in type 1 diabetes. MATERIALS AND METHODS: A randomized, two-arm ambulatory 16-week study compared ADO09 with insulin lispro in 80 participants with type 1 diabetes. We compared changes of weight, glycated haemoglobin, glycaemic patterns during continuous glucose monitoring, and insulin doses at baseline and at the end of treatment. RESULTS: A significant and continuing weight loss, the primary endpoint, was observed with ADO09 compared with lispro as prandial insulin. In the whole group, the weight loss with ADO09 relative to lispro was 2.1 kg. Glycaemic control was relatively good (7.7% mean glycated haemoglobin) in both groups and did not change during treatment. Prandial insulin doses were reduced by 21% in the ADO09 group, whereas basal insulin dosage was not modified. Gastrointestinal symptoms were more frequent with ADO09, but no clear difference in hypoglycaemia was observed. CONCLUSIONS: These results extend previous observations on the efficacy and safety of this insulin/pramlintide co-formulation. They show a beneficial effect on weight, using less mealtime insulin and without increased hypoglycaemia.

Facile synthesis of a new chiral polyimine macrocycle and its application for enantioseparation in high-performance liquid chromatography.

Macrocyclic compounds such as crown ethers and cyclodextrins play an important role in the field of chromatography and show excellent separation performance. The design of simple and convenient methods for the efficient synthesis of novel chiral macrocycles for chromatographic separation is of great significance. In this work, a novel chiral polyimine macrocycle (PIMC) was designed and synthesized by the simply one-step reaction of 2,6-diformyl-4-tert-butylphenol with (S)-(-)-1,2-propanediamine. Then, it was bonded onto silica by the thiol-ene click reaction to construct a new chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC). The chiral separation performance of the proposed CSP was examined by separating various racemates in the normal-phase (NP) and reversed-phase (RP) HPLC. In total, twelve and nine racemates, including ethers, esters, amines, alcohols, organic acids, ketones, and epoxides, were separated to varying degrees via NP-HPLC and RP-HPLC, respectively, Moreover, the CSP offered good chiral separation complementarity to Chiralcel OD-H and Chiralpak AD-H columns for resolution of these test racemates, and it can separate several racemic compounds that either cannot be separated or cannot be separated well be separated by the two commercially available columns. After the column was used for hundreds of injections, the relative standard deviations of the retention time and resolution were below 0.56 % and 0.45 %, respectively, showing the good reproducibility and stability of the CSP. This study provides a simple and convenient approach to synthesize a novel chiral macrocycle and CSP and also indicates the broad application prospects of such chiral PIMCs in HPLC chiral separation.

Fine-tuning of the dual-role transcription factor WRKY8 via differential phosphorylation for robust broad-spectrum plant immunity.

Plants utilize plasma membrane-localized pattern recognition receptors (PRRs) to perceive pathogen-associated molecular patterns (PAMPs) to activate broad-spectrum pattern-triggered immunity (PTI). However, the regulatory mechanism ensuring robust broad-spectrum plant immunity remains largely unknown. Here, we reveal the dual roles of the transcription factor WRKY8 in transcriptional regulation of PRR genes: repressing the nlp20/nlp24 receptor gene RLP23 whereas promoting the chitin receptor gene CERK1. Remarkably, SsNLP1 and SsNLP2, two nlp24 type PAMPs in the destructive fungal pathogen Sclerotinia sclerotiorum, activate two calcium-elicited kinases, CPK4 and CPK11 to phosphorylate WRKY8 and consequently release its inhibition on RLP23 expression to accumulate RLP23. Meanwhile, SsNLPs activate a RLCK type kinase, PBL19 to phosphorylate WRKY8 and consequently enhance the accumulation of CERK1. Intriguingly, RLP23 is repressed at late stage by PBL19-mediated phosphorylation of WRKY8, to avoid excessive immunity for normal growth. Our findings unveil a "killing two birds with one stone" strategy employed by plants to elicit robust broad-spectrum immunity, which is based on PAMP-triggered fine-tuning of a dual-role transcription factor to simultaneously amplify two PRRs recognizing PAMPs well conserved in a wide range of pathogens. Moreover, our results reveal a novel plant strategy based on fine-tuning of multiple PRR gene expression to balance the trade-off between growth and immunity.

Revolutionizing Oxygen Delivery: The Adjustable Oxygen Adapter for Uninterrupted Therapy and Enhanced Patient Safety.

This study introduces the "Adjustable Oxygen Adapter," designed to address interruptions in oxygen supply for patients transitioning from oxygen spray bottles, particularly in wards with single-outlet flowmeters. Inspired by the "Three-Way Piston Rotating Adapter," this innovative design, operated by a single switch, ensures uninterrupted oxygen supply during equipment changes. Stability testing, conducted with a flow monitor by a respiratory therapist, confirms that the adapter provides a stable flow rate and oxygen concentration, offering a practical solution for seamless transitions between oxygen devices in clinical settings.

Enhancing Citizen Health Literacy Through Digital Technology.

Contemporary society faces significant public health challenges with prevalent unhealthy behaviors and environmental risks leading non-communicable diseases. This study assesses health awareness campaigns'to effectiveness in a specific Taiwanese municipality, focusing on the impact of a health care management system. Objectives include enhancing public health literacy and evaluating community health promotion. The proposed system includes a personalized assistant app, personnel education, and events covering topics like hypertension, diabetes, diet, exercise, and chronic disease prevention. In summary, the research advocates for effective public health interventions, integrating digital technologies, personalized health management, and community engagement to promote health literacy and healthier lifestyles.

Integrated Assays of Genome-Wide Association Study, Multi-Omics Co-Localization, and Machine Learning Associated Calcium Signaling Genes with Oilseed Rape Resistance to Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum (Ss) is one of the most devastating fungal pathogens, causing huge yield loss in multiple economically important crops including oilseed rape. Plant resistance to Ss pertains to quantitative disease resistance (QDR) controlled by multiple minor genes. Genome-wide identification of genes involved in QDR to Ss is yet to be conducted. In this study, we integrated several assays including genome-wide association study (GWAS), multi-omics co-localization, and machine learning prediction to identify, on a genome-wide scale, genes involved in the oilseed rape QDR to Ss. Employing GWAS and multi-omics co-localization, we identified seven resistance-associated loci (RALs) associated with oilseed rape resistance to Ss. Furthermore, we developed a machine learning algorithm and named it Integrative Multi-Omics Analysis and Machine Learning for Target Gene Prediction (iMAP), which integrates multi-omics data to rapidly predict disease resistance-related genes within a broad chromosomal region. Through iMAP based on the identified RALs, we revealed multiple calcium signaling genes related to the QDR to Ss. Population-level analysis of selective sweeps and haplotypes of variants confirmed the positive selection of the predicted calcium signaling genes during evolution. Overall, this study has developed an algorithm that integrates multi-omics data and machine learning methods, providing a powerful tool for predicting target genes associated with specific traits. Furthermore, it makes a basis for further understanding the role and mechanisms of calcium signaling genes in the QDR to Ss.

Multiple serial correlations in global air temperature anomaly time series.

Serial correlations within temperature time series serve as indicators of the temporal consistency of climate events. This study delves into the serial correlations embedded in global surface air temperature (SAT) data. Initially, we preprocess the SAT time series to eradicate seasonal patterns and linear trends, resulting in the SAT anomaly time series, which encapsulates the inherent variability of Earth's climate system. Employing diverse statistical techniques, we identify three distinct types of serial correlations: short-term, long-term, and nonlinear. To identify short-term correlations, we utilize the first-order autoregressive model, AR(1), revealing a global pattern that can be partially attributed to atmospheric Rossby waves in extratropical regions and the Eastern Pacific warm pool. For long-term correlations, we adopt the standard detrended fluctuation analysis, finding that the global pattern aligns with long-term climate variability, such as the El Niño-Southern Oscillation (ENSO) over the Eastern Pacific. Furthermore, we apply the horizontal visibility graph (HVG) algorithm to transform the SAT anomaly time series into complex networks. The topological parameters of these networks aptly capture the long-term correlations present in the data. Additionally, we introduce a novel topological parameter, Δσ, to detect nonlinear correlations. The statistical significance of this parameter is rigorously tested using the Monte Carlo method, simulating fractional Brownian motion and fractional Gaussian noise processes with a predefined DFA exponent to estimate confidence intervals. In conclusion, serial correlations are universal in global SAT time series and the presence of these serial correlations should be considered carefully in climate sciences.

Glutamate Receptor-like (GLR) Family in Brassica napus: Genome-Wide Identification and Functional Analysis in Resistance to Sclerotinia sclerotiorum.

Plant glutamate receptor-like channels (GLRs) are homologs of animal ionotropic glutamate receptors. GLRs are critical in various plant biological functions, yet their genomic features and functions in disease resistance remain largely unknown in many crop species. Here, we report the results on a thorough genome-wide study of the GLR family in oilseed rape (Brassica napus) and their role in resistance to the fungal pathogen Sclerotinia sclerotiorum. A total of 61 GLRs were identified in oilseed rape. They comprised three groups, as in Arabidopsis thaliana. Detailed computational analyses, including prediction of domain and motifs, cellular localization, cis-acting elements, PTM sites, and amino acid ligands and their binding pockets in BnGLR proteins, unveiled a set of group-specific characteristics of the BnGLR family, which included chromosomal distribution, motif composition, intron number and size, and methylation sites. Functional dissection employing virus-induced gene silencing of BnGLRs in oilseed rape and Arabidopsis mutants of BnGLR homologs demonstrated that BnGLR35/AtGLR2.5 positively, while BnGLR12/AtGLR1.2 and BnGLR53/AtGLR3.2 negatively, regulated plant resistance to S. sclerotiorum, indicating that GLR genes were differentially involved in this resistance. Our findings reveal the complex involvement of GLRs in B. napus resistance to S. sclerotiorum and provide clues for further functional characterization of BnGLRs.

Contribution to the Chinese Intybia Pascoe, 1866 (Coleoptera, Melyridae, Malachiinae), with descriptions of two new species groups and one new species.

A contribution to the knowledge of the malachiine genus Intybia Pascoe, 1866 from China is given. Two new species groups: Intybiaklapperichi group and Intybiaeversi group are defined and described. A new species, Intybiahainanensis Wang & Liu, sp. nov., of the Intybiaklapperichi group is described from Hainan Province. Intybiaerectodentatus (Wittmer, 1982) and Intybiaconcha Asano, 2015 are redescribed based on new materials collected in mainland China. A key to species groups of the genus Intybia Pascoe, 1866 in China is provided.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

[Effect of Silica Fertilizer(Husk Ash) to Improve Soil Quality and Reduce Cd and As Accumulation in Rice].

A rice pot experiment was conducted to identify the effect of silica fertilizer prepared from husk ash on the soil bioavailability of cadmium (Cd) and arsenic (As), enzyme activities, microbial community structure, and heavy metal content in brown rice at different growth stages. The results showed that the application of 0.1%-1.0% silica fertilizer-husk ash increased the pH value of soil by 0.04-0.24 units and the content of soil available silicon by 44.2%-97.5%. It also decreased the content of available Cd and available As by 16.2%-21.4% and 16.0%-24.9%, respectively. With the increase in application amount, the soil enzyme activities increased at all growth stages, and the sucrase activity and the dehydrogenase activity significantly increased by 6.3%-145.7% and 6.7%-224.1%, respectively. The analysis of the soil microbial community composition structure at mature stages showed that the application of silica fertilizer-husk ash had no effect on microbial α-diversity, but it had a significant effect on microbial ß-diversity and then promoted microbial growth and maintained the stability of the community structure. With the increase in application amount, the contents of Cd in brown rice decreased by 29.3%-89.7%, and the contents of total As and inorganic As in brown rice decreased by 7.8%-42.3% and 17.2%-44.5%, respectively. Under the application of 0.5% and 1.0% silica fertilizer-husk ash, the Cd contents in brown rice were lower than 0.2 mg·kg-1, and the inorganic As contents in brown rice were lower than 0.35 mg·kg-1. In conclusion, the silica fertilizer-husk ash can improve soil quality and reduce the contents of Cd and As in brown rice, and it is eco-friendly and can be used to remedy the paddy soil contaminated with Cd and As.

Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.

Sepsis is characterized by organ dysfunction resulting from a dysregulated inflammatory response triggered by infection, involving multifactorial and intricate molecular mechanisms. Hypoxia-inducible factor-1α (HIF-1α), a notable transcription factor, assumes a pivotal role in the onset and progression of sepsis. This review aims to furnish a comprehensive overview of HIF-1α's mechanism of action in sepsis, scrutinizing its involvement in inflammatory regulation, hypoxia adaptation, immune response, and organ dysfunction. The review encompasses an analysis of the structural features, regulatory activation, and downstream signaling pathways of HIF-1α, alongside its mechanism of action in the pathophysiological processes of sepsis. Furthermore, it will delve into the roles of HIF-1α in modulating the inflammatory response, including its association with inflammatory mediators, immune cell activation, and vasodilation. Additionally, attention will be directed toward the regulatory function of HIF-1α in hypoxic environments and its linkage with intracellular signaling, oxidative stress, and mitochondrial damage. Finally, the potential therapeutic value of HIF-1α as a targeted therapy and its significance in the clinical management of sepsis will be discussed, aiming to serve as a significant reference for an in-depth understanding of sepsis pathogenesis and potential therapeutic targets, as well as to establish a theoretical foundation for clinical applications.

A novel endoscopic nasopharyngectomy by low-temperature plasma radiofrequency ablation in localized recurrent nasopharyngeal carcinoma.

OBJECTIVE: Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low-temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit. METHODS: A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse-free survival (LRFS) rate, progression-free survival (PFS) and distant metastasis-free survival (DMFS) were analyzed using the Kaplan-Meier method and compared by the log-rank test. RESULTS: All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15-100 min) and 101 min (range, 30-180 min). The average number of hospital days postoperation was 3 days (range, 2-5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re-epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow-up time was 44.3 months (range, 17.1-52.7 months, 95% CI: 40.4-48.2). The 3-year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862-0.996), 89.3% (95% CI: 0.813-0.973), 87.5% (95% CI: 0.789-0.961), and 92.9% (95% CI: 0.862-0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365-305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440-47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925-28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806-317.799). CONCLUSION: Radical endoscopic nasopharyngectomy by using low-temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow-up time are needed to prove its efficacy.

Ropivacaine inhibits the proliferation and metastasis of gastric cancer cells via the SNX10/SRC/STAT3 pathway.

Gastric cancer currently has no effective treatment due to its high metastasis and heterogeneity. It has been reported that ropivacaine (Rop) can inhibit the growth, migration, and invasion of gastric cancer. However, the therapeutic mechanism of Rop still needs to be further explored to provide insights for its clinical application. This study aimed to explore the effects of Rop on the growth, migration, and invasion of gastric cancer cells and the underlying mechanisms. The expression levels of SNX10 were assessed in gastric cancer tissues and cell line AGS by qRT-PCR. Cell Counting Kit-8 (CCK8) assay, wound-healing assay, and transwell assay were then used to examine the effects of Rop on the AGS cell viability, migration, invasion, and proliferation, respectively. Additionally, colony formation assay was used to measure cell proliferation ability, and flow cytometry was used to detect apoptosis level. Protein levels of SNX10, SRC, and STAT3 were detected by western blot. According to the experimental results, the decreased SNX10 mRNA expression was observed in gastric cancer tissue and cell line AGS. Rop inhibited the proliferation, migration, and invasion of AGS cells, but promoted apoptosis and upregulated SNX10 expression. Moreover, Rop inhibited the expression of MMP-2 and MMP-9, phosphorylation of SRC and STAT3. SNX10 knockdown could reverse Rop-induced anticancer effects. Collectively, Rop showed a potential role in preventing proliferation and metastasis of gastric cancer. The action mechanism of Rop may be related to the upregulation of SNX10 expression and further inhibition of SRC/STAT3 signaling pathway. Our findings provide new insights into the anticancer properties of Rop.

Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial.

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.

Effects of single and combined contamination of total petroleum hydrocarbons and heavy metals on soil microecosystems: Insights into bacterial diversity, assembly, and ecological function.

Deciphering the impact of single and combined contamination of total petroleum hydrocarbons (TPH) and heavy metals on soil microecosystems is essential for the remediation of contaminated habitats, yet it remains incompletely understood. In this study, we employed high-throughput sequencing to investigate the impact of single TPH contamination, single metal contamination, and their co-contamination on soil microbial diversity, assembly mechanisms, composition, ecological function, and resistome. Our results revealed that contamination led to a reduction in alpha diversity, with single contamination displaying lower diversity compared to co-contamination, depending on the concentration of pollutants. Community beta diversity was primarily driven by turnover rather than nestedness, and narrower ecological niches were detected under pollution conditions. The neutral community model suggested that homogenizing dispersal played a significant role in the community assembly process under single TPH or co-contamination, while homogeneous selection dominated under heavy metals pollution. Procrustes analysis demonstrated a correlation between community composition and functional divergence, while Mantel tests linked this divergence to concentrations of Cr, Cr6+, Pb, and TPH. Interestingly, soils co-polluted with TPH and heavy metals exhibited similar genera, community functions, and resistomes as soils contaminated with only metals, highlighting the significant impact of heavy metals. Ecological functions related to carbon (C), nitrogen (N), and sulfur (S) cycles were enhanced under TPH pollution but impaired under heavy metals stress. These findings enhance our understanding of soil microecosystems subjected to TPH, heavy metals, and their co-contamination, and carry significant implications for environmental microecology and pollutant risk assessment.

Engineering thiol-ene click chemistry for the preparation of a chiral stationary phase based on a [4+6]-type homochiral porous organic cage for enantiomeric separation in normal-phase and reversed-phase high performance liquid chromatography.

In this study, a new chiral stationary phase (CSP) was fabricated by covalent bonding of a [4+6]-type homochiral porous organic cage (POC) CC19-R onto thiolated silica via a thiol-ene click reaction. The CC19-R was synthesized via Schiff-base reaction between 2-hydroxybenzene-1,3,5-tricarbaldehyde and (1R, 2R)-(-)-1,2-diaminocyclohexane. The enantioseparation capability of the resulting CC19-R-based CSP was systematically evaluated upon separating various chiral compounds or chiral pharmaceuticals in normal phase HPLC (NP-HPLC) and reversed phase HPLC (RP-HPLC), including alcohols, organic acids, ketones, diols, esters, and amines. Fifteen racemates were enantioseparated in NP-HPLC and 11 racemates in RP-HPLC. Some racemates have been well separated, such as 4-chlorobenzhydrol, cetirizine (in the form of dihydrochloride), 1,2-diphenyl-1,2-ethanediol, and 3-(benzyloxy)propane-1,2-diol whose resolution values reached 3.66, 4.23, 6.50, and 3.50, respectively. When compared with a previously reported chiral POC-based column (NC1-R column), eight racemates were not separated on the NC1-R column in NP-HPLC and five racemates were not separated in RP-HPLC, but were well resolved on this column, revealing that the enantioselectivity and separable range of chiral POCs-type columns could be significantly widened using this fabricated CC19-R column. Moreover, the resolution performance of the CC19-R column was also compared with commercial Chiralpak AD-H [CSP: Amylose tris(3,5-dimethylphenylcarbamate)] and Chiralcel OD-H [CSP: Cellulose tris(3,5-dimethylphenylcarbamate)] columns. The column also can separate some racemates that could not be separated or not well be separated by the two commercial columns, showing its good complementarity to the two commercial columns on chiral separation. In addition, the column also had good stability and reproducibility with the relative standard deviation (n = 5) of the retention time and resolution lower than 1.0% and 1.8%, respectively, after it had undergone multiple injections (100, 200, 300, and 400 times). This work indicated that the features of good resolution ability and simple synthesis methods using with this POC-based CSP provided chiral POCs with potential application prospects in HPLC racemic separation.

[Oxalis inhibits prostate tumor in the mouse model of castration-resistant prostate cancer: Effect and mechanism].

OBJECTIVE: To investigate the inhibitory effect of oxalis on prostate tumor in the mouse model of castration-resistant prostate cancer (CRPC) and its action mechanism. METHODS: We established a CRPC model in 40 male C57/BL mice aged 6－8 weeks, divided them randomly into four groups of an equal number, and treated them intragastrically with normal saline (control), low-dose oxalis (5 mg/kg/d), medium-dose oxalis (10 mg/kg/d), and high-dose oxalis (15 mg/kg/d), respectively. After 28 days of treatment, we measured the tumor volume and body weight of the mice in different groups, calculated the tumor-inhibition rate, examined the histomorphological changes of the prostate tumors by HE staining, and detected the expressions of the nuclear factor-κB (NF-κB) signaling pathway and its downstream proteins in the tumor tissue by immunofluorescence assay. RESULTS: In comparison with the controls, the mice in the low-, medium- and high-dose oxalis groups showed a gradual decrease in tumor cell concentration and cell degeneration, and a gradually increased number of necrotic tumor cells. The volume and mean weight of prostate tumors were significantly reduced (P < 0.05), the expressions of NF-κB p65 and Ki67 proteins remarkably down-regulated (P < 0.05), and that of the Bax protein markedly up-regulated (P < 0.05) in the oxalis groups compared with the controls. CONCLUSION: Oxalis can inhibit the growth of prostate tumor in CRPC mice possibly by down-regulating the NF-κB signaling pathway and the expressions of p65 and Ki67 and up-regulating the expression of Bax, and thereby promoting the degeneration and necrosis of tumor cells.

RALF22 promotes plant immunity and amplifies the Pep3 immune signal.

Rapid alkalinization factors (RALFs) in plants have been reported to dampen pathogen-associated molecular pattern (PAMP)-triggered immunity via suppressing PAMP-induced complex formation between the pattern recognition receptor (PRR) and its co-receptor BAK1. However, the direct and positive role of RALFs in plant immunity remains largely unknown. Herein, we report the direct and positive roles of a typical RALF, RALF22, in plant immunity. RALF22 alone directly elicited a variety of typical immune responses and triggered resistance against the devastating necrotrophic fungal pathogen Sclerotinia sclerotiorum in a FERONIA (FER)-dependent manner. LORELEI (LRE)-like glycosylphosphatidylinositol (GPI)-anchored protein 1 (LLG1) and NADPH oxidase RBOHD were required for RALF22-elicited reactive oxygen species (ROS) generation. The mutation of cysteines conserved in the C terminus of RALFs abolished, while the constitutive formation of two disulfide bridges between these cysteines promoted the RALF22-elicited ROS production and resistance against S. sclerotiorum, demonstrating the requirement of these cysteines in the functions of RALF22 in plant immunity. Furthermore, RALF22 amplified the Pep3-induced immune signal by dramatically increasing the abundance of PROPEP3 transcript and protein. Supply with RALF22 induced resistance against S. sclerotiorum in Brassica crop plants. Collectively, our results reveal that RALF22 triggers immune responses and augments the Pep3-induced immune signal in a FER-dependent manner, and exhibits the potential to be exploited as an immune elicitor in crop protection.

A novel pillar[3]trianglimine macrocycle with a deep cavity used as a chiral selector to prepare a chiral stationary phase by thiol-ene click reaction for enantioseparation in high-performance liquid chromatography.

A chiral pillar[3]trianglimine (C60 H72 N6 O6 ) with a deep cavity has been developed as a chiral selector and bonded to thiolated silica by thiol-ene click reaction to fabricate a novel chiral stationary phase for enantioseparation in high-performance liquid chromatography. The enantioseparation performance of the fabricated chiral stationary phase has been evaluated by separating various racemic compounds, including alcohols, esters, amines, ketones, amino acids, and epoxides, in both normal-phase and reversed-phase elution modes. In total, 14 and 17 racemates have been effectively separated in these two separation modes, respectively. In comparison with two widely used chiral columns (Chiralcel OD-H and Chiralpak AD-H), our novel chiral stationary phase offered good chiral separation complementarity, separating some of the tested racemates that could not be separated or were only partially separated on these two commercial columns. The influences of analyte mass, mobile phase composition, and column temperature on chiral separation have been investigated. Good repeatability, stability, and column-to-column reproducibility of the chiral stationary phase for enantioseparation have been observed. After the fabricated column had been eluted up to 400 times, the relative standard deviations (n = 5) of resolution (Rs) and retention time of the separated analytes were < 0.39% and < 0.20%, respectively. The relative standard deviations (n = 3) of Rs and retention time for column-to-column reproducibility were < 4.6% and < 5.2%, respectively. This study demonstrated that the new chiral stationary phase has great prospects for chiral separation in high-performance liquid chromatography.