Effects of SvAPETALA1-5 gene on floral organ development in Senecio vulgaris.

Asteraceae is a large class of eudicots with complex capitulum, and little is known regarding the molecular regulation mechanism of flower development. APETALA1(AP1) belongs to the MADS-box gene family and plays a key role in plant floral induction and floral organ development. In this study, the bioinformatics and tissue-specific expression of AP1 homologous gene SvAP1-5 in Senecio vulgaris were analyzed. Based on VIGS technology, SvAP1-5 gene silencing plants were created, and SvAP1-5 was overexpressed in Solanum nigrum. The results of bioinformatics analysis showed that SvAP1-5 gene had typical MADS-box and K-box structure, and contains FUL motif and paleoAP1 motif at the C-terminal. SvAP1-5 belongs to the euFUL branch of AP1 gene. qRT-PCR results showed that SvAP1-5 was expressed in bracts, petals and carpels, and was highly expressed in carpels. Compared with the control group, SvAP1-5 gene silencing resulted in irregular petal dehiscence, increased stigma division, and carpel dysplasia. The fruit development of SvAP1-5 overexpressing S.nigrum plants was abnormal, and the hyperplastic tissue similar to fruit appeared. In summary, SvAP1-5 gene may be involved in the development of petals and carpels and plays an important role during the development of S.vulgaris.

Andrographolide sensitizes glioma to temozolomide by inhibiting DKK1 expression.

BACKGROUND: Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ. METHODS: Western blot, immunohistochemical staining, and qRT-PCR assays were used to explore the mechanisms underlying TMZ promoting DKK1 expression and andrographolide (AND) inhibiting DKK1 expression. HPLC was used to detect the ability of andrographolide (AND) to penetrate the blood-brain barrier. MTT assay, bioluminescence images, magnetic resonance imaging (MRI) and H&E staining were employed to measure the proliferative activity of glioma cells and the growth of intracranial tumors. RESULTS: TMZ can promote DKK1 expression in glioma cells and brain tumors of an orthotopic model of glioma. DKK1 could promote glioma cell proliferation and tumor growth in an orthotopic model of glioma. Mechanistically, TMZ increased EGFR expression and subsequently induced the activation of its downstream MEK-ERK and PI3K-Akt pathways, thereby promoting DKK1 expression in glioma cells. Andrographolide inhibited TMZ-induced DKK1 expression through inactivating MEK-ERK and PI3K-Akt pathways. Andrographolide can cross the blood-brain barrier, the combination of TMZ and andrographolide not only improved the anti-tumor effects of TMZ but also showed a survival benefit in an orthotopic model of glioma. CONCLUSION: Andrographolide can enhance anti-tumor activity of TMZ against glioma by inhibiting DKK1 expression.

Glyphosate-based herbicides reduced overwintering population and reproduction of agrobiont spiders.

Spiders are important in ecosystem and serve as predators in the biological control of pest insects in agroecosystem, where they encounter various harsh challenges including pesticides and low temperature in winter. Glyphosate-based herbicides (GBH) are widely and frequently applied to diminish weeds, exposing spiders a disturbed habitat, especially to overwintering spiders. We conducted a study combining field surveys and lab assays, to assess the effects of a GBH on the overwintering of the agrobiont wolf spider, Pardosa pseudoannulata. The GBH significantly reduced the overall overwintering spider population by about 69 %, and reduced the number of vulnerable juveniles by about 80 %. The survivors exhibited substantial fitness costs such as reproductive dysfunctions and enhanced oxidative stress responses. We then mimicked the overwinter process in lab. We housed spiders on soil patches with and without weeds to examine whether weeds contributed to the GBH's sublethal effects. Spiders overwintered independent of weeds when GBH was not applied. When GBH was applied before or during overwintering, juvenile spiders overwintered in weedy habitats exhibited reduced survival and fecundity, and increased oxidative stress compared to their counterparts in weed-free habitats. Therefore, GBH-containing weeds contributed to the persistent adverse effects of GBH on overwintering spiders. The findings revealed the cross-talk among weeds, herbicides, low temperature, and non-target organisms. The study provides novel information on the environmental risk assessment of pesticides and rational scheduling of pesticide application.

[Research advances in the response of soil nitrogen emissions from peatlands to climate warming and drying]. / æ³¥ç‚­åœ°åœŸå£¤æ°®æŽ’æ”¾å¯¹æ°”å€™æš–å¹²åŒ–å“åº”ç ”ç©¶è¿›å±•.

Climate warming and drying has led to a sharp increase in nitrogen (N) emissions from the boreal peatland soils, but the underlying microbial-mediated mechanism is still unclear. We reviewed the responses of soil N transformation and emission in alpine peatland to temperature increases and water table changes, the interaction between soil anaerobic ammonia oxidation (Anammox) and NO3- dissimilatory reduction processes, and soil N2O production pathways and their contributions. There are several knowledge gaps. First, the amount of N loss in peatlands in alpine areas is seriously underestimated because most studies focused only on soil N2O emissions and ignored the release of N2. Second, the contribution of Anammox process to N2 emissions from peatlands is not quantified. Third, there is a lack of quantification of the relative contributions of Anammox, bacterial denitrification, and fungal co-denitrification processes to N2 loss. Finally, the decoupling mechanism of Anammox and NO3- reduction processes under a warming and drying climate scenario is not clear. Considering aforementioned shortages in previous studies, we proposed the directions and contents for future research. Through building an experimental platform with field warming and water level controlling, combining stable isotope, molecular biology, and metagenomics technology, the magnitude, composition ratio and main controlling factors of N emissions (N2O, NO, and N2) in boreal peatlands should be systematically investigated. The interaction among the main N loss processes in soils as well as the relative contributions of nitrification, anaerobic ammonia oxidation, and denitrification to N2O and N2 productions should be investigated and quantified. Furthermore, the sensitive microbial groups and the coupling between soil N transformations and microbial community succession should be clarified to reveal the microbiological mechanism underlying the responses of soil N turnover process to climate warming and drying.

Effect of Paprika Powder on the Antioxidant Capacity of Emulsion-Type Sausages.

Antioxidant activity of freeze-dried paprika powder and storage properties of emulsion-type pork sausages containing diverse concentrations of this powder (0%, 1%, 2%, and 3%) were analyzed. Antioxidant activities of red and yellow paprika powders were analyzed by evaluating their 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP), total phenol content (TPC), and total flavonoid content (TFC). The yellow paprika powder exhibited remarkably higher DPPH radical scavenging activity, FRAP values, and TPC than the red paprika powder (p<0.05), while TFC showed no remarkable difference between them (p>0.05). Storage properties of sausages containing the yellow paprika powder were analyzed by evaluating their water holding capacity, cooking yield, and thiobarbituric acid reactive substance (TBARS), and volatile basic nitrogen (VBN) values. The 3% yellow paprika powder group showed remarkably higher water-holding capacity and cooking yield compared to the 0% group (p<0.05). TBARS values were remarkably lower in the 2% and 3% yellow paprika powder groups than in the 0% group at all weeks (p<0.05). VBN value was remarkably lower in the 3% yellow paprika powder group than in the 0% group at all weeks (p<0.05). Overall, addition of 3% yellow paprika powder improved the storage properties of emulsion-type sausages.

Analgesia strategy for inguinal hernia repair in children: a systematic review and network meta-analysis of randomized clinical trials based on regional blocks.

Background and objective: Despite its acknowledged benefits, the selection of an optimal regional block for analgesia pediatric hernia surgery remains a subject of debate. This study endeavored to conduct a network meta-analysis and systematic review of randomized clinical trials, aiming to amalgamate insights from both direct and indirect comparisons concerning the analgesic effectiveness and safety of various regional blocks post-inguinal hernia repair in children. Method: A comprehensive literature search was performed across PubMed, EMBASE, Web of Science, and the Cochrane Library up to 12 November 2022 by two independent reviewers, employing a standardized protocol. The inclusion criteria encompassed randomized trials focusing on children undergoing inguinal hernia repair utilizing either local infiltration analgesia or regional analgesia. The primary outcomes assessed were pain scores at 2, 6, and 24 h post-operation. Results: The initial search yielded 281 records relating to 1,137 patients. The analysis of ranking probability indicated that Paravertebral Block (PVB) holds the highest likelihood (88% and 48%) of being the most effective in alleviating pain at 2 h and 6 h post-surgery. Trans vs. Abdominis Plane Block (TAPB) emerged as the superior choice for mitigating pain (83%) and decreasing morphine consumption (93%) at 24 h following the operation. Local Anesthetic Infiltration (LAI) was identified as the most effective in shortening the hospital stay, with a 90% probability. Conclusions: Regional anesthesia significantly enhances postoperative pain management in pediatric inguinal hernia repair surgery. For short-term postoperative pain relief, PVB emerges as the most effective technique. Meanwhile, TAPB provides more prolonged analgesia. Although TAPB does not exhibit a pronounced advantage in short-term analgesia, its simplicity and the absence of a need for a special position render it a viable option. However, the interpretation of these results should be approached with caution due to the presence of limited data and heterogeneity. Systematic Review Registration: PROSPERO (CRD42022376435; www.crd.york.ac.uk/prospero).

Cellular and molecular mechanisms of gastrointestinal cancer liver metastases and drug resistance.

Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth. Metastatic tumors often exhibit greater resistance to drugs than primary tumors, posing extra challenges in treatment. The liver metastases and drug resistance of GI cancers are regulated by complex, intertwined, and tumor-dependent cellular and molecular mechanisms that influence tumor cell behavior (e.g. epithelial-to-mesenchymal transition, or EMT), tumor microenvironment (TME) (e.g. the extracellular matrix, cancer-associated fibroblasts, and tumor-infiltrating immune cells), tumor cell-TME interactions (e.g. through cytokines and exosomes), liver microenvironment (e.g. hepatic stellate cells and macrophages), and the route and mechanism of tumor cell dissemination (e.g. circulating tumor cells). This review provides an overview of recent advances in the research on cellular and molecular mechanisms that regulate liver metastases and drug resistance of GI cancers. We also discuss recent advances in the development of mechanism-based therapy for these GI cancers. Targeting these cellular and molecular mechanisms, either alone or in combination, may potentially provide novel approaches to treat metastatic GI malignancies.

The potential roles of HIF-1α in epithelial-mesenchymal transition and ferroptosis in tumor cells.

In tumors, the rapid proliferation of cells and the imperfect blood supply system lead to hypoxia, which can regulate the adaptation of tumor cells to the hypoxic environment through hypoxia-inducible factor-1α (HIF-1α) and promote tumor development in multiple ways. Recent studies have found that epithelial-mesenchymal transition (EMT) and ferroptosis play important roles in the progression of tumor cells. The activation of HIF-1α is considered a key factor in inducing EMT in tumor cells. When HIF-1α is activated, it can regulate EMT-related genes, causing tumor cells to gradually lose their epithelial characteristics and acquire more invasive mesenchymal traits. The occurrence of EMT allows tumor cells to better adapt to changes in the surrounding tissue, enhancing their migratory and invasive capabilities, thus promoting tumor progression. At the same time, HIF-1α also plays a crucial regulatory role in ferroptosis in tumor cells. In a hypoxic environment, HIF-1α may affect processes such as iron metabolism and oxidative stress responses, inducing ferroptosis in tumor cells. This article briefly reviews the dual role of HIF-1α in EMT and ferroptosis in tumor cells, helping to gain a deeper understanding of the regulatory pathways of HIF-1α in the development of tumor cells, providing a new perspective for understanding the pathogenesis of tumors. The regulation of HIF-1α may become an important strategy for future tumor therapy.

GJB2 Promotes HCC Progression by Activating Glycolysis Through Cytoplasmic Translocation and Generating a Suppressive Tumor Microenvironment Based on Single Cell RNA Sequencing.

Despite substantial breakthroughs in the treatment of hepatocellular carcinoma (HCC) in recent years, many patients are diagnosed in the middle or late stages, denying them the option for surgical excision. Therefore, it is of great importance to find effective therapeutic targets of HCC. In this study, it is found that Gap junction protein beta-2 (GJB2) is highly enriched in malignant cells based on single-cell RNA sequencing and higher expression of GJB2 indicates a worse prognosis. The localization of GJB2 in HCC cancer cells is changed compared with normal liver tissue. In cancer cells, GJB2 tends to be located in the cytoplasm and nucleus, while in normal tissues, GJB2 is mainly located on the cell membrane. GJB2 is related to glycolysis, promoting NF-κB pathway via inducing the ubiquitination degradation of IκBa, and activating HIF-1α/GLUT-1/PD-L1 pathway. In addition, GJB2 knockdown reshapes tumor immune microenvironment and Salvianolic acid B inhibits the activity of GJB2. In conclusion, GJB2 promotes HCC progression by activating glycolysis through cytoplasmic translocation and generating a suppressive tumor microenvironment. Salvianolic acid B inhibits the expression of GJB2 and enhances the sensitivity of anti-PD1 therapy, which may provide insights into the development of novel combination therapeutic strategies for HCC.

Intraoperative Fluorescent Navigation of the Ureters, Vessels, and Nerves during Robot-Assisted Sacrocolpopexy.

In this study, we aimed to demonstrate the feasibility and safety of navigating the ureters, middle sacral artery (MSA), and superior hypogastric nerve (SHN) using indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during robot-assisted sacrocolpopexy (RSCP). Overall, 15 patients who underwent RSCP for apical vaginal prolapse were retrospectively enrolled. All patients underwent cystoscopic intraureteric instillation of 5 cc ICG (2.5 mg/mL) before RSCP and intravenous injection of 3 cc ICG during presacral dissection and mesh fixation. In all patients, the fluorescent right ureter was clearly identified in real time. The MSA was visualized on ICG-NIRF images in 80% (13/15) of patients. The mean time from ICG injection to MSA visualization was 43.7 s; the mean duration of the arterial phase was 104.3 s. Fluorescent SHN was detected in 73.3% (11/15) of patients. The time from ICG injection to SHN fluorescence was 48.4 s; the duration of fluorescence was 177.2 s. There was no transfusion, iatrogenic ureteral injury, or bowel or urinary dysfunction. Our results indicated that intraoperative ureter, MSA, and SHN mapping using ICG-NIRF images during RSCP is a valuable and safe technique to avoid iatrogenic ureteral, vascular, and neural injuries and to simplify surgical procedures. Nonetheless, further studies are required.

Targeting DKK1 enhances the antitumor activity of paclitaxel and alleviates chemotherapy-induced peripheral neuropathy in breast cancer.

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.

Using status of secondary prevention medications in post-stroke dysphagia patients: time to raise awareness and develop special formulations.

Post-stroke dysphagia (PSD) is an increasingly common complication of stroke. Despite its intuitively unfavorable impact on secondary prevention medication use, limited awareness is available regarding this issue. Herein, a cross-sectional survey was conducted to determine the current use, patient-perceived needs and preferences for secondary prevention medications among PSD patients. To emphasize the unique context related to dysphagia, we recruited Chinese stroke patients with a duration of less than 5 years. These patients were initially categorized into PSD respondents with and without dysphagia. Among the 3490 eligible respondents, 42.7% reported experiencing dysphagia after stroke. Those PSD respondents were more likely to consume multiple medications and suffer from anticoagulants-associated gastrointestinal bleeding as compared to non-PSD ones (p < 0.001). More crucially, 40.2% of them had frequent difficulty in swallowing pills, 37.1% routinely crushed solid oral dosage forms (SODFs), and 23.5% coughed frequently when taking SODFs. In consequence, 87.4% responded a need for PSD-specific formulations where safe swallowing, easy swallowing, and reduced medication frequency were preferred pharmaceutical factors. These findings demonstrate an unsatisfactory situation and definite needs for PSD patients in using secondary prevention medications. Awareness should be increased to develop PSD-specific formulations for safe and effective secondary prevention.

Characterization and Dissolution Mechanism of Low-Molecular-Weight Organic Acids or Inorganic Mesoporous Particle-Based Piperine Amorphous Solid Dispersions.

The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance (1H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.

Pressure-Induced Re-Entrant Superconductivity in Transition Metal Dichalcogenide TiSe2.

Transition metal dichalcogenide TiSe2 exhibits a superconducting dome within a low pressure range of 2-4 GPa, which peaks with the maximal transition temperature Tc of ≈1.8 K. Here it is reported that applying high pressure induces a new superconducting state in TiSe2, which starts at ≈16 GPa with a substantially higher Tc that reaches 5.6 K at ≈21.5 GPa with no sign of decline. Combining high-throughput first-principles structure search, X-ray diffraction, and Raman spectroscopy measurements up to 30 GPa, It is found that TiSe2 undergoes a first-order structural transition from the 1T phase under ambient pressure to a new 4O phase under high pressure. Comparative ab initio calculations reveal that while the conventional phonon-mediated pairing mechanism may account for the superconductivity observed in 1T-TiSe2 under low pressure, the electron-phonon coupling of 4O-TiSe2 is too weak to induce a superconducting state whose transition temperature is as high as 5.6 K under high pressure. The new superconducting state found in pressurized TiSe2 requires further study on its underlying mechanism.

Comparative analysis of child injuries in passenger vehicles and school buses: a multicentre cross-sectional study.

OBJECTIVE: This study investigated the differences in injury profiles and safety device effectiveness among children with road traffic injuries (RTIs) involving passenger vehicles and school buses. METHODS: Using data from the Emergency Department-based Injury In-depth Surveillance database, this multicentre cross-sectional study investigated the injury profiles of 14 669 children aged 12 years old and younger who experienced RTIs from 2011-2021. Demographic factors, injury distribution, severity and effect of safety device use between RITs involving passenger vehicles and school buses were compared. RESULTS: RTIs in children most frequently occurred between 12:00 and 18:00 hours (46.9%). School bus-related RTIs peaked during school commute hours, that is, from 06:00 to 12:00 hours, and were associated with a higher prevalence of head (63.1% vs 58.9%, p<0.05) and extremity injuries (upper extremity: 8.0% vs 6.4% and lower extremity: 11.1% vs 7.6 %, p<0.05) compared with those involving passenger vehicles. However, passenger vehicle crashes showed higher proportions of neck and chest injuries, along with injuries requiring hospitalisation and intensive care. Safety devices exhibited preventive effects against head and lower extremity injuries in both vehicle types. While safety devices showed effective in reducing hospital admissions and severe injuries in passenger vehicles, their effectiveness in school buses was not observed. CONCLUSION: This study highlights the different epidemiology and injury profiles of RTIs among children involving passenger vehicles and school buses. Improved safety devices, particularly in school buses, are necessary to ensure the comprehensive protection of child passengers and reduce the risk of severe injuries during road traffic incidents.

Pre-existing sleep disturbances and risk of COVID-19: a meta-analysis.

Background: Sleep disturbances are widespread but usually overlooked health risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate the influence of pre-existing sleep disturbances on the susceptibility, severity, and long-term effects of COVID-19. Methods: We searched PubMed, Web of Science, and Embase for relevant articles from inception to October 27, 2023 and updated at May 8, 2024. Sleep disturbances included obstructive sleep apnea (OSA), insomnia, abnormal sleep duration, night-shift work, and any other sleep disturbances. Outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. The effect sizes were pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). This study is registered with PROSPERO (CRD42024503518). Findings: A total of 48 observational studies (n = 8,664,026) were included. Pre-existing sleep disturbances increased the risk of COVID-19 susceptibility (OR = 1.12, 95% CI 1.07-1.18), hospitalization (OR = 1.25, 95% CI 1.15-1.36), mortality (OR = 1.45, 95% CI 1.19-1.78), and long COVID (OR = 1.36 95% CI 1.17-1.57). Subgroup analysis showed that younger individuals with sleep disturbances were associated with higher susceptibility and hospitalization and a lower risk of mortality than older individuals. Males with sleep disturbances were associated with higher mortality. For specific sleep disturbances, the susceptibility and hospitalization of COVID-19 were associated with OSA, abnormal sleep duration, and night-shift work; mortality of COVID-19 was linked to OSA; risk of long COVID was related to OSA, abnormal sleep duration and insomnia. Interpretation: Pre-existing sleep disturbances, especially OSA, increased the risk of COVID-19 susceptibility, hospitalization, mortality, and long COVID. Age and sex played important roles in the effect of sleep disturbances on COVID-19. Funding: The National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province.

Daphnetin alleviates allergic airway inflammation by inhibiting T-cell activation and subsequent JAK/STAT6 signaling.

Allergic asthma is a major health burden on society as a chronic respiratory disease characterized by inflammation and muscle tightening around the airways in response to inhaled allergens. Daphne kiusiana Miquel is a medicinal plant that can suppress allergic airway inflammation; however, its specific molecular mechanisms of action are unclear. In this study, we aimed to elucidate the mechanisms by which D. kiusiana inhibits allergic airway inflammation. We evaluated the anti-inflammatory effects of the ethyl acetate (EA) fraction of D. kiusiana and its major compound, daphnetin, on murine T lymphocyte EL4 cells stimulated with phorbol 12-myristate 13-acetate and ionomycin in vitro and on asthmatic mice stimulated with ovalbumin in vivo. The EA fraction and daphnetin inhibited T-helper type 2 (Th2) cytokine secretion, serum immunoglobulin E production, mucus secretion, and inflammatory cell recruitment in vivo. In vitro, daphnetin suppressed intracellular Ca2+ mobilization (a critical regulator of nuclear factor of activated T cells) and functions of the activator protein 1 transcription factor to reduce interleukin (IL)-4 and IL-13 expression. Daphnetin effectively suppressed the IL-4/-13-induced activation of Janus kinase (JAK)/signal transducer and activator of transcription 6 (STAT6) signaling in vitro and in vivo, thereby inhibiting the expression of GATA3 and PDEF, two STAT6-target genes responsible for producing Th2 cytokines and mucins. These findings indicate that daphnetin suppresses allergic airway inflammation by stabilizing intracellular Ca2+ levels and subsequently inactivating the JAK/STAT6/GATA3/PDEF pathway, suggesting that daphnetin is a promising alternative to existing asthma treatments.

Rotational Stability, Footplate Position, and Visual Outcomes of Toric Implantable Collamer Lenses in Eyes With Low Vault.

PURPOSE: To evaluate the clinical outcomes, rotational stability, and footplate position of the toric Implantable Collamer Lens (TICL) (STAAR Surgical) in eyes with low vault and analyze factors related to rotational stability. METHODS: This prospective observational study included 59 eyes of 59 patients with insufficient vault (< 250 µm). Postoperative rotation was defined as the difference between the achieved angle and the intraoperative fixation angle, and assessed with a digital anterior segment photograph after full mydriasis at 1 week and 1, 3, and 6 months postoperatively. Ultrasound biomicroscopy was used to determine the ciliary body morphology and position of the footplate. Correlation analysis was employed to identify the risk factors associated with TICL rotation at 6 months postoperatively. RESULTS: At 6 months postoperatively, the mean central vault was 137.4 ± 61.0 µm (range: 40 to 236 µm), and the mean efficacy and safety indices were 1.04 and 1.15, respectively. The mean manifest refractive astigmatism decreased from -1.67 ± 0.82 diopters (D) preoperatively to -0.43 ± 0.33 D postoperatively, and the mean absolute rotation was 4.50 ± 3.08 degrees (range: 0 to 12.50 degrees). The angle of rotation was correlated with the preoperative spherical power (r = -0.318, P = .014), the average value of TICL footplates position (r = 0.284, P = .029), and postoperative astigmatism (r = -.469, P⩽ .001). CONCLUSIONS: TICL implantation is predictable, safe, and effective in correcting myopic astigmatism in eyes with low vault. The rotational stability was acceptable and related to the malposition of the footplate and preoperative spherical power. [J Refract Surg. 2024;40(7):e460-e467.].

Catalytic Enantioselective Synthesis of Inherently Chiral Calix[4]arenes via Sequential Povarov Reaction and Aromatizations.

Inherently chiral calix[4]arenes represent a unique type of chiral molecules with significant applications, yet their catalytic enantioselective synthesis remains largely underexplored. We report herein the catalytic enantioselective synthesis of inherently chiral calix[4]arenes through the sequential organocatalyzed enantioselective Povarov reaction and aromatizations. The chiral phosphoric acid catalyzed three-component Povarov reaction involving amino group-substituted calix[4]arenes, aldehydes and (di)enamides desymmetrized the prochiral calix[4]arene substrates, which was followed by various aromatization methods, resulting in a diverse array of novel quinoline-containing calix[4]arenes with good yields and high enantioselectivities (up to 75 % yield, 99 % ee). The large-scale enantioselective synthesis and diverse derivatizations of the chiral calix[4]arene products highlight the value of this method. Furthermore, preliminary exploration into their photophysical and chiroptical properties demonstrate the potential applications of these novel calix[4]arene molecules.