Mirids secrete a TOPLESS targeting protein to enhance JA-mediated defense and gossypol accumulation for antagonizing cotton bollworms on cotton plants.

Most coexisting insect species exhibit stunted growth compared to the single species on plants. This phenomenon reflects an interspecific antagonism that draws extensive attention while the underlying mechanisms remain largely unknown. Mirids (Apolygus lucorum) and cotton bollworms (Helicoverpa armigera) are two common pests in cotton fields. We identified a secretory protein, ASP1, from the oral secretion of mirids, which was found in the nucleus of mirid-infested cotton leaves. ASP1 specifically targets the transcriptional corepressor TOPLESS (TPL) and inhibits NINJA-mediated recruitment of TPL, thereby promoting plant defense response and gossypol accumulation in cotton glands. ASP1-enhanced defense inhibits the growth of cotton bollworms on cotton plants, while having little impact on mirids. The mesophyll-feeding characteristic allows mirids to avoid most cotton glands, thereby invalidating cotton defense. Our investigation reveals the molecular mechanism by which mirids employ cotton defense to selectively inhibit the feeding of cotton bollworms.

Stereotactic body radiotherapy using CyberKnife versus interstitial brachytherapy in accelerated partial breast irradiation on left-sided breast: A comparison of dosimetric characteristics and preliminary clinical results.

INTRODUCTION: We compared the dosimetric characteristics of the target and organs at risk (OARs) as well as the preliminary clinical outcomes between two accelerated partial breast irradiation (APBI) techniques. METHODS: Forty-four patients diagnosed with left-sided early breast cancer who underwent APBI using either interstitial brachytherapy (IB) or stereotactic body radiation therapy (SBRT) with CyberKnife (CK) were retrospectively reviewed. The dosimetric parameters of the target and OARs were compared. Preliminary clinical outcomes, including tumor control and acute toxicity, were analyzed. RESULTS: Treatment plans with CK demonstrated a better cardiac dose-sparing effect. Radiation doses to the heart at V150cGy for the CK and IB groups were 24.4 % and 60.4 %, respectively (p < 0.001), while the mean heart doses for the CK and IB groups were 107.4 cGy and 204 cGy, respectively (p < 0.001). The heart D1c.c. and the ipsilateral lung received a lower dose in the IB group, without any significant differences. The median follow-up time in the CK and IB groups was 28.6 and 61.3 months, respectively. No patients died from either breast cancer or cardiac events during follow-up. A locoregional recurrence event at the neck occurred in one patient within the IB group. CONCLUSIONS: APBI planned by CK was shown to have a better dose-sparing effect on the heart, as well as better conformity and homogeneity to the target. CK is a non-invasive treatment which showed minimal acute toxicity and promising tumor control.

The iPeer2Peer mentorship program for adolescent thoracic transplant recipients: An implementation-effectiveness evaluation.

BACKGROUND: An increase in self-management skills for adolescent thoracic transplant recipients may improve health outcomes and facilitate a successful transition to adulthood. The iPeer2Peer© program is an online peer mentorship program that has been successfully implemented as a self-management intervention in multiple chronic disease populations. This study aimed to determine the implementation and effectiveness outcomes of the iPeer2Peer program for adolescent thoracic transplant recipients. METHODS: A type III, hybrid implementation-effectiveness pilot study that comprised a quasi-experimental single-arm pre-post design was used to evaluate the iPeer2Peer program. Participant mentees, ages 12 to 17, were recruited from two large Canadian transplant centres. Peer mentors, ages 18 to 25, were thoracic transplant recipients who had successfully transitioned to adult care and self-manage their condition. A mixed methods approach for data collection was used, including interviews, focus groups, and standardized questionnaires. RESULTS: Twenty mentees (median 15.0 years, IQR 3.3 years; 65% female) completed the iPeer2Peer program with nine young adult mentors (median 21.0 years, IQR 3.0 years; 78% female). Implementation outcomes indicated that the iPeer2Peer intervention was perceived as feasible, adoptable, acceptable, and appropriate for adolescent thoracic transplant recipients. Significant findings were noted in mentees for increased self-management and a decrease in overall depression and anxiety symptoms. CONCLUSIONS: The successful implementation of the pilot iPeer2Peer program offers support to evaluate the scalability, sustainability, and cost-effectiveness of the program for adolescents with chronic illness, specifically thoracic transplant recipients. Changes to the iPeer2Peer program that facilitate a flexible delivery may help implementation and acceptance.

METTL3 silencing inhibits ferroptosis to suppress ovarian fibrosis in PCOS by upregulating m6A modification of GPX4.

Methyltransferase-like 3 (METTL3) is extensively reported to be involved in organ fibrosis. Ovarian fibrosis is a main characteristic of polycystic ovary syndrome (PCOS). However, the reaction mechanism of METTL3 in PCOS is poorly investigated. This paper was intended to reveal the role and the mechanism of METTL3 in PCOS. Animal and cell models of PCOS were induced by dehydroepiandrosterone (DHEA). H&E staining was performed to detect the pathological alterations in ovary tissues. Masson staining, immunofluorescence, along with western blot measured fibrosis both in vitro and in vivo. To evaluate estrous cycle, vaginal smear was performed. Lipid peroxidation and ferroptosis were evaluated by MDA assay kits, GSH assay kits, immunohistochemistry, Prussian blue staining and western blot. qRT-PCR and western blot were adopted to estimate METTL3 and GPX4 expression. The m6A and hormone secretion levels were respectively assessed by m6A RNA Methylation Quantitative Kit and corresponding kits. The interaction between METTL3 and GPX4 was testified by immunoprecipitation. The fibrosis and ferroptosis were aggravated and m6A and METTL3 expression were increased in ovarian tissues of DHEA-induced PCOS mice. METTL3 silencing alleviated pathological changes, affected hormone secretion level, and repressed fibrosis, lipid peroxidation and ferroptosis in the ovarian tissues of PCOS mice. In vitro, DHEA stimulation increased m6A and METTL3 expression and induced ferroptosis and fibrosis. METTL3 knockdown promoted GPX4 expression in DHEA-induced granulosa cells by m6A modification and restrained DHEA-induced fibrosis, lipid peroxidation and ferroptosis in granulosa cells via elevating GPX4. METTL3 silence inhibited ovarian fibrosis in PCOS, which was mediated through suppressing ferroptosis by upregulating GPX4 in m6A-dependent manner.

The impact of hydroxybutyl chitosan and 5-fluorouracil on the procedure of endoscopic endonasal dacryocystorhinostomy.

PURPOSE: To investigate the effects of hydroxybutyl chitosan (HBCS) with and without 5-fluorouracil (5-FU) during endoscopic endonasal dacryocystorhinostomy (Endo-DCR). In addition, the present study observed the impact of HBCS and 5-FU on the functions of the nasal mucosal cell population in vivo. METHODS: Patients were randomized into HBCS (group A), HBCS combined with 5-FU (group B), and gelatin sponge control group (group C). 16S rRNA high-throughput sequencing technology examined the conjunctival sac and nasal flora changes. In addition, CCK8, cell scratching, and flow cytometry were used to investigate the effects of HBCS and 5-FU on the nasal mucosal cell populations. RESULTS: Subjects in groups A, B, and C had anastomotic areas of 21.83 ± 12.69 mm2, 21.57 ± 14.53 mm2, and 12.45 ± 8.16 mm2, respectively (P = 0.0359). Group A had less severe epiphora than the other two groups at 1-, 2-, and 12-week postoperative follow-up (P < 0.05). Complications around the anastomosis in group A were the least severe of the three groups (P = 0.0259). After surgery, the proportion of pathogenic bacteria in the conjunctival sac and nasal cavity was higher in groups A and B than in healthy adults. At the 2-week follow-up, the structure of nasal flora in group A was more similar to that of the healthy adults compared to group B. CONCLUSION: Intraoperative use of HBCS at the anastomose improves the postoperative outcome of En-DCR. 5-FU cannot give better postoperative results in En-DCR and is detrimental to the normalization of the postoperative flora in patients with chronic dacryocystitis. At the cellular level, both HBCS and 5-FU inhibit the migration of nasal mucosal cell populations, and 5-FU inhibits proliferation but does not promote apoptosis.

Macrophage-mediated mechanisms of lung injury in the sensitization reaction to Echinococcus granulosus.

Objective: In this study, the impact of inhibiting the PI3K/AKT/NF-κB pathway on lung oxidative damage induced by Echinococcus granulosus cyst fluid was investigated. Methods: Twenty-four mice were randomly assigned to four groups. Three months after inoculation with hydatid cyst segments, mice in group A were treated with intraperitoneal and intratracheal saline injections; mice in group B were administered a caudal vein injection of a PI3K inhibitor, followed by cyst fluid sensitization; mice in group C received an AKT inhibitor via caudal vein, followed by cyst fluid sensitization; and mice in group D were subjected to cyst fluid sensitization without any inhibitor treatment. Cellular changes in lung tissues across all groups were evaluated, including pathological section analysis. Analysis of pulmonary tissue and serum from these mice included the assessment of PI3K/AKT/NF-κB pathway proteins, inflammatory factors, and related mRNA levels. Results: Mice in groups B and C exhibited a higher proportion of M2-type macrophages and significantly lower levels of PI3K/AKT/NF-κB pathway proteins, inflammatory factors (interleukin-6 [IL-6]/tumor necrosis factor-α [TNF-α]), and oxidative markers in lung tissues compared to mice in group D (P < 0.05). Conclusion: Our results in this study indicate that activation of the PI3K/AKT/NF-κB pathway contributed to an increase in the M1 macrophage phenotype, leading to enhanced secretion of peroxidases and inflammatory factors. This mechanism plays a crucial role in the oxidative and inflammatory lung damage associated with allergic reactions to E. granulosus cyst fluid.

Combination of Cytologic Findings and Circulating Tumor DNA From Cerebrospinal Fluid Revealed SCLC Transformation in Patients With Leptomeningeal Metastases of Lung Adenocarcinoma.

Introduction: Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce. Methods: We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing. Results: Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the EGFR mutation, including four patients with EGFR exon 19 deletion and three patients with EGFR exon 21 L858R mutation. Another patient harbored ERBB2 insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that TP53 and RB1 mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0-17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2-29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0-5.9 mo). Conclusions: SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

Elevated Risk of Adverse Prognosis in Patients with T2-3 Stage Breast Cancer Exhibiting Non-Pathological Complete Response Following Neoadjuvant Chemotherapy: Significance of Regenerating Islet-Derived Family Member 4.

Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR). Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes. Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR. Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

Causal association between mitochondrial function and psychiatric disorders: Insights from a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Previous observational studies have suggested that there appears to be a close association between mitochondrial function and psychiatric disorders, but whether a causal role exists remains unclear. METHODS: We extracted genetic instruments for 67 mitochondrial-related proteins and 10 psychiatric disorders from publicly available genome-wide association studies, and employed five distinct MR methods and false discovery rate correction to detect causal associations between them. Additionally, we conducted a series of sensitivity tests and additional model analysis to ensure the robustness of the results. For potential causal associations, we further performed reverse MR analyses to assess the impact of reverse causality. RESULTS: We identified a total of 2 significant causal associations and 24 suggestive causal associations. Specifically, Phenylalanine-tRNA ligase was found to increase the risk of Alzheimer's disease, while Mitochondrial glutamate carrier 2 decreased the risk of autism spectrum disorder. Furthermore, there was no evidence of significant pleiotropy, heterogeneity, or reverse causality. LIMITATIONS: This study was limited to individuals of European ancestry, and the conclusions drawn are merely revelatory. CONCLUSION: This study provides novel insights into the relationship between mitochondria and psychiatric disorders, as well as the pathogenesis and treatment strategies for psychiatric disorders.

Development of bait station to complement attract-and-kill agents of Zeugodacus tau (Diptera: Tephritidae).

Zeugodacus tau (Walker) (Diptera: Tephritidae) is an important agricultural pest currently managed primarily through the application of insecticides due to limited control strategies. Bait station devices are target specific and have emerged as a behaviorally based alternative to traditional insecticide sprays for managing Z. tau. In this study, we designed a bait station by integrating female-biased olfactory, visual, and gustatory elements, and a killing agent in a wax-matrix. Our results showed that the wax-matrix integrated with spinetoram showed the highest toxicity to immature and mature Z. tau females. Furthermore, the color and shape of the spinetoram bait station significantly influenced its attractiveness and toxicity to female Z. tau. Green sausage-shaped exteriors were the most effective color and shape examined. Subsequent experiments showed a length-dependent effect on mortality and visiting frequencies of Z. tau females when the bait stations were 9-13 cm long. The addition of the olfactory stimulus of 5% ammonium acetate to the bait station attracted a higher number of mature Z. tau females than the control. The killing efficacy of the weathered bait station was similar to that of the fresh station within an 8-week period (over 794 mm of rainfall). The bait station developed herein would provide new insight into the attract-and-kill strategy for Z. tau and alleviate the pressure of the actual management program for this pest.

Combining lymph node ratio to develop prognostic models for postoperative gastric neuroendocrine neoplasm patients.

BACKGROUND: Lymph node ratio (LNR) was demonstrated to play a crucial role in the prognosis of many tumors. However, research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm (NEN) patients was limited. AIM: To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models. METHODS: A total of 286 patients from the Surveillance, Epidemiology, and End Results database were divided into the training set and validation set at a ratio of 8:2. 92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set. Cox regression analysis was used to explore the relationship between LNR and disease-specific survival (DSS) of gastric NEN patients. Random survival forest (RSF) algorithm and Cox proportional hazards (CoxPH) analysis were applied to develop models to predict DSS respectively, and compared with the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging. RESULTS: Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death. The RSF model exhibited the best performance in predicting DSS, with the C-index in the test set being 0.769 [95% confidence interval (CI): 0.691-0.846] outperforming the CoxPH model (0.744, 95%CI: 0.665-0.822) and the 8th edition AJCC TNM staging (0.723, 95%CI: 0.613-0.833). The calibration curves and decision curve analysis (DCA) demonstrated the RSF model had good calibration and clinical benefits. Furthermore, the RSF model could perform risk stratification and individual prognosis prediction effectively. CONCLUSION: A higher LNR indicated a lower DSS in postoperative gastric NEN patients. The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set, showing potential in clinical practice.

Lipid-associated macrophages for osimertinib resistance and leptomeningeal metastases in NSCLC.

Leptomeningeal metastases (LMs) remain a devastating complication of non-small cell lung cancer (NSCLC), particularly following osimertinib resistance. We conducted single-cell RNA sequencing on cerebrospinal fluid (CSF) from EGFR-mutant NSCLC with central nervous system metastases. We found that macrophages of LMs displayed functional and phenotypic heterogeneity and enhanced immunosuppressive properties. A population of lipid-associated macrophages, namely RNASE1_M, were linked to osimertinib resistance and LM development, which was regulated by Midkine (MDK) from malignant epithelial cells. MDK exhibited significant elevation in both CSF and plasma among patients with LMs, with higher MDK levels correlating to poorer outcomes in an independent cohort. Moreover, MDK could promote macrophage M2 polarization with lipid metabolism and phagocytic function. Furthermore, malignant epithelial cells in CSF, particularly after resistance to osimertinib, potentially achieved immune evasion through CD47-SIRPA interactions with RNASE1_M. In conclusion, we revealed a specific subtype of macrophages linked to osimertinib resistance and LM development, providing a potential target to overcome LMs.

In Situ-Generated Formamidine as a Carbon/Nitrogen Source for Enaminone Formation: One-Pot Synthesis of Functionalized 4-Acyl-1,2,3-triazoles.

N,N-Dimethylformamide was reacted with hexamethyldisilazane to generate an N,N-dimethylformimidamide intermediate; thereafter, a reaction with acetophenones/ß-diketones was induced to form enaminones. The one-pot synthetic protocol described in this paper can be applied to synthesize 1,4-disubstituted 1,2,3-triazoles and 1,4,5-trisubstituted 1,2,3-triazoles, in which organic azides are used as substrates under optimized conditions. Furthermore, this protocol uses readily available materials, is nearly free of solvent, can be applied to gram-scale operations, and leads to the formation of structurally diverse products with favorable yields.

Realization of hydrogenation-induced superconductivity in two-dimensional Ti2N MXene.

Two-dimensional (2D) MXene superconductors have been currently attracting considerable interest due to their unique electronic properties and diverse applicability. Utilizing first-principles computational methods, we have designed two distinct configurations of hydrogenated 2D Ti2N MXene materials, namely Ti2NH2 and Ti2NH4, and have conducted an exhaustive analysis of their structural stability, electronic characteristics, and superconductivity. Hydrogenation endows monolayer Ti2N with inherent metallic characteristics, as evidenced by an elevated density of states (DOS) at the Fermi level (Ef). Notably, Ti2NH4 exhibits a superconducting critical temperature (Tc) of 15.8 K, which is predominantly ascribed to the electronic contributions stemming from the Ti 3d orbitals. Analysis of phonon dispersion underscores the pivotal role that diverse lattice vibrational modes play in electron-phonon coupling (EPC), particularly the significance of low-frequency vibrations for facilitating electron pairing and the emergence of superconductivity. Furthermore, strain engineering can effectively modulate the superconducting properties of Ti2NH4, with a 2% tensile strain enhancing the EPC strength (λ) to 0.857 and increasing Tc to 18.7 K. This research elucidates the superconducting mechanisms of hydrogenated Ti2N structures, offering valuable insights for the development of novel 2D superconducting materials.

Development of a 3D Hydrogel SERS Chip for Noninvasive, Real-Time pH and Glucose Monitoring in Sweat.

Traditional diagnostic methods, such as blood tests, are invasive and time-consuming, while sweat biomarkers offer a rapid physiological assessment. Surface-enhanced Raman spectroscopy (SERS) has garnered significant attention in sweat analysis because of its high sensitivity, label-free nature, and nondestructive properties. However, challenges related to substrate reproducibility and interference from the biological matrix persist with SERS. This study developed a novel ratio-based 3D hydrogel SERS chip, providing a noninvasive solution for real-time monitoring of pH and glucose levels in sweat. Encapsulating the probe molecule (4-MBN) in nanoscale gaps to form gold nanoflower-like nanotags with internal standards and integrating them into an agarose hydrogel to create a 3D flexible SERS substrate significantly enhances the reproducibility and stability of sweat analysis. Gap-Au nanopetals modified with probe molecules are uniformly dispersed throughout the porous hydrogel structure, facilitating the effective detection of the pH and glucose in sweat. The 3D hydrogel SERS chip demonstrates a strong linear relationship in pH and glucose detection, with a pH response range of 5.5-8.0 and a glucose detection range of 0.01-5 mM, with R2 values of 0.9973 and 0.9923, respectively. In actual sweat samples, the maximum error in pH detection accuracy is only 1.13%, with a lower glucose detection limit of 0.25 mM. This study suggests that the ratio-based 3D hydrogel SERS chip provides convenient, reliable, and rapid detection capabilities with substantial application potential for analyzing body fluid pH and glucose.

Abundant small microplastics hidden in water columns of the Yellow Sea and East China Sea: Distribution, transportation and potential risk.

Microplastics (MPs) pose significant concerns for marine ecological security due to their minuteness and ubiquity. However, comprehensive knowledge on their distribution and fate in seawater columns remains limited. This study investigated the abundances and characteristics of MPs across 3-6 water layers in the South Yellow Sea and East China Sea. Results indicate that high-abundance small MPs (< 100 µm) (average 6567 items/m3) were hidden beneath the sea-surface, predominantly fine-grained particles (< 20 µm) and high-density polymers (> 1.03 g/cm3). The total suspended MPs (5.0-834.2 µm) are estimated at 2.9-3.1 × 1017 particles, with most of them occurring in upper layers. In profiles, their distribution varied by physical properties with depth; fragment-shaped and high-density MPs increased in proportion at greater depths, contrasting with fibrous MPs. These MPs originated primarily from the Yangtze River and their winter transport was driven by the Yangtze River Dilution Water, East China Sea Coastal Current, and Yellow Sea Warm Current, resulting in their accumulation in coastal and estuarine regions. Consequently, the Yangtze River Estuary ecosystem faces substantial risks from MP pollution throughout the water column. This work unveils the prevalence of small MPs in coastal water columns and intricate interaction between their fate and hydrodynamic conditions.

Ventricular arrhythmias originating from different portions of the communicating vein of the left ventricular summit: electrocardiographic characteristics and catheter ablation.

BACKGROUND: Idiopathic ventricular arrhythmias (IVAs) arising from different portions of the communicating vein of the left ventricular summit (summit-CV) are not a rare phenomenon. Whereas its electrocardiographic (ECG) and electrophysiological characteristics are not fully investigated. OBJECTIVE: This study aimed to identify distinct ECG and electrophysiological features of IVAs originating from different portions of summit-CV. METHODS: Nineteen patients confirmed arising from summit-CV were included in this study. RESULTS: The 19 patients were divided into proximal and distal portion groups based on their target sites in summit-CV. In the proximal portion group, 100% (11/11) VAs showed dominant negative (rs or QS) waves in lead I, while in the distal portion group, 87.5% (7/8) showed dominant positive waves (R, Rs or r) (p < 0.000). In lead V1, 100% (11/11) of the proximal portion group showed dominant positive waves (R or Rs), while 62.50% (5/8) of the distal portion group showed positive and negative bidirectional or negative waves (RS or rS) (p < 0.005). RI>4mV, SI<3.5mV, RV1<13mV, SV1>3.5mV, RI/SI>0.83, and RV1/SV1< 2.6 indicated a distal portion of summit-CV with the predictive value of 0.909, 1.000, 0.653, 0.972, 0.903, 0.966, respectively. A more positive wave in lead I and a more negative wave in lead V1 indicated more distal origin in summit-CV. Target sites in proximal and distal summit-CV groups showed similar electrophysiological characteristics during mapping. CONCLUSIONS: There were significant differences in ECG characteristics of VAs at different portions of summit-CV, which could aid pre-procedure planning and facilitate radiofrequency catheter ablation (RFCA) procedures.

Metal-Free Perovskite Ferroelectrics with the Most Equivalent Polarization Axes.

Ferroelectricity in metal-free perovskites (MFPs) has emerged as an academic hotspot for their lightweight, eco-friendly processability, flexibility, and degradability, with considerable progress including large spontaneous polarization, high Curie temperature, large piezoelectric response, and tailoring coercive field. However, their equivalent polarization axes as a key indicator are far from enough, although multiaxial ferroelectrics are highly preferred for performance output and application flexibility that profit from as many equivalent polarization directions as possible with easier reorientation. Here, by implementing the synergistic overlap of regulating anionic geometries (from spherical I- to octahedral [PF6]- and to tetrahedral [ClO4]- or [BF4]-) and cationic asymmetric modification, we successfully designed multiaxial MFP ferroelectrics CMDABCO-NH4-X3 (CMDABCO = N-chloromethyl-N'-diazabicyclo[2.2.2]octonium; X = [ClO4]- or [BF4]-) with the lowest P1 symmetry. More impressively, systemic characterizations indicate that they possess 24 equivalent polarization axes (Aizu notations of 432F1 and m3̅mF1, respectively)─the maximum number achievable for ferroelectrics. Benefiting from the multiaxial feature, CMDABCO-NH4-[ClO4]3 has been demonstrated to have excellent piezoelectric sensing performance in its polycrystalline sample and prepared composite device. Our study provides a feasible strategy for designing multiaxial MFP ferroelectrics and highlights their great promise for use in microelectromechanical, sensing, and body-compatible devices.

Visible-Light Mediated Nickel-Catalyzed Asymmetric Difunctionalizations of Alkenes.

Difunctionalizations of alkenes represent one of the most straightforward protocols to build molecular complexity due to the simultaneous construction of two vicinal bonds cross π-bond of alkenes. It is extremely attractive yet challenging to control the stereochemistry outcome of this event. Over the past years, visible-light and Ni-catalyzed asymmetric difunctionalizations of alkenes provide an environmental benign and promising solution for the construction of saturated carbon centers with the control of regio- and enantioselectivity. In this Concept, the initiative and progress of regio- and enantioselective difunctionalizations of alkenes enabled by visible-light and nickel catalysis has been summarized. Moreover, further efforts and directions for the development of visible-light mediated Ni-catalyzed asymmetric difunctionalizations of alkenes has been discussed.

Epigenetic and oncogenic inhibitors cooperatively drive differentiation and kill KRAS-mutant colorectal cancers.

Current treatments for KRAS-mutant colorectal cancers (CRCs) are often limited by cellular plasticity and rewiring responses. Here we describe a promising therapeutic strategy that simultaneously targets epigenetic and oncogenic signals. Specifically, we show that inhibitors of the histone methyltransferase, EZH2, synergize with various RAS pathway inhibitors and promote dramatic tumor regression in vivo. Together these agents cooperatively suppress WNT-driven transcription and drive CRCs into a more differentiated cell state by inducing the Groucho/TLE corepressor, TLE4, along with a network of WNT pathway inhibitors and intestinal differentiation proteins. However, these agents also induce the pro-apoptotic protein BMF, which subsequently kills these more differentiated cells. Accordingly, cell death can be prevented by activating ß-catenin, blocking differentiation, or by ablating BMF expression. Collectively, these studies reveal a new therapeutic approach for treating KRAS-mutant CRCs and illustrate a critical convergence of EZH2 and RAS on oncogenic WNT signals, intestinal differentiation, and apoptosis.