Strong Acid Enabled Comprehensive Training of Poly (Sodium Acrylate) Hydrogel NetworksStrong Acid Enabled Comprehensive Training of Poly (Sodium Acrylate) Hydrogel Networks.

The design of admire hydrogel networks is of both practical and fundamental importance for diverse applications of hydrogels. Herein a general strategy of acid-assisted training is designed to enable multiple improvement of conventional poly (sodium acrylate) networks for hydrogels. Hydrophobic homogeneous crosslinked poly (sodium acrylate) hydrogels are prepared to verify the strategy. The acid-assisted training is simply achieved by immersing the hydrogel networks into 4 M H2SO4 solutions. The introduced acids would induce transformation of poly (sodium acrylate) into poly (acrylic acid) at hydrogel surface, which constructs dynamic hydrogen bonding interactions to tighten the network. The acid-containing poly (sodium acrylate) hydrogels newly generate anti-swelling and self-healing performance, and show mechanical improvement. The internal poly (sodium acrylate) of the pristine acid-containing hydrogels is further fully transformed via acid-infiltration after following cyclic stretch/release training to significantly improve the mechanical performance. The Young's modulus, stress, and toughness of the fully-trained hydrogels are 187.6 times, 35.6 times, and 5.4 times enhanced, respectively. The polymeric networks retain isotropic in fully-trained hydrogels to ensure superior stretchability of 8.6. The acid-assisted training performance of the hydrogels can be reversibly recovered by NaOH neutralization. The acid-assisted training strategy here is general for poly (sodium acrylate) hydrogels.

Cynarin alleviates acetaminophen-induced acute liver injury through the activation of Keap1/Nrf2-mediated lipid peroxidation defense via the AMPK/SIRT3 signaling pathway.

Overdose of Acetaminophen (APAP) is a major contributor to acute liver injury (ALI), a complex pathological process with limited effective treatments. Emerging evidence links lipid peroxidation to APAP-induced ALI. Cynarin (Cyn), a hydroxycinnamic acid derivative, exhibits liver protective effects, but whether it mitigates APAP-induced ALI is unclear. Our aim was to verify the protective impact of Cyn on APAP-induced ALI and elucidate the molecular mechanisms governing this process. Herein, the regulation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) interaction was determined to be a novel mechanism underlying this protective impact of Cyn against APAP-induced ALI. Nrf2 deficiency increased the severity of APAP-induced ALI and lipid peroxidation and counteracted the protective effect of Cyn against this pathology. Additionally, Cyn promoted the dissociation of Nrf2 from Keap1, enhancing the nuclear translocation of Nrf2 and the transcription of downstream antioxidant proteins, thereby inhibiting lipid peroxidation. Molecular docking demonstrated that Cyn bound competitively to Keap1, and overexpression of Keap1 reversed Nrf2-activated anti-lipid peroxidation. Additionally, Cyn activated the adenosine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)3 signaling pathway, which exhibits a protective effect on APAP-induced ALI. These findings propose that Cyn alleviates APAP-induced ALI by enhancing the Keap1/Nrf2-mediated lipid peroxidation defense via activation of the AMPK/SIRT3 signaling pathway.

Beware of atrial pacing-induced ventricular depolarization: A case of lead malfunction.

Although ventricular capture during the atrial threshold test is possible, there are rare reports on the insulation defect and inactive leads thereof. In this case, we present a pacemaker-dependent patient with a history of pacemaker generator replacements. The patient experienced ventricular capture induced by atrial pacing due to adhesion of the atrial and ventricular leads with an insulation defect. The atrial lead was abandoned and a new lead was implanted. However, there was a significant decrease in ventricular impedance detected shortly after the new lead was implanted. When observing the phenomenon of atrial pacing-induced ventricular depolarization, one uncommon reason to consider is lead adhesive wear. It is important to pay attention to the contact and bending sites of the leads.

UBDP1 pseudogene and UBD network competitively bind miR­6072 to promote glioma progression.

Increasing evidence suggests that pseudogenes play crucial roles in various cancers, yet their functions and regulatory mechanisms in glioma pathogenesis remain enigmatic. In the present study, a novel pseudogene was identified, UBDP1, which is significantly upregulated in glioblastoma and positively correlated with the expression of its parent gene, UBD. Additionally, high levels of these paired genes are linked with a poor prognosis for patients. In the present study, clinical samples were collected followed by various analyses including microarray for long non­coding RNAs, reverse transcription­quantitative PCR, fluorescence in situ hybridization and western blotting. Cell lines were authenticated and cultured then subjected to various assays for proliferation, migration, and invasion to investigate the molecular mechanisms. Bioinformatic tools identified miRNA targets, and luciferase reporter assays validated these interactions. A tumor xenograft model in mice was used for in vivo studies. In vitro and in vivo studies have demonstrated that UBDP1, localized in the cytoplasm, functions as a tumor­promoting factor influencing cell proliferation, migration, invasion and tumor growth. Mechanistic investigations have indicated that UBDP1 exerts its oncogenic effects by decoying miR­6072 from UBD mRNA, thus forming a competitive endogenous RNA network, which results in the enhanced oncogenic activity of UBD. The present findings offered new insights into the role of pseudogenes in glioma progression, suggesting that targeting the UBDP1/miR­6072/UBD network may serve as a potential therapeutic strategy for glioma patients.

Chickpea-Derived Modified Antimicrobial Peptides KTA and KTR Inactivate Staphylococcus aureus via Disrupting Cell Membrane and Interfering with Peptidoglycan Synthesis.

The widespread bacterial contamination caused by foodborne pathogens has continuously driven the development of advanced and potent food antimicrobial agents. In this study, two novel antimicrobial peptides (AMPs) named KTA and KTR were obtained by modifying a natural AMP, Leg2, from chickpea storage protein legumin hydrolysates. They were further predicted to be stable hydrophobic cationic AMPs of α-helical structure with no hemolytic toxicity by several online servers. Moreover, the AMPs exerted superior antibacterial activity against two representative Staphylococcus aureus strains thanks to the increased hydrophobicity and positive charge, with minimum inhibition concentration value (4.74-7.41 µM) significantly lower than that of Leg2 (>1158.70 µM). Further, this study sought to elucidate the specific antimicrobial mechanism against Gram-positive bacteria. It was found that the electrostatic interactions of the AMPs with peptidoglycan were vital for peptide activity in combating Gram-positive bacteria. Subsequently, the cell membrane of S. aureus cells was irreversibly disrupted by increasing permeability and impairing membrane components, which led to the massive release of intracellular substances and eventual cell death. Overall, this work demonstrated that KTA and KTR were active against Gram-positive bacteria via peptidoglycan targeting and membrane-disruptive mechanisms and paved the way for expanding their application potential to alleviate food contamination.

Comparison of the safety and efficacy of Neuroform Atlas stent deployed via Gateway balloon catheter and microcatheter for the treatment of intracranial stenosis.

OBJECTIVE: This study aimed to compare the safety and efficacy of the Atlas stent released by the Gateway catheter and microcatheter in the treatment of intracranial stenosis (IS). METHODS: The primary efficacy and safety outcomes were the in-stent restenosis (ISR) rate and post-procedural stroke or death within one month. RESULTS: Atlas stents were deployed using the Gateway catheter and microcatheter in 19 (57.6 %) and 14 (42.4 %) procedures, respectively. Follow-up imaging data were available for 26 patients; the incidence of ISR was 15.4 %, and the ISR rate was higher, though not significantly, in the microcatheter group than in the Gateway group (30.0% vs. 6.25 %, P = .39). Clinical follow-up data were available for 30 patients; the post-procedural stroke rate was 3.3 % within one month and 13.3 % from one month to one year. The post-procedural stroke rate within one month was higher, though not significantly, in the microcatheter group than in the Gateway group (7.7% vs. 0 %, P = .43). The Gateway group had a significantly lower rate of post-procedural stroke in the same territory than that of the microcatheter group (0% vs. 30.8 %, P = .026). A higher incidence of residual stenosis <30 % was found in the non-ISR group than in the ISR group (72.2% vs. 0 %, P = .014). CONCLUSIONS: This study provides preliminary evidence that the Atlas stent is safe and effective for IS treatment. The use of the Gateway catheter to deliver the Atlas stent appears to be safer than using microcatheter. The incidence of ISR may be related to the degree of the residual stenosis.

Determination of the refractive-index change in the excited state based on transient absorption microscopy.

Photoinduced excited-state carriers can affect both the absorption coefficient and refractive index of materials and influence the performance of photoelectric devices. Femtosecond time-resolved pump-probe transient absorption (TA) spectroscopy is usually used to detect carrier dynamics and excited-state absorption coefficients; however, measurements of transient refractive-index change are still difficult. We propose a method for determining the excited-state refractive-index change using TA microscopy. In TA measurements, a Fabry-Pérot cavity formed by the front and back surfaces of the sample could lead to interference of the probe light. As the wavelength of standing waves in the Fabry-Pérot cavity is closely related to the refractive index, the carrier-induced excited-state refractive-index change was obtained by comparing the transmission probe spectra between the ground and excited states. The proposed method was used to study the dynamics of excited-state refractive-index change in a perovskite film.

Epithelial N-methyl-D-aspartate (NMDA) receptors mediate renal vasodilation by affecting kidney autoregulation.

Background: N-methyl-D-aspartate receptor (NMDAR) are amino acid receptors that are well studied in brain physiology; however, their role in kidney is poorly understood. Nonetheless, NMDAR inhibitors can increase serum K+ and reduce GFR, which suggests they have an important physiological role in the kidney. We hypothesized that NMDARs in the distal nephron induce afferent-arteriole vasodilation through the vasodilator mechanism connecting-tubule-glomerular feedback (CNTGF) that involves ENaC activation. Methods and results: Using a tubule-specific transcriptome database combined with molecular biology and microscopy techniques, we showed kidney expression of NMDAR subunits along the nephron and specifically in ENaC-positive cells. This receptor is expressed in both male and female mice, with higher abundance in females (p=0.02). Microperfusing NMDAR agonists into the connecting tubule induced afferent-arteriole vasodilation (EC50 10.7 vs. 24.5 mM; p<0.001) that was blunted or eliminated with the use of NMDAR blocker MK-801 or with the ENaC inhibitor Benzamil, indicating a dependence on CNTGF of the NMDAR-induced vasodilation. In vivo, we confirmed this CNTGF-associated vasodilation using kidney micropuncture (Stop-flow pressure 37.9±2.6 vs. 28.6±1.9 mmHg, NMDAR agonist vs vehicle; p<0.01). We explored NMDAR and ENaC channel interaction by using mpkCCD cells and split-open connecting tubules. We observed increased amiloride-sensitive current following NMDAR activation that was prevented by MK-801 (1.14 vs. 0.4 µAmp; p=0.03). In split-open tubules, NMDAR activation increased ENaC activity (Npo Vehicle vs. NMDA; p=0.04). Conclusion: NMDARs are expressed along the nephron, including ENaC-positive cells, with higher expression in females. Epithelial NMDAR mediates renal vasodilation through the connecting-tubule-glomerular feedback, by increasing ENaC activity.

Factors affecting the accuracy of genomic prediction in joint pig populations.

Genomic prediction (GP) has greatly advanced animal and plant breeding over the past two decades. GP in joint populations is a feasible method to improve the accuracy of genomic estimated breeding values in small populations. However, there is still a need to understand the factors that influence GP in joint populations. This study used simulated data and real data from Duroc pig populations to examine the impact of linkage disequilibrium (LD), causal variants effect sizes (CVESs), and minor allele frequencies (MAF) of SNPs on the accuracy of genomic prediction in joint populations. Three prediction methods were used: genomic best linear unbiased prediction (GBLUP), single-step GBLUP and multi-trait GBLUP. Results from the simulated datasets showed that the accuracies of GP in joint populations were always higher than those in a single population when only LD inconsistencies existed. However, single-step GBLUP accuracy in joint populations decreased as the correlation of MAF between populations decreased, while the accuracy of GBLUP is consistently higher in joint populations than in a single population. As the correlation of CVES between populations decreased, the accuracy of both GBLUP and single-step GBLUP in joint populations declined. Analysis of real Duroc populations showed low genetic correlation, similar to the simulated relationship between the most distant populations. In most cases in Duroc populations, GP have higher accuracies in joint populations than in individual population. In conclusion, the consistency of CVES plays a more important role in multi-population GP. The genetic relatedness of the Duroc populations is so weak that the prediction accuracy of GP in joint populations is reduced in some traits. Multi-trait GBLUP is a competitive method for the joint breeding evaluation.

MiR-484 promotes the malignant progression of glioma by inhibiting CDKN2A expression.

INTRODUCTION: Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) is involved in glioma progression, but the specific molecular mechanism of CDKN2A in glioma cell migration and invasion needs to be further explored. MATERIAL AND METHODS: Data related to CDKN2A expression and glioma overall survival were obtained from The Cancer Genome Atlas (TCGA) database. Then, CDKN2A expression in glioma tissues/cells or paracancer tissues/astrocytes was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blot. Afterwards, Wound healing, Transwell and tube formation assay were performed to identify the invasion, migration and angiogenesis of glioma cells, respectively. TargetScan database predicted the targeted binding between miR-484 and CDKN2A, which was verified by dual luciferase reporter gene assay. Western blot and qRT-PCR were performed to detect the expression of VEGF, E-cadherin, N-cadherin and Vimentin in glioma cells. RESULTS: CDKN2A was low-expressed in glioma tissue/cells as compared to paracancer tissue/astrocytes, and was strongly associated to the poor prognosis of glioma. Further studies found that down-regulation of CDKN2A could promote migration, invasion and angiogenesis of glioma cells. Besides, miR-484 was high-expressed in glioma cells compared to astrocytes. Up-regulation of miR-484 could enhance migration, invasion and angiogenesis of glioma cells. In addition, up-regulated miR-484 suppressed the expression of E-cadherin, and promoted the expression of N-cadherin, Vimentin and VEGF. However, there was negative regulation of miR-484 and CDKN2A, and CDKN2A could partially offset the effect of miR-484. CONCLUSIONS: MiR-484 promoted cell migration, invasion and angiogenesis by inhibiting CDKN2A expression.

Visualization of Hot Carrier Dynamics in a Single CsPbBr3 Perovskite Microplate Using Femtosecond Kerr-Gated Wide-Field Fluorescence Spectroscopy.

Lead halide perovskites (LHPs) have excellent semiconductor properties. They have been used in many applications such as solar cells. Recently, the hot carrier dynamics in this type of material have received much attention as they are useful for enhancing the performance of optoelectrical devices fabricated from it. Here, we study the ultrafast hot carrier dynamics of a single CsPbBr3 microplate using femtosecond Kerr-gated wide-field fluorescence spectroscopy. The transient photoluminescence spectra have been measured under a variety of excitation fluences. The temporal evolution of bandgap renormalization and the competition between hot carrier cooling and the recovery of the renormalized bandgap are clearly revealed.

Arm-only combined transarterial and transvenous access for neurointerventional procedures: a double-center retrospective study.

OBJECTIVE: This study aims to share our experience with the arm-only combined transarterial and transvenous access approach for neurointerventional procedures and evaluate its efficacy and safety. METHODS: The arm-only combined transarterial and transvenous access approach was performed using the right/bilateral proximal radial arteries and the right forearm superficial vein system, guided by ultrasonic guidance. Arterial access closure was achieved using a transradial band radial compression device, while manual compression was utilized for venous approach closure. RESULTS: Thirteen procedures were successfully performed using the arm-only combined transarterial and transvenous access approach, yielding favorable outcomes. The procedures included dural arteriovenous fistula embolization (seven cases), cerebral arteriovenous malformation embolization (four cases), venous sinus thrombosis catheter-directed thrombolysis and intravenous thrombectomy (one case), and cerebral venous sinus stenosis manometry (one case). All procedures were uneventful, allowing patients to ambulate on the same day. At discharge, all patients exhibited modified Rankin scores of 0-2, without any access site or perioperative complications. CONCLUSION: This double-center study preliminarily demonstrates the feasibility and safety of arm-only combined transarterial and transvenous access applied in neurointerventional procedures for complicated cerebrovascular diseases. The proximal radial artery and forearm superficial vein are recommended as the primary access sites. Unobstructed compression is strongly recommended for radial approach closure. ADVANCES IN KNOWLEDGE: This study aimed to add evidence and experience on the arm-only combined transarterial and transvenous access, as a new approach, for neurointerventional treatment that required arteriovenous approaches.

Physiochemical characteristics, morphology, and lubricating properties of size-specific whey protein particles by acid or ion aggregation.

To investigate the influence of particle characteristics on their lubricating capacity, microparticles of controlled size (~300, ~700, and ~1900 nm) were prepared from whey proteins using two different approaches: reducing the pH and increasing the calcium ion concentration. The physiochemical, morphological, and tribological properties of the two types of particles were determined. Both treatments pronouncedly decreased the absolute value of zeta-potential and surface hydrophobicity of whey proteins, with calcium ions showing a more severe effect on zeta-potential. The viscosity of the particle suspensions increased with particle size, and ion-induced samples showed higher viscosity than acid-induced ones. Morphology investigation revealed that particle aggregation and irregularity increased with particle size increase. Distinct lubricating behaviors were observed for the two particle types within different size ranges. Viscosity played a more important role in lubrication when the particle size was small, while particle characteristics became more dominant for large particles.

Development of a Dihydroquinoline-Pyrazoline GluN2C/2D-Selective Negative Allosteric Modulator of the N-Methyl-d-aspartate Receptor.

Subunit-selective inhibition of N-methyl-d-aspartate receptors (NMDARs) is a promising therapeutic strategy for several neurological disorders, including epilepsy, Alzheimer's and Parkinson's disease, depression, and acute brain injury. We previously described the dihydroquinoline-pyrazoline (DQP) analogue 2a (DQP-26) as a potent NMDAR negative allosteric modulator with selectivity for GluN2C/D over GluN2A/B. However, moderate (<100-fold) subunit selectivity, inadequate cell-membrane permeability, and poor brain penetration complicated the use of 2a as an in vivo probe. In an effort to improve selectivity and the pharmacokinetic profile of the series, we performed additional structure-activity relationship studies of the succinate side chain and investigated the use of prodrugs to mask the pendant carboxylic acid. These efforts led to discovery of the analogue (S)-(-)-2i, also referred to as (S)-(-)-DQP-997-74, which exhibits >100- and >300-fold selectivity for GluN2C- and GluN2D-containing NMDARs (IC50 0.069 and 0.035 µM, respectively) compared to GluN2A- and GluN2B-containing receptors (IC50 5.2 and 16 µM, respectively) and has no effects on AMPA, kainate, or GluN1/GluN3 receptors. Compound (S)-(-)-2i is 5-fold more potent than (S)-2a. In addition, compound 2i shows a time-dependent enhancement of inhibitory actions at GluN2C- and GluN2D-containing NMDARs in the presence of the agonist glutamate, which could attenuate hypersynchronous activity driven by high-frequency excitatory synaptic transmission. Consistent with this finding, compound 2i significantly reduced the number of epileptic events in a murine model of tuberous sclerosis complex (TSC)-induced epilepsy that is associated with upregulation of the GluN2C subunit. Thus, 2i represents a robust tool for the GluN2C/D target validation. Esterification of the succinate carboxylate improved brain penetration, suggesting a strategy for therapeutic development of this series for NMDAR-associated neurological conditions.

Effect of Flaxseed Gum on the Textural, Rheological, and Tribological Properties of Acid-Induced Soy Protein Isolate Gels.

This study aimed to investigate the effects of incorporating different concentrations of flaxseed gum (FG) into acid-induced soy protein isolate (SPI) gels. The investigation focused on assessing the effects of FG on the textural, rheological, and tribological properties of the resultant SPI gels. The results showed that adding a small amount of FG (0.05%) to the SPI gel system increased the storage modulus (G') and enhanced gelation while improving textural properties including hardness, viscosity, elasticity, and adhesion. Moreover, these gels exhibited strong water-holding capacity, a desirable property in various food products. However, when the concentration was increased to 0.3%, the WHC of the gel decreased, as did the hardness and cohesiveness. The particle size of the gel also increased with increasing concentration. Tribological investigations revealed that at 0.05-0.2% FG addition, the coefficient of friction (µ) of the composite gel was decreased compared to the pure SPI gel. In the sliding speed range of 1-100 mm/s, the coefficient of friction gradually increased with increasing concentration. When the FG concentration was 0.05%, the µ of the gel system was the lowest. In summary, low concentration of FG (0.05%) was found to play an important role in improving the properties of SPI gel, including enhancing textural, rheological, and lubricating properties.

Predictors of pacing-induced cardiomyopathy detection and outcomes demonstration after conduction system pacing upgrade on patients with long-term persistent atrial fibrillation.

OBJECTIVE: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF). METHODS: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. RESULTS: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up. CONCLUSION: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population.

The feasibility and safety of his-purkinje conduction system pacing in patients with heart failure with severely reduced ejection fraction.

Objective: The purpose of this study was to evaluate the feasibility and outcomes of conduction system pacing (CSP) in patients with heart failure (HF) who had a severely reduced left ventricular ejection fraction (LVEF) of less than 30% (HFsrEF). Methods: Between January 2018 and December 2020, all consecutive HF patients with LVEF < 30% who underwent CSP at our center were evaluated. Clinical outcomes and echocardiographic data [LVEF and left ventricular end-systolic volume (LVESV)], and complications were all recorded. In addition, clinical and echocardiographic (≥5% improvement in LVEF or ≥15% decrease in LVESV) responses were assessed. The patients were classified into a complete left bundle branch block (CLBBB) morphology group and a non-CLBBB morphology group according to the baseline QRS configuration. Results: Seventy patients (66 ± 8.84 years; 55.7% male) with a mean LVEF of 23.2 ± 3.23%, LVEDd of 67.33 ± 7.47 mm and LVESV of 212.08 ± 39.74 ml were included. QRS configuration at baseline was CLBBB in 67.1% (47/70) of patients and non-CLBBB in 32.9%. At implantation, the CSP threshold was 0.6 ± 0.3 V @ 0.4 ms and remained stable during a mean follow-up of 23.43 ± 11.44 months. CSP resulted in significant LVEF improvement from 23.2 ± 3.23% to 34.93 ± 10.34% (P < 0.001) and significant QRS narrowing from 154.99 ± 34.42 to 130.81 ± 25.18 ms (P < 0.001). Clinical and echocardiographic responses were observed in 91.4% (64/70) and 77.1% (54/70) of patients. Super-response to CSP (≥15% improvement in LVEF or ≥30% decrease in LVESV) was observed in 52.9% (37/70) of patients. One patient died due to acute HF and following severe metabolic disorders. Baseline BNP (odds ratio: 0.969; 95% confidence interval: 0.939-0.989; P = 0.045) was associated with echocardiographic response. The proportions of clinical and echocardiographic responses in the CLBBB group were higher than those in the non-CLBBB group but without significant statistical differences. Conclusions: CSP is feasible and safe in patients with HFsrEF. CSP is associated with a significant improvement in clinical and echocardiographic outcomes, even for patients with non-CLBBB widened QRS.

Conduction system pacing improves the outcomes on patients with high percentage of ventricular pacing and heart failure with mildly reduced ejection fraction.

Aims: This study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF. Methods: Patients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%-49%. Results: CSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification (P < 0.001), LVEF (42.45 ± 1.84% vs. 49.97 ± 3.57%, P < 0.001) and left ventricular end diastolic diameter (LVEDD) (55.59 ± 6.17 mm vs. 51.66 ± 3.48 mm, P < 0.001) improved significantly. During follow-up, more than half (39/64,60.9%) of patients returned to normal LVEF and LVEDD with complete reverse remodeling. The pacing threshold in LBBP was lower (0.90 ± 0.27 V@0.4 ms vs. 1.61 ± 0.71 V@0.4 ms, P < 0.001) than that in HBP. No perforation, electrode dislodging, thrombosis or infection was observed during follow-up. Conclusions: CSP could improve the clinical outcomes in patients with HFmrEF and a high percentage of ventricular pacing. LBBP might be a better choice because of its feasibility and safety, especially in patients with infranodal atrioventricular block.

Genetic variation in ZmWAX2 confers maize resistance to Fusarium verticillioides.

Fusarium verticillioides (F. verticillioides) is a widely distributed phytopathogen that incites multiple destructive diseases in maize, posing a grave threat to corn yields and quality worldwide. However, there are few reports of resistance genes to F. verticillioides. Here, we reveal that a combination of two single nucleotide polymorphisms (SNPs) corresponding to ZmWAX2 gene associates with quantitative resistance variations to F. verticillioides in maize through a genome-wide association study. A lack of ZmWAX2 compromises maize resistance to F. verticillioides-caused seed rot, seedling blight and stalk rot by reducing cuticular wax deposition, while the transgenic plants overexpressing ZmWAX2 show significantly increased immunity to F. verticillioides. A natural occurrence of two 7-bp deletions within the promoter increases ZmWAX2 transcription, thus enhancing maize resistance to F. verticillioides. Upon Fusarium stalk rot, ZmWAX2 greatly promotes the yield and grain quality of maize. Our studies demonstrate that ZmWAX2 confers multiple disease resistances caused by F. verticillioides and can serve as an important gene target for the development of F. verticillioides-resistant maize varieties.