Mechanochemical Fabrication of Full-Color Luminescent Materials from Aggregation-Induced Emission Prefluorophores for Information Storage and Encryption.

The development of luminescent materials via mechanochemistry embodies a compelling yet intricate frontier within materials science. Herein, we delineate a methodology for the synthesis of brightly luminescent polymers, achieved by the mechanochemical coupling of aggregation-induced emission (AIE) prefluorophores with generic polymers. An array of AIE moieties tethered to the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical are synthesized as prefluorophores, which initially exhibit weak fluorescence due to intramolecular quenching. Remarkably, the mechanical coupling of these prefluorophores with macromolecular radicals, engendered through ball milling of generic polymers, leads to substantial augmentation of fluorescence within the resultant polymers. We meticulously evaluate the tunable emission of the AIE-modified polymers, encompassing an extensive spectrum from the visible to the near-infrared region. This study elucidates the potential of such materials in stimuli-responsive systems with a focus on information storage and encryption displays. By circumventing the complexity inherent to the conventional synthesis of luminescent polymers, this approach contributes a paradigm to the field of AIE-based polymers with implications for advanced technological applications.

Novel Near-Infrared-II In Vivo Visualization Revealed Rapid Calcium Intestine Turnover in Daphnia magna with Delayed Impact by Cadmium and Acidification.

Calcium is a highly demanded metal, and its transport across the intestine of Daphnia magna remains a significant unresolved question. Due to technical constraints, the visualization of the kinetic process of Ca passage through D. magna has been challenging. Here, we developed the second near-infrared Ca sensor (NIR-II Ca) and conducted real-time in vivo imaging of Ca in daphnids with a high signal-to-noise ratio, deep tissue penetration, and minimal damage. Through the utilization of the NIR-II Ca sensor, we for the first time visualized and quantified the kinetic process of Ca passage in the intestine in real time. The results revealed that trophically available Ca passed through the intestines in 24 h, whereas waterborne Ca required only 35 min. This rapid "flushing through" mechanism established waterborne Ca as the primary source of Ca absorption. However, environmental stressors such as water acidification and cadmium significantly delayed the Ca passage and absorption. The development of NIR imaging and sensors allows for real-time dynamic visualization of contaminants/nutrients in organisms and holds great potential as a powerful tool for future studies into material kinetic processes in living animals.

Acid Radical Tolerance of Silane Coatings on Calcium Silicate Hydrate Surfaces in Aggressive Environments: The Role of Nitrate/Sulfate Ratio.

Silane is known as an effective coating for enhancing the resistance of concrete to harmful acids and radicals that are usually produced by the metabolism of microorganisms. However, the mechanism of silane protection is still unclear due to its nanoscale attributes. Here, the protective behavior of silane on the calcium silicate hydrate (C-S-H) surface is examined under the attack environment of nitrate/sulfate ions using molecular dynamics simulations. The findings revealed that silane coating improved the resistance of C-S-H to nitrate/sulfate ions. This resistance is considered the origin of silane protection against harmful ion attacks. Further research on the details of molecular structures suggests that the interaction between the oxygen in the silane molecule and the calcium in C-S-H, which can prevent the coordination of sulfate and nitrate to calcium on the C-S-H surface, is the cause of the silane molecules' strong adsorption. These results are also proved in terms of free energy, which found that the adsorption free energy on the C-S-H surface followed the order silane > sulfate > nitrate. This research confirms the excellent protection performance of silane on the nanoscale. The revealed mechanism can be further used to help the development of high-performance composite coatings.

Prognosis and immunotherapy significances of a cancer-associated fibroblasts-related gene signature in lung adenocarcinoma.

Cells associated with cancer (CAFs) contribute significantly to the stroma of a tumor microenvironment (TME), which is related to the occurrence, treatment, and prognosis of lung adenocarcinoma (LUAD). Therefore, this study investigated the function of CAF-associated genes in the microenvironment of LUAD. The Cancer Genome Atlas (TCGA) database was used to download RNA-seq data from the TCGA Lung Adenocarcinoma cohort (TCGA-LUAD). The GSE68465 dataset, as the external validation set, was from the Gene Expression Omnibus (GEO) database. Besides, CAF-associated genes were sourced from the GeneCards and Molecular Signatures Database (MsigDB). For LUAD, differentially expressed CAF-related genes were selected from overlapping CAF and LUAD patient and control samples. Next, LASSO and Univariate Cox analyses were used to construct the risk model. Additionally, an analysis of Cox regression was used to construct a nomogram. Next, the immune infiltration in malignant tumour tissues was compared between high- and low-risk groups using Estimation of STromal and Immune cells in MAlignant Tumours (ESTIMATE) tissues and Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). The sensitivity differences of immunotherapy between the two risk groups were estimated by Tumor Immune Dysfunction and Exclusion (TIDE), and compared by rank-sum test. Finally, the model genes were detected by fluorescent real-time quantitative polymerase chain reaction (qRT-PCR). A total of 57 DE-CAFGs were acquired, and 9 of them (SHCBP1, CCNA2, AKAP12, CCNB1, GALNT3, SCGB1A1, CPS1, CDC6, and CXCL13) were selected as prognostic biomarkers. The Cox independent prognosis revealed the RiskScore and Stage were the two LUAD independent prognosis factors Moreover, 11 types of immune cells (memory B cells, resting natural killer cells (NK cells), Eosinophils, Macrophages M0, CD4 memory resting T cells, CD4 memory activated T cells, resting Mast cells, naive B cells, T cells regulatory (Tregs), neutrophils, and plasma cell), and 18 human leukocyte antigen (HLA) genes were different with the two risk groups. Lastly, the TIDE analysis showed differences between the two risk groups for TIDE, T cell dysfunction, and T cell exclusion, PD-L1 treatment scores. Lastly, Both LUAD and normal samples expressed the 9 model genes differently. A CAF-related prognostic model was constructed, which may have potential immunotherapy guiding significance for LUAD patients.

Turn-on Circularly Polarized Luminescence in Chiral Indium Chlorides by 5s2 Metal Centers.

Introducing chirality into the metal-halide hybrids has enabled many emerging properties including chiroptical activity, spin-dependent transport, and ferroelectricity. However, most of the chiral metal-halide hybrids to date are non-emissive, and the underlying mechanism remains elusive. Here, we show a new strategy to turn on the circularly polarized luminescence (CPL) in chiral metal-halide hybrids. We demonstrate that alloying Sb3+ into chiral indium-chloride hybrids dramatically increases the photoluminescence quantum yield in two new series of chiral indium-antimony chlorides. These materials exhibit strong CPL signals with tunable energy and a high dissymmetry factor up to 1.5×10-2 . Mechanistic studies reveal that the emission originates from the self-trapped excitons centered in 5s2 Sb3+ . Moreover, near-ultraviolet pumped white light is demonstrated with a polarization up to 6.0 %. Our work demonstrates new strategies towards highly luminescent chiral metal-halide hybrids.

Biodegradable, Breathable Leaf Vein-Based Tactile Sensors with Tunable Sensitivity and Sensing Range.

Resistive pressure sensors have been widely studied for application in flexible wearable devices due to their outstanding pressure-sensitive characteristics. In addition to the outstanding electrical performance, environmental friendliness, breathability, and wearable comfortability also deserve more attention. Here, a biodegradable, breathable multilayer pressure sensor based piezoresistive effect is presented. This pressure sensor is designed with all biodegradable materials, which show excellent biodegradability and breathability with a three-dimensional porous hierarchical structure. Moreover, due to the multilayer structure, the contact area of the pressure sensitive layers is greatly increased and the loading pressure can be distributed to each layer, so the pressure sensor shows excellent pressure-sensitive characteristics over a wide pressure sensing range (0.03-11.60 kPa) with a high sensitivity (6.33 kPa-1 ). Furthermore, the sensor is used as a human health monitoring equipment to monitor the human physiological signals and main joint movements, as well as be developed to detect different levels of pressure and further integrated into arrays for pressure imaging and a flexible musical keyboard. Considering the simple manufacturing process, the low cost, and the excellent performance, leaf vein-based pressure sensors provide a good concept for environmentally friendly wearable devices.

PEX1 is a mediator of α1-adrenergic signaling attenuating doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is a potent chemotherapeutic agent used for cancer treatment, however, DOX-induced cardiotoxicity is a serious clinical problem because it causes acute and chronic heart dysfunction. Many studies have indicated that the α1-adrenergic receptor protects the heart from pathologic stress through activation survival signaling, however, the mechanism remains largely unknown. Previous studies have detected that the phenylephrine-induced complex-1 (PEX1) transcription factor, also known as zinc-finger protein 260 (Zfp260), is an effector of α1-adrenergic signaling in cardiac hypertrophy. Our present study aimed to investigate the role and underlying mechanism of PEX1 in cardiomyocyte survival during DOX-induced cardiotoxicity. Mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. We found that PEX1 expression was downregulated in DOX-treated murine hearts. PEX1 deficiency resulted in increased apoptosis, and conversely, PEX1 overexpression alleviated apoptosis induced by DOX in primary cardiomyocytes, as well as upregulated antiapoptotic genes such as BCL-2 and BCL-XL. Mechanistically, we identified that PEX1 might exert its antiapoptosis effect by playing a pivotal role in the action of α1-adrenergic signaling activation, which depends on the presence of GATA-4. Based on these findings, we supposed that PEX1 may be a novel transcription factor involved in cardiac cell survival and a promising candidate target for DOX-induced cardiotoxicity.

Identification of TBX2 and TBX3 variants in patients with conotruncal heart defects by target sequencing.

BACKGROUND: Conotruncal heart defects (CTDs) are heterogeneous congenital heart malformations that result from outflow tract dysplasia; however, the genetic determinants underlying CTDs remain unclear. Increasing evidence demonstrates that dysfunctional TBX2 and TBX3 result in outflow tract malformations, implying that both of them are involved in CTD pathogenesis. We screened for TBX2 and TBX3 variants in a large cohort of CTD patients (n = 588) and population-matched healthy controls (n = 300) by target sequencing and genetically analyzed the expression and function of these variants. RESULTS: The probably damaging variants p.R608W, p.T249I, and p.R616Q of TBX2 and p.A192T, p.M65L, and p.A562V of TBX3 were identified in CTD patients, but none in controls. All altered amino acids were highly conserved evolutionarily. Moreover, our data suggested that mRNA and protein expressions of TBX2 and TBX3 variants were altered compared with those of the wild-type. We screened PEA3 and MEF2C as novel downstream genes of TBX2 and TBX3, respectively. Functional analysis revealed that TBX2R608W and TBX2R616Q variant proteins further activated HAS2 promoter but failed to activate PEA3 promoter and that TBX3A192T and TBX3A562V variant proteins showed a reduced transcriptional activity over MEF2C promoter. CONCLUSIONS: Our results indicate that the R608W and R616Q variants of TBX2 as well as the A192T and A562V variants of TBX3 contribute to CTD etiology; this was the first association of variants of TBX2 and TBX3 to CTDs based on a large population.

The Application of Regenerated Silk Fibroin in Tissue Repair.

Silk fibroin (SF) extracted from silk is non-toxic and has excellent biocompatibility and biodegradability, making it an excellent biomedical material. SF-based soft materials, including porous scaffolds and hydrogels, play an important role in accurately delivering drugs to wounds, creating microenvironments for the adhesion and proliferation of support cells, and in tissue remodeling, repair, and wound healing. This article focuses on the study of SF protein-based soft materials, summarizing their preparation methods and basic applications, as well as their regenerative effects, such as drug delivery carriers in various aspects of tissue engineering such as bone, blood vessels, nerves, and skin in recent years, as well as their promoting effects on wound healing and repair processes. The authors expect SF soft materials to play an important role in the field of tissue repair.

Lipidomics analysis of bone marrow in a mouse model of postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) is a major public health problem worldwide, afflicting many postmenopausal women. Although many studies have focused on the biological role of individual lipids in osteoporosis, no studies have systematically elucidated the lipid profile of osteoporosis. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology based on multiple reaction monitoring (MRM) method was used to compare the levels of lipid molecules in bone marrow cells of osteoporotic mice (OVX) group and sham-operation (Sham) group. Principal component analysis (PCA) was used for multivariate statistics. Differential lipids were obtained by bar graph, heatmap and volcano map. A total of 400 lipid molecules were identified. A total of 199 lipid molecules were identified to be associated with PMOP, including 6 phospholipids and 3 sphingolipids. These differential lipid molecules provide a systematic lipid profile for osteoporosis, which helps to discover new candidate osteoporosis biomarkers, and their changes at the molecular level can be used as new targets for diagnosis or prevention.

Inhalable cardiac targeting peptide modified nanomedicine prevents pressure overload heart failure in male mice.

Heart failure causes considerable morbidity and mortality worldwide. Clinically applied drugs for the treatment of heart failure are still severely limited by poor delivery efficiency to the heart and off-target consumption. Inspired by the high heart delivery efficiency of inhaled drugs, we present an inhalable cardiac-targeting peptide (CTP)-modified calcium phosphate (CaP) nanoparticle for the delivery of TP-10, a selective inhibitor of PDE10A. The CTP modification significantly promotes cardiomyocyte and fibroblast targeting during the pathological state of heart failure in male mice. TP-10 is subsequently released from TP-10@CaP-CTP and effectively attenuates cardiac remodelling and improved cardiac function. In view of these results, a low dosage (2.5 mg/kg/2 days) of inhaled medication exerted good therapeutic effects without causing severe lung injury after long-term treatment. In addition, the mechanism underlying the amelioration of heart failure is investigated, and the results reveal that the therapeutic effects of this system on cardiomyocytes and cardiac fibroblasts are mainly mediated through the cAMP/AMPK and cGMP/PKG signalling pathways. By demonstrating the targeting capacity of CTP and verifying the biosafety of inhalable CaP nanoparticles in the lung, this work provides a perspective for exploring myocardium-targeted therapy and presents a promising clinical strategy for the long-term management of heart failure.

[Mutation of the envelope stress-responsive protein CpxA capable of regulating the antimicrobial resistance and virulence of bacteria].

CpxA is a key member of the envelope stress-responsive Cpx two-component system ubiquitous in Gram-negative bacteria. It is responsible for signal sensing and has dual activities of phosphatase and kinase. CpxA has been revealed to participate in the regulation of physiological processes such as virulence and antimicrobial resistance of bacteria. In recent years, the development of novel antimicrobials targeting CpxA has attracted much attention. Drugs developed based on inhibition of the phosphatase activity of CpxA have shown effectiveness in the treatment of urinary tract infections caused by Escherichia coli. This review introduces the structure and functional domains of CpxA and the activation of Cpx pathways by CpxA. Furthermore, it summarizes the roles of CpxA in the development of antimicrobial resistance and the regulation of bacterial virulence and reviews the latest progress in the development of new antimicrobials targeting this protein. It is expected to assist in the exploration of CpxA-targeting anti-infection strategies for severely antimicrobial-resistant bacteria whose clinical infections are of urgent need to be controlled.

Mitochondria-Targeting AIEgens as Pyroptosis Inducers for Boosting Type-I Photodynamic Therapy of Tongue Squamous Cell Carcinoma.

The development of a photosensitizer (PS) that induces pyroptosis could be a star for photodynamic therapy (PDT), particularly with type-I PSs that produce reactive oxygen species (ROS) in a hypoxic tumor microenvironment. Since pyroptosis is a recently characterized cell death pathway, it holds promise for advancing PDT in oncology, with PSs playing a critical role. Herein, we develop a PS named Th-M with aggregation-induced emission (AIE) characteristics for type-I PDT against tongue squamous cell carcinoma (TSCC). Th-M stands out for its exceptional mitochondrial-targeting ability, which triggers mitochondrial dysfunction and leads to Caspase-3 and Gasdermin E (GSDME) cleavage under white light irradiation, inducing pyroptosis in TSCC cells. Our studies verify the effectiveness of Th-M in destroying cancer cells in vitro and suppressing tumor growth in vivo while also demonstrating a favorable biosafety profile. This work pioneers the application of Th-M as a mitochondria-targeted, type-I PS that leverages the mechanism of pyroptosis, offering a potent approach for the treatment of TSSC with promising implications for future PDT of cancers.

ESCRT-III Component CHMP4C Attenuates Cardiac Hypertrophy by Targeting the Endo-Lysosomal Degradation of EGFR.

BACKGROUND: Cardiac hypertrophy and subsequent heart failure impose a considerable burden on public health worldwide. Impaired protein degradation, especially endo-lysosome-mediated degradation of membrane proteins, is associated with cardiac hypertrophy progression. CHMP4C (charged multivesicular body protein 4C), a critical constituent of multivesicular bodies, is involved in cellular trafficking and signaling. However, the specific role of CHMP4C in the progression of cardiac hypertrophy remains largely unknown. METHODS: Mouse models with CHMP4C knockout or cardiadc-specific overexpression were subjected to transverse aortic constriction surgery for 4 weeks. Cardiac morphology and function were assessed through histological staining and echocardiography. Confocal imaging and coimmunoprecipitation assays were performed to identify the direct target of CHMP4C. An EGFR (epidermal growth factor receptor) inhibitor was administrated to determine whether effects of CHMP4C on cardiac hypertrophy were EGFR dependent. RESULTS: CHMP4C was significantly upregulated in both pressure-overloaded mice and spontaneously hypertensive rats. Compared with wild-type mice, CHMP4C deficiency exacerbated transverse aortic constriction-induced cardiac hypertrophy, whereas CHMP4C overexpression in cardiomyocytes attenuated cardiac dysfunction. Mechanistically, the effect of CHMP4C on cardiac hypertrophy relied on the EGFR signaling pathway. Fluorescent staining and coimmunoprecipitation assays confirmed that CHMP4C interacts directly with EGFR and promotes lysosome-mediated degradation of activated EGFR, thus attenuating cardiac hypertrophy. Notably, an EGFR inhibitor canertinib counteracted the exacerbation of cardiac hypertrophy induced by CHMP4C knockdown in vitro and in vivo. CONCLUSIONS: CHMP4C represses cardiac hypertrophy by modulating lysosomal degradation of EGFR and is a potential therapeutic candidate for cardiac hypertrophy.

Design of One-for-All Near-Infrared Aggregation-Induced Emission Nanoaggregates for Boosting Theranostic Efficacy.

Fluorescence-guided phototherapy, including photodynamic and photothermal therapy, is considered an emerging noninvasive strategy for cancer treatments. Organic molecules are promising theranostic agents because of their facile construction, simple modification, and good biocompatibility. Organic systems that integrated multifunctionalities in a single component and achieved high efficiency in both imaging and therapies are rarely reported as the inherently competitive energy relaxation pathways are hard to modulate, and fluorescence quenching occurs upon molecular aggregation. Herein, a versatile theranostic platform with near-infrared emission, high fluorescence quantum yield, robust reactive oxygen species production, and excellent photothermal conversion efficiency was developed based on an aggregation-induced emission luminogen, namely, TPA-TBT. In vivo studies revealed that the TPA-TBT nanoaggregates exhibit outstanding photodynamic and photothermal therapy efficacy to ablate tumors inoculated in a mouse model. This work offers a design strategy to develop one-for-all cancer theranostic agents by modulating and utilizing the relaxation energy of excitons in full.

Fast Delivery of Multifunctional NIR-II Theranostic Nanoaggregates Enabled by the Photoinduced Thermoacoustic Process.

Multifunctional nanoaggregates are widely used in cancer phototheranostics. However, it is challenging to construct their multifunctionality with a single component, and deliver them rapidly and efficiently without complex modifications. Herein, a NIR-absorbing small molecule named TBT-2(TP-DPA) is designed and certify its theranostic potentials. Then, their nanoaggregates, which are simply encapsulated by DSPE-PEG, demonstrate a photothermal efficiency of 51% while keeping a high photoluminescence quantum yield in the NIR region. Moreover, the nanoaggregates can be excited and delivered by an 808 nm pulse laser to solid tumors within only 40 min. The delivery efficiency and theranostic efficacy are better than that of the traditional enhanced permeability and retention (EPR) effect (generally longer than 24 hours). This platform is first termed as the photoinduced thermoacoustic (PTA) process, and confirm its application requires both NIR-responsive materials and pulse laser irradiation. This study not only inspires the design of multifunctional nanoaggregates, but also offers a feasible approach to their fast delivery. The platform reported here provides a promising prospect to boost the development of multifunctional theranostic drugs and maximize the efficacy of used medicines for their clinical applications.

Acidic electrolyzed water treatment retards softening and retains cell wall polysaccharides in pulp of postharvest fresh longans and its possible mechanism.

Effects of acidic electrolyzed water (AEW) treatment (pH = 2.5, ACC = 80 mg L-1, 10 min) on pulp firmness, amounts of CWM and CWP, activities and expression of relevant genes of CWDEs in pulp of Fuyan longan during storage at 25 °C were evaluated. Compared to control samples, during storage, AEW-treated fruit retained a higher pulp firmness, prevented WSP formation, reduced the degradation of CSP, cellulose and hemicellulose, and lowered CWDEs activities and their corresponding gene expression. When stored for 5 d, pulp firmness (113.6 g mm-1), CWM (13.9 g kg-1), and CSP (1.4 g kg-1) in AEW-treated fruit displayed the clearly higher contents than those in control samples. These data suggest that AEW treatment can slow down the pulp softening and retain higher pulp CWP levels in postharvest fresh longans, which was because AEW lowered activities of CWDEs and its gene expression levels, and maintained the cell wall structure's integrity.

On-surface synthesis and spontaneous segregation of conjugated tetraphenylethylene macrocycles.

Creating conjugated macrocycles has attracted extensive research interest because their unique chemical and physical properties, such as conformational flexibility, intrinsic inner cavities and aromaticity/antiaromaticity, make these systems appealing building blocks for functional supramolecular materials. Here, we report the synthesis of four-, six- and eight-membered tetraphenylethylene (TPE)-based macrocycles on Ag(111) via on-surface Ullmann coupling reactions. The as-synthesized macrocycles are spontaneously segregated on the surface and self-assemble as large-area two-dimensional mono-component supramolecular crystals, as characterized by scanning tunneling microscopy (STM). We propose that the synthesis benefits from the conformational flexibility of the TPE backbone in distinctive multi-step reaction pathways. This study opens up opportunities for exploring the photophysical properties of TPE-based macrocycles.

Aggregation-Induced Emission-Active Gels: Fabrications, Functions, and Applications.

Chromophores that exhibit aggregation-induced emission (i.e., aggregation-induced emission luminogens [AIEgens]) emit intense fluorescence in their aggregated states, but show negligible emission as discrete molecular species in solution due to the changes in restriction and freedom of intramolecular motions. As solvent-swollen quasi-solids with both a compact phase and a free space, gels enable manipulation of intramolecular motions. Thus, AIE-active gels have attracted significant interest owing to their various distinctive properties and promising application potential. Herein, a comprehensive overview of AIE-active gels is provided. The fabrication strategies employed are detailed, and the applications of AIEgens are summarized. In addition, the gel functions arising from the AIE moieties are revealed, along with their structure-property relationships. Furthermore, the applications of AIE-active gels in diverse areas are illustrated. Finally, ongoing challenges and potential means to address them are discussed, along with future perspectives on AIE-active gels, with the overall aim of inspiring research on novel materials and ideas.

Comparison of the Acute Effects of Different Pacing Sites on Cardiac Synchrony and Contraction Using Speckle-Tracking Echocardiography.

Background: Cardiac pacing in patients with bradyarrhythmia may employ variable pacing sites, which may have different effects on cardiac function. Left bundle branch pacing (LBBP) is a new physiological pacing modality, and the acute outcomes on cardiac mechanical synchrony during LBBP remain uncertain. We evaluated the acute effects of four pacing sites on cardiac synchrony and contraction using speckle-tracking echocardiography, and comparisons among four different pacing sites were rare. Methods: We enrolled 21 patients with atrioventricular block or sick sinus syndrome who each sequentially underwent acute pacing protocols, including right ventricular apical pacing (RVAP), right ventricular outflow tract pacing (RVOP), His bundle pacing (HBP), and left bundle branch pacing (LBBP). Electrocardiograms and echocardiograms were recorded at baseline and during pacing. The interventricular mechanical delay (IVMD), the standard deviation of the times to longitudinal peak strain during 17 segments (PSD), and the Yu index were used to evaluate ventricular mechanical synchrony. Layer-specific strain was computed using two-dimensional speckle tracking technique to provide in-depth details about ventricular synchrony and function. Results: Left ventricular ejection fraction (LVEF) and tricuspid annulus plane systolic excursion (TAPSE) were significantly decreased during RVAP and RVOP but were not significantly different during HBP and LBBP compared with baseline. RVAP and RVOP significantly prolonged QRS duration, whereas HBP and LBBP showed non-significant effects. IVMD and PSD were significantly increased during RVAP but were not significantly different during RVOP, HBP, or LBBP. LBBP resulted in a significant improvement in the IVMD and Yu index compared with RVAP. No significant differences in mechanical synchrony were found between HBP and LBBP. Conclusion: Among these pacing modalities, RVAP has a negative acute impact on cardiac synchrony and contraction. HBP and LBBP best preserve physiological cardiac synchrony and function.