KLF4 inhibited the senescence-associated secretory phenotype in ox-LDL-treated endothelial cells via PDGFRA/NAMPT/mitochondrial ROS.

BACKGROUND: Inflammation is one of the significant consequences of ox-LDL-induced endothelial cell (EC) dysfunction. The senescence-associated secretory phenotype (SASP) is a critical source of inflammation factors. However, the molecular mechanism by which the SASP is regulated in ECs under ox-LDL conditions remains unknown. RESULTS: The level of SASP was increased in ox-LDL-treated ECs, which could be augmented by KLF4 knockdown whereas restored by KLF4 knock-in. Furthermore, we found that KLF4 directly promoted PDGFRA transcription and confirmed the central role of the NAPMT/mitochondrial ROS pathway in KLF4/PDGFRA-mediated inhibition of SASP. Animal experiments showed a higher SASP HFD-fed mice, compared with normal feed (ND)-fed mice, and the endothelium of EC-specific KLF4-/- mice exhibited a higher proportion of SA-ß-gal-positive cells and lower PDGFRA/NAMPT expression. CONCLUSIONS: Our results revealed that KLF4 inhibits the SASP of endothelial cells under ox-LDL conditions through the PDGFRA/NAMPT/mitochondrial ROS. METHODS: Ox-LDL-treated ECs and HFD-fed mice were used as endothelial senescence models in vitro and in vivo. SA-ß-gal stain, detection of SAHF and the expression of inflammatory factors determined SASP and senescence of ECs. The direct interaction of KLF4 and PDGFRA promotor was analyzed by EMSA and fluorescent dual luciferase reporting analysis.

Transcatheter tricuspid valve replacement with LuX-valve device: Overview of key echocardiographic considerations.

Tricuspid regurgitation is a common valve disease with high incidence and poor prognosis. For elderly patients and those with a history of open heart surgery, second thoracotomy and valve replacement carry a high risk. Transcatheter tricuspid valve replacement (TTVR) has become an alternative treatment for patients with high surgical risk. LuX-Valve is a novel self-expandable valve that does not rely on radial force to anchor the valve annulus. The preliminary results have been satisfactory, and this technology is gradually being adopted in China and around the world. Successful implementation of this technique depends on echocardiographic preoperative screening, intraoperative guidance, and postoperative follow-up. The purpose of this article is to provide a state-of-the-art review of the key points and technical considerations for preoperative screening, intraoperative guidance, and postoperative follow-up for TTVR.

Reversible Snapping of Constrained Anisotropic Hydrogels Upon Light Stimulations.

Creatures, such as Venus flytrap and hummingbirds, capable of rapid predation through snap-through transition, provide paradigms for the design of soft actuators and robots with fast actions. However, these artificial "snappers" usually need contact stimulations to trigger the flipping. Reported here is a constrained anisotropic poly(N-isopropylacrylamide) hydrogel showing fast snapping upon light stimulation. This hydrogel is prepared by flow-induced orientation of nanosheets (NSs) within a rectangular tube. The precursor containing gold nanoparticles is immediately exposed to UV light for photopolymerization to fix the ordered structure of NSs. Two ends of the slender gel are clamped to form a buckle with bistability nature, which snaps to the other side upon laser irradiation. Systematic experiments are conducted to investigate the influences of power intensity and irradiation angle of the laser, as well as thickness and buckle height of the gel, on the snapping behaviors. The fast snapping is further used to kick a plastic bead and control the switch state. Furthermore, synergetic or oscillated snapping of the gel with two buckles of opposite directions is realized by inclined irradiation of a laser or horizontal irradiation with two lasers, respectively. Such light-steered snapping of hydrogels should merit designing soft robots, energy harvests, etc.

Apolipoprotein E is a prognostic factor for pancreatic cancer and associates with immune infiltration.

BACKGROUND: The expression level of apolipoprotein E (APOE) in pancreatic ductal adenocarcinoma (PDAC) and its effect on the prognosis of PDAC patients are not clear. The effect of APOE on the immune status of patients with PDAC has not been elucidated. METHODS: We obtained pancreatic cancer data from the TCGA and GETx databases. Patients with PDAC who underwent pancreatic surgery at the Second Affiliated Hospital of Jiaxing University between 2012 and 2021 were included. Clinical pathological data were recorded, plasma APOE levels were measured, and tissue samples were collected. A tissue microarray was generated using the collected tissue samples. APOE and CD4 staining was performed to determine immunoreactive scores (IRSs). The expression of APOE in the plasma and tumour tissues of pancreatic cancer patients was analysed and compared. The correlations between plasma APOE levels, tissue APOE levels and clinicopathological characteristics were analysed. Survival prognosis was analysed using Kaplan-Meier survival analysis and Cox multivariate regression analysis. The correlations between APOE expression levels and immune biomarkers and immune cells were further analysed. Single-cell analysis of APOE distribution in various cells was performed on the TISCH website. RESULTS: APOE was highly expressed in the tumour tissue of pancreatic cancer patients, and high plasma APOE levels were associated with poor prognosis. Females, patients with high-grade disease and patients with pancreatic head carcinoma had high plasma APOE levels. High APOE expression in tumour tissues was associated with good prognosis. Mononuclear macrophages in the pancreatic cancer microenvironment primarily expressed APOE. APOE levels positively correlated with immune biomarkers, such as CD8A, PDCD1, GZMA, CXCL10, and CXCL9, in the tumour microenvironment. APOE promoted CD4 + T cell or dendritic cell infiltration in the tumour microenvironment. CONCLUSIONS: APOE may affect the occurrence and development of pancreatic cancer by regulating the infiltration of immune cells in the tumour microenvironment.

A peptide-based pH-sensitive antibacterial hydrogel for healing drug-resistant biofilm-infected diabetic wounds.

Diabetic foot ulcers are a significant complication affecting roughly 15% of diabetic patients. These chronic wounds can be incredibly burdensome, leading to high treatment costs, potential amputations, and additional health complications. Microbiological studies reveal that bacterial infections are the primary culprit behind delayed wound healing. To solve the problem of infection at the wound site, the most fundamental thing is to kill the pathogenic bacteria. Herein, a neoteric strategy to construct novel antibacterial hydrogel COA-T3 that combined photosensitizers (PSs) and antimicrobial peptides (AMPs) via covalent coupling was proposed. Hydrogel COA-T3 composed of quaternized chitosan (QCS) and oxidized dextran (OD) was constructed for co-delivery of the photosensitizer TPI-PN and the antimicrobial peptide HHC10. In vitro and in vivo experiments demonstrated remarkable effectiveness of COA-T3 against drug-resistant bacteria. Furthermore, the hydrogel significantly promoted healing of diabetic infected wounds. This enhanced antibacterial activity is attributed to the pH-sensitive release of both PSs and AMPs within the hydrogel. Additionally, COA-T3 exhibits excellent biocompatibility, making it a promising candidate for wound dressing materials. These findings indicated that the COA-T3 hydrogel is a promising wound dressing material for promoting the healing of diabetic foot ulcers by providing an environment conducive to improved wound healing in diabetic patients.

Characteristic Changes of the Stance-Phase Plantar Pressure Curve When Walking Uphill and Downhill: Cross-Sectional Study.

BACKGROUND: Monitoring of gait patterns by insoles is popular to study behavior and activity in the daily life of people and throughout the rehabilitation process of patients. Live data analyses may improve personalized prevention and treatment regimens, as well as rehabilitation. The M-shaped plantar pressure curve during the stance phase is mainly defined by the loading and unloading slope, 2 maxima, 1 minimum, as well as the force during defined periods. When monitoring gait continuously, walking uphill or downhill could affect this curve in characteristic ways. OBJECTIVE: For walking on a slope, typical changes in the stance phase curve measured by insoles were hypothesized. METHODS: In total, 40 healthy participants of both sexes were fitted with individually calibrated insoles with 16 pressure sensors each and a recording frequency of 100 Hz. Participants walked on a treadmill at 4 km/h for 1 minute in each of the following slopes: -20%, -15%, -10%, -5%, 0%, 5%, 10%, 15%, and 20%. Raw data were exported for analyses. A custom-developed data platform was used for data processing and parameter calculation, including step detection, data transformation, and normalization for time by natural cubic spline interpolation and force (proportion of body weight). To identify the time-axis positions of the desired maxima and minimum among the available extremum candidates in each step, a Gaussian filter was applied (σ=3, kernel size 7). Inconclusive extremum candidates were further processed by screening for time plausibility, maximum or minimum pool filtering, and monotony. Several parameters that describe the curve trajectory were computed for each step. The normal distribution of data was tested by the Kolmogorov-Smirnov and Shapiro-Wilk tests. RESULTS: Data were normally distributed. An analysis of variance with the gait parameters as dependent and slope as independent variables revealed significant changes related to the slope for the following parameters of the stance phase curve: the mean force during loading and unloading, the 2 maxima and the minimum, as well as the loading and unloading slope (all P<.001). A simultaneous increase in the loading slope, the first maximum and the mean loading force combined with a decrease in the mean unloading force, the second maximum, and the unloading slope is characteristic for downhill walking. The opposite represents uphill walking. The minimum had its peak at horizontal walking and values dropped when walking uphill and downhill alike. It is therefore not a suitable parameter to distinguish between uphill and downhill walking. CONCLUSIONS: While patient-related factors, such as anthropometrics, injury, or disease shape the stance phase curve on a longer-term scale, walking on slopes leads to temporary and characteristic short-term changes in the curve trajectory.

Association between adding salt in food and dementia in European descent: A mendelian randomization study.

BACKGROUND: High salt intake has been proposed as a risk factor for dementia. However, causal relationship between salt intake and dementia remains uncertain. PURPOSE: The aim of this study was to employ a mendelian randomization (MR) design to investigate the causal impact of salt intake on the risk of dementia. METHODS: Genome-wide association study (GWAS) data of exposures and outcomes (any dementia, cognitive performance, different types of dementia, Alzheimer's disease [AD], and Parkinson's disease) were obtained from the IEU database. MR estimates were generated though inverse-variance weighted model. MR-Egger, weighted median, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method also used in our study. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, MR-PRESSO global test and outlier test, leave-one-out analysis, and funnel plot assessment. RESULTS: Our MR analysis provided evidence of a causal association between high salt added to food and dementia (odds ratio [OR] = 1.73, 95% confidence interval [CI]: 1.21-2.49, and p = .003), dementia in AD (OR = 2.10, 95% CI: 1.15-3.83, and p = .015), and undefined dementia (OR = 2.61, 95% CI: 1.26-5.39, and p = .009). Higher salt added was also associated with increased risk of AD (OR = 1.80, 95% CI: 1.12-2.87, and p = .014) and lower cognitive performance (ß = -.133, 95% CI: -.229 to -.038, and p = .006). CONCLUSION: This study provides evidence suggesting that high salt intake is causally associated with an increased risk of developing dementia, including AD and undefined dementia, highlighting the potential importance of reducing salt consumption as a preventive measure.

Unveiling the promise of PD1/PD-L1: A new dawn in immunotherapy for cholangiocarcinoma.

Cholangiocarcinoma (CCA), a rare yet notably aggressive cancer, has experienced a surge in incidence in recent years. Presently, surgical resection remains the most effective curative strategy for CCA. Nevertheless, a majority of patients with CCA are ineligible for surgical removal at the time of diagnosis. For advanced stages of CCA, the combination of gemcitabine and cisplatin is established as the standard chemotherapy regimen. Despite this, treatment efficacy is often hindered by the development of resistance. In recent times, immune checkpoint inhibitors, particularly those that block programmed death 1 and its ligand (PD1/PD-L1), have emerged as promising strategies against a variety of cancers and are being increasingly integrated into the therapeutic landscape of CCA. A growing body of research supports that the use of PD1/PD-L1 monoclonal antibodies in conjunction with chemotherapy may significantly improve patient outcomes. This article seeks to meticulously review the latest studies on PD1/PD-L1 involvement in CCA, delving into their expression profiles, prognostic significance, contribution to oncogenic processes, and their potential clinical utility.

The relationship between glycemic risk and longitudinal changes in total physiological atherosclerotic burden in patients with coronary artery disease.

Background: The effects of glycemic status on coronary physiology have not been well evaluated. This study aimed to investigate changes in coronary physiology by using angiographic quantitative flow ratio (QFR), and their relationships with diabetes mellitus (DM) and glycemic control status. Methods: This retrospective cohort study included 530 patients who underwent serial coronary angiography (CAG) measurements between January 2016 and December 2021 at Tongji Hospital of Tongji University. Based on baseline and follow-up angiograms, 3-vessel QFR (3V-QFR) measurements were performed. Functional progression of coronary artery disease (CAD) was defined as a change in 3V-QFR (Δ3V-QFR = 3V-QFRfollow-up - 3V-QFRbaseline) ≤-0.05. Univariable and multivariable logistic regression analyses were applied to identify the independent predictors of coronary functional progression. Subgroup analysis according to diabetic status was performed. Results: During a median interval of 12.1 (10.6, 14.3) months between the two QFR measurements, functional progression was observed in 169 (31.9%) patients. Follow-up glycosylated hemoglobin (HbA1c) was predictive of coronary functional progression with an area under the curve (AUC) of 0.599 [95% confidence interval (CI): 0.546-0.651; P<0.001] in the entire population. Additionally, the Δ3V-QFR values were significantly lower in diabetic patients with HbA1c ≥7.0% compared to those with well-controlled HbA1c or non-diabetic patients [-0.03 (-0.09, 0) vs. -0.02 (-0.05, 0.01) vs. -0.02 (-0.05, 0.02); P=0.002]. In a fully adjusted multivariable logistics analysis, higher follow-up HbA1c levels were independently associated with progression in 3V-QFR [odds ratio (OR), 1.263; 95% CI: 1.078-1.479; P=0.004]. Furthermore, this association was particularly strong in diabetic patients (OR, 1.353; 95% CI: 1.082-1.693; P=0.008) compared to patients without DM. Conclusions: Among patients with established CAD, on-treatment HbA1c levels were independently associated with progression in physiological atherosclerotic burden, especially in patients with DM.

Academic performance of students in an accelerated medical pathway.

Accelerated medical school curricula, such as three-year programs, have gained attention in recent years but studies evaluating their impact are still scarce. This study examines the Fully Integrated Readiness for Service Training (FIRST) program, a three-year accelerated pathway, to assess its impact on students' academic performance preparedness for residency. In this observational study, we compared the academic outcomes of FIRST program students to traditional four-year curriculum students from 2018 to 2023. We analyzed multiple metrics, including exam performance (United States Medical Licensing Examination Step scores, shelf exam scores, and pre-clinical course scores) and clinical performance scores during the application and individualization phases. Analysis of Variance was used to examine the effect of accelerated pathway program experience relative to traditional 4-year medical school curriculum on the learning outcomes. FIRST program students were on average 1.5 years younger upon graduation than their traditional peers. While FIRST program students scored slightly lower on Step 2 Clinical Knowledge (CK), they exhibited no significant differences in other exam scores or clinical performance relative to the traditional students. Notably, FIRST students achieved equivalent clinical performance ratings during critical clerkships and rotations. Our findings suggest that a three-year medical school curriculum can effectively prepare students for residency and produce graduates with comparable medical knowledge and clinical skills, offering potential benefits in terms of financial relief and personal well-being for medical students.

The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma.

Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

Clinical Characteristics and Analysis of Associated Risk Factors in Patients with Severe and Non-Severe COVID-19 Infection.

Objective: Our aim was to highlight the clinical characteristics and determine the risk factors associated with severe and non-severe COVID-19 infection. Study Method: A retrospective review was conducted on clinical data obtained from patients with COVID-19 infection, admitted to the emergency department between November 2022 and January 2023. Total of 1684 participants were categorized into severe (312 cases,18.53%) and non-severe (1,372 cases,81.47%) cohorts. Logistic regression was utilized for multivariate analysis, with a P-value less than 0.05 signifying a significant difference between the groups. Results: The study consisted of 952 males (56.53%) and 732 females (43.47%) participants. The age distribution ranged from 18 to 93 years in both cohorts. There were statistically significant differences between the clinical symptoms of the severe and non-severe cohorts (P < 0.05). According to the multivariate statistical analysis, patients with more pronounced clinical manifestations had significantly elevated values related to age(P < 0.05), diabetes(P < 0.01), hypertension(P < 0.01), C-reactive protein (CRP) (P < 0.05), and lactate dehydrogenase (LDH) (P < 0.01) as compared to those presenting with milder symptoms. Conclusion: The primary clinical presentations in both the cohorts were mostly similar. Predominant factors contributing to the severity of COVID-19 infection were age, diabetes, hypertension, elevated CRP levels, and increased LDH.

Visual function loss in fungal sphenoid sinusitis: clinical characteristics and outcomes.

Potentially fatal fungal sphenoid sinusitis (FSS) causes visual damage. However, few studies have reported on its visual impairment and prognosis. Five hundred and eleven FSS patients with ocular complications treated at Beijing Tongren Hospital were recruited and clinical features and visual outcomes were determined. Thirty-two of the 511 patients (6%) had visual impairment, with 13 and 19 patients having invasive and noninvasive FSS, respectively. Eighteen patients (56.25%) had diabetes and 2 patient (6.25%) had long-term systemic use of antibiotics (n = 1) and corticosteroids (n = 1). All patients had visual impairment, which was more severe in invasive FSS than in noninvasive FSS. Bony wall defects and sclerosis were observed in 19 patients (59.38%), and 11 patients (34.38%) had microcalcification in their sphenoid sinusitis on computed tomography (CT). After a 5-year follow-up, three patients (9.38%) died. Patients with noninvasive FSS had a higher improvement rate in visual acuity than their counterparts. In the multivariate analysis, sphenoid sinus wall sclerosis on CT was associated with better visual prognosis. FSS can cause vision loss with persistent headaches, particularly in those with diabetes. CT showed the sphenoid sinus wall sclerosis, indicating a better visual prognosis in FSS with visual impairment.

Optogenetic Control of Bacterial Cell-Cell Adhesion Dynamics: Unraveling the Influence on Biofilm Architecture and Functionality.

The transition of bacteria from an individualistic to a biofilm lifestyle profoundly alters their biology. During biofilm development, the bacterial cell-cell adhesions are a major determinant of initial microcolonies, which serve as kernels for the subsequent microscopic and mesoscopic structure of the biofilm, and determine the resulting functionality. In this study, the significance of bacterial cell-cell adhesion dynamics on bacterial aggregation and biofilm maturation is elucidated. Using photoswitchable adhesins between bacteria, modifying the dynamics of bacterial cell-cell adhesions with periodic dark-light cycles is systematic. Dynamic cell-cell adhesions with liquid-like behavior improve bacterial aggregation and produce more compact microcolonies than static adhesions with solid-like behavior in both experiments and individual-based simulations. Consequently, dynamic cell-cell adhesions give rise to earlier quorum sensing activation, better intermixing of different bacterial populations, improved biofilm maturation, changes in the growth of cocultures, and higher yields in fermentation. The here presented approach of tuning bacterial cell-cell adhesion dynamics opens the door for regulating the structure and function of biofilms and cocultures with potential biotechnological applications.

Deciphering the Roles of Extracellular Polymeric Substances (EPS) in Shaping Disinfection Kinetics through Permanent Removal via Genetic Disruption.

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.

Post-transcriptional splicing can occur in a slow-moving zone around the gene.

Splicing is the stepwise molecular process by which introns are removed from pre-mRNA and exons are joined together to form mature mRNA sequences. The ordering and spatial distribution of these steps remain controversial, with opposing models suggesting splicing occurs either during or after transcription. We used single-molecule RNA FISH, expansion microscopy, and live-cell imaging to reveal the spatiotemporal distribution of nascent transcripts in mammalian cells. At super-resolution levels, we found that pre-mRNA formed clouds around the transcription site. These clouds indicate the existence of a transcription-site-proximal zone through which RNA move more slowly than in the nucleoplasm. Full-length pre-mRNA undergo continuous splicing as they move through this zone following transcription, suggesting a model in which splicing can occur post-transcriptionally but still within the proximity of the transcription site, thus seeming co-transcriptional by most assays. These results may unify conflicting reports of co-transcriptional versus post-transcriptional splicing.

1-MCP treatment improves the postharvest quality of Jinxiu yellow peach by regulating cuticular wax composition and gene expression during cold storage.

This study aimed to analyze the effect of 1-methylcyclopropene (1-MCP) treatment on the postharvest quality, epidermal wax morphology, composition, and gene expression of Jinxiu yellow peach during cold storage. The results showed that 1-MCP treatment could maintain the postharvest quality of peach fruit as compared to control (CK) during cold storage. The wax crystals of peach fruit were better retained by 1-MCP, and they still existed in 0.6 and 0.9 µL/L 1-MCP treated fruit at 36 days. The total wax content in all the fruit increased first and then decreased during cold storage. Meanwhile, n-alkanes and primary alcohols were the main wax components. Compared to CK, 1-MCP treatment could delay the reduction of wax content during cold storage. The correlation analysis indicated that the postharvest quality of yellow peach was mainly affected by the contents of fatty acids and triterpenoids in cuticular wax. The transcriptomics results revealed PpaCER1, PpaKCS, PpaKCR1, PpaCYP86B1, PpaFAR, PpaSS2, and PpaSQE1 played the important roles in the formation of peach fruit wax. 1-MCP treatment upregulated PpaCER1 (18785414, 18786441, and 18787644), PpaKCS (18774919, 18789438, and 18793503), PpaKCR1 (18790432), and PpaCYP86B1 (18789815) to deposit more n-alkanes and fatty acids during cold storage. This study could provide a new perspective for regulating the postharvest quality of yellow peach in view of the application of cuticular wax. PRACTICAL APPLICATION: 'Jinxiu' yellow peach fruit is favorable among consumers because of its high commercial value. However, it ripens and deteriorates rapidly during storage, leading to serious economic loss and consumer disappointment. The effect of 1-methylcyclopropene (1-MCP) treatment on the postharvest quality, epidermal wax morphology, composition, and genes regulation of 'Jinxiu' yellow peach during cold storage was assessed. Compared to control, 1-MCP treatment could retain the storage quality of yellow peach by affecting cuticular wax composition and gene expression. This study could provide new perspective for regulating the postharvest quality of yellow peach in view of the application of cuticular wax.

Harnessing antimicrobial peptide-coupled photosensitizer to combat drug-resistant biofilm infections through enhanced photodynamic therapy.

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G-) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G- bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.