BODIPY-Based NIR Trackers with Acidity-Driven Amphiphilicity for STED Super-Resolution Imaging of Lysosomal Membranes.

Although super-resolution imaging provides a great opportunity to disclose the structures of living cells at the nanoscale level, resolving the structural details of organelles is highly dependent on the targeting accuracy and photophysical properties of fluorescence trackers. Herein, we report a series of ultrabright and photostable trackers of lysosomal membranes for super-resolution imaging using stimulated emission depletion microscopy (STED). These trackers are composed of lipophilic NIR BODIPY derivatives and ionizable tertiary amines. This structural feature enables accurate targeting of the lysosomal membrane through the formation of transient amphiphilicity driven by the acidity in the lysosome. As a representative, Lyso-700 is applied for STED-based super-resolution imaging of the lysosomal membrane of living macrophages. By use of Lyso-700, the interaction details between lysosomes of macrophages and fungi are visualized. Overall, these trackers display great potential as advanced lysosome trackers and merit further evaluation for lysosome-related studies.

Convolutional neural network-based measurement of crown-implant ratio for implant-supported prostheses.

STATEMENT OF PROBLEM: Research has revealed that the crown-implant ratio (CIR) is a critical variable influencing the long-term stability of implant-supported prostheses in the oral cavity. Nevertheless, inefficient manual measurement and varied measurement methods have caused significant inconvenience in both clinical and scientific work. PURPOSE: This study aimed to develop an automated system for detecting the CIR of implant-supported prostheses from radiographs, with the objective of enhancing the efficiency of radiograph interpretation for dentists. MATERIAL AND METHODS: The method for measuring the CIR of implant-supported prostheses was based on convolutional neural networks (CNNs) and was designed to recognize implant-supported prostheses and identify key points around it. The experiment used the You Only Look Once version 4 (Yolov4) to locate the implant-supported prosthesis using a rectangular frame. Subsequently, two CNNs were used to identify key points. The first CNN determined the general position of the feature points, while the second CNN finetuned the output of the first network to precisely locate the key points. The network underwent testing on a self-built dataset, and the anatomic CIR and clinical CIR were obtained simultaneously through the vertical distance method. Key point accuracy was validated through Normalized Error (NE) values, and a set of data was selected to compare machine and manual measurement results. For statistical analysis, the paired t test was applied (α=.05). RESULTS: A dataset comprising 1106 images was constructed. The integration of multiple networks demonstrated satisfactory recognition of implant-supported prostheses and their surrounding key points. The average NE value for key points indicated a high level of accuracy. Statistical studies confirmed no significant difference in the crown-implant ratio between machine and manual measurement results (P>.05). CONCLUSIONS: Machine learning proved effective in identifying implant-supported prostheses and detecting their crown-implant ratios. If applied as a clinical tool for analyzing radiographs, this research can assist dentists in efficiently and accurately obtaining crown-implant ratio results.

Tetrazine-Based Ratiometric Nitric Oxide Sensor Identifies Endogenous Nitric Oxide in Atherosclerosis Plaques by Riding Macrophages as a Smart Vehicle.

Atherosclerosis (AS) is the formation of plaques in blood vessels, which leads to serious cardiovascular diseases. Current research has disclosed that the formation of AS plaques is highly related to the foaming of macrophages. However, there is a lack of detailed molecular biological mechanisms. We proposed a "live sensor" by grafting a tetrazine-based ratiometric NO probe within macrophages through metabolic and bio-orthogonal labeling. This "live sensor" was proved to target the AS plaques with a diameter of only tens of micrometers specifically and visualized endogenous NO at two lesion stages in the AS mouse model. The ratiometric signals from the probe confirmed the participation of NO during AS and indicated that the generation of endogenous NO increased significantly as the lesion progressed. Our proposal of this "live sensor" provided a native and smart strategy to target and deliver small molecular probes to the AS plaques at the in vivo level, which can be used as universal platforms for the detection of reactive molecules or microenvironmental factors in AS.

Integration of TADF Photosensitizer as "Electron Pump" and BSA as "Electron Reservoir" for Boosting Type I Photodynamic Therapy.

Type I photosensitization provides an effective solution to the problem of unsatisfactory photodynamic therapeutic (PDT) effects caused by the tumor hypoxia. The challenge in the development of Type I mode is to boost the photosensitizer's own electron transfer capacity. Herein, we found that the use of bovine serum albumin (BSA) to encapsulate a thermally activated delayed fluorescence (TADF) photosensitizer PS can significantly promote the Type I PDT process to generate a mass of superoxide anions (O2•-). This Type I photosensitization opened a new strategy by employing BSA as "electron reservoir" and TADF photosensitizer as "electron pump". We integrated these roles of BSA and PS in one system by preparing nanophotosensitizer PS@BSA. The Type I PDT performance was demonstrated with tumor cells under hypoxic conditions. Furthermore, PS@BSA took full advantage of the tumor-targeting role of BSA and achieved efficient PDT for tumor-bearing mice in the in vivo experiments. This work provides an effective route to improve the PDT efficiency of hypoxic tumors.

Atmospheric Chemistry of NH2SO3H in Polluted Areas: An Unexpected Isomerization of NH2SO3H in Acid-Polluted Regions.

NH2SO3H is an effective nucleation agent for the formation of atmospheric aerosols and cloud particles. So, the ammonolysis of SO3 to form NH2SO3H without and with neutral (H2O) and basic (NH3) trace gases has been extensively investigated. However, the acidic trace gas X (X = H2SO4 and CH3SO3H)-assisted ammonolysis of SO3 is still up for debate. In this work, a comprehensive theoretical investigation of X-assisted ammonolysis of SO3 and its reverse reaction (the isomerization of NH2SO3H to form SO3-···NH3+) was carried out in the gas phase and at the air-water interface. The gas-phase results show that X-assisted isomerization of NH2SO3H to form SO3-···NH3+ is more energetically and kinetically favorable than its reverse reaction and the isomerization of NH2SO3H in the presence of H2O and NH3. Such unexpected findings revealed that gas-phase NH2SO3H is highly reactive in the presence of acidic trace gas in contrast to the high stability of NH2SO3H in neutral and basic conditions. At the air-water interface, the X-assisted isomerization reaction of NH2SO3H involves multiple water molecules. The loop structure of the reaction center (X···NH2SO3H···3H2O) promotes the transfer of protons in the water molecules to form the SO3-···NH3+ ion pair, which can then interact with several interfacial water molecules to form ammonium bisulfate. These interfacial reaction channels follow a stepwise mechanism and proceed at the picosecond time-scale. The findings of this study will contribute to a better understanding of the atmospheric behavior of NH2SO3H in polluted acidic trace gases.

Spectral pedestal during the kilowatt-level amplification of a random fiber laser operating near the lasing threshold.

The amplification of random fiber lasers (RFLs) attracts much attention due to their unique characteristics such as wavelength flexibility and low coherence. We present that, in the kilowatt-level amplification of RFL operating near its lasing threshold, a broad and flat spectral pedestal can co-exist with the narrow spectral peak of RFL. This phenomenon is different from the case in the amplification of fixed-cavity laser seeds. Time-domain measurements show that the broad and flat spectral pedestal, which extends to long wavelengths, is composed of temporal pulses, while few temporal pulses exist in the narrow spectral peak. We attribute the spectral pedestal to intensity fluctuations from the random seed laser and modulation instability in the amplification stage. Control experiments reveal that the working status of the random seed laser and the effective length of the amplifier can influence the spectral bandwidth. By taking advantage of this phenomenon, we propose a novel approach to achieve a high-power broadband light source through the amplification of RFLs operating near the lasing threshold.

Interleukin 25 and its biological features and function in intestinal diseases.

Interleukin 25 (IL-25), also known as IL-17E, is a member of the IL-17 cytokine family and an important regulator of the type 2 immune response. Accumulating evidence suggests that IL-25 interacts with diverse immune as well as non-immune cells and plays a rather complicated role in different backgrounds of multiple organs. IL-25 has been studied in the physiology and pathology of the intestine to some extent. With epithelial cells being an important source in the intestine, IL-25 plays a key role in intestinal immune responses and is associated with inappropriate allergic reactions, autoimmune diseases, and cancer tumorigenesis. In this review, we discuss the emerging comprehension of the biology of IL-25, as well as its cellular sources, targets, and signaling transduction. In particular, we discuss how IL-25 participates in the development of intestinal diseases including helminth infection, inflammatory bowel diseases, food allergy and colorectal cancer, as well as its underlying role in future therapy.

High-performance MoOx/n-Si heterojunction NIR photodetector with aluminum oxide as a tunneling passivation interlayer.

The most effective and potential approach to improve the performance of heterojunction photodetectors is to obtain favorable interfacial passivation by adding an insertion layer. In this paper, MoOx/Al2O3/n-Si heterojunction photodetectors with excellent photocurrents, responsivity and detectivity were fabricated, in which alumina acts as a tunneling passivation layer. By optimizing the post-annealing treatment temperature of the MoOxand the thickness of the ultra-thin Al2O3, the photodetector achieved a ratio of photocurrent to dark current of 3.1 × 105, a photoresponsivity of 7.11 A W-1(@980 nm) and a detective of 9.85 × 1012Jones at -5 V bias. Besides, a self-driven response of 0.17 A W-1and a high photocurrent/dark current ratio of 2.07 × 104were obtained. The result demonstrated that optimizing the interface of heterojunctions is a promising way to obtain a heterojunction photodetector with high-performance.

2.19 kW narrow linewidth FBG-based MOPA configuration fiber laser.

In this paper, we demonstrated a monolithic fiber-Bragg-grating-based (FBG-based) master oscillator power amplification configuration fiber laser with a narrow linewidth at high-power level. Several approaches were implemented to reduce the seed laser linewidth and the magnification of spectrum broadening in order to achieve a narrow output linewidth. The narrow seed laser linewidth was obtained by restricting the reflection bandwidth of the FBG. To reduce the magnification of spectrum broadening, a backward pumping scheme was employed in the amplifier stage after its capacity to suppress laser spectrum broadening was preliminarily investigated experimentally. Further, by intentionally shortening the length of the active fiber in the amplifier and sharing the backward pumping power with the oscillator, the spectrum broadening was further inhibited without sacrificing optical efficiency. A maximum output power of 2.19 kW was achieved with a 3 dB spectrum bandwidth of only 86.5 pm. The beam quality at the maximum power was measured to be M2~1.46. No sign of transverse mode instability was shown during the experiments.

A Cascade xDAWN EEGNet Structure for Unified Visual-Evoked Related Potential Detection.

Visual-based brain-computer interface (BCI) enables people to communicate with others by spelling words from the brain and helps professionals recognize targets in large numbers of images. P300 signals evoked by different types of stimuli, such as words or images, may vary significantly in terms of both amplitude and latency. A unified approach is required to detect variable P300 signals, which facilitates BCI applications, as well as deepens the understanding of the P300 generation mechanism. In this study, our proposed approach involves a cascade network structure that combines xDAWN and classical EEGNet techniques. This network is designed to classify target and non-target stimuli in both P300 speller and rapid serial visual presentation (RSVP) paradigms. The proposed approach is capable of recognizing more symbols with fewer repetitions (up to 5 rounds) compared to other models while possessing a better information transfer rate (ITR) as demonstrated on Dataset II (17.22 bits/min in the second repetition round) of BCI Competition III. Additionally, our approach has the highest unweighted average recall (UAR) performance for both 5 Hz ( 0.8134±0.0259 ) and 20 Hz ( 0.6527±0.0321 ) RSVP. The results show that the cascade network structure has better performance between both the P300 Speller and RSVP paradigms, manifesting that such a cascade structure is robust enough for dealing with P300-related signals (source code is available at https://github.com/embneural/Cascade-xDAWN-EEGNet-for-ERP-Detection).

Gut microbiota's influence on erysipelas: evidence from a two-sample Mendelian randomization analysis.

Background: Previous studies have suggested a link between gut microbiota and skin diseases, including erysipelas, an inflammatory skin condition. Despite this, the precise nature of the relationship between erysipelas and gut microbiota remains unclear and subject to debate. Methods: We conducted a Mendelian Randomization (MR) analysis using publicly available summary data from genome-wide association studies (GWAS) to explore the potential causal relationship between gut microbiota and erysipelas. Instrumental variables (IVs) were identified using a comprehensive set of screening methods. We then performed MR analyses primarily using the Inverse Variance Weighted (IVW) method, complemented by alternative approaches such as MR Egger, weighted median, simple mode, and weighted mode. A series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test, and a leave-one-out test, were executed to ensure the robustness and validity of our findings. Results: We identified potential associations between erysipelas and various gut microbiota, including Alcaligenaceae (OR 1.23; 95% CI 1.06-1.43; p=0.006), Rikenellaceae (OR 0.77; 95% CI 0.67-0.90; p=0.001), and others. Notably, associations with Actinomyces, Lachnospiraceae NC2004 group, Ruminiclostridium 9, Ruminococcaceae UCG014, Odoribacter, and Actinobacteria were also observed. Sensitivity analyses confirmed the robustness of these associations. Conclusion: Our MR analysis suggests both potentially beneficial and harmful causal relationships between various gut microbiota and the incidence of erysipelas. This study provides new theoretical and empirical insights into the pathogenesis of erysipelas and underscores the potential for innovative preventive and therapeutic approaches.

Scaffold Adhering to Peptide-Based Biomimetic Extracellular Matrix Composite Nanobioglass Promotes the Proliferation and Migration of Skin Fibroblasts Through the GSK-3ß/ß-Catenin Signaling Axis.

Introduction: Nano-mesoporous bioactive glass and RGD peptide-coated collagen membranes have great potential in wound healing. However, the application of their compound has not been further studied. Our purpose is to prepare a novel bioactive collagen scaffold containing both NMBG stent and adhesion peptides (BM), which then proves its promising prospect the assessment of physical properties, biocompatibility, GSK-3ß/ß-catenin signaling axis and toxicological effects. Methods: The structural and morphological changes of BM were analyzed using scanning electron microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). In vivo, wound healing of BM was assessed in SD rats through dynamic monitoring and calculation of wound healing rate. Immunohistofluorescence (IHF), H&E, and Masson staining were utilized; in vitro, primary cell culture, and a variety of assays including CCK-8, Transwell, Scratch, Immunocytofluorescence (ICF), and Western blot (WB) were performed, both for morphology and molecular analysis. Results and Discussion: Preparation of BM involved attaching NMBG to RGD-exposed collagen while avoiding the use of toxic chemical reagents. BM exhibited a distinctive superficial morphology with increased Si content, indicating successful NMBG attachment. In vivo studies on SD rats demonstrated the superior wound healing capability of BM, as evidenced by accelerated wound closure, thicker epithelial layers, and enhanced collagen deposition compared to the NC group. Additionally, BM promoted skin fibroblast migration and proliferation, possibly through activation of the GSK-3ß/ß-catenin signaling axis, which was crucial for tissue regeneration. This study underscored the potential of BM as an effective wound-healing dressing. Conclusion: A new method for synthesizing ECM-like membranes has been developed using nano-mesoporous bioactive glass and collagen-derived peptides. This approach enhances the bioactivity of biomaterials through surface functionalization and growth factor-free therapy.

Harnessing Machine Learning in Vocal Arts Medicine: A Random Forest Application for "Fach" Classification in Opera.

Vocal arts medicine provides care and prevention strategies for professional voice disorders in performing artists. The issue of correct "Fach" determination depending on the presence of a lyric or dramatic voice structure is of crucial importance for opera singers, as chronic overuse often leads to vocal fold damage. To avoid phonomicrosurgery or prevent a premature career end, our aim is to offer singers an improved, objective fach counseling using digital sound analyses and machine learning procedures. For this purpose, a large database of 2004 sound samples from professional opera singers was compiled. Building on this dataset, we employed a classic ensemble learning method, namely the Random Forest algorithm, to construct an efficient fach classifier. This model was trained to learn from features embedded within the sound samples, subsequently enabling voice classification as either lyric or dramatic. As a result, the developed system can decide with an accuracy of about 80% in most examined voice types whether a sound sample has a lyric or dramatic character. To advance diagnostic tools and health in vocal arts medicine and singing voice pedagogy, further machine learning methods will be applied to find the best and most efficient classification method based on artificial intelligence approaches.

The role of group 3 innate lymphoid cell in intestinal disease.

Group 3 innate lymphoid cells (ILC3s), a novel subpopulation of lymphocytes enriched in the intestinal mucosa, are currently considered as key sentinels in maintaining intestinal immune homeostasis. ILC3s can secrete a series of cytokines such as IL-22 to eliminate intestinal luminal antigens, promote epithelial tissue repair and mucosal barrier integrity, and regulate intestinal immunity by integrating multiple signals from the environment and the host. However, ILC3 dysfunction may be associated with the development and progression of various diseases in the gut. Therefore, in this review, we will discuss the role of ILC3 in intestinal diseases such as enteric infectious diseases, intestinal inflammation, and tumors, with a focus on recent research advances and discoveries to explore potential therapeutic targets.

New insights on IL­36 in intestinal inflammation and colorectal cancer (Review).

Interleukin (IL)-36 is a member of the IL-1 superfamily, which includes three receptor agonists and one antagonist and exhibits a familial feature of inflammatory regulation. Distributed among various tissues, such as the skin, lung, gut and joints, the mechanism of IL-36 has been most completely investigated in the skin and has been used in clinical treatment of generalized pustular psoriasis. Meanwhile, the role of IL-36 in the intestine has also been under scrutiny and has been shown to be involved in the regulation of various intestinal diseases. Inflammatory bowel disease and colorectal cancer are the most predominant inflammatory and neoplastic diseases of the intestine, and multiple studies have identified a complex role for IL-36 in both of them. Indeed, inhibiting IL-36 signaling is currently regarded as a promising therapeutic approach. Therefore, the present review briefly describes the composition and expression of IL-36 and focuses on the role of IL-36 in intestinal inflammation and colorectal cancer. The targeted therapies that are currently being developed for the IL-36 receptor are also discussed.

ST-CapsNet: Linking Spatial and Temporal Attention with Capsule Network for P300 Detection Improvement.

A brain-computer interface (BCI), which provides an advanced direct human-machine interaction, has gained substantial research interest in the last decade for its great potential in various applications including rehabilitation and communication. Among them, the P300-based BCI speller is a typical application that is capable of identifying the expected stimulated characters. However, the applicability of the P300 speller is hampered for the low recognition rate partially attributed to the complex spatio-temporal characteristics of the EEG signals. Here, we developed a deep-learning analysis framework named ST-CapsNet to overcome the challenges regarding better P300 detection using a capsule network with both spatial and temporal attention modules. Specifically, we first employed spatial and temporal attention modules to obtain refined EEG signals by capturing event-related information. Then the obtained signals were fed into the capsule network for discriminative feature extraction and P300 detection. In order to quantitatively assess the performance of the proposed ST-CapsNet, two publicly-available datasets (i.e., Dataset IIb of BCI Competition 2003 and Dataset II of BCI Competition III) were applied. A new metric of averaged symbols under repetitions (ASUR) was adopted to evaluate the cumulative effect of symbol recognition under different repetitions. In comparison with several widely-used methods (i.e., LDA, ERP-CapsNet, CNN, MCNN, SWFP, and MsCNN-TL-ESVM), the proposed ST-CapsNet framework significantly outperformed the state-of-the-art methods in terms of ASUR. More interestingly, the absolute values of the spatial filters learned by ST-CapsNet are higher in the parietal lobe and occipital region, which is consistent with the generation mechanism of P300.

A study of the role of multiple layer-by-layer assembled bionic extracellular matrix in promoting wound healing via activation of the Wnt signaling pathway.

Wound healing is a multicellular collaborative process in which the adhesion and proliferation of fibroblasts in the wound is the basis for ensuring rapid wound healing, and in this process, it can promote the regeneration and remodeling of tissue and extracellular matrix. Studies have shown that Arg-Gly-Asp adhesive peptide (RGD) and basic fibroblast growth factor (bFGF) can stimulate the adhesion and proliferation of fibroblasts by activating the Wnt/ß-catenin signaling pathway, respectively. This study adopts the principle of layer-by-layer self-assembly, and the binding force formed by electrostatic attraction and Schiff base was used to combine bFGF and RGD with collagen membrane to form a biomimetic membrane that is non-cytotoxic with strong biocompatibility that could promote soft tissue healing. The surface characteristics of MLCM and the sustained release concentration of bFGF in vitro were measured, and the effects of MLCM on cell viability, proliferation, migration, and wound healing by means of Wnt/catenin pathways were studied through cell experiments and animal experiments under the comparison of negative control groups and positive control groups. The results showed that MLCM could stimulate wound healing more actively and had a positive effect on cell activity, proliferation, and migration. During wound healing, MLCM activates the Wnt/ß-catenin signaling pathway and inhibition of Wnt/ß-catenin signaling pathway significantly reduces the positive effects of MLCM on wound healing.

Interferon-γ secreted by recruited Th1 cells in peritoneal cavity inhibits the formation of malignant ascites.

Type 1 T helper (Th1) cells generate an efficient antitumor immune response in multiple malignancies. The functions of Th1 cells in malignant ascites (MA) have not been elucidated. The distribution of helper T cells in peritoneal fluid and peripheral blood was determined in patients and animal models with malignant ascites. The effects of Th1-derived interferon-γ (IFN-γ) on the formation of malignant ascites were investigated. The mechanism underlying the recruitment of Th1 cells into peritoneal cavity was explored. In patients with malignant ascites and animal models of malignant ascites, the percentage of Th1 cells increased in peritoneal fluid compared with peripheral blood. Next, our experiment demonstrated that Th1 cells inhibited the growth of tumor cells by secreting IFN-γ in vitro. In murine models of malignant ascites, increased peritoneal fluid and shorter survival time were observed in IFN-γ-/- mice compared with wild-type (WT) mice. Then, the levels of C-X-C motif chemokine ligand (CXCL) 9/10 and the ratio of CXCR3+ Th1 cells indicated the involvement of CXCL9, 10/CXCR3 axis in the recruitment of Th1 cells into peritoneal cavity. As expected, in murine models of malignant ascites, the gradient between ascitic Th1 ratio and blood Th1 ratio decreased in CXCR3-/- mice compared with WT mice. IFN-γ secreted by recruited Th1 cells in peritoneal cavity inhibits the formation of malignant ascites. Hence, manipulation of Th1 cells or IFN-γ will provide a therapeutic candidate against malignant ascites.

Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection.

Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer (Lyso700D) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection.

Causal effects of gut microbiota on appendicitis: a two-sample Mendelian randomization study.

Background: Previous research has posited a potential correlation between the gut microbiota and the onset of appendicitis; however, the precise causal connection between appendicitis and the gut microbiota remains an unresolved and contentious issue. Methods: In this investigation, we performed a Mendelian randomization (MR) analysis employing publicly accessible summary data extracted from genome-wide association studies (GWAS) to elucidate the potential causal nexus between the gut microbiota and the development of appendicitis. We initially identified instrumental variables (IVs) through a comprehensive array of screening methodologies, subsequently executing MR analyses using the Inverse Variance Weighted (IVW) technique as our primary approach, supplemented by several alternative methods such as MR Egger, weighted median, simple mode, and weighted mode. Additionally, we implemented a series of sensitivity analysis procedures, encompassing Cochran's Q test, MR-Egger intercept test, Mendelian Randomized Polymorphism Residual and Outlier (MR-PRESSO) test, and a leave-one-out test, to affirm the robustness and validity of our findings. Results: Our investigation indicates that an elevated prevalence of Deltaproteobacteria, Christensenellaceae, Desulfovibrionaceae, Eubacterium ruminantium group, Lachnospiraceae NK4A136 group, Methanobrevibacter, Desulfovibrionales, and Euryarchaeota is inversely associated with the risk of appendicitis. Conversely, we observed a positive correlation between an increased abundance of Family XIII, Howardella, and Veillonella and the susceptibility to appendicitis. Sensitivity analyses have corroborated the robustness of these findings, and Mendelian randomization analyses provided no indications of reverse causality. Conclusion: Our Mendelian randomization (MR) analysis has unveiled potential advantageous or detrimental causal associations between the gut microbiota and the occurrence of appendicitis. This study offers novel theoretical and empirical insights into the understanding of appendicitis pathogenesis, along with its implications for preventive and therapeutic strategies.