Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation.

Cytosolic RNA/DNA sensing elicits primary defense against viral pathogens. Interferon regulatory factor 3 (IRF3), a key signal mediator/transcriptional factor of the antiviral-sensing pathway, is indispensible for interferon production and antiviral defense. However, how the status of IRF3 activation is controlled remains elusive. Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1 (Mst1), but not Mst2, profoundly inhibited cytosolic nucleic acid sensing. Mst1 associated with IRF3 and directly phosphorylated IRF3 at Thr75 and Thr253. This Mst1-mediated phosphorylation abolished activated IRF3 homodimerization, its occupancy on chromatin, and subsequent IRF3-mediated transcriptional responses. In addition, Mst1 also impeded virus-induced activation of TANK-binding kinase 1 (TBK1), further attenuating IRF3 activation. As a result, Mst1 depletion or ablation enabled an enhanced antiviral response and defense in cells and mice. Therefore, the identification of Mst1 as a novel physiological negative regulator of IRF3 activation provides mechanistic insights into innate antiviral defense and potential antiviral prevention strategies.

Targeting proteostasis of the HEV replicase to combat infection in preclinical models.

BACKGROUND & AIMS: Appropriate treatment options are lacking for hepatitis E virus (HEV)-infected pregnant women and immunocompromised individuals. Thus, we aimed to identify efficient anti-HEV drugs through high-throughput screening, validate them in vitro and in vivo (in a preclinical animal study), and elucidate their underlying antiviral mechanism of action. METHODS: Using appropriate cellular and rodent HEV infection models, we studied a critical pathway for host-HEV interactions and performed a preclinical study of the corresponding antivirals, which target proteostasis of the HEV replicase. RESULTS: We found 17 inhibitors that target HEV-HSP90 interactions by unbiased compound library screening on human hepatocytes harboring an HEV replicon. Inhibitors of HSP90 (iHSP90) markedly suppressed HEV replication with efficacy exceeding that of conventional antivirals (IFNα and ribavirin) in vitro. Mechanistically, iHSP90 treatment released the viral replicase ORF1 protein from the ORF1-HSP90 complex and triggered rapid ubiquitin/proteasome-mediated degradation of ORF1, resulting in abrogated HEV replication. Furthermore, a preclinical trial in a Mongolian gerbil HEV infection model showed this novel anti-HEV strategy to be safe, efficient, and able to prevent HEV-induced liver damage. CONCLUSIONS: In this study, we uncover a proteostatic pathway that is critical for host-HEV interactions and we provide a foundation from which to translate this new understanding of the HEV life cycle into clinically promising antivirals. IMPACT AND IMPLICATIONS: Appropriate treatment options for hepatitis E virus (HEV)-infected pregnant women and immunocompromised patients are lacking; hence, there is an urgent need for safe and effective HEV-specific therapies. This study identified new antivirals (inhibitors of HSP90) that significantly limit HEV infection by targeting the viral replicase for degradation. Moreover, these anti-HEV drugs were validated in an HEV rodent model and were found to be safe and efficient for prevention of HEV-induced liver injury in preclinical experiments. Our findings substantially promote the understanding of HEV pathobiology and pave the way for antiviral development.

Targeting TBK1 attenuates ocular inflammation in uveitis by antagonizing NF-κB signaling.

Uveitis with complex pathogenesis is a kind of eye emergency involving refractory and blinding inflammation. Dysregulation of TANK binding kinase 1 (TBK1), which plays an important role in innate immunity, often leads to inflammatory diseases in various organs. However, the role of TBK1 in uveitis remains elusive. In this study, we identified that the mRNA expression level of TBK1 and its phosphorylation level were significantly increased in peripheral blood mononuclear cells (PBMCs) of patients with uveitis. Consistent with this, the expression of Tbk1 was elevated in the ocular tissues of uveitis rats and primary peritoneal macrophages while its phosphorylation levels, which present activation forms, were upregulated as well, accompanied by an increase in the level of nuclear factor-κB (NF-κB) and proinflammatory cytokines. In addition, inhibition of TBK1 may effectively reduce the inflammatory response of uveitis rats by blocking NF-κB entry into the nucleus and impeding the initiation of NLRP3 inflammasome- and caspase-1-mediated pyroptosis pathways.

Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host.

Helicobacter pylori (H. pylori) is a highly successful human pathogen that colonizes stomach in around 50% of the global population. The colonization of bacterium induces an inflammatory response and a substantial rise in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), mostly derived from host neutrophils and gastric epithelial cells, which play a crucial role in combating bacterial infections. However, H. pylori has developed various strategies to quench the deleterious effects of ROS, including the production of antioxidant enzymes, antioxidant proteins as well as blocking the generation of oxidants. The host's inability to eliminate H. pylori infection results in persistent ROS production. Notably, excessive ROS can disrupt the intracellular signal transduction and biological processes of the host, incurring chronic inflammation and cellular damage, such as DNA damage, lipid peroxidation, and protein oxidation. Markedly, the sustained inflammatory response and oxidative stress during H. pylori infection are major risk factor for gastric carcinogenesis. In this context, we summarize the literature on H. pylori infection-induced ROS production, the strategies used by H. pylori to counteract the host response, and subsequent host damage and gastric carcinogenesis.

Advances in targeted therapy for gastric cancer based on tumor driver genes. / é¶å‘è‚¿ç˜¤é©±åŠ¨åŸºå› çš„èƒƒç™Œæ²»ç–—ç ”ç©¶è¿›å±•.

As the understanding of the pathogenic mechanisms of gastric cancer deepens and the identification of gastric cancer driver genes advances, drugs targeting gastric cancer driver genes have been applied in clinical practice. Among them, trastuzumab, as the first targeted drug for gastric cancer, effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed human epidermal growth factor receptor 2 (HER2). Trastuzumab has become the standard treatment for HER2-positive gastric cancer patients. Ramucirumab, on the other hand, inhibits tumor angiogenesis by targeting vascular endothelial growth factor receptor 2 (VEGFR2) and has been used as second-line therapy for advanced gastric cancer patients. In addition, bemarituzumab targets overexpressed fibroblast growth factor receptor 2 (FGFR2), while zolbetuximab targets overexpressed claudin 18.2 (CLDN18.2), significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials. This article reviews the roles of tumor driver genes in the progression of gastric cancer, and the treatment strategies for gastric cancer primarily based on targeting HER2, VEGF, FGFR2, CLDN18.2 and MET. This provides a reference for clinical application of targeted therapy for gastric cancer.

Color-Tunable Dual-Mode Organic Afterglow from Classical Aggregation-Caused Quenching Compounds for White-Light-Manipulated Anti-Counterfeiting.

Color-tunable dual-mode organic afterglow excited by ultraviolet (UV) and white light was achieved from classical aggregation-caused quenching compounds for the first time. Specifically, two luminescent systems, which could produce significant organic afterglow composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence under ambient conditions, were constructed by doping fluorescein sodium and calcein sodium into aluminum sulfate. Their lifetimes surpassed 600 ms, and the dopant concentrations were as low as 5×10-6  wt %. Moreover, the persistent luminescence colors of the materials could be tuned from blue to green and then to yellow by simply varying the concentrations of guest compounds or the temperature in the range of 260-340 K. Inspired by these exciting results, the afterglow materials were used for UV- and white-light-manipulated anti-counterfeiting and preparation of elastomers with different colors of persistent luminescence.

Efficient and Color-Tunable Dual-Mode Afterglow from Large-Area and Flexible Polymer-Based Transparent Films for Anti-Counterfeiting and Information Encryption.

It remains a great challenge to develop polymer-based materials with efficient and color-tunable organic afterglow. Two indolocarbazole derivatives IaCzA and IbCzA have been synthesized and doped into poly(vinyl alcohol) (PVA) matrices. It is found that the resulting films can produce unique dual-mode afterglow, which is composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence. Besides, the IbCzA-doped PVA film exhibits intense blue afterglow with Φafterglow and τafterglow up to 19.8 % and 1.81 s, respectively, representing state-of-the-art dual-mode organic afterglow performance. Moreover, our reported film has high flexibility, excellent transparency, and large-area producibility; and the afterglow color of the film can be linearly tuned by temperature. Inspired by these distinctive properties, the PVA doped with IbCzA was employed as temperature-sensitive security ink for anti-counterfeiting and information encryption.

Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1.

A machine learning approach has been applied to virtual screening for lysine specific demethylase 1 (LSD1) inhibitors. LSD1 is an important anti-cancer target. Machine learning models to predict activity were constructed using Morgan molecular fingerprints. The dataset, consisting of 931 molecules with LSD1 inhibition activity, was obtained from the ChEMBL database. An evaluation of several candidate algorithms on the main dataset revealed that the support vector regressor gave the best model, with a coefficient of determination (R2) of 0.703. Virtual screening, using this model, identified five predicted potent inhibitors from the ZINC database comprising more than 300,000 molecules. The virtual screening recovered a known inhibitor, RN1, as well as four compounds where activity against LSD1 had not previously been suggested. Thus, we performed a machine-learning-enabled virtual screening of LSD1 inhibitors using only the structural information of the molecules.

Potential serum biomarkers from a metabolomics study of autism.

BACKGROUND: Early detection and diagnosis are very important for autism. Current diagnosis of autism relies mainly on some observational questionnaires and interview tools that may involve a great variability. We performed a metabolomics analysis of serum to identify potential biomarkers for the early diagnosis and clinical evaluation of autism. METHODS: We analyzed a discovery cohort of patients with autism and participants without autism in the Chinese Han population using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS) to detect metabolic changes in serum associated with autism. The potential metabolite candidates for biomarkers were individually validated in an additional independent cohort of cases and controls. We built a multiple logistic regression model to evaluate the validated biomarkers. RESULTS: We included 73 patients and 63 controls in the discovery cohort and 100 cases and 100 controls in the validation cohort. Metabolomic analysis of serum in the discovery stage identified 17 metabolites, 11 of which were validated in an independent cohort. A multiple logistic regression model built on the 11 validated metabolites fit well in both cohorts. The model consistently showed that autism was associated with 2 particular metabolites: sphingosine 1-phosphate and docosahexaenoic acid. LIMITATIONS: While autism is diagnosed predominantly in boys, we were unable to perform the analysis by sex owing to difficulty recruiting enough female patients. Other limitations include the need to perform test-retest assessment within the same individual and the relatively small sample size. CONCLUSION: Two metabolites have potential as biomarkers for the clinical diagnosis and evaluation of autism.

Transition-state stabilization in Escherichia coli ribonuclease P RNA-mediated cleavage of model substrates.

We have used model substrates carrying modified nucleotides at the site immediately 5' of the canonical RNase P cleavage site, the -1 position, to study Escherichia coli RNase P RNA-mediated cleavage. We show that the nucleobase at -1 is not essential but its presence and identity contribute to efficiency, fidelity of cleavage and stabilization of the transition state. When U or C is present at -1, the carbonyl oxygen at C2 on the nucleobase contributes to transition-state stabilization, and thus acts as a positive determinant. For substrates with purines at -1, an exocyclic amine at C2 on the nucleobase promotes cleavage at an alternative site and it has a negative impact on cleavage at the canonical site. We also provide new insights into the interaction between E. coli RNase P RNA and the -1 residue in the substrate. Our findings will be discussed using a model where bacterial RNase P cleavage proceeds through a conformational-assisted mechanism that positions the metal(II)-activated H2O for an in-line attack on the phosphorous atom that leads to breakage of the phosphodiester bond.

Structure of AadA from Salmonella enterica: a monomeric aminoglycoside (3'')(9) adenyltransferase.

Aminoglycoside resistance is commonly conferred by enzymatic modification of drugs by aminoglycoside-modifying enzymes such as aminoglycoside nucleotidyltransferases (ANTs). Here, the first crystal structure of an ANT(3'')(9) adenyltransferase, AadA from Salmonella enterica, is presented. AadA catalyses the magnesium-dependent transfer of adenosine monophosphate from ATP to the two chemically dissimilar drugs streptomycin and spectinomycin. The structure was solved using selenium SAD phasing and refined to 2.5 Å resolution. AadA consists of a nucleotidyltransferase domain and an α-helical bundle domain. AadA crystallizes as a monomer and is a monomer in solution as confirmed by small-angle X-ray scattering, in contrast to structurally similar homodimeric adenylating enzymes such as kanamycin nucleotidyltransferase. Isothermal titration calorimetry experiments show that ATP binding has to occur before binding of the aminoglycoside substrate, and structure analysis suggests that ATP binding repositions the two domains for aminoglycoside binding in the interdomain cleft. Candidate residues for ligand binding and catalysis were subjected to site-directed mutagenesis. In vivo resistance and in vitro binding assays support the role of Glu87 as the catalytic base in adenylation, while Arg192 and Lys205 are shown to be critical for ATP binding.

Cleavage mediated by the P15 domain of bacterial RNase P RNA.

Independently folded domains in RNAs frequently adopt identical tertiary structures regardless of whether they are in isolation or are part of larger RNA molecules. This is exemplified by the P15 domain in the RNA subunit (RPR) of the universally conserved endoribonuclease P, which is involved in the processing of tRNA precursors. One of its domains, encompassing the P15 loop, binds to the 3'-end of tRNA precursors resulting in the formation of the RCCA-RNase P RNA interaction (interacting residues underlined) in the bacterial RPR-substrate complex. The function of this interaction was hypothesized to anchor the substrate, expose the cleavage site and result in re-coordination of Mg(2+) at the cleavage site. Here we show that small model-RNA molecules (~30 nt) carrying the P15-loop mediated cleavage at the canonical RNase P cleavage site with significantly reduced rates compared to cleavage with full-size RPR. These data provide further experimental evidence for our model that the P15 domain contributes to both substrate binding and catalysis. Our data raises intriguing evolutionary possibilities for 'RNA-mediated' cleavage of RNA.

The impact of varying trolley case usage modes and weights on body posture.

OBJECTIVE: To study the body posture characteristics when walking with trolley case, and to explore the effects of different usage methods and weights of trolley case on body posture characteristics. METHODS: Fifteen subjects pushed and pulled(Condition 1 and 2) the case with three load weights of 10 %, 20 % and 30 % of their own body weight with 0 % no load as baseline for both conditions. The basic gait parameters, kinematic and kinetic data were collected using the VICON infrared motion capture system and a 3D force platform. Two repeated measures factor (condition×weight) analysis of variance was used for statistical analysis of the gait temporal and spatial parameters, as well as trunk angle, kinetic ground reaction force, shoulder joint force, and trunk moment. RESULTS: Significant condition*weight interactions were detected in DLST (Double Limb Stance Time) (F=5.341，P = 0.006), GRF (Ground Reaction Force) in frontal plane (F=10.507, p < 0.001) and vertical plane (F=3.751, p = 0.021), shoulder joint force in sagittal plane (F=21.129, p < 0.001), and flexion-extension angle of the trunk in the sagittal plane (F=4.888, p < 0.010). Significant main effects were detected in walking speed (F=35.842, p < 0.001), right support time (F=12.156, p < 0.001), left swing time (F=8.506, p < 0.001), left support time (F=1.122, p < 0.001), right step length (F=33.900, p < 0.001), and left step length (F=14.960, p < 0.001) under different weights. A significant main effect was detected in sagittal GRF (F=11.77, p < 0.001), trunk rotation angle (F=4.124, p = 0.016), amplitude of COM (F=2.993, p = 0.046), under different weights. CONCLUSION: When the weight of the case exceeds 20 % of the body weight, from the perspective of energy efficiency, the push method is more advantageous than the pull method. When walking with luggage, people tend to maintain the stability of their trunk posture by adjusting the force on their arms more often.

Two-Dimensional Amorphous Titanium Dioxide/Silver (TiO2/Ag) Nanosheets as a Surface-Enhanced Raman Spectroscopy Substrate for Highly Sensitive Detection.

For the purpose of investigating the chemical enhancement of amorphous semiconductors as well as increasing the sensitivity of the surface-enhanced Raman spectroscopy (SERS) substrate, titanium dioxide (TiO2) precursors were calcined at different temperatures to generate crystallized TiO2 (c-TiO2) and amorphous TiO2 (a-TiO2) nanosheets, respectively. Afterward, a two-dimensional (2D) a-TiO2/Ag nanosheet SERS substrate was successfully fabricated using electrostatic interaction between a-TiO2 and Ag nanoparticles. In order to demonstrate a greater SERS sensitivity on a-TiO2/Ag compared to either c-TiO2 or Ag nanoparticles alone, the SERS probe molecules rhodamine 6G (R6G) and malachite green (MG) were utilized. Based on the results of SERS detections for probe molecules and contaminants, it demonstrates that a-TiO2/Ag nanosheets produce highly sensitive and repeatable Raman signals. The detectable concentration limits for R6G and MG were found to be 10-11 M and 10-10 M, respectively. And it has been determined that the system exhibits an enhancement factor (EF) of up to 1 × 108. The limit of detection for 4-mercaptobenzoic acid and alizarin red can both reach 1 × 10-8. Furthermore, a finite-difference time-domain simulation is performed in order to evaluate the magnetic field strength generated by Ag nanoparticles. As a result of the simulation, it is evident that the actual EF is smaller than the calculated one, leading support to the view that a-TiO2 nanosheets have a beneficial effect on the chemical enhancement of SERS.

Self-Assembled Three-Dimensional Polyamide/Silver Nanoparticle Pore Array as a Highly Sensitive and Reproducible SERS Substrate for Pesticide Detection in Water.

In this study, silver nanoparticles (AgNPs) are self-assembled onto the polyamide (PA) pore array through hydrogen bonding, resulting in and optimizing the PA/Ag 3D pore array substrates. The best surface-enhanced Raman scattering (SERS) substrate is obtained with a pore depth of 500 nm in the PA array, 30 nm AgNPs, at a pH of 5.0, and a 24 h assembly time. The SERS performance of the substrates is assessed using rhodamine 6G (R6G) as a probe molecule. The detection limit of the R6G molecule reaches 10-13 M, and the relative standard deviation is under 20%, indicating good enhancement ability and reproducibility. Furthermore, label-free detection of pesticide contaminant diquat with a detection limit of 2.69 × 10-9 M is achieved using the optimized 3D substrate, which meets environmental monitoring requirements for drinking water. The findings demonstrate that this 3D SERS substrate has promising potential for use and development in the fields of contaminant detection and chemical sensing.

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.

Cleavage of model substrates by archaeal RNase P: role of protein cofactors in cleavage-site selection.

RNase P is a catalytic ribonucleoprotein primarily involved in tRNA biogenesis. Archaeal RNase P comprises a catalytic RNase P RNA (RPR) and at least four protein cofactors (RPPs), which function as two binary complexes (POP5•RPP30 and RPP21• RPP29). Exploiting the ability to assemble a functional Pyrococcus furiosus (Pfu) RNase P in vitro, we examined the role of RPPs in influencing substrate recognition by the RPR. We first demonstrate that Pfu RPR, like its bacterial and eukaryal counterparts, cleaves model hairpin loop substrates albeit at rates 90- to 200-fold lower when compared with cleavage by bacterial RPR, highlighting the functionally comparable catalytic cores in bacterial and archaeal RPRs. By investigating cleavage-site selection exhibited by Pfu RPR (±RPPs) with various model substrates missing consensus-recognition elements, we determined substrate features whose recognition is facilitated by either POP5•RPP30 or RPP21•RPP29 (directly or indirectly via the RPR). Our results also revealed that Pfu RPR + RPP21•RPP29 displays substrate-recognition properties coinciding with those of the bacterial RPR-alone reaction rather than the Pfu RPR, and that this behaviour is attributable to structural differences in the substrate-specificity domains of bacterial and archaeal RPRs. Moreover, our data reveal a hierarchy in recognition elements that dictates cleavage-site selection by archaeal RNase P.

Effectiveness of "Stop the Bleed" Courses: A Systematic Review and Meta-analysis.

OBJECTIVE: Our object was to comprehensively analyze the existing body of evidence to evaluate the Stop the Bleed (STB) course effectiveness and satisfaction and find the direction of improvement for the future. STUDY DESIGN: A literature search with the term "Stop the Bleed" in the electronic databases PubMed, Web of Science, EMBASE, Cochrane Library was performed, retrieving records from January 1, 2013 to April 13, 2022 based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. In addition, all selected papers' references were examined for qualified studies that were missed during the first search. Original publications were included that reported on (1) clinical studies of the STB course implementation; and (2) studies comparing students' hemostasis ability and attitude (comfort, confidence, and willingness) before and after the STB course. The literature search and data extraction were done independently by 2 writers. To establish consensus, disagreements will be handled with the help of a third reviewer. For data synthesis, the most inclusive data from studies with repeated data were abstracted. Changes in hemostasis questionnaire scoring and operation evaluation after the STB course were the main outcomes. RESULTS: This systematic review and meta-analysis includes 36 trials with a total of 11,561 trainees. Thirty-one of them were undertaken in the USA, while the other 5, accounting for 13.9%, were conducted in other regions. Among various evaluation methods, 3 trials with 927 trainees indicated that scores of correct uses of tourniquet significantly increased after the STB course (mean difference of post versus pre groups, 44.28; 95% CI 41.24-47.32; p < 0.001). Significant difference was also observed in the willingness to apply a hemostatic dressing in a real-world situation (risk ratio for post versus pre groups, 1.28; 95% CI 1.08-1.52; p = 0.004) (7 studies and 2360 participants). The results indicate that hemostasis knowledge and skills after the STB course had improved, but statistics indicated that STB courses implemented in the USA were more effective than other regions. CONCLUSIONS AND RELEVANCE: Meta-analysis showed that comparison before and after the STB course were significantly different. However, the outcome measures in each study were different and could not, therefore, be compiled in all cases. The effectiveness and worth of implementation of STB in different countries should be continuously evaluated in the future.

Importance of residue 248 in Escherichia coli RNase P RNA mediated cleavage.

tRNA genes are transcribed as precursors and RNase P generates the matured 5' end of tRNAs. It has been suggested that residue - 1 (the residue immediately 5' of the scissile bond) in the pre-tRNA interacts with the well-conserved bacterial RNase P RNA (RPR) residue A248 (Escherichia coli numbering). The way A248 interacts with residue - 1 is not clear. To gain insight into the role of A248, we analyzed cleavage as a function of A248 substitutions and N-1 nucleobase identity by using pre-tRNA and three model substrates. Our findings are consistent with a model where the structural topology of the active site varies and depends on the identity of the nucleobases at, and in proximity to, the cleavage site and their potential to interact. This leads to positioning of Mg2+ that activates the water that acts as the nucleophile resulting in efficient and correct cleavage. We propose that in addition to be involved in anchoring the substrate the role of A248 is to exclude bulk water from access to the amino acid acceptor stem, thereby preventing non-specific hydrolysis of the pre-tRNA. Finally, base stacking is discussed as a way to protect functionally important base-pairing interactions from non-specific hydrolysis, thereby ensuring high fidelity during RNA processing and the decoding of mRNA.

Phenyl lactic acid alleviates Helicobacter pylori infection in C57BL/6 mice.

Helicobacter pylori is a gastric pathogen that colonizes approximately 50% of the world's population. Infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. In the present study, we found that phenyl lactic acid (PLA) derived from Lactobacillus plantarum ZJ316 (L. plantarum ZJ316) can directly inhibit the growth and urease activity of H. pylori in vitro with a minimum inhibitory concentration (MIC) of 2.5 mg mL-1. Moreover, PLA also caused a dramatic morphological transformation from a spiral to a coccoid form in H. pylori. In this work, we also analyzed the beneficial effects of PLA in mice. The results showed that PLA administration ameliorated H. pylori-induced gastric mucosal damage and significantly decreased lymphocyte infiltration and inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin 6 (IL-6), and interferon-γ (IFN-γ) by 59.93%, 63.95%, and 48.05%, respectively, but elevated the interleukin-10 (IL-10) and glutathione (GSH) levels. Furthermore, PLA administration improved microbiota diversity with increased Bacteroidetes abundance and decreased Proteobacteria abundance by 46.39% and 24.05%, respectively. PLA also significantly reduced the abundance of H. pylori but increased the relative abundances of potential beneficial bacteria, such as Faecalibacterium, Bifidobacterium, and Lactobacillus. These results demonstrated that PLA can ameliorate H. pylori-induced inflammation and support beneficial gut bacteria, providing a new perspective against H. pylori infection.