Identification of a 9-gene signature to enhance biochemical recurrence prediction in primary prostate cancer: A benchmarking study using ten machine learning methods and twelve patient cohorts.

Prostate cancer (PCa) is a prevalent malignancy among men worldwide, and biochemical recurrence (BCR) after radical prostatectomy (RP) is a critical turning point commonly used to guide the development of treatment strategies for primary PCa. However, the clinical parameters currently in use are inadequate for precise risk stratification and informing treatment choice. To address this issue, we conducted a study that collected transcriptomic data and clinical information from 1662 primary PCa patients across 12 multicenter cohorts globally. We leveraged 101 algorithm combinations that consisted of 10 machine learning methods to develop and validate a 9-gene signature, named BCR SCR, for predicting the risk of BCR after RP. Our results demonstrated that BCR SCR generally outperformed 102 published prognostic signatures. We further established the clinical significance of these nine genes in PCa progression at the protein level through immunohistochemistry on Tissue Microarray (TMA). Moreover, our data showed that patients with higher BCR SCR tended to have higher rates of BCR and distant metastasis after radical radiotherapy. Through drug target prediction analysis, we identified nine potential therapeutic agents for patients with high BCR SCR. In conclusion, the newly developed BCR SCR has significant translational potential in accurately stratifying the risk of patients who undergo RP, monitoring treatment courses, and developing new therapies for the disease.

Structurally colored semitransparent perovskite solar cells using one-step deposition of self-ordering microgel particles.

Semitransparent perovskite solar cells (STPSCs) have excellent potential for widespread application as building integrated photovoltaics. Widespread application of STPSCs could result in decreased CO2 footprints for buildings. Unfortunately, STPSCs tend to have poor aesthetic qualities (being usually red-brown in color) and low stability. Building on our previous work, here we use new poly(N-isopropylacrylamide) microgels (PNP MGs) to provide highly ordered non-close packed arrays within perovskite films that reflect some of the incident light to provide structural color to STPSCs. (MGs are swellable crosslinked polymer colloid particles.) We introduce PNP MGs into two different perovskites and achieve a wide gamut of reflected color and iridescence from the perovskite films. Devices containing the MGs have average visible transparency (AVT) values of greater than 25%. The best PCE for a MG-containing STPSC is 10.60% compared to 9.14% for the MG-free control. The MGs not only introduce structural color to the STPSCs but increase the PCE and stability. Equations are provided that enable the reflected color to be predicted from the formulation used to deposit the films. Our work shows that the self-ordering tendency of PNP MGs gives a viable new method for introducing structural color into STPSCs. Because our one-step method for introducing structural color into STPSCs is general, does not introduce any additional processing steps and is scalable whilst also improving device stability, this study may bring deployment of STPSCs closer.

Investigating the impact of high-altitude on vehicle carbon emissions: A comprehensive on-road driving study.

This study addresses the literature gap concerning accurately identifying vehicle carbon emission characteristics in high-altitude areas. Utilizing a portable emission measurement system (PEMS) for real-world testing, we quantified the influence of altitude on carbon emissions from light-duty gasoline (LDGV) and diesel vehicles (LDDV). The Random Forest (RF) algorithm was employed to analyze the complex nonlinear relationships between altitude, meteorological conditions, driving patterns, and carbon dioxide (CO2) emissions, enabling predictions across different altitudes. The results showed that CO2 emissions progressively increase with elevation. Furthermore, as altitude increases, combustion efficiency declines, and the overall impact of driving conditions on emission rates diminishes. Altitude and meteorological factors significantly contributed to CO2 emissions, whereas driving conditions and road grades contributed less. Compared with the COPERT model, the RF model demonstrates strong accuracy in predicting carbon emissions at different altitudes. Specifically, the CO2 emission rate nearly triples as altitude increases from 2.0 km to 4.5 km. This research bridges a critical gap in the understanding carbon emissions from high-altitude vehicles, offering insights into policy development for emission reduction strategies in such regions. Future studies should integrate diverse testing methodologies and comprehensive surveys to validate and extend the findings.

Assessment of Collateral Flow in Patients with Carotid Stenosis Using Random Vessel-Encoded Arterial Spin-Labeling: Comparison with Digital Subtraction Angiography.

BACKGROUND AND PURPOSE: Collateral circulation plays an important role in steno-occlusive internal carotid artery disease (ICAD) to reduce the risk of stroke. We aimed to investigate the utility of planning-free random vessel-encoded arterial spin-labeling (rVE-ASL) in assessing collateral flows in patients with ICAD. MATERIALS AND METHODS: Forty patients with ICAD were prospectively recruited. The presence and extent of collateral flow were assessed and compared between rVE-ASL and DSA by using Contingency (C) and Cramer V (V) coefficients. The differences in flow territory alterations stratified by stenosis ratio and symptoms, respectively, were compared between symptomatic (n = 19) and asymptomatic (n = 21) patients by using the Fisher exact test. RESULTS: Good agreement was observed between rVE-ASL and DSA in assessing collateral flow (C = 0.762, V = 0.833, both P < .001). Patients with ICA stenosis of ≥90% were more likely to have flow alterations (P < .001). Symptomatic patients showed a higher prevalence of flow alterations in the territory of the MCA on the same side of ICAD (63.2%), compared with asymptomatic patients (23.8%, P = .012), while the flow alterations in the territory of anterior cerebral artery did not differ (P = .442). The collateral flow to MCA territory was developed primarily from the contralateral internal carotid artery (70.6%) and vertebrobasilar artery to a lesser extent (47.1%). CONCLUSIONS: rVE-ASL provides comparable information with DSA on the assessment of collateral flow. The flow alterations in the MCA territory may be attributed to symptomatic ICAD.

Endovascular reconstruction of high cervical and long-segment carotid artery dissections with Leo plus stent.

PURPOSE: Endovascular reconstruction has emerged as a viable alternative for carotid artery dissections (CADs) that are unresponsive to antithrombotic therapy. However, high cervical and long-segment CADs pose challenges during endovascular treatment due to their distal location and tortuous anatomy. We presented our experiences using endovascular reconstruction with the Leo plus stent for this type of CAD. METHODS: We conducted a retrospective review of patients with high cervical and long-segment CADs treated using the Leo plus stent. We analyzed patient demographics, clinical presentations, procedural features, complications, and follow-up outcomes. RESULTS: A total of 17 patients (mean age, 48.1 years) with 17 CADs were identified. Seven of these dissections were accompanied by pseudoaneurysm. The mean length of the dissection was 5.7 cm, and the mean degree of stenosis was 92.3%. A single Leo plus stent was deployed in 15 patients, while another Wallstent carotid stent was used in 2 cases. All stents were successfully positioned in their intended sites. The average degree of residual stenosis was 22.2%. There were no perioperative complications. With a median follow-up duration of 29 months, no ischemic stroke events occurred. All but one Leo plus stent remained patent during follow-up, and all 7 pseudoaneurysms had disappeared at the last radiological assessment. CONCLUSION: Our experience in treating high cervical and long-segment CADs with the Leo plus stent demonstrates that this approach is practical, safe, and effective, as evidenced by long-term observations. The Leo Plus stent appears to be a suitable option for managing this type of CAD.

Periprocedural thromboembolic complications of LEO baby stent in endovascular treatment of intracranial aneurysms: Experience in 149 patients.

OBJECTIVE: To report periprocedural thromboembolic complications of LEO Baby stent-assisted coiling of wide-necked intracranial aneurysms and to analyze the possible influencing factors. METHODS: We retrospectively identified 149 patients with aneurysms who underwent LEO Baby stent-assisted embolization between October 2018 and March 2022. Clinical and radiographic data of patients were reviewed to determine whether a thromboembolic event had occurred. Multivariate logistic analysis was performed to identify significant factors associated with thromboembolic events. RESULTS: Successful stent deployment of the stent was achieved in all patients in the target artery. There were 66 patients (44.3%) with acutely ruptured aneurysms and 83 patients (55.7%) with unruptured aneurysms. Fourteen (9.4%, 95% confidence interval: 4.7%-14.1%) patients were confirmed to have developed a thromboembolic event, including nine patients with acute intraoperative thrombosis and five patients with postoperative thromboembolic events. The rate of thromboembolic events was 6.0% (5/83) in patients with unruptured aneurysms and 13.6% (9/66) in patients with acutely ruptured aneurysms. There was a trend toward an increased rate of thromboembolic events in patients with acute ruptured aneurysms (p = 0.087). Thromboembolic events were significantly associated with the parent-artery diameter (p = 0.010). CONCLUSIONS: Our study demonstrates a low rate of thromboembolic complications in unruptured aneurysms treated with LEO Baby stent. Thromboembolic events appear to be more common in ruptured aneurysms. A small diameter of the parent artery is associated with an increased risk of thromboembolic complications, and more relevant studies are still needed.

Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report.

BACKGROUND: Spinal subarachnoid hematoma (SSH) is a known but rare entity that can cause cauda equina compression. The occurrence of SSH associated with aneurysmal subarachnoid hemorrhage has rarely been described in the literature. CASE PRESENTATION: A 56-year-old woman presented with subarachnoid hemorrhage secondary to a ruptured middle cerebral artery aneurysm and was managed with coiling embolization without stent assistance. There was no history of either lumbar puncture or the use of anticoagulants. The patient developed severe lumbago radiating to bilateral legs nine days after the procedure. Subsequent magnetic resonance imaging demonstrated a SSH extending from L5 to S2 and wrapping around the cauda equina. The patient was treated with intravenous methylprednisolone (250 mg/day) for four consecutive days, followed by a taper of oral prednisolone (20 mg/day) until complete recovery. Magnetic resonance imaging at one month follow-up revealed complete resolution of the SSH. CONCLUSIONS: Here, we report a case of acute cauda equina syndrome caused by a SSH after aneurysmal subarachnoid hemorrhage, which will facilitate timely intervention of patients with this disorder.

Application of machine learning algorithms to predict lymph node metastasis in gastric neuroendocrine neoplasms.

Background: Neuroendocrine neoplasms (NENs) are tumors that originate from secretory cells of the diffuse endocrine system and typically produce bioactive amines or peptide hormones. This paper describes the development and validation of a predictive model of the risk of lymph node metastasis among gastric NEN patients based on machine learning platform. Methods: In this investigation, data from 1256 patients were used, of whom 119 patients from the First Affiliated Hospital of Soochow University in China and 1137 cases from the surveillance epidemiology and end results (SEER) database were combined. Six machine learning algorithms, including the logistic regression model (LR), random forest (RF), decision tree (DT), Naive Bayes (NB), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), were used to build the predictive model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: Among the 1256 patients with gastric NENs, 276 patients (21.97 %) developed lymph node metastasis. T stage, tumor size, degree of differentiation, and sex were predictive factors of lymph node metastasis. The RF model achieved the best predictive performance among the six machine learning models, with an AUC, accuracy, sensitivity, and specificity of 0.81, 0.78, 0.76, and 0.82, respectively. Conclusion: The RF model provided the best prediction and can help physicians determine the lymph node metastasis risk of gastric NEN patients to formulate individualized medical strategies.

Analysis of influencing factors of hemorrhagic transformation in patients with large vessel occlusion stroke after mechanical thrombectomy.

OBJECTIVE: To investigate the influencing factors of hemorrhagic transformation (HT) after mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke. METHODS: From September 2018 to December 2022, 270 eligible patients with LVO who underwent MT in the First Affiliated Hospital of Nanjing medical University were selected for this retrospective study, and the patients were divided into an occurrence group and a non-occurrence group based on the immediate and 24 h postoperative head CT results. The influencing factors of postoperative HT after MT were identified using univariate and logistic regression analyses. A Nomogram was constructed using logistic variables of significance. Then, area under the ROC curve (AUC) was used to verify the predictive efficacy of the Nomogram, and decision curve analysis (DCA) was used to test the clinical validity of the Nomogram. RESULTS: HT occurred in 60 patients (23.70%) after MT. Logistic regression analysis showed that, male (OR=2.099, 95% CI: 1.051-4.193), age ≥71.5 years (OR=3.780, 95% CI: 1.836-7.782), preoperative NIHSS score ≥16.5 (OR=2.328, 95% CI: 1.112-4.873), operation time ≥58.5 min (OR=2.930, 95% CI: 1.294-6.634), and admission blood glucose ≥7.65 mmol/L (OR=4.915, 95% CI: 2.373-10.178) were risk factors for the occurrence of HT in patients with LVO stroke after MT. Admission serum magnesium ≥0.845 mmol/L (OR=0.225, 95% CI: 0.127-0.513) was a protective factor for the occurrence of HT in the patients after MT. The ROC curve showed that the AUC of the nomogram in the training set and test set were 0.849 (95% CI: 0.787-0.910) and 0.754 (95% CI: 0.634-0.874), respectively. DCA suggested that the nomogram revealed good clinical validity in the training and test sets. CONCLUSION: Sex, age, preoperative NIHSS score, operation time, blood glucose and serum magnesium levels at admission are influencing factors for the occurrence of HT in patients with LVO stroke after MT. The nomogram in this study has a good predictive efficiency, which can improve the diagnostic efficiency of HT after MT in patients with LVO stroke. Therefore, male patients with age ≥71.5 years, preoperative NIHSS score ≥16.5, operation time ≥58.5 min, admission blood glucose ≥7.65 mmol/L, and admission serum magnesium ≤0.845 mmol/L should raise awareness about the risk of HT after MT.

Crosstalk between alternative splicing and inflammatory bowel disease: Basic mechanisms, biotechnological progresses and future perspectives.

BACKGROUND: Alternative splicing (AS) is an omnipresent regulatory mechanism of gene expression that enables the generation of diverse splice isoforms from a single gene. Recently, AS events have gained considerable momentum in the pathogenesis of inflammatory bowel disease (IBD). METHODS: Our review has summarized the complex process of RNA splicing, and firstly highlighted the potential involved molecules that target aberrant splicing events in IBD. The quantitative transcriptome analyses such as microarrays, next-generation sequencing (NGS) for AS events in IBD have been also discussed. RESULTS: Available evidence suggests that some abnormal splicing RNAs can lead to multiple intestinal disorders during the onset of IBD as well as the progression to colitis-associated cancer (CAC), including gut microbiota perturbations, intestinal barrier dysfunctions, innate/adaptive immune dysregulations, pro-fibrosis activation and some other risk factors. Moreover, current data show that the advanced technologies, including microarrays and NGS, have been pioneeringly employed to screen the AS candidates and elucidate the potential regulatory mechanisms of IBD. Besides, other biotechnological progresses such as the applications of third-generation sequencing (TGS), single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), will be desired with great expectations. CONCLUSIONS: To our knowledge, the current review is the first one to evaluate the potential regulatory mechanisms of AS events in IBD. The expanding list of aberrantly spliced genes in IBD along with the developed technologies provide us new clues to how IBD develops, and how these important AS events can be explored for future treatment.

Corrigendum: Seed coat pattern QTL and development in cowpea (Vigna unguiculata [L.] Walp.).

[This corrects the article DOI: 10.3389/fpls.2019.01346.].

Observation of Electronic Strong Correlation in VTe_{2}-2sqrt[3]×2sqrt[3] Monolayer.

Strong electron correlation under two-dimensional limit is intensely studied in the transition metal dichalcogenides monolayers, mostly within their charge density wave (CDW) states that host a star of David period. Here, by using scanning tunneling microscopy and spectroscopy and density functional theory calculations with on-site Hubbard corrections, we study the VTe_{2} monolayer with a different 2sqrt[3]×2sqrt[3] CDW period. We find that the dimerization of neighboring Te-Te and V-V atoms occurs during the CDW transition, and that the strong correlation effect opens a Mott-like full gap at Fermi energy (E_{F}). We further demonstrate that such a Mott phenomenon is ascribed to the combination of the CDW transition and on-site Coulomb interactions. Our work provides a new platform for exploring Mott physics in 2D materials.

Design and Validation of a Novel Evaluation Scale to Predict Inpatient Large Vessel Occlusion Strokes: Clinical Assessment Stroke Severity for Inpatient Scale.

OBJECTIVES: A large quantity of ischemic stroke events occur in patients hospitalized for non-stroke-related reason. No scale has been developed to identify the large vessel occlusion (LVO) among inpatient stroke alerts. We aimed to develop a novel evaluation scale to predict LVO from in-hospital stroke alerts. METHODS: Data from consecutive in-hospital stroke alerts were analyzed at a single high volume stroke center between January 2016 and October 2020. We developed a predictive scale based on the first half of patients (training group) using multivariate logistic regression and evaluated it in the remaining half of patients (validation group) adopting receiver operating curve. Receiver operating characteristics of the scale were analyzed to evaluate its value for the detection of LVO. RESULTS: A total of 243 patients were enrolled for further study, among them, 94 (38.7%) had confirmed LVO. Three risk factors independently predicted the presence of LVO: recent cardiac or pulmonary procedure (1 point), neurological deficit scale (≥1: 2 points), and history of atrial fibrillation (1 point). The CAPS scale was generated based on predictive factors and demonstrated highly effective discrimination in identifying the presence of LVO in the training group (area under curve = 0.956) and the validation group (area under curve = 0.940). When the score ≥2, CAPS scale showed 97.9% sensitivity, 79.2% specificity, 74.8% positive predictive value, and 98.3% negative predictive value for discriminating LVO. CONCLUSIONS: CAPS scale was developed for identifying LVO among inpatient stroke alerts with high sensitivity and specificity, which may help to quickly prompt responses by appropriate stroke teams.

Radiomics features on computed tomography reflect thrombus histological age prior to endovascular treatment of acute ischemic stroke.

PURPOSE: To investigate the role of radiomics features in thrombus age identification and establish a CT-based radiomics model for predicting thrombus age of large vessel occlusion stroke patients. METHODS: We retrospectively reviewed patients with middle cerebral artery occlusion receiving mechanical thrombectomy from July 2020 to March 2022 at our center. The retrieved clots were stained with Hematoxylin and Eosin (H&E) and determined as fresh or older thrombi based on coagulation age. Clot-derived radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression analysis, by which selected radiomics features were integrated into the Rad-score via the corresponding coefficients. The prediction performance of Rad-score in thrombus age was evaluated with the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 104 patients were included in our analysis, with 52 in training and 52 in validation cohort. Older thrombi were characterized with delayed procedure time, worse functional outcome and marginally associated with more attempts of device. We extracted 982 features from NCCT images. Following T test and LASSO analysis in training cohort, six radiomics features were selected, based on which the Rad-score was generated by the linear combination of features. The Rad-score showed satisfactory performance in distinguishing fresh with older thrombi, with the AUC of 0.873 (95 %CI: 0.777-0.956) and 0.773 (95 %CI: 0.636-0.910) in training and validation cohort, respectively. CONCLUSION: This study established and validated a CT-based radiomics model that could accurately differentiate fresh with older thrombi for stroke patients receiving mechanical thrombectomy.

Endovascular recanalization for symptomatic chronic internal carotid artery occlusion: proposal of a modified angiographic classification and clinical outcomes.

PURPOSE: To stratify angiographic images of chronic internal carotid artery occlusion (CICAO) into a newly modified angiographic classification, and identify suitable candidates for endovascular recanalization. METHODS: This study included 51 consecutive patients with symptomatic CICAO who underwent endovascular recanalization at our institution. Patients' clinical information, angiographic findings, procedural results, and outcomes were recorded. We attempted to stratify all angiographic images into categories based on morphological occlusive patterns and distal internal carotid artery (ICA) lumen reconstitution on digital subtraction angiography (DSA). RESULTS: Four types (I-IV) of CICAO were identified based on angiographic characteristics. We defined type I as having a tapered (IA) or blunt stump (IB) and distal ICA lumen reconstitution with collateral filling; type II as having no stump but with distal ICA lumen reconstitution; type III as having a tapered (IIIA) or blunt stump (IIIB) but no distal ICA lumen reconstitution; type IV as having no stump and no distal ICA lumen reconstitution. The rate of successful recanalization was 90.3 % for type I, 60.0 % for type II, 50.0 % for type III, 0 % for type IV, respectively (P = 0.002). The overall intraoperative complication rate was 11.8 %, and none of them led to severe neurological damage or death. The follow-up modified Rankin Scale (mRS) scores were significantly decreased in successfully revascularized patients, whilst there were no significant changes in the other failed patients. CONCLUSION: For symptomatic CICAO, our newly modified angiographic classification may be comprehensive and useful in selecting suitable patients for recanalization and grading the difficulty of the procedures.

Acute Vertebrobasilar Artery Occlusion with Underlying Atherosclerosis: Balloon Angioplasty Combined with Tirofiban as Initial Salvage Therapy.

OBJECTIVE: The optimal rescue endovascular treatment for patients with intracranial atherosclerotic stenosis in acute vertebrobasilar artery occlusion is not well established. We investigated the safety and efficacy of balloon angioplasty combined with tirofiban as the initial rescue strategy in these patients. METHODS: We retrospectively analyzed the records of 41 patients admitted between January 2014 and September 2022, with vertebrobasilar artery atherosclerotic occlusion. Balloon angioplasty in combination with tirofiban was used as the first-line salvage therapy after the failure of mechanical thrombectomy. The technical success rate, recanalization outcome, procedure-related complications, symptomatic intracranial hemorrhage, and functional outcome at 90 days were reviewed. RESULTS: Recanalization with a modified Thrombolysis in Cerebral Infarction grade of 2b-3 was achieved in 38 of the 41 patients (92.7%). Acute stents were deployed in 5 patients who did not achieve successful reperfusion after balloon angioplasty. Six patients (14.6%, 6/41) underwent stent angioplasty in the stable stage for severe residual stenosis detected on follow-up imaging. There was no procedure-related complication. Hemorrhagic transformation was detected on follow-up imaging in 11 patients (26.8%), while no symptomatic intracranial hemorrhage was recorded. Good functional outcome rate was 31.7% (13/41). CONCLUSIONS: Balloon angioplasty combined with intravenous tirofiban administration is a safe and effective salvage therapy in patients with acute atherosclerotic occlusion of the vertebrobasilar artery.

Metformin escape in prostate cancer by activating the PTGR1 transcriptional program through a novel super-enhancer.

The therapeutic efficacy of metformin in prostate cancer (PCa) appears uncertain based on various clinical trials. Metformin treatment failure may be attributed to the high frequency of transcriptional dysregulation, which leads to drug resistance. However, the underlying mechanism is still unclear. In this study, we found evidences that metformin resistance in PCa cells may be linked to cell cycle reactivation. Super-enhancers (SEs), crucial regulatory elements, have been shown to be associated with drug resistance in various cancers. Our analysis of SEs in metformin-resistant (MetR) PCa cells revealed a correlation with Prostaglandin Reductase 1 (PTGR1) expression, which was identified as significantly increased in a cluster of cells with metformin resistance through single-cell transcriptome sequencing. Our functional experiments showed that PTGR1 overexpression accelerated cell cycle progression by promoting progression from the G0/G1 to the S and G2/M phases, resulting in reduced sensitivity to metformin. Additionally, we identified key transcription factors that significantly increase PTGR1 expression, such as SRF and RUNX3, providing potential new targets to address metformin resistance in PCa. In conclusion, our study sheds new light on the cellular mechanism underlying metformin resistance and the regulation of the SE-TFs-PTGR1 axis, offering potential avenues to enhance metformin's therapeutic efficacy in PCa.

How does the pattern of root metabolites regulating beneficial microorganisms change with different grazing pressures?

Grazing disturbance can change the structure of plant rhizosphere microbial communities and thereby alter the feedback to promote plant growth or induce plant defenses. However, little is known about how such changes occur and vary under different grazing pressures or the roles of root metabolites in altering the composition of rhizosphere microbial communities. In this study, the effects of different grazing pressures on the composition of microbial communities were investigated, and the mechanisms by which different grazing pressures changed rhizosphere microbiomes were explored with metabolomics. Grazing changed composition, functions, and co-expression networks of microbial communities. Under light grazing (LG), some saprophytic fungi, such as Lentinus sp., Ramichloridium sp., Ascobolus sp. and Hyphoderma sp., were significantly enriched, whereas under heavy grazing (HG), potentially beneficial rhizobacteria, such as Stenotrophomonas sp., Microbacterium sp., and Lysobacter sp., were significantly enriched. The beneficial mycorrhizal fungus Schizothecium sp. was significantly enriched in both LG and HG. Moreover, all enriched beneficial microorganisms were positively correlated with root metabolites, including amino acids (AAs), short-chain organic acids (SCOAs), and alkaloids. This suggests that these significantly enriched rhizosphere microbial changes may be caused by these differential root metabolites. Under LG, it is inferred that root metabolites, especially AAs such as L-Histidine, may regulate specific saprophytic fungi to participate in material transformations and the energy cycle and promote plant growth. Furthermore, to help alleviate the stress of HG and improve plant defenses, it is inferred that the root system actively regulates the synthesis of these root metabolites such as AAs, SCOAs, and alkaloids under grazing interference, and then secretes them to promote the growth of some specific plant growth-promoting rhizobacteria and fungi. To summarize, grasses can regulate beneficial microorganisms by changing root metabolites composition, and the response strategies vary under different grazing pressure in typical grassland ecosystems.