Low NDRG2, regulated by the MYC/MIZ-1 complex and methylation, predicts poor outcomes in DLBCL patients.

Diffuse large B-cell lymphoma (DLBCL) represents the most common tumor in non-Hodgkin's lymphoma. N-Myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor highly expressed in healthy tissues but downregulated in many cancers. Although cell proliferation-related metabolism rewiring has been well characterized, less is known about the mechanism of metabolic changes with DLBCL. Herein, we investigated the expressions of NDRG2, MYC and Myc-interacting zinc finger protein 1 (MIZ-1) in seven human lymphoma (mostly DLBCLs) cell lines. NDRG2 expression was inversely correlated with the expressions of MYC and MIZ-1. Further, we explored the regulatory mechanism and biological functions underlying the lymphomagenesis involving NDRG2, MYC and MIZ-1. MYC and MIZ-1 promoted DLBCL cell proliferation, while NDRG2 induced apoptosis in LY8 cells. Moreover, NDRG2 methylation was reversed by the 5-Aza-2'-deoxycytidine (5-Aza-CDR) treatment, triggering the downregulation of MYC and inhibiting DLBCL cell survival. MYC interacts with NDRG2 to regulate energy metabolism associated with mTOR. Remarkably, supporting the biological significance, the converse correlation between NDRG2 and MYC was observed in human DLBCL tumor tissues (R = -0.557). Bioinformatics analysis further validated the association among NDRG2, MYC, MIZ-1, mTOR, and related metabolism genes. Additionally, NDRG2 (P = 0.001) and MYC (P < 0.001) were identified as promising prognostic biomarkers in DLBCL patients through survival analysis. Together, our data demonstrate that the MYC/MIZ-1 complex interplays with NDRG2 to influence the proliferation and apoptosis of DLBCL cells and show the characterizations of NDRG2, MYC and MIZ-1 for metabolism features and prediction prognosis in DLBCL.

Positive roles of the Ca2+ sensors GbCML45 and GbCML50 in improving cotton Verticillium wilt resistance.

As a universal second messenger, cytosolic calcium (Ca2+) functions in multifaceted intracellular processes, including growth, development and responses to biotic/abiotic stresses in plant. The plant-specific Ca2+ sensors, calmodulin and calmodulin-like (CML) proteins, function as members of the second-messenger system to transfer Ca2+ signal into downstream responses. However, the functions of CMLs in the responses of cotton (Gossypium spp.) after Verticillium dahliae infection, which causes the serious vascular disease Verticillium wilt, remain elusive. Here, we discovered that the expression level of GbCML45 was promoted after V. dahliae infection in roots of cotton, suggesting its potential role in Verticillium wilt resistance. We found that knockdown of GbCML45 in cotton plants decreased resistance while overexpression of GbCML45 in Arabidopsis thaliana plants enhanced resistance to V. dahliae infection. Furthermore, there was physiological interaction between GbCML45 and its close homologue GbCML50 by using yeast two-hybrid and bimolecular fluorescence assays, and both proteins enhanced cotton resistance to V. dahliae infection in a Ca2+-dependent way in a knockdown study. Detailed investigations indicated that several defence-related pathways, including salicylic acid, ethylene, reactive oxygen species and nitric oxide signalling pathways, as well as accumulations of lignin and callose, are responsible for GbCML45- and GbCML50-modulated V. dahliae resistance in cotton. These results collectively indicated that GbCML45 and GbCML50 act as positive regulators to improve cotton Verticillium wilt resistance, providing potential targets for exploitation of improved Verticillium wilt-tolerant cotton cultivars by genetic engineering and molecular breeding.

pH-responsive albumin-mimetic synthetic nanoprobes for magnetic resonance/fluorescence imaging of thyroid cancer.

The combination of magnetic resonance and fluorescence imaging in dual-modality imaging not only resolves the limitations of conventional single molecular imaging techniques in terms of specificity, sensitivity, and resolution but also expands the possibilities of molecular imaging techniques in diagnostics and therapeutic monitoring. Herein, a novel pH-responsive magnetic resonance/near-infrared fluorescence (MR/NIRF) nanoprobe (MnO2@BSA-Cy5.5) was successfully prepared by biomineralizing manganese dioxide (MnO2) with bovine serum albumin (BSA) while coupling fluorescent dye Cy5.5 for precise tumor detection and visualization. The synthesized MnO2@BSA-Cy5.5 nanoprobes were spherical particles of approximately 22.62 ± 3.31 nm in size, and their relaxation rates and T1 imaging signals were activated-enhanced in an acidic environment. Cytotoxicity assay and hematoxylin and eosin staining demonstrated that MnO2@BSA-Cy5.5 had low cytotoxicity and good biocompatibility. More importantly, active targeting via solid tumor albumin-binding protein receptor and enhanced permeability and retention effect, the probe can be specifically aggregated to the tumor site of the 8305C tumor model and exhibit excellent MR/NIRF imaging properties. Our results show that MnO2@BSA-Cy5.5 has high resolution and sensitivity in tumor imaging and is expected to be applied as an MR/NIRF contrast agent for accurate diagnosis of thyroid cancer.

Molecular analyses display the increasing diversity of Podostemaceae in China.

•Four newly recorded species of Podostemaceae from southern China were identified by molecular and morphological evidence.•17 plastomes of Podostemaceae were newly sequenced and two novel polymorphic barcodes (ccsA and ndhA) detected.•Our findings reveal greater species richness (15 species from five genera) of Podostemaceae in China and supply molecular resources for research on taxonomy and phylogenomics of this enigmatic aquatic family.

Intelligent technologies powering clean incineration of municipal solid waste: A system review.

Cleanliness has been paramount for municipal solid waste incineration (MSWI) systems. In recent years, the rapid advancement of intelligent technologies has fostered unprecedented opportunities for enhancing the cleanliness of MSWI systems. This paper offers a review and analysis of cutting-edge intelligent technologies in MSWI, which include process monitoring, intelligent algorithms, combustion control, flue gas treatment, and particulate control. The objective is to summarize current applications of these techniques and to forecast future directions. Regarding process monitoring, intelligent image analysis has facilitated real-time tracking of combustion conditions. For intelligent algorithms, machine learning models have shown advantages in accurately forecasting key process parameters and pollutant concentrations. In terms of combustion control, intelligent systems have achieved consistent prediction and regulation of temperature, oxygen content, and other parameters. Intelligent monitoring and forecasting of carbon monoxide and dioxins for flue gas treatment have exhibited satisfactory performance. Concerning particulate control, multi-objective optimization facilitates the sustainable utilization of fly ash. Despite remarkable progress, challenges remain in improving process stability and monitoring instrumentation of intelligent MSWI technologies. By systematically summarizing current applications, this timely review offers valuable insights into the future upgrade of intelligent MSWI systems.

Modular multi-degree-of-freedom soft origami robots with reprogrammable electrothermal actuation.

Soft robots often draw inspiration from nature to navigate different environments. Although the inching motion and crawling motion of caterpillars have been widely studied in the design of soft robots, the steering motion with local bending control remains challenging. To address this challenge, we explore modular origami units which constitute building blocks for mimicking the segmented caterpillar body. Based on this concept, we report a modular soft Kresling origami crawling robot enabled by electrothermal actuation. A compact and lightweight Kresling structure is designed, fabricated, and characterized with integrated thermal bimorph actuators consisting of liquid crystal elastomer and polyimide layers. With the modular design and reprogrammable actuation, a multiunit caterpillar-inspired soft robot composed of both active units and passive units is developed for bidirectional locomotion and steering locomotion with precise curvature control. We demonstrate the modular design of the Kresling origami robot with an active robotic module picking up cargo and assembling with another robotic module to achieve a steering function. The concept of modular soft robots can provide insight into future soft robots that can grow, repair, and enhance functionality.

Effects of Otago exercise program on physical function in older adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Maintaining physical function is critical for older adults to achieve healthy aging. The Otago exercise program (OEP) has been widely used to prevent falls for older adults. However, the effects of OEP on physical function remain controversial and the possible effects modifiers have not been assessed. OBJECTIVE: To evaluate the effects of OEP on physical function in older adults and to explore potential moderators underlying the effects of OEP. METHODS: We searched five electronic databases and relevant systematic reviews to identify studies. We included randomized controlled trials (RCTs) evaluating the effects of OEP as a single intervention on physical function among older adults aged 65 and over. Meta-analysis was performed using the random-effects model. Standardized mean differences (SMD) for physical function changes, pertinent to balance, strength, and mobility, were outcome measures. Subgroup analyses on exercise protocol and participants' characteristics were performed. RESULTS: Thirteen RCTs consisting of 2402 participants were included in this systematic review and meta-analysis. Results indicated a significant effect of OEP on balance (SMD = 0.59, 95 % CI: 0.22∼0.96), lower body strength (SMD = 0.93, 95 % CI: 0.31∼1.55), and mobility (SMD = -0.59, 95 % CI: -0.95∼-0.22) against control groups. No significant OEP effects were found on upper body strength (MD = 1.48, 95 % CI: -0.58∼3.55). Subgroup analysis revealed that the video-supported delivery mode was more effective for improving balance (P = 0.04) and mobility (P = 0.02) than the face-to-face mode. Session durations over 30 min was more effective on lower body strength (P < 0.001) and mobility (P < 0.001) than those 1-30 min. Program period of 13-26 weeks was more effective on mobility (P = 0.02) than those of 4-12 weeks. However, the effects of OEP on physical function were not associated with age groups, and baseline falling risks. CONCLUSION: The OEP could improve physical function including balance, lower body strength, and mobility in older adults. Implementing the OEP in video-supported, more than 30 min per session and 4-12 weeks may be the most appropriate and effective exercise protocol for improving physical function among older adults. More RCTs with rigorous design and larger scale are needed to further assess the effectiveness of diverse OEP protocols and quantify the dose-effect relationship.

Corrigendum: Tpr deficiency disrupts erythroid maturation with impaired chromatin condensation in zebrafish embryogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.709923.].

Distinct characteristics of distant metastasis in early-onset gastric cancer patients compared to late-onset patients: An observational study.

Presently, there is limited understanding of the features of distant metastasis in early-onset gastric cancer (GC). To explore these disparities, a retrospective study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was undertaken. The SEER database was utilized to extract patient data, and multivariate logistic regression analysis was employed to identify the risk factors associated with distant metastasis and liver metastasis. Propensity score matching (PSM) was used to compare the occurrence of liver metastasis among patients based on their age at diagnosis. The study included 2684 early-onset GC patients and 33,289 late-onset GC patients. Preliminary data analysis indicated that early-onset GC patients exhibited more aggressive characteristics such as poor cell differentiation, advanced T stage, and a higher incidence of distant metastasis, excluding liver metastasis. Multivariate logistic regression analysis identified younger age as an independent risk factor for distant metastasis, along with T stage, lymph node metastasis (LNM), and tumor size (>3 cm). Another regression analysis revealed that younger age, diffuse type, and female gender were protective factors against liver metastasis. Through PSM, 3276 early-onset GC patients were matched with an equal number of late-onset GC patients, revealing that patients with early-onset GC had fewer instances of liver metastasis but a higher prevalence of distant metastasis. Our findings suggest that early-onset serves as a protective factor against liver metastasis in GC, while it poses a risk for distant metastasis, likely influenced by the increased prevalence of diffuse-type GC in early-onset patients.

Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles.

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

CD44: a cancer stem cell marker and therapeutic target in leukemia treatment.

CD44 is a ubiquitous leukocyte adhesion molecule involved in cell-cell interaction, cell adhesion, migration, homing and differentiation. CD44 can mediate the interaction between leukemic stem cells and the surrounding extracellular matrix, thereby inducing a cascade of signaling pathways to regulate their various behaviors. In this review, we focus on the impact of CD44s/CD44v as biomarkers in leukemia development and discuss the current research and prospects for CD44-related interventions in clinical application.

Genome-Wide Identification and Expression Profile Analysis of the Phenylalanine Ammonia-Lyase Gene Family in Hevea brasiliensis.

The majority of the world's natural rubber comes from the rubber tree (Hevea brasiliensis). As a key enzyme for synthesizing phenylpropanoid compounds, phenylalanine ammonia-lyase (PAL) has a critical role in plant satisfactory growth and environmental adaptation. To clarify the characteristics of rubber tree PAL family genes, a genome-wide characterization of rubber tree PALs was conducted in this study. Eight PAL genes (HbPAL1-HbPAL8), which spread over chromosomes 3, 7, 8, 10, 12, 13, 14, 16, and 18, were found to be present in the genome of H. brasiliensis. Phylogenetic analysis classified HbPALs into groups I and II, and the group I HbPALs (HbPAL1-HbPAL6) displayed similar conserved motif compositions and gene architectures. Tissue expression patterns of HbPALs quantified by quantitative real-time PCR (qPCR) proved that distinct HbPALs exhibited varying tissue expression patterns. The HbPAL promoters contained a plethora of cis-acting elements that responded to hormones and stress, and the qPCR analysis demonstrated that abiotic stressors like cold, drought, salt, and H2O2-induced oxidative stress, as well as hormones like salicylic acid, abscisic acid, ethylene, and methyl jasmonate, controlled the expression of HbPALs. The majority of HbPALs were also regulated by powdery mildew, anthracnose, and Corynespora leaf fall disease infection. In addition, HbPAL1, HbPAL4, and HbPAL7 were significantly up-regulated in the bark of tapping panel dryness rubber trees relative to that of healthy trees. Our results provide a thorough comprehension of the characteristics of HbPAL genes and set the groundwork for further investigation of the biological functions of HbPALs in rubber trees.

Discovery and verification of antidepressant active ingredients of raw and vinegar-processed Bupleurum marginatum var. Stenophyllum based on plant metabolomics and serum pharmacology.

The dried root of Bupleurum marginatum var. stenophyllum (H. Wolff) R.H. Shan & Y. Li (BM), which has been used as a Bupleuri radix in Guizhou Province and is listed in the 2003 edition of the Guizhou Quality Standard for Traditional Chinese Medicines and Ethnic Materia Medica, is effective at dispersing the liver and relieving depression and often used in the form of raw or vinegar-processed product (VBM). However, the potential depression-relieving components of BM are unclear. The aim of this study was to determine the potential antidepressant constituents of BM and investigate the effect of vinegar processing on these components. The antidepressant effect and mechanism of BM and VBM were investigated in depressed mice and BV2 cells, respectively. The pharmacodynamic constituents were screened through serum pharmacochemistry, which combined the results of metabolomics analysis of BM and VBM, high-performance liquid chromatography (HPLC) content determination, and verification of the antidepressant effect and mechanism of differential components of SSb2 to clarify the connotation of vinegar processing. Our results demonstrated that BM can exert a significant antidepressant effect by inhibiting microglia polarization and that this effect was enhanced after vinegar processing. Thirty-eight components were identified in the BM, 13 of which were blood-absorbable, mainly saponins, and defined as potential antidepressant components of the BM. The contents of 17 components-6 of which were absorbed into the blood-changed considerably after processing. It was finally determined that vinegar processing can enhance the antidepressant effect of BM by increasing the contents of SSb1 and SSb2. SSb2 exerts this effect via the samemechanism as BM. In conclusion, in this study we clarified the antidepressant effects and potential active components of BM and examined the mechanism of vinegar processing. These findings lay a foundation for the future research on the antidepressant effects of BM as well as for the complete development and application of BM's ethnomedicinal resources.

Clinical Observation of Posterior-Chamber Phakic Implantable Collamer Lens V4c Implantation in Myopic Patients with Shallow Anterior Chamber Depth: A Retrospective, Consecutive Observational Study.

Purpose: The reference range for the preoperative anterior chamber angle width for ICL surgery is unclear. Our objective was to assess the clinical effect and the range of anterior chamber angle width of posterior-chamber implantable collamer lens V4c (ICL V4c) implantation in patients with anterior chamber depth (ACD) < 2.8 mm. Methods: Patients who underwent ICL V4c implantation with shallow ACD were included in this retrospective study. The patients' uncorrected and corrected distance visual acuity, angle of trabecular-iris (TIA), angle-opening distance (AOD500), trabecular-iris space area (TISA500), corneal endothelial cell density, vault, retinal nerve fiber layer thickness, intraocular pressure, visual field, and complications were analyzed. Results: Forty-one patients (68 eyes) completed at least 12 months of follow-up (median follow-up, 30 months). The effectiveness and safety indices were 1.09 ± 0.13 and 1.04 ± 0.21, respectively. The preoperative TIA values on the nasal and temporal sides were 39.78 ± 7.68 degree (range, 25.8-65.1 degree) and 41.54 ± 8.03 degree (range, 28.5-63.00 degree). Forty-seven eyes had uncorrected distance visual acuity ≥1.0, and 55 had corrected distance visual acuity ≥1.0 at the last follow-up visit. The TIA, AOD500, and TISA500 on the nasal and temporal sides were significantly reduced compared to those before surgery (all P < 0.01); no eye had an angle closure or elevated intraocular pressure. The ICL V4c vault was 290.88 ± 153.36 µm (range, 60.0-880.0 µm). No severe complications occurred in any patient. Conclusions: In patients with myopia with shallow ACD (2.55-2.79 mm), a preoperative TIA >25.8° is safe and effective for a relatively long time after surgery; however, an extended long-term close follow-up is needed.

Unraveling a Small Secreted Peptide SUBPEP3 That Positively Regulates Salt-Stress Tolerance in Pyrus betulifolia.

Small secreted peptides (SSPs) play important roles in regulating plants' growth and development in response to external stimulus, but the genes and functions of SSPs in many species are still unknown. Therefore, it is particularly significant to characterize and annotate SSP genes in plant genomes. As a widely used stock of pears, Pyrus betulifolia has strong resistance to biotic and abiotic stresses. In this study, we analyzed the SSPs genes in the genome of P. betulifolia according to their characteristics and homology. A total of 1195 SSP genes were identified, and most of them are signaling molecules. Among these, we identified a new SSP, subtilase peptide 3 (SUBPEP3), which derived from the PA region of preSUBPEP3, increasing the expression level under salt stress. Both adding synthetic peptide SUBPEP3 to the culture medium of pears and the overexpression of SUBPEP3 in tobacco can improve the salt tolerance of plants. In summary, we annotated the SSP genes in the P. betulifolia genome and identified a small secreted peptide SUBPEP3 that regulates the salt tolerance of P. betulifolia, which provides an important theoretical basis for further revealing the function of SSPs.

Recent advances in c-Met-based dual inhibitors in the treatment of cancers.

The cellular-mesenchymal epithelial transition factor (c-Met) is a receptor tyrosine kinase (RTK) located on the 7q31 locus encoding the Met proto-oncogene and plays a critical role in regulating cell proliferation, metastasis, differentiation, and apoptosis through various signaling pathways. However, its aberrant activation and overexpression have been implicated in many human cancers. Therefore, c-Met is a promising target for cancer treatment. However, the anticancer effect of selective single-targeted drugs is limited due to the complexity of the signaling system and the involvement of different proteins and enzymes. After inhibiting one pathway, signal molecules can be transmitted through other pathways, resulting in poor efficacy of single-targeted drug therapy. Dual inhibitors that simultaneously block c-Met and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, We introduced c-Met kinase and the synergism between c-Met and other anti-tumor targets, then dual-target inhibitors based on c-Met for the treatment of cancers were summarized and their design concepts and structure-activity relationships (SARs) were discussed elaborately, providing a valuable insight for the further development of novel c-Met-based dual inhibitors.

Effectiveness of video-based psychiatric rehabilitation for patients with early-phase schizophrenia spectrum: A randomized controlled trial.

AIM: This study aimed to establish a comprehensive set of recovery-oriented rehabilitation programs for individuals with schizophrenia, comparing the efficacy of video-based rehabilitation to traditional face-to-face interventions. The primary objective was to assess whether video-based rehabilitation could serve as a viable alternative for individuals with schizophrenia residing in remote areas. METHODS: A randomized controlled study was used to recruit 80 patients with schizophrenia in a stable post-hospitalization stage following discharge. Participants were categorized into three groups: 24 in the control group, 21 in the face-to-face group, and 35 in the remote group. Assessment parameters included psychiatric symptoms, social skills, family function and self-stigma. RESULTS: A total of 68 participants completed the program. The findings indicated significant differences (p < .05) between the control group and intervention group, particularly in the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance Scale (PSP). CONCLUSIONS: The rehabilitation program, tailored for patients in the early phase of the schizophrenia spectrum, demonstrates both effectiveness and feasibility in enhancing clinical symptoms and social functions. Notably, interventions conducted via video proved to be equally effective as those administered face-to-face.

SlCRCa is a key D-class gene controlling ovule fate determination in tomato.

Cell fate determination and primordium initiation on the placental surface are two key events for ovule formation in seed plants, which directly affect ovule density and seed yield. Despite ovules form in the marginal meristematic tissues of the carpels, angiosperm carpels evolved after the ovules. It is not clear how the development of the ovules and carpels is coordinated in angiosperms. In this study, we identify the S. lycopersicum CRABS CLAW (CRC) homologue SlCRCa as an essential determinant of ovule fate. We find that SlCRCa is not only expressed in the placental surface and ovule primordia but also functions as a D-class gene to block carpel fate and promote ovule fate in the placental surface. Loss of function of SlCRCa causes homeotic transformation of the ovules to carpels. In addition, we find low levels of the S. lycopersicum AINTEGUMENTA (ANT) homologue (SlANT2) favour the ovule initiation, whereas high levels of SlANT2 promote placental carpelization. SlCRCa forms heterodimer with tomato INNER NO OUTER (INO) and AGAMOUS (AG) orthologues, SlINO and TOMATO AGAMOUS1 (TAG1), to repress SlANT2 expression during the ovule initiation. Our study confirms that angiosperm basal ovule cells indeed retain certain carpel properties and provides mechanistic insights into the ovule initiation.

HD-Zip proteins modify floral structures for self-pollination in tomato.

Cleistogamy is a type of self-pollination that relies on the formation of a stigma-enclosing floral structure. We identify three homeodomain-leucine zipper IV (HD-Zip IV) genes that coordinately promote the formation of interlocking trichomes at the anther margin to unite neighboring anthers, generating a closed anther cone and cleistogamy (flower morphology necessitating strict self-pollination). These HD-Zip IV genes also control style length by regulating the transition from cell division to endoreduplication. The expression of these HD-Zip IV genes and their downstream gene, Style 2.1, was sequentially modified to shape the cleistogamy morphology during tomato evolution and domestication. Our results provide insights into the molecular basis of cleistogamy in modern tomato and suggest targets for improving fruit set and preventing pollen contamination in genetically modified crops.

Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis.

Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RAR-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for RAR-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-LDHA signaling as a driving force in MAIT17 responses.