In Situ Hydrogel Modulates cDC1-Based Antigen Presentation and Cancer Stemness to Enhance Cancer Vaccine Efficiency.

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high-performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti-tumor effect. Fms-like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap-CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co-encapsulated in an in situ hydrogel vaccine (FP/NCUM-Gel). FP/NCUM-Gel is gelated in situ after intra-tumoral injection. With the near-infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross-presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti-tumor potential, providing new ideas for clinical tumor vaccine design.

Corrigendum to "Optimization of a tannase-assisted process for obtaining teas rich in theaflavins from Camellia sinensis leaves" [Food Chemistry: X 13 (2022) 100203].

[This corrects the article DOI: 10.1016/j.fochx.2022.100203.].

New plant polyphenol-derived tannic acid-based chromium-free tanning agent for sustainable and clean leather production.

This study aimed to prepare a new bio-based chromium-free tanning agent. The green epoxide monocase ethylene glycol diglycidyl ether (EGDE) was grafted with tannic acid (TA) derived from natural plant using the one-pot method to synthesize new plant polyphenol-derived tannic acid-based chromium-free tanning agents (TA-EGDE) with abundant terminal epoxides. FTIR, 1H NMR, XPS, GPC, SEM, and other analytical techniques were used to characterize tanning agents. These consequences manifested that EGDE was successfully grafted with the phenol hydroxyl group of TA. The epoxide value of TA-EGDE showed a tendency to increase and then decrease with increasing EGDE dosage, and the epoxide value of TA-EGDE-2 attained a maximum of 0.262 mol/100 g. GPC analysis showed that the formula weight of the prepared TA-EGDE was partially distributed above 5000 Da. The tanning experiment demonstrated that the shrinkage temperatures (Ts) of the TA-EGDE-tanned leathers were all higher than 81.5 °C. Compared with the traditional commercial chromium-free tanning agent (F-90, TWS), TA-EGDE-tanned leathers exhibited higher Ts and better mechanical properties. The TA-EGDE prepared in this study not only has ecological environmental protection but also provides finished leather with good moisture, heat resistance, and mechanical properties.

Improved electronic uniformity and nanoscale homogeneity in template-grown CsPbBr3 nanorods.

One-dimensional metal halide perovskites are among the most promising candidate materials for optoelectronic devices. However, the heterogeneity and fast degradation of perovskite nanowires (NWs) and nanorods (NRs) synthesized using conventional approaches impose a bottleneck for their optoelectronic applications. Recently, all-inorganic perovskite CsPbBr3 NRs with tailored dimensions, crafted using an amphiphilic bottlebrush-like block copolymer (BBCP) as nanoreactors, have demonstrated enhanced stabilities. Herein, we report the electronic investigation into these template-grown CsPbBr3 NRs using dielectric force microscopy (DFM), a contactless, nondestructive imaging technique. All freshly prepared CsPbBr3 NRs exhibited ambipolar behaviors for up to two months after sample synthesis. A transition from ambipolar to p-type behaviors occurred after two months, and nearly all NRs completed the transition within two weeks. Moreover, template-grown CsPbBr3 NRs displayed better nanoscale electronic homogeneity compared to their conventional counterparts. The improved electronic uniformity and nanoscale homogeneity place the template-grown CsPbBr3 NRs in a unique advantageous position for optoelectronic applications.

Effects of warming on soil organic carbon pools mediated by mycorrhizae and hyphae on the Eastern Tibetan Plateau, China.

Mycorrhizae and their hyphae play critical roles in soil organic carbon (SOC) accumulation. However, their individual contributions to SOC components and stability under climate warming conditions remain unclear. This study investigated the effects of warming on the SOC pools of Picea asperata (an ectomycorrhizal plant) and Fargesia nitida (an arbuscular mycorrhizal plant) mycorrhizae/hyphae on the eastern Tibetan Plateau. The results indicated that mycorrhizae made greater contributions to SOC accumulation than hyphae did by increasing labile organic carbon (LOC) components, such as particle organic carbon (POC), easily oxidizable organic carbon, and microbial biomass carbon, especially under warming conditions. Plant species also had different effects on SOC composition, resulting in higher mineral-associated organic carbon (MAOC) contents in F. nitida plots than in P. asperata plots; consequently, the former favored SOC stability more than the latter, with a lower POC/MAOC. Partial least-squares path modelling further indicated that mycorrhizae/hyphae indirectly affected LOC pools, mainly by changing soil pH and enzyme activities. Warming had no significant effect on SOC content but did change SOC composition by reducing LOC through affecting soil pH and iron oxides and ultimately increasing SOC stability in the presence of mycorrhizae for both plants. Therefore, the mycorrhizae of both plants are major contributors to the variation of SOC components and stability under warming conditions.

Cardioid oscillator-based pattern generator for imitating the time-ratio-asymmetrical behavior of the lower limb exoskeleton.

Introduction: Periodicity, self-excitation, and time ratio asymmetry are the fundamental characteristics of the human gait. In order to imitate these mentioned characteristics, a pattern generator with four degrees of freedom is proposed based on cardioid oscillators developed by the authors. Method: The proposed pattern generator is composed of four coupled cardioid oscillators, which are self-excited and have asymmetric time ratios. These oscillators are connected with other oscillators through coupled factors. The dynamic behaviors of the proposed oscillators, such as phase locking, time ratio, and self-excitation, are analyzed via simulations by employing the harmonic balance method. Moreover, for comparison, the simulated trajectories are compared with the natural joint trajectories measured in experiments. Results and discussion: Simulation and experimental results show that the behaviors of the proposed pattern generator are similar to those of the natural lower limb. It means the simulated trajectories from the generator are self-excited without any additional inputs and have asymmetric time ratios. Their phases are locked with others. Moreover, the proposed pattern generator can be applied as the reference model for the lower limb exoskeleton controlling algorithm to produce self-adjusted reference trajectories.

Dynamic changes of key metabolites in Longjing green tea during processing revealed by widely targeted metabolomic profiling and sensory experiments.

In this study, widely targeted metabolomics and chemometrics were utilized to comprehensively analyse the formation of taste compounds in Longjing green tea. A total of 580 non-volatile metabolites were identified by using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and alterations in three metabolic pathways were investigated. Notably, the fixation process reduced phosphatidic acid levels, resulting in the formation of lyso-phosphatidylcholine and lyso-phosphatidylethanolamine, as well as the release of esterified polyunsaturated fatty acids. Baiye No.1 had high levels of L-glutamic acid and l-glutamine, while Longjing 43 showed elevated levels of flavones. Correlation analysis and sensory verification indicated that the specific concentration of L-leucine could decrease the umami of the tea. These findings advance our understanding of Longjing green tea quality improvement and cultivar development.

Prenatal Progesterone Treatment Modulates Fetal Brain Transcriptome and Impacts Adult Offspring Behavior in Mice.

Maternal exposure to elevated levels of steroid hormones during pregnancy is associated with the development of chronic conditions in offspring that manifest in adulthood. However, the effects of progesterone (P4) administration during early pregnancy on fetal development and subsequent offspring behavior remain poorly understood. In this study, we aimed to investigate the effects of P4 treatment during early pregnancy on the transcript abundance in the fetal brain and assess the behavioral consequences in the offspring during adolescence and adulthood. Using RNA-seq analysis, we examined the impact of P4 treatment on the fetal brain transcriptome in a dosage-dependent manner. Our results revealed differential regulation of genes involved in neurotransmitter transport, synaptic transmission, and transcriptional regulation. Specifically, we observed bidirectional regulation of transcription factors (TFs) by P4 at different doses, highlighting the critical role of these TFs in neurodevelopment. To assess behavioral outcomes, we conducted open field and elevated plus maze tests. Offspring treated with low-dose P4 (LP4) displayed increased exploratory behavior during both adolescence and adulthood. In contrast, the high-dose P4 (HP4) group exhibited impaired exploration and heightened anxiety-like behaviors compared to the control mice. Moreover, in a novel object recognition test, HP4-treated offspring demonstrated impaired object recognition memory during both developmental stages. Additionally, both LP4 and HP4 groups showed reduced social interaction in the three-chamber test. These results suggest that prenatal exposure to P4 exerts a notable influence on the expression of genes associated with neurodevelopment and may induce alterations in behavioral characteristics in progeny, highlighting the need to monitor progesterone levels during pregnancy for long-term impacts on fetal brain development and behavior.

Solitary Pulmonary Perivascular Epithelial Cell Tumor Mimicking Pulmonary Metastasis on 68Ga-DOTATATE PET/CT in a Patient With Pancreatic Neuroendocrine Tumor.

ABSTRACT: We report the findings of 68Ga-DOTATATE PET/CT in a 56-year-old woman with solitary pulmonary perivascular epithelioid cell tumor. 68Ga-DOTATATE PET/CT showed a lesion with intense uptake in the region of pancreatic head and a solitary nodule with moderate uptake in the left lung. Pancreatic neuroendocrine tumor with pulmonary metastasis was considered. The postoperative pathological results showed a benign perivascular epithelioid cell tumor of the lung. This case emphasizes the need to increase awareness of benign perivascular epithelioid cell tumors in the differential diagnosis of solitary pulmonary nodule with moderate DOTATATE activity.

Systematically assessing the quality of dental electronic health record data for an investigation into oral health care disparities.

OBJECTIVES: This work describes the process by which the quality of electronic health care data for a public health study was determined. The objectives were to adapt, develop, and implement data quality assessments (DQAs) based on the National Institutes of Health Pragmatic Trials Collaboratory (NIHPTC) data quality framework within the three domains of completeness, accuracy, and consistency, for an investigation into oral health care disparities of a preventive care program. METHODS: Electronic health record data for eligible children in a dental accountable care organization of 30 offices, in Oregon, were extracted iteratively from January 1, 2014, through March 31, 2022. Baseline eligibility criteria included: children ages 0-18 with a baseline examination, Oregon home address, and either Medicaid or commercial dental benefits at least once between 2014 and 2108. Using the NIHPTC framework as a guide, DQAs were conducted throughout data element identification, extraction, staging, profiling, review, and documentation. RESULTS: The data set included 91,487 subjects, 11 data tables comprising 75 data variables (columns), with a total of 6,861,525 data elements. Data completeness was 97.2%, the accuracy of EHR data elements in extracts was 100%, and consistency between offices was strong; 29 of 30 offices within 2 standard deviations of the mean (s = 94%). CONCLUSIONS: The NIHPTC framework proved to be a useful approach, to identify, document, and characterize the dataset. The concepts of completeness, accuracy, and consistency were adapted by the multidisciplinary research team and the overall quality of the data are demonstrated to be of high quality.

Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring.

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a Traditional Chinese Medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

Clinical phenotype of AAV, anti-GBM disease and double-positive patients after SARS-CoV-2 vaccination.

The number of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), anti-glomerular basement membrane (GBM) disease and double-positive patients (DPPs) following the coronavirus disease 2019 (COVID-19) vaccine reported in the literature is increasing, we reviewed the reported cases of AAV, anti-GBM disease and DPPs subsequent to COVID-19 vaccination, and compared the disparities in DPPs who received the COVID-19 vaccination and those who did not. We did not observe any differences in clinical phenotype of AAV, anti-GBM disease and DPPs before and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination.

Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC.

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to "cold" tumors' immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC.

Early statin exposure influences cardiac and skeletal development with implications for ion channel transcriptomes in zebrafish.

Statins, widely prescribed for cholesterol management by inhibiting HMG-CoA reductase in the cholesterol biosynthesis pathway, may also influence vertebrate development. In this study, we investigated the developmental effects of two widely used statins, atorvastatin (ATO) and pravastatin (PRA), on zebrafish offspring. For ATO, we administered doses classified as low (1 µM), medium (5 µM), and high (10 µM), while for PRA, the corresponding concentrations were set at low (18 µM), medium (180 µM), and high (270 µM). Our results showed significant reductions in birth and hatching rates, along with decreased body length in offspring at all ATO concentrations and medium to high PRA concentrations. A notable increase in malformation rates, especially in the spine and heart, was observed across all ATO treatments and in medium and high PRA groups. Additionally, we observed reduced heart contraction rates, decreased heart size, lower bone volumes, and diminished expression of mRNA osteogenic markers. Elevated venous sinus-artery bulb (SV-BA) ratios, increased thoracic area, and abnormal cartilage development were also prominent in all ATO-treated groups. Transcriptome analysis revealed alterations in genes predominantly associated with ion channels. These findings provide insights into the potential impacts of specific concentrations of statins on offspring development and highlight potential gene interactions with statins.

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy.

Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.

Yigansan ameliorates maternal immune activation-induced autism-like behaviours by regulating the IL-17A/TRAF6/MMP9 pathway: Network analysis and experimental validation.

BACKGROUND: Maternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HYPOTHESIS: Yigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. METHODS: Pregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. RESULTS: We demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. CONCLUSION: Overall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.

DNA methylation marker identification and poly-methylation risk score in prediction of healthspan termination.

Aim: To elucidate the epigenetic consequences of DNA methylation in healthspan termination (HST), considering the current limited understanding. Materials & methods: Genetically predicted DNA methylation models were established (n = 2478). These models were applied to genome-wide association study data on HST. Then, a poly-methylation risk score (PMRS) was established in 241,008 individuals from the UK Biobank. Results: Of the 63,046 CpGs from the prediction models, 13 novel CpGs were associated with HST. Furthermore, people with high PMRSs showed higher HST risk (hazard ratio: 1.18; 95% CI: 1.13-1.25). Conclusion: The study indicates that DNA methylation may influence HST by regulating the expression of genes (e.g., PRMT6, CTSK). PMRSs have a promising application in discriminating subpopulations to facilitate early prevention.

Environmental impacts on algal-bacterial-based aquaponics system by different types of carbon source addition: water quality and greenhouse gas emission.

Carbon source addition is an important way improving the carbon and nitrogen transformation in aquaculture system; however, its effectiveness of algal-bacterial-based aquaponics (AA) through carbon source addition is still vague. In this study, the influences of organic carbon (OC-AA system) and inorganic carbon (IC-AA system) addition and without carbon source addition (C-AA system) on the operational performance of AA system were investigated. Results showed that 10.1-19.5% increase of algal-bacterial biomass enhanced the purifying effect of ammonia nitrogen in OC-AA system and IC-AA system relative to C-AA system. Moreover, extra electron donor supply in the OC-AA system obtained the lowest NO3--N concentration. However, that was at the cost of aggravated N2O conversion ratio, which increased by more than 2.0-folds than other systems, attributing to 2.9-folds increase of nirS gene abundance. In addition, carbon source addition increased the pH and then decreased the fish biomass production of AA system. The results of this study would provide theoretical supports of carbon source addition on the performance of nutrient transformation and greenhouse gas effect in AA system.

STSN-Net: Simultaneous Tooth Segmentation and Numbering Method in Crowded Environments with Deep Learning.

Accurate tooth segmentation and numbering are the cornerstones of efficient automatic dental diagnosis and treatment. In this paper, a multitask learning architecture has been proposed for accurate tooth segmentation and numbering in panoramic X-ray images. A graph convolution network was applied for the automatic annotation of the target region, a modified convolutional neural network-based detection subnetwork (DSN) was used for tooth recognition and boundary regression, and an effective region segmentation subnetwork (RSSN) was used for region segmentation. The features extracted using RSSN and DSN were fused to optimize the quality of boundary regression, which provided impressive results for multiple evaluation metrics. Specifically, the proposed framework achieved a top F1 score of 0.9849, a top Dice metric score of 0.9629, and an mAP (IOU = 0.5) score of 0.9810. This framework holds great promise for enhancing the clinical efficiency of dentists in tooth segmentation and numbering tasks.

STAT5 is essential for inducing the suppressive subset and attenuate cytotoxicity of Vδ2+ T cells in acute myeloid leukemia.

Under the sustained exposure to tumor microenvironment, effector lymphocytes may transform into the suppressive populations. γδ T cells are recognized as a crucial mediator and effector of immune surveillance and thereby a promising candidate for anti-tumor immunotherapy. Emerging clinical studies implicate that some γδ T subsets play an important role in promoting tumor progression. Our previous study identified an abnormal Vδ2+ T cells subset with regulatory features (Reg-Vδ2) in the patients with newly diagnosed acute myeloid leukemia (AML), and demonstrated that Reg-Vδ2 cells significantly suppressed the anti-AML effects of effector Vδ2 cells (Eff-Vδ2). The molecular mechanism underlying the subset transformation of Vδ2 cells remains unclear. Here, we found that the expression and activity of STAT5 were significantly induced in Reg-Vδ2 cells compared with Eff-Vδ2 cells, which was consistent with the differences found in primary Vδ2 cells between AML patients and healthy donors. In-vitro experiments further indicated that STAT5 was required for the induction of Reg-Vδ2 cells. The combined immunophenotypical and functional assays showed that blockage of STAT5 alleviated the immunosuppressive effect of Reg-Vδ2 cells on Eff-Vδ2 cells and enhanced the anti-AML capacity of Vδ2 cells from health donors and AML patients. Collectively, these results suggest that STAT5 acts as a critical regulator in the transformation of effector Vδ2 cells into a subset with immunosuppressive characteristics, providing a potential target for the improvement the efficacy of γδ T cells-based immunotherapy to treat AML and other hematologic malignancies.