Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.

Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration.

Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release.

Effector-T-cell-mediated immunity depends on the efficient localization of antigen-primed lymphocytes to antigen-rich non-lymphoid tissue, which is facilitated by the expression of a unique set of "homing" receptors acquired by memory T cells. We report that engagement of the hepatocyte growth factor (HGF) receptor c-Met by heart-produced HGF during priming in the lymph nodes instructs T cell cardiotropism, which was associated with a specialized homing "signature" (c-Met(+)CCR4(+)CXCR3(+)). c-Met signals facilitated T cell recruitment to the heart via the chemokine receptor CCR5 by inducing autocrine CCR5 ligand release. c-Met triggering was sufficient to support cardiotropic T cell recirculation, while CCR4 and CXCR3 sustained recruitment during heart inflammation. Transient pharmacological blockade of c-Met during T cell priming led to enhanced survival of heart, but not skin, allografts associated with impaired localization of alloreactive T cells to heart grafts. These findings suggest c-Met as a target for development of organ-selective immunosuppressive therapies.

Development of a counterselectable system for rapid and efficient CRISPR-based genome engineering in Zymomonas mobilis.

BACKGROUND: Zymomonas mobilis is an important industrial bacterium ideal for biorefinery and synthetic biology studies. High-throughput CRISPR-based genome editing technologies have been developed to enable targeted engineering of genes and hence metabolic pathways in the model ZM4 strain, expediting the exploitation of this biofuel-producing strain as a cell factory for sustainable chemicals, proteins and biofuels production. As these technologies mainly take plasmid-based strategies, their applications would be impeded due to the fact that curing of the extremely stable plasmids is laborious and inefficient. Whilst counterselection markers have been proven to be efficient for plasmid curing, hitherto only very few counterselection markers have been available for Z. mobilis. RESULTS: We constructed a conditional lethal mutant of the pheS gene of Z. mobilis ZM4, clmPheS, containing T263A and A318G substitutions and coding for a mutated alpha-subunit of phenylalanyl-tRNA synthetase to allow for the incorporation of a toxic analog of phenylalanine, p-chloro-phenylalanine (4-CP), into proteins, and hence leading to inhibition of cell growth. We demonstrated that expression of clmPheS driven by a strong Pgap promoter from a plasmid could render the Z. mobilis ZM4 cells sufficient sensitivity to 4-CP. The clmPheS-expressing cells were assayed to be extremely sensitive to 0.2 mM 4-CP. Subsequently, the clmPheS-assisted counterselection endowed fast curing of genome engineering plasmids immediately after obtaining the desired mutants, shortening the time of every two rounds of multiplex chromosome editing by at least 9 days, and enabled the development of a strategy for scarless modification of the native Z. mobilis ZM4 plasmids. CONCLUSIONS: This study developed a strategy, coupling an endogenous CRISPR-based genome editing toolkit with a counterselection marker created here, for rapid and efficient multi-round multiplex editing of the chromosome, as well as scarless modification of the native plasmids, providing an improved genome engineering toolkit for Z. mobilis and an important reference to develope similar genetic manipulation systems in other non-model organisms.

Mechanisms of T cell organotropism.

Protective immunity relies upon T cell differentiation and subsequent migration to target tissues. Similarly, immune homeostasis requires the localization of regulatory T cells (Tregs) to the sites where immunity takes place. While naïve T lymphocytes recirculate predominantly in secondary lymphoid tissue, primed T cells and activated Tregs must traffic to the antigen rich non-lymphoid tissue to exert effector and regulatory responses, respectively. Following priming in draining lymph nodes, T cells acquire the 'homing receptors' to facilitate their access to specific tissues and organs. An additional level of topographic specificity is provided by T cells receptor recognition of antigen displayed by the endothelium. Furthermore, co-stimulatory signals (such as those induced by CD28) have been shown not only to regulate T cell activation and differentiation, but also to orchestrate the anatomy of the ensuing T cell response. We here review the molecular mechanisms supporting trafficking of both effector and regulatory T cells to specific antigen-rich tissues.

Dendritic cell modification as a route to inhibiting corneal graft rejection by the indirect pathway of allorecognition.

Dendritic cell (DC) modification is a potential strategy to induce clinical transplantation tolerance. We compared two DC modification strategies to inhibit allogeneic T-cell proliferation. In the first strategy, murine DCs were transduced with a lentiviral vector expressing CTLA4-KDEL, a fusion protein that prevents surface CD80/86 expression by retaining the co-stimulatory molecules within the ER. In the second approach, DCs were transduced to express the tryptophan-catabolising enzyme IDO. CTLA4-KDEL-expressing DCs induced anergy in alloreactive T cells and generated both CD4(+) CD25(+) and CD4(+) CD25(-) Treg cells (with direct and indirect donor allospecificity and capacity for linked suppression) both in vitro and in vivo. In contrast, T-cell unresponsiveness induced by IDO(+) DCs lacked donor specificity. In the absence of any immunosuppressive treatment, i.v. administration of CTLA4-KDEL-expressing DCs resulted in long-term survival of corneal allografts only when the DCs were capable of indirect presentation of alloantigen. This study demonstrates the therapeutic potential of CTLA4-KDEL-expressing DCs in tolerance induction.

Exploring road safety using alignment perspective features in real driving images: A case study on mountain freeways.

INTRODUCTION: While driving, drivers frequently adapt their driving behaviors according to their perception of the road's alignment features. However, traditional two-dimensional alignment methods lack the ability to capture these features from the driver's perspective. METHOD: This study introduces a novel method for road alignment recognition, employing image recognition technology to extract alignment perspective features, namely alignment perspective skewness (APS) and alignment perspective kurtosis (APK), from in-real driving images. Subsequently, the K-means clustering algorithm is utilized for road segment classification based on APS and APK indicators. Various sliding step length for clustering are employed, with step length ranging from 100m to 400m. Furthermore, the accident rates for different segment clusters are analyzed to explore the relationship between alignment perspective features and traffic safety. A 150 km mountain road section of the Erlianhaote-Guangzhou freewway from Huaiji to Sihui is selected as a case study. RESULTS: The results demonstrate that using alignment perspective features as classification criteria produces favorable clustering outcomes, with superior clustering performance achieved using shorter segment lengths and fewer cluster centers. The road segment classification based on alignment perspective features reveals notable differences in accident rates across categories; while traditional two-dimensional parameters-based classification methods fail to capture these differences. The most significant differences in accident rates across categories are observed with segment length of 100m, with the significance gradually diminishing as segment length increases and disappearing entirely when the length exceeds 300m. IMPLICATION: These findings validate the reliability of using alignment perspective features (APS and APK) for road alignment classification and road safety analysis, providing valuable insights for road safety management.

Combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of a mid-distal adjacent finger defect: a retrospective study.

PURPOSE: Assessing the clinical effectiveness of combining with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold to repair mid-distal defects in adjacent fingers. METHODS: From September 2012 to April 2022, 21 patients with 42 mid-distal defects of adjacent fingers underwent treatment using combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold. The flaps size ranged from 2.1 cm * 1.6 to 4.9 cm * 3.2 cm. Follow-up evaluations included assessing function, sensation, and appearance, etc. of the injured fingers and donor areas. RESULTS: All 42 flaps survived in 21 patients without any vascular crises, and the wounds healed in phase I. The mean follow-up time was 12.2 months (range 7-22 months). During follow-up, in injured fingers, according to the Michigan Hand Outcomes Questionnaire (MHOQ), the functional recovery and appearance were satisfactory; in Dargan Function Evaluation (DFE), the results were both "excellent" in fourteen patients, "excellent" and "good" in five patients, both "good" in one patient, "good" and "general" in one. In static two-point discrimination (2PD), the variation ranges from 4 to 9 mm in injured fingers and 6-10 mm in donor toes. Cold Intolerance Severity Score (CISS) is mild in all patients. The visual analogue score (VAS) showed no pain in the injured fingers and donor toes. No deformities or other complications were noted at the donor toes. According to Chinese Manchester Foot Pain and Disability Index (C-MFPDI), there was no morbidity on foot function in all donor areas. CONCLUSION: The surgical procedure of combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of mid-distal adjacent fingers defect is highly satisfactory. This approach helps the injured fingers to achieve good function, sensibility and appearance, while also achieving satisfactory results in the donor toes.

Ig gene-like molecule CD31 plays a nonredundant role in the regulation of T-cell immunity and tolerance.

CD31 is an Ig-like molecule expressed by leukocytes and endothelial cells with an established role in the regulation of leukocyte trafficking. Despite genetic deletion of CD31 being associated with exacerbation of T cell-mediated autoimmunity, the contribution of this molecule to T-cell responses is largely unknown. Here we report that tumor and allograft rejection are significantly enhanced in CD31-deficient mice, which are also resistant to tolerance induction. We propose that these effects are dependent on an as yet unrecognized role for CD31-mediated homophilic interactions between T cells and antigen-presenting cells (APCs) during priming. We show that loss of CD31 interactions leads to enhanced primary clonal expansion, increased killing capacity, and diminished regulatory functions by T cells. Immunomodulation by CD31 signals correlates with a partial inhibition of proximal T-cell receptor (TCR) signaling, specifically Zap-70 phosphorylation. However, CD31-deficient mice do not develop autoimmunity due to increased T-cell death following activation, and we show that CD31 triggering induces Erk-mediated prosurvival activity in T cells either in conjunction with TCR signaling or autonomously. We conclude that CD31 functions as a nonredundant comodulator of T-cell responses, which specializes in sizing the ensuing immune response by setting the threshold for T-cell activation and tolerance, while preventing memory T-cell death.

Comparison between traditional and new obesity measurement index for screening metabolic associated fatty liver disease.

Objectives: Obesity measurement indexes have certain screening value for metabolic diseases. To investigate associations between metabolic associated fatty liver disease (MAFLD) and obesity measurement indexes, including traditional indexes (BMI, WC, WHtR) and new indexes (ABSI, BRI, VAI, LAP), and assess their screening ability. Methods: 12,658 subjects aged 18-75 at the Health Center of a Class III Grade A Hospital were included, who were divided into MAFLD and non-MAFLD groups. Spearman's rank correlation was used to study the correlation between MAFLD and obesity measurement indexes. Receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) to evaluate their screening accuracy. Results: MAFLD had strong correlation with traditional BMI and new index LAP. ROC analysis showed that BMI had the highest AUC (0.89), followed by LAP (0.87). Stratification by BMI, LAP had the highest AUC (0.90) for MAFLD in population without obesity (BMI< 23kg/m2), and its optimal cutoff value was 20.75, with a sensitivity and specificity of 85.9% and 79.0%, respectively. Conclusions: We proposed a two-step screening strategy for MAFLD, combining BMI and LAP, and defined a high-risk population for MAFLD as follows: 1) BMI ≥ 23 kg/m2; and 2) BMI< 23 kg/m2 and LAP ≥ 20.75.

The glucose transporter 2 regulates CD8+ T cell function via environment sensing.

T cell activation is associated with a profound and rapid metabolic response to meet increased energy demands for cell division, differentiation and development of effector function. Glucose uptake and engagement of the glycolytic pathway are major checkpoints for this event. Here we show that the low-affinity, concentration-dependent glucose transporter 2 (Glut2) regulates the development of CD8+ T cell effector responses in mice by promoting glucose uptake, glycolysis and glucose storage. Expression of Glut2 is modulated by environmental factors including glucose and oxygen availability and extracellular acidification. Glut2 is highly expressed by circulating, recently primed T cells, allowing efficient glucose uptake and storage. In glucose-deprived inflammatory environments, Glut2 becomes downregulated, thus preventing passive loss of intracellular glucose. Mechanistically, Glut2 expression is regulated by a combination of molecular interactions involving hypoxia-inducible factor-1 alpha, galectin-9 and stomatin. Finally, we show that human T cells also rely on this glucose transporter, thus providing a potential target for therapeutic immunomodulation.

Molecular mechanisms of metabolic reprogramming in proliferating cells: implications for T-cell-mediated immunity.

To engage in proliferation, cells need to increase their biomass and replicate their genome. This process presents a substantial bioenergetic challenge: proliferating cells must increase ATP production and acquire or synthesize raw materials, including lipids, proteins and nucleic acids. To do so, proliferating cells actively reprogramme their intracellular metabolism from catabolic mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis and other anabolic pathways. This metabolic reprogramming, which directs nutrient uptake and metabolism during cell activation and proliferation, is under the control of specific signal transduction pathways. The underlying molecular mechanisms of cell metabolism reprogramming and their relevance to physiology and disease are currently under intense study. Several reports have uncovered the mechanisms of metabolic reprogramming that drive high rates of cell proliferation in cancer. Some recent studies have elucidated the physiological role of metabolic reprogramming during T-cell activation, differentiation and trafficking, which are potentially relevant to inflammatory disorders. This review describes the impact of metabolic reprogramming on the pathogenesis of cancer and the physiology of T-cell-mediated immune responses, with an emphasis on the phosphatidyl inositol 3-kinase-serine/threonine kinase-mammalian target of rapamycin pathway and the recently discovered metabolic processes regulated by nuclear factor-κB. These discoveries will hopefully translate into a better understanding of the role of metabolic reprogramming as a key regulator of T-cell-mediated immune responses and offer novel, immune-based therapeutic approaches.

Arginine depletion as a mechanism for the immune privilege of corneal allografts.

The cornea is an immune privileged tissue. Since arginase has been found to modulate T-cell function by depleting arginine, we investigated the expression of arginase in the cornea and its possible role in immune privilege using a murine transplant model. We found that both the endothelium and epithelium of murine corneas express functional arginase I, capable of down-regulating T-cell proliferation in an in vitro culture system. The administration of the specific arginase inhibitor N-hydroxy-nor-L-Arg to recipient mice resulted in an accelerated rejection of allogeneic C57BL/6 (B6) corneal grafts. In contrast, in vivo blockade of arginase activity had no effect in altering the course of rejection of primary skin grafts that express little, if any, arginase. In addition, the inhibition of arginase did not alter systemic T-cell proliferation. These data show that arginase is functional in the cornea and contributes to the immune privilege of the eye, and that modulation of arginase contributes to graft survival.

Associations of lipid parameters with non-alcoholic fatty liver disease in type 2 diabetic patients according to obesity status and metabolic goal achievement.

Aims: Non-obese non-alcoholic fatty liver disease (NAFLD) phenotype has sparked interest and frequently occurred in type 2 diabetes mellitus (T2DM). Information on associations between lipid parameters and NAFLD in non-obese patients with diabetes has been lacking. We aimed to investigate the relationships between lipid parameters and NAFLD according to obesity status and metabolic goal achievement in T2DM patients. Methods: A total of 1,913 T2DM patients who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed. We used logistic regression models to estimate the associations of lipid parameters with NAFLD risk according to obesity and metabolic goal achievement status. Results: Higher triglycerides, non-HDL-cholesterol, and all lipid ratios including (total cholesterol/HDL-cholesterol, triglyceride/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol, non-HDL-cholesterol/HDL-cholesterol), and lower HDL-cholesterol were associated with NAFLD risk in both non-obese and obese patients. The associations were stronger in non-obese patients than in obese patients. Further, the inverse associations of total cholesterol and LDL-cholesterol with NAFLD risk were only detected in non-obese patients. Triglycerides, HDL-cholesterol, and all lipid ratios studied were significantly associated with NAFLD risk, irrespective of whether the patients achieved their HbA1c, blood pressure, and LDL-cholesterol goal. The presence of poor lipids and lipid ratios were more strongly associated with NAFLD in patients who attained the HbA1c, blood pressure, and/or LDL-cholesterol goal than in those who did not achieve the goal attainment. Conclusions: The associations of lipids and lipid ratios with NAFLD risk were stronger in T2DM patients who were non-obese and achieved the HbA1c, blood pressure, and/or LDL-cholesterol goal attainment.

Loss of voltage-gated hydrogen channel 1 expression reveals heterogeneous metabolic adaptation to intracellular acidification by T cells.

Voltage-gated hydrogen channel 1 (Hvcn1) is a voltage-gated proton channel, which reduces cytosol acidification and facilitates the production of ROS. The increased expression of this channel in some cancers has led to proposing Hvcn1 antagonists as potential therapeutics. While its role in most leukocytes has been studied in depth, the function of Hvcn1 in T cells remains poorly defined. We show that Hvcn1 plays a nonredundant role in protecting naive T cells from intracellular acidification during priming. Despite sharing overall functional impairment in vivo and in vitro, Hvcn1-deficient CD4+ and CD8+ T cells display profound differences during the transition from naive to primed T cells, including in the preservation of T cell receptor (TCR) signaling, cellular division, and death. These selective features result, at least in part, from a substantially different metabolic response to intracellular acidification associated with priming. While Hvcn1-deficient naive CD4+ T cells reprogram to rescue the glycolytic pathway, naive CD8+ T cells, which express high levels of this channel in the mitochondria, respond by metabolically compensating mitochondrial dysfunction, at least in part via AMPK activation. These observations imply heterogeneity between adaptation of naive CD4+ and CD8+ T cells to intracellular acidification during activation.

Suppression of MHC class I surface expression by calreticulin's P-domain in a calreticulin deficient cell line.

Calreticulin (CRT) is an important chaperone protein, comprising an N-domain, P-domain and C-domain. It is involved in the folding and assembly of multi-component protein complexes in the endoplasmic reticulum, and plays a critical role in MHC class I antigen processing and presentation. To dissect the functional role and molecular basis of individual domains of the protein, we have utilized individual domains to rescue impaired protein assembly in a CRT deficient cell line. Unexpectedly, both P-domain fragment and NP domain of CRT not only failed to rescue defective cell surface expression of MHC class I molecules but further inhibited their appearance on the surface of cells. Formation of the TAP-associated peptide-loading complex and trafficking of the few detectable MHC class I molecules were not significantly impaired. Instead, this further suppression of MHC class I molecules on the cell surface appears due to the complex missing antigenic peptides, the third member of fully assembled MHC class I molecules. Therefore the P-domain of calreticulin appears to play a significant role in antigen presentation by MHC class I molecules.

Proteomics Analysis of Serum from COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic. To understand the changes in plasma proteomics upon SARS-CoV-2 infection, we analyzed the protein profiles of plasma samples from 10 COVID-19 patients and 10 healthy volunteers by using the DIA quantitative proteomics technology. We compared and identified differential proteins whose abundance changed upon SARS-CoV-2 infection. Bioinformatic analyses were then conducted for these identified differential proteins. The GO/KEEG database was used for functional annotation and enrichment analysis. The interaction relationship of differential proteins was evaluated with the STRING database, and Cytoscape software was used to conduct network analysis of the obtained data. A total of 323 proteins were detected in all samples. Difference between patients and healthy donors was found in 44 plasma proteins, among which 36 proteins were up-regulated and 8 proteins were down-regulated. GO functional annotation showed that these proteins mostly composed of cellular anatomical entities and proteins involved in biological regulation, cellular processes, transport, and other processes. KEEG functional annotation further showed that these proteins were mainly involved in complement system activation and infectious disease processes. Importantly, a KEEG pathway (natural killer cell-mediated cytotoxicity) was enriched, with three important activators of this pathway, ICAM1/2 and IgG, being up-regulated. Protein-protein interaction (PPI) statistics indicated that, among these 44 proteins, 6 were the most significantly up-regulated (DBH, SHGB, TF, ICAM2, THBS1, and C1RL) while 2 were the most significantly down-regulated (APCS and ORM1). Results from this study showed that a few proteins associated with immune activation were up-regulated in patient plasma. In addition, this study established a method for extraction and quantitative determination of plasma components in convalescent plasma from COVID-19 patients.

Comparative transcriptome profiles of large and small bodied large-scale loaches cultivated in paddy fields.

Fish culture in paddy fields is a traditional aquaculture mode, which has a long history in East Asia. Large-scale loach (Paramisgurnus dabryanus) fast growth is suitable for paddy fields aquaculture in China. The objective of this study was to identify differential expression genes (DEGs) in the brain, liver and muscle tissues between large (LG, top 5% of maximum total length) and small (SG, top 5% of minimum total length) groups using RNA-seq. In total, 150 fish were collected each week and 450 fish were collected at twelfth week from three paddy fields for all the experimental. Histological observation found that the muscle fibre diameter of LG loaches was greater than that of SG loaches. Transcriptome results revealed that the high expression genes (HEGs) in LG loaches (fold change ≥ 2, p < 0.05) were mainly concentrated in metabolic pathways, such as "Thyroid hormone signalling pathway", "Citrate cycle (TCA cycle)", "Carbon metabolism", "Fatty acid metabolism", and "Cholesterol metabolism", and the HEGs in SG loaches were enriched in the pathways related to environmental information processing such as "Cell adhesion molecules (CAMs)", "ECM- receptor interaction" and "Rap1 signalling pathway"; cellular processes such as "Tight junction", "Focal adhesion", "Phagosome" and "Adherens junction". Furthermore, IGFs gene family may play an important role in loach growth for their different expression pattern between the two groups. These findings can enhance our understanding about the molecular mechanism of different growth and development levels of loaches in paddy fields.

Memory T-cell trafficking: new directions for busy commuters.

The immune system is unique in representing a network of interacting cells of enormous complexity and yet being based on single cells travelling around the body. The development of effective and regulated immunity relies upon co-ordinated migration of each cellular component, which is regulated by diverse signals provided by the tissue. Co-ordinated migration is particularly relevant to the recirculation of primed T cells, which, while performing continuous immune surveillance, need to promptly localize to antigenic sites, reside for a time sufficient to carry out their effector function and then efficiently leave the tissue to avoid bystander damage. Recent advances that have helped to clarify a number of key molecular mechanisms underlying the complexity and efficiency of memory T-cell trafficking, including antigen-dependent T-cell trafficking, the regulation of T-cell motility by costimulatory molecules, T-cell migration out of target tissue and fugetaxis, are reviewed in this article.

[Expression of fragile histidine triad (FHIT) protein and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust].

OBJECTIVE: To study the expression and significance of fragile histidine triad (FHIT) and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust. METHODS: Every second generation of immortalized human bronchial epithelial cells (BEAS-2B) and human embryo lung fibroblasts (WI-38) were exposed to 100 µg/ml Yunnan tin mine dust for 72 h, until the ninth generation. The cells were subsequently co-cultured from the 11th generation. Experimental setup: B group, B (W) group, B (W 100) group, B100 group, B100 (W) group, B100 (W100) group. The expressions of FHIT and Ki-67 in epithelial cells were determined by the method of immunocytochemistry at the 16th, 26th and 36th generation. The percentage of Ki-67 positive cells was calculated as proliferation index. RESULTS: The expression of FHIT was observed in BEAS-2B cells. The expression levels of FHIT among B group, B (W) group and B (W 100) group had not instinctive difference. At the 16th generation, the expression of FHIT in the B100 group was decreased compared with that in the B group and the expression of FHIT between B100 (W) group and B100 (W100) group was lower than that in the B100 group. At the 26th generation, the expression of FHIT was decreased compared with that at the 16th generation in the B100, B100 (W) and B100 (W100) groups. However, At the 36th generation, positive expression were observed again in the B100, B100 (W) and B100 (W100) groups and the expression levels were in incremental order. At the 16th, 26th and 36th generation, the proliferation indexes of B group, B (W) group and B (W 100) group were all < 3%. The proliferation indexes of B100, B100 (W) and B100 (W100) were increased step by step with the generation elongation. CONCLUSIONS: FHIT could be a target at which Yunnan tin mine dust induces transformation of BEAS-2B cells. The proliferation activation of BEAS-2B cells can be improved by Yunnan tin mine dust.