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Background Huanglianjiedu decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) prescription with thousand years of clinical use against various malignancies, including pancreatic adenocarcinoma (PAAD). However, its potential bioactive component and molecular mechanism remains unclear. Aims This study is to inspect the HLJDD mechanisms of action against PAAD via integrated computational and pharmacochemistry strategy, in vivo and in vitro experiments to validate associated targets and pathways. Methods A PAAD xenograft model was established by subcutaneous injecting Panc02 cells into C57BL/6 mice. Ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was engaged to determine constituents of HLJDD and assessed for pharmacokinetic scheme using the TCM Systems Pharmacology Platform (TCM-SP). Differentially expressed genes (DEGs) of PAAD was retrieved from the transcriptome dataset GSE43795, followed by recognizing overlapping targets the oncogenes and target genes of PAAD and HLJDD, respectively. Putative signaling pathways of HLJDD in treating PAAD were enriched using KEGG and GO analyses. The anti-PAAD effects of HLJDD was assessed in vivo and in vitro , besides, the potential mechanism was validated using immunoblotting and immunohistochemical assays. Results HLJDD significantly suppressed the growth of transplanted PAAD tumors, constrained PAAD progression, and induced apoptosis and S-phase arrest. Seventy-five active components meeting the drug-likeness criteria and 278 target genes of HLJDD were identified. KEGG analysis indicated that the top three enriched pathways were cancer, AGE-RAGE signaling, and IL-17 signaling pathways. Disease enrichment analysis highlighted immune, pharmacological, and cancer-related diseases as the top three categories. A total of 47 potential target genes were identified. Immunoblotting revealed that HLJDD inhibited PI3K and MAPK-related signaling pathways, while immunohistochemical staining confirmed that HLJDD suppressed the expression of phosphorylated MAPK and ERK1/2. Conclusion HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.

Hexavalent chromium (Cr (VI)) and para-chlorophenol (4-CP) are prevalent industrial wastewater contaminants that are recalcitrant to natural degradation and prone to migration in aquatic systems, thereby harming biological health and destabilizing ecosystems. Consequently, their removal is imperative. Compared to conventional chemical treatment methods, CW-MFC technology offers broader application potential. Leersia hexandra Swartz can enhance Cr (VI) and 4-CP absorption, thereby improving wastewater purification and electricity generation in CW-MFC systems. In this study, three CW-MFC reactors were designed with L. hexandra Swartz in distinct configurations, namely, stacked, multistage, and modular, to optimize the removal of Cr (VI) and 4-CP. By evaluating wastewater purification, electrochemical performance, and plant growth, the optimal influent hydraulic retention time (HRT) was determined. The results indicated that the modular configuration at an HRT of 5 days achieved superior removal rates and power generation. The modular configuration also supported the best growth of L. hexandra, with optimal photosynthetic parameters, and physiological and biochemical responses. These results underscore the potential of modular CW-MFC technology for effective detoxification of complex wastewater mixtures while concurrently generating electricity. Further research could significantly advance wastewater treatment and sustainable energy production, addressing water pollution, restoring aquatic ecosystems, and mitigating the hazards posed by Cr (VI) and 4-CP to water and human health.

Abstract Non-alcoholic steatohepatitis (NASH) has received great attention due to its high incidence. Here, we show that lysosomal-associated protein transmembrane 5 (LAPTM5) is associated with NASH progression through extensive bioinformatical analysis. The protein level of LAPTM5 bears a negative correlation with NAS score. Moreover, LAPTM5 degradation is mediated through its ubiquitination modification by the E3 ubquitin ligase NEDD4L. Discovered by experiments conducted on male mice, hepatocyte-specific depletion of Laptm5 exacerbates mouse NASH symptoms. In contrast, Laptm5 overexpression in hepatocytes exerts diametrically opposite effects. Mechanistically, LAPTM5 interacts with CDC42 and promotes its degradation through a lysosome-dependent manner under the stimulation of palmitic acid, thus inhibiting activation of the mitogen-activated protein kinase signaling pathway. Finally, adenovirus-mediated hepatic Laptm5 overexpression ameliorates aforementioned symptoms in NASH models.

Abstract Background Protein kinases play a pivotal role in the malignant evolution of pancreatic cancer (PC) through mediating phosphorylation. Many kinase inhibitors have been developed and translated into clinical use, while the complex pathology of PC confounds their clinical efficacy and warrants the discovery of more effective therapeutic targets. Methods Here, we used the Gene Expression Omnibus (GEO) database and protein kinase datasets to map the PC-related protein kinase-encoding genes. Then, applying Gene Expression and Profiling Interactive Analysis (GEPIA), GEO and Human Protein Atlas, we evaluated gene correlation, gene expression at protein and mRNA levels, as well as survival significance. In addition, we performed protein kinase RIPK2 knockout and overexpression to observe effects of its expression on PC cell proliferation, migration and invasion in vitro, as well as cell apoptosis, reactive oxygen species (ROS) production and autophagy. We established PC subcutaneous xenograft and liver metastasis models to investigate the effects of RIPK2 knockout on PC growth and metastasis. Co-immunoprecipitation and immunofluorescence were utilized to explore the interaction between protein kinases RIPK2 and PRKCI. Polymerase chain reaction and immunoblotting were used to evaluate gene expression and protein phosphorylation level. Results We found fourteen kinases aberrantly expressed in human PC and nine kinases with prognosis significance. Among them, RIPK2 with both serine/threonine and tyrosine activities were validated to promote PC cells proliferation, migration and invasion. RIPK2 knockout could inhibit subcutaneous tumor growth and liver metastasis of PC. In addition, RIPK2 knockout suppressed autophagosome formation, increased ROS production and PC cell apoptosis. Importantly, another oncogenic kinase PRKCI could interact with RIPK2 to enhance the phosphorylation of downstream NF-κB, JNK and ERK. Conclusion Paired protein kinases PRKCI-RIPK2 with multiple phosphorylation activities represent a new pathological mechanism in PC and could provide potential targets for PC therapy.

IntroductionAortic aneurysms (AA) are prevalent worldwide with a notable absence of drug therapies. Thus, identifying potential drug targets is of utmost importance. AA often presents in the elderly, coupled with consistently raised serum inflammatory markers. Given that ageing and inflammation are pivotal processes linked to the evolution of AA, we have identified key genes involved in the inflammaging process of AA development through various bioinformatics methods, thereby providing potential molecular targets for further investigation.MethodsThe transcriptome data of AA was procured from the datasets GSE140947, GSE7084, and GSE47472, sourced from the NCBI GEO database, whilst gene data of ageing and inflammation were obtained from the GeneCards Database. To identify key genes, differentially expressed analysis using the “Limma” package and WGCNA were implemented. Protein-protein intersection (PPI) analysis and machine learning (ML) algorithms were employed for the screening of potential biomarkers, followed by an assessment of the diagnostic value. Following the acquisition of the hub inflammaging and AA-related differentially expressed genes (IADEGs), the TFs-mRNAs-miRNAs regulatory network was established. The CIBERSORT algorithm was utilized to investigate immune cell infiltration in AA. The correlation of hub IADEGs with infiltrating immunocytes was also evaluated. Lastly, wet laboratory experiments were carried out to confirm the expression of hub IADEGs.Results342 and 715 AA-related DEGs (ADEGs) recognized from GSE140947 and GSE7084 datasets were procured by intersecting the results of “Limma” and WGCNA analyses. After 83 IADEGs were obtained, PPI analysis and ML algorithms pinpointed 7 and 5 hub IADEGs candidates respectively, and 6 of them demonstrated a high diagnostic value. Immune cell infiltration outcomes unveiled immune dysregulation in AA. In the wet laboratory experiments, 3 hub IADEGs, including BLNK, HLA-DRA, and HLA-DQB1, finally exhibited an expression trend in line with the bioinformatics analysis result.DiscussionOur research identified three genes - BLNK, HLA-DRA, and HLA-DQB1- that play a significant role in promoting the development of AA through inflammaging, providing novel insights into the future understanding and therapeutic intervention of AA.

IntroductionCurrently, the treatment strategies for angular pregnancy in the first trimester after assisted reproduction technology (ART) are unclear. Improper treatment will cause unnecessary losses to patients, especially infertile patients, after ART. The purpose of this study was to clarify the pregnancy outcomes of expectant treatment for angular pregnancy post-ART and to provide a basis for the formulation of clinical treatment strategies.MethodThis retrospective case series study was performed at the Reproductive Medicine Center of a university hospital. Maternal data and pregnancy outcomes were collected and analyzed for all patients diagnosed with angular pregnancies after ART between January 2016 and August 2021. The outcomes included live birth, term birth, premature birth, early pregnancy loss, fetal death, placental abruption, uterine rupture, maternal death, and hysterectomy.ResultsA total of 78 patients were analyzed in this study, of whom 54 (69.2%) had live births, 44 (56.4%) had term births, 21 (26.9%) had an early pregnancy loss, 1 (1.3%) had mid-trimester missed abortion, 1 (1.3%) underwent mid-trimester labor induction due to fetal malformation, and 1 (1.3%) underwent uterine rupture. There were no cases of maternal death, placental abruption, or hysterectomies.DiscussionAngular pregnancy after ART is not as dangerous as that described in previous studies; most cases could be treated expectantly under close-interval follow-up and obtain live birth.

BackgroundIn observational and experimental studies, allergic diseases (AD) have been reported to be associated with some types of cardiovascular diseases (CVD), as both share common pathophysiological processes involving inflammation and metabolic disorders. However, the direction of the causal association between them remains unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between AD and CVD.MethodsWe utilized publicly available genome-wide association study (GWAS) summary statistics data from European participants in the UK Biobank and the IEU Open GWAS database. Genetic variants associated with AD, asthma, and CVD were identified and used as instrumental variables to investigate the genetically causal association between them. MR analyses were performed using various analytical methods, including inverse variance weighted-fixed effects (IVW-FE), inverse variance weighted-multiplicative random effects (IVW-RE), MR-Egger, weighted median, weighted mode, and maximum likelihood. Sensitivity tests were conducted to assess the validity of the causality.ResultsThe MR analysis with the IVW method revealed a genetically predicted association between AD and essential hypertension [odds ratio (OR)=0.9987, 95% confidence interval (CI): 0.9976-0.9998, P=0.024], as well as between asthma and atrial fibrillation (OR=1.001, 95% CI: 1.0004-1.0017, P=6.43E-05). In the reverse MR analyses, heart failure was associated with allergic diseases (OR=0.0045, 95% CI: 1.1890E-04 - 0.1695, P=0.004), while atherosclerosis (OR=8.7371E-08, 95% CI: 1.8794E-14 - 4.0617E-01, P=0.038) and aortic aneurysm and dissection (OR=1.7367E-07, 95% CI: 3.8390E-14 – 7.8567E-01, P=0.046) might be protective factors of asthma. However, after a Bonferroni correction, only the association between asthma and atrial fibrillation remained robust.ConclusionThe MR study revealed that asthma is a predominant risk of atrial fibrillation in European individuals, consistent with most experimental and observational studies. Whether AD affects other CVD and the causality between them needs further investigation.

Abstract Nonalcoholic fatty liver disease (NAFLD) is an ubiquitous disease that exists across a wide spectrum ranging from steatosis, steatohepatitis, advanced fibrosis, and liver cirrhosis. Hallmarks of NAFLD are lipid accumulation, insulin resistance, and chronic low-grade inflammation. However, there currently are no medications approved for NAFLD. B-cell lymphoma 6 (BCL6) is a transcriptional inhibitor that is vital for germinal center B-cell formation. Our study identified BCL6 as a critical modulator of hepatic lipid metabolism and appears to contribute to the initiation and progression of NAFLD. In our research, we induced hepatic BCL6 overexpression using adeno-associated virus (AAV), as well as conditional liver-specific BCL6 knockout mice (BCL6-CKO). With these models, we noted that BCL6 overexpression improved insulin resistance and hepatic steatosis in mice models maintained on a HFD diet. Conversely, these parameters worsened in the livers of mice with downregulated BCL6 levels. Mechanistically, the translocase fatty acid CD36 was determined to be a transcriptional target of BCL6 that influences its role in hepatic steatosis. BCL6 bound directly to the CD36 promoter region, restraining CD36 transcription under physiological conditions. We conclude that the hepatocyte BCL6 inhibits the NAFLD progression in mice, including deranged lipid accumulation and glucose metabolism, through a CD36-dependent manner. These results indicate that BCL6 may potentially be targeted in NAFLD treatment.

The Chinese government encourages rural economic entities to use farmland management rights as collateral for loans, which helps to alleviate multi-level financing needs in rural areas. Based on the panel data of counties in Hubei Province, this paper adopts the Difference-in-Differences (DID) and the intermediary effect model to evaluate the impact of farmland management rights mortgage loans (FMRML) on the agri-food industrial agglomeration (AIA) in China. The study found that the pilot policy has significantly promoted the AIA. Moreover, the regression results remain robust after conducting the placebo test and the Propensity Score Matching Difference-in-Differences (PSM-DID) model, which demonstrates that the improvement effect is stable and long-lasting. From the heterogeneity analysis, it can be seen that the policy of FMRML has a more significant effect on the AIA in mountainous and hilly areas. By further analysis of the mechanism of action, it can be concluded that the pilot policy promotes the AIA by enhancing agricultural specialized production. The main findings can provide information for policymakers in China. The recommendations we have summarized encompass gradually expanding the scope of the pilot policy of FMRML, advancing the institutionalization and legalization of the policy, and promoting agricultural production specialization.

BackgroundDamp-heat syndrome is one of the most important syndrome types in the traditional Chinese medicine (TCM) syndrome differentiation and treatment system, as well as the core pathogenesis of pancreatic cancer (PC) which remains a challenge to medical researchers due to its insidious onset and poor prognosis. Great attention has been given to the impact of damp-heat syndrome on tumorigenesis and progression, but less attention has been given to damp-heat modeling per se. Studying PC in a proper damp-heat syndrome animal model can recapitulate the actual pathological process and contribute to treatment strategy improvement.MethodsHere, an optimized damp-heat syndrome mouse model was established based on our prior experience. The Fibonacci method was applied to determine the maximum tolerated dosage of alcohol for mice. Damp-heat syndrome modeling with the old and new methods was performed in parallel of comparative study about general appearance, food intake, water consumption and survival. Major organs, including the liver, kidneys, lungs, pancreas, spleen, intestines and testes, were collected for histological evaluation. Complete blood counts and biochemical tests were conducted to characterize changes in blood circulation. PC cells were subcutaneously inoculated into mice with damp-heat syndrome to explore the impact of damp-heat syndrome on PC growth. Hematoxylin-eosin staining, Masson staining and immunohistochemistry were performed for pathological evaluation. A chemokine microarray was applied to screen the cytokines mediating the proliferation-promoting effects of damp-heat syndrome, and quantitative polymerase chain reaction and Western blotting were conducted for results validation.ResultsThe new modeling method has the advantages of mouse-friendly features, easily accessible materials, simple operation, and good stability. More importantly, a set of systematic indicators was proposed for model evaluation. The new modeling method verified the pancreatic tumor-promoting role of damp-heat syndrome. Damp-heat syndrome induced the proliferation of cancer-associated fibroblasts and promoted desmoplasia. In addition, circulating and tumor-located chemokine levels were altered by damp-heat syndrome, characterized by tumor promotion and immune suppression.ConclusionsThis study established a stable and reproducible murine model of damp-heat syndrome in TCM with systematic evaluation methods. Cancer associated fibroblast-mediated desmoplasia and chemokine production contribute to the tumor-promoting effect of damp-heat syndrome on PC.

BackgroundHypoxemia is common in patients undergoing cardiac surgery, however, few studies about severe hypoxemia (SH) after cardiac surgery exist. The objectives of this study were to clarify the incidence, risk factors, and outcomes of SH after cardiac surgery.MethodsPatients undergoing cardiac surgery from 2016 to 2019 in a single center were enrolled and were divided into two groups based on whether postoperative SH developed. Independent risk factors for SH were identified by univariate and multivariate analysis. Model selection statistics were applied to help determine the most parsimonious final model.ResultsSevere hypoxemia developed in 222 of the 5,323 included patients (4.2%), was associated with poorer clinical outcomes. Six independent risk factors for SH after cardiac surgery were identified by multivariate analysis, such as surgical types, white blood cell (WBC) count, body mass index (BMI), serum albumin, cardiopulmonary bypass (CPB) time, and intraoperative transfusion of red blood cells (RBCs). After comprehensively considering the discrimination, calibration, and simplicity, the most appropriate and parsimonious model was finally established using four predictors, such as WBC count, BMI, CPB time, and intraoperative transfusion of RBCs. A nomogram and a web-based risk calculator based on the final model were constructed to facilitate clinical practice. Patients were stratified into three risk groups based on the nomogram and clinical practice.ConclusionSevere hypoxemia was common after cardiac surgery and was associated with poorer clinical outcomes. A parsimonious final model with good discrimination, calibration, and clinical utility was constructed, which may be helpful for personalized risk assessment and targeted intervention.

Abstract Purpose The aim of this meta-analysis was to evaluate the effect of growth hormone (GH) supplementation in poor responders undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Methods PubMed, MEDLINE and Cochrane Library databases were searched for the identification of relevant randomized controlled trials. Outcome measures were live birth rate, clinical pregnancy rate, miscarriage rate, cycle cancelation rate, number of retrieved oocytes and total dose of gonadotropin. Results Fifteen randomized controlled trails (RCTs) involving 1448 patients were eligible for the analysis. GH supplementation improved live birth rate (RR, 1.74; 95% CI, 1.19–2.54), clinical pregnancy rate (RR, 1.65; 95% CI, 1.31–2.08) and retrieved oocytes number (SMD, 0.72; 95% CI, 0.28–1.16), while reducing cancelled cycles rate (RR, 0.62; 95% CI, 0.44–0.85) and dose of Gonadotropin (SMD,-1.05 95% CI, − 1.62 - -0.49) for poor ovarian response patients. Besides, there was no significant difference in the miscarriage rate between GH group and control group. Conclusions Based on the limited available evidence, growth hormone supplementation seems to improve IVF/ICSI outcomes for poor ovarian responders. Further randomized controlled trials with large sample sizes are required to clarify the effect of GH adjuvant therapy in the treatment of women with poor ovarian response.

Psoriasis is a chronic inflammatory skin disease, and elevation of proinflammatory cytokine levels is a critical driver of the pathogenesis of psoriasis. Extracellular cold-inducible RNA-binding protein (eCIRP) has been shown to play a role in various acute and chronic inflammatory diseases. C23, a short peptide derived from CIRP, competitively binds CIRP receptors and reduces damage in inflammatory diseases. However, the effect of eCIRP in psoriasis has not been studied. In the present study, we investigated the role of eCIRP in the expression of proinflammatory cytokines in keratinocytes. Our data show that eCIRP expression was increased in the sera of psoriasis patients and imiquimod- (IMQ-) induced psoriatic mice and cells stimulated with proinflammatory cytokines (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α; mix M5). Recombinant human CIRP (rhCIRP) promoted the expression of the proinflammatory cytokines TNF-α, IL-6, and IL-8 and the activation of NF-kappaB (NF-κB) and ERK1/2 in cultured keratinocytes. We then found that the above effects of eCIRP could be blocked by C23 in both normal keratinocytes and M5-stimulated psoriatic keratinocytes. In addition, in vivo experiments revealed that C23 could effectively ameliorate IMQ-induced psoriatic dermatitis. TNF-α and IL-6 mRNA expressions were reduced in the skin lesions of mice with C23-treated IMQ-induced psoriasis, and this effect was accompanied by inhibition of the NF-κB and ERK1/2 signaling pathways. In summary, eCIRP plays an important role in the pathogenesis of psoriasis and may become a new target for psoriasis treatment.

BackgroundThe scoring system for human blastocysts is traditionally based on morphology; however, there are controversies on the effect of morphology parameters on pregnancy outcomes. The aim of this study is to evaluate the predicting value of each morphology parameter on pregnancy outcomes in a setting of single embryo transfer.MethodsThis is a retrospective cohort study on patients undergoing frozen-thawed single blastocyst transfer at our center, between Jan. 2009 and Dec. 2018. A total of 10,482 cycles were analyzed. The blastocysts were scored according to the expansion and hatching status, morphology of inner cell mass (ICM), and cells of trophectoderm (TE). The primary outcome measure was live birth rate. One-way analysis of variance, chi-square test, and multiple logistic regression were used for statistical analysis.ResultsThe clinical pregnancy rate was lower in the blastocysts of stage 3 (48.15%), compared with those of stage 4 (56.15%), stage 5 (54.91%), and stage 6 (53.37%). The live birth rate was lower in the blastocysts of stage 3 (37.07%), compared with those of stage 4 (44.21%) and stage 5 (41.67%). The rates of clinical pregnancy (A: 66.60%, B: 53.25%, C: 39.33%) and live birth (A: 54.62%, B: 41.29%, C: 28.45%) were both decreased with decreasing grade of ICM morphology, and these differences were pairwise significant. The miscarriage rate of blastocysts with ICM grade A was lower, compared with ICM grade C (17.53 vs. 27.66%). Blastocysts with TE morphology of C had lower rates of clinical pregnancy (43.53%) and live birth (32.57%), compared with those with TE morphology of A and B (clinical pregnancy rate: 64.26% for A, 58.11% for B; live birth rate: 52.74% for A, 45.64% for B). There were no significant differences in rates of clinical pregnancy, live birth, and miscarriage between the blastocysts with TE grade A and B.ConclusionsThe blastocyst expansion stage, ICM grade, and TE grade are all associated with pregnancy outcomes. ICM grade is the strongest predictor of live birth. A blastocyst with stage 4–5, ICM grade A, and TE grade A/B should be given priority for single embryo transfer.

Carver and White developed the Behavioral Inhibition/Behavioral Activation Scales (the BIS/BAS Scales) based on Reinforcement Sensitivity Theory proposed by Gray. Subsequent studies proposed that substance abuse was closely related to Behavioral Inhibition System (BIS) and Behavioral Activation System (BAS). However, researches on the psychometric properties of the BIS/BAS scales in clinical samples are scarce. The present study was conducted to analyze the applicability of the BIS/BAS scales in a sample suffering from a substance use disorder (SUD) and undergoing treatment in compulsory detoxification institutions (n = 1117). Meanwhile, 822 community residents were selected for comparison. Confirmatory factor analysis was carried out to examine the construct validity and the results showed that the five-factor model was the best fit for people with a substance use disorder’ data. Besides, Cronbach’s alpha coefficient for the total scale was 0.808, indicating the satisfactory internal consistency reliability. Analysis of the correlation coefficient of the questionnaire with the corresponding personality traits showed that BAS was more associated with the impulsive trait. Surprisingly, participants with a substance use disorder showed more insensitivity for the reward dimension compared with that of community residents and the result of comparison between two samples supported joint subsystems hypothesis. Generally, the BIS/BAS scales showed good reliability and validity. These findings provide more direct evidence on the personality traits of people with a substance use disorder and should form the basis for further research.

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive T-cell malignancy. This study was designed to explore the expression and functional significance of microRNA (miR)-212 in ATL. The expression of miR-212 in human ATL tissues and cell lines were investigated. Gain-of-function experiments were carried out to determine the roles of miR-212 in cell proliferation, tumorigenesis, cell cycle progression, and apoptosis. We also identified and functionally characterized the target genes of miR-212 in ATL cells. Compared with normal lymph node biopsies, lymphoma samples from ATL patients displayed underexpression of miR-212 (p=0.0032). Consistently, miR-212 was downregulated in human ATL cell lines, compared with normal T lymphocytes. Restoration of miR-212 significantly (p<0.05) inhibited ATL cell proliferation and tumorigenesis in mice. Overexpression of miR-212 led to an accumulation of G0/G1-phase cells and a concomitant reduction of S-phase cells. Moreover, enforced expression of miR-212-induced significant apoptosis in ATL cells. CCND3, which encodes a cell cycle regulator cyclin D3, was identified as a direct target of miR-212 in ATL cells. Rescue experiments with a miR-212-resistant variant of CCND3 demonstrated that overexpression of CCND3 restored cell-cycle progression and attenuated apoptotic response in miR-212-overexpressing ATL cells. Taken together, miR-212 exerts growth-suppressive effects in ATL cells largely by targeting CCND3 and may have therapeutic potential in ATL. [ABSTRACT FROM AUTHOR]