Hexokinase 2 nonmetabolic function-mediated phosphorylation of IκBα enhances pancreatic ductal adenocarcinoma progression.

Aberrant signaling in tumor cells induces nonmetabolic functions of some metabolic enzymes in many cellular activities. As a key glycolytic enzyme, the nonmetabolic function of hexokinase 2 (HK2) plays a role in tumor immune evasion. However, whether HK2, dependent of its nonmetabolic activity, plays a role in human pancreatic ductal adenocarcinoma (PDAC) tumorigenesis remains unclear. Here, we demonstrated that HK2 acts as a protein kinase and phosphorylates IκBα at T291 in PDAC cells, activating NF-κB, which enters the nucleus and promotes the expression of downstream targets under hypoxia. HK2 nonmetabolic activity-promoted activation of NF-κB promotes the proliferation, migration, and invasion of PDAC cells. These findings provide new insights into the multifaceted roles of HK2 in tumor development and underscore the potential of targeting HK2 protein kinase activity for PDAC treatment.

Disruption of Cdk5-GluN2B complex by a small interfering peptide attenuates social isolation-induced escalated intermale attack behavior and hippocampal oxidative stress in mice.

Social isolation has emerged as a significant issue during the COVID-19 pandemic that can adversely impact human mental health and potentially lead to pathological aggression. Given the lack of effective therapeutic interventions for aggressive behavior, alternative approaches are necessary. In this study, we utilized a genetic method combined with a pharmacological approach to identify and demonstrate the crucial role of Cdk5 in escalated intermale attack behavior induced by 2-week social isolation. Moreover, we developed a small peptide that effectively disrupts the interaction between Cdk5 and GluN2B, given the known involvement of this complex in various neuropsychiatric disorders. Administration of the peptide, either systemically or via intrahippocampal injection, significantly reduced oxidative stress in the hippocampus and attenuated intermale attack behavior induced by 2-week social isolation. These findings highlight the previously unknown role of the hippocampal Cdk5-GluN2B complex in social isolation-induced aggressive behavior in mice and propose the peptide as a promising therapeutic strategy for regulating attack behavior and oxidative stress.

Monitoring Electron Flow in Nickel Single-Atom Catalysts during Nitrogen Photofixation.

An efficient catalytic system for nitrogen (N2) photofixation generally consists of light-harvesting units, active sites, and an electron-transfer bridge. In order to track photogenerated electron flow between different functional units, it is highly desired to develop in situ characterization techniques with element-specific capability, surface sensitivity, and detection of unoccupied states. In this work, we developed in situ synchrotron radiation soft X-ray absorption spectroscopy (in situ sXAS) to probe the variation of electronic structure for a reaction system during N2 photoreduction. Nickel single-atom and ceria nanoparticle comodified reduced graphene oxide (CeO2/Ni-G) was designed as a model catalyst. In situ sXAS directly reveals the dynamic interfacial charge transfer of photogenerated electrons under illumination and the consequent charge accumulation at the catalytic active sites for N2 activation. This work provides a powerful tool to monitor the electronic structure evolution of active sites under reaction conditions for photocatalysis and beyond.

Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer.

BACKGROUND: B and T lymphocyte attenuator (BTLA) is a co-signaling protein belonging to the CD28 immunoglobulin superfamily. However, the role of BTLA in prognosis and immunotherapy of colorectal cancer (CRC) remains unclear. METHODS: We evaluated the expression of BTLA via the Oncomine and the cancer genome atlas (TCGA) database. We research the outcome among different BTLA expression patients by Kaplan-Meier curve. We used the Chi-Squared test and Cox regression analysis to identify potential risk factors. Besides, the correlations between BTLA and cancer immune infiltration were investigated via CIBERSORT. RESULTS: Various cohorts showed that BTLA expression was lower in CRC compared to corresponding normal tissue. Moreover, low BTLA expression was correlated with poor overall survival in TCGA cohorts and Gene Expression Omnibus cohorts (GSE29623 and GSE17536). Low BTLA expression was associated with less lymph node metastasis (p = 0.0123). In the Cox proportional hazards model, BTLA was identified as a favorable prognostic factor. Naive B cells, memory B cells, CD8 T cells, CD4 memory resting T cells, follicular helper T (Tfh) cells, monocytes, resting natural killing (NK) cells, M0 macrophages, M1 macrophages, resting mast cells, and activated mast cells were affected by BTLA expression (all p < 0.01). Correlated immune markers and functional enrichment analysis revealed BTLA functioned in the T cell receptor signaling pathway, B cell receptor signaling pathway, and NK cell-mediated cytotoxicity pathway. CONCLUSION: These analyses suggest BTLA is a potential factor for extended survival and closely related to CD8 T cells, Tfh cells, B cells, and NK cells in CRC. We summarize these results that BTLA can be used as a prognostic biomarker and might contribute to developing novel CRC immunological treatment strategies.

Interstitial pneumonia as the initial presentation in an infant with a novel mutation of CD40 ligand-associated X-linked hyper-IgM syndrome: A case report.

INTRODUCTION: X-linked hyper-IgM syndrome is a type of primary combined immunodeficiency disorder caused by mutations in CD40 ligand. Opportunistic infections caused by P jirovecii, cytomegalovirus (CMV), or fungi are frequently the first presenting symptom of the patients with X-linked hyper-IgM syndrome. PATIENT CONCERNS: Here, we report a 10-month-old infant who presented with cyanosis and shortness of breath. The infant exhibited no medical or birth history indicating a primary immune deficiency and was first diagnosed with interstitial pneumonia and acute respiratory failure on admission. DIAGNOSES: The infant was diagnosed with Pneumocystis jirovecii pneumonia combined with CMV and fungal infection through gene sequencing by nasopharyngeal swab and G-test. Whole-exome sequencing from a blood sample was performed and identified a functional mutation across the CD40 ligand gene (NM_000074;exon1;C.86_87del) resulting in an amino acid change (P.T29Sfl*18) attributed to X-linked hyper IgM syndrome. INTERVENTIONS: The infant received continuous positive airway pressure ventilation treatment combined with trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia, ganciclovir for CMV, voriconazole for fungal infection and substitution of high-dose immunoglobulin. OUTCOMES: Six months after discharge from our hospital, the infant remained well. CONCLUSION: Opportunistic infections should be suspected in infants presenting with severe interstitial pneumonia. Primary immune deficiency diseases should also be considered in infants diagnosed with opportunistic infections.

In situ observation of void evolution in 1,3,5-triamino-2,4,6-trinitrobenzene under compression by synchrotron radiation X-ray nano-computed tomography.

The formation and development of voids in 1,3,5-triamino-2,4,6-trinitrobenzene crystals under compression were characterized in situ by X-ray nano-computed tomography. Benefiting from high spatial resolution (30 nm) and excellent imaging contrast, the X-ray nano-computed tomography images revealed the presence of a small fraction of inhomogeneous structures in the original crystal (volume ratio ∼1.2%). Such an inhomogeneity acts as a nucleation of voids and produces stress concentration during compression, which leads to continuous growth of the voids under loading. Meanwhile, the results further reveal that the developing voids are not isotropic: voids with higher surface roughness and irregular structures are easier to break and form new micro-voids. These new voids with higher irregular structures are weaker and easier to break into smaller ones compared with the originals, leading to the development of voids along these weak zones. Finally large voids form. The experiments allow direct investigation of void formation and development, which helps in studying the mechanisms of void development and energetic materials deterioration during manufacturing and transporting.

Effects of thymosin ß4 on oxygen­glucose deprivation and reoxygenation­induced injury.

Cerebral ischemia causes severe brain injury and results in selective neuronal death through programmed cell death mechanisms, including apoptosis and autophagy. Minimizing neuronal injury has been considered a hot topic among clinicians. The present study elucidated the effect of thymosin ß4 (Tß4) on neuronal death induced by cerebral ischemia/reperfusion in PC12 cells that were subjected to oxygen­glucose deprivation and reoxygenation (OGD/R). The survival, apoptotic and autophagy rates of PC12 cells were investigated. Tß4 pre­conditioning prior to OGD/R was performed to evaluate PC12­cell viability and the protective mechanisms of Tß4. Tß4 significantly increased cell survival after OGD/R. Tß4 inhibited the release of lactate dehydrogenase, downregulated malondialdehyde and upregulated the activities of glutathione peroxidase and superoxide dismutase. In addition, Tß4 attenuated OGD/R­associated decreases in the expression of P62 and the anti­apoptotic protein B­cell lymphoma­2, as well as the upregulation of autophagy mediators, including autophagy­related protein­5 and the ratio of microtubule­associated protein 1 light chain 3 (LC3) II vs. LC3 I. These results suggested that Tß4 effectively inhibits cell apoptosis and autophagy induced by OGD/R. To the best of our knowledge, the present study was the first to report on the antioxidant, anti­apoptotic and anti­autophagic effects of Tß4 in neuronal­like PC12 cells. These results suggested that Tß4 may be explored as a potential treatment for cerebral ischemia.

The Effect of Immunonutrition on the Postoperative Complications in Thymoma with Myasthenia Gravis.

Object. To test whether preoperative immunonutrition is efficacious in reducing postoperative complications in patients of thymoma with myasthenia gravis (MG). Material and Methods. A total of 244 patients operated on for thymoma with myasthenia gravis were prospectively assigned to two groups, each receiving seven-day preoperative and seven-day postoperative nutrition. The patients in immunonutrition group were given oral immunonutrition (IN). The patients in control group received oral standard nutrition. Immunonutritional and inflammatory biomarkers (IgA, IgG, IgM, CD3t, CD4t, CD8t, CD4t/CD8t ratio, NK-cell, prealbumin, albumin, white blood cells counts, and C-reactive protein) and clinical variables (age, gender, BMI, performance status, type of thymoma, type of MG, operative time, pathology, operative approach, postoperative complications, quantity of drainage, hospital stays) were examined. Results. A significant reduction in the length of hospital stay, quantity of drainage, and postoperative complications was observed in the IN group (p < 0.05). An increase in the level of IgA, IgG, IgM, CD3+T, CD4+T, CD4+T/CD8+T, WBC, CRP, and NK-cell in the IN group was observed after thymectomy, while a decrease was seen with regard to prealbumin and albumin (p < 0.05). Conclusion. Preoperative immunonutrition support is effective in reducing postoperative complications in patients of thymoma with MG. It helps to lower the risk of postoperative infectious complications and hospital stays.

A 20-year study on treating childhood infective endocarditis with valve replacement in a single cardiac center in China.

BACKGROUND: Children with infective endocarditis (IE) have to undergo valve replacement instead of valve repair in China due to severe valve damage. The present study is to review our experience on surgical treatment of children with IE in reference to the incidence, pathologic status, diagnosis, surgical strategies and outcomes. METHODS: We reviewed 35 patients with a mean age of 13.7±2.2 years who were underwent valve replacement surgery for IE during the period from January 1993 to December 2013. Preoperative transthoracic echocardiographic (TTE) evaluation and transesophageal echocardiography during operation were performed in all patients. All the children underwent chart review and retrospective risk-hazard analysis. RESULTS: Among the patients surveyed congenital cardiac lesions were present in 15 (42.8%), rheumatic heart valve disease in 2 (5.7%) and previous heart surgery in 2 (5.7%). The median stay of intensive care unit was 6 days. Intraoperative findings showed that the endocarditis involved mostly the mitral and aortic valves (88.5%). Triple or quadruple valve involvement was found in one patient each. Ten-year freedom from IE-related death and re-intervention was 94.2% and 91.6%, respectively. CONCLUSIONS: Children undergoing surgery for IE frequently have advanced disease with embolic complications. Although valve replacement is not the primary option for pediatric IE, the rate of 5-year survival and freedom from re-operation was optimal prognostically. Pediatric physicians should pay attention to the common clinical features of IE so that the native valve is preserved well.

An Adjusted Calculation Model of Reduced Heparin Doses in Cardiopulmonary Bypass Surgery in a Chinese Population.

OBJECTIVE: To investigate the safety and efficacy of an adjusted regimen of heparin infusion in cardiopulmonary bypass (CPB) surgery in a Chinese population. DESIGN: Prospective, single-center, observational study. SETTING: University teaching hospital. PARTICIPANTS: Patients having cardiac surgery with CPB were selected for this study using the following criteria: 18 to 75 years of age, undergoing first-time cardiac surgery with conventional median sternotomy, aortic clamping time between 40 and 120 minutes, and preoperative routine blood tests showing normal liver, renal, and coagulation functions. The exclusion criteria include salvage cases, a history of coagulopathy in the family, and long-term use of anticoagulation or antiplatelet drugs. INTERVENTIONS: Sixty patients were divided randomly into a control group (n = 30) receiving a traditional heparin regimen and an experimental group (n = 30) receiving an adjusted regimen. MEASUREMENTS AND MAIN RESULTS: Activated coagulation time (ACT) was monitored at different time points, ACT>480 seconds was set as the safety threshold of CPB. Heparin doses (initial dose, added dose, and total dose), protamine doses (initial dose, added dose, and total dose), CPB time, aortic clamping time, assisted circulation time, sternal closure time, blood transfusion volume, and drainage volume 24 hours after surgery were recorded. There was no significant difference in achieving target ACT after the initial dose of heparin between the 2 groups; CPB time, aortic clamping time, assisted circulation time, postoperative complication rate, and drainage volume between the 2 groups were not significantly different (p>0.05). However, initial and total dosage of heparin, initial and total dosage of protamine, sternal closure time, and intraoperative blood transfusion volume in the experimental group were significantly lower (p< 0.05). CONCLUSIONS: Adjusted regimen of heparin infusion could be used safely and effectively in Chinese CPB patients, which might reduce the initial and total dosage of heparin and protamine as well as sternal closure time and intraoperative blood transfusion volume.

Effects of MIAVS on Early Postoperative ELWI and Respiratory Mechanics.

BACKGROUND: The effects of minimally invasive aortic valve surgery (MIAVS) on the early postoperative extravascular lung water index (ELWI) and respiratory mechanics have rarely been studied. MATERIAL/METHODS: A total of 90 patients were divided into 3 groups: a conventional full sternotomy (CS) group (n=30), an upper ministernotomy (US) group (n=30), and a right anterior thoracotomy (RT) group (n=30). Hemodynamic and respiratory mechanics parameters were recorded at perioperative time points, including before skin incision (T(-1)); at sternum closing (T0); and 4 h (T4), 8 h (T8), 12 h (T12), and 24 h (T24) after the operation. The ventilator support time, ICU length of stay, and postoperative hospitalization time, as well as the thoracic drainage volume and blood transfusion volume, were recorded. RESULTS: The ELWI and pulmonary vascular permeability index (PVPI) increased at T4, and the values were significantly lower in the US group than in the RT group and CS group (P<0.05). At T8, the ELWI and PVPI in the US group and RT group were significantly lower than in the CS group. At T12, there were no significant differences among the 3 groups. In addition, at T4 static lung compliance decreased, plateau airway pressure increased, and airway resistance changed non-significantly. There were no significant differences between the US group and the RT group, but both groups showed better results than the CS group did. CONCLUSIONS: The ELWI and PVPI may transiently increase after aortic valve surgery with cardiopulmonary bypass. Compared with the 12 h required to recover from a conventional sternotomy operation, it may only take 8 h to recover from MIAVS.

Treating cardiac myxomas: a 16-year Chinese single-center study.

AIMS: Currently, myxoma is the most common type of primary cardiac tumor diagnosed. This article describes the experience over the past 16 years with cases of cardiac myxoma in Chinese patients and elucidated the differences between solid and papillary myxomas. METHODS: The clinical details of 68 patients with cardiac myxomas who underwent surgery between January 1996 and January 2012 at our center were retrospectively analyzed. RESULTS: The left atrium was the primary tumor site in 88% of the patients included in this study. The most common implant site was the interatrial septum (69%), especially for patients with solid tumors. Common clinical symptoms included dyspnea and palpitation, whereas embolic events occurred in 12 patients. Myxoma resection involved a midline sternotomy utilizing cardiopulmonary bypass. According to pathological classification, solid myxomas were present in 28 patients (47%), whereas papillary myxomas were detected in 40 patients (53%). In the solid group, arrhythmias and a larger tumor volume were more common. Correspondingly, in 97.4  ±  2.5% of cases, secondary surgery was not needed after 10 years. Overall, the actuarial survival for patients undergoing surgical excision of myxoma was 98.4  ±  1.6% at 5 years and 96.0  ±  2.8% at 10 years. CONCLUSION: Solid myxomas were associated with more arrhythmias, a larger tumor volume, implantation in the interatrial septum, and a need for concomitant surgery compared with papillary myxomas. Further studies should determine whether serum or histological markers could be routinely used in combination with echocardiograms, MRI and computed tomography for the predictions of recurrent myxomas during annual follow-up examinations.

In vitro cytotoxicity of gold nanorods in A549 cells.

Gold nanoparticles, which have unique physicochemical characteristics, are being used for an increasingly wide range of applications in biomedical research. In this study, gold nanorods (width of 25 nm, length of 52 nm) were found to be internalized by A549 cells and were primarily localized in the lysosomes and membranous vesicles. The integrity of the membranes of A549 cells exposed to gold nanorods for 4h was damaged, as indicated by laser scanning confocal microscopy (LSCM). Increased lactate dehydrogenase (LDH) leakage and decreased cell viability further indicated the concentration-dependent cytotoxicity of the gold nanorods to the A549 cells. Reactive oxygen species (ROS) production was induced in the A549 cells by the gold nanorods, and this effect was positively correlated with the concentration of the gold nanorods. The results of this study indicated that exposure to gold nanorods caused dose-dependent cytotoxicity in A549 cells and that oxidative stress may be the main factor causing cytotoxicity.

Ulinastatin protects cardiomyocytes against ischemia­reperfusion injury by regulating autophagy through mTOR activation.

Autophagy is significant in myocardial ischemia-reperfusion (IR) injury. Ulinastatin has been demonstrated to protect cardiomyocytes against IR through inducing anti-inflammatory effects. However, whether ulinastatin has an anti­autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of ulinastatin on the regulation of autophagy during IR injury. Cardiomyocytes of neonatal rats were randomly divided into control, hypoxia-reoxygenation (HR) and ulinastatin groups. In order to investigate whether mammalian target of rapamycin (mTOR) is involved in mediating the protective effect of ulinastatin, cells were treated with the mTOR inhibitor, rapamycin 30 min prior to ulinastatin treatment. To demonstrate the anti-autophagic effect of ulinastatin in vivo, a rat IR model was established. Ulinastatin (1x104 U/kg body weight) was administered 30 min prior to the induction of IR via peritoneal injection. Light chain 3 (LC3), phosphorylated (p)­mTOR, p­protein kinase B (Akt) and p­P70S6 kinase (p­P70S6K) protein expression were assessed using western blot analysis. In addition, cell vitality, myocardial infarct size and lactate dehydrogenase (LDH) levels were measured. LC3­â…¡ protein expression was found to be downregulated, while p­Akt, p­mTOR and p­P70S6K protein expression were observed to be upregulated by ulinastatin. In addition, cell vitality was found to increase and LDH was observed to decrease in the ulinastatin group compared with the HR group in vitro. Furthermore, rapamycin was found to attenuate the myocardial protective effect that is induced by ulinastatin. In vivo, ulinastatin was found to downregulate LC3­â…¡ protein expression, and reduce myocardium infarct size and LDH serum levels. These findings indicate that ulinastatin exhibits a myocardial protective effect against IR injury by regulating autophagy through mTOR activation.

Raised expression of APRIL in Chinese children with acute lymphoblastic leukemia and its clinical implications.

This study was to determine the expression of a proliferation-inducing ligand (APRIL) and its receptors, B-cell maturation antigen (BCMA) and transmembrane activator and calcium-modulating cyclophilin ligand interactor in childhood acute lymphoblastic leukemia (ALL). The correlation between the plasma APRIL levels and clinical status was also evaluated. Plasma samples from 20 untreated children with ALL, 23 children with ALL in remission, and 15 normal controls were assayed for APRIL plasma concentration by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction was performed to determine the mRNA expression of APRIL and its receptors in blood mononuclear cells in 20 untreated ALL children and 15 normal controls. The untreated ALL patients had higher plasma APRIL levels than the remission group and the normal controls (P<0.001, respectively). No significant difference was found between the remission group and the normal controls in the plasma APRIL levels (P=0.339). The plasma APRIL levels in the untreated patients correlated with white blood cell count at diagnosis (P=0.002) and risk category (P=0.013). The mRNA expression of both APRIL and BCMA in blood mononuclear cells of the ALL patients were higher than those of the normal controls (both P<0.001). No significant difference was found between the patients and the normal controls in the transmembrane activator and calcium-modulating cyclophilin ligand interactor expression (P>0.05). These findings indicate that APRIL and BCMA are over expressed in untreated ALL children. The levels of APRIL correlate with the progression of childhood ALL, which may provide certain clues for monitoring ALL clinically.

Pulmonary fungus ball caused by Penicillium capsulatum in a patient with type 2 diabetes: a case report.

BACKGROUND: Following the recent transfer of all accepted species of Penicillium subgenus Biverticillium to Talaromyces (including Talaromyces marneffei, formerly Penicillium marneffei), Penicillium species are becoming increasingly rare causal agents of invasive infections. Herein, we present a report of a type 2 diabetes patient with a fungus ball in the respiratory tract caused by Penicillium capsulatum. CASE PRESENTATION: A 56-year-old Chinese female gardener with a 5-year history of type 2 diabetes presented at the Shanghai Changzheng Hospital with fever, a cough producing yellow-white sputum, and fatigue. The therapeutic effect of cefoxitin was poor. An HIV test was negative, but the ß-D-glucan test was positive (459.3 pg/ml). Chest radiography revealed a cavitary lesion in the left upper lobe, and a CT scan showed globate cavities with a radiopaque, gravity-dependent ball. The histopathologic features of the tissue after haematoxylin-eosin staining showed septate hyphae. The fungus was isolated from the gravity-dependent ball and identified as Penicillium capsulatum based on the morphological analysis of microscopic and macroscopic features and on ribosomal internal transcribed spacer sequencing. After surgery, the patient was cured with a sequential treatment of fluconazole 400 mg per day for 90 days and caspofungin 70 mg per day for 14 days. CONCLUSIONS: Although the prognosis is often satisfactory, clinicians, mycologists and epidemiologists should be aware of the possibility of infection by this uncommon fungal pathogen in diabetes patients, since it may cause severe invasive infections in immunocompromised hosts such as diabetes and AIDS patients.

MicroRNA-223 regulates FOXO1 expression and cell proliferation.

In HCT116 colorectal cancer cells, HeLa cervical cancer cells and HuH-7 hepatoma cells, miR-223 is expressed at a low level. Through infection with lentivirus containing miR-223 precursor, miR-223 [corrected] was overexpressed in all these cells. Interestingly, the expression levels of FOXO1 mRNA and protein, and phosphorylation levels became significantly lower than those of their control. FOXO1 was down-regulated mainly in the cytoplasm, while the nuclear FOXO1 level became relatively high compared to the cytoplasm. As the unphosphorylated active form of FOXO1 increased in the cells, cyclin D1/p21/p27 were up-regulated at either mRNA or protein level. Proliferation of the cells was also greatly inhibited when miR-223 was over-expressed. Therein, our data suggest that miR-223 regulates FOXO1 expression and cell proliferation.

Multiple schwannomas in a single costal interval: report of two cases.

Schwannomas of the intercostal nerve, typically, are solitary and rarely originate from the mediastinum. Here, we describe two cases of multiple schwannomas occurring within a single costal interval. Both patients were misdiagnosed prior to surgery, and the correct diagnosis was made by pathological examination following surgery. Upon retrospective review of the preoperative radiographic examination, we found that such misdiagnoses may be avoided by performing 3-dimensional reconstruction.

A novel function of microRNA let-7d in regulation of galectin-3 expression in attention deficit hyperactivity disorder rat brain.

In this study we investigated the locomotor activity and non-selective attention in spontaneously hypertensive rats (SHR) with control Wistar-Kyoto (WKY) rats, which were employed as an attention deficit hyperactivity disorder (ADHD) model. In open-field test and làt maze, SHR rats were found to be much more spontaneously active than WKY rats. As compared with WKY rats, a lower level of galectin-3 was observed in SHR brain prefrontal cortex (PFC), which was the major affected brain area of ADHD. Through miRNA microarray screening, rno-let-7d was noted to be solely upregulated in SHR PFC. Interestingly, rno-let-7d had a binding site at galectin-3 mRNA and was shown to regulate galectin-3 3' untranslated region (UTR) directly. Mutation of galectin-3 3'UTR by one nucleotide of the seed sequence prevented rno-let-7d regulation of the 3' UTR completely. Although rno-let-7d did not directly regulate tyrosine hydroxylase (TH) 3'UTR, the level of galectin-3 was important for cAMP response element binding protein, the major transcript factor for TH gene. Either overexpression or downexpression of galectin-3 could result in modulation of TH expression in both PC12H and PC12L cells. In conclusion, our data suggested a novel function of rno-let-7d in regulation of galectin-3 and in ADHD development. Rno-let-7d, which is increased in the PFC of SHR brain, negatively regulated galectin-3, which is coupled with TH expression regulation.