Role for Biochemical Assays and Kayser-Fleischer Rings in Diagnosis of Wilson's Disease.

BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that impairs copper homeostasis and is caused by homozygous or compound heterozygous mutations in ATP7B, which encodes a copper-transporting P-type ATPase. Patients have variable clinical manifestations and laboratory test results, resulting in diagnostic dilemmas. We aimed to identify factors associated with symptoms and features of Wilson disease from a large cohort, over 15 years. METHODS: We collected data from 715 patients (529 with symptoms, 146 without symptoms, and 40 uncategorized) and a genetic confirmation of Wilson's disease (mean age of diagnosis, 18.84 years), recruited from 3 hospitals in China from 2004 through 2019. We analyzed clinical data along with serum levels of ceruloplasmin (available from 636 patients), 24-hr urinary copper excretion (collected from 131 patients), Kayser-Fleisher rings (copper accumulation in eyes, with neurologic data from 355 patients), and magnetic resonance imaging (MRI) abnormalities. Differences among the groups were analyzed using 1-way analysis of variance followed by Tukey multiple comparison test. RESULTS: Of the 529 patients with symptoms, 121 had hepatic features, 355 had neurologic features, 28 had osteomuscular features (premature osteoarthritis, skeletal deformities, and pathological bone fractures), and 25 had psychiatric symptoms. Age of onset was significantly younger in patients with hepatic (16.94 ± 1.03 years; P = .0105) or osteomuscular features (13 ± 1.33 years; P = .0001) than patients with neurological features (19.48 ± 0.46 years). Serum levels of ceruloplasmin differed among asymptomatic patients and patients with osteomuscular or neurologic symptoms of Wilson disease. Serum levels of ceruloplasmin ranged from 18.93 mg/L to approximately 120.00 mg/L (quantiles of 0.025 to approximately 0.975). Fifty-one of 131 patients (39%) had urinary copper excretion levels below 100 µg/24 hr; there was significant variation in levels of urinary copper excretion between patients older than 14 years vs 14 years or younger. Of the 355 patients with neurologic features, 244 patients (69%) had abnormal findings from MRI and Kayser-Fleisher rings; only 1 patient with abnormal findings from brain MRI was negative for Kayser-Fleisher rings. CONCLUSIONS: Serum level of ceruloplasmin, 24-hour urinary copper excretion, and Kayser-Fleisher rings can be used to identify patients who might have Wilson disease. Patients with serum levels of ceruloplasmin below 120 mg/L and children with urinary copper excretion above 40 µg should undergo genetic testing for Wilson's disease. Patients with movement disorders and brain MRI abnormalities without Kayser-Fleisher rings are not likely to have Wilson disease.

Genetic profile and clinical characteristics of Chinese patients with spinocerebellar ataxia type 2: A multicenter experience over 10 years.

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 2 (SCA2) is the second most common type of spinocerebellar ataxia in China. However, data on the clinical and genetic features of Chinese SCA2 patients are scarce. This study aims to provide a comprehensive description of in the Chinese SCA2 cohort. METHODS: A total of 135 patients with SCA2 from 92 families and 104 unrelated normal controls were recruited from three medical centers between 2008 and 2020. Sanger sequencing and TA cloning were used to determine the CAG repeat length and intrinsic structure. The clinical data of patients with SCA2, including electromyography, magnetic resonance imaging, positron-emission tomography, and clinical scale scores, were recorded. RESULTS: The mean ± SD age at onset of SCA2 patients was 32.6 ± 11.9 years and the corresponding CAG repeat length was 42.1 ± 3.6. CAG repeat length accounted for 64% of the age-at-onset variance. We observed that patients had a significantly lower proportion of (CAG)8 CAA(CAG)4 CAA(CAG)8 within normal alleles than normal controls (48.8% vs. 64.9%; p = 0.003), while the distribution of the proportion of (CAG)13 CAA (CAG)8 was the opposite. Peripheral neuropathy was frequent, occurring in 75.9% of the patients. Parkinsonism was relatively common, with a frequency of 11.8%. Two patients with parkinsonism had a significantly more severe reduction in dopamine transporter levels in the bilateral striatum than the one patient with pure ataxia. An infant-onset case of SCA2 with more than 180 CAG repeats was characterized by global development delay, hypotonia and hearing impairment. CONCLUSIONS: This study describes the genetic profile and clinical characteristics of the largest SCA2 cohort to date in the Chinese population and analyzes inter-population differences. Many aspects of this study population were different from other populations with SCA2.

A novel ceruloplasmin mutation identified in a Chinese patient and clinical spectrum of aceruloplasminemia patients.

Aceruloplasminemia (ACP) is a rare disorder of iron overload resulting from ceruloplasmin (CP) variants. Because of its rarity and heterogeneity, the diagnosis of ACP is often missed or misdiagnosed. Here, we aim to present a clinical spectrum of ACP and raise more attention to the early diagnosis. Whole exome sequencing (WES) was performed in a Chinese female patient suspected with ACP and her clinical data were collected in detail. The PubMed databases was searched for published ACP patients within the last decade, and we present a systematic review of their clinical features with data extracted from these researches. A novel pathogenic variant (c.2689delC) and a known pathogenic variant (c.606dupA) within ceruloplasmin gene were identified in our patient and confirmed the diagnosis of ACP. Then we reviewed 51 ACP patients including the case we reported here. A possible timeline of symptoms was discovered, anemia appears first (29.7 years old on average), followed by diabetes (37.3 years old) and finally neurological symptoms (50.7 years old). The delay in diagnosis was significantly shortened in patients without neurological symptoms. Biochemical triad including anemia, low to undetectable serum ceruloplasmin, low serum iron and/or hyperferritinemia, showed better sensitivity in diagnosis than clinical triad including diabetes, neurological symptoms, and retinal degeneration. Due to the variable symptom spectrum, patients with ACP often visit different departments, which can lead to misdiagnosis. Clinical attention needs to be paid to symptoms and tests that have a warning effect. Prompt diagnosis in the early stage of the disease can be beneficial.

3,4-dihydroxyacetophenone inhibits hypoxia-associated human pulmonary artery smooth muscle cell proliferation by reducing Ca2+ influx.

The present study aimed to assess the effects of 3,4-dihydroxyacetophenone (DHAP) on human pulmonary artery smooth muscle cells (HPASMCs). HPASMCs were divided into the normoxia group (NG), hypoxia group (HG), and hypoxia and 0.6×10-4 mol/L (HD1), 1.9×10-4 mol/L (HD2) and 6.0×10-4 mol/L (HD3) DHAP treatment groups. Cell cycle was analyzed by flow-cytometrically. HPASMC growth was examined by the proliferating cell nuclear antigen (PCNA) and MTT assays. Intracellular Ca2+ ([Ca2+]i) was measured by laser scanning confocal microscopy. Compared with the NG, the HG showed significantly increased HPASMC proliferation (P<0.05); meanwhile, cells treated with DHAP showed decreased proliferation compared with the HG (P<0.05). Hypoxia enhanced cell cycle progression and DHAP partly restored cell cycle distribution toward the status of NG cells. Furthermore, CDK2 levels were markedly increased in hypoxic cells (P<0.05), while DHAP treatment starkly decreased CDK2 levels in comparison with the HG (P<0.05). Moreover, hypoxia increased intracellular [Ca2+] levels compared with normoxia (P<0.05); meanwhile, DHAP treatment decreased [Ca2+]i compared with the HG (P<0.05). These findings suggested that DHAP inhibits hypoxia-induced proliferation of HPASMCs involving [Ca2+]i reduction. Therefore, DHAP should be considered an ideal candidate for the prevention and/or treatment of hypoxia-associated pulmonary hypertension and pulmonary vascular remodeling.

3,4-dihydroxyacetophenone inhibits hypoxia-associated human pulmonary artery smooth muscle cell proliferation by reducing Ca2+ influx.

The present study aimed to assess the effects of 3,4-dihydroxyacetophenone (DHAP) on human pulmonary artery smooth muscle cells (HPASMCs). HPASMCs were divided into the normoxia group (NG), hypoxia group (HG), and hypoxia and 0.6×10-4 mol/L (HD1), 1.9×10-4 mol/L (HD2) and 6.0×10--4 mol/L (HD3) DHAP treatment groups. Cell cycle was analyzed by flow-cytometrically. HPASMC growth was examined by the proliferating cell nuclear antigen (PCNA) and MTT assays. Intracellular Ca2+ ([Ca2+]i) was measured by laser scanning confocal microscopy. Compared with the NG, the HG showed significantly increased HPASMC proliferation (P<0.05); meanwhile, cells treated with DHAP showed decreased proliferation compared with the HG (P<0.05). Hypoxia enhanced cell cycle progression and DHAP partly restored cell cycle distribution toward the status of NG cells. Furthermore, CDK2 levels were markedly increased in hypoxic cells (P<0.05), while DHAP treatment starkly decreased CDK2 levels in comparison with the HG (P<0.05). Moreover, hypoxia increased intracellular [Ca2+] levels compared with normoxia (P<0.05); meanwhile, DHAP treatment decreased [Ca2+]i compared with the HG (P<0.05). These findings suggested that DHAP inhibits hypoxia-induced proliferation of HPASMCs involving [Ca2+]i reduction. Therefore, DHAP should be considered an ideal candidate for the prevention and/or treatment of hypoxia-associated pulmonary hypertension and pulmonary vascular remodeling.

Clinical features and outcome in patients with osseomuscular type of Wilson's disease.

BACKGROUND: Wilson's disease with osseomuscular type is a rare condition, which often lacks typical hepatic and neurological symptoms and causes misdiagnoses easily. During the past 10 years, eight Chinese patients of osseomuscular type of Wilson's disease were identified in our clinic. METHODS: Clinical information was gathered from medical records and follow-ups. The genetic testing was performed in each patient. Serum ceruloplasmin, Kayser-Fleischer rings, liver function, brain magnetic resonance imaging and abdominal ultrasonography were also evaluated. RESULTS: The median age of onset is 12 years of age. The patients had their initial musculoskeletal conditions with arthralgia or joint deformity, while the hepatic or neurologic signs were minimal. Most patients (6/8) eventually developed clinical neurological symptoms afterwards with a median interval of 36 months. All of them had normal liver function and low serum ceruloplasmin (<0.1 g/L). Most patients (6/8) present with Kayser-Fleischer rings and abnormal hepatic ultrasonography. The arthralgia was resolved with copper chelation therapy. CONCLUSIONS: Wilson's disease with osseomuscular type occurs without typical hepatic or neurological symptoms, which makes the clinical diagnosis challenging. Serum ceruloplasmin, abdominal ultrasonography, ophthalmic examination and genetic testing help to establish the diagnosis. Early diagnosis can initiate an effective treatment and prevent the further damage.

Clinical features of familial amyloid polyneuropathy carrying transthyretin mutations in four Chinese kindreds.

Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a rare hereditary disorder, characterized by a length-dependent polyneuropathy and dysfunction of various organs. Wide phenotypic heterogeneity makes early diagnosis difficult. In this study, we reviewed the clinical and electrophysiological features of four unrelated Chinese families with genetically confirmed TTR-FAP. Sequence analysis of TTR gene revealed the presence of four different mutations: Thr49Ala(p.Thr69Ala), Leu55Arg(p.Leu75Arg), Tyr116Ser(p.Tyr136Ser), and Ala36Pro(p.Ala56Pro) from six affected patients and two asymptomatic individuals. Two mutations, Thr49Ala(p.Thr69Ala) and Tyr116Ser(p.Tyr136 Ser), were detected in Chinese FAP patients for the first time. All affected patients manifested a progressive sensorimotor polyneuropathy starting in the lower limbs. The majority of the examined patients displayed cardiomyopathy and vitreous opacities. To avoid misdiagnosis, clinicians should consider screening for TTR variants in patients presenting with progressive polyneuropathy of undetermined origins.

Defective roles of ATP7B missense mutations in cellular copper tolerance and copper excretion.

Wilson's disease (WD) is a hereditary disorder of copper metabolism resulting from mutations within ATP7B. Clinical investigations showed that ATP7B missense mutations cause a wide variety of symptoms in WD patients, which implies that those mutations might affect ATP7B function in a number of ways and each would have deleterious consequences on normal copper distribution and lead to WD. Nonetheless, it is still unknown about the influences of those mutations on ATP7B function of increasing copper excretion and enhancing cellular copper tolerance. Here we established the stable expression cell lines of wild-type (WT) ATP7B and its four missense mutants (R778L, R919G, T935M and P992L), tested cellular copper tolerance and copper excretion using those cell lines, and also observed cellular distribution of WT ATP7B proteins and those mutants in transiently transfected cells. We found that extrinsic expressing WT ATP7B reduced CuCl2-induced copper accumulation and enhanced cellular copper tolerance by accelerating copper excretion, which was selectively compromised by R778L and P992L mutations. Further investigation showed that R778L mutation disrupted the subcellular localization and trafficking of ATP7B proteins, whereas P992L mutation only affected the trafficking of ATP7B. This indicates that ATP7B missense mutants have distinct effects on cellular copper tolerance.

A series of simple oligomer-like small molecules based on oligothiophenes for solution-processed solar cells with high efficiency.

A series of acceptor-donor-acceptor simple oligomer-like small molecules based on oligothiophenes, namely, DRCN4T-DRCN9T, were designed and synthesized. Their optical, electrical, and thermal properties and photovoltaic performances were systematically investigated. Except for DRCN4T, excellent performances were obtained for DRCN5T-DRCN9T. The devices based on DRCN5T, DRCN7T, and DRCN9T with axisymmetric chemical structures exhibit much higher short-circuit current densities than those based on DRCN6T and DRCN8T with centrosymmetric chemical structures, which is attributed to their well-developed fibrillar network with a feature size less than 20 nm. The devices based on DRCN5T/PC71BM showed a notable certified power conversion efficiency (PCE) of 10.10% under AM 1.5G irradiation (100 mW cm(-2)) using a simple solution spin-coating fabrication process. This is the highest PCE for single-junction small-molecule-based organic photovoltaics (OPVs) reported to date. DRCN5T is a rather simpler molecule compared with all of the other high-performance molecules in OPVs to date, and this might highlight its advantage in the future possible commercialization of OPVs. These results demonstrate that a fine and balanced modification/design of chemical structure can make significant performance differences and that the performance of solution-processed small-molecule-based solar cells can be comparable to or even surpass that of their polymer counterparts.

Splenectomy as a treatment for adults with relapsed hemophagocytic lymphohistiocytosis of unknown cause.

Our aim was to evaluate the clinical value of splenectomy as a treatment for relapsed hemophagocytic lymphohistiocytosis (HLH) of unknown cause in adults. We retrospectively reviewed the clinical data from medical records of 19 adults with relapsed HLH of unknown cause treated with splenectomy in our institution from June 2007 to March 2014. To rule out possible underlying diseases, including infection, autoimmune disease, neoplasms, and primary HLH, the patients had undergone examinations including F18 fluoro-2-deoxyglucose positron emission tomography/computed tomography, HLH-associated gene defects, and lymph node biopsies. Twelve patients (63.2%) achieved partial responses (PR), whereas seven patients (36.8%) had no response (NR) prior to splenectomy. Infection and hemorrhage were the main complications of splenectomy. Eighteen cases were evaluable after follow-up. Seven cases with histopathologic diagnoses of lymphoma had received chemotherapy, four of whom had achieved complete responses (CR), one PR, and two NR. Maintenance treatment was ceased 2 or 3 months after splenectomy in the other 11 cases, five of whom had CR, four PR, and two NR. Eleven of 18 cases (61.1%) survived with a median follow-up of 25 months (range 3-79 months) for survivors. Twelve- and 36-month progression-free survival rates were 48 and 24%, respectively; 12- and 36-month overall survival rates were 57 and 25%, respectively. Median survival time was 22 months. Our results indicate splenectomy may be an effective means of diagnosis and treatment of relapsed HLH of unknown cause. Further study is required to establish the mechanism and value of splenectomy in this disease.

Device characterization and optimization of small molecule organic solar cells assisted by modelling simulation of the current-voltage characteristics.

In order to understand the photovoltaic performance differences between the recently reported DR3TBTT-HD and DR3TBDT2T based solar cells, a modified two-diode model with Hecht equation was built to simulate the corresponding current-voltage characteristics. The simulation results reveal that the poor device performance of the DR3TBDTT-HD based device mainly originated from its insufficient charge transport ability, where an average current of 5.79 mA cm(-2) was lost through this pathway at the maximum power point for the DR3TBDTT-HD device, nearly three times as large as that of the DR3TBDT2T based device under the same device fabrication conditions. The morphology studies support these simulation results, in which both Raman and 2D-GIXD data reveal that DR3TBTT-HD based blend films exhibit lower crystallinity. Spin coating at low temperature was used to increase the crystallinity of DR3TBDTT-HD based blend films, and the average current loss through insufficient charge transport at maximum power point was suppressed to 2.08 mA cm(-2). As a result, the average experimental power conversion efficiency of DR3TBDTT-HD based solar cells increased by over 40%.

Solution-processed organic solar cells based on dialkylthiol-substituted benzodithiophene unit with efficiency near 10%.

A small molecule named DR3TSBDT with dialkylthiol-substituted benzo[1,2-b:4,5-b']dithiophene (BDT) as the central unit was designed and synthesized for solution-processed bulk-heterojunction solar cells. A notable power conversion efficiency of 9.95% (certified 9.938%) has been achieved under AM 1.5G irradiation (100 mW cm(-2)), with an average PCE of 9.60% based on 50 devices.

[The correlation of vitamin D level and vitamin D-binding protein gene polymorphism in chronic obstructive pulmonary disease].

OBJECTIVE: To assess the correlation of serum 25-hydroxyvitamin D (25-OHD) levels with vitamin D-binding protein (the group-specific component, GC) gene polymorphism in chronic obstructive pulmonary disease (COPD). METHODS: In a cross-sectional case-control study, 250 participants, including 116 COPD patients with smoking history and 134 healthy smokers, were investigated. A questionnaire about smoking history, vitamin D intake and comorbidities was collected. General pulmonary function was done by routine. Serum 25-OHD levels were detected by ELISA. The genetic variants (rs4588 and rs7041) were genotyped by real time fluorescence polymerase chain reaction (RT-PCR) with TaqMan probe technology. RESULTS: The COPD patients had lower serum vitamin D level than the smoker subjects (36.58 nmol/L vs 43.80 nmol/L, P < 0.001). In the COPD patients, vitamin D level was 39.43 nmol/L in those with percentage of predicted forced expiratory volume in 1 second (FEV1%pred) greater than or equal to 80%.In other groups with FEV1%pred 50%-80%, 30%-50% and lower than 30%, vitamin D levels were 35.32 nmol/L, 32.21 nmol/L, 26.25 nmol/L respectively (P < 0.01). Moreover, there was a significant relevance of 25-OHD levels with FEV1%pred in both COPD patients and healthy smokers (r(2) = 1.911; P < 0.000 1). The mean 25-OHD concentration had a negative correlation with Global Initiative for Obstructive Lung Disease (GOLD) stages. Homozygous carriers of vitamin D-binding protein gene rs7041 T allele were independently related to 25-OHD levels and susceptibility of COPD (P < 0.01; OR = 2.140, 95%CI 1.157-3.959, P = 0.015 respectively). CONCLUSIONS: Patients with COPD are at high risk of vitamin D deficiency and the severity of COPD is inversely correlated with vitamin D levels. Furthermore, homozygous carrier of rs7041 T allele influences 25-OHD serum levels and is related to susceptibility of COPD, which may be a potential candidate gene for screening COPD.

A variant within FGF1 is associated with Alzheimer's disease in the Han Chinese population.

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by the accumulation of amyloid beta (Aß) plaques and Tau-containing neurofibrillary tangles in vulnerable brain areas. The progression of AD is well correlated with hippocampal neuron loss which highly suggests genes associated with neuron survival would be important for AD pathogenesis. According to the recent results of genome-wide association studies (GWAS) and other reported studies, we selected two single nucleotide polymorphisms (SNPs), rs3765728 within tumor protein p73 (P73), and rs34011 within fibroblast growth factor 1 (FGF1), both genes were related to neuron survival. We analyzed the distribution of rs3765728 and rs34011 in 1,083 Chinese subjects including 429 unrelated sporadic AD patients and 654 unrelated age and gender-matched control subjects. We found that the genotype distribution of rs34011 was significantly different between AD and control group (χ(2) = 9.048, df = 2, P = 0.011). Logistic regression manifested the risk of AD increased in TT genotype carriers in total subjects (Wald = 8.892, df = 1, P = 0.003, odds ratio [OR]:2.009, 95% confidence interval [95%CI]: 1.270-3.178). This effect was also found in APOE ϵ4 carrier group (Wald = 7.844, df = 1, P = 0.005, OR: 4.201, 95%CI: 1.539-11.472), suggesting the rs34011 has a synergetic effect of APOE on AD risk. However, no association was observed between rs3765728 and AD in the Han Chinese population (χ(2) = 0.431, df = 2, P = 0.806).

Solution-processed and high-performance organic solar cells using small molecules with a benzodithiophene unit.

Three small molecules named DR3TBDTT, DR3TBDTT-HD, and DR3TBD2T with a benzo[1,2-b:4,5-b']dithiophene (BDT) unit as the central building block have been designed and synthesized for solution-processed bulk-heterojunction solar cells. Power conversion efficiencies (PCEs) of 8.12% (certified 7.61%) and 8.02% under AM 1.5G irradiation (100 mW cm(-2)) have been achieved for DR3TBDTT- and DR3TBDT2T-based organic photovoltaic devices (OPVs) with PC71BM as the acceptor, respectively. The better PCEs were achieved by improving the short-circuit current density without sacrificing the high open-circuit voltage and fill factor through the strategy of incorporating the advantages of both conventional small molecules and polymers for OPVs.

Graphene quantum dots as the hole transport layer material for high-performance organic solar cells.

We present an investigation of organic photovoltaic (OPV) cells with solution-processable graphene quantum dots (GQDs) as hole transport layers (HTLs). GQDs, with uniform sizes and good conductivity, are demonstrated to be excellent HTLs in both polymer solar cells (PSCs) and small-molecule solar cells (SMSCs) with the blend of poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PC61BM) and small molecule DR3TBDT:[6,6]-phenyl-C71-butyric acid methyl ester (DR3TBDT:PC71M) as the active layer, respectively. The PSCs and SMSCs based on GQDs yield power conversion efficiencies of 3.51% and 6.82%, respectively, both comparable to those of solar cells with PEDOT:PSS as the HTLs. In addition, the cells with GQDs as HTLs exhibit much more reproducible performance and longer lifetime. In light of the high stability, low cost and easy processing, these results indicate that GQDs can be potentially used to replace PEDOT:PSS for producing high-performance and stable organic photovoltaic cells.

Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3ß and Nrf2/NQO1 pathways.

Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3ß (p-GSK3ß) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3ß and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.

Small molecules based on benzo[1,2-b:4,5-b']dithiophene unit for high-performance solution-processed organic solar cells.

Small molecules, namely, DCAO(3)TBDT and DR(3)TBDT, with 2-ethylhexoxy substituted BDT as the central building block and octyl cyanoacetate and 3-ethylrhodanine as different terminal units with the same linkage of dioctyltertthiophene, have been designed and synthesized. The photovoltaic properties of these two molecules as donors and fullerene derivatives as the acceptors in bulk heterojunction solar cells are studied. Among them, DR(3)TBDT shows excellent photovoltaic performance, and power conversion efficiency as high as 7.38% (certified 7.10%) under AM 1.5G irradiation (100 mW cm(-2)) has been achieved using the simple solution spin-coating fabrication process, which is the highest efficiency reported to date for any small-molecule-based solar cells. The results demonstrate that structure fine turning could cause significant performance difference and with that the performance of solution-processed small-molecule solar cells can indeed be comparable with or even surpass their polymer counterparts.

[The expression of macrophage migration inhibition factor in pulmonary tissues of smokers with or without chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the expression of macrophage migration inhibition factor (MIF) in pulmonary tissues of the smokers with and without chronic obstructive pulmonary disease (COPD). METHODS: The subjects were assigned into three groups: non-smokers without COPD (control group, n = 12), smokers without COPD (smoker group, n = 13) and smokers with COPD (COPD group, n = 16). The specimens were obtained from lung tissues as far away from cancer focus as possible (> 5 cm). Real-time quantitative PCR and immunohistochemistry were used to investigate the expression and distribution of MIF in pulmonary tissues. The relationship between the severity of airflow obstruction and the differential expressions of MIF in lung tissues of the smokers with or without COPD was analyzed. RESULTS: (1) MIF mRNA expression in COPD group (4.87 ± 1.79) was higher than that in the smoker group (2.16 ± 0.72; P < 0.01), which was higher than that in the control group (1.09 ± 0.48; P < 0.01). (2) Immunohistochemistry analysis showed that MIF protein expression in lung tissues of the COPD group (0.277 ± 0.025) was higher than that in the smokers group (0.199 ± 0.034; P < 0.01), which was significantly higher than that in control group (0.130 ± 0.021; P < 0.01). (3) Correlation analysis of MIF mRNA expression in the lung tissues and pulmonary function parameters of forced expired volume in one second (FEV(1)) percentage of predicted (FEV(1) pred)and ratio of FEV(1) to forced vital capacity (FEV(1)/FVC) suggested that MIF mRNA expression in the lung tissues was negatively related with FEV(1) pred (r = -0.578, P < 0.01) and FEV(1)/FVC (r = -0.607, P < 0.01). CONCLUSIONS: MIF expression significantly increases in the smokers with COPD, and MIF level in the lung is positively correlated with airflow limitation. The results suggest that MIF may play an important role in the pathogenesis of smoking-induced COPD.

[Expression of ß-catenin in human pulmonary tissues of smokers with and without chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the expression of ß-catenin in pulmonary tissues of smokers with and without chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary tissues were obtained from patients who had underwent pneumonectomy in Tongji Hospital. The subjects were assigned into non-smokers without COPD (control group), smokers without COPD (smoker group) and smokers with COPD (smoker + COPD group) based on their pulmonary functions and smoking history, with 12 subjects each group. The specimens were obtained as far from the tumor focus (> 5 cm) as possible. Immunofluorescence staining, Western blot and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were used to investigate the expression and localization of ß-catenin in pulmonary tissues. Numerical data were expressed as the mean ± standard deviation, and were assessed for significance by one-way analysis of variance followed by a Student-Newman-Keuls test for multiple comparisons. The difference of enumeration data was detected by Chi-Square test. Relationship was estimated by Pearson correlation. RESULTS: Immunofluorescence analysis revealed that ß-catenin mainly expressed in the cell membrane of epithelial cells. There was also a positive expression in the cytoplasm and the nuclei of the epithelial cells. The number of alveolar epithelial cells with ß-catenin expressed in the cytoplasm and(or) nucleus was (1.2 ± 0.6)/HP in smokers + COPD group. And the protein and mRNA expression of ß-catenin in pulmonary tissues in smokers + COPD group were 0.26 ± 0.11 and 0.351 ± 0.129, respectively, which were significantly less than those of the smoker group and the control group [(5.0 ± 2.5)/HP and (8.4 ± 3.5)/HP, 0.62 ± 0.23 and 1.00 ± 0.50, 0.60 ± 0.14 and 1.03 ± 0.27]. The differences among the 3 groups were significant (F = 12.809 - 38.776, P < 0.05). Correlation analysis between ß-catenin expression and pulmonary function suggested that the protein and mRNA expression of ß-catenin positively related with FEV(1)%pred (P < 0.05) and FEV(1)/FVC (r = 0.402 - 0.558, P < 0.05). CONCLUSION: ß-catenin expression significantly was decreased in smokers with COPD, and ß-catenin level in the lungs was positively correlated with pulmonary function.