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Abstract: Titanocene dichloride and budotitane have opened a new chapter in medicinal chemistry of titanium(IV) complexes being novel non-platinum antitumor metallic agents. Numerous efforts have led to the discovery of the diamino bis-phenolato titanium(IV) complexes. Among which, the [ONNO] and [ONON] type ligands namely Salan, Salen and Salalen coordinated titanium(IV) alkoxyl complexes have demonstrated significantly enhanced aqueous stability, their in vitro and in vivo antitumor efficacy, mechanism of action, structure-activity relationships and combined tumor therapy have been intensively investigated. Replacement of the labile alkoxyls with a second chelator resulted in structural rigid titanium(IV) complexes, which showed exceedingly good aqueous stability and potent antitumor activity both in vitro and in vivo. The unique ligand system successfully allowed the access of isotopic [45Ti]Titanium(IV) complexes, post-synthetic modification, facile synthetic protocols and antitumor congeneric zirconium(IV) and hafnium(IV) complexes. This review presents recent research progress in the field of antitumor group 4 metal complexes stabilized with phenolato ligands; especially their structure-activity relationships are summarized.

A simple and practical protocol for the C3–H regioselective halogenation of 4-quinolones by the action of potassium halide salt and PIFA/PIDA in good to excellent yields was developed. The current approach provides feasible access to the diversity of C3-halgenated 4-quinolones at room temperature with high regioselectivity and good functional group tolerance, from which bioactive compounds can be easily constructed. Moreover, the current method featured eco-friendly, operational convenience and is suitable for halogenation in a gram scale of 4-quinolones in water without sacrificing yields.

Four novel Salan Hf

Graphene is a promising electrode for the flexible perovskite solar cells (PSCs), whereas electron transport layer (ETL) oxides, prepared by atomic layer deposition (ALD), render high performance i...

BACKGROUND: Many studies have investigated the association between matrix metalloproteinase polymorphisms and lung cancer susceptibility. However, the results are still controversial. To clarify these associations, we conducted a meta-analysis. METHODS: A systematic search of studies was conducted in PubMed, Embase, and China National Knowledge Infrastructure. Overall and subgroup analysis stratified by ethnicity was conducted. OR with 95% CI was used to assess the strength of the association. Furthermore, false-positive report probability (FPRP) tests were also performed for associations obtained in this meta-analysis. RESULTS: Twenty-four studies, including 10,099 cases and 9,395 controls, were analyzed. Nine polymorphisms were reported. For MMP1 -1607 1G/2G and MMP7 -181 A/G, increased lung cancer risk was found in Asians. For MMP2 -1306 C/T and MMP2 -735 C/T, decreased lung cancer risk was found in both “diverse populations” and Asians. For MMP9 -1562, C/T decreased lung cancer risk was found in both “diverse populations” and Caucasians. For MMP13 -77A/G, the A/G genotype decreased lung cancer risk in Asians. However, only associations between MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -735 C/T, and MMP7 -181 A/G and lung cancer risk were considered noteworthy according to FPRP tests. There was no association between MMP3 -1171 5A/6A, MMP9 R279Q, and MMP12 -82A/G and lung cancer risk. CONCLUSIONS: Our meta-analysis suggested that MMP1 -1607 1G/2G and MMP7 -181 A/G were risk factors for lung cancer, while MMP2 -1306 C/T, MMP2 -735 C/T, MMP9 -1562 C/T, and MMP13 -77A/G might be protective factors. However, results for MMP9 -1562 C/T and MMP13 -77A/G should be interpreted with caution due to the probability of false-positive reports.

Moyamoya disease (MMD) and Moyamoya syndrome (MMS) are referring to a progressive steno-occlusive vasculopathy at terminal portions of the bilateral internal carotid arteries and their proximal branches with prominent collateral artery formation. They can be found throughout the world and cause irreversible damage to the cerebral hemodynamics due to the progressive nature. Prompt diagnosis and accurate assessment could significantly improve the prognosis of MMD and MMS. Some imaging modalities could be used for diagnosis and nonquantitative evaluation of MMD and MMS, such as conventional computed tomography (CT) and magnetic resonance imaging (MRI), digital subtraction angiography, CT angiography (CTA), and magnetic resonance angiography. Some could quantitatively evaluate the cerebral hemodynamics of MMD and MMS, such as single-photon emission CT, positron emission tomography, xenon-enhanced CT, perfusion CT, dynamic susceptibility contrast MRI, arterial spin labeling MRI, and the hemodynamic parameters measured by those imaging methods could guide treatment of MMD and MMS. All the imaging modalities have their merits and demerits, and they can play a part in certain situation. We need establish standardized protocols for preoperative and postoperative evaluation with different imaging techniques in the further science for MMD and MMS.

We used chemical doping method (using AuCl3 solution in nitromethane) to incorporate gold into graphene sheets. Gold cations reduced on the surface of the graphene film forming pure gold particles. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) showed that the sizes of gold particles were proportional to the doping time. Gold particles mainly accumulated at the graphene defects and wrinkles, effectively reducing the surface resistance and increasing the carrier concentration without significantly affecting the optical properties of graphene. Resistance of the doped single-layer graphene (SLG) sheet can be reduced from 365Ω/sq to 190Ω/sq. Optical transmittance slightly decreased with the soaking time: the light transmittance at 550 nm gradually decreased from 87.6% (for undoped graphene) to 85.6% (for graphene soaked in 1 mg/ml AuCl3 solution for 10 min). Organic light-emitting device (OLED) prepared based on the doped SLG transparent conductive electrode showed much higher performance than a device made of pure graphene as an anode. The maximum luminance of the OLED with doped graphene anode was increased by 135% and the maximum current efficiency was improved by 25.2%.

The aim of this retrospective study was to investigate the clinical characteristics and therapeutic outcomes of pulmonary arterial hypertension (PAH) secondary to congenital portosystemic shunts (CPSS). Thirty-three pediatric patients diagnosed in our institution with CPSS between 2012 and 2019 were enrolled in this study. The patients were divided into PAH and non-PAH groups. The PAH group included 15 patients who presented with unexplained PAH when CPSS was diagnosed. Two patients with microangiopathic hemolytic anemia died of right heart failure shortly after diagnosis. One patient received a liver transplant at the age of 4.3 years and showed a mild decrease in pulmonary artery pressure (PAP) 4 years after the operation. Seven patients underwent one-stage shunt closure at a median age of 2.8 years (1.4-13 years). Follow-up examinations, from 1.6 to 4.1 years after intervention, showed marked reduction of PAP in one patient and stabilization of PAH in six others. However, in one patient who underwent two-stage shunt closure, a marked increase in PAP was noted after partial ligation of the shunt. The remaining four patients received only pulmonary vasodilator therapy, and one of them died of right heart failure 12 years after the PAH diagnosis. The non-PAH group included 18 patients without evidence of PAH upon CPSS diagnosis. Shunt closure was carried out in eight of these patients, but one patient subsequently developed PAH after the resolution of hepatopulmonary syndrome.Conclusion: CPSS may be a more likely cause of unexplained PAH in pediatric patients than previously thought. Shunt closure or liver transplantation may prevent the progression of PAH, or even improve it for the majority of CPSS patients.

Three different IBV genotypes/serotypes, designated ck/CH/LDL/150434-I (LDL/150434-I), ck/CH/LDL/150434-II (LDL/150434-II) and ck/CH/LDL/150434-III (LDL/150434-III), were detected in a single tracheal sample from a chicken showing signs of respiratory disease. The viruses were isolated using a cross-neutralization test and limiting dilution in embryonated specific-pathogen-free (SPF) eggs. Isolate LDL/150434-I was a re-isolation of H120 vaccine strain that was introduced into the chicken flock by vaccination, transmitted between chickens, and later accumulated several genomic mutations. Isolate LDL/150434-II was a novel variant that originated from recombination events between H120 and ck/CH/LDT3/03-like viruses. The widespread use of H120 vaccine, which offered incomplete protection against heterotypic IBVs in the fields, may play important roles in the emergence of such a novel genetic variant. Based on the analysis of S1 and complete genomic sequence, isolate LDL/150434-III was related genetically but distinct from the established strains of nrTW I type viruses of GI-7 lineage circulating in Mainland China since 2009. The three IBV isolates were avirulent when they infected SPF chickens. Furthermore, synergistic effects on pathogenicity were not observed when the different types co-infected the SPF chickens. However, the isolates persisted in the respiratory tracts longer in combined infected birds than those in individual infected birds. The results provide insights into the evolution of the viruses and co-infection of chickens with different virus serotypes.

Transparent conductive films are important components of organic optoelectronic devices. However, current organic light-emitting devices (OLEDs) used in flexible wearable applications are severely restricted by the fragility and poor conductivity of composing ultra-thin electrodes. In this study, poly(methyl methacrylate) (PMMA)/trimethylaluminum (TMA) was prepared through an atomic layer half-reaction and used as a self-encapsulating nucleation layer. The study suggested coordination between the Au atoms with the functional methyl groups of PMMA/TMA to yield an entire substrate surface. The Au nuclei were evenly and densely distributed on the substrate surface, and island growth of Au film was prevented, leading to good flexibility and photoelectric properties of the Au film deposited on the nucleation layer. For instance, a 7 nm thick layer resulted in a sheet resistance of 18.19 ± 0.44 Ω/◻ at 85.89% transmittance. Furthermore, the use of the as-obtained high-performance electrode in flexible organic optoelectronic devices led to repeated bending over 1000 cycles to a radius of 1 mm without significant reduction in the optoelectronic performances. The nucleation induction layer could also function as a bottom encapsulation with a water vapor transmission rate as low as 2.123 × 10−3 g/cm2/day (60 °C/80% relative humidity). Additionally, the nucleation induction layer exhibited excellent performances in fully transparent devices (75.72% transmittance). In sum, these findings look promising for future flexible wearable applications.

Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting human immunodeficiency virus escape mutants. In this study, the affinity of a T-cell receptor specific for the HLA-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM. These HATs could also target HCV NS3 naturally occurring variants, including an escape variant vrt1 (KLVVLGINAV), with high affinities. The HATs can be used as high-affinity targeting molecules at the centre of the immune synapse for the HLA-restricted NS3 antigen. By fusing the HAT with a T-cell activation molecule, an anti-CD3 single-chain variable fragment, we constructed a molecule called high-affinity T-cell activation core (HATac), which can redirect functional CTLs possessing any specificity to recognize and kill cells presenting HCV NS3 antigens. This capability was verified with T2 cells loaded with prototype or variant peptides and HepG2 cells expressing the truncated NS3 prototype or variant proteins. The results indicate that HATac targeting the HLA-restricted NS3 antigen may provide a useful tool for circumventing immune escape mutants and T-cell exhaustion caused by HCV infection.

Background Transarterial chemoembolization (TACE) is the recommended treatment for hepatocellular carcinoma (HCC) patients at Barcelona Clinic Liver Cancer (BCLC) B-stage, whereas sorafenib is an orally administered small molecule target drug for BCLC C-stage. This updated systemic review and meta-analysis focuses on identifying the efficacy of the combination of TACE with sorafenib, which remains controversial despite years of exploration. Methods PubMed, EMBASE, Scopus and the Cochrane Library were systematically reviewed to search for studies published from January 1990 to May 2017. Studies focusing on the efficacy of combination therapy for unresectable HCC were eligible. The hazard ratio (HR) with 95% confidence intervals (95% CIs) for time to progression (TTP), overall survival (OS), disease control rate (DCR) and aetiology were collected. The data were then analysed through fixed/random effects meta-analysis models with STATA 13.0. The incidence and severity of treatment-related adverse events (AEs) were also evaluated. Results Twenty-seven studies were included. Thirteen non-comparative studies reported median OS (ranging from 18.5 to 20.4 months), median TTP (ranging from 7 to 13.9 months) and DCR (ranging from 18.4 to 95%). Fourteen comparative studies provided median OS (ranging from 7.0 to 29.7 months) and median TTP (ranging from 2.6 to 10.2 months). Five comparative studies provided DCR (ranging from 32 to 97.2%). Forest plots showed that combination therapy significantly improved TTP (HR = 0.66, 95% CI 0.50–0.81, P = 0.002) rather than OS (HR = 0.63, 95% CI 0.55–0.71, P = 0.058), compared to TACE alone. DCR increased significantly in the combination therapy group (OR = 2.93, 95% CI 1.59–5.41, P = 0.005). Additional forest plots were drawn and no significant differences were observed with regard to survival outcome among various aetiologies. Forest plots for separate analysis of regions showed the HR for TTP was 0.62 (95% CI 0.45–0.79, P = 0.002) in the Asian countries group, and 0.82 (95% CI 0.59–1.05, P = 0.504)) in western countries. The HR for OS was 0.61 (95% CI 0.48–0.75, P = 0.050) in the Asian countries group and was 0.88 (95% CI 0.56–1.20, P = 0.845) in western countries. These data may indicate positive TTP outcome in Asian patients but not in European patients while no positive findings regarding OS were observed in either region. The most common AEs included fatigue, hand-foot skin reaction, diarrhoea and hypertension. Conclusions Combination therapy may benefit unresectable HCC patients in terms of prolonged TTP and DCR. More well-designed studies are needed to investigate its superiority for OS. Electronic supplementary material The online version of this article (10.1186/s12876-018-0849-0) contains supplementary material, which is available to authorized users.

Table S3. The AEs occurred during combination therapy in 13 non-comparative studies. (DOCX 21 kb)

Table S1. Tumor response criteria, DCR, TTP and OS in 13 non-comparative studies. (DOCX 21 kb)

Table S2. DCR in 5 comparative studies. (DOCX 19 kb)

Residents of Québec typically give less money and volunteer less time compared to residents of all other provinces. This article employs the most recent General Social Survey: Giving, Volunteering and Participating (2013) data set and Tobit procedures and finds that Quebeckers give less money largely because of smaller endowments of two important determinants, religiosity and household income. Once demographic and socioeconomic characteristics are controlled, Quebeckers’ financial donations are comparable to those of residents of Ontario and Atlantic Canada and exceed those of residents of British Columbia. Quebeckers moreover are similar to others when it comes to volunteering for religious organizations, but they volunteer significantly less than others for secular organizations, which cannot be explained in this article.Typiquement, les résidents du Québec donnent moins d’argent et consacrent moins de temps au bénévolat que les résidents des autres provinces. Cet article, en recourant aux données provenant de la dernière « Enquête sociale générale : dons, bénévolat et participation, 2013 » et au modèle Tobit, conclut que les Québécois donnent moins d’argent en grande partie parce qu’ils ont des lacunes dans deux domaines importants, à savoir la religiosité et le revenu du ménage. Cependant, après un contrôle des caractéristiques démographiques et socioéconomiques, on constate que les dons de la part des Québécois sont au fait comparables à ceux des résidents de l’Ontario et des provinces de l’Atlantique et supérieures à ceux des résidents de la Colombie-Britannique. D’autre part, les Québécois sont comparables aux résidents des autres provinces pour ce qui est du bénévolat dans les organismes religieux, mais ils font beaucoup moins de bénévolat dans les organismes séculaires, fait que cet article ne parvient pas à expliquer.