Research progress of STAT3-based dual inhibitors for cancer therapy.

Signal transducer and activator of transcription 3 (STAT3), a transcription factor, regulates gene levels that are associated with cell survival, cell cycle, and immune reaction. It is correlated with the grade of malignancy and the development of various cancers and targeting STAT3 protein is a potentially promising therapeutic strategy for tumors. Over the past 20 years, various compounds have been found to directly inhibit STAT3 activity via different strategies. However, numerous difficulties exist in the development of STAT3 inhibitors, such as serious toxic effects, poor therapeutic effects, and intrinsic and acquired drug resistance. STAT3 inhibitors synergistically suppress cancer development with additional anti-tumor drugs, such as indoleamine 2,3-dioxygenase 1 inhibitors (IDO1i), histone deacetylase inhibitors (HDACi), DNA inhibitors, pro-tumorigenic cytokine inhibitors (PTCi), NF-κB inhibitors, and tubulin inhibitors. Therefore, individual molecule- based dual-target inhibitors can be the candidate alternative or complementary treatment to overcome the disadvantages of just STAT3 or other targets as a monotherapy. In this review, we discuss the theoretical basis for formulating STAT3-based dual-target inhibitors and also summarize their structure-activity relationships (SARs).

Asymmetric Synthesis of Tetrahydroisoquinoline Derivatives through 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with Allyl Alkyl Ketones.

A [3 + 2] 1,3-Dipolar cycloaddition of C,N-cyclic azomethine imines with allyl alkyl ketones has been achieved. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. An array of tetrahydroisoquinoline derivatives is generally constructed with good diastereoselectivities and enantioselectivities (up to >25:1 dr, >95% ee). Moreover, the absolute configuration of the product was previously determined by using the quantum electronic circular dichroism calculation and ECD spectrum method.

Facile Synthesis of Sulfonyl Chlorides/Bromides from Sulfonyl Hydrazides.

A simple and rapid method for efficient synthesis of sulfonyl chlorides/bromides from sulfonyl hydrazide with NXS (X = Cl or Br) and late-stage conversion to several other functional groups was described. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides and sulfonates. In most cases, these reactions are highly selective, simple, and clean, affording products at excellent yields.

Validation of Moorong Self-Efficacy Scale among Chinese stroke survivors.

PURPOSE: To examine the psychometric properties of a Chinese version of the Moorong Self-Efficacy Scale (MSES-C) among stroke survivors. METHODS: A cross-sectional descriptive study was conducted with 160 stroke survivors recruited from the three neurology departments in China. Reliability, concurrent validity, and construct validity of the scale were determined. RESULTS: The MSES-C whole scale showed good internal consistency with a Cronbach's α of 0.953. There was a moderate to a strong positive correlation between the MSES-C and Chinese version of the General Self-Efficacy Scale (r = 0.695, p < 0.000), a strong positive correlation between the MSES-C and Chinese version of the stroke specific self-efficacy scale (r = 0.801, p < 0.000), positive correlations between the MSES-C and Chinese versions of the Modified Barthel Index (r = 0.695, p < 0.000), and a negative correlation between the MSES-C and National Institutes of Health Stroke Scale (r = -0.511, p < 0.000). Known-group validity was also supported. CONCLUSIONS: The MSES-C is a reliable and valid instrument for assessing self-efficacy in Chinese stroke survivors.Implications for RehabilitationThe Chinese version of the Moorong Self-Efficacy Scale demonstrated good internal consistency and showed satisfactory concurrent and construct validity among stroke survivors.The Moorong Self-Efficacy Scale can be used to assess stroke recovery among the Chinese population in clinical and research settings.

Copper-catalyzed cross coupling reaction of sulfonyl hydrazides with 3-aminoindazoles.

A novel Cu-catalyzed radical-radical cross coupling reaction of 3-aminoindazoles with sulfonyl hydrazides has been disclosed, enabling the production of diverse 1,3-substituted aminoindazoles in good yields. This methodology is distinguished by readily available starting materials, wide substrate scope and operational simplicity. In addition, a gram-scale reaction has been well demonstrated.

Synthesis of 2'-deoxyguanosine from 2'-deoxyadenosine via C2 nitration.

An efficient synthetic method has been developed for the synthesis of 2'-deoxyguanosine from the more commercially available 2'-deoxyadenosine via late-stage C2 nitration in 48.7% total yield by a 5-step synthetic procedure. Crucially, 2'-deoxyadenosine was fully protected by bennzoyl groups and then nitrated at C2 by tetrabutylammonium nitrate/trifluoroacetic anhydride. The resulting 2-NO2 moiety was converted into 2-NH2 by Ni-catalyzed hydrogenolysis. Finally, 2'-deoxyguanosine was obtained from the diaminopurine intermediate by deaminase-catalyzed reaction. Furthermore, the 2-NO2 moiety also appeared to be a versatile handle to introduce a variety of functional groups, resulting in a divergent access to 2-substituted 2'-deoxyadenosine analogues.

[Epidemic condition and biological characteristics of non-O1/non-O139 Vibrio cholerae in Haizhu District of Guangzhou].

OBJECTIVE: To understand the epidemic condition, distribution and biological characteristics of non-O1/non-O139 Vibrio cholerae from 2001 to 2009 in Haizhu District, to provide a scientific basis for the prevention and control of acute diarrhea. METHODS: Referring to the detecting method written in "Cholera control handbook" in the fifth edition, 764 specimens from outside environment (including the water in the Pearl River, drinking water, water for breeding fish, aquatic products and delicatessen foods), 189 specimens of healthy population and 3398 intestinal samples of patients with diarrhea, summing up to 4351 specimens for non-O1/non-O139 Vibrio cholerae test. RESULTS: 4,351 specimens were detected of 101 strains of non O1/non O139 Vibrio cholerae, the total detection rate was 2.32%; 66 strains were identified by serotyping and grouped into 26 different serotypes, the typing rate was 65.3%. The strains VBO9, VBO38 and VBO76 were the dominant bacteria.Nine strains of the same type of non-O1/non-O139 Vibrio cholerae were found from external environments also from patients with diarrhea, suggesting that there might be a correlation between the two. CONCLUSION: Non-O1/non-O139 Vibrio cholerae have diversified serotypes, causing certain infection rate among the population in this region. These bacteria exist extensively in external environment and they are the potential hazard to the citizens.

[Multiplayer white organic light-emitting diodes with different order and thickness of emission layers].

In multilayer OLED devices, the order and thickness of the emission layers have great effect on their spectrum. Based on the three basic colours of red, blue and green, a series of white organic light-emitting diodes(WOLEDS)with the structure of ITO/CuPc(12 nm)/NPB(50 nm)/EML/LiF(1 nm)/Al(100 nm) and a variety of emission layer's orders and thicknesses were fabricated. The blue emission material: 2-t-butyl-9,10-di-(2-naphthyl)anthracene (TBADN) doped with p-bis(p-N, N-diphenyl-amono-styryl)benzene(DSA-Ph), the green emission material: tris-[8-hydroxyquinoline]aluminum(Alq3) doped with C545, and the red emission material: tris-[8-hydroxyquinoline]aluminum( Alq3) doped with 4-(dicyanomethylene)-2-t-butyl-6-(1, 1, 7, 7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) were used. By adjusting the order and thickness of each emission layer in the RBG structure, we got a white OLED with current efficiency of 5.60 cd x A(-1) and Commission Internationale De L'Eclairage (CIE) coordinates of (0. 34, 0.34) at 200 mA x cm(-2). Its maximum luminance reached 20 700 cd x m(-2) at current density of 400 mA x cm(-2). The results were analyzed on the basis of the theory of excitons' generation and diffusion. According to the theory, an equation was set up which relates EL spectra to the luminance efficiency, the thickness of each layer and the exciton diffusion length. In addition, in RBG structure with different thickness of red layer, the ratio of th e spectral intensity of red to that of blue was calculated. It was found that the experimental results are in agreement with the theoretical values.

PARP1-siRNA suppresses human prostate cancer cell growth and progression.

Poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib or rucaparib, have shown treatment efficacy in BRCA1/2-deficient tumors. However, since PARP inhibitors (PARPi) mainly modulate the activation of PARP but not its expression, whether small interfering RNA (siRNA) specific to PARP has the same function as PARPi has not been well defined. In the present study it was demonstrated that PARP1-siRNA could reduce prostate cancer (PCa) cell progression regardless of the BRCA1/2 mutation. PARP1 silencing could significantly inhibit PC3 cell migration and invasion. Additionally, PARP1-siRNA also inhibited the proliferation of PC3 and Du145 cells. After the induction of apoptosis by docetaxel, cleaved-caspase3 of DU145 and C4-2 cells increased significantly in the PARP1-siRNA group. In the xenograft nude mouse model, PARP1-siRNA could suppress xenograft tumor size of PC3 cells and produce a more regular morphology. In vitro and in vivo, PARP1 silencing significantly downregulated vimentin expression and upregulated E-cadherin expression, both of which are epithelial-mesenchymal transition (EMT) markers. It has been revealed that PI3K inhibition could sensitize the effect of PARPi. Notably, PARP1-siRNA could suppress the expression of EGFR and p-GSK3ß (Ser9) in PCa cells, which was different from PARPi. Our results indicated that PARP1-siRNA can suppress the growth and invasion capacity of PCa cells, thereby suggesting that PARP1-siRNA, which is different from PARPi, may provide a potential treatment method for PCa.

Metabolic disturbances in Chinese children with urolithiasis: a single center report.

Urinary stones and urine composition are the first steps in the process of recurrence prevention, but data concerning the association between the two compositions are scarce in Chinese children with urolithiasis. We retrospectively analyzed the records of children (age range 0-18 years) with urolithiasis in our center between March 2004 and December 2013. Stone analysis was carried out in 382 children and 24-hour urine analysis in 80 children. Analysis of both stone and 24-hour urine composition was completed in 56 children. Stone samples were analyzed by Fourier transform-infrared spectrometry. The major stone constituents were calcium oxalate (78.8 %). Of 80 children with 24 h urine analysis, only 2.5 % were without urinary metabolic abnormalities. Hypocitraturia was recorded in 97.5 %, high sodium excretion in 50.0 %, cystinuria in 48.7 %, hypercalciuria in 18.8 %, small urine volumes in 12.5 %, hyperoxaluria in 5.0 % and hyperuricosuria in 1.3 %. Interestingly, higher urine volumes were recorded in girls than in boys (73.2 ± 58.5 vs 51.3 ± 45.3 mL/kg, p = 0.036). Urine sodium (p = 0.002) and oxalate (p = 0.004) were significantly higher in children >9 year old. Moreover, compared with calcium oxalate stone formers, the urine volume (p = 0.040), citrate (p = 0.007) and cystine (p = 0.004) were higher in patients with cystine stones. Hypocitraturia was the common abnormality among Chinese children with urolithiasis. The surprisingly high incidence of cystinuria is of note.

[Multiple emissions in organic electroluminescent device using a mixed layer as an emitter].

A organic electroluminescent device has been fabricated by using a mixed layer as an emitter. The configuration of the device is ITO/TPD/TPD: PBD(equimole)/PBD/A1, in which TPD (N,N'-diphenyl-N,N'-bis(3-methylphenyl)-1,1'-biphenyl-4,4'-diamine) and PBD (2-(4'-biphenyl)-5-(4''-tert-butylphenyl)-1,3,4-oxadiazole) are used as hole transport material and electron transport material, respectively. Broad and red-shifted electroluminescent spectra related to the fluorescence of constituent materials were observed. It is suggested that the monomer, exciplex and electroplex emissions are simultaneously involved in EL spectra by comparison of the EL with the PL spectra and decomposition of the EL spectrum. The type of exciplex is the interaction between the excited state TPD (TPD*) and PBD in the ground state, and the type of electroplex is a (D+-A-)* complex by cross-recombination of hole on the charged hole transport molecule (D+) and electron on the charged electron transport molecule (A-). All types of excited states show different formation mechanisms and recombination processes under electric field. The change of emission strengths from monomer and excited complexes lead to a blue-shift of the emissive spectra with an increasing electric field. The maximum luminance and external quantum efficiency of this device are 240 cd x (cm2)(-1) and 0.49%, respectively. The emissions from exciplex or electroplex formation at the organic solid interface generally present a broad and red-shifted emissive band, providing an effective method for tuning of emission color in organic electroluminescent devices.

Collection and storage of urine specimens for measurement of urolithiasis risk factors.

OBJECTIVE: To evaluate how different methods for storage and preservation of urine samples affected the outcome of analysis of risk factors for stone formation. METHODS: Spot urine samples were collected from 21 healthy volunteers. Each fresh urine sample was divided into ten 10-mL aliquots: 2 without preservative, 2 with thymol, 2 with toluene, 2 with hydrochloric acid (HCl), and 2 with sodium azide. One sample of each pair was stored at 4 °C and the other at room temperature. The concentrations of calcium, magnesium, sodium, phosphate, urate, oxalate, citrate, and pH in each urine sample were analyzed immediately after collection (0 hour) and after 24 and 48 hours. RESULTS: There were no significant differences in calcium, oxalate, magnesium, phosphate, sodium, urate or pH (without acidification) between samples with different preservation methods (P >.05). Urinary citrate, however, was significantly lower in the urine collected with HCl than when other preservatives were used, both at room temperature and at 4 °C. Urine pH was significantly higher after 48 hours than after 24 hours, whether the samples were stored at room temperature or at 4 °C. CONCLUSION: Antibacterial preservatives (eg, thymol or toluene) can be recommended as preservatives for 24-hour urine collections. Ideally, the samples should be stored at 4 °C. When HCl is used as a preservative, it seems essential to neutralize the samples before analysis. This is particularly obvious with the chromatographic method used for analysis of citrate that was used in this study.

Synthesis of hierarchically structured ZnO nanomaterials via a supercritical assisted solvothermal process.

Hierarchically structured ZnO nanomaterials with flower-sheet-particle morphologies were synthesized via a supercritical assisted solvothermal process free from any other auxiliary chemicals.

A new synthesis of 2-chloro-2'-deoxyadenosine (Cladribine), CdA).

A new efficient route for the synthesis of 2-chloro-2';-deoxyadenosine (Cladribine), CdA) has been developed. The key step of this method was selective deprotection of the acetyl group at the 2' position; the 3', 5' acetyl groups were not affected. This can be accomplished efficiently with hydroxylamine hydrochloride and sodium acetate in pyridine. The 2' hydroxyl group was removed by the Barton-McCombie reaction. Using this strategy, CdA was prepared in five steps and 31.0% yields.