Investigation of the Distribution of Thalassemia in Children in Jiangxi Province, the People's Republic of China.

Thalassemia is one of southern China's most common inherited disorders. Little is known about the genotypes of thalassemia in children in Jiangxi Province, the People's Republic of China (PRC). Two thousand, nine hundred and fifty-two children with suspected thalassemia were recruited from August 2016 to December 2020 at the Jiangxi Provincial Children's Hospital, Nanchang, PRC. Reverse dot-blot hybridization was used to detect α- and ß-thalassemia (α- and ß-thal) genotypes. A rare mutation was detected using gap-polymerase chain reaction (gap-PCR) and gene sequencing. The overall distribution of thalassemia (1534 cases) was 51.96%, and the detection rate of α-thal (616 cases), ß-thal (888 cases) and concurrent α- and ß-thalassemias (30 cases) was 20.86, 30.08, and 1.02%, respectively. A rare α-thal genotype, -α27.6/- -SEA (Southeast Asian), was identified. Seventy-eight cases of severe ß-thal were detected, accounting for 8.78% of the cases, including 56 double heterozygous cases and 22 cases that were homozygous. Both α- and ß-thalassemias are widely distributed in the children of Jiangxi Province. Thalassemia genetic testing is essential to establish a comprehensive thalassemia prevention program and improve public education.

An "Umpolung Relay" Strategy: One-Pot, Twice Polarity Inversion Cascade Synthesis of Diversified [60]Fulleroindoles.

An "umpolung relay" strategy, which includes an one-pot, twice polarity inversion cascade of C60 via carbanion and carbocation polarity reversed relay pathway, has been developed for the synthesis of a diverse range of novel [60]fulleroindole derivatives.

In-Situ-Bloomed Micrometer-Scale Ultrathin Nanosheets in Tumor-Microenvironment for Intensive Photothermal-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT), as the emerging modality of cancer therapy based on Fenton or Fenton-like reactions, still suffers from low efficacy of hydroxyl radical generation, which requires full exposure of reaction sites of CDT nanoagents to intracellular H2O2. However, the amount of exposed reaction sites is severely restrained by the controlled size (<200 nm) and the limited specific surface area of nanoagents. Herein, we highlight the in-situ bloomed micrometer-scale CoMn-based layered double hydroxide (CoMn-LDH) ultrathin nanosheets, which are derived from CoMn boride-based CMB@ss-SF nanospheres in response to overexpressed glutathione (GSH) and dissolved oxygen in tumor microenvironment (TME), accomplishing intensive photothermal-enhanced CDT. The micrometer-scale CoMn-LDH ultrathin nanosheets would provide abundant reactive sites to accelerate heterogeneous Fenton-like reaction as well as GSH depletion, eliciting quick release of metal ions and further realizing intensive homogeneous Fenton-like reactions for ·OH generation. Moreover, the nanoagent can harvest 808 nm light into heat, which can be utilized to promote the CDT efficacy and realize photoacoustic imaging (PAI). Because of acidity and overexpressed GSH in TME, the nanoagent exhibited superior biodegradability. Benefiting from the synergistic advantages, CMB@ss-SF with negligible cytotoxicity completely eradicated the tumors in mouse. This work provides avenue for developing CDT nanoagents.

A water-soluble, upconverting Sr2Yb0.3Gd0.7F7:Er3+/Tm3+@PSIoAm bio-probe for in vivo trimodality imaging.

Multi-modality in vivo bioimaging has great renown for offering more comprehensive information in medical diagnosis and research. Incorporating different bioimaging capabilities into one biocompatible nanoprobe requires an elegant structural design. Considering optical and magnetic properties, X-ray absorption ability, and clinical safety, we prepared a water-soluble and upconverting PSIoAm-modified Sr2Yb0.3Gd0.7F7:Er3+/Tm3+ bio-probe that not only had high photostability and excellent cell membrane permeability, but could also distinguish the four types of cancer cells and normal cells tested within the scope of our study. What's more, it could realize the in vivo trimodality imaging of upconversion fluorescence, X-ray computed tomography and magnetic resonance. The histological analysis of visceral sections further demonstrated that the multifunctional bio-probe was highly safe, which could be applied to clinical diagnosis.

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells.

The present study aims to investigate the radiosensitization effect of the migration and invasion inhibitory protein (MIIP) gene on nasopharyngeal carcinoma (NPC) cells. The MIIP gene was transfected into NPC 5-8F and CNE2 cells. The level of MIIP was analyzed by quantitative reverse transcription-polymerase chain reaction analysis and western blot. The changes in radiosensitivity of the cells were analyzed by colony formation assay. The changes in cell apoptosis and cycle distribution following irradiation were detected by flow cytometry. The expression of BCL2 associated X, apoptosis regulator/B-cell lymphoma 2 was evaluated using western blot. DNA damage was analyzed by counting γ-H2AX foci. The expression levels of γ-H2AX were evaluated by immunofluorescence and western blot. In a previous study by the authors, the results indicated that the expression of MIIP gene evidently increased in MIIP-transfected 5-8F (5-8F OE) and MIIP-transfected CNE2 (CNE2 OE) cells compared with the parental or negative control cells. In the present study, the survival rate of 5-8F OE and CNE2 OE cells markedly decreased following irradiation (0, 2, 4, 6 and 8 Gy) compared with the negative control (5-8F NC and CNE2 NC) and the untreated (5-8F and CNE2) groups. The expression of MIIP was able to increase apoptosis, which resulted in G2/M cell cycle arrest and DNA damage repair was attenuated in 5-8F and CNE2 cells following irradiation as measured by the accumulation of γ-H2AX. It was indicated that MIIP expression is associated with the radiosensitivity of NPC cells and has a significant role in regulating cell radiosensitivity.

A novel flurophore-cyano-carboxylic-Ag microhybrid: Enhanced two photon absorption for two-photon photothermal therapy of HeLa cancer cells by targeting mitochondria.

In this study, a novel two-photon photothermal therapy (TP-PTT) agent based on an organic-metal microhybrid with surface Plasmon resonance (SPR) enhanced two-photon absorption (TPA) characteristic was designed and synthesized using a fluorescent cyano-carboxylic derivative 2-cyano-3-(9-ethyl-9H-carbazol-3-yl) -acrylic acid (abbreviated as CECZA) and silver nanoparticles through self-assembly process induced by the interfacial coordination interactions between the O/N atom of CECZA and Ag+ion at the surface of Ag nanoparticles. The coordination interactions caused electron transfer from the Ag nanoparticles to CECZA molecules at the excited state, resulting in a decreased fluorescence quantum yield. The interfacial coordination interactions also enhanced the nonlinear optical properties, including 13 times increase in the TPA cross-section (δ). The decreased fluorescence quantum yield and increased two photon absorption caused by the SPR effect led excellent two-photon photothermal conversion, which was beneficial for the TP-PTT effect on HeLa cancer cells.

A specific HeLa cell-labelled and lysosome-targeted upconversion fluorescent probe: PEG-modified Sr2YbF7:Tm3+ .

In this study, water-soluble PEG-modified Sr2YbF7:Tm3+ was prepared conveniently by a one-pot solvothermal method, where the molar ratio of Sr2+ to Yb3+ was controlled between 3 : 2 and 1 : 1. The optimum red-light emission at 677-699 nm was modulated via 0.7% Tm3+ doped under irradiation at 980 nm. Interestingly, biological experimental results showed that the PEG-modified Sr2YbF7:Tm3+ with low toxicity, excellent cell membrane permeability and high photostability can not only distinguish HeLa cells from mouse embryonic fibroblasts but also target the subcellular organelle lysosome in HeLa cells; therefore it can be anticipated that the as-prepared material would be a potential tool for cancer diagnosis.

Selective and Real-Time Detection of Nitric Oxide by a Two-Photon Fluorescent Probe in Live Cells and Tissue Slices.

Nitric oxide (NO) is an important signaling molecule involved in many physiological and pathological processes. To understand these NO-mediated processes, it is a key to develop rapid and specific detection methods for NO. In the past 2 decades, numerous excellent fluorescent probes for NO have been designed; however, it still remains limitations such as slow response, low selectivity, and short excitation wavelength (<600 nm). In this Article, a two-photon fluorescent probe, NO-QA5, has been developed with 3-dimethylaminophenyl linking at the 6-position of 5-aminoquinoline as both the active site and prefluorophore for detection of NO. The nonfluorescent NO-QA5 can fast react with NO via a diazonium intermediate to generate two azoic regioisomers, one of which exhibits intramolecular charge transfer (ICT) emission, and two-photon absorption behavior (Î´Φ = 57 GM), giving a turn-on fluorescence rapid response. The sensing reaction is pH-insensitive in the range of 6-11 and highly selective and well sensitive (LOD = 15 nM), possible undergoing the same intermediate diazonium with the reaction under diazotization condition (NaNO2/HCl). Also, as a nitrite fluorescent probe NO-QA5 exhibits highly sensitive (LOD = 7 nM). Therefore, NO-QA5 can serve as a dual functional fluorescent probe for NO and NO2-. Furthermore, NO-QA5 as a specific imaging agent has been demonstrated by achieving both exogenous and endogenous detections of NO in living cells under both one- and two-photon excitation and high resolution in tissue slices under two-photon excitation.

[Effects of recombinant fusion protein interleukin-18 on expression of immune-inflammatory factors in mice infected with Staphylococcus aureus].

OBJECTIVE: To observe the effects of recombinant fusion protein interleukin (IL)-18 on the expression of immune-inflammatory factors in the mice infected with Staphylococcus aureus (SA), and to investigate the mechanism of action of IL-18 in defense of SA infection in vivo. METHODS: A total of 40 specific pathogen-free female BLAB/c mice were randomly divided into four groups: control, SA infection, immunized, and intervention. A mouse model of SA infection was established by nasal inoculation with SA liquid. The immunized group and the intervention group were intranasally given IL-18 before SA modeling, and then the SA infection group and the intervention group received the nasal inoculation with SA liquid; the control group was treated with phosphate buffered saline instead. The levels of IL-4, interferon (IFN)-γ, tumor necrosis factor (TNF), granulocyte colony-stimulating factor (G-CSF), IgM in the serum and bronchoalveolar lavage fluid (BALF) of mice were measured by enzyme-linked immunosorbent assay. The expression of macrophage inflammatory protein (MIP)-1α mRNA and MIP-2ß mRNA in the lung tissue of mice were determined by real-time fluorescent quantitative PCR. RESULTS: Compared with the control group, the SA infection group and the immunized group had significantly higher levels of IL-4, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA and MIP-2ß mRNA in the lung tissue (P<0.05); the SA infection group had a significantly lower level of IFN-γ and a significantly higher level of TNF in the serum and BALF (P<0.05); the immunized group had a significantly higher level of IFN-γ in the serum and BALF (P<0.05). Compared with the SA infection group, the intervention group had significantly higher levels of IL-4, IFN-γ, G-CSF, and IgM in the serum and BALF and expression of MIP-1α mRNA in the lung tissue. In contrast, the intervention group showed a significantly lower level of TNF in the serum and BALF and expression of MIP-2ß mRNA in the lung tissue (P<0.05). All the above indicators in the intervention group were significantly higher than those in the control group (P<0.05), except the serum level of IFN-γ. CONCLUSIONS: In the mice infected with SA, the recombinant fusion protein IL-18 by mucosal immunity can affect inflammatory factors in the serum and BALF and the expression of MIP-1α mRNA and MIP-2ß mRNA in the lung tissue to promote the anti-infective immune response and enhance the ability to clear pathogens.

Coordination coupling enhanced two-photon absorption of a ZnS-based microhybrid for two-photon microscopy imaging in HepG2.

Coordination coupling induced self-assembly of ZnS microparticles was performed with the help of a π-conjugated sulphur-terminal Zn(ii) complex ZnS2L (L = N-hexyl-3-{2-[4-2,2':6',2''-terpyridin-4'-yl-phenyl]ethenyl}-carbazole). The interactions between ZnS and ZnS2L components at the interface, which were analyzed by far-IR and XPS, resulted in a tunable single-photon excited fluorescence and an enhanced nonlinear optical response, including a two-photon absorption cross section and a two-photon excited fluorescence. Such an enhancement in nonlinear optical properties was triggered by the coordination coupling effect between terminal S atoms of ZnS2L and naked Zn2+ ions at the surface of ZnS particles. Thus, the novel hybrid system displayed a unique two-photon excited fluorescence to facilitate promising two-photon microscopy imaging of HepG2 cells upon NIR light illumination at 840 nm. The hybrid shows a stronger ability to enter the cells than free ZnS2L.

Silver(I) supramolecular complexes generated from isophorone-based ligands: crystal structures and enhanced nonlinear optical properties through metal complexation.

By self-assembly of (E)-2-(3-(4-(1H-imidazol-1-yl)styryl)-5,5-dimethylcyclohex-2-enylidene)malononitrile (L(1)) and (E)-2-(3-(4-(1H-1,2,4-triazol-1-yl)styryl)-5,5-dimethylcyclohex-2-enylidene)malononitrile (L(2)) with silver(I) salts, eight new complexes, namely AgL(1)2ClO4 (1), AgL(1)2NO3 (2), [AgL(1)2NO3]·C6H6 (3), [AgL(1)2OOCCF3]·C6H6 (4), [AgL(1)2PF6]·C6H6 (5), AgL(2)2NO3 (6), [AgL(2)OOCCF3]2 (7) and AgL(2)2PF6 (8), are presented along with an analysis of their structural features. The structures are built up through the combination of coordination bonds, Ag···π, Ag···F (or O), hydrogen bonding, and π···π stacking interactions to generate new supramolecular architectures. We observed the formation of two-dimensional coordination polymers for complex 7. Solvent benzene molecules and anions are dispersed in the supramolecular structure and play a vital role in building the supramolecular structures of the complexes. The nonlinear optical (NLO) properties of the complexes were investigated using the Z-scan technique and complexes 1, 2, 3, 4 and 7 show obviously nonlinear absorption compared with ligands (L(1) and L(2)).

A self-assembled nanohybrid composed of fluorophore-phenylamine nanorods and Ag nanocrystals: energy transfer, wavelength shift of fluorescence and TPEF applications for live-cell imaging.

A fluorophore-phenylamine derivative (L) has been coupled with silver nanocrystals (NCs) to construct an L-Ag nanohybrid. Owing to synergic effects of the L and Ag components, the exciton-plasmon interactions between L and Ag increase the strength of the donor-acceptor interaction within the nanohybrid, a fact that results in an energy-transfer process and further brings about a dramatic redshift of single-photon absorption and fluorescence, and a decreased fluorescence FL lifetime. The coupling effect also leads to enhancement of a series of nonlinear optical properties, including two-photon-excited fluorescence (TPEF), two-photon-absorption (TPA) cross section (δ), two-photon-absorption coefficient (ß), nonlinear refractive index (γ), and third order nonlinear optical susceptibility (χ((3))). The enhanced two-photon fluorescence of the nanohybrid is proven to be potentially useful for two-photon microscopy of live cells, such as HepG2. Moreover, cytotoxicity tests show that the low-micromolar concentrations of the nanohybrid do not cause significant reduction in cell viability over a period of at least 24 h and should be safe for further biological studies.

Bis((E)-2-{3-[4-(1H-imidazol-1-yl-κN (3))styr-yl]-5,5-di-methyl-cyclo-hex-2-enyl-idene}malono-nitrile)-diiodido-mercury(II).

In the title compound, [HgI2(C22H20N4)2], the Hg(II) cation is situated on a twofold rotation axis and is coordinated by two iodide anions and two imidazolyl N atoms in a distorted tetra-hedral geometry. In the crystal, C-H⋯I inter-actions link the mol-ecules into chains extending in [010], which are further linked into sheets parallel to (100) through C-H⋯N hydrogen bonding inter-actions.

Bis((E)-2-{5,5-di-methyl-3-[4-(1H-1,2,4-triazol-1-yl-κN (4))styr-yl]cyclo-hex-2-enyl-idene}malono-nitrile)-diiodido-mercury(II).

In the title complex, [HgI2(C21H19N5)2], the Hg(II) ion is located on a twofold rotation axis and is coordinated by two I atoms and two N atoms from two (E)-2-{5,5-di-methyl-3-[4-(1H-1,2,4-triazol-1-yl)styr-yl]cyclo-hex-2-enyl-idene}malono-nitrile ligands in a distorted tetra-hedral geometry. In the crystal, the mol-ecules are linked by inter-molecular π-π inter-actions between the triazole and benzene rings [centroid-centroid distance = 3.794 (3) Å] into a band extending in [010]. These bands are further connected by C-H⋯N hydrogen bonds into a two-dimensional network parallel to (100).

2-[4-(1H-1,2,4-Triazol-1-yl)phen-yl]-1H-benzimidazole.

In the title compound, C(15)H(11)N(5), the benzimidazole ring system is nearly planar [maximum deviation = 0.039 (2) Å], and is oriented at a dihedral angle of 28.85 (10)° with respect to the benzene ring; the dihedral angle between the triazole and benzene rings is 17.30 (15)°. In the crystal N-H⋯N hydrogen bonds link the mol-ecules into chains. Weak C-H⋯N inter-actions are also present.

[The protective effect of N-acetylcysteine magnesium against liver cirrhosis with portal hypertension in rat].

OBJECTIVE: To study the effects of acetylcysteine magnesium on the vasoactive substances and hepatic fibrosis indexes in liver cirrhosis and portal hypertension of rats. METHODS: The rat liver cirrhosis model was made with 12 microg/kg dimethylnitrosamines. Then acetylcysteine magnesium was injected respectively with 25, 50, and 100 mg x kg(-1) dose daily into abdominal cavity. After 8 weeks treatment, pathological section, TGF-beta1, NO, TNOS and iNOS of hepatic tissue were detected to assess the effect of acetylcysteine magnesium against cirrhosis portal hypertension. RESULTS: After the DMNA modeling was completed, the HE and Sweet reticulocyte staining of liver pathological section showed that cirrhosis of the liver was in the III-IV phase, the infiltration of lymphocytes and formation of pseudolobuli in liver were alleviated in three acetylcysteine magnesium treatment groups (low, medium, and high dose), and the degree of liver fiber sclerosis in three groups was significantly lower than control group. Compared with control group, TGF-beta1, NO, TNOS and iNOS were significantly reduced in all treatment groups (P < 0.05). CONCLUSION: Acetylcysteine magnesium is probably a distinctive antioxidant which can remove various free radical in body and modulate ligand-dependent signal transduction and the growth of cell. It also have protection in the liver cirrhosis and portal hypertension of rats induced by dimethylnitrosamine.

1-(4-Carb-oxy-phen-yl)-1H-imidazol-3-ium chloride dihydrate.

In the crystal structure of the title compound, C(10)H(9)N(2)O(2) (+)·Cl(-)·2H(2)O, the components are linked by O-H⋯O, N-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonds. In the cation, the imidazole ring is oriented at a dihedral angle of 13.67 (17)° with respect to the benzene ring. In the crystal, π-π stacking occurs between nearly parallel benzene rings, which are oriented at a dihedral angle of 3.4 (1)°, the centroid-centroid distance being 3.798 (3) Å.

4-(Imidazol-1-yl)benzoic acid.

In the title mol-ecule, C(10)H(8)N(2)O(2), the imidazole and benzene rings form a dihedral angle of 14.5 (1)°. In the crystal, inter-molecular O-H⋯N hydrogen bonds link the mol-ecules into chains extending in [01], which are further linked into sheets parallel to (102) through weak C-H⋯O inter-actions.

Synthesis, crystal structure, electrochemistry and in situ FTIR spectroelectrochemistry of a bisferrocene pyrazole derivative.

One novel bisferrocene pyrazole derivative, bis [2-(5-trifluoromethyl-3-ferrocenyl) pyrazolyl] methane (abbreviated as (3)), was synthesized and fully characterized. A single crystal of (3) was obtained and solved by X-ray diffraction analysis. The bisferrocene derivative exhibits MLCT (metal to ligand charge transfer) and π→π* transitions in the UV-visible range, which have been verified by density functional theory (DFT) calculations. Its electrochemical properties were studied with the aid of cyclic voltammetry (CV), differential pulse voltammetry (DPV) and rapid scan time-resolved Fourier transform infrared spectroscopy (RS-TRS FT-IR) analysis. Furthermore, the electrochemical mechanism was elucidated based on the results from the cyclic voltabsorptometry (CVA) determination technique. (3) apparently shows a single wave in the cyclic voltammetric experiments which indicates there is no intermediate, however, the intermediate of (3) was observed by employing the RS-TRS FT-IR spectroelectrochemistry technique. The detailed investigation brought us safely to the conclusion that the methylene can also act as a linker, leading to electronic communication in either D-π-D and A-π-A systems.