Suppressing the virulence factors of Candida auris with baicalein through multifaceted mechanisms.

Candida auris, a rapidly spreading multi-drug-resistant fungus, is causing lethal infections under certain conditions globally. Baicalin (BE), an active ingredient extracted from the dried root of Scutellaria baicalensis Georgi, exhibits antifungal activity. However, studies have shown the distinctive advantages of Traditional Chinese medicine in combating fungal infections, while the effect of BE, an active ingredient extracted from the dried roots of Scutellaria baicalensis Georgi, on C. auris, remains unknown. Therefore, this study aims to evaluate the potential of BE as an antifungal agent against the emerging multidrug-resistant C. auris. Various assays and models, including microbroth dilution, time growth curve analysis, spot assays, adhesion tests, flocculation test, cell surface hydrophobicity assay, hydrolase activity assays, XTT assay, violet crystal assay, scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), flow cytometry, Live/dead fluorescent staining, reactive oxygen species (ROS), cell wall assay, aggregation assay, porcine skin model, Galleria mellonella larvae (G. mellonella larvae) infection model, and reverse transcription-quantitative polymerase chain reaction (RT-PCR) were utilized to investigate how baicalein suppresses C. auris through possible multifaceted mechanisms. The findings indicate that BE strongly inhibited C. auris growth, adhesion, and biofilm formation. It also effectively reduced drug resistance and aggregation by disrupting the cell membrane and cell wall while reducing colonization and invasion of the host. Transcriptome analysis showed significant modulation in gene expression related to different virulence factors post-BE treatment. In conclusion, BE exhibits significant effectiveness against C. auris, suggesting its potential as a viable treatment option due to its multifaceted suppression mechanisms.

Cell-Derived N/P/S-Codoped Fluorescent Carbon Nanodots with Intrinsic Targeting Ability for Tumor-Specific Phototheranostics.

Combining targeting ability, imaging function, and photothermal/photodynamic therapy into a single agent is highly desired for cancer theranostics. Herein, we developed a one-for-all nanoplatform with N/P/S-codoped fluorescent carbon nanodots (CNDs) for tumor-specific phototheranostics. The CNDs were prepared via a one-pot hydrothermal process using cancer cells as sources of carbon, nitrogen, phosphorus, and sulfur. The obtained N/P/S-codoped CNDs exhibit wide light absorption in the range of 200-900 nm and excitation-dependent emission with high photostability. Importantly, the cancer cell-derived N/P/S-codoped CNDs have outstanding biocompatibility and naturally intrinsic targeted ability for cancer cells as well as dual photothermal/photodynamic effects under 795 nm laser irradiation. Moreover, the photothermal conversion efficiency and singlet oxygen (1O2) generation efficiency were calculated to be 52 and 34%, respectively. These exceptional properties enable CNDs to act as fine theranostic agents for targeted imaging and photothermal-photodynamic synergistic therapy within the NIR therapeutic window. The CNDs prepared in this work are promising for construction as a universal tumor phototheranostic platform.

A FRET Based Composite Sensing Material Based on UCNPs and Rhodamine Derivative for Highly Sensitive and Selective Detection of Fe3.

The existence of excessive concentration of iron ion (Fe3+) in water will do harm to the environment and biology. Presently, sensitive and selective determination of Fe3+ directly in real environment samples is still a challenging job because of the high complexity of the sample matrix. In this work, we reported a new sensor system for Fe3+ based on fluorescence resonance energy transfer (FRET) from upconversion nanoparticles (UCNPs) to Rhodamine derivative probe (RhB). The NaYF4: Yb, Er@SiO2@P(NIPAM-co-RhB) nanocomposites was constructed, in which PNIPAm was used as the probe carrier. The nanocomposites can not only be excited by infrared light to avoid the interference of background light in the Fe3+ detection process, but also enhance the detection signal output through temperature control. Under the optimum conditions, the RSD (Relative standard deviation) of actual sample measurements ranges was from 1.95% to 4.96%, with the recovery rate from 97.4% to 103.3%, which showed high reliability for Fe3+ detection. This work could be extended to sensing other target ions or molecules and may promote the widespread use of FRET technique.

rhTPO Ameliorates Radiation-Induced Long-Term Hematopoietic Stem Cell Injury in Mice.

Exposure to medium and high doses of ionizing radiation (IR) can induce long-term bone marrow (BM) suppression. We previously showed that recombinant human thrombopoietin (rhTPO) significantly promotes recovery from hematopoietic-acute radiation syndrome, but its effect on long-term BM suppression remains unknown. C57BL/6 mice were exposed to 6.5 Gy γ-rays of total body irradiation (TBI) at a dose-rate of 63.01 cGy per minute, and the mice were treated with rhTPO (100 µg; intramuscular injection) or vehicle at 2 h after TBI. All mice were killed one or two months after TBI for analysis of peripheral blood cell counts, long-term hematopoietic stem cell (HSC) frequency, and BM-derived clonogenic activity. The HSC self-renewal capacity was analyzed by BM transplantation. The levels of reactive oxygen species (ROS) production and ratios of γH2AX+ and p16, p53, and p21 mRNA in HSCs were measured by flow cytometry and real-time polymerase chain reaction, respectively. Treatment with rhTPO reduced long-term myelosuppression by improving long-term hematopoietic reconstitution (p < 0.05) after transplantation and resting state maintenance of HSCs (p < 0.05). Moreover, rhTPO treatment was associated with a sustained reduction in long-term ROS production, reduction of long-term DNA damage, diminished p53/p21 mRNA expression, and prevention of senescence after TBI. This study suggests rhTPO is an effective agent for treating IR-induced long-term BM injury because it regulates hematopoietic remodeling and HSC cycle disorder through the ROS/p53/p21/p16 pathway long term after IR.

Synthesis, Optical Properties, and Fluorescence Cell Imaging of Novel Mixed Fluorinated Subphthalocyanines.

Subphthalocyanines (SubPcs) are a kind of tripyrrolic macrocycle with a boron atom at their core. Incorporating different units onto the SubPc periphery can endow them with various unique properties. Herein, a series of novel fluorinated low-symmetry SubPc derivatives containing chlorine groups (F8-Cl4-SubPc, F4-Cl8-SubPc) and methoxy groups (F8-(OCH3)2-SubPc) were synthesized and characterized by spectral methods (MS, FT-IR, 1H, 13C, 11B, and 19F NMR spectroscopy), and the effect of the peripheral substituents on their electronic structure of low-symmetry macrocycle was investigated by cyclic voltammetry, theoretical calculation, electronic absorption, and emission spectroscopy. In contrast to perfluorinated SubPcs, these low-symmetry SubPcs revealed non-degenerate LUMO and LUMO + 1 orbitals, especially F8-(OCH3)2-SubPc, which was consistent with the split Q-band absorptions. The cyclic voltammetry revealed that these SubPcs exhibited two or three reduction waves and one oxidation wave, which is consistent with the reported SubPcs. Finally, an intracellular fluorescence imaging study of these compounds revealed that these compounds could enter cancer cells and be entrapped in the lysosomes, which provides a possibility of future applications in lysosome fluorescence imaging and targeting.

Light-Promoted Low-Valent-Tungsten-Catalyzed Ambient Temperature Amination of Boronic Acids with Nitroaromatics.

Triggering C-N bond formation with nitroaromatics and boronic acids at mild conditions is highly desirable, since most prior works were carried out under harsh conditions and sometimes suffered from poor chemo- or regioselectivity. Herein, a low-valent-tungsten-catalyzed reaction that enables the ambient temperature amination of boronic acids with nitroaromatics is disclosed. With readily available W(CO)6 as a precatalyst under external-photosensitizer-free conditions, nitroaromatics smoothly undergo C-N coupling reactions with their boronic acid partners, delivering structurally diverse secondary amines in good yields (>50 examples, yields up to 96%). This methodology is both scalable and highly chemoselective and engages both aliphatic and aromatic boronic acid partners. The catalysis is initiated by the deoxygenation of nitroaromatics by a trans-[W(CO)4(PPh3)2] (trans-W, PPh3 = triphenylphosphine) complex, which forms in situ via ligand replacement.

Comparative analysis of loop-mediated isothermal amplification combined with microfluidic chip technology and q-PCR in the detection of clinical infectious pathogens.

BACKGROUND: Rapid diagnosis of infectious pathogens at an early stage is crucial to stabilize the patient's condition, reduce medical costs, and shorten hospital stays. Currently, some point-of-care tests have their own shortcomings. Therefore, we built a microfluidic chip based on loop-mediated isothermal amplification to can quickly and sensitively detect infectious pathogens. METHODS: We extracted the DNA of S. aureus, MRSA, Shigella and Klebsiella pneumoniae. Then, the DNA samples were diluted by 10-fold and examined by two methods: LAMP-microfluidic chip and q-PCR, the sensitivity of whom was also compared. In addition, the specificity of the two was also examined by detecting the target bacteria and other microorganisms using the same methods. Finally, we extracted and tested the DNA of clinically infected humoral samples to determine the coincidence rate between the two methods and the bacterial culture method. RESULTS: For S. aureus, MRSA, Shigella, and Klebsiella pneumoniae, the detection limits of the chip were 2.25 × 103 copies/µl, 5.32 × 103 copies/µl, 2.89 × 103 copies/µl, 6.53 × 102 copies/µl, and the detection limits of q-PCR were 2.25 × 102 copies/µl, 5.32 × 101 copies/µl, 2.89 × 102 copies/µl, 6.53 × 101 copies/µl, respectively. In terms of detection specificity, neither method cross-reacted with other strains. For the detection of infectious humoral samples, the total coincidence rate between the q-PCR and bacterial culture method was 85.7%, 95%, 95%, and 95.5%, and the total coincidence rate between the chip and bacterial culture method was 81%, 95%, 90%, and 86.4%, respectively. CONCLUSION: LAMP-microfluidic chip provides a simple, sensitive, specific, convenient, and rapid pathogen detection method for clinically infected humoral samples without relying on expensive equipment or technical personnels.

Bis(1,3-dithiol-2-ylidene)-Substituted Subtriazachlorin: A Subphthalocyanine Analogue with Redox Properties.

Bis(1,3-dithiol-2-ylidene)-substituted subtriazachlorin was formed because of an unusual reaction of a 1,3-dithiole-2-one-fused subphthalocyanine in a triethylphosphite-mediated tetrathiafulvalene synthesis. In this novel molecule, the bis(1,3-dithiol-2-ylidene)ethane moiety and subtriazachlorin structure are fused, resulting in an electron-donating ability and broad absorption in the near-infrared region.

[Effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy].

To study the effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy. A total of 205 cases of patient with early diabetic nephropathy treated in our hospital from March 2014 to April 2016 were selected and divided into two groups according to the admitted order, with 103 cases in clinical group and 102 in control group. Patients in control group were treated with melbine and captopril, which may be adjusted according to the clinical symptom. The clinical group was given Shenqi Dihuang decoction. Then the clinical efficady, inflammatory factors, renal function, endothelial function and hemorheology index were compared. Compared with 77.45% in the control group, the total effective rate of the clinical group was 92.23%. There was a significant increase (P<0.05). The comparison of the values of IL-6, IL-8, TNF-α and CRP between the two groups before and after treatment showed significant differences. The values of inflammatory factors in treatment group were lower than in control group (P<0.05). The comparison of the values of ß2-MG, Cys-C and urine m-ALB between the two groups before and after treatment showed significant differences. The values of renal function in treatment group were lower than those in control group (P<0.05). Compared with before treatment, ET-1 of the two groups after treatment decreased, while NO increased (P<0.05). Compared with the control group, the value of ET-1 in patients of the experimental group was lower after treatment, while NO was higher (P<0.05). The comparison of the values of whole blood viscosity, plasma viscosity, whole blood reduction viscosity, platelet aggregation rate and fibrinogen between the two groups before and after treatment showed significant differences. The value of hemorheology index in treatment group was lower than that in control group (P<0.05). Shenqi Dihuang decoction has a better effect on patients with early diabetic nephropathy. It can significantly intervene with inflammatory response, reduce proteinuria, protect the renal function of patients, and improve the patient's vascular endothelial function and blood rheology, so as to make microcirculation to recover to the normal level.

Synthesis, characterization, and electrochemistry of the manganese(I) complexes of meso-substituted [14]tribenzotriphyrins(2.1.1).

Metalation of 6,13,20,21-tetraaryl-22H-[14]tribenzotriphyrins(2.1.1) (TriP, 1 a-d) with [Mn(CO)5 Br] provided Mn(I) tricarbonyl complexes of [14]tribenzotriphyrins(2.1.1) 2 a-d in 85-93 % yield. The complexes were characterized by mass spectrometry and UV/Vis absorption, IR, and NMR spectroscopy. Single-crystal X-ray analyses revealed that 2 b and 2 c adopt bowl-shaped conformations. The redox properties of [(TriP)Mn(I) (CO)3 ] (2 a-d) were studied by cyclic voltammetry. Each compound undergoes two reversible one-electron reductions to form a porphyrin π anion radical and a dianion in CH2 Cl2 . Two oxidation waves were observed, the first of which corresponds to a metal-centered electron-transfer process. The redox potentials of 2 a-d are consistent with the optical spectroscopic data and the relatively narrow HOMO-LUMO gaps that were predicted in DFT calculations. The optical spectra can be assigned by using Michl's perimeter model. TDDFT calculations predict the presence of several metal-to-ligand charge-transfer bands in the L-band region between 500 and 700 nm.

Synthesis and Characterization of Palladium(II) Complexes of meso-Substituted [14]Tribenzotriphyrin(2.1.1).

Metalation of 6,13,20,21-tetrakis-aryl-22H-[14]tribenzotriphyrin(2.1.1) (TriPs) with PdCl2 provides Pd(II)-TriP complexes in 45-56% yields. The complexes were characterized by mass spectrometry, and UV-visible absorption, magnetic circular dichroism, and (1)H NMR spectroscopy. A single crystal X-ray analysis reveals that the Pd(II)-TriPs adopts a deeply saddled conformation. The palladium(II) ion is coordinated by two pyrrole nitrogen atoms and two chloride ions to form the square-planar coordination environment. The redox properties of the Pd(II)-TriPs were studied by cyclic voltammetry. Each compound undergoes one irreversible and two reversible one-electron reductions. There is a marked red-shift of the main spectral bands, relative to those of the free-base TriP ligand, due to a marked relative stabilization of the LUMO upon coordination by PdCl2.

Transcriptomics Reveals Effect of Pulsatilla Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling.

The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf Candida albicans (C. albicans). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited C. albicans hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1ß, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC.

Prolonged near-infrared fluorescence imaging of microRNAs and proteases in vivo by aggregation-enhanced emission from DNA-AuNC nanomachines.

Developing a comprehensive strategy for imaging various biomarkers (i.e., microRNAs and proteases) in vivo is an exceptionally formidable task. Herein, we have designed a deoxyribonucleic acid-gold nanocluster (DNA-AuNC) nanomachine for detecting tumor-related TK1 mRNA and cathepsin B in living cells and in vivo. The DNA-AuNC nanomachine is constructed using AuNCs and DNA modules that incorporate a three component DNA hybrid (TD) and a single-stranded fuel DNA (FD). Upon being internalized into tumor cells, the TK1 mRNA initiates the DNA-AuNC nanomachine through DNA strand displacement cascades, leading to the amplified self-assembly and the aggregation-enhanced emission of AuNCs for in situ imaging. Furthermore, with the aid of a protease nanomediator consisting of a mediator DNA/peptide complex and AuNCs (DpAuNCs), the DNA-AuNC nanomachine can be triggered by the protease-activated disassembly of the DNA/peptide complex on the nanomediator, resulting in the aggregation of AuNCs for in vivo protease amplified detection. It is worth noting that our study demonstrates the impressive tumor permeability and accumulation capabilities of the DNA-AuNC nanomachines via in situ amplified self-assembly, thereby facilitating prolonged imaging of TK1 mRNA and cathepsin B both in vitro and in vivo. This strategy presents a versatile and biomarker-specific paradigm for disease diagnosis.

Interaction between Vitamin D Status and Calcium Intake in Association with Blood Pressure and Hypertension.

Vitamin D deficiency and inadequate calcium intake are supposed to be potentially related to cardiovascular outcomes, however, their combined association with hypertension remains unclear. In this cross-sectional study among 2,352 subjects, dietary calcium intake was assessed by using a valid food frequency questionnaire, and serum 25-hydroxyvitamin D (25OHD) was measured by the Ultra Performance Liquid Chromatography system. Hypertension was defined as a level of systolic pressure ≥140 mmHg or diastolic pressure ≥90 mmHg, or both, or administration of antihypertensive medications. Vitamin D status was classified into deficiency (25OHD<20 ng/mL), insufficiency (20 ng/mL≤25OHD<30 ng/mL) and sufficiency (25OHD≥30 ng/mL), while dietary calcium intake was divided into tertiles as low, medium, and high. Two-way analysis of variance (ANOVA) and multivariable logistic regression models were adopted. A significant interaction between vitamin D status and dietary calcium intake in relations to systolic blood pressure (p=0.042) and hypertension (p=0.029) indicates the associations of dietary calcium intake with systolic blood pressure and hypertension depend on the vitamin D status, and vice versa. Only in the vitamin D deficiency group, dietary calcium intake was significantly associated with systolic blood pressure level (ß=-0.162, p<0.001) and prevalence of hypertension (odd ratio=2.20, p<0.001). The significance was not substantially compromised after further adjustment for confounding factors. In conclusion, the combination of vitamin D deficiency and low dietary calcium intake, rather than alone, is associated with hypertension.

Genetically determined serum bilirubin level and the risk of heart failure: A mendelian randomization study.

Background: The association between serum bilirubin level and heart failure (HF) was controversial in previous observational studies and the causal effects of bilirubin on HF have not been investigated. Here, we conducted a Mendelian randomization (MR) study to investigate the associations between genetically determined bilirubin level and HF. Methods: Summary data on the association of single nucleotide polymorphisms (SNPs) with serum bilirubin levels were obtained from genome-wide association study (GWAS) for individuals of European descent and East Asian descent separately. Statistical data for gene-HF associations were extracted from three databases: the HERMES Consortium (47,309 cases and 930,014 controls), FinnGen study (30,098 cases and 229,612 controls) for European population and Biobank Japan (2,820 HF cases and 192,383 controls) for East Asian population. We applied a two-sample Mendelian randomization framework to investigate the causal association between serum bilirubin and HF. Results: Findings from our MR analyses showed that genetically determined serum bilirubin levels were not causally associated with HF risk in either European or East Asian population (odds ratio [OR] = 1.01 and 95% confidence interval [CI] = .97-1.05 for HERMES Consortium; OR = 1.01 and 95% CI = .98-1.04 for FinnGen Study; OR = .82, 95% CI: .61-1.10 for Biobank Japan). These results remained unchanged using different Mendelian randomization methods and in sensitivity analyses. Conclusion: Our study did not find any evidence to support a causal association between serum bilirubin and HF.

[Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism].

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 µg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). CONCLUSION: The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.

[Therapeutic Effect of Single Intramuscular Administration of Recombinant Human Thrombopoietin on Rhesus Monkeys with Acute radiation Sickness].

OBJECTIVE: To confirm the therapeutic effect of recombinant human thrombopoietin (rhTPO) on rhesus monkeys irradiated with 5.0 Gy 60Co γ-ray, and provide experimental basis for clinical treatment of similar patients. METHODS: Fourteen adult rhesus monkeys were irradiated with 60Co γ-ray on both sides at the dose of 5.0 Gy (dose rate 69.2 cGy/min) to establish the acute radiation sickness model. The monkeys were divided into irradiation group (n=5), rhTPO 5 µg/kg group (n=4) and rhTPO 10 µg/kg group (n=5). Two hours after irradiation, the three groups of monkeys were injected with saline 0.1 ml/kg, rhTPO 5 µg/kg（0.1 ml/kg） and rhTPO 10 µg/kg(0.2 ml/kg), respectively. The general signs, survival, peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation, and the differences between rhTPO group and irradiation control group were compared. RESULTS: After total body irradiation with 5.0 Gy60Co γ-ray, rhesus monkeys successively showed fever, hemorrhage, sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes. Compared with the irradiated control group, a single intramuscular injection of rhTPO 5 µg/kg or 10 µg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding, increase the nadir of peripheral red blood cells and platelets counts, shorten the duration of hemocytopenia, and advance the time for blood cells to return to the pre-irradiation level. The serum biochemical results showed that rhTPO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent. Compared with the two administration groups, the therapeutic effect of rhTPO 10 µg/ kg was better. CONCLUSION: A single injection of rhTPO 5 µg/ kg or 10 µg/ kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gy γ-ray. It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.

1,3-Dithiole-2-one-Fused Subphthalocyanine and Subporphyrazine: Synthesis and Properties Arising from the 1,3-Dithiole-2-one Units.

Subphthalocyanine (SubPc) and its benzo ring-removed analogue, subporphyrazine (SubPz), bearing 1,3-dithiole-2-one (S2CO) groups as a new class of substituents were synthesized. In addition to the perturbed optical properties due to the presence of electron-withdrawing S2CO units, the deep bowl-shaped structure of the SubPz derivative allowed concave-convex interaction to form a unique co-crystal structure with C60. Finally, using the reactivity of the peripheral S2CO units, S2CO-fused SubPc was successfully converted into tetrathiafulvalene (TTF)-annulated SubPc in a yield higher than that of the direct synthesis from a TTF-fused phthalonitrile.

Three-dimensional aromaticity in an antiaromatic cyclophane.

Understanding of interactions among molecules is essential to elucidate the binding of pharmaceuticals on receptors, the mechanism of protein folding and self-assembling of organic molecules. While interactions between two aromatic molecules have been examined extensively, little is known about the interactions between two antiaromatic molecules. Theoretical investigations have predicted that antiaromatic molecules should be stabilized when they stack with each other by attractive intermolecular interactions. Here, we report the synthesis of a cyclophane, in which two antiaromatic porphyrin moieties adopt a stacked face-to-face geometry with a distance shorter than the sum of the van der Waals radii of the atoms involved. The aromaticity in this cyclophane has been examined experimentally and theoretically. This cyclophane exhibits three-dimensional spatial current channels between the two subunits, which corroborates the existence of attractive interactions between two antiaromatic π-systems.

Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases around the world, and is closely associated with obesity, diabetes, and insulin resistance. Ursolic acid (UA), an ubiquitous triterpenoid with multifold biological roles, is distributed in various plants. This study was conducted to investigate the therapeutic effect and potential mechanisms of UA against hepatic steatosis in a high-fat diet (HFD)-induced obese non-alcoholic fatty liver disease (NAFLD) rat model. METHODOLOGY/PRINCIPAL FINDINGS: Obese NAFLD model was established in Sprague-Dawley rats by 8-week HFD feeding. Therapeutic role of UA was evaluated using 0.125%, 0.25%, 0.5% UA-supplemented diet for another 6 weeks. The results from both morphologic and histological detections indicated that UA significantly reversed HFD-induced hepatic steatosis and liver injury. Besides, hepatic peroxisome proliferator-activated receptor (PPAR)-α was markedly up-regulated at both mRNA and protein levels by UA. Knocking down PPAR-α significantly inhibited the anti-steatosis role of UA in vitro. HFD-induced adverse changes in the key genes, which participated in hepatic lipid metabolism, were also alleviated by UA treatment. Furthermore, UA significantly ameliorated HFD-induced metabolic disorders, including insulin resistance, inflammation and oxidative stress. CONCLUSIONS/SIGNIFICANCE: These results demonstrated that UA effectively ameliorated HFD-induced hepatic steatosis through a PPAR-α involved pathway, via improving key enzymes in the controlling of lipids metabolism. The metabolic disorders were accordingly improved with the decrease of hepatic steatosis. Thereby, UA could be a promising candidate for the treatment of NAFLD.